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Abstract Setting the cosmological constant to be dynamical, we study the bulk and boundary thermodynamics of charged Anti-de Sitter black holes. We develop mass/energy formulas in terms of thermodynamic state functions for the extended thermodynamics, mixed thermodynamics, and boundary conformal field theory thermodynamics. We employ the residue method to study the topological properties of the phase transitions. Our analysis reveals that the bulk and boundary thermodynamics are topologically equivalent for both criticalities and first-order phase transitions in the canonical ensembles, as well as for the Hawking-Page(-like) phase transitions in the grand canonical ensembles. Additionally, those three kinds of phase transitions are shown to be distinguished by their unique topological charges. Our results exemplify the gravity-gauge duality in terms of topology.

Abstract Background There is a mutual influence between COVID-19, diabetes ketoacidosis, and acute pancreatitis, with clinical manifestations overlapping each other, which can lead to misdiagnosis and delayed treatment that could aggravate the condition and affect the prognosis. COVID-19-induced diabetes ketoacidosis and acute pancreatitis are extremely rare, with only four case reports in adults and no cases yet reported in children. Case presentation We reported a case of acute pancreatitis associated with diabetic ketoacidosis in a 12-year-old female child post novel coronavirus infection. The patient presented with vomiting, abdominal pain, shortness of breath, and confusion. Laboratory findings showed elevated levels of inflammatory markers, hypertriglyceridemia, and high blood glucose. The patient was treated with fluid resuscitation, insulin, anti-infection treatments, somatostatin, omeprazole, low-molecular-weight heparin, and nutritional support. Blood purification was administered to remove inflammatory mediators. The patient's symptoms improved, and blood glucose levels stabilized after 20 days of admission. Conclusion The case highlights the need for greater awareness and understanding of the interrelated and mutually promoting conditions of COVID-19, diabetes ketoacidosis, and acute pancreatitis among clinicians, to reduce misdiagnosis and missed diagnoses.

Abstract The violation of strong cosmic censorship (SCC) in RNdS black holes by a minimally coupled neutral massless scalar field has recently been discovered. This paper investigates the stability of the Cauchy horizon of a spherically charged de-Sitter black hole surrounded by dark matter under perturbations from a massless scalar field. Our results show that SCC can also be destroyed in the nearly extremal region, regardless of the presence of dark matter. However, the existence of dark matter can mitigate the extent of SCC violation, particularly when the cosmological constant and dark matter energy density are both small. Notably, the violation region of SCC as a function of the dark matter state parameter does not exhibit a simple monotonic decrease, suggesting that the influence of dark matter on SCC is not straightforward and may be complex.

Abstract Objectives Primary pulmonary lymphoepithelioma‐like carcinoma (PLELC) is a subtype of lung carcinoma associated with the Epstein–Barr virus (EBV). The clinical predictive biomarkers of immune checkpoint blockade (ICB) in PLELC require further investigation. Methods We prospectively analysed EBV levels in the blood and immune tumor biomarkers of 31 patients with ICB‐treated PLELC. Viral EBNA‐1 and BamHI‐W DNA fragments in the plasma were quantified in parallel using quantitative polymerase chain reaction. Results Progression‐free survival (PFS) was significantly longer in EBNA‐1 high or BamHI‐W high groups. A longer PFS was also observed in patients with both high plasma EBNA‐1 or BamHI‐W and PD‐L1 ≥ 1%. Intriguingly, the tumor mutational burden was inversely correlated with EBNA‐1 and BamHI‐W. Plasma EBV load was negatively associated with intratumoral CD8+ immune cell infiltration. Dynamic changes in plasma EBV DNA level were in accordance with the changes in tumor volume. An increase in EBV DNA levels during treatment indicated molecular progression that preceded the imaging progression by several months. Conclusions Plasma EBV DNA could be a useful and easy‐to‐use biomarker for predicting the clinical activity of ICB in PLELC and could serve to monitor disease progression earlier than computed tomography imaging.

Abstract Clusteroluminescence (CL) has recently gained significant attention due to its unique through‐space interactions associated with a high dependence on the aggregation of subgroups. These distinct features could easily transform the stimuli into visual fluorescence and monitor the fluctuation of the environment but have not received sufficient attention before. In this work, supramolecular films are designed based on the neutralization reaction of anhydride groups and the self‐assembly of dynamic covalent disulfide bonds in NaOH aqueous solution. The self‐assembly of hydrophilic carboxylate chromophores and hydrophobic disulfide‐containing five‐membered rings could be observed by the variation of the aggregation state of carboxylate in CL. Furthermore, the dynamic cross‐linking films obtained with water‐sensitive carboxylate chromophores could alter the aggregation distance stimulated by surrounding water vapor, causing the emission wavelength to change from 534 to 508 nm by varying the relative humidity. This work not only provides an approach to monitor the self‐assembly of clusteroluminogens but also offers new strategies for designing stimuli‐responsive materials that utilize the intrinsic features of CL.

Summary: TDP-43 is an RNA/DNA-binding protein that forms aggregates in various brain disorders. TDP-43 engages in many aspects of RNA metabolism, but its molecular roles in regulating genes and transposable elements (TEs) have not been extensively explored. Chronic TDP-43 knockdown impairs cell proliferation and cellular responses to DNA damage. At the molecular level, TDP-43 chronic deficiency affects gene expression either locally or distally by concomitantly altering the crosstalk between R-loops and 5-hydroxymethylcytosine (5hmC) in gene bodies and long-range enhancer/promoter interactions. Furthermore, TDP-43 knockdown induces substantial disease-relevant TE activation by influencing their R-loop and 5hmC homeostasis in a locus-specific manner. Together, our findings highlight the genomic roles of TDP-43 in modulating R-loop-5hmC coordination in coding genes, distal regulatory elements, and TEs, presenting a general and broad molecular mechanism underlying the contributions of proteinopathies to the etiology of neurodegenerative disorders.

Resistance traits of plants can be activated both at the damaged site and undamaged parts. Systemic resistance induced by local exogenous abscisic acid (ABA) application alleviated negative effect of low water availability on growth performance of clonal plant. However, timing of systemic resistance was poorly understood. Timing of systemic resistance refers to its activation and decay time within clonal network. Clonal fragment of Centella asiatica with four successive ramets (including first-oldest, second-older, third-old and fourth-young ramets) subjected to low water availability (20% soil moisture content) was used to explore effects of local exogenous ABA application on the timing of resistance activation and decay. Systemic resistance activated by local exogenous ABA application after 4 days remained at least 28 days. Compared with control, biomass accumulation of whole clonal fragment, root biomass and ratio of belowground to aboveground biomass significantly increased by local exogenous ABA application after 28 days. It is suggested that rapid activation and delay of resistance response induced by local exogenous ABA application within clonal network may improve fitness of clonal plant subjected to abiotic stress.

Mineral nutrients play a significant role in influencing the quality of tea. In order to detect the quantitative relationships between tea quality and mineral elements from the soil and tea plant, samples of soil and tea leaves from 'Baiyeyihao' and 'Huangjinya' cultivars were collected from 160 tea plantations, and these were used to determine 16 types of soil mineral elements, 16 leaf nutrient elements, and 10 key tea quality compositions. Three predictive models including linear regression, multiple linear regression (MLR) and random forest (RF) were applied to predict the main constituents of tea quality. The usage of mineral elements in the soil and tea leaves improved the estimation accuracy of tea quality compositions, the RF performed best for EGCG (R2 = 0.67–0.77), amino acid (R2 = 0.61–0.88), tea polyphenols (R2 = 0.68–0.77) and caffeine (R2 = 0.59–0.68), while the MLR performed well for predicting the soluble sugars (R2 = 0.54–0.84). The multi-source information demonstrated a superior accuracy in predicting the biochemical components of tea when compared to individual mineral elements.

ABSTRACTThe traditional von Neumann architecture is gradually failing to meet the urgent need for highly parallel computing, high-efficiency, and ultra-low power consumption for the current explosion of data. Brain-inspired neuromorphic computing can break the inherent limitations of traditional computers. Neuromorphic devices are the key hardware units of neuromorphic chips to implement the intelligent computing. In recent years, the development of optogenetics and photosensitive materials has provided new avenues for the research of neuromorphic devices. The emerging optoelectronic neuromorphic devices have received a lot of attentions because they have shown great potential in the field of visual bionics. In this paper, we summarize the latest visual bionic applications of optoelectronic synaptic memristors and transistors based on different photosensitive materials. The basic principle of bio-vision formation is first introduced. Then the device structures and operating mechanisms of optoelectronic memristors and transistors are discussed. Most importantly, the recent progresses of optoelectronic synaptic devices based on various photosensitive materials in the fields of visual perception are described. Finally, the problems and challenges of optoelectronic neuromorphic devices are summarized, and the future development of visual bionics is also proposed.

ABSTRACTEnterovirus 76 (EV-A76) is a serotype of enterovirus A and has been rarely reported. In this paper, we present the genetic characteristics of 15 EV-A76 isolates reported to circulate in the Xinjiang Uighur autonomous region of China in 2011. Sequence analysis revealed that all Chinese EV-A76 isolates had high similarity (> 98.3%) in the VP1 region, and five Chinese EV-A76 isolates were selected for whole genome sequencing based on VP1 nucleotide divergence. Similarity plots and boot-scanning analyses revealed frequent intertypic recombination in the nonstructural region of the EV-A76 isolate, as found with the EV-A89 donor sequence (also isolated in Xinjiang). The breakpoint of recombination is around nucleotide 3960, and the recombinant fragments covered part 2C and all P3 regions. This study increases publicly available EV-A76 nucleotide sequence and further our understanding EV-A76 molecular epidemiology.

Background: There is an inconsistent association between overweight/obesity and chronic obstructive pulmonary disease (COPD). Considering that different metabolic characteristics exist among individuals in the same body mass index (BMI) category, the classification of overweight/obesity based on metabolic status may facilitate the risk assessment of COPD. Our study aimed to explore the relationship between metabolic overweight/obesity phenotypes and unplanned readmission in patients with COPD.Methods: We conducted a retrospective cohort study using the Nationwide Readmissions Database (NRD). According to metabolic overweight/obesity phenotypes, patients were classified into four groups: metabolically healthy non-overweight/obesity (MHNO), metabolically unhealthy non-overweight/obesity (MUNO), metabolically healthy with overweight/obesity (MHO), and metabolically unhealthy with overweight/obesity (MUO). The primary outcome was unplanned readmission to hospital within 30 days of discharge from index hospitalization. Secondary outcomes included in-hospital mortality, length of stay (LOS) and total charges of readmission within 30 days.Results: Among 1,445,890 patients admitted with COPD, 167,156 individuals were unplanned readmitted within 30 days. Patients with the phenotype MUNO [hazard ratio (HR), 1.049; 95%CI, 1.038–1.061; p < 0.001] and MUO (HR, 1.061; 95%CI, 1.045–1.077; p < 0.001) had a higher readmission risk compared with patients with MHNO. But in elders (≥65yr), MHO also had a higher readmission risk (HR, 1.032; 95%CI, 1.002–1.063; p = 0.039). Besides, the readmission risk of COPD patients with hyperglycemia or hypertension regardless of overweight/obesity increased (p < 0.001).Conclusion: In patients with COPD, overweight/obesity alone had little effect on unplanned readmission, whereas metabolic abnormalities regardless of overweight/obesity were associated with an increased risk of unplanned readmission. Among the metabolic abnormalities, particular attention should be paid to hyperglycemia and hypertension. But in elders (≥65yr) overweight/obesity and metabolic abnormalities independently exacerbated the adverse outcomes.

Seed coating is the most important type of pretreatment. Since cotton is an important economic crop, the cost of its cultivation and the resulting economic benefits are undoubtedly important aspects to be considered. In recent years, the high cost of coating materials and complex production processes have prevented the widespread application of cotton seed coating. Moreover, cotton plants emerge from cotyledons, and the coating material on the seed coat does not play a role after the seed emerges. Given the above shortcomings, to adapt to the mechanized direct seeding method and to include a large number of fertilizers and fungicides, insecticides can be used together with the seed direct seeding into the soil; at the same time, this will improve the cotton seedling emergence rate, the physiological qualities of cotton seedlings after the emergence of cotton seedlings, and the resilience of cotton seedlings in the early stage of resistance ability. In this study, we devised a technique for balling cotton seeds employing components such as cassava starch, bentonite, diatomite, attapulgite, and seedling substrate. The compositional ratios of the method were determined via a growth chamber trial, and we evaluated its effect throughout the cotton reproductive period using field trials. The results showed that the emergence and emergence hole rates of the balled cotton seeds increased by 34.42% and 28.84%, respectively, compared with the uncoated control. In terms of cotton yield, the seed balling treatment increased the number of bolls per plant and the overall cotton yield. Seed balling technology is different from traditional seed pelleting or seed coating techniques. It gathers one or more seeds in seed balls, enabling the simultaneous sowing of multiple seeds of the same variety or different varieties in the same crop. Additionally, seed balls can encourage seeds to carry fertilizer and pesticides into the soil, further weakening soil-borne diseases and abiotic stresses, form a relatively stable internal environment in the soil, and ensure the germination of cotton seeds. Our findings provide a reference point to improve cotton seedling emergence through the utilization of this novel technology.

Real-timely monitoring of the crop water status can improve irrigation scheduling to increase water saving and enhance agricultural sustainability, whereas the canopy temperature measured by thermal imaging is an essential indicator for determining the rice water status. The primary goal of this study was to propose a new temperature index based on the temporal variance of the daily temperature and to develop the rice water status estimation model. Two field experiments involving two rice varieties and multi-irrigation regimes were conducted from 2019 to 2020. A thermal imaging camera was used to measure the canopy temperature from 8:00–16:00 at 2-hour intervals across all growth stages. Three plant water parameters, namely plant water content (PWC), canopy water content (CWC), and canopy equivalent water thickness (CEWT), were collected simultaneously. The results showed that canopy temperature and plant water parameters differed obviously among different irrigation treatments. The relative canopy temperature velocity (RCTV) was developed based on the temporal variance of the daily temperature, and the RCTV8–12 performed well in distinguishing different irrigation treatments and quantifying the rice water status. The coefficient of determination (R2) values of the exponential relationships between the optimal RCTV and plant water parameters reached 0.47 (PWC), 0.39 (CWC) and 0.18 (CEWT). The random forest model, which integrates the multi-temperature indices, achieved a good estimation for PWC (R2 = 0.78), CWC (R2 = 0.77), and CEWT (R2 = 0.64) across all growth stages. In summary, combining the multi-temperature indices derived from the thermal infrared imagery and machine learning algorithm can facilitate the non-destructive estimation of the rice water status and improve the precision irrigation schedule.

Rainfall and wind speed are two important meteorological variables that have a significant impact on agriculture, human health, and socio-economic development. While individual rainfall or wind events have been widely studied, little attention has been devoted to studying the lead–lag relationship between rainfall and wind speed, particularly in coastal regions where strong dependence between rainfall and wind speed is expected. Taking China's coastline as the case study, this paper aims to explore the variation trends of wind speed and rainfall and reveal the relationships between rainfall events and wind speeds on days before and after rainfall occurrence, by using meteorological station data from 1960 to 2018. The results show that wind speed tended to decrease while rainfall showed a slight increase for most stations. The daily wind speed increased 2 days before rainfall occurrence and decreased after then, with the highest wind speed observed during rainfall onset regardless of rainfall amount. Moreover, heavier rainfall events are more likely to occur with higher wind speeds. The findings of this study potentially improve the understanding of the dependence of rainfall and wind speed, which could help rainfall or wind-related disaster mitigation. HIGHLIGHTS Dependence of daily rainfall and wind speed over China's coastline is investigated.; Daily wind speed increased 2 days before rainfall occurrence and decreased after then.; Heavier rainfall events are more likely to occur with higher wind speeds.;

Abstract Clear cell renal cell carcinoma (ccRCC) is a main subtype of renal cancer, and advanced ccRCC frequently has poor prognosis. Many studies have found that lipid metabolism influences tumor development and treatment. This study was to examine the prognostic and functional significance of genes associated with lipid metabolism in individuals with ccRCC. Using the database TCGA, differentially expressed genes (DEGs) associated with fatty acid metabolism (FAM) were identified. Prognostic risk score models for genes related to FAM were created using univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses. Our findings demonstrate that the prognosis of patients with ccRCC correlate highly with the profiles of FAM-related lncRNAs (AC009166.1, LINC00605, LINC01615, HOXA-AS2, AC103706.1, AC009686.2, AL590094.1, AC093278.2). The prognostic signature can serve as an independent predictive predictor for patients with ccRCC. The predictive signature's diagnostic effectiveness was superior to individual clinicopathological factors. Between the low- and high-risk groups, immunity research revealed a startling difference in terms of cells, function, and checkpoint scores. Chemotherapeutic medications such lapatinib, AZD8055, and WIKI4 had better outcomes for patients in the high-risk group. Overall, the predictive signature can help with clinical selection of immunotherapeutic regimens and chemotherapeutic drugs, improving prognosis prediction for ccRCC patients.

Alkaloids are a large class of secondary metabolites in plants with significant pharmacological activity. As the active ingredients of many Chinese herbal medicines, they have great application value in clinical medicine. However, most alkaloids have obvious toxic effects and can be transmitted into the human body through the food chain, becoming an emerging potential risk factor for public health. This article reviews the types, sources and analytical methods of high-risk toxic and harmful alkaloids in food, aiming to provide warnings and reference for the detection and research of toxic and harmful alkaloids and the policy formulation of relevant regulatory authorities.

Abstract In this paper, we study the scalarization of the static and spherically symmetric dyonic Reissner–Nordstrom (RN) black holes in the Einstein–Maxwell-scalar theory where the scalar field is coupled to an electromagnetic Chern–Simons term. When both electric and magnetic charges are present, there exists an unstable region of parametric space for the dyonic RN black holes where the scalarization of black holes should occur. That is to say, mixing electric and magnetic charges can reduce the scalarization in this theory. Firstly, we calculate the perturbation field equations under the dyonic RN black hole background and obtain the corresponding asymptotic-flat perturbation solutions, which are the bifurcation points at the dyonic RN branch. The results show that the perturbation scalarization demands a lower bound of the coupling constant. Then, we calculate the scalarized black hole solutions bifurcating from the dyonic RN solutions. We find that there exist a lot of discrete branches of the scalarized solutions. Contract to the dyonic RN solutions, these scalarized solutions can be overcharged and their mass could even approach zero. After illustrating the behavior of the entropy for the scalarized black holes, we demonstrate that the scalarized configurations might be thermodynamically more stable than GR configurations. Moreover, we also show that for each scalarized branch, the black hole cannot reach the extremal limit with vanishing temperature.

Abstract Black hole echo is an important observable that can help us better understand gravitational theories. The non-linear electrodynamic black holes can admit multi-horizon, and the destruction of outer horizons does not violate the weak cosmic censorship, which leads to the multi-peak effective potential for the scalar perturbations and give rise to the echoes. Putting the initial wave packet released outside the peaks, we find that the time-domain profile of the echo will split when the peaks of the effective potential change from two to three. This is a distinctive phenomenon of black hole echo and it might be possible to determine the geometric structure of the non-linear electrodynamic black hole. We also analyse the properties of echo produced by different kinds of effective potentials.

Abstract Phosphoenolpyruvate carboxykinase 1 (PCK1) is the rate-limiting enzyme in gluconeogenesis. PCK1 is considered an anti-oncogene in several human cancers. In this study, we aimed to determine the functions of PCK1 in colorectal cancer (CRC). PCK1 expression in CRC tissues was tested by western blot and immunohistochemistry analyses and associations of PCK1 level with clinicopathological characteristics and disease survival evaluated. Further, we studied the effect of PCK1 on CRC cell proliferation and the underlying mechanisms. Our results show that PCK1 is expressed at significantly lower levels in CRC than in control tissues. High PCK1 expression was correlated with smaller tumor diameter and less bowel wall invasion (T stage). Overexpression and knockdown experiments demonstrated that PCK1 inhibits CRC cell growth both in vitro and in vivo. Mechanistically, PCK1 antagonizes CRC growth via inactivating UBAP2L phosphorylation at serine 454 and enhancing autophagy. Overall, our findings reveal a novel molecular mechanism involving PCK1 and autophagy, and highlight PCK1 as a promising candidate therapeutic target in CRC.

Abstract Osteosarcoma has the worst prognosis among malignant bone tumors, and effective biomarkers are lacking. Our study aims to explore m6A-related and immune-related biomarkers. Gene expression profiles of osteosarcoma and healthy controls were downloaded from multiple public databases, and their m6A-based gene expression was utilized for tumor typing using bioinformatics. Subsequently, a prognostic model for osteosarcoma was constructed using the least absolute shrinkage and selection operator and multivariate Cox regression analysis, and its immune cell composition was calculated using the CIBERSORTx algorithm. We also performed drug sensitivity analysis for these two genes. Finally, analysis was validated using immunohistochemistry. We also examined the RBM15 gene by qRT-PCR in an in vitro experiment. We collected routine blood data from 1738 patients diagnosed with osteosarcoma and 24,344 non-osteosarcoma patients and used two independent sample t tests to verify the accuracy of the CIBERSORTx analysis for immune cell differences. The analysis based on m6A gene expression tumor typing was most reliable using the two typing methods. The prognostic model based on the two genes constituting RNA-binding motif protein 15 (RBM15) and YTDC1 had a much lower survival rate for patients in the high-risk group than those in the low-risk group (P

The heat dome explains about 55% of the 2021 Western North American high temperatures. The intensity of heat extremes associated with such circulations are increasing faster than background global warming due to soil moisture feedbacks.

Abstract Background In the elderly, osteoporotic vertebral compression fractures (OVCFs) of the thoracolumbar vertebra are common, and percutaneous vertebroplasty (PVP) is a common surgical method after fracture. Machine learning (ML) was used in this study to assist clinicians in preventing bone cement leakage during PVP surgery. Methods The clinical data of 374 patients with thoracolumbar OVCFs who underwent single-level PVP at The First People's Hospital of Chenzhou were chosen. It included 150 patients with bone cement leakage and 224 patients without it. We screened the feature variables using four ML methods and used the intersection to generate the prediction model. In addition, predictive models were used in the validation cohort. Results The ML method was used to select five factors to create a Nomogram diagnostic model. The nomogram model's AUC was 0.646667, and its C value was 0.647. The calibration curves revealed a consistent relationship between nomogram predictions and actual probabilities. In 91 randomized samples, the AUC of this nomogram model was 0.7555116. Conclusion In this study, we invented a prediction model for bone cement leakage in single-segment PVP surgery, which can help doctors in performing better surgery with reduced risk.

Abstract At present, the impact of cuproptosis-related genes in the study of osteosarcoma is largely unknown. Genome-wide data of osteosarcoma and controls were downloaded from 3 different databases, and specific diagnostic models associated with cuproptosis in osteosarcoma were constructed by support vector machines with artificial intelligence, random forest trees and LASSO regression. Differential analysis of immune cell infiltration was examined using routine blood data from 25,665 cases. Differential expression was examined using immunohistochemistry and PCR. PDHA1 and CDKN2A were obtained as specific cuproptosis-related biomarkers for osteosarcoma after artificial intelligence analysis. PDHA1, CDKN2A and neutrophils were differentially expressed in OS and control groups. PDHA1 and CDKN2A are significantly dysregulated in OS and are able to serve as biomarkers of OS.

Abstract Background Circular RNAs (circRNAs) can be encapsulated into exosomes to participate in intercellular communication, affecting the malignant progression of a variety of tumors. Dysfunction of CD8 + T cells is the main factor in immune escape from hepatocellular carcinoma (HCC). Nevertheless, the effect of exosome-derived circRNAs on CD8 + T-cell dysfunction needs further exploration. Methods The effect of circCCAR1 on the tumorigenesis and metastasis of HCC was assessed by in vitro and in vivo functional experiments. The function of circCCAR1 in CD8 + T-cell dysfunction was measured by enzyme-linked immunosorbent assay (ELISA), western blotting and flow cytometry. Chromatin immunoprecipitation, biotinylated RNA pull-down, RNA immunoprecipitation, and MS2 pull-down assays were used to the exploration of mechanism. A mouse model with reconstituted human immune system components (huNSG mice) was constructed to explore the role of exosomal circCCAR1 in the resistance to anti-PD1 therapy in HCC. Results Increased circCCAR1 levels existed in tumor tissues and exosomes in the plasma of HCC patients, in the culture supernatant and HCC cells. CircCCAR1 accelerated the growth and metastasis of HCC in vitro and in vivo. E1A binding protein p300 (EP300) and eukaryotic translation initiation factor 4A3 (EIF4A3) promoted the biogenesis of circCCAR1, and Wilms tumor 1-associated protein (WTAP)-mediated m6A modification enhanced circCCAR1 stability by binding insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3). CircCCAR1 acted as a sponge for miR-127-5p to upregulate its target WTAP and a feedback loop comprising circCCAR1/miR-127-5p/WTAP axis was formed. CircCCAR1 is secreted by HCC cells in a heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1)-dependent manner. Exosomal circCCAR1 was taken in by CD8 + T cells and caused dysfunction of CD8 + T cells by stabilizing the PD-1 protein. CircCCAR1 promoted resistance to anti-PD1 immunotherapy. Furthermore, increased cell division cycle and apoptosis regulator 1 (CCAR1) induced by EP300 promoted the binding of CCAR1 and β-catenin protein, which further enhanced the transcription of PD-L1. Conclusions The circCCAR1/miR-127-5p/WTAP feedback loop enhances the growth and metastasis of HCC. Exosomal circCCAR1 released by HCC cells contributes to immunosuppression by facilitating CD8 + T-cell dysfunction in HCC. CircCCAR1 induces resistance to anti-PD1 immunotherapy, providing a potential therapeutic strategy for HCC patients.

Abstract The development of high-precision large-area optical coatings and devices comprising low-dimensional materials hinges on scalable solution-based manufacturability with control over exfoliation procedure-dependent effects. As such, it is critical to understand the influence of technique-induced transition metal dichalcogenide (TMDC) optical properties that impact the design, performance, and integration of advanced optical coatings and devices. Here, we examine the optical properties of semiconducting MoS2 films from the exfoliation formulations of four prominent approaches: solvent-mediated exfoliation, chemical exfoliation with phase reconversion, redox exfoliation, and native redox exfoliation. The resulting MoS2 films exhibit distinct refractive indices (n), extinction coefficients (k), dielectric functions (ε1 and ε2), and absorption coefficients (α). For example, a large index contrast of Δn ≈ 2.3 is observed. These exfoliation procedures and related chemistries produce different exfoliated flake dimensions, chemical impurities, carrier doping, and lattice strain that influence the resulting optical properties. First-principles calculations further confirm the impact of lattice defects and doping characteristics on MoS2 optical properties. Overall, incomplete phase reconfiguration (from 1T to mixed crystalline 2H and amorphous phases), lattice vacancies, intraflake strain, and Mo oxidation largely contribute to the observed differences in the reported MoS2 optical properties. These findings highlight the need for controlled technique-induced effects as well as the opportunity for continued development of, and improvement to, liquid phase exfoliation methodologies. Such chemical and processing-induced effects present compelling routes to engineer exfoliated TMDC optical properties toward the development of next-generation high-performance mirrors, narrow bandpass filters, and wavelength-tailored absorbers.

Objective: This study aimed to compare the efficiency of these two combined surgeries [prolapse and hemorrhoids (PPH) combined with the external hemorrhoidectomy and inferior internal hemorrhoid ligation; tissue selecting technique with mega-window stapler (TST-MS) combined with anal canal epithelial preservation operation]. Methods: This is a single-center, evaluator-blinded randomized controlled trial (RCT). A total of 204 participants were randomly divided into the two groups. The anal function, reoccurrence, intraoperative variables, and operative complications were assessed. The measurement data were compared by paired t test and rank sum test. Chi-squared or Fisher's exact test was used for count data and rank sum test for ranked data. To assess differences within each group in different time points, the repeated-measures analysis of variance was conducted. Results: TST-MS combined with anal canal epithelial preservation operation had lower Wexner score of anal incontinence (Z = 3.062, P = 0.002), higher patients’ satisfaction degree (t = 7.32, P 0.05). Conclusions: TST-MS combined with anal canal epithelial preservation operation showed better clinical efficiency in the treatment of prolapsed hemorrhoids. Trial registration: This study has been registered in Chinese Clinical Trial Registry (ChiCTR2000038533)

Bio-based epoxy resins have received significant attention in terms of concerns regarding carbon emission. Epoxidized soybean oil (ESO) derived from sustainable feedstock has been widely used to blend with traditional diglycidyl ether of bisphenol-A (DGEBA) to replace some of the petroleum-based components. In this work, molecular dynamics (MD) simulations were applied to track the network formation and predict the performance of methyl hexahydrophthalic anhydride (MHHPA)-cured ESO/DGEBA blend systems. The effects of ESO content and cross-linking degree on the mass density, volumetric shrinkage, glass transition temperature (Tg), coefficient of thermal expansion (CTE), Young’s modulus, yield strength, and Poisson’s ratio of the epoxy resin were systematically investigated. The results show that systems with high ESO content achieve gelation at low cross-linking degree. The Tg value, Young’s modulus, and yield strength increase with the increase in cross-linking degree, but the CTE at the glassy state and Poisson’s ratio decrease. The comparison results between the simulated and experimental data demonstrated that the MD simulations can accurately predict the thermal and mechanical properties of ESO-based thermosets. This study gains insight into the variation in thermo-mechanical properties of anhydride-cured ESO/DGEBA-based epoxy resins during the cross-linking process and provides a rational strategy for optimizing bio-based epoxy resins.

Significant columnar grains usually occur in the metallurgical microstructure of laser additive manufacturing, and plastic deformation introduced into additive manufacturing can significantly refine grain size. Due to the high deformation resistance and difficult deformation of titanium alloys, reducing the high-temperature deformation resistance of additive manufacturing titanium alloys is essential to facilitating the implementation of online rolling processes. High-temperature compression of titanium alloys was performed on a Gleeble-3800. It was found that the flow stress of the alloy decreased when the strain of the alloy decreased or the deformation temperature increased. The flow behavior of titanium alloys at high temperatures was investigated with the help of a Z-parameter flow model and multiple linear regression model. A positive correlation was found between the experimental and predicted values of the alloy under the multiple linear regression model, with a correlation coefficient of 0.98 and its error of 13.5%, which could better predict the flow stress values. In addition, hot processing maps were established, and the optimal deformation conditions were determined to provide some theoretical guidance for subsequent experiments.

Acellular fish swim bladders (AFSBs) are a promising biomaterial in tissue engineering, however, they may suffer from rapid degradation due to enzyme invasion. In this work, natural polyphenols, including epigallocatechin gallate (EGCG), proanthocyanidin (PC), tannic acid (TA) and protocatechuic acid (PCA), were utilized to improve the properties of AFSBs through crosslinking modifications. Fourier transform infrared (FTIR) results indicate that the triple helix of the collagen in AFSBs is well preserved after crosslinking. The differential scanning calorimetry (DSC), water contact angle (WCA) and in vitro degradation tests indicate that the polyphenol-crosslinked AFSBs exhibit improved thermal stability, enzymatic stability, hydrophilicity and mechanical properties. Among them, EGCG with multiple phenolic hydroxyl groups and low potential resistance is more favorable for the improvement of the mechanical properties and enzymatic stability of AFSBs, as well as their biocompatibility and integrity with the collagen triple helix. Moreover, the crosslinking mechanism was demonstrated to be due to the hydrogen bonds between polyphenols and AFSBs, and was affected by the molecular size, molecular weight and the hydroxyl groups activity of polyphenol molecules, as clarified by molecular dynamic (MD) simulations. The approach presented in this work paves a path for improving the properties of collagen materials.

Geobacter sulfurreducens mediates extracellular electron transfer (EET) reactions with different substrates, such as solid-phase Fe(III)-containing minerals, anodes and the cells of Geobacter metallireducens. To compare their roles in EET, the pilA-N, omcE, omcS, omcT and omcZ genes of G. sulfurreducens were systematically deleted. All mutants showed impaired and varied ability to form biofilms on nonconductive surface. Deletion of omcE also impaired bacterial ability to reduce ferrihydrite, but its impacts on the ability for anode reduction and the co-culture of G. metallireducens-G. sulfurreducens were minimal. The mutant without omcS showed diminished ability to reduce ferrihydrite and to form the co-culture, but was able to regain its ability to reduce anodes. Deletion of omcT, omcZ or pilA-N alone impaired bacterial ability to reduce ferrihydrite and anodes and to form the co-culture. Deletion of all tested genes abolished bacterial ability to reduce ferrihydrite and anodes. Triple-deletion of all omcS, omcT and omcZ abolished the ability of G. sulfurreducens to co-culture with G. metallireducens. However, deletion of only omcZ or pilA-N or both omcS and omcT abolished the ability of G. sulfurreducens without hydrogenase gene hybL to co-culture with G. metallireducens, which show their indispensable roles in direct electron transfer from G. metallireducens to G. sulfurreducens. Thus, the roles of pilA-N, omcE, omcS, omcT and omcZ for G. sulfurreducens in EET vary substantially, which also suggest that possession of PilA-N and multiple cytochromes of different structures enables G. sulfurreducens to mediate EET reactions efficiently with substrates of different properties.

Acidovorax citrulli is a seed-borne bacterium that causes bacterial fruit blotch of watermelon and other cucurbit plants worldwide. It uses a type III secretion system to inject type III effectors (T3Es) into plant cells, which affect the host immune responses and facilitate pathogen colonization. However, the current understanding of the specific molecular mechanisms and targets of these effectors in A. citrulli is limited. In this study, we characterized a novel T3E called AopU in A. citrulli group II strain Aac5, which shares homology with XopU in Xanthomonas oryzae. The Agrobacterium-mediated gene transient expression system was used to study the effect of AopU on host immunity. The results showed that AopU localized on the cell membrane and nucleus of Nicotiana benthamiana, inhibited reactive oxygen species burst induced by flg22 and the expression of marker genes associated with pathogen-associated molecular pattern-triggered immunity, but activated salicylic acid and jasmonic acid signal pathways. Further investigations revealed that AopU interacts with E3 ubiquitin ligase ClE3R in watermelon, both in vitro and in vivo. Interestingly, the deletion of aopU did not affect the virulence of A. citrulli, suggesting that AopU may have functional redundancy with other effectors in terms of its role in virulence. Collectively, these findings provide new insights into the mechanism of plant immune responses regulated by A. citrulli T3Es.

Renal interstitial fibrosis (RIF), a progressive process affecting the kidneys in chronic kidney disease (CKD), currently lacks an effective therapeutic intervention. Traditional Chinese medicine (TCM) has shown promise in reducing RIF and slowing CKD progression. In this study, we demonstrated the dose-dependent attenuation of RIF by Ootheca mantidis (SPX), a commonly prescribed TCM for CKD, in a mouse model of unilateral ureteral obstruction (UUO). RNA-sequencing analysis suggested that SPX treatment prominently downregulated apoptosis and inflammation-associated pathways, thereby inhibiting the fibrogenic signaling in the kidney. We further found that transplantation of fecal microbiota from SPX-treated mice conferred protection against renal injury and fibrosis through suppressing apoptosis in UUO mice, indicating that SPX ameliorated RIF via remodeling the gut microbiota and reducing apoptosis in the kidneys. Further functional exploration of the gut microbiota combined with fecal metabolomics revealed increased levels of some probiotics, including Akkermansia muciniphila (A. muciniphila), and modulations in glutamine-related amino acid metabolism in UUO mice treated with SPX. Subsequent colonization of A. muciniphila and supplementation with glutamine effectively mitigated cell apoptosis and RIF in UUO mice. Collectively, these findings unveil a functionally A. muciniphila- and glutamine-involved gut–renal axis that contributes to the action of SPX, and provide important clue for the therapeutic potential of SPX, A. muciniphila, and glutamine in combatting RIF.

Abstract A decline of anthropogenic aerosol (AA) emission is expected worldwide over the coming decades. But the climate effects of aerosol removal and greenhouse gases (GHG) emission at regional scale are poorly distinguished and constrained. Taking the Tibetan Plateau (TP) as an instance, analyses of the state‐of‐the‐art climate models participating in the Detection and Attribution Model Intercomparison Project imply that while the observed warming from 1961 to 2020 is predominantly attributed to GHG emission, the future temperature rise will be influenced by the combined effects of persistent increase in GHG concentration and reduction of AA emission. Here, we develop a new constraint method considering the changed contribution of AA forcing. Constrained by detected individual external forcings, the joint contributions of GHG (1.74°C) and AA forcings (0.10°C) will lead to a warming around 1.85°C over the TP during mid‐century (2041–2060) relative to 1995–2014 under SSP2‐4.5 scenario, which is 0.44°C cooler than the raw projection.

Abstract The robust and stable expression of CD38 in T‐cell acute lymphoblastic leukemia (T‐ALL) blasts makes CD38 chimeric antigen receptor (CAR)‐T/natural killer (NK) a potential therapy for T‐ALL. However, CD38 expression in normal T/NK cells causes fratricide of CD38 CAR‐T/NK cells. Here a “2‐in‐1” gene editing strategy is developed to generate fratricide‐resistant locus‐specific CAR‐T/NK cells. CD38‐specific CAR is integrated into the disrupted CD38 locus by CRISPR/Cas9, and CAR is placed under the control of either endogenous CD38 promoter (CD38KO/KI) or exogenous EF1α promoter (CD38KO/KIEF1α). CD38 knockout reduces fratricide and allows the expansion of CAR‐T cells. Meanwhile, CD38KO/KIEF1α results in higher CAR expression than CD38KO/KI in both CAR‐T and CAR‐NK cells. In a mouse T‐ALL model, CD38KO/KIEF1α CAR‐T cells eradicate tumors better than CD38KO/KI CAR‐T cells. Surprisingly, CD38KO/KI CAR‐NK cells show superior tumor control than CD38KO/KIEF1α CAR‐NK cells. Further investigation reveals that endogenous regulatory elements in NK cells lead to higher expression of CD38 CAR than in T cells, and the expression levels of CAR affect the therapeutic outcome of CAR‐T and CAR‐NK cells differently. Therefore, these results support the efficacy of CD38 CAR‐T/NK against T‐ALL and demonstrate that the “2‐in‐1” strategy can resolve fratricide and enhance tumor eradication, paving the way for clinical translation.

BackgroundThere is growing concern regarding elevated levels of circulating unmetabolized folic acid (UMFA) due to excessive intake of folic acid (FA). However, no randomized clinical trial has been conducted to examine the FA-UMFA dose-response relationship.ObjectiveThis study aimed to investigate the FA-UMFA dose-response relationship in Chinese adults with hypertension and elevated homocysteine (H-type hypertension), a population with clear clinical indication for FA treatment.MethodsThe data for this study were derived from a randomized, double-blind, multicenter clinical trial of 8 FA dosages on efficacy of homocysteine (Hcy) lowering. The parent trial had three 3 stages: screening period (2–10 days), run-in period (0–2 weeks, baseline visit), and double-blind treatment period (8 weeks) with follow-up visits at the end of the 2nd, 4th, 6th, and 8th weeks of treatment. Participants were randomly assigned to 8 treatment groups corresponding to FA dosages of 0, 0.4, 0.6, 0.8, 1.2, 1.6, 2.0 mg to 2.4 mg.ResultsThis study included 1,567 Chinese adults aged ≥45 years with H-type hypertension. There was a positive but non-linear association between FA supplementation and UMFA levels in the dosage range of 0 mg to 2.4 mg. In the regression analysis, the coefficients for the linear and quadratic terms of FA dosage were both statistically significant (P < 0.001). Notably, the slope for UMFA was greater for FA dosages >0.8 mg (ß = 11.21, 95% CI: 8.97, 13.45) compared to FA dosages ≤0.8 mg (ß = 2.94, 95% CI: 2.59, 3.29). Furthermore, FA dosages higher than 0.8 mg did not confer additional benefits in terms of increasing 5-methyl tetrahydrofolic acid (5-MTHF, active form of folate) or reducing homocysteine (Hcy).ConclusionIn Chinese adults with H-type hypertension, this study showed a positive, non-linear, dosage-response relationship between FA supplementation ranging from 0 to 2.4 mg and circulating UMFA levels. It revealed that 0.8 mg FA is an optimal dosage in terms of balancing efficacy (increasing 5-MTHF and lowering Hcy) while minimizing undesirable elevation of UMFA.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03472508?term=NCT03472508&draw=2&rank=1, identifier NCT03472508.

Ferroptosis is a form of regulated cell death that was first formally proposed a decade ago. While its role in cancer cell death was initially understudied, it has recently gained considerable interest from researchers. In recent years, a growing number of studies have focused on the role of ferroptosis in cancer progression, with the goal of developing novel ferroptosis-inducing cancer therapies. This study aims to present the developmental trend and hotspots of research on ferroptosis-inducing cancer therapy using bibliometric analysis. A literature search was conducted using the Web of Science Core Collection on October 1st, 2022, to retrieve articles and reviews pertaining to ferroptosis and cancer published from 2012 to 2022. Microsoft Excel 2016, VOSviewer 1.6.18 and CiteSpace (version 6.1. R6) were utilized to conduct the bibliometric analysis of publication trends, authorship, and citation networks, with a focus on identifying countries, institutions, journals, and authors contributing to the field. These analyses were used to predict future trends in this area. A total of 2839 articles were identified and extracted for analysis. The number of publications has increased almost every year, with a sharp increase after 2018. China produced the most publications in this area, followed by the United States. Central South University was the institution that published the most papers. Frontiers in Oncology was the journal with the highest number of publications, while Cell had the greatest impact factor. Daolin Tang was the most productive author and Dixon SJ was the most influential author. Co-occurrence and burst analyses of keywords and references were conducted to identify the developmental trends and hotspots in ferroptosis-inducing cancer therapy research. Main research directions have shifted from investigating the mechanism of ferroptosis to developing novel ferroptosis-targeting cancer therapies. Emerging topicsfocus on the role of ferroptosis in solid tumor therapy. Based on our bibliometric analysis, we predict that research on ferroptosis in cancer therapy will continue to be a hot topic in the future, with a growing number of treatment modalities related to ferroptosis being developed. Our study provides valuable insights into the current state and future trends of research in this field, serving as a useful guide for researchers seeking to make important contributions in this area.

Background: Long-term ambient particulate matter (PM) exposure has been found associated with chronic obstructive pulmonary disease (COPD) mortality in an increasing body of research. However, limited evidence was available on the potential causal links between PM1 and COPD mortality, especially in highly exposed areas. Objectives: To examine the COPD mortality risk following long-term ambient PM1 exposure in south China. Methods: The cohort included 580,757 participants recruited during 2009–2015. Satellite-based annual concentrations of PM1 were estimated at a spatial resolution of 1 km × 1 km and assigned to each participant based on their residential addresses. We analyzed the potential causal links between time-varying PM1 exposure and COPD mortality using marginal structural cox models within causal frameworks. Stratified analyses were also performed to identify the potential susceptible groups. Results: The annual average PM1 concentration continuously decreased over time. After adjusting for confounders, each 1 μg/m3 increase in PM1 concentration corresponded to an 8.1 % (95% confidence interval: 6.4–9.9 %) increment in the risk of COPD mortality. The impact of PM1 was more pronounced among the elderly and those with low exercise frequency, with a 1.9–6.9 % higher risk than their counterparts. We further observed a 0.1–9.7 % greater risk among those who lived in lower greenness settings. Additionally, we observed higher effect estimates in participants with long-term low PM1 exposure compared to the general population. Conclusions: COPD mortality risk significantly increased following long term ambient PM1 exposure, particularly among groups with certain demographics or long-term low exposure.

The product of leaf area index (LAI) and clumping index (CI) quantifies the effective leaf abundance and distribution across the landscape, and therefore, governs the radiation absorption, evapotranspiration, and carbon assimilation processes in the terrestrial ecosystems. Previous studies were mainly focused on developing inversion methods applicable to large scale for retrieving LAI and CI from multi-angular satellite observations. However, a few studies focused on quantifying the sensitivity of canopy bidirectional reflectance distribution function (BRDF) to changes in CI in a forward manner, hampering an accurate understanding of the relationship between CI and BRDF. In this study, we simulated how BRDF responds to changes in CI in Qinghai spruce (Picea crassifolia) forests based on a 3D radiative transfer model LESS and ground-measured data. We found that the LESS model effectively simulated the hot-spot, roof, and bowl-edge characteristics of the canopy BRDF by changing the sun-sensor geometry. We constructed forest scenes with variable CI (ranging from 0.4 to 0.8) to investigate the clumping effect on BRDF with different solar and observation angles. The red band bidirectional reflectance factor (BRF) showed higher sensitivity to changes in CI than that in the near-infrared (NIR) band. Canopy BRFs in the red band along the principal plane and cross principal planes measured in different seasons showed consistent sensitivity to changes in CI, suggesting that the red band BRF is helpful for CI inversion for forests with different levels of foliage clumping. In the NIR band, canopy BRFs along the principal plane measured in growing seasons [with solar zenith angle (SZA) 40°) were sensitive to changes in CI in highly clumped forests (with CI ranging from 0.4 to 0.6). However, canopy BRF in the NIR band showed low sensitivity to changes in CI in highly clumped forests (CI

Introduction To explore the epidemiological characteristics of ankylosing spondylitis (AS) in Guangxi Province of China through a large sample survey of more than 50 million aboriginal aboriginal population. Material and methods A systematic search was conducted using the International Classification of Diseases 10 (ICD-10) codes M45.x00(AS), M45.x03+(AS with iridocyclitis), and M40.101(AS with kyphosis) to search the database in the National Health Statistics Network Direct Reporting System (NHSNDRS). 14004 patients were eventually included in the study. The parameters analyzed included the number of patients, gender, marriage, blood type, occupation, age at diagnosis, and location of household registration data each year, and statistical analysis was performed. Results AS incidence rates increased from 1.30 (95% CI: 1.20–1.40) per 100,000 person-years in 2014 to 5.71 (95% CI: 5.50–5.92) in 2020 in Guangxi Province, and decreased slightly in 2021. Males have a higher incidence than females; the ratio was 5.61 : 1. The mean age of diagnosis in male patients was 45.4 (95% CI: 45.1–45.7) years, in females 47.6 (95% CI: 46.8–48.4) years. The most frequent blood type was O, and the most frequent occupation was farmer. The AS incidence rate was disparate in different cities. Liuzhou city had the highest eight-year average AS incidence rates from 2014 to 2021, and Chongzuo city had the lowest (p 0.05). Conclusions The AS person-years incidence rate was increasing in Guangxi province of China from 2014 to 2020, which had obvious gender and regional differences, showing the characteristics of local area aggregation.

Permeable reactive barrier (PRB) remediation technology has been widely used in the remediation of groundwater contamination. In numerical simulations, neglecting the non-uniform distribution of heavy metal contamination along the depth may lead to deviations between simulation results and reality. The distribution of heavy metals in the soil layer around a non-ferrous mining area in Hezhou, Guangxi, southern China was investigated, and it was found that the standard Gaussian function could well describe the non-uniform distribution of heavy metals in the soil layer. A two-dimensional analytical model solved by the finite element method was used to simulate the migration process of heavy metal contamination in the aquifer and PRB. The results show that the uniform distribution of contaminants along the depth ignores the dilution effect, which may underestimate the service life of the PRB and lead to an overly conservative design of the PRB. The breakthrough time of the PRB decreases with the increase of the maximum initial concentration (Cin,max) and the high concentration range (σ), and increases almost linearly with the barrier thickness (Lw). An optimal design method for PRB location and thickness is proposed, which can provide a reference for the engineering application of PRB. HIGHLIGHTS Consider the non-uniform distribution of heavy metal contaminants.; Investigate the distribution of heavy metals in the soil layer of the mining area.; Developing a two-dimensional numerical model.; Discussion of the effect of various factors on the adsorption performance of PRB.;

Abstract Progestin resistance is a problem for patients with endometrial carcinoma (EC) who require conservative treatment with progestin, and its underlying mechanisms remain unclear. YAP and TAZ (YAP/TAZ), downstream transcription coactivators of Hippo pathway, promote viability, metastasis and also drug resistance of malignant tumors. According to our microarray analysis, YAP/TAZ were upregulated in progestin resistant IshikawaPR cell versus progestin sensitive Ishikawa cell, which implied that YAP/TAZ may be a vital promotor of resistance to progestin. We found YAP/TAZ had higher expression levels among the resistant tissues than sensitive tissues. In addition, knocking down YAP/TAZ decreased cell viability, inhibited cell migration and invasion and increased the sensitivity of IshikawaPR cell to progestin. On the contrary, overexpression of YAP/TAZ increased cell proliferation, metastasis and promoted progestin resistance. We also confirmed YAP/TAZ were involved in progestin resistant process by regulating PI3K-Akt pathway. Furthermore, Verteporfin as an inhibitor of YAP/TAZ could increase sensitivity of IshikawaPR cells to progestin in vivo and in vitro. Our study for the first time indicated that YAP/TAZ play an important role in progestin resistance by regulating PI3K-Akt pathway in EC, which may provide ideas for clinical targeted therapy of progestin resistance.

Abstract In the generalized off-shell free energy landscape, black holes can be treated as thermodynamic topological defects. The local topological properties of the spacetime can be reflected by the winding numbers at the defects, while the global topological nature can be classified by the topological number which is the sum of all local winding numbers. We propose that the winding numbers can be calculated via the residues of isolated one-order pole points of characterized functions constructed from the off-shell free energy. Using the residue method, we show that the topologies of black holes can be divided into three classes with the topological numbers being -1, 0, and 1, respectively, being consistent with the results obtained in [Phys. Rev. Lett. 129, 191101 (2022)] by using the topological current method. Moreover, we point out that standard defect points, generation and annihilation points, and critical points can be distinguished by coefficients of the Laurent series of the off-shell characterized function at those singular points.

Abstract Ferroelectric tunnel junctions (FTJs) have great potential for application in high-density non-volatile memories. Recently, α-In2Se3 was found to exhibit robust in-plane and out-of-plane ferroelectric polarizations at a monolayer thickness, which is ideal to serve as a ferroelectric component in miniaturized electronic devices. In this work, we design two-dimensional van der Waals heterostructures composed of an α-In2Se3 ferroelectric and a hexagonal IV–VI semiconductor and propose an in-plane FTJ based on these heterostructures. Our first-principles calculations show that the electronic band structure of the designed heterostructures can be switched between insulating and metallic states by ferroelectric polarization. We demonstrate that the in-plane FTJ exhibits two distinct transport regimes, tunneling and metallic, for OFF and ON states, respectively, leading to a giant tunneling electroresistance effect with the OFF/ON resistance ratio exceeding 1 × 104. Our results provide a promising approach for the high-density ferroelectric memory based on the 2D ferroelectric/semiconductor heterostructures.

A record-breaking heavy rainfall swept across Suizhou of Hubei province in China on August 12, 2021. It was characterized by suddenness and extremeness and caused severe socio-economic losses. To deepen the understanding of such an urban rainstorm and to improve the forecasting ability, this study revealed the dominant atmospheric circulation and moisture sources for this event. We performed a Lagrangian model FLEXPART to understand this event in terms of moisture sources and transport trajectories. Three key circulation systems affecting this extreme event were identified, including the western Pacific subtropical high (WPSH), the low-level southwesterly jet and an anticyclone over northern China. The low-level jet was lifted along the northern dry and cold air mass to form a front, resulting in the heavy rain. The moisture sources located on land contributed about 64% of the moisture. The development of the low-level southwesterly jet in southern China was strengthened near the time of the precipitation occurrence, providing the main moisture supply. Southern China (23°–32.5°N, 98°–122°E) was the most important source region, which contributed the most to the precipitation (43.6%). The results highlight the prominent role of the terrestrial water cycle in this extreme precipitation event over Hubei.

Abstract Endometrial cancer is a common gynecological malignancy. With the onset of EC patients younger, conservative treatment with progesterone has become an important option for patients trying to preserve reproductive function. However, progesterone resistance is a key factor affecting the efficacy of therapy and it is urgent to clarify the mechanism so as to propose a potential target and inhibit the development of endometrial adenocarcinoma and progesterone resistance. MGLL, an important factor involved in lipid mobilization, is overexpressed in many tumors, however the biological function of MGLL in the development of endometrial adenocarcinoma and the process of progesterone resistance still remains unclear. In this study, we first found MGLL was highly expressed in progesterone resistant samples of endometrial adenocarcinoma, and then we verified its expression was increased in endometrial adenocarcinoma. Through in vitro and in vivo experiments, we demonstrated that overexpression of MGLL promoted tumor proliferation, metastasis and the occurrence of progestogen resistance, knockdown MGLL inhibited tumor proliferation, metastasis and reversed progestogen resistance. In addition, knockdown of MGLL can sensitize endometrial adenocarcinoma cells to progesterone, possibly by affecting ROS generation and reducing the expression of AKR1C1. Finally, it was verified that ABX-1431, MGLL inhibitor, reversed progesterone resistance and enhanced the sensitivity of endometrial adenocarcinoma to progesterone both in vitro and in vivo. In conclusion, the high expression of MGLL is involved in the occurrence and development of endometrial adenocarcinoma and progesterone resistance. Targeted inhibition of MGLL by inhibitors may be an effective method for the treatment of progesterone resistance in endometrial adenocarcinoma.

Abstract Background and objectives Vaccine is the most essential avenue to prevent hepatitis B virus (HBV) infection in infants and preschool children in China, with the largest populations carrying HBV in the world. This study aimed to evaluate the factors associating the response level of anti-HBs in children, providing instructions for HBV prevention clinically. Methods The children taking physical examinations in the Third Xiangya Hospital from January 2013 to April 2020 were recruited. Telephone follow-up were adopted to collect further information. Univariate logistic regression was used to analyse the relationship between age and anti-HBs expression. Grouping by age and anti-HBs expression, we used chi-square test and T test to compare qualitative and quantitative data between positive group and negative group in each age subgroup. The meaningful variables (P

Abstract Nonalcoholic steatohepatitis (NASH) is a rapidly developing pathology around the world, with limited treatment options available. Some farnesoid X receptor (FXR) agonists have been applied in clinical trials for NASH, but side effects such as pruritus and low‐density lipoprotein elevation have been reported. Intestinal FXR is recognized as a promising therapeutic target for metabolic diseases. Glycine‐β‐muricholic acid (Gly‐MCA) is an intestine‐specific FXR antagonist previously shown to have favorable metabolic effects on obesity and insulin resistance. Herein, we identify a role for Gly‐MCA in the pathogenesis of NASH, and explore the underlying molecular mechanism. Gly‐MCA improved lipid accumulation, inflammatory response, and collagen deposition in two different NASH models. Mechanistically, Gly‐MCA decreased intestine‐derived ceramides by suppressing ceramide synthesis–related genes via decreasing intestinal FXR signaling, leading to lower liver endoplasmic reticulum (ER) stress and proinflammatory cytokine production. The role of bile acid metabolism and adiposity was excluded in the suppression of NASH by Gly‐MCA, and a correlation was found between intestine‐derived ceramides and NASH severity. This study revealed that Gly‐MCA, an intestine‐specific FXR antagonist, has beneficial effects on NASH by reducing ceramide levels circulating to liver via lowering intestinal FXR signaling, and ceramide production, followed by decreased liver ER stress and NASH progression. Intestinal FXR is a promising drug target and Gly‐MCA a novel agent for the prevention and treatment of NASH.

It was shown that unbounded solutions of the Neumann initial-boundary value problem to the two-dimensional Keller–Segel system can be induced by initial data having large negative energy if the total mass $ \Lambda \in (4\pi, \infty)\setminus 4\pi \cdot \mathbb{N} $ and an example of such an initial datum was given for some transformed system and its associated energy in Horstmann–Wang (2001). In this work, we provide an alternative construction of nonnegative nonradially symmetric initial data enforcing unbounded solutions to the original Keller–Segel model.

Energy-efficient artificial photonic synapse is designed based on photo-sensitive BP/CdS heterostructure device, which can be used for high-performance brain-inspired neuromorphic computing.

Abstract Background Aerobic glycolysis has been recognized as one of the growth-promoting metabolic alterations of cancer cells. Emerging evidence indicates that nuclear factor κB (NF-κB) plays significant roles in metabolic adaptation in normal cells and cancer cells. However, whether and how NF-κB regulates metabolic reprogramming in hepatocellular carcinoma (HCC), specifically hepatitis B virus X protein (HBx)-initiated HCC, has not been determined. Methods A dataset of the HCC cohort from the TCGA database was used to analyse the expression of NF-κB family members. Expression of NF-κBp65 and phosphorylation of NF-κBp65 (p-p65) were detected in liver tissues from HBV-related HCC patients and normal controls. A newly established HBx +/+/NF-κBp65 f/f and HBx +/+ /NF-κBp65 Δhepa spontaneous HCC mouse model was used to investigate the effects of NF-κBp65 on HBx-initiated hepatocarcinogenesis. Whether and how NF-κBp65 is involved in aerobic glycolysis induced by HBx in hepatocellular carcinogenesis were analysed in vitro and in vivo. Results NF-κBp65 was upregulated in HBV-related HCC, and HBx induced NF-κBp65 upregulation and phosphorylation in vivo and in vitro. Hepatocyte-specific NF-κBp65 deficiency remarkably decreased HBx-initiated spontaneous HCC incidence in HBx-TG mice. Mechanistically, HBx induced aerobic glycolysis by activating NF-κBp65/hexokinase 2 (HK2) signalling in spontaneous hepatocarcinogenesis, and overproduced lactate significantly promoted HCC cell pernicious proliferation via the PI3K (phosphatidylinositide 3-kinase)/Akt pathway in hepatocarcinogenesis. Conclusion The data elucidate that NF-κBp65 plays a pivotal role in HBx-initiated spontaneous HCC, which depends on hyperactive NF-κBp65/HK2-mediated aerobic glycolysis to activate PI3K/Akt signalling. Thus, phosphorylation of NF-κBp65 will be a potential therapeutic target for HBV-related HCC.