Tracing fossil-based plastics, chemicals and fertilizers production in China.

Phasing down fossil fuels is crucial for climate mitigation. Even though 80-90% of fossil fuels are used to provide energy, their use as feedstock to produce plastics, fertilizers, and chemicals, is associated with substantial CO2 emissions. However, our understanding of hard-to-abate chemical production remains limited. Here we developed a chemical process-based material flow model to investigate the non-energy use of fossil fuels and CO2 emissions in China. Results show in 2017, the chemical industry used 0.18 Gt of coal, 88.8 Mt of crude oil, and 12.9 Mt of natural gas as feedstock, constituting 5%, 15%, and 7% of China's respective total use. Coal-fed production of methanol, ammonia, and PVCs contributes to 0.27 Gt CO2 emissions ( ~ 3% of China's emissions). As China seeks to balance high CO2 emissions of coal-fed production with import dependence on oil and gas, improving energy efficiency and coupling green hydrogen emerges as attractive alternatives for decarbonization.

Intraoperative transcutaneous electroacupoint stimulation on early postoperative fatigue in patients with Parkinson's disease undergoing deep brain stimulation surgery.

Background: In this clinical trial, we evaluated the effects of transcutaneous electroacupoint stimulation (TEAS) on postoperative fatigue (POF) in Parkinson disease (PD) patients undergoing deep brain stimulation (DBS) surgery. Methods: A total 60 PD patients undergoing DBS surgery were enrolled. They were randomized to receive either electrical stimulation [alternative frequency 2/10 Hz, dense and disperse, intensity adjusted to the maximum tolerated by the participants (6-15 mAmp)] via surface electrodes (TEAS group) or surface electrodes only without electrical stimulation (Con group) at bilateral Zusanli and Sanyinjiao acupuncture points. All participants received their assigned intervention (TEAS or Con) during the 1st stage of surgery [(except during microelectrode recording (MER)] and the entire 2nd stage of surgery. Intraoperative anesthetic requirements were adjusted based on bispectral index (BIS) monitor. POF was assessed by Christensen fatigue scales (ChrFS), along with Quality of Recovery-15 (QoR-15) and mini-mental state examination (MMSE) postoperatively over a 7-day-period. We recorded the usage of rescue analgesics and anti-emetics. Results: Fifty-nine patients' datasets were included for final analyses. Fewer patients in TEAS experienced severe POF (defined as ChrFS ≥6) at T3 than those in the Con group (TEAS vs. Con: 7 vs. 22, p < 0.001). During the 1st stage of surgery, more patients in Con group required dexmedetomidine infusion (TEAS vs. Con: 2 vs. 6; P < 0.01). Total dosages of propofol and remifanil during the 2nd stage of surgery were TEAS vs. Con: 374.7 ± 61.2 vs 421.5 ± 81.9; p < 0.001 and 572.3 ± 82.0 vs. 662 ± 148.2; P < 0.001, respectively. Postoperative rescue analgesics (TEAS vs. Con: 2 vs. 6; P < 0.001) were used less in the TEAS group. TEAS patients reported better POF, MMSE and QoR15 scores than those in the Con group during most of the assessment period. Conclusions: Intraoperative TEAS decreased the severity of POF, reduced intraoperative anesthetic requirements and facilitated post-DBS recovery in this group of PD patients.

An Overview of Recycling Phenolic Resin.

Over a century ago, phenolic formaldehyde (PF) resin was developed and continues to increase in yield due to its diverse applications. However, PF resin is a thermosetting plastic lacking fluidity and moldability, which are nondegradable in natural environments, leading to severe threats to fossil resources as well as global environmental crises. As a result, recycling PF resin is extremely important. In this review, we provide the recent advances in the recycling of PF resin, which includes mechanical recycling, chemical recycling, and utilization of carbon-based materials. The advantages and disadvantages of each strategy are evaluated from a green chemistry perspective. This article aims to attract interest in PF resin design, synthesizing, application and recycling, offering useful suggestions.

Translational selenium nanoparticles boost GPx1 activation to reverse HAdV-14 virus-induced oxidative damage.

Human adenovirus (HAdV) can cause severe respiratory infections in immunocompromised patients, but its clinical treatment is seriously limited by side effects of drugs such as poor efficacy, low bioavailability and severe nephrotoxicity. Trace element selenium (Se) has been found will affect the disease progression of pneumonia, but its antivirus efficacy could be improved by speciation optimization. Therefore, herein we performed anti-HAdV effects of different Se speciation and found that lentinan (LNT)-decorated selenium nanoparticles (SeNPs) exhibited low cytotoxicity and excellent anti-HAdV antiviral activity. Furthermore, SeNPs@LNT reduced the HAdV infection-induced mitochondrial damage and excessive production of reactive oxygen species (ROS). It was also involved in the repair of host cell DNA damage and inhibition of viral DNA replication. SeNPs@LNT inhibited HAdV-induced apoptosis mainly by modulating the p53/Bcl-2 apoptosis signaling pathway. In vivo, SeNPs@LNT replenished Se by targeting the infected site through the circulatory system and was involved in the synthesis of Glutathione peroxidase 1 (GPx1). More importantly, GPx1 played an antioxidant and immunomodulatory role in alleviating HAdV-induced inflammatory cytokine storm and alleviating adenovirus pneumonia in Se-deficient mice. Collectively, this study provides a Se speciation of SeNPs@LNT with anti-HAdV activity, and demonstrate that SeNPs@LNT is a promising pharmaceutical candidate for the treatment of HAdV.

Study on quality control methods and pharmacodynamic material basis of different specifications of Corydalis Rhizoma produced in Zhejiang Province.

ETHNOPHARMACOLOGICAL RELEVANCE: The quality control methods of different specifications of Corydalis Rhizoma in Zhejiang China (ZJ CR) are the same, so the quality of each specification couldnot be guaranteed. To clarify the quality control methods and pharmacodynamic material basis of ZJ CR with different specifications could provide reference for the quality control of ZJ CR. AIM OF THE STUDY: The purpose of this study was to establish a quality control method for ZJ CR with different specifications and to screen out the pharmacodynamic material basis of ZJ CR with different specifications. MATERIALS AND METHODS: Firstly, according to the existing grading standards, the medicinal materials were divided into specifications, and the character indexes of ZJ CR with different specifications were established. The quality indexes were established by HPLC, network pharmacology and literature retrieval. The correlation between the trait indexes and quality indexes of ZJ CR with different specifications was analyzed, and the best quality control method was established. Further combined with the pharmacodynamic indexes of ZJ CR with different specifications, the pharmacodynamic material basis of ZJ CR with different specifications was screened out by spectrum-effect analysis. The correlation between trait indexes and pharmacodynamic indexes was analyzed to verify the rationality of grade standard. RESULTS: The three specifications of ZJ CR were CR (Diameter ≥ 1.1cm), CR (Diameter < 1.1cm), and CR (No size distinction). Diameter, width, thickness, grain weight, volume and 50 g grain number could be used as the trait indexes of ZJ CR. Protopine (CR1), palmatine hydrochloride (CR2), berberine hydrochloride (CR3), dehydrocorydaline (CR4), tetrahydropalmatine (CR5), tetrahydroberberine (CR6), corydaline (CR7), stylopine (CR8) and isoimperatorin (CR9) were identified. Total components, core components (CR5, CR6, CR7 and CR8), alcohol-soluble extracts (ASE) could be used as quality indexes. The best quality control methods of the three specifications respectively were: the larger the diameter and grain weight, the smaller the number of 50 g grains; The larger the diameter, the smaller the volume, thickness, width and number of 50 g particles; The larger the grain weight and volume, the smaller the number of 50 g grains. The main analgesic components of the three specifications respectively were: CR1, CR2 and core components; CR2, CR4; CR8, CR9. The larger the diameter and the less the number of 50 g grains, the better the analgesic effect of ZJ CR, and the grade standard was reasonable. CONCLUSIONS: This study showed that the quality control methods and pharmacodynamic material basis of ZJ CR with different specifications were different, which may be caused by the differences in traits and the contribution of main active ingredients. This study constructed an evaluation model combining external traits, internal quality and overall efficacy, and provided theoretical support for the rationality of ZJ CR grade standard.

Enhancing Energy Harvesting Efficiency of Flapping Wings with Leading-Edge Magnus Effect Cylinder.

According to the Magnus principle, a rotating cylinder experiences a lateral force perpendicular to the incoming flow direction. This phenomenon can be harnessed to boost the lift of an airfoil by positioning a rotating cylinder at the leading edge. In this study, we simulate flapping-wing motion using the sliding mesh technique in a heaving coordinate system to investigate the energy harvesting capabilities of Magnus effect flapping wings (MEFWs) featuring a leading-edge rotating cylinder. Through analysis of the flow field vortex structure and pressure distribution, we explore how control parameters such as gap width, rotational speed ratio, and phase difference of the leading-edge rotating cylinder impact the energy harvesting characteristics of the flapping wing. The results demonstrate that MEFWs effectively mitigate the formation of leading-edge vortices during wing motion. Consequently, this enhances both lift generation and energy harvesting capability. MEFWs with smaller gap widths are less prone to induce the detachment of leading-edge vortices during motion, ensuring a higher peak lift force and an increase in the energy harvesting efficiency. Moreover, higher rotational speed ratios and phase differences, synchronized with wing motion, can prevent leading-edge vortex generation during wing motion. All three control parameters contribute to enhancing the energy harvesting capability of MEFWs within a certain range. At the examined Reynolds number, the optimal parameter values are determined to be a∗ = 0.0005, R = 3, and ϕ0 = 0°.

Epidemiological Characteristics of Human Parainfluenza Viruses Infections - China, 2019-2023.

Introduction: A retrospective study based on sentinel surveillance was conducted in 10 provincial-level administrative divisions (PLADs) in China to enhance the understanding of the epidemiological characteristics of human parainfluenza viruses (HPIVs). Methods: From January 2019 to June 2023, respiratory specimens were collected from individuals with acute respiratory infections (ARIs) and screened for four HPIVs serotypes and other common respiratory viruses using multiplex real-time polymerase chain reaction (PCR). This study analyzed the association of HPIVs infections with seasonal patterns, geographical distribution, demographic profiles, clinical features, and co-infection status. Results: During the study period, a total of 12,866 ARIs were included. The overall detection rate of HPIVs was 6.15%, varying from 5.04% in 2022 to 9.70% in 2020. The median age of HPIVs-infected patients was 3 years. HPIV2 was more prevalent among individuals aged 5-17 years (42.57%), while HPIV4 was more common in those over 65 years (12.24%). HPIV3 (54.16%) and HPIV1 (27.18%) were the predominant serotypes, and their prevalence exhibited significant seasonal fluctuations post- coronavirus disease 2019 (COVID-19) pandemic. The peak of HPIV3 shifted three months later in 2020 compared to 2019 and returned to a summer peak thereafter. Two peaks of HPIV1 were observed in 2021 following the peak of HPIV3. Additionally, co-infections were frequent in HPIVs cases (overall rate: 22.12%), with human rhinovirus being the most common co-infecting virus. Conclusions: The prevalence of HPIVs in China was predominantly due to HPIV3 and HPIV1, and their seasonal patterns were altered by pandemic restrictions. Hence, continuous surveillance of HPIVs is essential.

Association between urinary BTEX metabolites and dyslexic odds among school-aged children.

Benzene, toluene, ethylbenzene, and xylene (BTEX) are ubiquitous in the environment, and all of them can cause neurotoxicity. However, the association between BTEX exposure and dyslexia, a disorder with language network-related regions in left hemisphere affected, remains unclear. We aimed to assess the relationship between BTEX exposure and dyslexic odds among school-aged children. A case-control study, including 355 dyslexics and 390 controls from three cities in China, was conducted. Six BTEX metabolites were measured in their urine samples. Logistic regression model was used to explore the association between the BTEX metabolites and the dyslexic odds. Urinary trans,trans-muconic acid (MU: a metabolite of benzene) was significantly associated with an increased dyslexic odds [odds ratio (OR) = 1.23, 95% confidence interval (CI): 1.01, 1.50], and the adjusted OR of the dyslexic odds in the third tertile was 1.72 (95% CI: 1.06, 2.77) compared to that in the lowest tertile regarding urinary MU concentration. Furthermore, the association between urinary MU level and the dyslexic odds was more pronounced among children from low-income families based on stratified analyses. Urinary metabolite levels of toluene, ethylbenzene, and xylene were not found to be associated with the dyslexic odds. In summary, elevated MU concentrations may be associated with an increased dyslexic odds. We should take measures to reduce MU related exposure among children, particularly those with low family income.

"3E" Analysis and Working Fluid Selection for a Cogeneration System for Geothermal Large Temperature Difference Utilization.

Widespread utilization of geothermal energy as a clean energy source can reduce the use of fossil fuels and thereby protect the environment. Previous combined heat and power (CHP) systems using low-temperature geothermal heat as a heat source have limited utilization of geothermal heat. In this study, a cogeneration system based on organic Rankine cycle (ORC) and absorption heat exchanger (AHE) is designed. We analyzed the thermal efficiency, exergy efficiency, and economics of the proposed system utilizing 85 °C low-temperature geothermal heat, and the optimal operating fluid for this system is discussed. The results show that the optimal working fluid for the proposed system is R245fa. Using R245fa as the working fluid, the proposed system can achieve an exergy efficiency of 61.39%, when the heat source outlet temperature can be as low as 23 °C, while the proposed system can achieve the lowest LCOE of 0.082 ($/kW ·h) when using R22 as the working fluid.

CD14 facilitates perinatal human cytomegalovirus infection in biliary epithelial cells via CD55.

Background & Aims: A high human cytomegalovirus (HCMV) infection rate accompanied by an increased level of bile duct damage is observed in the perinatal period. The possible mechanism was investigated. Methods: A total of 1,120 HCMV-positive and 9,297 HCMV-negative children were recruited, and depending on age, their liver biochemistry profile was compared. Fetal and infant biliary epithelial cells (F-BECs and I-BECs, respectively) were infected with HCMV, and the differences in cells were revealed by proteomic analysis. Protein-protein interactions were examined by coimmunoprecipitation and mass spectrometry analyses. A murine cytomegalovirus (MCMV) infection model was established to assess treatment effects. Results: Perinatal HCMV infection significantly increased the level of bile duct damage. Neonatal BALB/c mice inoculated with MCMV showed obvious inflammation in the portal area with an abnormal bile duct structure. Proteomics analysis showed higher CD14 expression in F-BECs than in I-BECs. CD14 siRNA administration hindered HCMV infection, and CD14-knockout mice showed lower MCMV-induced bile duct damage. HCMV infection upregulated CD55 and poly ADP-ribose polymerase-1 (PARP-1) expression in F-BECs. Coimmunoprecipitation and mass spectrometry analyses revealed formation of the CD14-CD55 complex. siRNA-mediated inhibition of CD55 expression reduced sCD14-promoted HCMV replication in F-BECs. In MCMV-infected mice, anti-mouse CD14 antibody and PARP-1 inhibitor treatment diminished cell death, ameliorated bile duct damage, and reduced mortality. Conclusions: CD14 facilitates perinatal HCMV infection in BECs via CD55, and PARP-1-mediated cell death was detected in perinatal cytomegalovirus-infected BECs. These results provide new insight into the treatment of perinatal HCMV infection with bile duct damage. Impact and implications: Perinatal human cytomegalovirus (HCMV) infection is associated with bile duct damage, but the underlying mechanism is still unknown. We discovered that CD14 expression is increased in biliary epithelial cells during perinatal HCMV infection and facilitates viral entry through CD55. We also detected PARP-1-mediated cell death in perinatal HCMV-infected biliary epithelial cells. We showed that blocking CD14 or inhibiting PARP-1 reduced bile duct damage and mortality in a mouse model of murine cytomegalovirus infection. Our findings provide a new insight into therapeutic strategies for perinatal HCMV infection.

Ehrlichia chaffeensis TRP120 ubiquitinates tumor suppressor APC to modulate Hippo and Wnt signaling.

Ehrlichia chaffeensis: TRP120 is a multifunctional effector that acts as a ligand mimic to activate evolutionary conserved eukaryotic signaling pathways Notch, Wnt, Hedgehog and Hippo. In addition, TRP120 is also a HECT E3 ubiquitin ligase known to ubiquitinate several host cell regulatory proteins (FBW7, PCGF5 and ENO-1) for degradation. We previously determined that TRP120 ubiquitinates the Notch negative regulator, FBW7, to maintain Notch signaling and promote infection. In this study, we investigated a potential mechanism used by Ehrlichia chaffeensis to maintain Hippo and Wnt signaling by ubiquitinating the tumor suppressor, adenomatous polyposis coli (APC), a negative regulator of Wnt and Hippo signaling. We determined that APC was rapidly degraded during E. chaffeensis infection despite increased APC transcription. Moreover, RNAi knockdown of APC significantly increased E. chaffeensis infection and coincided with increased active Yap and ß-catenin in the nucleus. We observed strong nuclear colocalization between TRP120 and APC in E. chaffeensis-infected THP-1 cells and after ectopic expression of TRP120 in HeLa cells. Additionally, TRP120 interacted with both APC full length and truncated isoforms via co-immunoprecipitation. Further, TRP120 ubiquitination of APC was demonstrated in vitro and confirmed by ectopic expression of a TRP120 HECT Ub ligase catalytic site mutant. This study identifies APC as a TRP120 HECT E3 Ub ligase substrate and demonstrates that TRP120 ligase activity promotes ehrlichial infection by degrading tumor suppressor APC to positively regulate Hippo and Wnt signaling.

Vision-based finite-time prescribed performance control for uncooperative UAV target-tracking subject to field of view constraints.

This paper presents a vision-based finite-time prescribed performance controller for unmanned aerial vehicle (UAV) tracking of uncooperative aerial targets. The relative states between UAV and target are estimated by an onboard monocular camera. The inability of visual measurements to accurately determine the initial state of the target renders conventional prescribed performance controllers ineffective in such situations. As a result, it becomes essential to address the problem of prescribed performance control under conditions of uncertain initial values By utilizing an auxiliary transforming function, an Asymmetric Barrier Lyapunov Function (ABLF) and a finite-time prescribed performance function, a robust adaptive controller based on backstepping framework is proposed to deal with state constraints under unknown initial tracking conditions. It is proved that, the closed-loop relative position is capable of reaching the prescribed performance bound before the preset transforming time and converging to the prescribed steady-state error before a finite setting time. Simulation examples are provided to illustrated the effectiveness of the proposed tracking algorithm.

Development and validation of machine learning models and nomograms for predicting the surgical difficulty of laparoscopic resection in rectal cancer.

BACKGROUND: The objective of this study is to develop and validate a machine learning (ML) prediction model for the assessment of laparoscopic total mesorectal excision (LaTME) surgery difficulty, as well as to identify independent risk factors that influence surgical difficulty. Establishing a nomogram aims to assist clinical practitioners in formulating more effective surgical plans before the procedure. METHODS: This study included 186 patients with rectal cancer who underwent LaTME from January 2018 to December 2020. They were divided into a training cohort (n = 131) versus a validation cohort (n = 55). The difficulty of LaTME was defined based on Escal's et al. scoring criteria with modifications. We utilized Lasso regression to screen the preoperative clinical characteristic variables and intraoperative information most relevant to surgical difficulty for the development and validation of four ML models: logistic regression (LR), support vector machine (SVM), random forest (RF), and decision tree (DT). The performance of the model was assessed based on the area under the receiver operating characteristic curve(AUC), sensitivity, specificity, and accuracy. Logistic regression-based column-line plots were created to visualize the predictive model. Consistency statistics (C-statistic) and calibration curves were used to discriminate and calibrate the nomogram, respectively. RESULTS: In the validation cohort, all four ML models demonstrate good performance: SVM AUC = 0.987, RF AUC = 0.953, LR AUC = 0.950, and DT AUC = 0.904. To enhance visual evaluation, a logistic regression-based nomogram has been established. Predictive factors included in the nomogram are body mass index (BMI), distance between the tumor to the dentate line ≤ 10 cm, radiodensity of visceral adipose tissue (VAT), area of subcutaneous adipose tissue (SAT), tumor diameter >3 cm, and comorbid hypertension. CONCLUSION: In this study, four ML models based on intraoperative and preoperative risk factors and a nomogram based on logistic regression may be of help to surgeons in evaluating the surgical difficulty before operation and adopting appropriate responses and surgical protocols.

Continuous peripheral electrical nerve stimulation improves cardiac function via autonomic nerve regulation in MI rats.

BACKGROUND: Peripheral electrical nerve stimulation (PENS) reportedly improves cardiac function after myocardial ischemia (MI) by rebalancing the cardiac autonomic nervous system. The dynamic and continuous influence of PENS on autonomic and cardiac functioning based on cardiac self-repair is not well understood. OBJECTIVES: This study aimed to explore the relationship between autonomic nervous balance and functional cardiac repair after MI and to clarify the optimal acupoint selection and time course for PENS. METHODS: The activities of the superior cervical cardiac sympathetic nerve and vagus nerve were recorded to reflect the autonomic tone directly. The Millar pressure-volume loop system was used for left ventricular diastolic and systolic function. Noninvasive continuous electrocardiography and echocardiography were performed to analyze heart rate, heart rate variability, and left ventricular function. The effect of continuous PENS (cPENS) or instant PENS (iPENS) on autonomic and cardiac indications was tested. RESULTS: Sympathetic nerve activity and vagus nerve activity increased as compensatory self-regulation on days 7 and 14 post-MI, followed by an imbalance of autonomic tone and cardiac dysfunction on day 28. cPENS-PC6 maintained autonomic hyperexcitability, improved myocardial systolic and diastolic abilities, and reduced myocardial fibrosis on day 28 post-MI, whereas cPENS-ST36 had a limited effect. Both iPENS-PC6 and iPENS-ST36 improved the autonomic and cardiac function of rats in the cPENS groups. CONCLUSION: Rats showed autonomic fluctuations and cardiac dysfunction 28 days post-MI. cPENS produced sympathomimetic action to sustain cardiac self-compensation, but with acupoint specificity. On the basis of cPENS, iPENS evoked autonomic regulation and cardiac benefits without acupoint differentiation.

[Expression and significance of hypoxia-inducible factor 1α and Bcl-2/adenovirus E1B19kDa-interacting protein 3 in children with traumatic brain injury]. / ç¼ºæ°§è¯±å¯¼å› å­1α、Bcl-2/è ºç— æ¯’E1B19kDa相互作用蛋白3在儿童创伤性脑损伤中的表达及意义.

OBJECTIVES: To dynamically observe the changes in hypoxia-inducible factor 1α (HIF-1α) and Bcl-2/adenovirus E1B19kDa-interacting protein 3 (BNIP3) in children with traumatic brain injury (TBI) and evaluate their clinical value in predicting the severity and prognosis of pediatric TBI. METHODS: A prospective study included 47 children with moderate to severe TBI from January 2021 to July 2023, categorized into moderate (scores 9-12) and severe (scores 3-8) subgroups based on the Glasgow Coma Scale. A control group consisted of 30 children diagnosed and treated for inguinal hernia during the same period, with no underlying diseases. The levels of HIF-1α, BNIP3, autophagy-related protein Beclin-1, and S100B were compared among groups. The predictive value of HIF-1α, BNIP3, Beclin-1, and S100B for the severity and prognosis of TBI was assessed using receiver operating characteristic (ROC) curves. RESULTS: Serum levels of HIF-1α, BNIP3, Beclin-1, and S100B in the TBI group were higher than those in the control group (P<0.05). Among the TBI patients, the severe subgroup had higher levels of HIF-1α, BNIP3, Beclin-1, and S100B than the moderate subgroup (P<0.05). Correlation analysis showed that the serum levels of HIF-1α, BNIP3, Beclin-1, and S100B were negatively correlated with the Glasgow Coma Scale scores (P<0.05). After 7 days of treatment, serum levels of HIF-1α, BNIP3, Beclin-1, and S100B in both non-surgical and surgical TBI patients decreased compared to before treatment (P<0.05). ROC curve analysis indicated that the areas under the curve for predicting severe TBI based on serum levels of HIF-1α, BNIP3, Beclin-1, and S100B were 0.782, 0.835, 0.872, and 0.880, respectively (P<0.05), and for predicting poor prognosis of TBI were 0.749, 0.775, 0.814, and 0.751, respectively (P<0.05). CONCLUSIONS: Serum levels of HIF-1α, BNIP3, and Beclin-1 are significantly elevated in children with TBI, and their measurement can aid in the clinical assessment of the severity and prognosis of pediatric TBI.

Antiviral memory B cells exhibit enhanced innate immune response facilitated by epigenetic memory.

The long-lasting humoral immunity induced by viral infections or vaccinations depends on memory B cells with greatly increased affinity to viral antigens, which are evolved from germinal center (GC) responses. However, it is unclear whether antiviral memory B cells represent a distinct subset among the highly heterogeneous memory B cell population. Here, we examined memory B cells induced by a virus-mimicking antigen at both transcriptome and epigenetic levels and found unexpectedly that antiviral memory B cells exhibit an enhanced innate immune response, which appeared to be facilitated by the epigenetic memory that is established through the memory B cell development. In addition, T-bet is associated with the altered chromatin architecture and is required for the formation of the antiviral memory B cells. Thus, antiviral memory B cells are distinct from other GC-derived memory B cells in both physiological functions and epigenetic landmarks.

H2AK119ub1 differentially fine-tunes gene expression by modulating canonical PRC1- and H1-dependent chromatin compaction.

Polycomb repressive complex 1 (PRC1) is a key transcriptional regulator in development via modulating chromatin structure and catalyzing histone H2A ubiquitination at Lys119 (H2AK119ub1). H2AK119ub1 is one of the most abundant histone modifications in mammalian cells. However, the function of H2AK119ub1 in polycomb-mediated gene silencing remains debated. In this study, we reveal that H2AK119ub1 has two distinct roles in gene expression, through differentially modulating chromatin compaction mediated by canonical PRC1 and the linker histone H1. Interestingly, we find that H2AK119ub1 plays a positive role in transcription through interfering with the binding of canonical PRC1 to nucleosomes and therefore counteracting chromatin condensation. Conversely, we demonstrate that H2AK119ub1 facilitates H1-dependent chromatin condensation and enhances the silencing of developmental genes in mouse embryonic stem cells, suggesting that H1 may be one of several possible pathways for H2AK119ub1 in repressing transcription. These results provide insights and molecular mechanisms by which H2AK119ub1 differentially fine-tunes developmental gene expression.

Development of a new Cox model for predicting long-term survival in hepatitis cirrhosis patients underwent transjugular intrahepatic portosystemic shunts.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) placement is a procedure that can effectively treat complications of portal hypertension, such as variceal bleeding and refractory ascites. However, there have been no specific studies on predicting long-term survival after TIPS placement. AIM: To establish a model to predict long-term survival in patients with hepatitis cirrhosis after TIPS. METHODS: A retrospective analysis was conducted on a cohort of 224 patients who underwent TIPS implantation. Through univariate and multivariate Cox regression analyses, various factors were examined for their ability to predict survival at 6 years after TIPS. Consequently, a composite score was formulated, encompassing the indication, shunt reasonability, portal venous pressure gradient (PPG) after TIPS, percentage decrease in portal venous pressure (PVP), indocyanine green retention rate at 15 min (ICGR15) and total bilirubin (Tbil) level. Furthermore, the performance of the newly developed Cox (NDC) model was evaluated in an internal validation cohort and compared with that of a series of existing models. RESULTS: The indication (variceal bleeding or ascites), shunt reasonability (reasonable or unreasonable), ICGR15, postoperative PPG, percentage of PVP decrease and Tbil were found to be independent factors affecting long-term survival after TIPS placement. The NDC model incorporated these parameters and successfully identified patients at high risk, exhibiting a notably elevated mortality rate following the TIPS procedure, as observed in both the training and validation cohorts. Additionally, in terms of predicting the long-term survival rate, the performance of the NDC model was significantly better than that of the other four models [Child-Pugh, model for end-stage liver disease (MELD), MELD-sodium and the Freiburg index of post-TIPS survival]. CONCLUSION: The NDC model can accurately predict long-term survival after the TIPS procedure in patients with hepatitis cirrhosis, help identify high-risk patients and guide follow-up management after TIPS implantation.

Transcriptomics analysis revealed that TAZ regulates the proliferation of KIRC cells through mitophagy.

Transcriptional Co-Activator with PDZ-Binding Motif (TAZ, also known as WWTR1) is a downstream effector of the Hippo pathway, involved in the regulation of organ regeneration and cell differentiation in processes such as development and regeneration. TAZ has been shown to play a tumor-promoting role in various cancers. Currently, many studies focus on the role of TAZ in the process of mitophagy. However, the molecular mechanism and biological function of TAZ in renal clear cell carcinoma (KIRC) are still unclear. Therefore, we systematically analyzed the mRNA expression profile and clinical data of KIRC in The Cancer Genome Atlas (TCGA) dataset. We found that TAZ expression was significantly upregulated in KIRC compared with normal kidney tissue and was closely associated with poor prognosis of patients. Combined with the joint analysis of 36 mitophagy genes, it was found that TAZ was significantly negatively correlated with the positive regulators of mitophagy. Finally, our results confirmed that high expression of TAZ in KIRC inhibits mitophagy and promotes KIRC cell proliferation. In conclusion, our findings reveal the important role of TAZ in KIRC and have the potential to be a new target for KIRC therapy.