The synergistic effect of high temperature and relative humidity on non-accidental deaths at different urbanization levels.

Numerous studies have examined the impact of temperature on mortality, yet research on the combined effect of temperature and humidity on non-accidental deaths remains limited. This study investigates the synergistic impact of high temperature and humidity on non-accidental deaths in China, assessing the influence of urban development and urbanization level. Utilizing the distributed lag nonlinear model (DLNM) of quasi-Poisson regression, we analyzed the relationship between Wet Bulb Globe Temperature (WBGT) and non-accidental deaths in 30 Chinese cities from 2010 to 2016, including Guangzhou during 2012-2016. We stratified temperature and humidity across these cities to evaluate the influence of varying humidity levels on deaths under high temperatures. Then, we graded the duration of heat and humidity in these cities to assess the impact of deaths with different durations. Additionally, the cities were categorized based on gross domestic product (GDP), and a vulnerability index was calculated to examine the impact of urban development and urbanization level on non-accidental deaths. Our findings reveal a pronounced synergistic effect of high temperature and humidity on non-accidental deaths, particularly at elevated humidity levels. The synergies of high temperature and humidity are extremely complex. Moreover, the longer the duration of high temperature and humidity, the higher the risk of non-accidental death. Furthermore, areas with higher urbanization exhibited lower relative risks (RR) associated with the synergistic effects of heat and humidity. Consequently, it is imperative to focus on damp-heat related mortality among vulnerable populations in less developed regions.

A membrane-targeting magnolol derivative for the treatment of methicillin-resistant Staphylococcus aureus infections.

Multidrug-resistant bacterial infections are a major global health challenge, especially the emergence and rapid spread of methicillin-resistant Staphylococcus aureus (MRSA) urgently require alternative treatment options. Our study has identified that a magnolol derivative 6i as a promising agent with significant antibacterial activity against S. aureus and clinical MRSA isolates (MIC = 2-8 µg/mL), showing high membrane selectivity. Unlike traditional antibiotics, 6i demonstrated rapid bactericidal efficiency and a lower propensity for inducing bacterial resistance. Compound 6i also could inhibit biofilm formation and eradicate bacteria within biofilms. Mechanistic studies further revealed that 6i could target bacterial cell membranes, disrupting the integrity of the cell membrane and leading to increased DNA leakage, resulting in potent antibacterial effects. Meanwhile, 6i also showed good plasma stability and excellent biosafety. Notably, 6i displayed good in vivo antibacterial activity in a mouse skin abscess model of MRSA-16 infection, which was comparable to the positive control vancomycin. These findings indicated that the magnolol derivative 6i possessed the potential to be a novel anti-MRSA infection agent.

Building Synthetic Yeast Factories to Produce Fat-soluble Antioxidants.

Fat-soluble antioxidants play a vital role in protecting the body against oxidative stress and damage. The rapid advancements in metabolic engineering and synthetic biology have offered a promising avenue for economically producing fat-soluble antioxidants by engineering microbial chassis. This review provides an overview of the recent progress in engineering yeast microbial factories to produce three main groups of lipophilic antioxidants: carotenoids, vitamin E, and stilbenoids. In addition to discussing the classic strategies employed to improve precursor availability and alleviate carbon flux competition, this review delves deeper into the innovative approaches focusing on enzyme engineering, product sequestration, subcellular compartmentalization, multistage fermentation, and morphology engineering. We conclude the review by highlighting the prospects of microbial engineering for lipophilic antioxidant production.

Puerarin-containing rhein-crosslinked tyramine-modified hyaluronic acid hydrogel for antibacterial and anti-inflammatory wound dressings.

Wound infections, posing a grave risk of severe physical consequences and even mortality, exact a substantial financial toll on society, rendering them among the most formidable challenges confronting our world today. A critical imperative is the development of hydrogel dressings endowed with immune-regulating and antibacterial properties. This study is founded upon the symbiotic physical and efficacious attributes of two small natural molecules. An injectable hydrogel is meticulously crafted by encapsulating puerarin (PUE) into tyramine-modified hyaluronic acid, subsequently introducing rhein (RHE), and catalyzing the formation of inter-phenol crosslinks with H2O2/horseradish peroxidase (HA-Tyr-R@P). Exhibiting a favorable microenvironmental impact the developed hydrogel attains an antibacterial efficacy exceeding 95 %, coupled with a wound closure rate twice that of the control group. HA-Tyr-R@P hydrogels not only inhibit bacterial growth but also mitigate inflammation, fostering wound healing, owing to their harmonized physicochemical characteristics and synergistic therapeutic effects. This work underscores the creation of a singular, versatile hydrogel platform, negating the complexities and side effects associated with pharmaceutical preparations. Furthermore, it offers new ideas for the formulation of RHE-based hydrogels for wound healing, emphasizing the pivotal role of natural small molecules in advancing biological materials.

Loss of Bcl-3 regulates macrophage polarization by promoting macrophage glycolysis.

M1/M2 macrophage polarization plays an important role in regulating the balance of the microenvironment within tissues. Moreover, macrophage polarization involves the reprogramming of metabolism, such as glucose and lipid metabolism. Transcriptional coactivator B-cell lymphoma-3 (Bcl-3) is an atypical member of the IκB family that controls inflammatory factor levels in macrophages by regulating nuclear factor kappa B pathway activation. However, the relationship between Bcl-3 and macrophage polarization and metabolism remains unclear. In this study, we show that the knockdown of Bcl-3 in macrophages can regulate glycolysis-related gene expression by promoting the activation of the nuclear factor kappa B pathway. Furthermore, the loss of Bcl-3 was able to promote the interferon gamma/lipopolysaccharide-induced M1 macrophage polarization by accelerating glycolysis. Taken together, these results suggest that Bcl-3 may be a candidate gene for regulating M1 polarization in macrophages.

Human ß-defensin-1 affects the mammalian target of rapamycin pathway and autophagy in colon cancer cells through long non-coding RNA TCONS_00014506.

BACKGROUND: Colorectal cancer has a low 5-year survival rate and high mortality. Human ß-defensin-1 (hBD-1) may play an integral function in the innate immune system, contributing to the recognition and destruction of cancer cells. Long non-coding RNAs (lncRNAs) are involved in the process of cell differentiation and growth. AIM: To investigate the effect of hBD-1 on the mammalian target of rapamycin (mTOR) pathway and autophagy in human colon cancer SW620 cells. METHODS: CCK8 assay was utilized for the detection of cell proliferation and determination of the optimal drug concentration. Colony formation assay was employed to assess the effect of hBD-1 on SW620 cell proliferation. Bioinformatics was used to screen potentially biologically significant lncRNAs related to the mTOR pathway. Additionally, p-mTOR (Ser2448), Beclin1, and LC3II/I expression levels in SW620 cells were assessed through Western blot analysis. RESULTS: hBD-1 inhibited the proliferative ability of SW620 cells, as evidenced by the reduction in the colony formation capacity of SW620 cells upon exposure to hBD-1. hBD-1 decreased the expression of p-mTOR (Ser2448) protein and increased the expression of Beclin1 and LC3II/I protein. Furthermore, bioinformatics analysis identified seven lncRNAs (2 upregulated and 5 downregulated) related to the mTOR pathway. The lncRNA TCONS_00014506 was ultimately selected. Following the inhibition of the lncRNA TCONS_00014506, exposure to hBD-1 inhibited p-mTOR (Ser2448) and promoted Beclin1 and LC3II/I protein expression. CONCLUSION: hBD-1 inhibits the mTOR pathway and promotes autophagy by upregulating the expression of the lncRNA TCONS_00014506 in SW620 cells.

Associations between cardiometabolic indices and the risk of diabetic kidney disease in patients with type 2 diabetes.

BACKGROUND: This study was designed to assess the associations between emerging cardiometabolic indices-the atherogenic index of plasma (AIP), the stress hyperglycemia ratio (SHR), the triglyceride-glucose (TyG) index, and the homeostasis model assessment of insulin resistance (HOMA-IR)-and the incidence of diabetic kidney disease (DKD) in type 2 diabetes (T2D) patients. METHODS: We consecutively enrolled 4351 T2D patients. The AIP, SHR, TyG index, and HOMA-IR were calculated from baseline parameters. DKD was defined as a urine albumin/creatinine ratio > 30 mg/g or an eGFR < 60 mL/min per 1.73 m. All participants were categorized into tertiles based on the cardiometabolic indices. Multivariate logistic regression models, restricted cubic splines, and receiver operating characteristic (ROC) curves were used for analysis. RESULTS: A total of 1371 (31.5%) patients were diagnosed with DKD. A restricted cubic spline showed a J-shaped association of the AIP and TyG index with DKD, a log-shaped association between HOMA-IR and DKD, and a U-shaped association between the SHR and DKD incidence. Multivariate logistic regression revealed that individuals in the highest tertile of the four cardiometabolic indices had a significantly greater risk of DKD than did those in the lowest tertile (AIP: OR = 1.08, 95% CI = 1.02-1.14, P = 0.005; SHR: OR = 1.42, 95% CI = 1.12-1.81, P = 0.004; TyG index: OR = 1.86, 95% CI = 1.42-2.45, P < 0.001; HOMA-IR: OR = 2.24, 95% CI = 1.52-3.30, P < 0.001). The receiver operating characteristic curves showed that the HOMA-IR score was better than other indices at predicting the risk of DKD, with an optimal cutoff of 3.532. CONCLUSIONS: Elevated AIP, SHR, TyG index and HOMA-IR are associated with a greater risk of DKD in patients with T2D. Among these indices, the HOMA-IR score demonstrated the strongest association with and predictive value for DKD incidence.

Comparison of the perioperative outcomes of robot-assisted laparoscopic transperitoneal versus retraperitoneal partial nephrectomy for posterior-lateral renal tumors: a systematic review and meta-analysis.

The study aims to assess the available literature and compare the perioperative outcomes of robotic-assisted partial nephrectomy (RAPN) for posterior-lateral renal tumors using transperitoneal (TP) and retroperitoneal (RP) approaches. Systematically searched the Embase, PubMed, and Cochrane Library databases for literature. Eligible studies were those that compared TP-RAPN and RP-RAPN for posterior-lateral renal tumors. The data from the included studies were analyzed and summarized using Review Manager 5.3, which involved comparing baseline patient and tumor characteristics, intraoperative and postoperative outcomes, and oncological outcomes. The analysis included five studies meeting the inclusion criteria, with a total of 1440 patients (814 undergoing RP-RAPN and 626 undergoing TP-RAPN). Both groups showed no significant differences in age, gender, BMI, R.E.N.A.L. score, and tumor size. Notably, compared to TP-RAPN, the RP-RAPN group demonstrated shorter operative time (OT) (MD: 17.25, P = 0.01), length of hospital stay (LOS) (MD: 0.37, P < 0.01), and lower estimated blood loss (EBL) (MD: 15.29, P < 0.01). However, no significant differences were found between the two groups in terms of warm ischemia time (WIT) (MD: -0.34, P = 0.69), overall complications (RR: 1.25, P = 0.09), major complications (the Clavien-Dindo classification ≥ 3) (RR: 0.97, P = 0.93), and positive surgical margin (PSM) (RR: 1.06, P = 0.87). The systematic review and meta-analysis suggests RP-RAPN may be more advantageous for posterior-lateral renal tumors in terms of OT, EBL, and LOS, but no significant differences were found in WIT, overall complications, major complications, and PSM. Both surgical approaches are safe, but a definitive advantage remains uncertain.

The MYB Transcription Factor GmMYB78 Negatively Regulates Phytophthora sojae Resistance in Soybean.

Phytophthora root rot is a devastating disease of soybean caused by Phytophthora sojae. However, the resistance mechanism is not yet clear. Our previous studies have shown that GmAP2 enhances sensitivity to P. sojae in soybean, and GmMYB78 is downregulated in the transcriptome analysis of GmAP2-overexpressing transgenic hairy roots. Here, GmMYB78 was significantly induced by P. sojae in susceptible soybean, and the overexpressing of GmMYB78 enhanced sensitivity to the pathogen, while silencing GmMYB78 enhances resistance to P. sojae, indicating that GmMYB78 is a negative regulator of P. sojae. Moreover, the jasmonic acid (JA) content and JA synthesis gene GmAOS1 was highly upregulated in GmMYB78-silencing roots and highly downregulated in overexpressing ones, suggesting that GmMYB78 could respond to P. sojae through the JA signaling pathway. Furthermore, the expression of several pathogenesis-related genes was significantly lower in GmMYB78-overexpressing roots and higher in GmMYB78-silencing ones. Additionally, we screened and identified the upstream regulator GmbHLH122 and downstream target gene GmbZIP25 of GmMYB78. GmbHLH122 was highly induced by P. sojae and could inhibit GmMYB78 expression in resistant soybean, and GmMYB78 was highly expressed to activate downstream target gene GmbZIP25 transcription in susceptible soybean. In conclusion, our data reveal that GmMYB78 triggers soybean sensitivity to P. sojae by inhibiting the JA signaling pathway and the expression of pathogenesis-related genes or through the effects of the GmbHLH122-GmMYB78-GmbZIP25 cascade pathway.

The EIN3 transcription factor GmEIL1 improves soybean resistance to Phytophthora sojae.

Phytophthora root and stem rot of soybean (Glycine max), caused by the oomycete Phytophthora sojae, is an extremely destructive disease worldwide. In this study, we identified GmEIL1, which encodes an ethylene-insensitive3 (EIN3) transcription factor. GmEIL1 was significantly induced following P. sojae infection of soybean plants. Compared to wild-type soybean plants, transgenic soybean plants overexpressing GmEIL1 showed enhanced resistance to P. sojae and GmEIL1-silenced RNA-interference lines showed more severe symptoms when infected with P. sojae. We screened for target genes of GmEIL1 and confirmed that GmEIL1 bound directly to the GmERF113 promoter and regulated GmERF113 expression. Moreover, GmEIL1 positively regulated the expression of the pathogenesis-related gene GmPR1. The GmEIL1-regulated defence response to P. sojae involved both ethylene biosynthesis and the ethylene signalling pathway. These findings suggest that the GmEIL1-GmERF113 module plays an important role in P. sojae resistance via the ethylene signalling pathway.

Molecular characterization of hybrid virulence plasmids in ST11-KL64 KPC-2-producing multidrug-resistant hypervirulent Klebsiella pneumoniae from China.

Introduction: Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-HvKP) strains combining virulence and multidrug resistance (MDR) features pose a great public health concern. The aim of this study is to explore the evolutionary characteristics of virulence in CR-HvKP by investigating the genetic features of resistance and virulence hybrid plasmids. Methods: The resistance and virulence phenotypes were determined by using antimicrobial susceptibility testing and the mouse bacteremia infection model, respectively. Plasmid profiles were investigated by S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern blotting, conjugation assay, and whole genome sequencing (WGS). Bioinformatics tools were used to uncover the genetic features of the resistance and virulence hybrid plasmids. Results: Two ST11-KL64 CRKP clinical isolates (KP18-3-8 and KP18-2079), which exhibited enhanced virulence compared with the classic CRKP, were detected positive for blaKPC-2 and rmpA2. The virulence level of the hypermucoviscous strain KP18-3-8 was higher than that of KP18-2079. S1-PFGE, Southern hybridization and WGS analysis identified two novel hybrid virulence plasmids in KP18-3-8 (pKP1838-KPC-vir, 228,158 bp) and KP18-2079 (pKP1838-KPC-vir, 182,326 bp), respectively. The IncHI1B/repB-type plasmid pKP1838-KPC-vir co-harboring blaKPC-2 and virulence genes (rmpA2, iucABCD and iutA) but lacking type IV secretion system could transfer into non-hypervirulent ST11 K. pneumoniae with the assistance of a helper plasmid in conjugation. The IncFII/IncR-type virulence plasmid pKP18-2079-vir may have been generated as a result of recombination between a typical pLVPK-like virulence plasmid and an MDR plasmid. Conclusion: Our studies further highlight co-evolution of the virulence and resistance plasmids in ST11-CRKP isolates. Close surveillance of such hybrid virulence plasmids in clinical K. pneumoniae should be performed.

Low cycle number multiplex PCR: A novel strategy for the construction of amplicon libraries for next-generation sequencing.

Multiplex PCR is a critical step when preparing amplicon library for next-generation sequencing. However, there are several challenges related to multiplex PCR including poor uniformity, nonspecific amplification, and primer-dimers. To address these issues, we propose a novel solution strategy that involves using a low cycle number (<10 cycles) in multiplex PCR and then employing carrier DNAs and magnetic beads for the selection of targeted products. This technique improves the amplicon uniformity while also reducing primer-dimers and PCR artifacts. To evaluate our technique, we initially utilized 120 DNA fragments from mouse genome containing single nucleotide polymorphism (SNP) sites. Sequencing results demonstrated that with only 7 cycles of multiplex PCR, 95.8% of the targeted SNP sites were mapped, with a coverage of at least 1×. The average sequencing depth of all amplicons was 1705.79 ± 1205.30×; 87% of them reached a coverage depth that exceeded 0.2-fold of the average sequencing depth. Our method had a greater uniformity (87%) when compared to Hi-Plex PCR (53.3%). Furthermore, we validated our strategy by randomly selecting 90 primer pairs twice from the initial set of 120 primer-pairs. Next, we used the same protocol to prepare amplicon libraries. The two groups had an average sequencing depth of 1013.30 ± 585.57× and 219.10 ± 158.27×, respectively; over 84% of the amplicons had a sequencing depth that exceeded 0.2-fold of average depth. These results suggest that the use of a low cycle number in multiplex PCR is a cost-effective and efficient approach for the preparation of amplicon libraries.

Positive psychological capital, post-traumatic growth, social support, and quality of life in patients with systemic lupus erythematosus: A cross-sectional study.

OBJECTIVE: This study aimed to investigate the correlation between positive psychological capital, post-traumatic growth, social support, and quality of life (QOL) in patients with systemic lupus erythematosus (SLE). METHODS: A cross-sectional study was conducted at the First Affiliated Hospital of Xinjiang Medical University from October 2022 to May 2023. A sample of 330 hospitalized SLE patients was selected for this study. The collected data included demographic information, the SLE disease activity index, the Positive Mental Capital Questionnaire, the Chinese version of the Post-Traumatic Growth Scale, the Social Support Rating Scale, and the Chinese version of the Lupus Quality of Life Scale. RESULTS: The QOL score among the 330 SLE patients was measured as M(P25, P75) of 105 (83.00,124.00). Positive psychological capital, post-traumatic growth, and social support demonstrated significant positive correlations with the QOL in SLE patients (p < 0.05). Multiple linear regression analysis revealed that literacy, disease level, disease duration, occupation, marital status, psychological capital, social support, and post-traumatic growth were influential factors associated with the QOL in SLE patients. CONCLUSION: Medical professionals should be attentive to the psychological well-being of SLE patients and should consider implementing early psychological interventions. These interventions are crucial for enhancing the QOL for individuals diagnosed with SLE.

Genomic insights into the chromosomal elongation in a family of Collembola.

Collembola is a highly diverse and abundant group of soil arthropods with chromosome numbers ranging from 5 to 11. Previous karyotype studies indicated that the Tomoceridae family possesses an exceptionally long chromosome. To better understand chromosome size evolution in Collembola, we obtained a chromosome-level genome of Yoshiicerus persimilis with a size of 334.44 Mb and BUSCO completeness of 97.0% (n = 1013). Both genomes of Y. persimilis and Tomocerus qinae (recently published) have an exceptionally large chromosome (ElChr greater than 100 Mb), accounting for nearly one-third of the genome. Comparative genomic analyses suggest that chromosomal elongation occurred independently in the two species approximately 10 million years ago, rather than in the ancestor of the Tomoceridae family. The ElChr elongation was caused by large tandem and segmental duplications, as well as transposon proliferation, with genes in these regions experiencing weaker purifying selection (higher dN/dS) than conserved regions. Moreover, inter-genomic synteny analyses indicated that chromosomal fission/fusion events played a crucial role in the evolution of chromosome numbers (ranging from 5 to 7) within Entomobryomorpha. This study provides a valuable resource for investigating the chromosome evolution of Collembola.

High intensity interval training vs. moderate intensity continuous training on aerobic capacity and functional capacity in patients with heart failure: a systematic review and meta-analysis.

Background: Exercise training is commonly employed as a efficacious supplementary treatment for individuals suffering from heart failure, but the optimal exercise regimen is still controversial. The objective of the review was to compare the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on the exercise capacity, cardiac function, quality of life (QoL) and heart rate among patients with heart failure with reduced ejection fraction. Methods: A systematic search was performed using the following eight databases from their inception to July 5, 2023: PubMed, Web of Science, Embase, Cochrane Library, Clinical Trials, China Knowledge Network, Wan fang Data, and the China Biology Medicine databases. The meta-analysis results were presented as mean difference (MD) and 95% confidence interval (CI). The Cochrane Risk of Bias tool was used for the included studies. The Grading of Recommendations Assessment, Development, and Evaluations was used to assess the certainty of evidence. Results: Thirteen randomized controlled trials were included in the study. The results showed that HIIT had a significant positive effect on peak oxygen uptake (MD = 1.78, 95% CI for 0.80-2.76), left ventricular ejection fraction (MD = 3.13, 95% CI for 1.25-5.02), six-minute walk test (MD = 28.13, 95% CI for 14.56-41.70), and Minnesota Living with Heart Failure Questionnaire (MD = -4.45, 95% CI for -6.25 to -2.64) compared to MICT. However, there were no statistically significant differences observed in resting heart rate and peak heart rate. Conclusions: HIIT significantly improves peak oxygen uptake, left ventricular ejection fraction, six-minute walk test, and Minnesota Living with Heart Failure Questionnaire in patients with heart failure with reduced ejection fraction. Additionally, HIIT exhibits greater effectiveness in improving peak oxygen uptake among patients with lower body mass index. Systematic Review Registration: https://www.doi.org/10.37766/inplasy2023.7.0100, identifier (INPLASY2023.7.0100).

Clinical and radiographic outcomes of lateral sinus floor elevation with simultaneous hydrophilic implants placement: A retrospective study of 2-5 years.

AIMS: To investigate the clinical and radiographic outcomes of a chemically modified sandblasted large-grit acid-etched implant (hydrophilic) in lateral sinus floor elevation (LSFE), compared with a conventional one (hydrophobic). MATERIALS AND METHODS: A retrospective study design was adopted. Patients who received LSFE with simultaneous implant placement were recruited. According to different types of implant surfaces, patients were divided into two groups (the hydrophilic group and the hydrophobic group). Implant survival rate (SR), endo-sinus bone stability on the radiographs, mean probing depths, percentage of bleeding on probing, marginal bone loss, and patient satisfaction were evaluated. RESULTS: A total of 106 patients with 180 implants (hydrophilic:101, hydrophobic:79) in 119 maxillary sinuses were included. The follow-up period ranged from 2 to 5 years. Three hydrophobic implants and one hydrophilic implant in four different patients failed. The SR of the hydrophilic group was higher than that of the hydrophobic group but without a significant difference (p > .05). The change and change rate of endo-sinus bone height (ΔESBH and RΔESBH) and bone volume (ΔESBV and RΔESBV) in the hydrophilic group were less than those in the hydrophobic group, with a significant difference at 6 months after implantation. No other significant difference was found between the two groups. CONCLUSION: Within the limitations of this study, both hydrophilic and hydrophobic implants were suitable for LSFE with predictable clinical outcomes. Meanwhile, hydrophilic implants could contribute to the grafted endo-sinus bone stability during healing time.

Enhanced denitrification performance in iron-carbon wetlands through biomass addition: Impact on nitrate and ammonia transformation.

This study investigated the influence of biomass addition on the denitrification performance of iron-carbon wetlands. During long-time operation, the effluent NO3--N concentration of CW-BFe was observed to be the lowest, registering at 0.418 ± 0.167 mg/L, outperforming that of CW-Fe, which recorded 1.467 ± 0.467 mg/L. However, the effluent NH4+-N for CW-BFe increased to 1.465 ± 0.121 mg/L, surpassing CW-Fe's 0.889 ± 0.224 mg/L. Within a typical cycle, when establishing first-order reaction kinetics based on NO3--N concentrations, the introduction of biomass was found to amplify the kinetic constants across various stages in the iron-carbon wetland, ranging between 2.4 and 5.4 times that of CW-Fe. A metagenomic analysis indicated that biomass augments the reduction of NO3--N and NO2--N nitrogen and significantly bolsters the dissimilation nitrate reduction to ammonia pathway. Conversely, it impedes the reduction of N2O, leading to a heightened proportion of 2.715 % in CW-BFe's nitrogen mass balance, a stark contrast to CW-Fe's 0.379 %.

Polarized Th2 cells attenuate high-fat-diet induced obesity through the suppression of lipogenesis.

Immune cells, such as macrophages, B cells, neutrophils and T cell subsets, have been implicated in the context of obesity. However, the specific role of Th2 cells in adipose tissue function has remained elusive. Eight-week-old male CD3ε─/─ mice were randomly divided into two groups (≥ 5 mice per group): one received intravenous injection of Th2 cells isolated from LATY136F mice, while the other receiving PBS as a control. Both of groups were subjected to a high-fat diet (HFD). The adoptive transfer of polarized Th2 cells led to a significant reduction in obesity following a HFD. This reduction was accompanied by improvements in hepatic steatosis, glucose intolerance, and insulin resistance. Mechanistically, Th2 cell treatment promoted oxidative phosphorylation of adipocytes, thereby contributing to a reduction of lipid droplet accumulation. These findings suggest that Th2 cell therapy represents a novel approach for treating diet-induced obesity and other diseases involving lipid droplet accumulation disorders.

Conformational plasticity of SpyCas9 induced by AcrIIA4 and AcrIIA2: Insights from molecular dynamics simulation.

CRISPR-Cas9 systems constitute bacterial adaptive immune systems that protect against phage infections. Bacteriophages encode anti-CRISPR proteins (Acrs) that mitigate the bacterial immune response. However, the structural basis for their inhibitory actions from a molecular perspective remains elusive. In this study, through microsecond atomistic molecular dynamics simulations, we demonstrated the remarkable flexibility of Streptococcus pyogenes Cas9 (SpyCas9) and its conformational adaptability during interactions with AcrIIA4 and AcrIIA2. Specifically, we demonstrated that the binding of AcrIIA4 and AcrIIA2 to SpyCas9 induces a conformational rearrangement that causes spatial separation between the nuclease and cleavage sites, thus making the endonuclease inactive. This separation disrupts the transmission of signals between the protospacer adjacent motif recognition and nuclease domains, thereby impeding the efficient processing of double-stranded DNA. The simulation also reveals that AcrIIA4 and AcrIIA2 cause different structural variations of SpyCas9. Our research illuminates the precise mechanisms underlying the suppression of SpyCas9 by AcrIIA4 and AcrIIA2, thus presenting new possibilities for controlling genome editing with higher accuracy.

COVID-19 and chronic kidney disease: a bibliometric analysis.

Background: The COVID-19 pandemic has caused over 656 million confirmed cases and over 6.6 million deaths worldwide. Chronic kidney disease (CKD) is considered a high-risk factor for COVID-19; therefore, considerable research has been conducted in this field. Therefore, this study aims to conduct a bibliometric analysis of publications related to COVID-19 and CKD. Methods: Publications were retrieved from the Web of Science Core Collection database on 16 January 2023 and screened based on inclusion criteria. Then the authors used Microsoft Excel and CiteSpace to analyze the included publications from the following seven aspects: countries/regions, institutions, journals, authors, cited references, and keywords. Results: In total, 622 publications were included in the study. The USA has the most publications in this field, followed by China. The Icahn School of Medicine at Mount Sinai and Harvard Medical School had the highest number of publications in the field. Journal of Clinical Medicine had the largest number of publications, and Lancet was the most cited journal. Alberto Ortiz was the author with the largest number of publications, but there were no influential authors in this field. The highly cited references are mainly clinical studies on COVID-19. Research hotspots in this field include end-stage recent disease, cardiovascular disease, kidney metastasis, diabetes Mellitus, acute kidney injury, meta-analysis, and consistent plasma. Conclusions: The USA, China, and some European countries and their institutions are major contributors to these publications. End-stage renal disease, acute kidney injury, kidney transplantation and convalescent plasma are current hot topics in the field.