Mesenchymal stem cells therapy for acute kidney injury: A systematic review with meta-analysis based on rat model

Objective: To systematically evaluate the efficacy of mesenchymal stem cells (MSCs) for acute kidney injury (AKI) in preclinical studies and to explore the optimal transplantation strategy of MSCs by network meta-analysis with the aim of improving the efficacy of stem cell therapy.Methods: Computer searches of PubMed, Web of Science, Cochrane, Embase, CNKI, Wanfang, VIP, and CBM databases were conducted until 17 August 2022. Literature screening, data extraction and quality evaluation were performed independently by two researchers.Results and Discussion: A total of 50 randomized controlled animal studies were included. The results of traditional meta-analysis showed that MSCs could significantly improve the renal function and injured renal tissue of AKI rats in different subgroups. The results of network meta-analysis showed that although there was no significant difference in the therapeutic effect between different transplant routes and doses of MSCs, the results of surface under the cumulative ranking probability curve (SUCRA) showed that the therapeutic effect of intravenous transplantation of MSCs was better than that of arterial and intrarenal transplantation, and the therapeutic effect of high dose (>1×106) was better than that of low dose (≤1×106). However, the current preclinical studies have limitations in experimental design, measurement and reporting of results, and more high-quality studies, especially direct comparative evidence, are needed in the future to further confirm the best transplantation strategy of MSCs in AKI.Systematic Review Registration: identifier https://CRD42022361199, https://www.crd.york.ac.uk/prospero

Enhanced Spontaneous Antibacterial Activity of delta-MnO2 by Alkali Metals Doping

Recently, the widespread use of antibiotics is becoming a serious worldwide public health challenge, which causes antimicrobial resistance and the occurrence of superbugs. In this context, MnO2 has been proposed as an alternative approach to achieve target antibacterial properties on Streptococcus mutans (S. mutans). This requires a further understanding on how to control and optimize antibacterial properties in these systems. We address this challenge by synthesizing delta-MnO2 nanoflowers doped by magnesium (Mg), sodium (Na), and potassium (K) ions, thus displaying different bandgaps, to evaluate the effect of doping on the bacterial viability of S. mutans. All these samples demonstrated antibacterial activity from the spontaneous generation of reactive oxygen species (ROS) without external illumination, where doped MnO2 can provide free electrons to induce the production of ROS, resulting in the antibacterial activity. Furthermore, it was observed that delta-MnO2 with narrower bandgap displayed a superior ability to inhibit bacteria. The enhancement is mainly attributed to the higher doping levels, which provided more free electrons to generate ROS for antibacterial effects. Moreover, we found that delta-MnO2 was attractive for in vivo applications, because it could nearly be degraded into Mn ions completely following the gradual addition of vitamin C. We believe that our results may provide meaningful insights for the design of inorganic antibacterial nanomaterials.Peer reviewe

Forebrain E-I balance controlled in cognition through coordinated inhibition and inhibitory transcriptome mechanism

IntroductionForebrain neural networks are vital for cognitive functioning, and their excitatory-inhibitory (E-I) balance is governed by neural homeostasis. However, the homeostatic control strategies and transcriptomic mechanisms that maintain forebrain E-I balance and optimal cognition remain unclear.MethodsWe used patch-clamp and RNA sequencing to investigate the patterns of neural network homeostasis with suppressing forebrain excitatory neural activity and spatial training.ResultsWe found that inhibitory transmission and receptor transcription were reduced in tamoxifen-inducible Kir2.1 conditional knock-in mice. In contrast, spatial training increased inhibitory synaptic connections and the transcription of inhibitory receptors.DiscussionOur study provides significant evidence that inhibitory systems play a critical role in the homeostatic control of the E-I balance in the forebrain during cognitive training and E-I rebalance, and we have provided insights into multiple gene candidates for cognition-related homeostasis in the forebrain

Measuring dynamic changes in the spatial pattern and connectivity of surface waters based on landscape and graph metrics: A case study of henan province in central china

An understanding of the scientific layout of surface water space is crucial for the sustainable development of human society and the ecological environment. The objective of this study was to use land-use/land-cover data to identify the spatiotemporal dynamic change processes and the influencing factors over the past three decades in Henan Province, central China. Multidisciplinary theories (landscape ecology and graph theory) and methods (GIS spatial analysis and SPSS correlation analysis) were used to quantify the dynamic changes in surface water pattern and connectivity. Our results revealed that the water area decreased significantly during the periods of 1990–2000 and 2010–2018 due to a decrease in tidal flats and linear waters, but increased significantly in 2000–2010 due to an increase in patchy waters. Human construction activities, socioeconomic development and topography were the key factors driving the dynamics of water pattern and connectivity. The use of graph metrics (node degree, betweenness centrality, and delta probability of connectivity) in combination with landscape metrics (Euclidean nearest-neighbor distance) can help establish the parameters of threshold distance between connected habitats, identify hubs and stepping stones, and determine the relatively important water patches that require priority protection or development

The Relative Risk and Incidence of Immune Checkpoint Inhibitors Related Pneumonitis in Patients With Advanced Cancer: A Meta-Analysis

Background: Recently, immune checkpoint inhibitors (ICIs) have been proved one of the most promising anti-cancer therapy, series clinical trials have confirmed their efficacy. But they are also associated with distinctive set of toxic effects, which are recognized as immune-related adverse events. Among those immune-related adverse events, pneumonitis is rare, but it is often clinically serious and potentially life-threatening. Although many clinical trial results of PD-1/PD-L1 inhibitors had been reported incidence of pneumonitis, the knowledge based on the individual cohort data from each clinical trial is limited. So we conducted a meta-analysis of trials of PD-1/PD-L1 inhibitors in patients with advanced cancer and compared relative risk and incidence among different tumor types and therapeutic regimens. Such an analysis may provide important knowledge of this rare but clinically significant and potentially serious immune-related adverse event.Methods: Electronic databases were used to search eligible literatures, include randomized controlled trials (RCTs) comparing immune checkpoint inhibitors vs. standard therapies. All-grade (1–4) or high-grade (3–4) pneumonitis events were extracted. The summary relative risk, summary incidence, and 95% confidence intervals were calculated.Results: The incidence of all-grade and high-grade pneumonitis in non-small cell lung cancer (NSCLC) was significantly higher compared with other tumor types, such as Melanoma, urothelial carcinoma (UC), head and neck squamous cell carcinoma (HNSCC) (3.1% vs. 2.0%; p = 0.02, 1.4% vs. 0.6%; p = 0.03). The risk of all-grade pneumonitis was obtained from all patients in both experimental arm and control arm. Treatment with immune checkpoint inhibitors targeting PD-1/PD-L1 did significantly increase the risk of all-grade and high-grade pneumonitis compared with controls (fixed effects, RR: 4.70; 95% CI: 2.81–7.85; p < 0.00001, RR: 3.33; 95% CI: 1.68–6.59; p = 0.0006).Conclusion: The incidence of immune checkpoint inhibitors related pneumonitis was higher in NSCLC than other tumor types. Patients treated with immune checkpoint inhibitor in experiment arms are more likely to experience any grade pneumonitis than control arms. These findings suggest that clinician need to draw more attention on this rare but serious adverse event

Experimental research on kinematics of breaking waves

One important kinematic properties of breaking waves is the wave celerity. Constant wave celerity has been used for the wave breaking criterion by many researchers. However, this approach does not consider the variation of wave celerity at different phases before breaking. Hence, this article examines the aspects of the wave breaking criterion and dynamics of wave celerity before wave breaking. Breaking waves were generated using the JONSWAP focused spectrum and a semi-empirical formula for the wave celerity estimation was established

Burden of falls attributable to low bone mineral density among people aged 60 years and over in China from 1990 to 2019

ObjectiveFalls in older people have become a major public health, economic and societal problem. Osteoporosis predisposes older adults to high risk of falls, which were the most common outcome attributable to low bone mineral density (LBMD). In this study, we analyze the long-term trends in falls burden attributable to LBMD among people aged 60 years and over from 1990 to 2019, using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019).MethodsData from GBD 2019 were used to assess the long-term trends in mortality and disability-adjusted life-year (DALY) rates by Joinpoint regression. The age-period-cohort (APC) model was used to evaluate the effects of age, period and cohort on mortality rate of falls attributable to LBMD.ResultsThe mortality and DALYs rates of falls attributable to LBMD among people aged 60 years and over increased from 1990 to 2019, with average annual percentage changes (AAPCs) of 1.74% (95% CI: −1.47 to 2.01%) and 0.99% (95% CI: 0.80–1.19%), respectively. APC analysis revealed that the mortality rate due to LBMD significantly increased among the older people over the age of 75 years. The risk of falls mortality due to LBMD during the period of 1990–2019 initially declined but later elevated. An overall increasing risk for falls death attributable to LBMD was presented across birth cohorts, but in cohorts born after 1930, the upward trend has slowed down. The overall net drift per year attributable to LBMD was above 0. The corresponding results showed that the negative impact of period and cohort effects among males was more pronounced than those among females.ConclusionsFalls attributable to LBMD remain an ongoing health burden in the older people in China, and the mortality has been on the rise from 1990 to 2019, especially among the older people aged 80+ years group. The prevention and treatment of LBMD should be emphasized, especially among males and oldest-old people. Furthermore, there is an urgent need to strengthen the implementation of system-wide, integrated and effective public health policies and other health interventions in China

Centrally Administered Cortistation-14 Induces Antidepressant-Like Effects in Mice via Mediating Ghrelin and GABAA Receptor Signaling Pathway

Cortistatin-14 (CST-14), a recently discovered cyclic neuropeptide, can bind to all five cloned somatostatin receptors (SSTRs) and ghrelin receptor to exert its biological activities and co-exists with GABA within the cortex and hippocampus. However, the role of CST-14 in the control of depression processes is not still clarified. Here, we tested the behavioral effects of CST-14 in the in a variety of classical rodent models of depression [forced swimming test (FST), tail suspension test (TST) and novelty-suppressed feeding test]. In the models of depression, CST-14 produced antidepressant-like effects, and does not altered locomotor activity levels. And, we found that CST-14 mRNA and BDNF mRNA were significantly decreased in the hippocampus and cortex after mice exposed to stress. Further data show that i.c.v. administration of CST-14 produce rapid antidepressant effects, and does not altered locomotor activity levels. Then these antidepressant-like effects were significantly reversed by [D-Lys3]GHRP-6 (ghrelin receptor antagonist), but not c-SOM (SSTRs antagonist). Meanwhile, the effects of some neurotransmitter blockers indicates that only GABAA system, but not CRF1 receptor, α/β-adrenergic receptor, is involved in the antidepressant effect of CST-14. The effects of the mTOR inhibitor (rapamycin), the PI3K inhibitor (LY294002) and the p-ERK1/2 inhibitor (U0126) suggesting that the ERK/mTOR or PI3K/Akt/mTOR signaling pathway is not involved in the antidepressant effects of CST-14. Interestingly, intranasal administration of CST-14 led to reducing depressive-like behavior, and near-infrared fluorescent experiments showed the real-time in vivo bio-distribution in brain after intranasal infusion of Cy7.5-CST-14. Taken all together, the results of present study point to a role for CST-14 in the modulation of depression processes via the ghrelin and GABAA receptor, and suggest cortistation may represent a novel strategy for the treatment of depression disorders.Highlights:-CST-14 and BDNF mRNA are decreased in hippocampus and cortex once mice exposed to stress.-i.c.v. or intranasal administration of CST-14 produce rapid antidepressant effects.-NIR fluorescence imaging detected the brain uptake and distribution after intranasal CST-14.-Antidepressant effects of CST-14 were only related to ghrelin and GABAA system.-Co-injection of CST-14 and NPS produce antidepressant effect, and do not impair memory

Assessment of geriatric and clinical domains for development and validation of a novel nomogram to predict the prognosis of older patients with breast cancer: a real-world retrospective cohort study

BackgroundBreast cancer is a relatively heterogeneous disease in the older population. Survival in older breast cancer patients is not only affected by tumor-related factors, but also by geriatric assessment domains. How tumor clinical factors and geriatric factors specifically affect the survival rate of older patients and how to combine these two factors to predict the risk of death in older patients with breast cancer remain clinical questions to be addressed.MethodWe used the Peking Union Medical College Hospital database to identify older patients (≥65 years) who were newly diagnosed with breast cancer between January 2013 and December 2019. Of the 641 eligible patients, we retrospectively analyzed the clinical and geriatric data of 556 patients who formed our study population. The primary outcomes were overall survival (OS) and breast cancer-specific survival (BCSS). Univariate and multivariate Cox regression analyses were conducted to identify independent prognostic factors and construct a nomogram to predict the 1-, 3-, and 5-year survival rates. The performance of the constructed nomogram was evaluated using calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA).ResultsMultivariate Cox regression analysis revealed seven independent prognostic factors associated with OS in older patients with breast cancer: age, tumor stage, lymph node stage, intrinsic molecular subtype, functional status, comorbidities, and psychological state. Nomogram based on these seven factors yielded excellent performance, with area under the ROC curve (AUROC) of 0.748. Similarly, the nomogram for BCSS had an AUROC of 0.760. Moreover, the calibration curve and DCA revealed good predictive accuracy between the actual and predicted probabilities.ConclusionIndependent prognostic factors for OS and BCSS in older patients with breast cancer in China were determined in our study. A novel nomogram for predicting the 1-, 3-, and 5-year OS and BCSS in this patient population was developed and validated. The nomogram exhibited good accuracy, indicating its potential for clinical decision making and improving outcomes

InternVid: A Large-scale Video-Text Dataset for Multimodal Understanding and Generation

This paper introduces InternVid, a large-scale video-centric multimodal dataset that enables learning powerful and transferable video-text representations for multimodal understanding and generation. The InternVid dataset contains over 7 million videos lasting nearly 760K hours, yielding 234M video clips accompanied by detailed descriptions of total 4.1B words. Our core contribution is to develop a scalable approach to autonomously build a high-quality video-text dataset with large language models (LLM), thereby showcasing its efficacy in learning video-language representation at scale. Specifically, we utilize a multi-scale approach to generate video-related descriptions. Furthermore, we introduce ViCLIP, a video-text representation learning model based on ViT-L. Learned on InternVid via contrastive learning, this model demonstrates leading zero-shot action recognition and competitive video retrieval performance. Beyond basic video understanding tasks like recognition and retrieval, our dataset and model have broad applications. They are particularly beneficial for generating interleaved video-text data for learning a video-centric dialogue system, advancing video-to-text and text-to-video generation research. These proposed resources provide a tool for researchers and practitioners interested in multimodal video understanding and generation.Comment: Data and Code: https://github.com/OpenGVLab/InternVideo/tree/main/Data/InternVi