Cullenrees6400

Their distribution in sediments was influenced by multiple factors including geographic separation and the key environmental variables of total organic carbon and total phosphorus, and responded to terrestrial inputs and coastal aquaculture activities. The results of this study provide novel insights into the benthic virus communities potentially participating in phosphorus cycling in the ocean.Over the past few decades, rapid advances of nucleic acid nanotechnology always drive the development of nanoassemblies with programmable design, powerful functionality, excellent biocompatibility and outstanding biosafety. Nowadays, nucleic acid-based self-assembling nanocarriers (NASNs) play an increasingly greater role in the research and development in biomedical studies, particularly in drug delivery, release and targeting. In this review, NASNs are systematically summarized the strategies cooperated with their broad applications in drug delivery. We first discuss the self-assembling methods of nanocarriers comprised of DNA, RNA and composite materials, and summarize various categories of targeting media, including aptamers, small molecule ligands and proteins. Furthermore, drug release strategies by smart-responding multiple kinds of stimuli are explained, and various applications of NASNs in drug delivery are discussed, including protein drugs, nucleic acid drugs, small molecule drugs and nanodrugs. Lastly, we propose limitations and potential of NASNs in the future development, and expect that NASNs enable facilitate the development of new-generation drug vectors to assist in solving the growing demands on disease diagnosis and therapy or other biomedicine-related applications in the real world.As a research hotspot, immune checkpoint inhibitors (ICIs) is often combined with other therapeutics in order to exert better clinical efficacy. To date, extensive laboratory and clinical investigations into the combination of ICIs and chemotherapy have been carried out, demonstrating augmented effectiveness and broad application prospects in anti-tumor therapy. However, the administration of these two treatment modalities is usually randomized or fixed to a given chronological order. Nevertheless, the pharmacological effect of drug is closely related to its exposure behavior in vivo, which may consequently affect the synergistic outcomes of a combined therapy. In this study, we prepared a lipid nanoparticle encapsulating docetaxel (DTX-VNS), and associated it with the immune checkpoint inhibitor anti-PD-1 antibody (αPD-1) for the treatment of malignant tumors. To identify the optimum timing and sequencing for chemotherapy and immunotherapy, we designed three administration regimes, including the simultaneous delivery of DTX-VNS and αPD-1(DTX-VNS@αPD-1), DTX-VNS delivery before (DTX-VNS plus αPD-1) or post (αPD-1 plus DTX-VNS) PD-1 blockade with an interval of two days. Analysis from mass spectrometry, multi-factor detection and other techniques indicated that DTX-VNS plus αPD-1 initiated a powerful anti-tumor response in multiple tumor models, contributing to a remarkably reshaped tumor microenvironment landscape, which may attribute to the maximum therapeutic additive effects arise from a concomitant exposure of DTX-VNS and αPD-1 at the tumor site. By profiling the exposure kinetics of nanoparticles and αPD-1 in vivo, we defined the administration schedule with utmost therapeutic benefits, which may provide a valuable clinical reference for the rational administration of immunochemotherapy.

Enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 methyltransferase, has been shown to play a role in kidney diseases. However, its role in hyperoxaluria-induced renal tubular epithelial cells (TECs) injury remains unclear.

A hyperoxaluria rat model was established by providing 0.5% ammonium chloride and drinking water containing 1% ethylene glycol. TECs were exposed to oxalate stress. The 3-DZNeP, a selective EZH2 inhibitor, was administered in vivo and in vitro. Cell viability, ROS production, and apoptosis ratio were evaluated. Crystal deposition was detected by Von Kossa staining and kidney tissue injury was detected by HE staining and TUNEL. EZH2, H3K27me3, cleaved-caspase3, IL-6, and MCP-1 were examined by western blot or immunohistochemistry.

Inhibition of EZH2 by 3-DZNeP significantly attenuated hyperoxaluria-induced oxidative and inflammatory injury and CaOx crystal deposition in vivo. Similarly, inhibition of EZH2 using 3-DZNeP or shRNA restored cell viability, suppressed LDH release and the production of intracellular ROS in vitro. Furthermore, the MAPK signaling pathway and FoxO3a levels were activated or elevated in TECs exposed to oxalate. EZH2 inhibition using 3-DZNeP blocked these effects. CC90003 (ERK inhibitor) or SB203580 (p38 inhibitor) did not significantly affect the expression of FoxO3a in TECs treated with 3-DZNeP and oxalate; only SP600125 (JNK inhibitor) significantly decreased FoxO3a expression.

EZH2 inhibition protects against oxalate-induced TECs injury and reduces CaOx crystal deposition in the kidney may by modulating the JNK/FoxO3a pathway; EZH2 may be a promising therapeutic target in TECs injury.

EZH2 inhibition protects against oxalate-induced TECs injury and reduces CaOx crystal deposition in the kidney may by modulating the JNK/FoxO3a pathway; EZH2 may be a promising therapeutic target in TECs injury.

The progressive decline in estrogen level puts postmenopausal women at a higher risk of developing cardiometabolic diseases. Thus, we evaluated the potential beneficial effects of yacon-based product (YBP) on glycemic profile and intestinal health of postmenopausal rats.

Eighty Wistar rats were randomized into 4 ovariectomized (OVX) groups or 4 celiotomized groups treated with a standard diet (SD) or diet supplemented with YBP at 6% of fructooligosaccharide (FOS)/inulin.

The continued consumption of YBP at 6% of FOS/inulin did not generate liver damage and gastrointestinal disorders. Rats fed with YBP displayed higher food consumption, but this did not increase the body weight gain, abdominal circumference and body fat percentual of OVX rats. Furthermore, we also found that the FOS/inulin fermentation present in the YBP resulted in cecum, ileum and colon crypts hypertrophy and increased the lactic acid levels in the cecal content. We observed an increase of glucagon-like peptide-1 (GLP-1) immunoreactive cells and there was no change in the glucose and insulin plasma levels of YBP-fed OVX rats.

Our findings indicated that YBP when consumed previously and after the menopausal period has important effects on the morphology and function of intestinal mucous of rats and has potential to modulate indirectly the glycemic and insulinemic profiles, weight gain and body fat percentual in the hypoestrogenic period through metabolites produced in the fermentation process.

Our findings indicated that YBP when consumed previously and after the menopausal period has important effects on the morphology and function of intestinal mucous of rats and has potential to modulate indirectly the glycemic and insulinemic profiles, weight gain and body fat percentual in the hypoestrogenic period through metabolites produced in the fermentation process.Tumor cells can develop resistance to cell death which is divided into necrosis and programmed cell death (PCD). PCD, including apoptosis, autophagy, ferroptosis, pyroptosis, and necroptosis. Ferroptosis and pyroptosis, two new forms of cell death, have gradually been of interest to researchers. Boosting ferroptosis and pyroptosis of tumor cells could be a potential cancer therapy. Nitric oxide (NO) is a ubiquitous, lipophilic, highly diffusible, free-radical signaling molecule that plays various roles in tumorigenesis. In addition, NO also has regulatory mechanisms through S-nitrosylation that do not depend on the classic NO/sGC/cGMP signaling. The current tumor treatment strategy for NO is to promote cell death through promoting S-nitrosylation-induced apoptosis while multiple drawbacks dampen this tumor therapy. However, numerous studies have suggested that suppression of NO is perceived to active ferroptosis and pyroptosis, which could be a better anti-tumor treatment. In this review, ferroptosis and pyroptosis are described in detail. We summarize that NO influences ferroptosis and pyroptosis and infer that S-nitrosylation mediates ferroptosis- and pyroptosis-related signaling pathways. It could be a potential cancer therapy different from NO-induced apoptosis of tumor cells. Finally, the information shows the drugs that manipulate endogenous production and exogenous delivery of NO to modulate the levels of S-nitrosylation.

We investigated the association between cardiovascular autonomic neuropathy (CAN) and incident diabetic kidney disease (DKD).

This retrospective longitudinal study included 2,033 patients with type 2 diabetes (mean age 57.2years, 57.4% male, and median diabetes duration 8.0years), free of renal dysfunction or cardiovascular disease at initiation. Cardiovascular autonomic reflex tests were performed once at baseline, and CAN was defined as≥2 abnormal parasympathetic test results. Urine ACR and eGFR were concurrently measured at baseline and every 3-6months thereafter. Incident DKD was defined as the development of ACR≥30mg/g at two or more follow-up examinations or eGFR<60ml/min/1.73m

with≥25% decrease from baseline.

During a median follow-up of 2.9years (1.1 - 4.8), 290 (14.3%) patients developed DKD, comprising 79.7% (N=231) cases of new-onset albuminuria alone, 14.5% (N=42) cases of eGFR decline alone, and 5.8% (N=17) cases of both. Compared to those without CAN, patients with CAN had a significantly higher risk of incident DKD in a multivariable Cox regression model (HR 1.56, 95% CI 1.15 - 2.12; P=0.005).

CAN is may be a useful marker for long-term complications including DKD in patients with type 2 diabetes. Monitoring of CAN helps to identify high risk patients of future renal impairment.

CAN is may be a useful marker for long-term complications including DKD in patients with type 2 diabetes. Monitoring of CAN helps to identify high risk patients of future renal impairment.

Cardiovascular events in the context of COVID-19 infection increase the risk of negative patient outcomes, but large cohort studies describing this association are limited. The purpose of the current study was to investigate the potential associations between cardiovascular events and mortality in patients hospitalized due to COVID-19.

A retrospective chart review was performed in 2450 patients hospitalized for confirmed COVID-19 infection within a single hospital network between March 15 and June 15, 2020. Logistic regression analysis was used to identify predictors of mortality.

In the study population, 57% of patients had elevated high sensitivity troponin (hs-TnT) levels. Acute heart failure occurred in 23% of patients and arrhythmias were observed in 8% of patients. Of the 1401 patients with elevated hs-TnT levels, a primary cardiac etiology (e.g., myocardial infarction) was identified in 653 (47%) patients. In the remaining 748 (53%) patients, there was evidence of a primary non-cardiac etiology for hs-TnT elevation such as renal failure (n=304) and critical illness (n=286).