Lysgaardkarlsson7259

These data support examining mevidalen for symptomatic treatment of patients with Parkinson disease and Lewy body dementia.

Recent guidelines recommend a systolic blood pressure (SBP) target below 130mmHg in heart failure patients with preserved ejection fraction (HFpEF), whatever their age. We investigated whether this intensive SBP control was associated with better survival in very old adults hospitalized for acute HFpEF.

We conducted an observational study in an acute geriatric unit all consecutive patients discharged from hospital for acute heart failure from 1 March 2019 to 29 February 2020 with a diagnosis of HFpEF were included. Re-hospitalization and all-cause mortality at 1year were compared according to the mean SBP at discharge (patients with a mean SBP<130mmHg vs. those with SBP≥130mmHg). We included 81 patients with a mean age of 89years. Among them, 47 (58%) were re-hospitalized and 37 (46%) died at 1year. All-cause mortality (hazard ratio [HR] [95% confidence interval] 1.50 [0.75-2.98], P=0.2) and re-hospitalization rate (HR 1.04 [0.58-1.86], P=0.90) at 1year did not significantly differ between patients witF.

Cetuximab is used for colorectal cancer (CRC) treatment. However, the early biomarker of treatment efficacy of cetuximab has not been identified.

After 1year of cetuximab treatment, patients were divided into an effective group and an ineffective group. The interleukin-33 (IL-33) level and the distribution of lymphatic cells in patients were investigated by analyzing the peripheral blood mononuclear cells via flow cytometry analysis and ELISA. The correlation between IL-33 immunomodulatory effect and cetuximab treatment efficacy was determined through experiments in vivo and in vitro.

The IL-33level in the peripheral blood was increased at 4weeks after cetuximab administration of effective group, meanwhile, the osteopontin (OPN) was reduced. Whereas neither IL-33level nor OPN level of ineffective patients changed. In the effective group, the number of natural killer (NK) and CD8

T cells were increased. Moreover, CD137 and CD107a expression on NK cells were higher in the effective group compared to the of cetuximab treatment efficacy.Constructing the heterostructures is considered to be one of the most effective methods to improve the poor electrical conductivity and insufficient electrocatalytic properties of metal sulfide catalysts. In this work, MnCo2 S4 -CoS1.097 nanotubes are successfully prepared via a reflux- hydrothermal process. This novel cathode catalyst delivers high discharge/charge specific capacities of 21 765/21 746 mAh g-1 at 200 mA g-1 and good rate capability. In addition, a favorable cycling stability with a fixed specific capacity of 1000 mAh g-1 at high current density of 1000 mA g-1 (167 cycles) and 2000 mA g-1 (57 cycles) are delivered. It is proposed that fast transmission of ions and electrons accelerated by the built-in electric field, multiple active sites from the heterostructure, and nanotube architecture with large specific surface area are responsible for the superior electrochemical performance. To some extent, the rational design of this heterostructured metal sulfide catalyst provides guidance for the development of the stable and efficient cathode catalysts for Li-O2 batteries that can be employed under high current conditions.Ultimately soft electronics seek affordable and high mechanical performance universal self-healing materials that can autonomously heal in harsh environments within short times scales. As of now, such features are not found in a single material. Herein, interpenetrated elastomer network with bimodal chain length distribution showing rapid autonomous healing in universal conditions ( less then 7200 s) with high efficiency (up to 97.6 ± 4.8%) is reported. The bimodal elastomer displays strain-induced photoelastic effect and reinforcement which is responsible for its remarkable mechanical robustness (≈5.5 MPa stress at break and toughness ≈30 MJ m-3 ). The entropy-driven elasticity allows an unprecedented shape recovery efficiency (100%) even after fracturing and 100% resiliency up to its stretching limit (≈2000% strain). The elastomers can be mechanically conditioned leading to a state where they recover their shape extremely quickly after removal of stress (nearly order of magnitude faster than pristine elastomers). As a proof of concept, universal self-healing mechanochromic strain sensor is developed capable of operating in various environmental conditions and of changing its photonic band gap under mechanical stress.The synergistic combination of chemotherapy and photodynamic therapy has attracted considerable attention for its enhanced antitumoral effects; however, it remains challenging to successfully delivery photosensitizers and anticancer drugs while minimizing drug leakage at off-target sites. A red-light-activatable metallopolymer, Poly(Ru/PTX), is synthesized for combined chemo-photodynamic therapy. The polymer has a biodegradable backbone that contains a photosensitizer Ru complex and the anticancer drug paclitaxel (PTX) via a singlet oxygen (1 O2 ) cleavable linker. The polymer self-assembles into nanoparticles, which can efficiently accumulate at the tumor sites during blood circulation. The distribution of the therapeutic agents is synchronized because the Ru complex and PTX are covalently conjugate to the polymer, and off-target toxicity during circulation is also mostly avoided. Red light irradiation at the tumor directly cleaves the Ru complex and produces 1 O2 for photodynamic therapy. Sequentially, the generated 1 O2 triggers the breakage of the linker to release the PTX for chemotherapy. Therefore, this novel sequential dual-model release strategy creates a synergistic chemo-photodynamic therapy while minimizing drug leakage. This study offers a new platform to develop smart delivery systems for the on-demand release of therapeutic agents in vivo.

This study aimed to assess the effect of application of QMix and common root canal irrigating solutions on the bond strength of fiber post to root dentin.

In this in-vitro study, 60 extracted incisor teeth were decoronated such that 15 mm of root length remained. The canals were prepared with ProTaper rotary system to F5 and filled with gutta-percha and AH26 sealer. Prior to post placement, the teeth were divided into four groups based on the type of final irrigating solution namely saline, 5.25% NaOCl, 2% chlorhexidine, and QMix. The fiber posts were then cemented with Panavia F2 resin cement. The roots were sectioned perpendicular to their longitudinal axis, and four sections with 1 mm thickness were made at the middle and coronal thirds of the roots. The push-out bond strength of fiber posts was measured by a universal testing machine in megapascals. Data were analyzed by two-way ANOVA and Tukey's test.

The maximum and minimum bond strength values were noted in QMix and NaOCl groups in both the middle and coronal third of the root, respectively. But, there was no significant difference between the push-out bond strength in the middle or coronal third of the root (p=0.054). Adhesive failure was the most common mode of failure in all groups.

Use of QMix for post space irrigation does not compromise the bond strength of fiber post to root dentin, and can be used for final rinsing of the post space.

Use of QMix for post space irrigation does not compromise the bond strength of fiber post to root dentin, and can be used for final rinsing of the post space.

To report on the clinical outcome of patients undergoing combined arthroscopic treatment of labral resection and microfracture at the rim of acetabulum at a minimum 2-year follow-up.

The retrospective study included 38 patients undergoing hip arthroscopy for irreparable labral injury from 24 February 2014 to 26 February 2018. Thirteen patients were excluded owing to patient refusal of participation and concomitant diseases like synovial chondromatosis and dysplasia hip. The study group consisted of patients undergoing combined arthroscopic labral resection and microfracture at the rim of acetabulum (MICRO Group 20 patients), arthroscopic labral resection alone (RESEC Group five patients). Postoperative three-dimensional (3D) double-echo steady-state (DESS) sequence with radial imaging at 3 Tesla were obtained and fluoroscopic image of the involved hip under distraction were used to observe the restoration of vacuum effect. Patient-reported outcome scores (PROs) including the Harris Hip Score (HHS), Visual(52.4 vs 87.0, P < 0.05); HOS-SSS (48.1 vs 86.5, P < 0.05); VAS (6.3 vs 1.6, P < 0.05). One patient of MICRO group had transient neurapraxias of the pudendal nerve that resolved completely by 3 months. There showed no statistically significant difference between groups regarding the preoperative and postoperative PROs.

Compared to labral resection, combined arthroscopic labral resection and microfracture at the rim of acetabulum is able to fulfill the labral defect area with the potential to restore the seal effect of labrum as an effective and safe option for irreparable segmental labral tears.

Compared to labral resection, combined arthroscopic labral resection and microfracture at the rim of acetabulum is able to fulfill the labral defect area with the potential to restore the seal effect of labrum as an effective and safe option for irreparable segmental labral tears.

To analyze the learning curve experience of hip arthroscopy based on patient demographics, surgical time, portal setup time, and postoperative complications and to find the key point in the learning curve.

From May 2016 to February 2019, a prospective study on the learning curve experience of hip arthroscopy was performed in our hospital. We evaluated the first 50 consecutive hip arthroscopy procedures performed by a single surgeon. There were nine females and 41 males with a mean age of 30.8 years. We divide the patients into early group and late group according to the date of their operation, with each group including 25 patients. Data on patient demographics, types of procedure, surgical time, portal setup time, and postoperative complications were collected. Functional scores were assessed with the modified Harris Hip Score (mHHS).

Patients were followed up for 16.4 months on average (range, 13-27 months). The early group of patients had a mean age of 35.2 years and the late group a mean age of 26.5ollow-up.

The steep learning curve of hip arthroscopy is mainly caused by the challenge of portal setup and portalrelated complications were more common in the early group than in the late group. Surgical time is not an effective indicator for evaluating progress on the learning curve of hip arthroscopy.

The steep learning curve of hip arthroscopy is mainly caused by the challenge of portal setup and portalrelated complications were more common in the early group than in the late group. Surgical time is not an effective indicator for evaluating progress on the learning curve of hip arthroscopy.

To retrospectively assess the mid-term clinical and radiological results of hip arthroscopic treatment of labral tears in patients with borderline developmental dysplasia of the hip (BDDH).

From January 2010 and December 2019, data were retrospectively reviewed for all patients who underwent arthroscopic surgery of the hip for the treatment of intra-articular abnormalities. Only the Patients who had borderline developmental dysplasia (BDDH) were included. All operations were performed by two senior surgeons, the arthroscopic treatment including labral repair, labral debridement, minimal acetabuloplasty, femoroplasty and capsular closure. The evaluation consisted of pain evaluation (visual analog scale [VAS]), the modified Harris hip score (MHHS), range of motion, the radiological evaluation of plain film and MRI analysis of the hip joint. The plain film evaluation included anteroposterior views of the pelvis to assess lateral center-edge angle (LCEA) and acetabular inclination (AI), frog-leg lateral viewsion periacetabular osteotomies (PAO) because of subluxation of the hip joint with permanent pain after 6 months failed conservative treatment.

Arthroscopic treatment of labral tears in patients with BDDH may provide safe and durable favorable results at midterm follow-up. The best outcome could be expected in patients with labral repair and closure of the capsule with strict patient selection criteria.

Arthroscopic treatment of labral tears in patients with BDDH may provide safe and durable favorable results at midterm follow-up. The best outcome could be expected in patients with labral repair and closure of the capsule with strict patient selection criteria.

To investigate the efficacy and safety of core decompression (CD) with local administration of zoledronate and enriched bone marrow mononuclear cells (BMMCS) for the treatment of non-traumatic osteonecrosis of femoral head (ONFH).

A total of 17 patients (30 hips) diagnosed with stage II and III ONFH according to the 2019 revised Association for Research on Osseous Circulation (ARCO) staging criteria from 2012 to 2014 were retrospectively reviewed. The patients received the following therapy the BMMCs and zoledronate were injected into the necrotic zone, respectively, along with CD. The mean age of the patients was 36.8 years; 14 were men and three were women. All patients included had non-traumatic ONFH and a minimum follow-up of 5 years, which ended when total hip arthroplasty (THA) was performed. Imaging modalities, including plain radiography, computed tomography (CT), and magnetic resonance imaging (MRI) were taken pre- and postoperatively. Harris hip score (HHS) was used to evaluate the functional ou0.012; P = 0.031). However, no correlation was found between conversion to THA and the known risk factors. No major complication was reported, with only four patients complaining about general weakness and muscle soreness, and all disappeared within 2-3 days.

The novel treatment modality could relieve pain, delay the progression of collapse, which might be an effective and safe method for hip preservation of early and mid-term ONFH. However, the effect of this method may be related to ARCO stage, JIC type, and corticosteroid exposure.

The novel treatment modality could relieve pain, delay the progression of collapse, which might be an effective and safe method for hip preservation of early and mid-term ONFH. However, the effect of this method may be related to ARCO stage, JIC type, and corticosteroid exposure.

To evaluate the risk of bleeding in elderly patients undergoing early hip fracture surgery with/without clopidogrel administration.

This was a retrospective study, and patients over 65 years with fresh hip fracture were enrolled. For the patients taking clopidogrel, early surgical treatment was performed without 5-7 days waiting time. The patients were divided into groups according to their fracture type and the surgical method. Within each fracture/surgery group, the patients were further divided into subgroups according to whether they had clopidogrel administration. The patients' age, gender, American Society of Anesthesiologists (ASA) score, hemoglobin level at admission, and the time from admission to surgery were compared in the different groups. The bleeding outcomes, such as intraoperative blood loss and blood transfusion status, as well as secondary outcomes, such as operation duration and length of hospital stay, were also compared in these groups.

There were no statistically significant diffeith patients without clopidogrel administration, elderly patients with hip fractures who receive clopidogrel as long-term anti-platelet therapy are relatively safe for surgery in less than 5-7 days after discontinuation of clopidogrel.

This study indicated that compared with patients without clopidogrel administration, elderly patients with hip fractures who receive clopidogrel as long-term anti-platelet therapy are relatively safe for surgery in less than 5-7 days after discontinuation of clopidogrel.

To investigate the clinical and radiographic short-term results of arthroscopic treatment for posterior labrum tears with an attached bony fragment after traumatic posterior hip dislocation.

Between July 2014 and May 2019, a consecutive series of nine patients diagnosed with a posterior labrum tear with an attached bony fragment after traumatic posterior hip dislocation were treated by hip arthroscopic techniques. The patients had been injured in traffic accidents (n = 6) or high falls (n = 3). All patients were provided primary treatment at the emergency department of our institution, and then were transferred to our department for arthroscopy. Demographic data (e.g. gender, age, etc), intraoperative findings, the preoperative and postoperative multiple clinical scores and radiological results were subsequently assessed. Visual analogue scale for pain (VAS) and modified Harris hip scores (mHHSs) were measured and compared before surgery, and at the last follow-up.

A total of nine patients were enrolled2 years after surgery (P < 0.05). At the final follow-up, all patients had regained full range of motion (ROM) and were satisfied with the results. None of the patients showed signs of heterotopic ossification, avascular necrosis or progression of osteoarthritis of the hip joint.

Traumatic dislocation is accompanied by a variety of intra-articular hip joint pathologies. Managing posterior acetabular rim fracture after traumatic posterior hip dislocation using arthroscopic reduction and fixation with anchors is a safe and minimally invasive option and delays the progression of traumatic osteoarthritis.

Traumatic dislocation is accompanied by a variety of intra-articular hip joint pathologies. Managing posterior acetabular rim fracture after traumatic posterior hip dislocation using arthroscopic reduction and fixation with anchors is a safe and minimally invasive option and delays the progression of traumatic osteoarthritis.

To explore the development of hip arthroscopy in China through reviewing the change of the application of hip arthroscopy operation on treating femoracetabular impingement (FAI).

Papers were retrieved from January 1, 2005 to November 1, 2019, from databases CNKI, Wanfang Data, VIP, PubMed, and Embase. The keywords are Hip Impingement, Femoroacetabular impingement, Hip arthroscopy, Arthroscopic operation, Hip Arthroscopy operation, and Arthroscope, etc. The quality of papers was assessed through MINORS , and statistics and meta-analysis were performed by Word, Excel, and Revman 5.3 Zurich, Switzerland.

From a total of 8,953 papers, 46 review articles without data and 48 articles with data were involved, and 25 papers were included in the Meta-analysis. The twenty-five papers were selected from 48 papers with data, of which 41 were reported in Chinese, 11 were missing complete Harris scores, five did not mention the number of patients who had lost follow-up, three had minors quality scores below 7, one did not have enough FAI cases, and three did not have standard deviations in Harris scores. Overall, in China, the application of hip arthroscopy regarding FAI has flourished while maintaining a high level of treatment and has reached its peak in the past 2 years.

With the rapid development of hip arthroscopy in China, hip operation is widely recognized, many reports on its application on FAI have emerged successively, and the scope of application and technical level have been improved.

With the rapid development of hip arthroscopy in China, hip operation is widely recognized, many reports on its application on FAI have emerged successively, and the scope of application and technical level have been improved.Hepatic ischaemia-reperfusion (I/R) injury constitutes a tough difficulty in liver surgery. Dexmedetomidine (Dex) plays a protective role in I/R injury. This study investigated protective mechanism of Dex in hepatic I/R injury. The human hepatocyte line L02 received hypoxia/reoxygenation (H/R) treatment to stimulate cell model of hepatic I/R. The levels of pyroptosis proteins and inflammatory factors were detected. Functional rescue experiments were performed to confirm the effects of miR-494 and JUND on hepatic I/R injury. The levels of JUND, PI3K/p-PI3K, AKT/p-AKT, Nrf2, and NLRP3 activation were detected. The rat model of hepatic I/R injury was established to confirm the effect of Dex in vivo. Dex reduced pyroptosis and inflammation in H/R cells. Dex increased miR-494 expression, and miR-494 targeted JUND. miR-494 inhibition or JUND upregulation reversed the protective effect of Dex. Dex repressed NLRP3 inflammasome by activating the PI3K/AKT/Nrf2 pathway. In vivo experiments confirmed the protective effect of Dex on hepatic I/R injury. Overall, Dex repressed NLRP3 inflammasome and alleviated hepatic I/R injury via the miR-494/JUND/PI3K/AKT/Nrf2 axis.

Undetected cystic fibrosis transmembrane regulator (CFTR) mutations may predispose individuals to develop CRS independent of formal CF diagnosis. The objective of this study was to determine the prevalence of CFTR mutations among individuals with CRS.

A systematic search following PRISMA guidelines was performed. A meta-analysis was performed to calculate pooled estimates for the prevalence of any CFTR mutation and for the DF508mutation.

The systematic search included all studies identifying adults diagnosed with CRS, with no limitation to region or publication date. Studies had to identify a sample of patients previously diagnosed with CRS but not with CF and reporting testing for the prevalence of CF or the CFTR gene mutation.

Prevalence of CFTR mutations among the general CRS population, with subgroup analysis of individuals with the dF508mutation.

The 6 included studies represented five countries the United States, the UK, France, Poland and Finland. The pooled prevalence of CFTR mutations of ann CRS patients who have not been diagnosed with CF is currently unclear. Future studies should include sweat chloride testing as a measure of CFTR function.

To confirm the feasibility of hypofractionated proton beam therapy (PBT), we compared the acute adverse event rates and International Prostate Symptom Score (IPSS) in prostate cancer patients treated with hypofractionated versus conventionally fractionated (2.0Gy relative biological effectiveness (RBE)/fraction) PBT.

We reviewed 289 patients with prostate cancer, of whom 73, 100, and 116 patients were treated with 2.0, 2.5, and 3.0Gy (RBE)/fraction, respectively. The endpoints were acute genitourinary and gastrointestinal toxicities and the IPSS, evaluated up to 6months after PBT initiation.

No significant differences were found in acute toxicity rates or the IPSS among the fractionation schedules. Diabetes mellitus, age, and androgen deprivation therapy were not identified as factors associated with the IPSS.

There were no significant differences in adverse events or quality of life among the three fractionation schedules early after PBT.

There were no significant differences in adverse events or quality of life among the three fractionation schedules early after PBT.Cardiogenic shock (CS) is a complex multifactorial clinical syndrome, developing as a continuum, and progressing from the initial insult (underlying cause) to the subsequent occurrence of organ failure and death. There is a large phenotypic variability in CS, as a result of the diverse aetiologies, pathogenetic mechanisms, haemodynamics, and stages of severity. Although early revascularization remains the most important intervention for CS in settings of acute myocardial infarction, the administration of timely and effective antithrombotic therapy is critical to improving outcomes in these patients. In addition, other clinical settings or non-acute myocardial infarction aetiologies, associated with high thrombotic risk, may require specific regimens of short-term or long-term antithrombotic therapy. In CS, altered tissue perfusion, inflammation, and multi-organ dysfunction induce unpredictable alterations to antithrombotic drugs' pharmacokinetics and pharmacodynamics. Other interventions used in the management of CS, such as mechanical circulatory support, renal replacement therapies, or targeted temperature management, influence both thrombotic and bleeding risks and may require specific antithrombotic strategies. In order to optimize safety and efficacy of these therapies in CS, antithrombotic management should be more adapted to CS clinical scenario or specific device, with individualized antithrombotic regimens in terms of type of treatment, dose, and duration. In addition, patients with CS require a close and appropriate monitoring of antithrombotic therapies to safely balance the increased risk of bleeding and thrombosis.Understanding the mechanisms underlying evasive resistance in cancer is an unmet medical need to improve the efficacy of current therapies. In this study, a combination of shRNA-mediated synthetic lethality screening and transcriptomic analysis revealed the transcription factors YAP/TAZ as key drivers of Sorafenib resistance in hepatocellular carcinoma (HCC) by repressing Sorafenib-induced ferroptosis. Mechanistically, in a TEAD-dependent manner, YAP/TAZ induce the expression of SLC7A11, a key transporter maintaining intracellular glutathione homeostasis, thus enabling HCC cells to overcome Sorafenib-induced ferroptosis. At the same time, YAP/TAZ sustain the protein stability, nuclear localization, and transcriptional activity of ATF4 which in turn cooperates to induce SLC7A11 expression. Our study uncovers a critical role of YAP/TAZ in the repression of ferroptosis and thus in the establishment of Sorafenib resistance in HCC, highlighting YAP/TAZ-based rewiring strategies as potential approaches to overcome HCC therapy resistance.

This study aimed to compare the efficacy of angiotensin receptor-neprilysin inhibitor (ARNI) therapy with angiotensin converting enzyme inhibitor or angiotensin receptor blocker (ACEI/ARB) therapy for cardiovascular outcomes in patients with acute myocardial infarction (AMI).

Data were collected from the Biobank of the First Affiliated Hospital of Xi'an Jiaotong University between January 2016 and December 2020. A total of 7556 AMI patients were screened for eligibility. Propensity score matching based on age, sex, blood pressure, kidney function, baseline left ventricular ejection fraction (LVEF), and cardiovascular medication were conducted, resulting in 291 patients with AMI being assigned to ARNI, ACEI, and ARB group, respectively. Patients receiving ARNI had significantly lower rates of the composite cardiovascular outcome than ACEI hazard ratio [HR] 0.51, [95% confidence interval (CI), 0.27-0.95], P=0.02, and ARB users [HR 0.47, (95%CI, 0.24-0.90), P=0.02]. Patients receiving ARNI showed lower rates of cardiovascular death than ACEI [HR 0.37, (95%CI, 0.18-0.79), P=0.01] and ARB users [HR 0.41, (95%CI, 0.18-0.95), P=0.04]. Subgroup analysis indicated that patients with LVEF no more than 40% tend to benefit more from ARNI as compared with ACEI [HR 0.30, (95%CI, 0.11-0.86), P=0.01] or ARB [HR 0.21, (95%CI, 0.04-1.1), P=0.05]. Patients aged no more than 60years exhibited reduced composite endpoints [HR for ARNI vs. ARB 0.11, (95%CI, 0.03-0.46), P=0.002].

In patients with AMI, ARNI was superior to ACEI/ARB in reducing the long-term adverse cardiovascular outcomes. Subgroup analysis further indicates that ARNI is more likely to benefit patients with LVEF less than 40% and aged less than 60years.

In patients with AMI, ARNI was superior to ACEI/ARB in reducing the long-term adverse cardiovascular outcomes. Subgroup analysis further indicates that ARNI is more likely to benefit patients with LVEF less than 40% and aged less than 60 years.Anticancer agent doxorubicin-loaded liposomes (DoxLs) were drawn spontaneously into nanotubes comprising multilayers of polyelectrolytes and gold nanoparticles (PAuNTs). We describe a unique structure of PAuNTs incorporating DoxLs (DoxL-PAuNT). The number of DoxLs adsorbed on the tube interior surface was ascertained as 2.4×103 . Heating stimuli engendered gel-liquid crystal phase transition of DoxL in the capillary, subsequently inducing efficient release of Dox without structural changes of the tubule or liposome. Furthermore, antitumor activity of the DoxL-PAuNTs on cancer cells was elucidated.The chemisorption and catalysis of lithium polysulfides (LiPSs) are effective strategies to suppress the shuttle effect in lithium-sulfur (Li-S) batteries. Herein, multisize CoS 2 particles intercalated/coated-montmorillonite (MMT) as an efficient sulfur host is synthesized. As expected, the obtained S/CoS 2 @MMT cathode achieves an absorption-catalysis synergistic effect through the polar MMT aluminosilicate sheets and the well-dispersed nano-micron CoS 2 particles. Furthermore, efficient interlamellar ion pathways and interconnected conductive network are constructed within the composite host due to the intercalation/coating of CoS 2 in/on MMT. Therefore, the S/CoS 2 @MMT cathode achieves an outstanding rate performance up to 5 C (~548 mAh·g -1 ) and a high cycling stability with low capacity decay of 0.063 and 0.067% per cycle for 500 cycles at 1 and 2 C, respectively. With a higher sulfur loading of 4.0 mg·cm -2 , the cathode still delivers satisfactory rate and cycling performance. It shows that the CoS 2 @MMT host has great application prospects in Li-S batteries.Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) which was established in 1993 has been working with the mission to develop general academic research and knowledge on hepato-biliary-pancreatic (HBP) surgery and, further, to pursue the patient safety and patient's best interest in HBP surgery with the cooperated work of international HBP surgeons.

Chemotherapy is an essential treatment to combat solid tumours and mitigate metastasis. Chemotherapy causes side effects including muscle wasting and weakness. Regulated in Development and DNA Damage Response 1 (REDD1) is a stress-response protein that represses the mechanistic target of rapamycin (mTOR) in complex 1 (mTORC1), and its expression is increased in models of muscle wasting. The aim of this study was to determine if deletion of REDD1 is sufficient to attenuate chemotherapy-induced muscle wasting and weakness in mice.

C2C12 myotubes were treated with carboplatin, and changes in myotube diameter were measured. Protein synthesis was measured by puromycin incorporation, and REDD1 mRNA and protein expression were analysed in myotubes treated with carboplatin. Markers of mTORC1 signalling were measured by western blot. REDD1 global knockout mice and wild-type mice were treated with a single dose of carboplatin and euthanized 7days later. Body weight, hindlimb muscle weights, forelimb grip strength, 626) and prevented muscle weakness.

Carboplatin caused loss of body weight, muscle atrophy, muscle weakness, and inhibition of protein synthesis. Loss of REDD1 attenuates muscle atrophy and weakness in mice treated with carboplatin. Our study illustrates the importance of REDD1 in the regulation of muscle mass with chemotherapy treatment and may be an attractive therapeutic target to combat cachexia.

Carboplatin caused loss of body weight, muscle atrophy, muscle weakness, and inhibition of protein synthesis. Loss of REDD1 attenuates muscle atrophy and weakness in mice treated with carboplatin. Our study illustrates the importance of REDD1 in the regulation of muscle mass with chemotherapy treatment and may be an attractive therapeutic target to combat cachexia.Naturally occurring post-transcriptional chemical modifications serve critical roles in impacting RNA structure and function. More directly, modifications may affect RNA stability, intracellular transport, translational efficiency, and fidelity. The combination of effects caused by modifications are ultimately linked to gene expression regulation at a genome-wide scale. The latter is especially true in systems that undergo rapid metabolic and or translational remodeling in response to external stimuli, such as the presence of stressors, but beyond that, modifications may also affect cell homeostasis. Although examples of the importance of RNA modifications in translation are accumulating rapidly, still what these contribute to the function of complex physiological systems such as muscle is only recently emerging. In the present review, we will introduce key information on various modifications and highlight connections between those and cellular malfunctions. In passing, we will describe well-documented roles for modifications in the nervous system and use this information as a stepping stone to emphasize a glaring paucity of knowledge on the role of RNA modifications in heart and skeletal muscle, with particular emphasis on mitochondrial function in those systems. This article is categorized under RNA in Disease and Development > RNA in Disease RNA Processing > RNA Editing and Modification.

Direct oral anticoagulants (DOACs) do not require concentration monitoring. However, whether DOAC concentrations are stable and their variation between and within patients is not well studied.

Patients on vitamin K antagonists (VKA) who switched to rivaroxaban, apixaban, or dabigatran were included between 2018 and 2020. Blood was drawn at DOAC trough and peak concentrations at week 0, 2, and 8. Plasma drug concentrations were determined by anti-factor Xa concentrations (rivaroxaban, apixaban) or diluted thrombin time (dabigatran). Inter- and intra-individual variability was assessed by calculating the coefficient of variation (CV). Linear regression models were employed to evaluate associations between DOAC trough concentrations and previous VKA dosage, creatinine clearance, and body mass index (BMI).

One hundred fifty-two patients were included, of whom 96 (63%) were male and with a mean age of 73.9±8.4years. For the inter-individual variability, the CV ranged between 48% and 81% for trough values andt further study into an optimal target range, in which the risks of both bleeding and thrombosis are minimal.Adrenocortical carcinoma (ACC) is a rare but highly aggressive malignancy. Nearly half of ACC tumours overproduce and secrete adrenal steroids. Excess cortisol secretion, in particular, has been associated with poor prognosis among ACC patients. Furthermore, recent immunotherapy clinical trials have demonstrated significant immunoresistance among cortisol-secreting ACC (CS-ACC) patients when compared to their non-cortisol-secreting (nonCS-ACC) counterparts. The immunosuppressive role of excess glucocorticoid therapies and hypersecretion is known; however, the impact of the cortisol hypersecretion on ACC tumour microenvironment (TME), immune expression profiles and immune cell responses remain largely undefined. In this study, we characterized the TME of ACC patients and compared the immunogenomic profiles of nonCS-ACC and CS-ACC tumours to assess the impact of differentially expressed genes (DEGs) by utilizing The Cancer Genome Atlas (TCGA) database. Immunogenomic comparison (CS- vs. nonCS-ACC tumour TMEs) demonstrated an immunosuppressive expression profile with a direct impact on patient survival. We identified several primary prognostic indicators and potential targets within ACC tumour immune landscape. Differentially expressed immune genes with prognostic significance provide additional insight into the understanding of potential contributory mechanisms underlying failure of initial immunotherapeutic trials and poor prognosis of patients with CS-ACC.Xanthorrhizol (XNT) is a sesquiterpenoid agent isolated from Curcuma xanthorrhiza; It is known to exhibit various pharmacological activities including anti-cancer. We investigated the anti-cell proliferative and proapoptotic effects of XNT on Non-small cell carcinoma (A549) cells were analyzed by the generation of reactive oxygen species (ROS), alteration of mitochondrial membrane potential (ΔΨm), oxidative DNA damage, and apoptosis morphological changes were explored by Hoechst and AO/EtBr staining. Our study demonstrated that XNT treatment significantly reduced the viability of A549 cells in a concentration-dependent manner. We observed that XNT-induced oxidative stress-mediated apoptotic cell death by increasing intracellular ROS generation, depleting antioxidant levels, enhancing lipid peroxidation, increased apoptotic morphological changes, and % of DNA damage on human lung cancer cells. Furthermore, we observed that the XNT induce apoptosis through inhibits phosphorylation of PI3K, AKTand inhibit NF-κBp65 transcriptional signaling activity. In addition, XNT treatment alters the ΔΨm, thereby induces apoptosis was closely coordinated with the induction of pro-apoptotic markers Bax, Bad, caspase- 3, 9 and cytochrome c, and suppression of anti-apoptotic (Bcl-2, Bcl-XL) protein expression. According to our results, XNT-inducing apoptosis in A549 cells by causing oxidative damage and modulating apoptotic signaling events. Finally, XNT-induced apoptotic cell death was confirmed by the TUNEL assay. Therefore, XNT might be used as a chemotherapeutic agent for the treatment of lung cancer.In the present study, we investigated the microbial community composition and their associated metabolic potentials using the 16S rRNA gene (V3-V4) and ITS (ITS1) amplicon sequencing approach in the Patsio glacier. The bacterial community composition was mainly dominated by Bacteroidota (18%-38% of total reads) and Cyanobacteria (9%-30%), along with a rare Candidate phylum Patescibacteria. Ferruginibacter (13%) and Polaromonas (8%) were the most dominant genera identified across the samples known to have potential ecological roles in colonization, driving the functioning of supraglacial habitats. The prevalence of metabolic genes associated with nitrogen, carbon and sulfur cycling processes was identified in the present study. The fungal diversity was dominated by members of unclassified phyla, followed by Ascomycota (up to 6%) and Basidiomycota (up to 4%), in terms of its relative abundance. The relative abundance of Fusarium and Didymella (8%-14%) was higher among the high altitude, cryoconite samples (P1-P5), while Rhodotorula (12%-29%) dominated in the glacial ice debris samples (P6-P8). Thus, our study provides significant insights into dynamics of microbial communities and its potential ecological roles in the changing climate.The B cell compartment provides innate and adaptive immune defenses against pathogens. Different B cell subsets, reflecting the maturation stages of B cells, have noninterchangeable functions and roles in innate and adaptive immune responses. In this review, we provide an overview of the B cell subsets present in peripheral blood of healthy individuals. A specific gating strategy is also described to clearly and univocally identify B cell subsets based on the their phenotypic traits by flow cytometric analysis.Dispersal is a key demographic process involving three stages emigration, transience and settlement; each of which is influenced by individual, social and environmental determinants. An integrated understanding of species dispersal is essential for demographic modelling and conservation planning. Here, we review the dispersal patterns and determinants documented in the scientific literature for the grey wolf (Canis lupus) across its distribution range. We showed a surprisingly high variability within and among study areas on all dispersal parameters - dispersal rate, direction, distance, duration and success. We found that such large variability is due to multiple individual, social and environmental determinants, but also due to previously overlooked methodological research issues. We revealed a potential non-linear relationship between dispersal rate and population density, with dispersal rate higher at both ends of the gradient of population density. We found that human-caused mortality reduces distance, duration and success of dispersal events. Furthermore, dispersers avoid interaction with humans, and highly exposed areas like agricultural lands hamper population connectivity in many cases. We identified numerous methodological research problems that make it difficult to obtain robust estimates of dispersal parameters and robust inferences on dispersal patterns and their determinants. In particular, analyses where confounding factors were not accounted for led to substantial knowledge gaps on all aspects of dispersal in an otherwise much-studied species. Our understanding of wolf biology and management would significantly benefit if wolf dispersal studies reported the results and possible factors affecting wolf dispersal more transparently.

Numerous studies in hepatocellular carcinoma (HCC) have proposed tissue-based gene signatures for individualized prognostic assessments. Here, we develop a novel circulating tumor cell (CTC)-based transcriptomic profiling assay to translate tissue-based mRNA signatures into a liquid-biopsy setting for non-invasive HCC prognostication.

The HCC CTC mRNA Scoring System combines the NanoVelcro CTC Assay for enriching HCC CTCs and the NanoString nCounter platform for quantifying the HCC-CTC Risk Score (RS) panel in enriched HCC CTCs. The prognostic role of HCC-CTC RS was assessed in the Cancer Genome Atlas (TCGA) HCC cohort (n=362) and validated in an independent clinical CTC cohort (n=40).

The HCC-CTC RS panel was developed through our integrated data analysis framework of 8 HCC tissue-based gene signatures, and identified the top 10 prognostic genes (DDR1, EHHADH, AR, LUM, HSD1786, PMEPA1, TSKU, NECAB2, LAD1, SLC27A5) highly expressed in HCC with low expression in white blood cells. The panel accurately discriminated overall survival in TCGA HCC cohort (hazard ratio [HR] 2.01, 95% confidence intervals [CI] 1.39-2.91). Combined use of Scoring System and HCC-CTC RS panel successfully distinguished artificial blood samples spiked with an aggressive HCC cell type, SNU-387, from those spiked with PLC/PRF/5 cells (P=0.02). In the CTC validation cohort (n=40), HCC-CTC RS remained an independent predictor of survival (HR 5.71, 95% CI 1.53-21.27, P=0.009) after controlling for MELD score, BCLC stage, and CTC enumeration count.

Our study demonstrates a novel interdisciplinary approach to translate tissue-based gene signatures into a liquid biopsy setting. This non-invasive approach will allow real-time disease profiling and dynamic prognostication of HCC.

Our study demonstrates a novel interdisciplinary approach to translate tissue-based gene signatures into a liquid biopsy setting. This non-invasive approach will allow real-time disease profiling and dynamic prognostication of HCC.

The corneal back surface is known to add some astigmatism against-the-rule, which has to be considered in cataract surgery with toric lens implantation. The purpose of this study was to set up a deep learning algorithm which predicts the total corneal power from keratometry and biometric measures.

Based on a large data set of measurements with the IOLMaster 700 from two clinical centres, data from N=21108 eyes were included, each record containing valid data for keratometry K, total keratometry TK, axial length AL, central corneal thickness CCT, anterior chamber depth ACD, lens thickness LT and horizontal corneal diameter W2W from an individual eye. After a vector decomposition of K and TK into equivalent power (.EQ) and projections of astigmatism to the 0°/90° (.AST

) and 45°/135° (.AST

) axis, a multi-output feedforward shallow neural network was derived to predict TK from K, AL, CCT, ACD, LT, W2W and patient age.

After some trial and error, the neural network having a Levenberg-Marquardt trainingy fixed correction term, which can compensate only for a static intercept of the astigmatic components TKEQ, TKAST0° and TKAST45° compared with KEQ, KAST0° and KAST45° , our trained neural network was able to reduce the variance in the prediction error significantly. This neural network could be used to account for the corneal back surface astigmatism for biometers where the corneal back surface measurement or total keratometry is not available.The vertebrate Six (Sine oculis homeobox) family of homeodomain transcription factors plays critical roles in the development of several organs. Six1 plays a central role in cranial placode development, including the precursor tissues of the inner ear, as well as other cranial sensory organs and the kidney. In humans, mutations in SIX1 underlie some cases of Branchio-oto-renal (BOR) syndrome, which is characterized by moderate-to-severe hearing loss. We utilized CRISPR/Cas9 technology to establish a six1 mutant line in Xenopus tropicalis that is available to the research community. We demonstrate that at larval stages, the six1-null animals show severe disruptions in gene expression of putative Six1 target genes in the otic vesicle, cranial ganglia, branchial arch, and neural tube. At tadpole stages, six1-null animals display dysmorphic Meckel's, ceratohyal, and otic capsule cartilage morphology. This mutant line will be of value for the study of the development of several organs as well as congenital syndromes that involve these tissues.Postbariatric loss of muscle tissue could negatively affect long-term health due to its role in various bodily processes, such as metabolism and functional capacity. This meta-analysis aimed to unravel time-dependent changes in the magnitude and progress of lean body mass (LBM), fat-free mass (FFM), and skeletal muscle mass (SMM) loss following bariatric surgery. A systematic literature search was conducted in Pubmed, Embase, and Web of Science. Fifty-nine studies assessed LBM (n = 37), FFM (n = 20), or SMM (n = 3) preoperatively and ≥1 time points postsurgery. Random-effects meta-analyses were performed to determine pooled loss per outcome parameter and follow-up time point. At 12-month postsurgery, pooled LBM loss was -8.13 kg [95%CI -9.01; -7.26]. FFM loss and SMM loss were -8.23 kg [95%CI -10.74; -5.73] and -3.18 kg [95%CI -5.64; -0.71], respectively. About 55% of 12-month LBM loss occurred within 3-month postsurgery, followed by a more gradual decrease up to 12 months. Similar patterns were seen for FFM and SMM. In conclusion, >8 kg of LBM and FFM loss was observed within 1-year postsurgery. LBM, FFM, and SMM were predominantly lost within 3-month postsurgery, highlighting that interventions to mitigate such losses should be implemented perioperatively.Lotus seed pod (LSP) has been used as traditional herbal cuisine to modulate immunity. From the EtOAc-soluable extract of LSP, one new aporphine alkaloid, N -[2-((3,4-methylenedioxy)phenanthrenyl)ethyl]acetamide (nelunucine A, 1 ) was obtained along with 19 known ones. Their structures were established by detailed analysis of the 1D-, 2D-NMR, and HRESIMS data. N-Nornuciferine ( 9 ) and lirinidine ( 10 ) showed potent in vitro anti-food allergic activity with IC50 values of 40.0 and 55.4 μM, respectively, compared to 91.4 μM for loratadine, the positive control.We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that can cause infertility; however, the underlying mechanisms remain ill-defined, and there are no available drugs or strategies for the treatment of PCOS. This study examined the therapeutic effect of resveratrol in a rat model of PCOS.

PCOS is induced in rats by administration of letrozole and a high fat diet to determine whether resveratrol has a protective effect. Oral administration of resveratrol significantly decreased body weight, as well as the serum levels of testosterone and follicle stimulating hormone. Resveratrol improved the estrous cycle by restoring the thickness and number of granular cells. Resveratrol increased the levels of lactate and ATP, decreased pyruvate levels, and restored the glycolytic process, upregulating LDHA, HK2, and PKM2. Resveratrol also upregulated SIRT2, thereby modulating the expression of rate-limiting enzymes of glycolysis.

Resveratrol suppressed damage to the ovaries in PCOS rats by restoring glycolytic activity, providing potential targets for the treatment of PCOS.

Resveratrol suppressed damage to the ovaries in PCOS rats by restoring glycolytic activity, providing potential targets for the treatment of PCOS.In the recent past, Caenorhabditis elegans has emerged as one of the leading nematode models for studying host-microbe interactions on molecular, cellular, or organismal levels. In general, morphological and functional similarities of the gut of C. elegans with respect to that of human has brought in speculations on the study of the intestinal microbiota. On the other hand, probiotics have proved their efficacy in metabolism, development, and pathogenesis thereby inducing an immune response in C. elegans. Nurturing C. elegans with probiotics has led to immunomodulatory effects in the intestinal microbiota, proposing C. elegans as one of the in vivo screening criteria to select potential probiotic bacteria for host health-promoting factors. The major prospect of these probiotics is to exert longevity toward the host in diverse environmental conditions. The extent of research on probiotic metabolism has shed light on mechanisms of the immunomodulatory effect exerted by the nematode model. This review discusses various aspects of the effects of probiotics in improving the health and mechanisms involved in conferring immunity in C. elegans.