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Abstract The reconstruction of critical-size calvarial defects remains a fundamental challenge. Recombinant collagen has gained significant attention in bone tissue engineering owing to its remarkable bioactivity and non-immunogenicity. Herein, we have for the first time developed a bioactive poly(ethylene glycol)-chondroitin sulfate-triple helical recombinant collagen (PEG-ChS-THRC) hydrogel for enhanced bone regeneration in cranial defects. A simple and mild crosslinking reaction of two-arm polyethylene glycol active ester (NHS-PEG-NHS), adipic dihydrazide modified chondroitin sulfate (ChS-ADH) and triple helical recombinant collagen (THRC) leads to the formation of the PEG-ChS-THRC hydrogel. The hydrogel demonstrates interconnected porous structures, enhanced mechanical strength, diminished swelling ratios and adjustable biodegradability. It possesses exceptional biocompatibility and bioactivity, significantly facilitating cell proliferation, adhesion, migration, and osteogenic differentiation of BMSCs. Micro-computed tomography (micro-CT), magnetic resonance imaging (MRI) and histological characterization of rat models with critical-size cranial defects have consistently demonstrated that the PEG-ChS-THRC hydrogel significantly promotes bone tissues regeneration. The innovative bioactive scaffold provides a remarkably improved remedy for critical-size cranial defects, holding greatly promising applications in the fields of bone tissue regeneration. Graphical Abstract

Abstract Data sources The Global Burden of Diseases, Injuries, and Risk Factors study (GBD) 2019. Background To describe burden, and to explore cross-country inequalities according to socio-demographic index (SDI) for stroke and subtypes attributable to diet. Methods Death and years lived with disability (YLDs) data and corresponding estimated annual percentage changes (EAPCs) were estimated by year, age, gender, location and SDI. Pearson correlation analysis was performed to evaluate the connections between age-standardized rates (ASRs) of death, YLDs, their EAPCs and SDI. We used ARIMA model to predict the trend. Slope index of inequality (SII) and relative concentration index (RCI) were utilized to quantify the distributive inequalities in the burden of stroke. Results A total of 1.74 million deaths (56.17% male) and 5.52 million YLDs (55.27% female) attributable to diet were included in the analysis in 2019.Between 1990 and 2019, the number of global stroke deaths and YLDs related to poor diet increased by 25.96% and 74.76% while ASRs for death and YLDs decreased by 42.29% and 11.34% respectively. The disease burden generally increased with age. The trends varied among stroke subtypes, with ischemic stroke (IS) being the primary cause of YLDs and intracerebral hemorrhage (ICH) being the leading cause of death. Mortality is inversely proportional to SDI (R = -0.45, p

Abstract Bladder cancer (BLCA) is a common malignant tumor in urinary system all over the world. However, due to its high recurrence rate and complex causes, clinicians often have limited options for surgical and drug treatments. Recent researchs on the molecular mechanism of BLCA have reveals its biological progress and potential for early diagnosis. Serine hydroxymethyltransferase 1/2 (SHMT1/2) is a crucial enzyme in the one-carbon metabolism of tumor cells, and the expression levels of these isozymes have been found to be associated with the biological progression of various malignant tumors. However, the impact of SHMT1/2 on the biological progression of bladder cancer and its molecular regulation mechanism remain unclear. In this research utilizes BLCA clinical sample data, the TCGA database, and in vitro cell experiments to predict the expression levels of SHMT1/2 in BLCA. The findings indicate that SHMT1 remained unchanged, while SHMT2 expression is increased in BLCA, which was related to poor prognosis. Additionally, SHMT2 affects the growth, migration, and apoptosis of bladder cancer cells in vitro. It also influences the expression levels of E-cadherin and N-cadherin, ultimately impacting the malignant biological progression of bladder tumors. These results establish a correlation between SHMT2 and the malignant biological progression of BLCA, providing a theoretical basis for the early diagnosis and treatment of bladder cancer.

Abstract Breast tumor‐initiating cells (BTICs) of triple‐negative breast cancer (TNBC) tissues actively repair DNA and are resistant to treatments including chemotherapy, radiotherapy, and targeted therapy. Herein, it is found that a previously reported secreted protein, sclerostin domain containing 1 (SOSTDC1), is abundantly expressed in BTICs of TNBC cells and positively correlated with a poor patient prognosis. SOSTDC1 knockdown impairs homologous recombination (HR) repair, BTIC maintenance, and sensitized bulk cells and BTICs to Olaparib. Mechanistically, following Olaparib treatment, SOSTDC1 translocates to the nucleus in an importin‐α dependent manner. Nuclear SOSTDC1 interacts with the N‐terminus of the nucleoprotein, chromatin helicase DNA‐binding factor (CHD1), to promote HR repair and BTIC maintenance. Furthermore, nuclear SOSTDC1 bound to β‐transducin repeat‐containing protein (β‐TrCP) binding motifs of CHD1 is found, thereby blocking the β‐TrCP‐CHD1 interaction and inhibiting β‐TrCP‐mediated CHD1 ubiquitination and degradation. Collectively, these findings identify a novel nuclear SOSTDC1 pathway in regulating HR repair and BTIC maintenance, providing insight into the TNBC therapeutic strategies.

Abstract Background Adaptive immunity is an important disease mediator of pulmonary vascular remodeling during pulmonary hypertension (PH) development, especially T‐cells lymphocytes. However, data for bibliometric analysis of T cell immunity in PH is currently vacant. This aimed to provide a comprehensive and visualized view of T‐cells research in PH pathogenesis and to lay a solid foundation for further studies. Methods The data was acquired from the Web of Science Core Collection database. Web of Science analytic tool was used to analysis the publication years, authors, journals, countries, and organizations. CiteSpace 6.2.R3, VOSviewer 1.6.16, and Scimago Graphica 1.0.35.0 were applied to conduct a visualization bibliometric analysis about authors, countries, institutions, journals, references, and keywords. Results Nine hundred and eight publications from 1992 to 2022 were included in the analysis. The results showed that Humbert Marc was the most prolific author. American Journal of Physiology Lung Cellular and Molecular Physiology had the most related articles. The institution with the most articles was Udice French Research University. The United States was far ahead in the article output. Keywords analysis showed that “Pulmonary hypertension” was the most usually appeared keyword in the relevant literature, and included “T‐cells”, “Regulatory T cells”, and “Activated T cell.” “miRNA” of reference co‐citation clustering analysis demonstrated the possible T‐cell immunity activation mechanisms in PH. The most cited literature was published in the European Heart Journal by Galie N in 2016. The strongest citation burst of keyword is “gene expression” and terms such as “vascular remodeling,” “growth,” “proliferation,” and “fibrosis” are among the list, indicating that T‐cells interact with stromal vascular cells to induce pulmonary vascular remodeling. The strongest burst of cited reference is “Galie N, 2016.” Conclusions T‐cell immunity is an important pathogenesis mechanism for PH development, which may have interaction with miRNAs and stromal vascular cells, but the possible T‐cell immunity activation mechanisms in PH need to be investigated further.

BackgroundUndifferentiated small round-cell sarcomas (uSRCSs) are a subgroup of sarcomas that are difficult to diagnose. Some uSRCSs have specific gene re-arrangements, but others do not. Currently, there is no specific treatments for advanced uSRCSs, and its treatment is largely based on general experience with sarcomas, which includes chemotherapy, targeted therapy, and immunotherapy. In this article, we report a patient with uSRCS who responded to treatment with anti-VEGF inhibitor surufatinib and anti-PD-1 inhibitor camrelizumab after progression on first-line chemotherapy, second-line anlotinib combined with immunotherapy, and third-line chemotherapy.Case descriptionIn July 2020, a 37-year-old female patient was diagnosed with advanced uSRCS. Results for the Ewing sarcoma RNA binding protein 1 and Wilms tumor suppressor (EWSR1/WT1) fusion gene were negative. The patient was also negative with BCOR (BCL6 co-repressor) and CIC (capicua transcriptional repressor) fusion gene. The next-generation sequencing results revealed point mutations on Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Beta (PIK3CB), Transcription Factor Binding To IGHM Enhancer 3 (TFE3), Mucin 16 (MUC16), and AXL (Axl, also called UFO, ARK, and Tyro7, is part of a family of receptor tyrosine kinases). The patient received 4 cycles of the Ifosfamide and epirubicin hydrochloride regimen, and her best objective response was stable disease. On November 3, 2020, a computed tomography (CT) scan revealed progressive disease (PD). Two cycles of camrelizumab (a programmed death-1 inhibitor) plus anlotinib (an anti- vascular endothelial growth factor drug) were administered, but PD was again observed. Thus, a regimen of gemcitabine plus docetaxel was adopted. Unfortunately, the disease progressed once again after two cycles of the treatment. On February 4, 2021, the patient began to receive targeted therapy with surufatinib combined with camrelizumab. A CT scan showed that the tumor achieved a partial response. As of April 2023, the patient had a progression-free survival time of 26 months.ConclusionsSurufatinib in combination with camrelizumab could be effective in the treatment of advanced uSRCSs.

Acoustic streaming enabled by a Lamb wave resonator (LWR) is efficient for particle trapping and enrichment in microfluidic channels. However, because Lamb waves combine the features of bulk acoustic waves and surface acoustic waves, the resulting acoustic streaming in the LWR occurs in multiple planes, and the particle flow behavior in this acoustofluidic system is largely unknown. Reported here are numerical simulations and laboratory experiments conducted to investigate the boundary conditions for particle motion inside a microvortex induced by an LWR. Upon dynamic capture, the particles’ trajectories become orbital paths within an acoustic vortex. The suspended particles encounter two distinct acoustic phenomena, i.e., the drag force resulting from acoustic streaming and the acoustic radiation force, which exert forces in various directions on the particles. When the acoustic radiation force and the fluid drag force are dominant for large and small particles in a mixed solution, respectively, the large particles reside within the vortex while the small particles remain at its periphery. Conversely, when the acoustic radiation force is dominant for both types of particles, the distribution pattern is reversed.

Exposure to fine particulate matter (PM) is associated with the neurodegenerative diseases. Coke oven emissions (COEs) in occupational environment are important sources of PM. However, its neurotoxicity is still unclear. Therefore, evaluating the toxicological effects of COE on the nervous system is necessary. In the present study, we constructed mouse models of COE exposure by tracheal instillation. Mice exposed to COE showed signs of cognitive impairment. This was accompanied by a decrease in miR-145a-5p and an increase in SIK1 expression in the hippocampus, along with synaptic structural damage. Our results demonstrated that COE-induced miR-145a-5p downregulation could increase the expression of SIK1 and phosphorylated SIK1, inhibiting the cAMP/PKA/CREB pathway by activating PDE4D, which was associated with reduced synaptic structural plasticity. Furthermore, restoring of miR-145a-5p expression based on COE exposure in HT22 cells could partially reversed the negative effects of COE exposure through the SIK1/PDE4D/cAMP axis. Collectively, our findings link epigenetic regulation with COE-induced neurotoxicity and imply that miR-145a-5p could be an early diagnostic marker for neurological diseases in patients with COE occupational exposure.

The study presents the Multi-Strategy Learning Fusion Slime Mould Algorithm (MFSMA), a novel method designed to optimize parameters in photovoltaic systems, thereby increasing the efficiency of solar energy conversion. MFSMA employs an advanced technique that incorporates elite opposition-based learning to quickly identify optimal solutions while preserving diversity within the population. Additionally, it integrates a ranking mechanism from the Grey Wolf Algorithm, which categorizes individuals according to their fitness levels, ensuring a balanced approach between exploratory diversity and exploitative precision during the optimization journey. Through rigorous testing on various benchmark functions, MFSMA has demonstrated its exceptional ability to outperform existing algorithms widely used in the sector. The algorithm’s effectiveness is further validated through its application in determining the parameters of single, double, and triple-junction photovoltaic modules. Moreover, the durability and effectiveness of the MFSMA algorithm have been rigorously evaluated using data from manufacturers’ datasheets across different temperature and irradiance conditions. Statistical analysis supports the conclusion that MFSMA offers superior accuracy and dependability in estimating vital parameters for photovoltaic modules, making it an invaluable tool for overcoming the challenges of parameter identification in solar energy technologies.

The big data of rolling bearings for on-site monitoring usually contains very few failure samples and easily affected by noise and monitoring errors, so it is difficult to extract and identify useful fault information in normal samples. In addition, the rolling bearing samples of field test are un-labeled dataset of unknown fault types. If the existing fault diagnosis approaches are directly used for extraction and identification, it is easy to cause misjudgment or missing judgment. To solve this problem, a novel intelligent fault diagnosis approach using deep transfer learning based on joint generalized sliced Wasserstein distances (JGSWD) deep transfer learning is proposed. Firstly, the joint discrepancy between the data from real-case scenarios (DRS) and the data from laboratory equipment (DLE) is minimized by calculating the generalized sliced Wasserstein distances. Following, the marginal and conditional dataset distribution between source domain and target domain is balanced by using the dynamic domain alignment. Then, the top K correlated pseudo labels are calculated for reducing the conditional distribution and improving better transfer capability. Finally, the deep transfer learning from laboratory bearing dataset to field bearing dataset is carried out. The result shows that the proposed JGSWD method can achieve 97.56% fault diagnosis accuracy, which is higher than the other methods. Therefore, it is a practical semi-supervised learning approach for bearing fault diagnosis with small samples.

Abstract Perturbations in gene regulation during palatogenesis can lead to cleft palate, which is among the most common congenital birth defects. Here, we perform single-cell multiome sequencing and profile chromatin accessibility and gene expression simultaneously within the same cells (n = 36,154) isolated from mouse secondary palate across embryonic days (E) 12.5, E13.5, E14.0, and E14.5. We construct five trajectories representing continuous differentiation of cranial neural crest-derived multipotent cells into distinct lineages. By linking open chromatin signals to gene expression changes, we characterize the underlying lineage-determining transcription factors. In silico perturbation analysis identifies transcription factors SHOX2 and MEOX2 as important regulators of the development of the anterior and posterior palate, respectively. In conclusion, our study charts epigenetic and transcriptional dynamics in palatogenesis, serving as a valuable resource for further cleft palate research.

Abstract Background Various factors have been found to be associated with high levels of death anxiety experienced by oncology nurses. The aim of this study was to use a person-oriented approach to examine the death anxiety patterns of Chinese oncology nurses and to analyze the differences in anxiety characteristics and their associated influencing factors. Methods A cross-sectional survey regarding palliative care among registered oncology nurses was conducted in Jiangsu Province, China.Latent class analyses was applied to identify their patterns of death anxiety. The score of PCQN-C (The Chinese version of the Palliative Care Quiz for Nursing) and FATCOD-B-C (The Chinese version of the Frommelt Attitude Toward Care of the Dying scale), the demographic and working characteristics were further analyzed through covariance analysis (ANCOVA) and multivariate (or logistic) regression across the subgroups. Results A two-potential-category model was selected based on the fit index. The results showed that 79% of oncology nurses belonged to the high pressure and pain group and 21% belonged to the low death anxiety group. The high pressure and pain group had significantly higher scores in the dimensions of emotion, stress and pain, time awareness, and cognition compared to the low death anxiety group. Factors influencing the high pressure and pain group included shorter working years, non-national or provincial oncology nursing specialists, non-national palliative care specialists, never discussing the topic of death with patients or family members, no palliative care related training, and PCQN and FATCOD scores. Conclusions Our study suggests that oncology nurses’ death anxiety can be divided into two categories: low death anxiety and high stress pain, and certain factors, such as being female, having a short work experience, and lacking palliative care-related training, increase the likelihood of death anxiety.

Most of the existing accurate positioning systems for underground personnel adopt UWB positioning technology, which is based on the layout mode of personnel positioning card + positioning substation to achieve centimeter-level high precision positioning. However, the existing models ignore the complexity of the working face environment, the influence of the change of the location of the base station installed with hydraulic support on the positioning accuracy, as well as the difficulty of field installation and other factors. To solve the above problems, a low power consumption positioning system for fully mechanized mining face is designed, which adopts Bluetooth positioning and LoRa wireless technology. The locator is used as a beacon and powered by battery, which can be installed in any position of the working face. Personnel positioning card integrates Bluetooth positioning and LoRa wireless technology, and integrates with mining lamp to form information mining lamp; the substation fusion LoRa wireless module is installed at both ends of the fully mechanized face to collect and transmit location information. The system can be compatible with the existing personnel accurate positioning system, and avoid the problems that the existing technology is difficult to solve in the positioning of fully mechanized mining face. It has the advantages of convenient installation, low cost and easy maintenance.

In hydrated soft biological tissues experiencing edema, which is typically associated with various disorders, excessive fluid accumulates and is encapsulated by impermeable membranes. In certain cases of edema, an indentation induced by pressure persists even after the load is removed. The depth and duration of this indentation are used to assess the treatment response. This study presents a mixture theory-based approach to analyzing the edematous condition. The finite element analysis formulation was grounded in mixture theory, with the solid displacement, pore water pressure, and fluid relative velocity as the unknown variables. To ensure tangential fluid flow at the surface of tissues with complex shapes, we transformed the coordinates of the fluid velocity vector at each time step and node, allowing for the incorporation of the transmembrane component of fluid flow as a Dirichlet boundary condition. Using this proposed method, we successfully replicated the distinct behavior of pitting edema, which is characterized by a prolonged recovery time from indentation. Consequently, the proposed method offers valuable insights into the finite element analysis of the edematous condition in biological tissues.

The two-phase seepage fluid (i.e., air and water) behaviors in undisturbed granite residual soil (U-GRS) have not been comprehensively studied due to a lack of accurate and representative models of its internal pore structure. By leveraging X-ray computed tomography (CT) along with the lattice Boltzmann method (LBM) enhanced by the Shan–Chen model, this study simulates the impact of internal pore characteristics of U-GRS on the water–gas two-phase seepage flow behaviors. Our findings reveal that the fluid demonstrates a preference for larger and straighter channels for seepage, and as seepage progresses, the volume fraction of the water/gas phases exhibits an initial increase/decrease trend, eventually stabilizing. The results show the dependence of two-phase seepage velocity on porosity, while the local seepage velocity is influenced by the distribution and complexity of the pore structure. This emphasizes the need to consider pore distribution and connectivity when studying two-phase flow in undisturbed soil. It is observed that the residual gas phase persists within the pore space, primarily localized at the pore margins and dead spaces. Furthermore, the study identifies that hydrophobic walls repel adjacent fluids, thereby accelerating fluid movement, whereas hydrophilic walls attract fluids, inducing a viscous effect that decelerates fluid flow. Consequently, the two-phase flow rate is found to increase with then-enhanced hydrophobicity. The apex of the water-phase volume fraction is observed under hydrophobic wall conditions, reaching up to 96.40%, with the residual gas-phase constituting 3.60%. The hydrophilic wall retains more residual gas-phase volume fraction than the neutral wall, followed by the hydrophobic wall. Conclusively, the investigations using X-ray CT and LBM demonstrate that the pore structure characteristics and the wettability of the pore walls significantly influence the two-phase seepage process.

In this study, we analyzed GATA2 mutations (GATA2mut) and co-mutations in 166 Chinese patients with cytogenetically normal acute myeloid leukemia. This was done through targeted next-generation sequencing of 34 genes associated with myeloid leukemia. GATA2mut was identified in 17 (10%) patients being significantly correlated with co-mutations in CCAAT/enhancer-binding protein alpha (CEBPA) double mutation (P = 0.001). We observed that the N-terminal zinc finger domain (ZF1) was linked to CEBPA mutations, while the C-terminal zinc finger domain (ZF2) was associated with Wilms' tumor 1 (WT1) mutations. It was also noted that patients with GATA2mut had lower platelet counts at diagnosis (P = 0.032). In the entire cohort, GATA2mut had no significant prognostic impact on overall survival (OS) (P = 0.762) and relapse-free survival (RFS) (P = 0.369) compared to patients with GATA2wt. The OS (P = 0.737) and RFS (P = 0.894) of the ZF1 mutation were similar to those of the ZF2 mutation. Most patients with GATA2 mutations were classified in the ELN2022 favorable- and intermediate-risk groups. GATA2mut patients in the favorable-risk group were divided into GATA2High and GATA2Low groups using a median cutoff variant allele frequency (VAF) of 40.13%. GATA2High patients were associated with worse OS (P = 0.031) and RFS (P = 0.021) than GATA2Low patients. In the intermediate-risk group, the high median VAF of GATA2 (≥38.51%) had no significant effect in OS and RFS compared with the low median VAF (

Heart Failure (HF) continues to be a complex public health issue with increasing world population prevalence. Although overall mortality has decreased for HF and hypertrophic cardiomyopathy (HCM), a precursor for HF, their prevalence continues to increase annually. Because the etiology of HF and HCM is heterogeneous, it has been difficult to identify novel therapies to combat these diseases. Isoproterenol (ISP), a non-selective β-adrenoreceptor agonist, is commonly used to induce cardiotoxicity and cause acute and chronic HCM and HF in mice. However, the variability in dose and duration of ISP treatment used in studies has made it difficult to determine the optimal combination of ISP dose and delivery method to develop a reliable ISP-induced mouse model for disease. Here we examined cardiac effects induced by ISP via subcutaneous (SQ) and SQ-minipump (SMP) infusions across 3 doses (2, 4, and 10mg/kg/day) over 2 weeks to determine whether SQ and SMP ISP delivery induced comparable disease severity in C57BL/6J mice. To assess disease, we measured body and heart weight, surface electrocardiogram (ECG), and echocardiography recordings. We found all 3 ISP doses comparably increase heart weight, but these increases are more pronounced when ISP was administered via SMP. We also found that the combination of ISP treatment and delivery method induces contrasting heart rate, RR interval, and R and S amplitudes that may place SMP treated mice at higher risk for sustained disease burden. Mice treated via SMP also had increased heart wall thickness and LV Mass, but mice treated via SQ showed greater increase in gene markers for hypertrophy and fibrosis. Overall, these data suggest that at 2 weeks, mice treated with 2, 4, or 10mg/kg/day ISP via SQ and SMP routes cause similar pathological heart phenotypes but highlight the importance of drug delivery method to induce differing disease pathways.

Abstract Objective The study aimed to conduct a bibliometric analysis of mucosal immunity in IgA nephropathy (IgAN) and indicate its current status, hot sopts, and direction of future studies. Methods The literature data was collected from the Web of Science Core Collection. CiteSpace 6.1.R3 was employed to conduct a visualization bibliometric analysis of mucosal immunity in IgA nephropathy, including authors, countries, journals, keywords, organizations, references, the bursts of keywords and references, and the timeline of keyword clusters and reference clusters. Results A total of 315 publications from 1990 to 2022 were included. The number of articles in this field has increased in recent years. Suzuki H, Coppo R, and Feehally J took the first place parallelly with 18 articles. Japan contributes the most articles, accounting for 27.3% of all the publications. The institutions with the most publications were Juntendo University and University of Alabama Birmingham. 453 keywords were concluded in the analysis, which mainly focus on the mucosal pathogenesis and therapy of the IgAN. The top five co‐cited reference cluster are “aberrantly glycosylated IgA,” “corticosteroids,” “animal models,” “o‐glycosylationm” and “microRNA‐630.” The most recently burst of keyword is “tonsillectomy” and “gut.” Conclusion This was the first bibliometric analysis to systematically analyze the mucosal immunity in IgAN, which obtained the current status and indicated the future research hotspots and development trends. The gut microbiota and the related therapy‐targeted mucosal immunity might be the future research hotspot.

Cuproptosis is a novel discovered mode of programmed cell death. To identify the molecular regulatory patterns related to cuproptosis, this study was designed for exploring the correlation between cuproptosis-related genes (CRGs) and the prognosis, metabolism, and treatment of hepatocellular carcinoma (HCC). Cancer Genome Atlas (TCGA) database was used to screen 363 HCC samples, which were categorized into 2 clusters based on the expression of CRGs. Survival analysis demonstrated that overall survival (OS) was better in Cluster 1 than Cluster 2 which might to be relevant to differences in metabolic based on functional analysis. With LASSO regression analysis and univariate COX regression, 8 prognosis-related genes were screened, a differently expressed genes (DEGs) were then constructed (HCC patients' DEGs)-based signature. The signature's stability was also validated in the 2 independent cohorts and test cohorts (GSE14520, HCC dataset in PCAWG). The 1-year, 3-year, and 5-year area under the curve (AUC) were 0.756, 0.706, and 0.722, respectively. The signature could also well predict the response to chemotherapy, targeted and transcatheter arterial chemoembolization (TACE) by providing a risk score. Moreover, the correlation was uncovered by the research between the metabolism and risk score. In conclusion, a unique cuproptosis-related signature that be capable of predicting patients' prognosis with HCC, and offered valuable insights into chemotherapy, TACE and targeted therapies for these patients has been developed.

Background: Postoperative delirium (POD) is a common complication following cardiac surgery and increases postoperative morbidity and mortality. Intraoperative electroencephalogram (EEG) burst suppression suggests excessively deep anesthesia and predicts POD. Use of remimazolam provides a stable hemodynamic status and an appropriate depth of anesthesia. We aim to assess remimazolam administered for anesthesia and sedation in elderly patients having cardiac surgery. Methods: This is a randomized controlled clinical trial with noninferiority design. A total of 260 elderly patients aged equal to or greater than 60 years undergoing cardiac surgery will be randomly allocated to receive remimazolam or propofol (1:1) for general anesthesia and postoperative sedation until extubation. The primary outcome is the cumulative time with EEG burst suppression which is obtained from the SedLine system. The noninferiority margin is 2.0 min. The secondary outcomes include the POD occurrence within the first 5 days postoperatively and the duration of perioperative hypotension. Discussion: This noninferiority trial is the first to evaluate the effect of perioperative remimazolam administration on EEG burst suppression, POD occurrence, and duration of hypotension in elderly patients who undergo cardiac surgery. Trial registration: Chinese Clinical Trial Registry (ChiCTR2200056353).

IntroductionOvulation dysfunction is now a widespread cause of infertility around the world. Although the impact of immune cells in human reproduction has been widely investigated, systematic understanding of the changes of the immune atlas under female ovulation remain less understood.MethodsHere, we generated single cell transcriptomic profiles of 80,689 PBMCs in three representative statuses of ovulation dysfunction, i.e., polycystic ovary syndrome (PCOS), primary ovarian insufficiency (POI) and menopause (MENO), and identified totally 7 major cell types and 25 subsets of cells.ResultsOur study revealed distinct cluster distributions of immune cells among individuals of ovulation disorders and health. In patients with ovulation dysfunction, we observed a significant reduction in populations of naïve CD8 T cells and effector memory CD4 T cells, whereas circulating NK cells and regulatory NK cells increased.DiscussionOur results highlight the significant contribution of cDC-mediated signaling pathways to the overall inflammatory response within ovulation disorders. Furthermore, our data demonstrated a significant upregulation of oxidative stress in patients with ovulation disorder. Overall, our study gave a deeper insight into the mechanism of PCOS, POI, and menopause, which may contribute to the better diagnosis and treatments of these ovulatory disorder.

AbstractDiabetic kidney disease (DKD) is the main complication in diabetes mellitus (DM) and the main cause of end-stage kidney disease worldwide. However, sodium glucose cotransporter 2 (SGLT2) inhibition, glucagon-like peptide-1 (GLP-1) receptor agonist, mineralocorticoid receptor antagonists and endothelin receptor A inhibition have yielded promising effects in DKD, a great part of patients inevitably continue to progress to uremia. Newly effective therapeutic options are urgently needed to postpone DKD progression. Recently, accumulating evidence suggests that targeted drug delivery strategies, such as macromolecular carriers, nanoparticles, liposomes and so on, can enhance the drug efficacy and reduce the undesired side effects, which will be a milestone treatment in the management of DKD. The aim of this article is to summarize the current knowledge of targeted drug delivery strategies and select the optimal renal targeting strategy to provide new therapies for DKD.

Abstract Purpose To investigate the role of mammalian target of rapamycin (mTOR) signal in Toll‐like receptor (TLR) 8‐mediated regulation of glucose metabolism and its effect on reversing immunosuppression in CD4+ regulatory T‐cells (Tregs) in ovarian cancer (OC). Methods Fluorescence‐activated cell sorting was used to detect the expression levels of mTOR+ and 4E‐BP1+ cells in CD4+ Tregs. The prognosis and immune infiltration analysis of mTOR mRNA in OC were performed using the TIMER and Kaplan–Meier plotter database. Furthermore, real‐time polymerase chain reaction (RT‐PCR) and western blot (WB) were used to detect expression levels of glucose metabolism‐related genes and proteins in CD4+ Tregs. Glucose uptake and glycolysis levels were detected by colorimetry, while the effects of CD4+ Tregs on the proliferation of CD4+ T‐effector cells (Teffs) were evaluated by carboxyfluorescein diacetate succinimidyl ester (CFSE). Results mTOR expression in CD4+ Tregs was significantly higher in patients with OC compared with controls and in CD4+ Tregs than in CD4+ Teffs in OC. Additionally, the expression level of mTOR mRNA was related to prognosis and immune infiltration levels in patients with OC. Blocking the mTOR signal resulted in downregulation of glucose metabolism in CD4+ Tregs. Simultaneous inhibition of the mTOR signal while activation of the TLR8 signal had a coordinated inhibitory effect on glucose metabolism and the immunosuppressive function of CD4+ Tregs. Furthermore, the mTOR signal played an essential role in TLR8‐mediated reversal of immunosuppressive function in CD4+ Tregs. Conclusion These findings imply that activation of the TLR8 signal inhibits glucose metabolism in CD4+ Tregs by downregulating mTOR signaling, thereby reversing the immunosuppressive function of these cells in an OC cell growth environment.

Background: Conventional regimens for refractory idiopathic membranous nephropathy (IMN) still have limitations. Rituximab (RTX) has a good effect in the treatment of refractory IMN. However, whether RTX single or combined with immunosuppressive therapy is more effective and whether adverse events will increase are still inconclusive. Aims: To investigate the efficacy and safety of RTX combined with low-dose tacrolimus (TAC) versus RTX alone in the treatment of refractory IMN. Study Design: A retrospective cohort study. Methods: We retrospectively studied 91 cases of refractory IMN diagnosed between January 2018 and June 2021, all of which immunosuppressive regimens had failed. Thirty-four patients received RTX combined with TAC (RTX + TAC group), and 57 patients were treated with RTX alone (RTX group). The RTX + TAC group was given RTX 1 g once every 2 weeks, two times, and TAC 0.03 mg/kg/day orally. In the RTX group, RTX was given at the same dosage as the RTX + TAC group. Clinical data were collected at 12 months of follow-up to compare the complete and partial remission rates and the incidence of adverse reactions between the two groups. Results: The overall effectiveness rate of RTX + TAC in the treatment of refractory IMN was 87.14%, of which the partial and complete remission rates were 50.01% and 37.13%, respectively, and the median time to complete remission was 9 (interquartile range [IQR] 6.0, 12.0) months. The overall effectiveness rate of RTX was 65.87%, of which the partial and complete remission rates were 39.48% and 26.39%, respectively, and the median time to complete remission was 10.5 (IQR 6.0, 12.0) months. Adverse events occurred in 6 (17.65%) patients in the RTX + TAC group and in 11 (19.30%) in the RTX group (P = 0.473). Proteinuria and high titer of PLA2R are risk factors for non-remission. Conclusion: The complete and partial remission rates of RTX combined with low-dose TAC in the treatment of refractory IMN are higher than those of RTX alone, and no significant increase in adverse events was noted.

Abstract Background Carbon dots (CDs), as excellent antibacterial nanomaterials, have gained great attention in treating infection-induced diseases such as periodontitis and stomatitis. Given the eventual exposure of CDs to the intestine, elucidating the effect of CDs on intestinal health is required for the safety evaluation of CDs. Results Herein, CDs extracted from ε-poly-l-lysine (PL) were chosen to explore the modulation effect of CDs on probiotic behavior in vitro and intestinal remodeling in vivo. Results verify that PL-CDs negatively regulate Lactobacillus rhamnosus (L. rhamnosus) growth via increasing reactive oxygen species (ROS) production and reducing the antioxidant activity, which subsequently destroys membrane permeability and integrity. PL-CDs are also inclined to inhibit cell viability and accelerate cell apoptosis. In vivo, the gavage of PL-CDs is verified to induce inflammatory infiltration and barrier damage in mice. Moreover, PL-CDs are found to increase the Firmicutes to Bacteroidota (F/B) ratio and the relative abundance of Lachnospiraceae while decreasing that of Muribaculaceae. Conclusion Overall, these evidences indicate that PL-CDs may inevitably result in intestinal flora dysbiosis via inhibiting probiotic growth and simultaneously activating intestinal inflammation, thus causing pathological damage to the intestine, which provides an effective and insightful reference for the potential risk of CDs from the perspective of intestinal remodeling.

Abstract To refine the biological and prognostic significance of DNMT3A mutations in acute myeloid leukemia (AML), we assessed the impact of DNMT3A variant allele frequency (VAF) and its comutations in this study. Using targeted next‐generation sequencing, we analyzed 171 adult patients with de novo cytogenetically normal AML for DNMT3A mutations and associated comutations. DNMT3Amut was detected in 35 patients. DNMT3Amut patients were divided into DNMT3AHigh and DNMT3ALow using a cut‐off VAF value of 42%. We observed that DNMT3AHigh patients at diagnosis had increasing white blood cell (WBC) counts (p

Abstract The Laser Interferometer Space Antenna (LISA) will be a transformative experiment for gravitational wave astronomy, and, as such, it will offer unique opportunities to address many key astrophysical questions in a completely novel way. The synergy with ground-based and space-born instruments in the electromagnetic domain, by enabling multi-messenger observations, will add further to the discovery potential of LISA. The next decade is crucial to prepare the astrophysical community for LISA’s first observations. This review outlines the extensive landscape of astrophysical theory, numerical simulations, and astronomical observations that are instrumental for modeling and interpreting the upcoming LISA datastream. To this aim, the current knowledge in three main source classes for LISA is reviewed; ultra-compact stellar-mass binaries, massive black hole binaries, and extreme or interme-diate mass ratio inspirals. The relevant astrophysical processes and the established modeling techniques are summarized. Likewise, open issues and gaps in our understanding of these sources are highlighted, along with an indication of how LISA could help making progress in the different areas. New research avenues that LISA itself, or its joint exploitation with upcoming studies in the electromagnetic domain, will enable, are also illustrated. Improvements in modeling and analysis approaches, such as the combination of numerical simulations and modern data science techniques, are discussed. This review is intended to be a starting point for using LISA as a new discovery tool for understanding our Universe.

ABSTRACT Heat-stable antifungal factor (HSAF), produced by Lysobacter enzymogenes OH11, is regarded as a potential biological pesticide due to its broad-spectrum antifungal activity and novel mode of action. However, the current production of HSAF is low and cannot meet the requirements for large-scale production. Herein, we discovered that iron ions greatly promoted HSAF production, and the ferric uptake regulator (Fur) was involved in this regulatory process. Fur was also found to participate in the regulation of iron homeostasis in OH11 via the classic inhibition mechanism of Holo-Fur. Furthermore, Fur was collectively observed to directly bind to the promoter of the HSAF biosynthesis gene, and its DNA-binding affinity was attenuated by the addition of iron ions in vitro and in vivo. Its regulatory mechanism followed the uncommon inhibition mechanism of Apo-Fur. In summary, Fur exhibited a bidirectional regulatory mechanism in OH11. This study reveals a novel regulatory mechanism whereby Fur upregulates the biosynthesis of secondary metabolites. These findings contribute to the improvement of HSAF production and may guide its development into biological pesticides. IMPORTANCE HSAF possesses potent and broad antifungal activity with a novel mode of action. The HSAF yield is critical for fermentation production. In this study, iron ions were found to increase HSAF production, and the specific mechanism was elaborated. These results provide theoretical support for genetic transformation to improve HSAF yield, supporting its development into biological pesticides.

Objective To investigate whether S-ketamine affects the Surgical Pleth Index (SPI) during video-assisted thoracoscopic surgery. Methods Eighty-four patients undergoing video-assisted thoracoscopic lung lobectomy were enrolled. They were randomly assigned to an S-ketamine group (group S) and an equivalent normal saline group (group N). SPI values were recorded; and pain score on a numerical rating scale (NRS), the consumption of opioids, rescue analgesia, and post-operative nausea and vomiting (PONV) were evaluated. Results The SPI and heart rate of the S-ketamine group were significantly lower 30 minutes after the start of surgery and at the end. The NRS score was lower in the S-ketamine group 6 and 12 hours postoperatively, but there were no differences in mean blood pressure or the NRS score 24 and 48 hours postoperatively. Rescue analgesia was required less frequently by the S-ketamine group, but the incidence of PONV did not differ between the groups. Conclusions S-ketamine was associated with lower intraoperative SPI 30 minutes after the start and at the end of surgery. It also reduced opioid use intraoperatively and the NRS scores 6 and 12 hours postoperatively. Trial registration: Chinese Clinical Trial Registry (ChiCTR2000040012), 18/11/2020.

Low frequency (LF) noise is a powerful and non-destructive technique for evaluating the oxide-semiconductor interface and an effective evaluating tool in characterizing electronic device’s structure and reliability. In this study, we present a systematic analysis of the striking abnormal 1/f noise behavior of the hot carrier induced defects in highspeed polysilicon emitter bipolar transistors (PE-BJTs) and SiGe HBTs. Here, the comparative results before and after hot carrier degradation reveal that low frequency noise spectra are not correlated with the density and distribution of the interfacial defects, which related to Si dangling bonds reside at the SiO2/Si interface in PE-BJTs and SiGe HBTs.

Extreme-mass-ratio inspirals (EMRIs) could be detected by space-borne gravitational-wave (GW) detectors, such as the Laser Interferometer Space Antenna (LISA), TianQin, and Taiji. Localizing EMRIs by GW detectors can help us select candidate host galaxies, which can be used to infer the cosmic expansion history. In this paper, we demonstrate that the localization information can also be used to infer the formation channel of EMRIs, and can hence allow us to extract more precisely the redshift probability distributions. By conducting mock observations of the EMRIs that can be detected by TianQin and LISA, as well as the galaxies that can be provided by the future Chinese Space Station Telescope, we find that TianQin can constrain the Hubble–Lemaître constant H _0 to a precision of ∼3%–8% and the dark energy equation-of-state parameter w _0 to ∼10%–40%. The TianQin+LISA network, by increasing the localization accuracy, can improve the precisions of H _0 and w _0 to ∼0.4%–7% and ∼4%–20%, respectively. Then, considering an illustrative case in which all EMRIs originate in active galactic nuclei (AGNs), and combining the mock EMRI observation with a mock AGN catalog, we show that TianQin can recognize the EMRI–AGN correlation with ∼1300 detections. The TianQin+LISA network can reduce this required number to ∼30. Additionally, we propose a statistical method to directly estimate the fraction of EMRIs produced in AGNs, f _agn , and show that observationally deriving this value could significantly improve the constraints on the cosmological parameters. These results demonstrate the potentials of using EMRIs as well as galaxy and AGN surveys to improve the constraints on cosmological parameters and the formation channel of EMRIs.

Recent astrophysical models predict that stellar-mass binary black holes (BBHs) could form and coalesce within a few gravitational radii of a supermassive black hole (SMBH). Detecting the gravitational waves (GWs) from such systems requires numerical tools that can track the dynamics of the binaries while capturing all the essential relativistic effects. This work develops upon our earlier study of a BBH moving along a circular orbit in the equatorial plane of a Kerr SMBH. Here we modify the numerical method to simulate a BBH falling toward the SMBH along a parabolic orbit of arbitrary inclination with respect to the equator. By tracking the evolution in a frame freely falling alongside the binary, we find that the eccentricity of the BBH is more easily excited than it is in the previous equatorial case, and that the cause is the asymmetry of the tidal tensor imposed on the binary when the binary moves out of the equatorial plane. Since the eccentricity reaches maximum around the same time as the BBH becomes the closest to the SMBH, multiband GW bursts could be produced that are simultaneously detectable by space- and ground-based detectors. We show that the effective spin parameters of such GW events also undergo significant variation due to the rapid reorientation of the inner BBHs during their interaction with SMBHs. These results demonstrate the richness of three-body dynamics in the region of strong gravity, and highlight the necessity of building new numerical tools to simulate such systems.

Upper limb movement is vital in daily life. A biomechanical simulation of the forearm with consideration of the physiological characteristics of the muscles is instrumental in gaining deeper insights into the upper limb motion mechanisms. In this study, we established a finite element model of the forearm, including the radius, biceps brachii, and tendons. We simulated the motion of the forearm resulting from the contraction of the biceps brachii by using a Hill-type transversely isotropic hyperelastic muscle model. We adjusted the contraction velocity of the biceps brachii muscle in the simulation and found that a slower muscle contraction velocity facilitated forearm flexion. Then, we changed the percentage of fast-twitch fibers, the maximum muscle strength, and the neural excitation values of the biceps brachii muscle to investigate the forearm flexion of elderly individuals. Our results indicated that reduced fast-twitch fiber percentage, maximum muscle strength, and neural excitation contributed to the decline in forearm motion capability in elderly individuals. Additionally, there is a threshold for neural excitation, below which, motion capability sharply declines. Our model aids in understanding the role of the biceps brachii in forearm flexion and identifying the causes of upper limb movement disorders, which is able to provide guidance for enhancing upper limb performance.

Cervical cancer remains a significant health burden in China, characterized by high incidence and mortality rates, which are exacerbated by low Human Papillomavirus (HPV) vaccination coverage, leading to substantial loss of productivity, emotional suffering, and family strain. Understanding factors that influence HPV awareness and knowledge is crucial for developing effective educational strategies. This cross-sectional study, conducted from September to October 2022, involved 2,679 college students from various educational institutions in Jiangsu Province, China. Data were collected via an online questionnaire covering demographics, HPV knowledge, and vaccination behaviors. Statistical analyses, including Chi-square tests and multifactorial logistic regression, were used to identify factors influencing HPV knowledge. The study revealed that while over 90% of students correctly identified HPV’s transmission and risks, significant knowledge gaps and misconceptions persist, particularly regarding HPV’s association with HIV/AIDS and its treatment. Factors significantly associated with better HPV knowledge included age (22–24 years), female gender, being a medical major, being in a relationship, familiarity with HPV, and participation in sexual education programs. Despite a high willingness to receive the HPV vaccine (91.64%), actual vaccination rates remained low. These findings suggest that while Chinese college students were generally aware of HPV, targeted educational interventions are essential to address knowledge gaps and promote HPV vaccination effectively.

ABSTRACTObjectives Identifying the specific biomarkers and molecular signatures of MM might provide novel evidence for MM prognosis and targeted therapy.Methods Bioinformatic analyses were performed through GEO and TCGA datasets. The differential expression of HIST1H2BH in MM sample was validated by the qRT-PCR. And the CCK-8 assay was performed to detect the proliferation activity of HIST1H2BH on MM cell lines.Results A total of 793 DEGs were identified between bone marrow plasma cells from newly diagnosed myeloma and normal donors in GSE6477. Among them, four vital genes (HIST1H2AC, HIST1H2BH, CCND1 and TCF7L2) modeling were constructed. The increased HIST1H2BH expression was correlated with worse survival of MM based on TCGA datasets. The transcriptional expression of HIST1H2BH was significantly up-regulated in primary MM patients. And knockdown HIST1H2BH decreased the proliferation of MM cell lines.Conclusions We have identified up-regulated HIST1H2BH in MM patients associated with poor prognosis using integrated bioinformatical methods.

Abstract Background Mesenchymal stromal/stem cells (MSCs) have been intensively investigated in both pre-clinical and clinical studies. However, the therapeutic efficacy varies resulting from the heterogenicity of MSCs. Therefore, purifying the specific MSC subpopulation with specialized function is necessary for their therapeutic applications. Methods The large-scale RNA sequencing analysis was performed to identify potential cell markers for the mouse MSCs. Then, the immune suppression activities of the purified MSC subpopulation were assessed in vitro and in vivo. Results The TNFAIP6 (tumor necrosis factor alpha-induced protein 6) has been identified as a potential cell marker for mouse MSCs, irrespective of tissue origin and laboratory origin. The TNFAIP6+ mouse MSCs showed enhanced immune suppression activities and improved therapeutic effects on the mouse model of acute inflammation, resulting from faster response to immune stimulation. Conclusions Therefore, we have demonstrated that the TNFAIP6+ MSC subpopulation has enhanced immune suppression capabilities.

Abstract Background Oculopharyngodistal myopathy (OPDM) is an adult-onset neuromuscular disease characterized by progressive ocular, facial, pharyngeal, and distal limb muscle involvement. Recent research showed that GGC repeat expansions in the NOTCH2NLC gene were observed in a proportion of OPDM patients, and these patients were designated as having OPDM type 3 (OPDM3). Heterogeneous neuromuscular manifestations have been described previously in studies of OPDM3; however, kidney involvement in this disease has rarely been reported. Case presentation Here, we report the case of a 22-year-old Chinese patient with typical manifestations of OPDM complicated with focal segmental glomerular sclerosis (FSGS). This patient with sporadic FSGS exhibited distal motor neuropathy and rimmed vacuolar myopathy in clinical and pathological examinations. An expansion of 122 CGG repeats located in the 5’ untranslated region (UTR) of the NOTCH2NLC gene was identified as the causative mutation in this patient. The clinical and histopathological findings fully met the criteria for the diagnosis of OPDM3. In addition, intranuclear inclusions were detected in the renal tubule epithelial cells of this patient, indicating that the kidney may also be impaired in NOTCH2NLC-related GGC repeat expansion disorders (NREDs). Conclusions Our case report demonstrated the clinicopathological cooccurrence of sporadic FSGS and OPDM3 in a patient, which highlighted that the kidney may show inclusion depositions in OPDM3, thus expanding the clinical spectrum of NREDs.

Abstract Adenoid cystic carcinoma (AdCC) of the breast is a rare indolent carcinoma of salivary gland-type tumors, frequently associated with MYB genetic alteration. Solid and basaloid adenoid cystic carcinoma (SB-AdCC) is considered a sparse variant of AdCC. This study sought to search for clinicopathological and genomic features in SB-AdCC. Registered clinicopathological data on a cohort of 13 AdCC of the breast cases, including six conventional adenoid cystic carcinoma (C-AdCC) cases and seven SB-AdCC cases, were collected. MYB gene rearrangement via fluorescent in situ hybridization was investigated and MYB protein expression was evaluated by immunohistochemistry. Compared with C-AdCC, we found that the distribution of SB-AdCC cases were shifted to older age and were more frequently distant metastasis. Moreover, metastasis cases also showed a high (exceed 30%) Ki-67 index. Both groups showed MYB rearrangements and MYB protein expression, but they were less frequent in SB-AdCC than C-AdCC. To conclude, our results suggest that SB-AdCC is an aggressive variant of mammary AdCC with a higher incidence of distant metastases compared with C-AdCC, though they share common molecular features. A high Ki-67 index may be an adverse prognostic factor for metastasis.

Abstract Background Most nurses in China have not been trained to take care of end-of-life patients appropriately due to lack of educational resources and insufficient training. A palliative care program was launched by the Jiangsu Nursing Association (JNA training program) and to identify gaps in palliative care training. The main aim of this study was to evaluate the training effects of the JNA training program on nurses’ knowledge and attitudes to palliative care. Methods A cross-sectional study was conducted with 10 048 registered nurses in all regions of Jiangsu. All participants completed an online questionnaire using the Chinese version of The Palliative Care Quiz for Nursing (PCQN-C) and the Frommelt Attitude Toward Care of the Dying scale (FATCOD-B-C). A propensity score matched analysis was performed between the nurses who had attended the JNA training program and whose who hadn’t. Results The average score of PCQN-C among all nurses was 8.79, while the mean score of the FATCOD-B-C was 103.62. Those participants who attended the JNA training program had significantly better scores than those who did not. Propensity score matching analysis showed that the palliative care training program failed to improve nurses’ knowledge in psychosocial and spiritual care or their attitudes towards the necessity of family support although there was positive impact on other aspects of palliative care. Conclusions Knowledge of palliative care among Chinese nurses remains low. Training programs may improve general knowledge and attitudes to palliative care. However, important aspects of knowledge such as communication skills, family support, and psychosocial aspects of care, are missing. These gaps should be filled in future palliative care training programs targeting nurses with oriental culture background.

Dual-wavelength lasers are gaining importance for photonic applications. In this work the authors demonstrate that by incorporating a lanthanidedoped material into the size-mismatched coupled microcavities, it is possible to achieve laser switch with high uniformity, long-term stability, and an extremely wide spectral range up to 300 nm

Friedreich's ataxia is a rare disorder resulting from deficiency of frataxin, a mitochondrial protein implicated in the synthesis of iron-sulfur clusters. Preclinical studies in mice have shown that gene therapy is a promising approach to treat individuals with Friedreich's ataxia. However, a recent report provided evidence that AAVrh10-mediated overexpression of frataxin could lead to cardiotoxicity associated with mitochondrial dysfunction. While evaluating an AAV9-based frataxin gene therapy using a chicken β-actin promoter, we showed that toxic overexpression of frataxin could be reached in mouse liver and heart with doses between 1 × 1013 and 1 × 1014 vg/kg. In a mouse model of cardiac disease, these doses only corrected cardiac dysfunction partially and transiently and led to adverse findings associated with iron-sulfur cluster deficiency in liver. We demonstrated that toxicity required frataxin's primary function by using a frataxin construct bearing the N146K mutation, which impairs binding to the iron-sulfur cluster core complex. At the lowest tested dose, we observed moderate liver toxicity that was accompanied by progressive loss of transgene expression and liver regeneration. Together, our data provide insights into the toxicity of frataxin overexpression that should be considered in the development of a gene therapy approach for Friedreich's ataxia.

IntroductionThe malacoplakia of the bladder is a rare chronic acquired infection- associated granulomatous disease and even less common in combination with urinary stones.Case PresentationWe report the case of a 58-year-old female patient with malacoplakia of the bladder combined with renal calculi. The patient was admitted to the hospital with bilateral low back pain for one month and space-occupying lesions of the bladder for three days. Preoperative imaging suggested space-occupying lesions of the bladder: high probability of bladder cancer. Following the anti-infection treatment, the transurethral electrodesiccation was performed on the space-occupying lesions of the bladder. Pathological examination confirmed the diagnosis of malacoplakia of the bladder. Left-sided percutaneous nephrolithotomy was performed electively to remove the predisposing factors of infection. After the operation, the patient continued to receive anti-infection treatment for two months. The patient had a good prognosis in the six-month follow-up.ConclusionsMalacoplakia of the bladder is easily misdiagnosed as bladder cancer before operation, and the diagnosis depends on pathological diagnosis. Complete removal of urinary calculi, infection and other inducing factors, is beneficial to the treatment of malacoplakia of the bladder.

Small bowel adenocarcinoma (SBA), particularly duodenal adenocarcinoma (DA), is a rare gastrointestinal cancer with a dismal prognosis. Data on SBA treatments are limited, and the therapeutic strategy remains uncertain. Currently, chemotherapy is the most used treatment; however, it has a poor median progression-free survival (mPFS) of no more than five months in the second-line setting. We report a case with DA that responded well to the immune checkpoint inhibitor (ICI) tislelizumab plus irinotecan in the second-line treatment. To our knowledge, this is the first report of administering ICIs plus chemotherapy to SBA. Despite the absence of microsatellite instability-high (MSI-H) and high tumor mutational burden (TMB), the patient with TP53/KRAS mutation achieved a significantly long PFS of 17 months, and the benefit is still ongoing. The mechanism of this remarkable efficacy might be associated with an increase in tumor immunogenicity after chemotherapy. The current study presents a promising effect of ICIs plus chemotherapy on SBA, affirming the need to investigate the clinical value of this combination in SBA and the underlying mechanism behind it.

Constructing ultraviolet lasing is of great significance for basic research and medical use. Here the authors present a strategy for generating ultraviolet lasing through a tandem upconversion process with ultralarge anti-Stokes shift (1260 nm).

Breakthrough of the exploration of deep shale gas in the Sichuan Basin, Southwest China, has been achieved for decades, there are still some controversies about the adsorption performance and occurrence state of shale gas in deep strata. Isothermal adsorption experiments were carried out under high temperature and high pressure with typical shale samples from deep stratum of the Lower Silurian Longmaxi Formation in Fuling and Dingshan areas in the southeastern Sichuan Basin. Results show that there is a big difference between absolute adsorption and excess adsorption, thus, it is proposed that the excess adsorption capacity should be corrected to the absolute adsorption capacity when evaluating the adsorption performance of deep shale gas. After correction, the variation of absolute shale adsorption with pressure appeared to have three stages including "rapid rise", "slow rise" and "steady rise". The absolute adsorption capacity of deep shale samples from Fuling and Dingshan areas is higher than 2.0 m3/t at 110℃ and 70 MPa, and combined with the adsorption and free gas ratios of deep shale, the total gas content is more than 4.0 m3/t, indicating that deep shale may still have good adsorption performance under high temperature and high pressure. The evaluation of deep shale adsorption capacity can provide reliable parameters for the study of shale gas content and the evaluation of resource potential and reserve for shale gas. Considering the difference of ratio of free gas to adsorbed gas between deep shale and shallow-medium shale, different exploration and production methods can be adopted to effectively improve the production capacity and production cycle of shale gas.

Abstract Background New evidence from clinical and fundamental researches suggests that SNHG7 is involved in the occurrence and development of carcinomas. And the increased levels of SNHG7 are associated with poor prognosis in various kinds of tumors. However, the small sample size was the limitation for the prognostic value of SNHG7 in clinical application. The aim of the present meta-analysis was to conduct a qualitative analysis to explore the prognostic value of SNHG7 in various cancers. Methods Articles related to the SNHG7 as a prognostic biomarker for cancer patients, were comprehensive searched in several electronic databases. The enrolled articles were qualified via the preferred reporting items for systematic reviews and meta-analysis of observational studies in epidemiology checklists. Additionally, an online database based on The Cancer Genome Atlas (TCGA) was further used to validate our results. Results We analyzed 2418 cancer patients that met the specified criteria. The present research indicated that an elevated SNHG7 expression level was significantly associated with unfavorable overall survival (OS) (HR = 2.45, 95% CI: 2.12–2.85, p

Introducing a coating shell between the filler and matrix is an effective way to reduce the dielectric loss of the particle/matrix dielectric composites. It found that besides the improvement in interface compatibility, there may be some other effects of the coating shell, such as the elimination of the dielectric mismatch. However, the specific mechanism is still unclear due to the absence of an effective model for the quantitative analysis of the relationship between core–shell structure and dielectric loss, hindering the progress of the dielectric composite design. Here, a phase-field model for simulating high-frequency, alternating-field polarization is employed to study the relationship between high-frequency polarization loss and the coating shell in the silicon dioxide coating boron nitride polytetrafluoroethylene-based (BN@SiO2/PTFE) composite. The results show that the dielectric mismatch makes the high-frequency polarization loss spatially localized and periodically time-variant. The reduction of polarization loss depends on the polarization loss of SiO2. To reduce the high-frequency dielectric loss of the composite, the coating shell should not only eliminate the dielectric mismatch, but its dielectric loss must also be lower than that of the core filler. Furthermore, the model provided in this work has the potential to extend the quantitative calculation of non-intrinsic polarization loss and conduction loss.