Exosomes from Hypoxia Preconditioned Muscle-Derived Stem Cells Enhance Cell-Free Corpus Cavernosa Angiogenesis and Reproductive Function Recovery.

Tissue engineering for penile corpora cavernosa defects requires microvascular system reconstruction.GelMA hydrogels show promise for tissue regeneration. However, using stem cells faces challenges such as immune rejection, limited proliferation and differentiation, and biosafety concerns. Therefore, acellular tissue regeneration may avoid these issues. Exosomes are used from muscle-derived stem cells (MDSCs) to modify 3D-printed hydrogel scaffolds for acellular tissue regeneration. Hypoxia-preconditioned MDSC-derived exosomes are obtained to enhance the therapeutic effect. In contrast to normoxic exosomes (N-Exos), hypoxic exosomes (H-Exos) are found to markedly enhance the proliferation, migration, and capillary-like tube formation of human umbilical vein endothelial cells (HUVECs). High-throughput sequencing analysis of miRNAs isolated from both N-Exos and H-Exos revealed a significant upregulation of miR-21-5p in H-Exos following hypoxic preconditioning. Further validation demonstrated that the miR-21-5p/PDCD4 pathway promoted the proliferation of HUVECs. Epigallocatechin gallate (EGCG) is introduced to improve the mechanical properties and biocompatibility of GelMA hydrogels. EGCG-GelMA scaffolds loaded with different types of Exos are transplanted to repair rabbit penile corpora cavernosa defects, observed the blood flow and repair status of the defect site through color Doppler ultrasound and magnetic resonance imaging, and ultimately restored the rabbit penile erection function and successfully bred offspring. Thus, acellular hydrogel scaffolds offer an effective treatment for penile corpora cavernosa defects.

Interplay among manures, vegetable types, and tetracycline resistance genes in rhizosphere microbiome.

The rapid global emergence of antibiotic resistance genes (ARGs) is a substantial public health concern. Livestock manure serves as a key reservoir for tetracycline resistance genes (TRGs), serving as a means of their transmission to soil and vegetables upon utilization as a fertilizer, consequently posing a risk to human health. The dynamics and transfer of TRGs among microorganisms in vegetables and fauna are being investigated. However, the impact of different vegetable species on acquisition of TRGs from various manure sources remains unclear. This study investigated the rhizospheres of three vegetables (carrots, tomatoes, and cucumbers) grown with chicken, sheep, and pig manure to assess TRGs and bacterial community compositions via qPCR and high-throughput sequencing techniques. Our findings revealed that tomatoes exhibited the highest accumulation of TRGs, followed by cucumbers and carrots. Pig manure resulted in the highest TRG levels, compared to chicken and sheep manure, in that order. Bacterial community analyses revealed distinct effects of manure sources and the selective behavior of individual vegetable species in shaping bacterial communities, explaining 12.2% of TRG variation. Firmicutes had a positive correlation with most TRGs and the intl1 gene among the dominant phyla. Notably, both the types of vegetables and manures significantly influenced the abundance of the intl1 gene and soil properties, exhibiting strong correlations with TRGs and elucidating 30% and 17.7% of TRG variance, respectively. Our study delineated vegetables accumulating TRGs from manure-amended soils, resulting in significant risk to human health. Moreover, we elucidated the pivotal roles of bacterial communities, soil characteristics, and the intl1 gene in TRG fate and dissemination. These insights emphasize the need for integrated strategies to reduce selection pressure and disrupt TRG transmission routes, ultimately curbing the transmission of tetracycline resistance genes to vegetables.

Deep Amplicon Sequencing Reveals Culture Selection of Mycobacterium Tuberculosis by Clinical Samples.

The commonly-used drug susceptibility testing (DST) relies on bacterial culture and faces shortcomings such as long turnaround time and clone/subclone selection. We developed a targeted deep amplification sequencing (DAS) method directly applied to clinical specimens. In this DAS panel, we examined 941 drug-resistant mutations associated with 20 anti-tuberculosis drugs with an initial amount of 4 pg DNA and reduced clinical testing time from 20 days to two days. A prospective study was conducted using 115 clinical specimens mainly with Xpert® Mycobacterium tuberculosis/rifampicin (Xpert MTB/RIF) assay positive to evaluate drug-resistant mutation detection. DAS was performed on culture-free specimens, while culture-dependent isolates were used for phenotypic DST, DAS, and whole-genome sequencing (WGS). For in silico molecular DST, our result based on DAS panel revealed the similar accuracy to three published reports based on WGS. For 82 isolates, application of DAS showed better sensitivity (93.03% vs. 92.16%), specificity (96.10% vs. 95.02%), and accuracy (91.33% vs. 90.62%) than Mykrobe software using WGS. Compared to culture-dependent WGS, culture-free DAS provides a full picture of sequence variation at population level, exhibiting in detail the gain-and-loss variants caused by bacterial culture. Our study performs a systematic verification of the advantages of DAS in clinical applications and comprehensively illustrates the discrepancy in Mycobacterium tuberculosis before and after culture.

Long-term antiviral therapy is associated with changes in the profile of transcriptionally active HBV integration in the livers of patients with CHB.

Hepatitis B virus (HBV) integration exists throughout the clinical course of chronic hepatitis B (CHB). This study investigated the effects of long-term antiviral therapy on the level and profiles of transcriptionally active HBV integration. Serial liver biopsies and paired blood samples were obtained from 16, 16, and 22 patients with CHB at baseline, 78, and 260 weeks of entecavir monotherapy or combined with pegylated interferon alfa, respectively. Serum HBV biomarkers were longitudinally assessed. RNA-seq and HIVID2 program was used to identify HBV-host chimeric RNAs transcribed from integrated DNA. The counts of HBV integration reads were positively related to both serum HBV DNA levels (r = 0.695, p = 0.004) and HBeAg titers (r = 0.724, p = 0.021) at baseline, but the positive correlation exited only to the serum HBsAg levels after 260 weeks of antiviral therapy (r = 0.662, p = 0.001). After 78 weeks of antiviral therapy, the levels of HBV integration expression decreased by 12.25 folds from baseline. The viral junction points were enriched at the S and HBx genes after the long-term antiviral therapy. HBs-FN1 became one of the main transcripts, with the mean proportion of HBs-FN1 in all integrated expression increased from 2.79% at baseline to 10.54% at Week 260 of antiviral treatment. Antiviral therapy may reduce but not eliminate the HBV integration events and integration expression. Certain integration events, such as HBs-FN1 can persist in long-term antiviral treatment.

Real-time driving risk prediction using a self-attention-based bidirectional long short-term memory network based on multi-source data.

Early warning of driving risks can effectively prevent collisions. However, numerous studies that predicted driving risks have suffered from the use of single data sources, insufficiently advanced models, and lack of time window analysis. To address these issues, this paper proposes a self-attention-based bidirectional long short-term memory (Att-Bi-LSTM) network model to predict driving risk based on multi-source data. First, driving simulation tests are conducted. Driver demographic, operation, visual, and physiological data as well as kinematic data are collected. Then, the driving risks are classified into no risk, low risk, medium risk, and high risk. Next, the Att-Bi-LSTM model is constructed, and convolutional neural network (CNN), CNN-LSTM, CatBoost, LightGBM, and XGBoost are employed for comparison. To generate the inputs and outputs of the models, observation, interval, and prediction time windows are introduced. The results show that the Att-Bi-LSTM model using early-fusion method significantly outperforms the five comparison models, with a macro-average F1-score of 0.914. The results of ablation studies indicate that the Bi-LSTM layers and self-attention layer have achieved the expected effect, which is crucial for improving the model's performance. As the interval or prediction time window is extended, the accuracy of the prediction results gradually decreases. However, as the observation time window is extended, the results first improve and then become stable. Compared to using only relative kinematic data, using all data (i.e., multi-source data) is shown to improve the F1-score by 0.061. This study provides an effective method for driving risk prediction and supports the improvement of advanced driver assistance systems.

Effects of plant taxonomic position on soil nematode communities in Antarctica.

Antarctica terrestrial ecosystems are facing the most threats from global climate change, which is altering plant composition greatly. These transformations may cause major reshuffling of soil community composition, including functional traits and diversity, and therefore affect ecosystem processes in Antarctica. We used high-throughput sequencing analysis to investigate soil nematodes under 3 dominant plant functional groups (lichens, mosses, and vascular plants) and bare ground in the Antarctic region. We calculated functional diversity of nematodes based on their diet, life histories, and body mass with kernel density n-dimensional hypervolumes. We also calculated taxonomic and functional beta diversity of the nematode communities based on Jaccard dissimilarity. The presence of plants had no significant effect on the taxonomic richness of nematodes but significantly increased nematode functional richness. The presence of plants also significantly decreased taxonomic beta diversity (homogenization). Only mosses and vascular plants decreased nematode functional beta diversity, which was mostly due to a decreased effect of the richness difference component. The presence of plants also increased the effect of deterministic processes potentially because environmental filtering created conditions favorable to nematodes at low trophic levels with short life histories and small body size. Increasing plant cover in the Antarctic due to climate change may lead to increased diversity of nematode species that can use the scarce resources and nematode taxonomic and functional homogenization. In a future under climate change, community restructuring in the region is possible.

Efectos de la posición taxonómica de las plantas sobre las comunidades de nemátodos del suelo en la Antártida Resumen Los ecosistemas terrestres de la Antártida enfrentan las mayores amenazas del cambio climático global, que está alterando gravemente la composición de plantas. Estas transformaciones pueden provocar una reorganización importante de la composición de la comunidad del suelo, incluyendo atributos y diversidad funcionales, y por lo tanto afectar los procesos ecosistémicos en la Antártida. Utilizamos análisis de secuenciación de alto rendimiento para investigar nemátodos del suelo debajo de tres grupos funcionales de plantas dominantes (líquenes, musgos y plantas vasculares) y de suelo desnudo en la región de la Antártida. Calculamos la diversidad funcional de nemátodos con base en su dieta, historia de vida y masa corporal mediante hipervolúmenes n­dimensionales de densidad del núcleo. También calculamos la diversidad beta taxonómica y funcional de las comunidades de nemátodos con base en la disimilitud de Jacard. La presencia de plantas no tuvo efecto significativo sobre la riqueza taxonómica de nemátodos, pero incrementó su riqueza funcional significativamente. La presencia de plantas también disminuyó la diversidad beta taxonómica (homogenización) significativamente. Solo musgos y plantas vasculares disminuyeron la diversidad beta funcional de nemátodos, lo cual se debió principalmente a un menor efecto del componente de diferencia de riqueza. La presencia de plantas también incrementó el efecto de los procesos determinísticos posiblemente porque el filtrado ambiental creó condiciones favorables para los nemátodos de niveles tróficos inferiores con historias de vida corta y tamaño corporal pequeño. El incremento de la cobertura de plantas en la Antártida debido al cambio climático puede conducir a una mayor diversidad de especies de nemátodos que pueden utilizar los escasos recursos y a la homogenización taxonómica y funcional de los nemátodos. En un futuro bajo el cambio climático, es posible la reestructuración comunitaria en la región.

Influence of emotions on the aggressive driving behavior of online -car-hailing drivers based on association rule mining.

Emotion is an important factor that can lead to the occurrence of aggressive driving. This paper proposes an association rule mining-based method for analysing contributing factors associated with aggressive driving behaviour among online car-hailing drivers. We collected drivers' emotion data in real time in a natural driving setting. The findings show that 29 of the top 50 association rules for aggressive driving are related to emotions, revealing a strong relationship between driver emotions and aggressive driving behaviour. The emotions of anger, surprised, happy and disgusted are frequently associated with aggressive driving behaviour. Negative emotions combined with other factors (for example, driving at high speeds and high acceleration rates and with no passengers in the vehicle) are more likely to lead to aggressive driving behaviour than negative emotions alone. The results of this study provide practical implications for the supervision and training of car-hailing drivers.

Based on the association rule mining method, we found a close connection between drivers' emotional states and the manifestation of aggressive driving behaviours. The findings indicate that the combination of negative emotions and various contributing factors significantly amplifies the likelihood of aggressive driving.

OsALKBH9-mediated m6A demethylation regulates tapetal PCD and pollen exine accumulation in rice.

The N6-methyladenosine (m6A) mRNA modification is crucial for plant development and stress responses. In rice, the male sterility resulting from the deficiency of OsFIP37, a core component of m6A methyltransferase complex, emphasizes the significant role of m6A in male fertility. m6A is reversible and can be removed by m6A demethylases. However, whether mRNA m6A demethylase regulates male fertility in rice has remained unknown. Here, we identify the mRNA m6A demethylase OsALKBH9 and demonstrate its involvement in male fertility regulation. Knockout of OsALKBH9 causes male sterility, dependent on its m6A demethylation activity. Cytological analysis reveals defective tapetal programmed cell death (PCD) and excessive accumulation of microspores exine in Osalkbh9-1. Transcriptome analysis of anthers shows up-regulation of genes involved in tapetum development, sporopollenin synthesis, and transport pathways in Osalkbh9-1. Additionally, we demonstrate that OsALKBH9 demethylates the m6A modification in TDR and GAMYB transcripts, which affects the stability of these mRNAs and ultimately leads to excessive accumulation of pollen exine. Our findings highlight the precise control of mRNA m6A modification and reveal the pivotal roles played by OsALKBH9-mediated m6A demethylation in tapetal PCD and pollen exine accumulation in rice.

Effects of positive psychological interventions on positive and negative emotions in depressed individuals: a systematic review and meta-analysis.

BACKGROUND: Positive psychological interventions (PPIs) are known to be effective in alleviating depression. However, the effect of PPIs on positive and negative emotions in depressed participants is not unclear. AIMS: To systematically investigate the effects of PPIs on positive and negative emotions in depressed individuals. METHODS: 6 databases were searched for randomized controlled trials of PPIs in individuals with depressive disorders or depressive symptoms. Hedges' g value was computed using a random-effects model to determine effect sizes. RESULTS: 14 trials from 13 studies were included. Our meta-analysis showed that PPIs had significant but small effects on improving positive affect (g = 0.33, p = .02), life satisfaction (g = 0.26, p = .03), happiness (g = 0.62, p = .03) and depression (g = -0.32, p = .001), and negligible effects on improving well-being (g = 0.13, p = .24) and negative affect (g = -0.15, p = .31). Subgroup analyses of depression showed that PPIs have experienced benefits in improving depression in most subgroups. In addition, none of the subgroup analyses performed for outcomes other than depression found PPIs to be more effective than controls. CONCLUSION: PPIs can improve positive affect, life satisfaction, happiness and depression in depressed individuals, but further studies are needed to validate their effects on well-being, and negative affect.

Liver fibrosis showed a two-phase regression rate during long-term anti-HBV therapy by three-time biopsies assessments.

BACKGROUND: Evidence has proven that liver fibrosis or even cirrhosis can be reversed by anti-HBV treatment. However, the difference of fibrosis regression rates in short-term and long-term antiviral therapy remain unclear. Therefore, we aimed to identify the dynamic changes in fibrosis regression rate in patients with three-time liver biopsies during 5 years antiviral therapy. METHODS: CHB patients with three times of liver biopsies (baseline, after 1.5-year and 5-year antiviral therapy) from a prospective cohort were enrolled. All patients were biopsy-proved Ishak stage ≥ 3 at baseline (n = 92). Fibrosis regression was defined as Ishak stage decreased ≥ 1 or predominantly regressive categorized by P-I-R score. RESULTS: Totals of 65.2% (60/92) and 80.4% (74/92) patients attained fibrosis regression after 1.5-year and 5-year therapy, respectively. Median HBV DNA level declined from 6.5 log IU/ml (baseline) to 0 log IU/ml (1.5 years and 5 years, P < 0.001). The mean level of Ishak fibrosis stage in all patients decreased from stage 4.1 (baseline) to 3.7 (1.5 years) then 3.2 (5 years). Fibrosis regression rates were 0.27 stage/year between baseline to year 1.5 and 0.14 stage/year between year 1.5 and year 5. Furthermore, for patients who attained fibrosis regression after 5-year antiviral therapy, the two-phase regression rates were 0.39 stage/year (0 year-1.5 years) and 0.20 stage/year (1.5 years-5 years). This two-phase feature of regression rate was further confirmed by fully-quantification assessment of liver fibrosis based on SHG/TPEF. CONCLUSION: During the 5 years of long-term antiviral treatment, liver fibrosis rapidly regresses in the first 1.5 years before slowing down in the following 3.5 years.

Chronic trans fatty acid consumption shortens lifespan in male Drosophila melanogaster on a high-sugar and high-fat diet.

Aging entails the progressive decline in the body's self-regulation and functionality over time. Notably, obesity and aging exhibit parallel phenotypes, with obesity further accelerating the aging process across multiple dimensions and diminishing lifespan. In this study, we explored the impact of trans fatty acid (TFA) consumption on the overall health and lifespan of male Drosophila melanogaster under an isocaloric high-sugar and high-fat diet. Our results indicate that TFA intake results in a shortened lifespan, elevated body weight, and increased triglyceride levels in flies fed a high-sugar and high-fat diet with equivalent caloric intake. Additionally, TFA exposure induces oxidative stress, locomotor deficits, and damage to the intestinal barrier in flies. Collectively, chronic TFA consumption expedites the aging process and reduces the lifespan of male Drosophila melanogaster. These results contribute supplementary evidence regarding the adverse health effects associated with TFAs.

Warming enhances the negative effects of shrub removal on phosphorus mineralization potential.

Shrubs have developed various mechanisms for soil phosphorus utilization. Shrub encroachment caused by climate warming alters organic phosphorus mineralization capability by promoting available phosphorus absorption and mediating root exudates. However, few studies have explored how warming regulates the effects of dominant shrubs on soil organic phosphorus mineralization capability. We provide insights into warming, dominant shrub removal, and their interactive effects on the soil organic phosphorus mineralization potential in the Qinghai-Tibetan Plateau. Real-time polymerase chain reaction was used to quantify the soil microbial phosphatase genes (phoC and phoD), which can characterize the soil organic phosphate mineralization potential. We found that warming had no significant effect on the soil organic phosphate-mineralized components (total phosphate, organic phosphate, and available phosphate), genes (phoC and phoD), or enzymes (acid and alkaline phosphatases). Shrub removal negatively influenced the organic phosphate-mineralized components and genes. It significantly decreased soil organic phosphate mineralization gene copy numbers only under warming conditions. Warming increased fungal richness and buffered the effects of shrub removal on bacterial richness and gene copy numbers. However, the change in the microbial community was not the main factor affecting organic phosphate mineralization. We found only phoC copy number had significant correlation to AP. Structural equation modelling revealed that shrub removal and the interaction between warming and shrub removal had a negative direct effect on phoC copy numbers. We concluded that warming increases the negative effect of shrub removal on phosphorus mineralization potential, providing a theoretical basis for shrub encroachment on soil phosphate mineralization under warming conditions.

Exosomal hsa_circ_0093884 derived from endothelial progenitor cells promotes therapeutic neovascularization via miR-145/SIRT1 pathway.

Therapeutic neovascularization is a strategy to promote blood vessel growth and improve blood flow, which is critical to tissue repair and regeneration in ischemic diseases. Here, we investigated the role of endothelial progenitor cell - derived exosomes (EPC-Exos) in therapeutic neovascularization and clarified the mechanism of hsa_circ_0093884 in EPC-Exos mediated neovascularization. Injection of EPC-Exos improved mouse ischemic hindlimb perfusion, promoted angiogenesis in Matrigel plugs and mouse skin wound healing. In vitro coculture with EPC-Exos improved HUVEC proliferation, angiogenic and migration ability, while alleviated hypoxia-induced apoptosis. hsa_circ_0093884 was identified from eleven types of circRNA derived from SIRT1 and proved to be enriched in EPC-Exos. Overexpression of hsa_circ_0093884 in EPC-Exos further enhanced the angiogenic capacity, while knockdown of hsa_circ_0093884 abolished the benefits. Mechanistically, EPC-Exos mediated shuttling of hsa_circ_0093884 induced cytoplasmic sponge of miR-145, thereby releasing repression of SIRT1. In vitro co-transfection indicated silence of miR-145 further strengthened the angiogenic effect of hsa_circ_0093884, while overexpression of miR-145 inhibited hsa_circ_0093884 mediated angiogenesis and abolished the beneficial effect of EPC-Exos. Furthermore, in vivo experiments using endothelial specific SIRT1 conditional knockout mice indicated hsa_circ_0093884 overexpressing EPC-Exos failed to promote therapeutic neovascularization in SIRT1cKO mice. Collectively, our results demonstrated that EPC-Exos promoted therapeutic neovascularization through hsa_circ_0093884/miR-145/SIRT1 axis.

Perceived social support mediates the effect of COVID-19 pandemic on job adaptation disorders of workers: An exploratory cross-sectional study.

COVID-19 lockdown can lead to job adaptation disorders, which are heterogeneous among individuals. The purpose of this study was to explore the association between perceived social support and job adaptation disorders among workers in China during the COVID-19 pandemic. The questionnaires of Psychological Questionnaire for Public Health Emergencies, Multidimensional Scale of Perceived Social Support, Work Attitude Scale were used for this cross-section study via an online survey. The study included 626 employees. Hierarchical regression analysis and Bootstrap method were used to investigate the mediation effect of perceived social support between the emergency and job adaptation disorders. The percentages of the 5 dimensions of depression, neurasthenia, fear, compulsion-anxiety, and hypochondria in workers were 59.7%, 56.1%, 92.3%, 42.0%, and 18.7%, respectively. Social support mediated the relationship between depression, neurasthenia, obsessive-compulsive anxiety and job adaptation disorder, accounting for 18.1%, 16.1%, and 17.5% of the total effect (ab/c), respectively. Perceived social support could alleviate COVID-19 pandemic-related depression, neurasthenia, compulsion-anxiety, and job adaptation disorder in Chinese workers. Improving their perception of social support, workers may better adapt themselves to work in the challenging of the public health emergency during COVID-19 pandemic.

A biomarker panel of secondary hypertension is simultaneously quantified by coupling of magnetic solid-phase extraction and liquid chromatography-tandem mass spectrometry.

RATIONALE: Secondary hypertension is often caused by activation of complex multi-organ endocrine systems, while renin activity indicated by angiotensins (Angs), aldosterone (ALD) and cortisol (COR) in such systems are generally accepted as its diagnostic markers. As antibody-based methods cannot offer comparable quantification for these biomarkers, a liquid chromatography (LC)-tandem mass spectrometry (MS/MS)-based approach was developed to quantify them simultaneously and accurately. METHODS: Five different beads for magnetic solid-phase extraction (MSPE) were evaluated towards their enrichment efficiency for these biomarkers. An LC system with optimized elution gradient and a triple-quadrupole MS with tuned parameters were coupled to quantitatively monitor the extracted analytes. The method performance was further examined such as linearity, precision, stability, recovery rate and matrix effect. Based on the developed method, the abundance of Ang II, ALD and COR in plasma was measured and the quantification was compared with that derived from commercial ELISA kits. RESULTS: As compared with other MSPEs, Angs, ALD and COR were highly enriched by the HLB magnetic beads with satisfactory recoveries. These analytes were simultaneously quantified by LC/MS/MS and all the method parameters for quantification were well matched with the requirements of clinical testing. Comparison of the quantitative results derived from ELISA and LC/MS/MS exhibited that the two methods offered basically comparable values with Pearson r values at 0.896, 0.895 and 0.835, respectively. The stability test for plasma Angs at room temperature indicated that the abundance of Ang II was relatively stable within 3 h, whereas that of Ang I and Ang 1-7 was time-dependently changed. CONCLUSIONS: Coupling of HLB beads and LC/MS/MS thus enables simultaneous quantification of a set of biomarkers related to secondary hypertension.

Contrasting responses of α- and ß-multifunctionality to aboveground plant community in the Qinghai-Tibet Plateau.

The aboveground plant communities are crucial in driving ecosystem functioning, particularly being the primary producers in terrestrial ecosystems. Numerous studies have investigated the impacts of aboveground plant communities on multiple ecosystem functions at α-scale. However, such critical effects have been unexplored at ß-scale and the comparative assessment of the effects and underlying mechanisms of aboveground plant communities on α- and ß-multifunctionality has been lacking. In this study, we examined the effects of aboveground plant communities on soil multifunctionality both at α- and ß-scale in the alpine meadow of the Tibetan Plateau. Additionally, we quantified the direct effects of aboveground plant communities, as well as the indirect effects mediated by changes in biotic and abiotic factors, on soil multifunctionality at both scales. Our findings revealed that: 1) Aboveground plant communities had significantly positive effects on α-multifunctionality whereas, ß-multifunctionality was not affected significantly. 2) Aboveground plant communities directly influence α- and ß-multifunctionality in contrasting ways, with positive and negative effects, respectively. Apart from the direct effects of plant community, we found that soil water content and bacterial ß-diversity serving as the primary predictors for the responses of α- and ß-multifunctionality to the presence of aboveground plant communities, respectively. And ß-soil biodiversity appeared to be a stronger predictor of multifunctionality relative to α-soil biodiversity. Our findings provide novel insights into the drivers of ecosystem multifunctionality at different scales, highlight the importance of maintaining biodiversity at multiple scales and offer valuable knowledge for the maintenance of ecosystem functioning and the restoration of alpine meadow ecosystems.

Epigenetic reshaping through damage: promoting cell fate transition by BrdU and IdU incorporation.

BACKGROUND: Thymidine analogs have long been recognized for their ability to randomly incorporate into DNA. However, the precise mechanisms through which thymidine analogs facilitate cell fate transition remains unclear. RESULTS: Here, we discovered a strong correlation between the dosage dependence of thymidine analogs and their ability to overcome reprogramming barrier. The extraembryonic endoderm (XEN) state seems to be a cell's selective response to DNA damage repair (DDR), offering a shortcut to overcome reprogramming barriers. Meanwhile, we found that homologous recombination repair (HRR) pathway causes an overall epigenetic reshaping of cells and enabling them to overcome greater barriers. This response leads to the creation of a hypomethylated environment, which facilitates the transition of cell fate in various reprogramming systems. We term this mechanism as Epigenetic Reshaping through Damage (ERD). CONCLUSION: Overall, our study finds that BrdU/IdU can activate the DNA damage repair pathway (HRR), leading to increased histone acetylation and genome-wide DNA demethylation, regulating somatic cell reprogramming. This offers valuable insights into mechanisms underlying cell fate transition.

Filament coating system assists recovery of ablative fCO2 laser treatment: A split-face clinical observation.

BACKGROUND: The current nursing procedure after fractional carbon dioxide (fCO2) is complex and needs to be optimized. The present study was conducted to evaluate the assisting effect of filament coating system after fCO2 laser treatment. METHODS: Chinese individuals aged from 18 to 65 years diagnosed as photoaging or atrophic acne scar were recruited and each participant was treated with one single pass of fCO2 laser. A split face was randomly assigned as treatment side or control side. For control side, conventional procedure was topically applied respectively, including desonide cream two times for 3 days, fusidic acid cream two times for 7 days, and recombinant human epidermal growth factor (RhEGF) gel four times for 7 days; for treating side, a filament coating system was applied immediately after one application of fusidic acid cream, desonide cream and RhEGF, and removed 3 h later, for 3 days. Erythema, edema, crust, and pain on both sides were scored from 0 to 10 before and 1, 2, 4, and 7 days after fCO2 laser treatment. Stratum corneum hydration (SCH) and sebum of forehead and cheek on both sides were also measured by using Corneometer-Sebumeter. RESULTS: Twenty photoaging and 11 atrophic acne scar participants finished the observation. All of them complained of erythema, edema, crust, and pain after fCO2 laser treatment, and the scores decreased as time passed by. There were no statistical significances of erythema, edema, crust, pain, SCH, and sebum between treating side and control side at each observation time. CONCLUSION: Filament coating system was effective, safe, convenient, and economic in assisting recovery of ablative fCO2 laser, which might be a new option for additional nursing procedure.

Carvedilol Plus NUC for Patients With HBV-Compensated Cirrhosis Under Virological Suppression: A Randomized Open-Label Trial.

INTRODUCTION: Portal hypertension progression can be relieved after controlling the etiology of liver cirrhosis. Whether beta-blockers could additionally enhance the effects during treatment, particularly for small esophageal varices (EV), was unclear. This study aims to assess the efficacy of add-on carvedilol to delay EV progression during anti-hepatitis B virus (HBV) treatment in HBV-related cirrhosis. METHODS: This randomized controlled trial enrolled patients with virologically suppressed HBV-compensated cirrhosis and small/medium EV. The participants were randomly assigned to receive nucleos(t)ide analog (NUC) or carvedilol 12.5 mg plus NUC (1:1 allocation ratio). The primary end point was the progression rate of EV at 2 years of follow-up. RESULTS: A total of 238 patients (small EV, 77.3%) were randomized into 119 NUC and 119 carvedilol plus NUC (carvedilol [CARV] combination group). Among them, 205 patients (86.1%) completed paired endoscopies. EV progression rate was 15.5% (16/103) in the NUC group and 12.7% (13/102) in the CARV combination group (relative risk = 0.79, 95% confidence interval 0.36-1.75, P = 0.567). Subgroup analysis on medium EV showed the CARV combination group had a more favorable effect in promoting EV regression (43.5% vs 13.1%, P = 0.022) than NUC alone, but not in small cases ( P = 0.534). The incidence of liver-related events (decompensation, hepatocellular carcinoma, or death/liver transplantation) within 2 years was similar between the 2 groups (11.2% vs 10.4%, P = 0.881). DISCUSSION: The overall results did not show statistically significant differences between the added carvedilol strategy and NUC monotherapy in preventing EV progression in patients with virologically suppressed HBV-compensated cirrhosis. However, the carvedilol-added approach might offer improved outcomes specifically for patients with medium EV (NCT03736265).