Central-cell-produced attractants control fertilization recovery.

Animal fertilization relies on hundreds of sperm racing toward the egg, whereas, in angiosperms, only two sperm cells are delivered by a pollen tube to the female gametes (egg cell and central cell) for double fertilization. However, unsuccessful fertilization under this one-pollen-tube design can be detrimental to seed production and plant survival. To mitigate this risk, unfertilized-gamete-controlled extra pollen tube entry has been evolved to bring more sperm cells and salvage fertilization. Despite its importance, the underlying molecular mechanism of this phenomenon remains unclear. In this study, we report that, in Arabidopsis, the central cell secretes peptides SALVAGER1 and SALVAGER2 in a directional manner to attract pollen tubes when the synergid-dependent attraction fails or is terminated by pollen tubes carrying infertile sperm cells. Moreover, loss of SALs impairs the fertilization recovery capacity of the ovules. Therefore, this research uncovers a female gamete-attraction system that salvages seed production for reproductive assurance.

Eukaryotic origin-dependent DNA replication in vitro reveals sequential action of DDK and S-CDK kinases.

Proper eukaryotic DNA replication requires temporal separation of helicase loading from helicase activation and replisome assembly. Using an in vitro assay for eukaryotic origin-dependent replication initiation, we investigated the control of these events. After helicase loading, we found that the Dbf4-dependent Cdc7 kinase (DDK) but not S phase cyclin-dependent kinase (S-CDK) is required for the initial origin recruitment of Sld3 and the Cdc45 helicase-activating protein. Likewise, in vivo, DDK drives early-firing-origin recruitment of Cdc45 before activation of S-CDK. After S-CDK activation, a second helicase-activating protein (GINS) and the remainder of the replisome are recruited to the origin. Finally, recruitment of lagging but not leading strand DNA polymerases depends on Mcm10 and DNA unwinding. Our studies identify distinct roles for DDK and S-CDK during helicase activation and support a model in which the leading strand DNA polymerase is recruited prior to origin DNA unwinding and RNA primer synthesis.

The utility of P-I-R classification in predicting the on-treatment histological and clinical outcomes of patients with hepatitis B and advanced liver fibrosis.

BACKGROUND AND AIMS: The predominantly progressive, indeterminate, and predominantly regressive (P-I-R) classification extends beyond staging and provides information on dynamic changes of liver fibrosis. However, the prognostic implication of P-I-R classification is not elucidated. Therefore, in the present research, we investigated the utility of P-I-R classification in predicting the on-treatment clinical outcomes. APPROACH AND RESULTS: In an extension study on a randomized controlled trial, we originally enrolled 1000 patients with chronic hepatitis B and biopsy-proven histological significant fibrosis, and treated them for more than 7 years with entecavir-based therapy. Among the 727 patients with a second biopsy at treatment week 72, we compared P-I-R classification and Ishak score changes in 646 patients with adequate liver sections for the histological evaluation. Progressive, indeterminate, and regressive cases were observed in 70%, 17%, and 13% of patients before treatments and 20%, 14%, and 64% after 72-week treatment, respectively, which could further differentiate the histological outcomes of patients with stable Ishak scores. The 7-year cumulative incidence of HCC was 1.5% for the regressive cases, 4.3% for the indeterminate cases, and 22.8% for the progressive cases ( p <0.001). After adjusting for age, treatment regimen, platelet counts, cirrhosis, Ishak fibrosis score changes, and Laennec staging, the posttreatment progressive had a HR of 17.77 (vs. posttreatment regressive; 95% CI: 5.55-56.88) for the incidence of liver-related events (decompensation, HCC, and death/liver transplantation). CONCLUSIONS: The P-I-R classification can be a meaningful complement to the Ishak fibrosis score not only in evaluating the histological changes but also in predicting the clinical outcomes.

Regression of Liver Fibrosis in Patients on Hepatitis B Therapy Is Associated With Decreased Liver-Related Events.

BACKGROUND & AIMS: Liver fibrosis in patients with chronic hepatitis B can regress with successful antiviral therapy. However, the long-term clinical benefits of fibrosis regression have not been fully elucidated. This study investigated the association between biopsy-proven fibrosis regression by predominantly progressive, indeterminate, and predominantly regressive (P-I-R) score and liver-related events (LREs) in chronic hepatitis B patients. METHODS: Patients with on-treatment liver biopsy and significant fibrosis/cirrhosis (Ishak stage ≥3) were included in this analysis. Fibrosis regression was evaluated according to the P-I-R score of the Beijing Classification. LREs were defined as decompensations, hepatocellular carcinoma, liver transplantation, or death. The Cox proportional hazards model was used to determine associations of fibrosis regression with LREs. RESULTS: A total of 733 patients with Ishak stages 3/4 (n = 456; 62.2%) and cirrhosis (Ishak stages 5/6; n = 277; 37.8%) by on-treatment liver biopsy were enrolled. According to the P-I-R score, fibrosis regression, indeterminate, and progression were observed in 314 (42.8%), 230 (31.4%), and 189 (25.8%) patients, respectively. The 7-year cumulative incidence of LREs was 4.1%, 8.7%, and 18.1% in regression, indeterminate, and progression, respectively (log-rank, P < .001). Compared with patients with fibrosis progression, those with fibrosis regression had a lower risk of LREs (adjusted hazard ratio, 0.40; 95% CI, 0.16-0.99; P = .047), followed by the indeterminate group (adjusted hazard ratio, 0.86; 95% CI, 0.40-1.85; P = .691). Notably, this favorable association also was observed in patients with cirrhosis or low platelet counts (<150 × 109/L). CONCLUSIONS: Antiviral therapy-induced liver fibrosis regression assessed by P-I-R score is associated with reduced LREs. This shows the utility of histologic fibrosis regression assessed by on-treatment P-I-R score as a surrogate endpoint for clinical events in patients with hepatitis B virus-related fibrosis or early cirrhosis.

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).

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.

Matrisome gene-based subclassification of patients with liver fibrosis identifies clinical and molecular heterogeneities.

BACKGROUND AIMS: Excessive deposition and crosslinking of extracellular matrix increases liver density and stiffness, promotes fibrogenesis, and increases resistance to fibrinolysis. An emerging therapeutic opportunity in liver fibrosis is to target the composition of the extracellular matrix or block pathogenic communication with surrounding cells. However, the type and extent of extracellular changes triggering liver fibrosis depend on the underlying etiology. Our aim was to unveil matrisome genes not dependent on etiology, which are clinically relevant to liver fibrosis. APPROACH RESULTS: We used transcriptomic profiles from liver fibrosis cases of different etiologies to identify and validate liver fibrosis-specific matrisome genes (LFMGs) and their clinical and biological relevance. Dysregulation patterns and cellular landscapes of LFMGs were further explored in mouse models of liver fibrosis progression and regression by bulk and single-cell RNA sequencing. We identified 35 LFMGs, independent of etiology, representing an LFMG signature defining liver fibrosis. Expression of the LFMG signature depended on histological severity and was reduced in regressive livers. Patients with liver fibrosis, even with identical pathological scores, could be subclassified into LFMG Low and LFMG High , with distinguishable clinical, cellular, and molecular features. Single-cell RNA sequencing revealed that microfibrillar-associated protein 4 + activated HSC increased in LFMG High patients and were primarily responsible for the LFMG signature expression and dysregulation. CONCLUSIONS: The microfibrillar-associated protein 4 + -activated HSC-derived LFMG signature classifies patients with liver fibrosis with distinct clinical and biological characteristics. Our findings unveil hidden information from liver biopsies undetectable using traditional histologic assessments.

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.

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.

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.

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.

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.

Construction and application of the conditionally essential gene knockdown library in Klebsiella pneumoniae to screen potential antimicrobial targets and virulence genes via Mobile-CRISPRi-seq.

Klebsiella pneumoniae is a ubiquitous human pathogen, and its clinical treatment faces two major challenges: multidrug resistance and the pathogenesis of hypervirulent K. pneumoniae. The discovery and study of conditionally essential (CE) genes that can function as potential antimicrobial targets has always been a research concern due to their restriction in the development of novel antibiotics. However, the lack of essential functional genomic data has hampered the study of the mechanisms of essential genes related to antimicrobial susceptibility. In this study, we developed a pooled CE genes mobile clustered regularly interspaced short palindromic repeat (CRISPR) interference screening method (Mobile-CRISPRi-seq) for K. pneumoniae to identify genes that play critical roles in antimicrobial fitness in vitro and host immunity in vivo. Targeting 870 predicted CE genes in K. pneumoniae, Mobile-CRISPRi-seq uncovered the depletion of tetrahydrofolate synthesis pathway genes folB and folP under trimethoprim pressure. Our screening also identified genes waaE and fldA related to polymyxin and ß-lactam susceptibility by applying a screening strategy based on Mobile-CRISPRi-seq and comparative genomics. Furthermore, using a mouse infection model and Mobile-CRISPRi-seq, multiple virulence genes were identified, and among these genes, pal, yciS, and ribB were demonstrated to contribute to the pathogenesis of K. pneumoniae. This study provides a simple, rapid, and effective platform for screening potential antimicrobial targets and virulence genes in K. pneumoniae, and this broadly applicable system can be expanded for high-throughput functional gene study in multiple pathogenic bacteria, especially in gram-negative bacteria. IMPORTANCE The discovery and investigation of conditionally essential (CE) genes that can function as potential antimicrobial targets has always been a research concern because of the restriction of antimicrobial targets in the development of novel antibiotics. In this study, we developed a pooled CE gene-wide mobile clustered regularly interspaced short palindromic repeat (CRISPR) interference sequencing (Mobile-CRISPRi-seq) strategy in Klebsiella pneumoniae to identify genes that play critical roles in the fitness of antimicrobials in vitro and host immunity in vivo. The data suggest a robust tool to screen for loss-of-function phenotypes in a pooled gene knockdown library in K. pneumoniae, and Mobile-CRISPRi-seq may be expanded to multiple bacteria for screening and identification of genes with crucial roles in the fitness of antimicrobials and hosts.

A new glutamine synthetase index to evaluate hepatic lobular restoration in advanced fibrosis during anti-HBV therapy.

Hepatic lobular architecture distortion is a deleterious turning point and a crucial histological feature of advanced liver fibrosis in chronic liver diseases. Regression of fibrosis has been documented in chronic hepatitis B (CHB) patients. However, whether lobular architecture could be restored following fibrosis regression after antiviral therapy is still unclear. Glutamine synthetase (GS) is generally expressed by perivenular hepatocytes around hepatic veins (HV). In this study, we defined abnormal lobular architecture (GSPT ) as GS expressing in the vicinity of portal tracts (PT), which denotes parenchymal extinction and lobular collapse. We defined normal lobular architecture (GSHV ) as GS positivity area not approximating PTs. Therefore, we propose a new GS-index, defined as the percentage of GSHV /(GSHV + GSPT ), to evaluate the extent of architectural disruption and restoration. We evaluated 43 CHB patients with advanced fibrosis (Ishak stage ≥4). Posttreatment liver biopsy was performed after 78 weeks of anti-HBV therapy. The median GS-index improved from 7% (interquartile range [IQR]: 0%-23%) at baseline to 36% (IQR: 20%-57%) at Week 78 (p < 0.001). Totals of 22 patients (51%) had significant GS-index improvement from 0% (IQR: 0%-13%) to 55% (IQR: 44%-81%), while the other half had almost no change between 17% (IQR: 0%-33%) to 20% (IQR: 12%-31%). When GS-index78w ≥ 50% was used to define hepatic lobular restoration, 37% of patients (16/43) achieved lobular restoration, with much improvement in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (median value of ∆/Baseline in ALT: restored vs. nonrestored was 79.1% vs. 48.8%, p = 0.018; median value of ∆/Baseline in AST: restored vs. nonrestored was 69.1% vs. 32.5%, p = 0.005). More importantly, lobular restoration correlated with fibrosis regression (median value of ∆/Baseline in Ishak stage: restored vs. nonrestored was 25.0% vs. 0%, p = 0.008). Therefore, in the era of antiviral therapy for CHB, restoration of hepatic lobular architecture is achievable in patients with advanced fibrosis. GS-index provides additional insight into fibrosis regression that goes beyond collagen degradation.

Persistent steatosis correlates with decreased fibrosis regression during anti-HBV treatment in patients with chronic HBV infection.

Despite the increasing prevalence of steatosis in patients with chronic hepatitis B (CHB), whether the changes in steatosis impact fibrosis regression during antiviral therapy remain unclear. We aimed to identify the association between histological changes of steatosis and fibrosis in patients undergone antiviral treatment. Patients with paired liver biopsies before and after 78 weeks of antiviral therapy were enrolled in this study. Liver fibrosis was assessed by the Ishak score combined with Beijing Classification predominantly progressive, indeterminate, and predominately regressive score. Steatosis was evaluated by the nonalcoholic fatty liver disease activity score. Collagen in each site was quantitated by second harmonic generation/two photon excitation fluorescence technology. Serum proteomic changes after treatment were characterized by mass-based spectrometry. A total of 239 CHB patients were included and divided into four groups according to the changes in steatosis: 162 (67.8%) had no steatosis throughout, 24 (10.0%) developed new-onset steatosis, 21 (8.8%) had initial steatosis which disappeared, and 32 (13.4%) had persistent steatosis. The persistent steatosis group showed the lowest rate of fibrosis regression (14/32, 43.8%). Persistent steatosis correlated with decreased fibrosis regression significantly after adjusting for age, sex, fibrosis stage, and metabolic factors at baseline, as well as the viral response (adjusted odds ratio = 0.380, 95% confidence interval 0.145-0.996, p = 0.049). This decreased fibrosis regression was associated with accumulated collagen in the perisinusoidal area. Patients with persistent steatosis showed unique changes in glycolipid metabolism according to the serum proteomic atlas. Persistent steatosis correlated with decreased fibrosis regression during antiviral therapy in patients with CHB.

Shrub and precipitation interactions shape functional diversity of nematode communities on the Qinghai-Tibet Plateau.

Land use and climate change alter biodiversity patterns and ecosystem functioning worldwide. Land abandonment with consequent shrub encroachment and changes in precipitation gradients are known factors in global change. Yet, the consequences of interactions between these factors on the functional diversity of belowground communities remain insufficiently explored. Here, we investigated the dominant shrub effects on the functional diversity of soil nematode communities along a precipitation gradient on the Qinghai-Tibet Plateau. We collected three functional traits (life-history C-P value, body mass, and diet) and calculated the functional alpha and beta diversity of nematode communities using kernel density n-dimensional hypervolumes. We found that shrubs did not significantly alter the functional richness and dispersion, but significantly decreased the functional beta diversity of nematode communities in a pattern of functional homogenization. Shrubs benefited nematodes with longer life-history, larger body mass, and higher trophic levels. Moreover, the shrub effects on the functional diversity of nematodes depended strongly on precipitation. Increasing precipitation reversed the effects shrubs have on the functional richness and dispersion from negative to positive but amplified the negative effects shrubs have on functional beta diversity of nematodes. Benefactor shrubs had stronger effects on the functional alpha and beta diversity of nematodes than allelopathic shrubs along a precipitation gradient. A piecewise structural equation model showed that shrubs and its interactions with precipitation indirectly increased the functional richness and dispersion through plant biomass and soil total nitrogen, whereas it directly decreased the functional beta diversity. Our study reveals the expected changes in soil nematode functional diversity following shrub encroachment and precipitation, advancing our understanding of global climate change on nematode communities on the Qinghai-Tibet Plateau.

Exosomal miR-218 derived from mesenchymal stem cells inhibits endothelial-to-mesenchymal transition by epigenetically modulating of BMP2 in pulmonary fibrosis.

Endothelial-to-mesenchymal transition (EndMT), the process by which endothelial cells lose their characteristics and acquire mesenchymal phenotypes, participates in the pathogenic mechanism of idiopathic pulmonary fibrosis. Recently, exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-Exos) has been introduced as a promising treatment in organ fibrosis. This study aimed to explore the effects as well as the molecular mechanism for hucMSC-Exo in pulmonary fibrosis. The intravenous administration of hucMSC-Exos alleviated bleomycin-induced pulmonary fibrosis in vivo. Moreover, hucMSC-Exos elevated miR-218 expression and restored endothelial properties weakened by TGF-ß in endothelial cells. Knockdown of miR-218 partially abrogated the inhibition effect of hucMSC-Exos on EndMT. Our mechanistic study further demonstrated that MeCP2 was the direct target of miR-218. Overexpressing MeCP2 aggravated EndMT and caused increased CpG islands methylation at BMP2 promoter, which lead to BMP2 post-transcriptional gene silence. Transfection of miR-218 mimic increased BMP2 expression as well, which was downregulated by overexpression of MeCP2. Taken together, these findings indicate exosomal miR-218 derived from hucMSCs may possess anti-fibrotic properties and inhibit EndMT through MeCP2/BMP2 pathway, providing a new avenue of preventive application in pulmonary fibrosis.

Translation, cross-cultural adaptation, and psychometric investigation of Chinese version of the Orbach & Mikulincer Mental Pain Scale in patients with depressive disorder.

PURPOSE: This study aimed to translate, cross-culturally adapt, and preliminarily test the psychometric properties of the Chinese version of the Orbach & Mikulincer Mental Pain Scale (OMMP). METHODS: Psychometric investigation was performed on 240 depressed patients. The reliability of the Chinese version of the OMMP scale was expressed by internal consistency reliability and test-retest reliability (2-week interval), and confirmatory factor analysis (CFA) on the 8-factor, 31-item OMMP was conducted to examine the construct validity. RESULTS: The CFA showed that the modified model with 31 items had good reliability (Cronbach's α range = 0.691-0.871; ICC = 0.818). Criterion-related validity was also supported by significant and positive correlations between the eight factors and worst-ever suicidal ideation as well as depressive symptoms. CONCLUSION: The results indicated the usefulness of the OMMP-31 for Chinese depressed patients. It is necessary to estimate psychological pain to improve suicide management in the clinical setting.

Psychological pain in depressive disorder: A concept analysis.

AIM AND OBJECTIVES: The purpose of this paper is to identify a precise definition of the concept of psychological pain in the field of depressive disorder. BACKGROUND: Psychological pain is widespread in patients with depressive disorder and plays a central role in the suicide process. However, psychological pain is currently complex and broadly defined and does not reflect the unique nature of psychological pain in depressed patients. DESIGN: A concept analysis. METHODS: Rodgers' evolutionary approach was used to analyse the concept of psychological pain in depressive disorders. PubMed, CINAHL, Embase, PsycINFO, Sinomed, CNKI, and Wanfang were searched and 49 articles met the inclusion criteria. RESULTS: The key attributes of psychological pain were identified as negative affective perception, passive cognition and ineffective response, extreme behavioural tendency, and both state and trait characteristics. Antecedents included stressful life events, frustrated psychological needs, disease factors, physical factors, and negative cognitive biases. Consequences were the promotion of personal growth, enhanced meaning in life, low quality of life, barriers to treatment, high rates of psychiatric morbidity, self-harm, and suicide. CONCLUSION: Psychological pain is a subjectively widespread, intense, and complex affective experience centered on feelings of suffering resulting from negative self-perceptions and ineffective coping based on personality traits. In addition, psychological pain has two traits: an immediate affective reflection arising from experiencing stressful life events and a persistent and stable emotional trait, respectively. RELEVANCE TO CLINICAL PRACTICE: This study provides a conceptual framework to help clinical staff expand their knowledge of psychological pain and distinguish it from related terms. Interventions should address both the antecedents and the consequences and so this study suggests that future interventions could be developed in terms of positive emotions. NO PATIENT OR PUBLIC CONTRIBUTION: This study did not recruit participants, therefore details of participants will not be involved.