Explore the vast range of titles available.

Objectives: Polybutylcyanoacrylate (PBCA) nanoparticles (NPs) were prepared by emulsion polymerization and loaded with an enhanced green fluorescent protein plasmid (pEGFP) encoding human brain-derived neurotrophic factor (BDNF). This study investigated the potential effects of PBCA-pEGFP-BDNF NPs for the treatment of experimental cerebral hemorrhage mouse model animals. Methods: Eight-week-old male mice (30 ± 5 g) were randomly divided into four groups (sham, intracerebral hemorrhage (ICH), ICH+PBCA NPs, and ICH+ PBCA-pEGFP-BDNF NPs; n = 14). An ICH model was constructed by right striatum injection of bacterial collagenase VII. Neurological function was evaluated by modified Garcia score after treatment of ICH mice with PBCA-pEGFP-BDNF NPs. The area of cerebral hematoma was measured and the water content of brain tissues was calculated by the wet/dry ratio method. Finally, immunofluorescence staining was used to detect neuron-specific nuclear protein (NeuN) positive cells around hematomas. Enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (qPCR), and western blot were used to detect inflammatory BDNF, nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and either interleukin-1 beta (IL-1β) mRNA or protein levels. Results: Treatment with PBCA-pEGFP-BDNF NPs significantly improved neurological function and reduced acute brain edema and neuroinflammation in the mouse model of ICH. qPCR, ELISA, and western blot results showed that PBCA-pEGFP-BDNF NPs increased BDNF expression, inhibited NF-κB signaling pathway activity, and decreased the levels of inflammatory factors (IL-6, TNF-α, IL-1β) when compared with the recombinant plasmid pEGFP-BDNF. Conclusion: PBCA-pEGFP-BDNF NPs improves neurological function in experimental ICH mice at least in part related to increased BDNF expression and decreased p65 NF-κB signaling axis activation, suggesting that PBCA NPs might be a suitable pEGFP-BDNF-carrying delivery system for ICH treatment.

Estimating the grassland carbon budget is critically important for ensuring that grassland resources are used sustainably. However, the spatiotemporal dynamics of the carbon budget and the response to grazing have not yet been characterized in Qinghai grasslands. Here, we estimated the gross primary productivity (GPP) and net ecosystem exchange (NEE) in Qinghai grasslands using the improved Biome-BGCMuSo model to characterize the spatiotemporal dynamics of the carbon budget and the response to grazing in this region from 1979 to 2018. The GPP of Qinghai grasslands fluctuated during the study period, with an average annual value of 118.78 gC/m 2 . The NEE of Qinghai grasslands fluctuated from 1979 to 2018, with an average value of −5.16 gC/m 2 . After 2,000, GPP increased, and NEE decreased in a fluctuating manner. There were clear regional differences in GPP and NEE. GPP was low in most areas of Qinghai, and GPP was high in eastern and southern Qinghai. The southern, southeastern, and northeastern parts of Qinghai were mainly carbon sinks, and the northwestern part of Qinghai and the region between the southeastern and northeastern parts of Qinghai were mainly carbon sources. Grazing generally decreased GPP and increased NEE in Qinghai grasslands from 1979 to 2018. There was spatial heterogeneity in the effect of grazing on GPP and NEE. Under grazing, GPP and NEE were significantly decreased mainly in eastern Qinghai, and GPP and NEE were significantly increased mainly in southern and eastern Qinghai. NEE was most affected by grazing in eastern Qinghai. The results of this study aid our understanding of the mechanism driving variation in the grassland carbon budget and provide new data that could be used to support local grassland management.

WSGP has demonstrated significant potential for various bioactive effects. However, limited research has explored their anti-ulcerative colitis (UC) effects and mechanism on the colonic system and gut microbial metabolites. We evaluated the ameliorative effects of WSGP on the UC mice model. Using H&E to assess histological injury of colon morphology, AB-PAS staining to detect mucin secretion from goblet cells and the mucous layer, IF to evaluate the expression of intercellular tight junction proteins, ELISA to measure inflammatory factors, WB analysis to measure protein expression of inflammatory signaling pathways, RT-qPCR to quantify gene transcription of inflammatory factors, and LC-MS to analyze metabolites in mouse cecum contents. WSGP supplementation increased food intake, body weight, and colon length while reducing disease activity and histological scores in colitis-afflicted mice. WSGP mitigated colonic tissue damage and restored intestinal barrier integrity by suppressing NF-κB/STAT3 signaling, thereby decreasing gene transcription, protein expression of proinflammatory factors, and nitric oxide production. Additionally, WSGP improved UC by altering the variety of intestinal microbial metabolites. This study demonstrates that WSGP supplementation attenuates UC mice by suppressing the NF-κB/STAT3 signaling pathway, enhancing mucosal barrier function, reducing pro-inflammatory cytokines, and modulating gut microbial metabolites.

Acute kidney injury (AKI) is prevalent and a leading cause of in-hospital death worldwide. Early prediction of AKI-related clinical events and timely intervention for high-risk patients could improve outcomes. We develop a deep learning model based on a nationwide multicenter cooperative network across China that includes 7,084,339 hospitalized patients, to dynamically predict the risk of in-hospital death (primary outcome) and dialysis (secondary outcome) for patients who developed AKI during hospitalization. A total of 137,084 eligible patients with AKI constitute the analysis set. In the derivation cohort, the area under the receiver operator curve (AUROC) for 24-h, 48-h, 72-h, and 7-day death are 95·05%, 94·23%, 93·53%, and 93·09%, respectively. For dialysis outcome, the AUROC of each time span are 88·32%, 83·31%, 83·20%, and 77·99%, respectively. The predictive performance is consistent in both internal and external validation cohorts. The model can predict important outcomes of patients with AKI, which could be helpful for the early management of AKI. Early prediction of AKI-related clinical events and timely intervention for high-risk patients could improve outcomes. Here, the authors show a deep learning model that can identify patients with acute kidney injury (AKI) who are at high risk of death or dialysis at certain time points.

Dihydroquercetin (DHQ) is a flavonoid compound known for its anti-oxidant effects. Oxidative stress plays a dominant role in regulating the pathways associated with systemic inflammatory immune activation during endotoxemia. Whether and how DHQ regulates inflammatory responses in endotoxemia remains elusive. Here we show DHQ pretreatment effectively reduced the Ten-day mortality in bacterial endotoxin lipopolyssacharide (LPS)-challenged mice, suppressing LPS-induced inflammatory responses reflected by impaired production of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in the serum of mice. In Raw 264.7 cells, DHQ pretreatment significantly inhibited the transcriptional upregulation of TNF-α, interferon-γ (IFN-γ), interleukin-10 (IL-10) and toll-like receptor 4 (TLR-4) after LPS stimulation. Additionally, knockdown of heme oxygenase-1 (HO-1), one of the most important DHQ induced antioxidant genes, cancelled the inhibition of DHQ treatment on LPS induced TNF-α, IFN-γ production. Nuclear factor erythroid 2-related factor 2 (Nrf2) expression and AMP-activated protein kinase (AMPK) phosphorylation were both enhanced by DHQ in Raw 264.7 cells, indicating a DHQ induced AMPK/Nrf2/HO-1 signal axis. In conclusion, DHQ pretreatment could protect mice against the inflammation and mortality associated with endotoxemia.

With high resolution and wide coverage, satellite precipitation products like Global Precipitation Measurement (GPM) could support hydrological/ecological research in the Tianshan Mountains, where the spatial heterogeneity of precipitation is high, but where rain gauges are sparse and unevenly distributed. Based on observations from 46 stations from 2014–2015, we evaluated the accuracies of three satellite precipitation products: GPM, Tropical Rainfall Measurement Mission (TRMM) 3B42, and the Climate Prediction Center morphing technique (CMORPH), in the Tianshan Mountains. The satellite estimates significantly correlated with the observations. They showed a northwest–southeast precipitation gradient that reflected the effects of large-scale circulations and a characteristic seasonal precipitation gradient that matched the observed regional precipitation pattern. With the highest correlation (R = 0.51), the lowest error (RMSE = 0.85 mm/day), and the smallest bias (1.27%), GPM outperformed TRMM and CMORPH in estimating daily precipitation. It performed the best at both regional and sub-regional scales and in low and mid-elevations. GPM had relatively balanced performances across all seasons, while CMORPH had significant biases in summer (46.43%) and winter (−22.93%), and TRMM performed extremely poorly in spring (R = 0.31; RMSE = 1.15 mm/day; bias = −20.29%). GPM also performed the best in detecting precipitation events, especially light and moderate precipitation, possibly due to the newly added Ka-band and high-frequency microwave channels. It successfully detected 62.09% of the precipitation events that exceeded 0.5 mm/day. However, its ability to estimate severe rainfall has not been improved as expected. Like other satellite products, GPM had the highest RMSE and bias in summer, suggesting limitations in its way of representing small-scale precipitation systems and isolated deep convection. It also underestimated the precipitation in high-elevation regions by 16%, suggesting the difficulties of capturing the orographic enhancement of rainfall associated with cap clouds and feeder–seeder cloud interactions over ridges. These findings suggest that GPM may outperform its predecessors in the mid-/high-latitude dryland, but not the tropical mountainous areas. With the advantage of high resolution and improved accuracy, the GPM creates new opportunities for understanding the precipitation pattern across the complex terrains of the Tianshan Mountains, and it could improve hydrological/ecological research in the area.

The role of statin therapy in the development of kidney disease in patients with type 2 diabetes mellitus (DM) remains uncertain. We aimed to determine the relationships between statin initiation and kidney outcomes in patients with type 2 DM. Through a new-user design, we conducted a multicentre retrospective cohort study using the China Renal Data System database (which includes inpatient and outpatient data from 19 urban academic centres across China). We included patients with type 2 DM who were aged 40 years or older and admitted to hospital between Jan. 1, 2000, and May 26, 2021, and excluded those with pre-existing chronic kidney disease and those who were already on statins or without follow-up at an affiliated outpatient clinic within 90 days after discharge. The primary exposure was initiation of a statin. The primary outcome was the development of diabetic kidney disease (DKD), defined as a composite of the occurrence of kidney dysfunction (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2 and > 25% decline from baseline) and proteinuria (a urinary albumin-to-creatinine ratio ≥ 30 mg/g and > 50% increase from baseline), sustained for at least 90 days; secondary outcomes included development of kidney function decline (a sustained > 40% decline in eGFR). We used Cox proportional hazards regression to evaluate the relationships between statin initiation and kidney outcomes, as well as to conduct subgroup analyses according to patient characteristics, presence or absence of dyslipidemia, and pattern of dyslipidemia. For statin initiators, we explored the association between different levels of lipid control and outcomes. We conducted analyses using propensity overlap weighting to balance the participant characteristics. Among 7272 statin initiators and 12 586 noninitiators in the weighted cohort, statin initiation was associated with lower risks of incident DKD (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.62–0.83) and kidney function decline (HR 0.60, 95% CI 0.44–0.81). We obtained similar results to the primary analyses for participants with differing patterns of dyslipidemia, those prescribed different statins, and after stratification according to participant characteristics. Among statin initiators, those with intensive control of high-density lipoprotein cholesterol (LDL-C) (< 1.8 mmol/L) had a lower risk of incident DKD (HR 0.51, 95% CI 0.32–0.81) than those with inadequate lipid control (LDL-C ≥ 3.4 mmol/L). For patients with type 2 DM admitted to and followed up in academic centres, statin initiation was associated with a lower risk of kidney disease development, particularly in those with intensive control of LDL-C. These findings suggest that statin initiation may be an effective and reasonable approach for preventing kidney disease in patients with type 2 DM.

Background Urinary tract infections (UTIs) are an important concomitant condition among patients with intracerebral hemorrhage (ICH). Data regarding predictors, outcomes and trends relating to UTIs in ICH are lacking. Methods A retrospective analysis of data from the Nationwide Inpatient Sample (NIS) for the years January 1, 2010–December 31, 2022 was conducted, employing multivariable logistic regression to examine the associated factors and temporal trends of UTIs in patients with ICH. Results Between 1 January 2010 and 31 December 2022, the NIS database contained an unweighted total of 311,581 hospitalizations (weighted estimate, 1,554,702) with ICH coded as either a primary or secondary diagnosis. Among these, 42,271 hospitalizations were combined with UTIs. Our analysis revealed a significant down-trend in the occurrence of UTIs among patients with ICH over the 12-year period, resulting in an overall occurrence rate of 13.6%. The identified associated factors for UTIs included advanced age (≥ 45), female individuals, Black individuals, Hispanic individuals, comorbidities (≥ 1), Charlson comorbidity index (CCI) ≥ 3, medium/large hospital and treatment in South regional hospital. Significant comorbidities that increased the odds of UTIs included deficiency anemia, depression, diabetes (with complications), congestive heart failure, fluid and electrolyte disorders, paralysis, psychoses, peptic ulcer disease excluding bleeding and weight loss. Patients who developed UTIs were associated with worse clinical outcomes, including more frequent conditions (pressure ulcer, pneumonia, transfusion, acute renal failure, deep vein thrombosis, delirium, malnutrition, sepsis), significantly longer hospitalization periods (median 10 vs. 5 days), and substantially increased healthcare expenditures (median $100,923 vs. $62,928). Interestingly, patients with UTIs were associated with lower in-hospital mortality (13.0% vs. 22.9%) ( P  < 0.001). Conclusions There is an association between UTIs and increased healthcare utilization in the setting of ICH. This study revealed several predictors/associated factors of UTIs occurrence with ICH among a nationally representative sample in the United States. These data may assist physicians and healthcare providers in identifying patients at increased risk for UTIs in ICH and, hence, initiate timely interventions.

Neuroinflammation is a common feature of many neurological diseases, and remains crucial for disease progression and prognosis. Activation of microglia and astrocytes can lead to neuroinflammation. However, little is known about the role of lncRNA xist and miR-122-5p in the pathogenesis of sepsis-associated neuroinflammation (SAN). This study aims to investigate the role of lncRNA xist and miR-122-5p in the pathogenesis of SAN. Levels of miR-122-5p and proinflammatory mediators were detected in the cerebrospinal fluid (CSF) of patients with intracranial infection (ICI) by ELISA and qRT-PCR. miRNA expression in the periventricular white matter (PWM) in rats was analyzed by high-throughput sequencing. Levels of lncRNA xist, miR-122-5p and proinflammatory mediators in the PWM were measured using qRT-PCR and western blot. Bioinformatics analysis was used to predict the upstream and downstream of miR-122-5p. The interaction between miR-122-5p and its target protein was validated using luciferase reporter assay. BV2 and astrocytes were used to detect the expression of lncRNA xist, miR-122-5p. The level of miR-122-5p was significantly decreased in the CSF of ICI patients, while the expression of IL-1β and TNF-α were significantly upregulated. Furthermore, it was found that the expression of IL-1β and TNF-α were negatively correlated with the level of miR-122-5p. A high-throughput sequencing analysis showed that miR-122-5p expression was downregulated with 1.5-fold changes in the PWM of CLP rats compared with sham group. Bioinformatics analysis found that lncRNA xist and PKCη were the upstream and downstream target genes of miR-122-5p, respectively. The identified lncRNA xist and PKCη were significantly increased in the PWM of CLP rats. Overexpression of miR-122-5p or knockdown of lncRNA xist could significantly downregulate the level of PKCη and proinflammatory mediators from activated microglia and astrocytes. Meanwhile, investigation showed that silencing lncRNA xist or PKCη or enhancing the expression of miR-122-5p could obviously inhibit the release of proinflammatory mediators in activated BV2 cells and astrocytes. LncRNA xist could regulate microglia and astrocytes activation in the PWM of CLP rats via miR-122-5p/PKCη axis, further mediating sepsis associated neuroinflammation.