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echniques could help enhance the quality of these metagenomic analyses by providing more accurate identification of the genetic and functional potential of a microbial community.Scleroderma, or systemic sclerosis, is a multi-organ connective tissue disease resulting in fibrosis of the skin, heart, and lungs with no effective treatment. Endocannabinoids acting via cannabinoid-1 receptors (CB1R) and increased activity of inducible NO synthase (iNOS) promote tissue fibrosis including skin fibrosis, and joint targeting of these pathways may improve therapeutic efficacy. Recently, we showed that in mouse models of liver, lung and kidney fibrosis, treatment with a peripherally restricted hybrid CB1R/iNOS inhibitor (MRI-1867) yields greater anti-fibrotic efficacy than inhibiting either target alone. Here, we evaluated the therapeutic efficacy of MRI-1867 in bleomycin-induced skin fibrosis. Skin fibrosis was induced in C57BL/6J (B6) and Mdr1a/b-Bcrp triple knock-out (KO) mice by daily subcutaneous injections of bleomycin (2 IU/100 µL) for 28 days. Starting on day 15, mice were treated for 2 weeks with daily oral gavage of vehicle or MRI-1867. Skin levels of MRI-1867 and endocannabinoids were We conclude that combined inhibition of CB1R and iNOS is an effective anti-fibrotic strategy for scleroderma. As bleomycin induces an artifact in testing antifibrotic drug candidates that are substrates of drug-efflux transporters, using Mdr1a/b-Bcrp KO mice for preclinical testing of such compounds avoids this pitfall.The acclimatization of brown adipose tissue (BAT) to sustained cold exposure requires an adaptive increase in proteasomal protein quality control. Ubiquilins represent a recently identified family of shuttle proteins with versatile functions in protein degradation, such as facilitating substrate targeting and proteasomal degradation. However, whether ubiquilins participate in brown adipocyte function has not been investigated so far. mTOR inhibition Here, we determine the role of ubiquilins for proteostasis and non-shivering thermogenesis in brown adipocytes. We found that Ubqln1, 2 and 4 are highly expressed in BAT and their expression was induced by cold and proteasomal inhibition. Surprisingly, silencing of ubiquilin gene expression (one or multiple in combinations) did not lead to aggravated ER stress or inflammation. Moreover, ubiquitin level and proteasomal activity under basal conditions were not impacted by loss of ubiquilins. Also, non-shivering thermogenesis measured by norepinephrine-induced respiration remained intact after loss of ubiquilins. In conclusion, ubiquilin proteins are highly abundant in BAT and regulated by cold, but they are dispensable for brown adipocyte proteostasis and thermogenesis.

It has been well documented that left ventricular hypertrophy (LVH) is highly associated with the incidence of cardiovascular disease (CVD). Evidence indicated that high sodium intake was closely related with LVH in general population. However, information is not available regarding the association between urinary sodium excretion and LVH in patients with type 2 diabetes mellitus (T2DM). This study aimed to explore the association between urinary sodium excretion and LVH in patients with T2DM.

This cross-sectional analysis included baseline data from 1,556 individuals with T2DM enrolled in the NanFang Prospective Diabetes Study (NFPDS). Urinary sodium excretion levels were measured from 24-hour urine samples of inpatients and morning fasting urine samples of outpatients. Left ventricular dimensions were assessed by echocardiography. The associations between urinary sodium excretion and the risks of cardiovascular events, LVH and left ventricular mass index (LVMI) were examined using linear regression anal that high urinary sodium excretion was independently associated with increased risk of LVH and CVD in patients with T2DM, suggesting that control of sodium intake may be valuable for the prevention of diabetic cardiovascular complications.Sarcopenia and osteoporosis are common musculoskeletal comorbidities of chronic obstructive pulmonary disease (COPD) that seriously affect the quality of life and prognosis of the patient. In addition to spatially mechanical interactions, muscle and bone can also serve as endocrine organs by producing myokines and osteokines to regulate muscle and bone functions, respectively. As positive and negative regulators of skeletal muscles, the myokines irisin and myostatin not only promote/inhibit the differentiation and growth of skeletal muscles, but also regulate bone metabolism. Both irisin and myostatin have been shown to be dysregulated and associated with exercise and skeletal muscle dysfunction in COPD. During exercise, skeletal muscles produce a large amount of IL-6 which acts as a myokine, exerting at least two different conflicting functions depending on physiological or pathological conditions. Remarkably, IL-6 is highly expressed in COPD, and considered to be a biomarker of systemic inflammation, which is associated with both sarcopenia and bone loss. For osteokines, receptor activator of nuclear factor kappa-B ligand (RANKL), a classical regulator of bone metabolism, was recently found to play a critical role in skeletal muscle atrophy induced by chronic cigarette smoke (CS) exposure. In this focused review, we described evidence for myokines and osteokines in the pathogenesis of skeletal muscle dysfunction/sarcopenia and osteoporosis in COPD, and proposed muscle-bone crosstalk as an important mechanism underlying the coexistence of muscle and bone diseases in COPD.The present study aimed to assess whether women with polycystic ovarian syndrome (PCOS) ≥35 years age undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles experienced a higher cumulative live birth rate (CLBR) over a two-year period compared with age- and body mass index (BMI)-matched patients with tubal factor infertility. Through propensity score matching (PSM) approach, the authors retrospectively analyzed the IVF/ICSI outcomes of 263 PCOS patients (35-46 years of age [mean, 37 years]) and 526 age- and BMI-matched tubal factor controls two years after oocyte retrieval. Multivariate regression analysis was performed to explore factors influencing cumulative live birth. Women with PCOS exhibited better ovarian reserve and response, and higher CLBR in two years compared with age- and BMI-matched controls (CLBR 55.51% in PCOS vs. 38.02% in control, p less then 0.001). Multivariate logistic regression analysis revealed that the number of transferable embryos and antral follicle counts were both significant independent factors predicting cumulative live birth after adjusting for female age, female body mass index, percentage of transferred blastocysts, number of embryos transferred per embryo-transfer cycle, diagnosis of PCOS and freeze-all cycles (p less then 0.001, p=0.045). Women with PCOS ≥ 35 years of age demonstrated a higher CLBR over two years compared with age- and BMI-matched controls. This could be explained by favorable oocyte reserve and more available embryos compared with controls, which overcome the compromised oocyte quality in aged PCOS patients.Objective The clinical characteristics of patients with PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) and PANS (pediatric acute-onset neuropsychiatric syndrome) and the efficacy of antibiotic therapy with psychotherapy and antipsychotics were investigated to improve neurological symptoms as well as obsessive compulsive disorder (OCD). Methods We retrospectively analyzed 62 patients with a clinical diagnosis of PANDAS/PANS enrolled from May 14, 2013 to September 15, 2020 in the Neurology Childhood Division, Department of Pediatrics at Sapienza, Rome. Clinical manifestations, neurological and psychiatric, laboratory investigations, and familiar history were collected to evaluate the differences between the two groups. The effects of various therapeutic approaches were examined. Descriptive and comparative statistical analyses were performed. Results The mean age at onset of PANDAS/PANS symptoms was 6.2 ± 1.2 years. The most common diagnosis was PANDAS, followedhildren with PANS and the levels of anti-streptolysin O and anti-DNAse B were higher in PANDAS. Another relevant finding is the efficacy of psychotherapy, especially for obsessive-compulsive disorder, and of antibiotic prophylaxis in managing acute neurological symptoms.Hypertension with high homocysteine (Hcy, ≥10 μmol/L) is also known as H-type hypertension (HHT) and proposed as an independent risk factor for stroke and cognitive impairment. Although previous studies have established the relationships among hypertension, Hcy levels, and cognitive impairment, how they affect brain neuroanatomy remains unclear. Thus, we aimed to investigate whether and to what extent hypertension and high Hcy may affect gray matter volume in 52 middle-aged HHT patients and 51 demographically matched normotensive subjects. Voxel-based morphological analysis suggested that HHT patients experienced significant gray matter loss in the default network. The default network atrophy was significantly correlated with Hcy level and global cognitive function. These findings provide, to our knowledge, novel insights into how HHT affects brain gray matter morphology through blood pressure and Hcy.It is an unmet need to estimate survival duration for patients with progressive supranuclear palsy (PSP). The objective of this study was to identify factors associated with the survival duration in patients with PSP. We followed up 23 patients with probable PSP-RS (Richardson syndrome) or PSP-P (parkinsonism) in our PSP center until death from 2011 to 2019. We prospectively and quantitatively rated their downgaze palsy whenever first noticed in our clinic. This was utilized along with the disease duration, motor function, medication use for parkinsonism, sex, age at onset of PSP, comorbid pulmonary and cardiovascular diseases, and the total survival duration from the onset of PSP to death for prediction analysis. A well-fitted linear regression model and a multivariant Cox model were applied to identify predicting factors for total survival duration. All patients had the specific hummingbird sign on brain MRI for PSP when downgaze palsy was documented. We found that the severity of downgaze palsy and the disease duration at the assessment were consistently correlated with the total survival duration in both models. The total survival duration could be further estimated by a formed regression equation. We conclude that severity and time to develop downgaze palsy could help to estimate the total survival duration in patients with probable PSP-RS and PSP-P, the major forms of PSP, which has significant clinical applications in clinical counseling and trial enrollment.Background The management of patients with symptomatic non-acute intracranial artery occlusion (sNA-ICAO), which is a special subset with high morbidity and a high probability of recurrent serious ischemic events despite standard medical therapy (SMT), has been clinically challenging. A number of small-sample clinical studies have also discussed endovascular recanalization (ER) for sNA-ICAO; however, there is currently a lack of evidence from multicenter, prospective, large-sample cohort trials. The purpose of our present study was to evaluate the technical feasibility and safety of ER for sNA-ICAO. Methods Our group is currently undertaking a multisite, non-randomized cohort, prospective registry study enrolling consecutive patients presenting with sNA-ICAO at 15 centers in China between January 1, 2020 and December 31, 2022. A cohort of patients who received SMT and a cohort of similar patients who received ER plus SMT were constructed and followed up for 2 years. The primary outcome is any stroke from enrollment to 2 years of follow-up.