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Abstract Thermal properties of quantum fields at finite temperature are crucial to understanding strongly interacting matter and recent development in quantum computing has provided an alternative and promising avenue of study. In this work, we study thermal field theories involving only fermions using quantum algorithms. We first delve into the presentations of fermion fields via qubits on digital quantum computers alongside the quantum algorithms such as quantum imaginary time evolutions employed to evaluate thermal properties of generic quantum field theories. Specifically, we show numerical results such as the thermal distribution and the energy density of thermal field theories for Majorana fermions in 1+1 dimensions using quantum simulators. In addition to free field theory, we also study the effects of interactions resulting from coupling with a spatially homogeneous Majorana field. In both cases, we show analytically that thermal properties of the system can be described using phase-space distributions, and the quantum simulation results agree with analytical and semiclassical expectations. Our work is an important step to understand thermal fixed points, preparing for quantum simulation of thermalization in real time.

Abstract Background Aripiprazole is the most frequently recommended antipsychotic for the treatment of tics in children and adolescents with Tourette’s disorder (TD). However, to date, a randomized controlled trial for aripiprazole oral solution has not been conducted despite being widely preferred by children. Therefore, we examined whether aripiprazole oral solution is effective for treating tics. Methods All patients received a flexible dose of aripiprazole oral solution (1 mg/mL, range: 2–20 mg) with a starting dose of 2 mg. The target dose for patients weighing

Abstract Associations of adipose tissue insulin resistance index (AT-IR, a product of fasting insulin and free fatty acids) with body fat mass and distribution and appendicular skeletal muscle mass (ASM) were compared with results of homeostasis-model assessment-insulin resistance (HOMA-IR) in 284 Japanese female university students and 148 their biological mothers whose BMI averaged

Abstract Background The progression of non-small cell lung cancer (NSCLC) is significantly influenced by circular RNAs (circRNAs), especially in tumor hypoxia microenvironment. However, the precise functions and underlying mechanisms of dysregulated circRNAs in NSCLC remain largely unexplored. Methods Differentially expressed circRNAs in NSCLC tissues were identified through high-throughput RNA sequencing. The characteristics of circ_0007386 were rigorously confirmed via Sanger sequencing, RNase R treatment and actinomycin D treatment. The effects of circ_0007386 on proliferation and apoptosis were investigated using CCK8, cloning formation assays, TUNEL staining, and flow cytometry assays in vitro. In vivo, xenograft tumor models were used to evaluate its impact on proliferation. Mechanistically, the regulatory relationships of circ_0007386, miR-383-5p and CIRBP were examined through dual luciferase reporter assays and rescue experiments. Additionally, we detected the binding of EIF4A3 to CRIM1 pre-mRNA by RNA immunoprecipitation and the interaction between YAP1 and EIF4A3 under hypoxic conditions by co-immunoprecipitation. Results Our investigation revealed a novel circRNA, designated as circ_0007386, that was upregulated in NSCLC tissues and cell lines. Circ_0007386 modulated proliferation and apoptosis in NSCLC both in vitro and in vivo. Functionally, circ_0007386 acted as a sponge for miR-383-5p, targeting CIRBP, which influenced NSCLC cell proliferation and apoptosis via the PI3K/AKT signaling pathway. Furthermore, under hypoxic conditions, the interaction between YAP1 and EIF4A3 was enhanced, leading to the displacement of EIF4A4 from binding to CRIM1 pre-mRNA. This facilitated the back-splicing of CRIM1 pre-mRNA, increasing the formation of circ_0007386. The circ_0007386/miR-383-5p/CIRBP axis was significantly associated with the clinical features and prognosis of NSCLC patients. Conclusions Circ_0007386, regulated by YAP1-EIF4A3 interaction under hypoxia conditions, plays an oncogenic role in NSCLC progression via the miR-383-5p/CIRBP axis.

Abstract We first assemble a full set of the Boltzmann Equation in Diffusion Approximation (BEDA) for studying thermalization/hydrodynamization as well as the production of massless quarks and antiquarks in out of equilibrium systems. In the BEDA, the time evolution of a generic system is characterized by the following space-time dependent quantities: the jet quenching parameter, the effective temperature, and two more for each quark flavor that describe the conversion between gluons and quarks/antiquarks via the 2 ↔ 2 processes. Out of the latter two quantities, an effective net quark chemical potential is defined, which equals the net quark chemical potential after thermal equilibration. We then study thermalization and the production of three flavors of massless quarks and antiquarks in spatially homogeneous systems initially filled only with gluons. A parametric understanding of thermalization and quark production is obtained for either initially very dense or dilute systems, which are complemented by detailed numerical simulations for intermediate values of initial gluon occupancy f 0. For a wide range of f 0, the final equilibration time is determined to be about one order of magnitude longer than that in the corresponding pure gluon systems. Moreover, during the final stage of the thermalization process for f 0 ≥ 10−4, gluons are found to thermalize earlier than quarks and antiquarks, undergoing the top-down thermalization.

Abstract As global environmental issues increase, sustainable use, disposal, and production of materials play an important role. The world produces 1.3 billion tons of food waste annually, of which about 15% are edible fruit peels. Here, we use freeze-dried orange peels as the main material in a hydrogel to prepare a flexible, natural, biocompatible, and sustainably produced electronic skin. We introduce the lyophilized mesocarp of orange and a copper-based metal-organic framework into a polyvinyl alcohol/hyaluronic acid matrix hydrogel, which can occur under mild conditions. The design allows the polymers to connect through intermolecular interactions rather than covalent bonding, which improves the material’s mechanical properties while retaining the self-healing ability. The orange peel-based hydrogel exhibits high elongation at break (290%), enhanced tensile stress, self-healing, conductivity (0.14 S/m), and antibacterial properties (95.3%). These results demonstrate an option for environmentally friendly materials for electronic skin.

Abstract Background A retrospective cohort study was conducted to collect the data of pregnant women who received hospital delivery in Hangzhou Women's Hospital from January 2018 to December 2020, and who participated in the second trimester (15–20+6 weeks) of free beta human chorionic gonadotropin (free β-hCG). And the study was conducted to explore the relationship between maternal serum free β-hCG and adverse pregnancy outcomes (APO). Methods We retrospectively analyzed the clinical data of 1,978 women in the elevated maternal serum free β-hCG group (free β-hCG ≥ 2.50 multiples of the median, MoM) and 20,767 women in the normal group (0.25 MoM ≤ free β-hCG

Background/Aims: This study aimed to analyze the trends in mortality attributed to hepatitis B and C around the Western Pacific region from 1990 to 2019. Methods: We used data from the Global Burden of Disease Study for a systematic analysis. The deaths related to hepatitis B and C were analyzed by age, sex, year, risk factors, geographical location, and Socio-demographic Index (SDI). Results: From 1990 to 2019, the annual total deaths from hepatitis B decreased from 0.266 to 0.210 million and those from hepatitis C increased from 0.119 to 0.142 million in the Western Pacific region. The age-standardized mortality rate (ASMR) of hepatitis B and C decreased by 63.5% and 48.0%, respectively. The declines in the ASMR related to hepatitis B and C were only detected in 12 and two Western Pacific countries, respectively. As the major risk factors, the contribution of alcohol use to hepatitis B deaths was 52% and drug use to hepatitis C was 80%. In males and females, the ASMR attributed to hepatitis B decreased by 61% and 71%, respectively, and the ASMR attributed to hepatitis C decreased by 43% and 55%, respectively. The association between SDI and ASMRs suggested that hepatitis B and C, respectively, showed an overall decline and stable trends as the SDI improved in the Western Pacific region. Conclusions: Although the mortality rate from hepatitis B and C decreased from 1990 to 2019, notable variation was observed among 27 Western Pacific countries. Efforts targeting hepatitis B and C prevention and treatment are still required in this region, especially for the pandemic countries.

Abstract In response to the low matching accuracy of stereo matching algorithms in image regions with specular reflection, this paper proposes a multidimensional fusion stereo matching algorithm named MFANet. The algorithm embeds a multispectral attention module into the residual feature extraction network, utilizing two‐dimensional discrete cosine transforms to extract frequency features. In the pyramid pooling module, a coordinated attention mechanism is introduced to capture relevant positional information. In the cost aggregation part, the MFANet algorithm incorporates a three‐dimensional attention mechanism, focusing on the more important semantic information in high‐level features. By combining detailed information from low‐level features, semantic information from high‐level features, and contextual information, the algorithm generates features that are more conducive to disparity prediction. The MFANet algorithm is evaluated on three standard datasets (SceneFlow, KITTI2015, and KITTI2012). Experimental results demonstrate its robustness against specular reflection interference, accurate prediction of disparities in specular reflection pathological regions, and promising application prospects.

Abstract The storage process has a significant impact on tea quality. Few is known about effect of storage on quality of oolong tea. This study aimed to assess the effect of different storage times on the key chemical components of oolong tea by measuring changes in catechin, free amino acid, and alkaloid content. Variation in the main substances was determined by principal component analysis and heat map analysis. The results revealed notable effects of the storage process on the levels of theanine, epigallocatechin gallate (EGCG), and glutamine. These findings suggest that these compounds could serve as indicators for monitoring changes in oolong tea quality during storage. Additionally, the study observed an increase in the antibacterial ability of tea over time. Correlation analysis indicated that the antibacterial ability against Micrococcus tetragenus and Escherichia coli was influenced by metabolites such as aspartic acid, threonine, serine, gamma-aminobutyric acid, ornithine, alanine, arginine, and EGCG. Overall, this study presents an approach for identifying key metabolites to monitor tea quality effectively with relatively limited data.

In order to quantitatively analyze the risk caused by each operational step of coal mine blasting and comprehensively and objectively assess its risk, with the help of Monte Carlo method, this paper establishes a risk assessment model of coal mine blasting operation steps, makes cumulative probability distribution of the behavioral risk consequence value of the operation process, and finally determines the risk size and risk level of each operation step based on the mean result of Monte Carlo simulation and the overall risk result of the operation process, and puts forward the measures for the control of the occurrence of such unsafe behaviors. The results of the study show that the order of risk of the blasting operation process is in the following order: clearing the items into the warehouse, loading, linkage, guarding, safety inspection after detonation, receiving and checking the blasting items, detonation, delivery of blasting items, acceptance of the task of blasting, preoperational safety inspection, pre-detonation safety inspection, sealing the holes.

Abstract In real‐world scenarios, pedestrian images often suffer from occlusion, where certain body features become invisible, making it challenging for existing methods to accurately identify pedestrians with the same ID. Traditional approaches typically focus on matching only the visible body parts, which can lead to misalignment when the occlusion patterns vary. To address this issue and alleviate misalignment in occluded pedestrian images, the authors propose a novel framework called body topology information generation and matching. The framework consists of two main modules: the body topology information generation module and the body topology information matching module. The body topology information generation module employs an adaptive detection mechanism and capsule generative adversarial network to restore a holistic pedestrian image while preserving the body topology information. The body topology information matching module leverages the restored holistic image from body topology information generation to overcome spatial misalignment and utilises cosine distance as the similarity measure for matching. By combining the body topology information generation and body topology information matching modules, the authors achieve consistency in the body topology information features of pedestrian images, ranging from restoration to retrieval. Extensive experiments are conducted on both holistic person re‐identification datasets (Market‐1501, DukeMTMC‐ReID) and occluded person re‐identification datasets (Occluded‐DukeMTMC, Occluded‐ReID). The results demonstrate the superior performance of the authors proposed model, and visualisations of the generation and matching modules are provided to illustrate their effectiveness. Furthermore, an ablation study is conducted to validate the contributions of the proposed framework.

Abstract The rapid emergence and spread of colistin-resistant gram-negative bacteria has raised worldwide public health concerns, and phosphoethanolamine (PEtn) transferase modification-mediated colistin resistance has been widely documented in multiple gram-negative bacterial species. However, whether such a mechanism exists in the zoonotic pathogen Pasteurella multocida is still unknown. Recently, a novel PEtn transferase, PetL, was identified in P. multocida, but whether it is associated with colistin resistance remains to be elucidated. In this study, we found that PetL in P. multocida (PetLPM) exhibited structural characteristics similar to those of the mobile-colistin-resistant (MCR) protein and the PEtn transferase characterized in Neisseria meningitidis. The transformation of petL PM into E. coli or K. pneumoniae changed the phenotype of several tested strains from colistin sensitive to colistin resistant. Deletion of this gene decreased the colistin minimum inhibitory concentration (MIC) of P. multocida by 64-fold. Our extensive analysis by MALDI-TOF–MS demonstrated that PetLPM participated in the modification of bacterial lipopolysaccharide (LPS)-lipid A. Deletion of petL PM led to an increase in membrane charge but a decrease in cell-surface hydrophobicity and cell permeability in P. multocida. The present study is the first to report the presence of PEtn transferase-mediated colistin resistance in the zoonotic pathogen P. multocida.

Abstract RNA decay is vital for regulating mRNA abundance and gene expression. Existing technologies lack the spatiotemporal precision or transcript specificity to capture the stochastic and transient decay process. We devise a general strategy to inducibly recruit protein factors to modulate target RNA metabolism. Specifically, we introduce a Rapid Inducible Decay of RNA (RIDR) technology to degrade target mRNAs within minutes. The fast and synchronous induction enables direct visualization of mRNA decay dynamics in cells. Applying RIDR to endogenous ACTB mRNA reveals rapid formation and dissolution of RNA granules in pre-existing P-bodies. Time-resolved RNA distribution measurements demonstrate rapid RNA decay inside P-bodies, which is further supported by knocking down P-body constituent proteins. Light and oxidative stress modulate P-body behavior, potentially reconciling the contradictory literature about P-body function. This study reveals compartmentalized RNA decay kinetics, establishing RIDR as a pivotal tool for exploring the spatiotemporal RNA metabolism in cells.

With the expansion of vaccination programs, the policy of terminating nonpharmaceutical interventions for preventing the SARS-CoV-2 pandemic should become more flexible. The current study investigated the clinical and economic outcomes of intervention policies combining nonpharmaceutical interventions and vaccination programs for dealing with the SARS-CoV-2 pandemic. An agent-based transmission model was adopted that describes how a SARS-CoV-2 virus spreads in the populations of China. The model inputs were derived from the literature and expert opinion. The following intervention policies were simulated: no intervention, strict nonpharmaceutical interventions, and nonpharmaceutical interventions for workplace, community, school and home gradually terminated by combining vaccination programs for specified age groups (vaccination age in years: 20–60, 20–70, 20–80, ≥ 20, ≥ 10 and whole population). Cumulative infections and deaths in one calendar year, costs and quality-adjusted life years (QALYs) were measured. When the vaccination program was taken up in at least the ≥ 20 years age group in all populations, nonpharmaceutical interventions for workplace and community settings could be gradually terminated because the cumulative number of infections was < 100 per 100,000 persons. Further ending nonpharmaceutical interventions in school and home settings could not meet the target even when the vaccination program had been taken up in all populations. When cumulative deaths were used as the endpoint, nonpharmaceutical interventions in workplace, community and school settings could be gradually terminated. Vaccine efficacy and coverage have substantial impacts. Terminating nonpharmaceutical interventions in workplace settings could produce the lowest cost when vaccination programs are taken up at least in the ≥ 10 years age group; this method dominates most intervention strategies due to its lower costs and higher QALYs. According to our findings, nonpharmaceutical interventions might be gradually terminated in Chinese settings.

Abstract After ecological restoration of high and steep slopes in the project disturbed area, soil properties, soil microorganisms, litter types and root types change with the succession of vegetation cover communities. However, the effects of different vegetation successional stages on soil respiration dynamics remain unclear. To elucidate trends and drivers of soil respiration in the context of vegetation succession, we used spatio-temporal alternative applied research. Vegetated concrete-restored slopes (VC) with predominantly herbaceous (GS), shrub (SS), and arborvitae (AS) vegetation were selected, and naturally restored slopes (NS) were used as control. SRS1000 T soil carbon flux measurement system was used to monitor soil respiration rate. The results showed that soil respiration (RS) and fractions of all four treatments showed a single-peak curve, with peaks concentrated in July and August. During the succession of vegetation from herbaceous to arborvitae on VC slopes, RS showed a decreasing trend, and GS was significantly higher than AS by 45%; Compared to NS, RS was 29.81% and 21.56% higher in GS and SS successional stages, respectively, and 27.51% lower in AS stage. RS was significantly and positively correlated with nitrate nitrogen (NO3 –-N) and microbial biomass nitrogen (MBN), both of which are important factors in regulating RS under vegetation succession. A bivariate model of soil temperature and water content explains the variability of Rs better. Overall, RS was higher than NS in the transition stage and lower than NS in the equilibrium stage of the vegetation community on VC slopes, and the RS decreases gradually with the vegetation succession of artificial ecological restoration slopes.

Abstract Background Diarrheal diseases caused by viral agents have led to a great morbidity, mortality, and economic loss in global pig industry. Porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and group A porcine rotavirus (RVA) are main causative agents of swine viral diarrhea with similar clinical signs on Chinese farms and their co-infection is also common. However, it is still lack of a convenient method to detect these four agents. Methods A TaqMan multiplex qPCR method was developed to detect PEDV, TGEV, PDCoV, and RVA, simultaneously. This method was then applied to investigate 7,342 swine fecal samples or rectal swabs, as well as 1,246 swine intestinal samples collected from 2075 farms in China in 2022. Results Minimum detection limits of this method were 3 copies/µL for PEDV, 4 copies/µL for TGEV, 8 copies/µL for RVA, and 8 copies/µL for PDCoV, suggesting a good sensitivity. No signals were observed by using this method detecting other viral agents commonly prevalent in pigs, which is suggestive of a good specificity. Application of this method on investigating clinical samples demonstrated a relatively high positive rate for PEDV (22.21%, 1907/8588) and RVA (44.00%, 3779/8588). In addition, co-infection between PEDV and RVA was observed on 360 investigated farms, accounting for 17.35% (360/2075) of the farms where co-infection events were screened. Conclusions A TaqMan multiplex qPCR method targeting PEDV, TGEV, PDCoV, and RVA was developed in this study. This method demonstrated a good specificity and sensitivity on investigating these four common viruses responsible for viral diarrhea on Chinese pig farms, which represents a convenient method for the monitoring and differential diagnosis of swine viral diarrhea.

Abstract Aiming at the problems of identifying storage pest tobacco pest beetles from images that have few object pixels and considerable image noise, and therefore suffer from lack of information and identifiable features, this paper proposes an automatic monitoring method of tobacco beetle based on Multi-scale Global residual Feature Pyramid Network and Dual-path Deformable Attention (MGrFPN-DDrGAM). Firstly, a Multi-scale Global residual Feature Pyramid Network (MGrFPN) is constructed to obtain rich high-level semantic features and more complete information on low-level features to reduce missed detection; Then, a Dual-path Deformable receptive field Guided Attention Module (DDrGAM) is designed to establish long-range channel dependence, guide the effective fusion of features and improve the localization accuracy of tobacco beetles by fitting the spatial geometric deformation features of and capturing the spatial information of feature maps with different scales to enrich the feature information in the channel and spatial. Finally, to simulate a real scene, a multi-scene tobacco beetle dataset is created. The dataset includes 28,080 images and manually labeled tobacco beetle objects. The experimental results show that under the framework of the Faster R-CNN algorithm, the detection precision and recall rate of this method can reach 91.4% and 98.4% when the intersection ratio (IoU) is 0.5. Compared with Faster R-CNN and FPN, when the intersection ratio (IoU) is 0.7, the detection precision is improved by 32.9% and 6.9%, respectively. The proposed method is superior to the current mainstream methods.

Abstract The phenomenon of phase separation is quite common in cells, and it is involved in multiple processes of life activities. However, the current research on the correlation between protein modifications and phase separation and the interference with the tendency of phase separation has some limitations. Here we focus on several post-translational modifications of proteins, including protein phosphorylation modification at multiple sites, methylation modification, acetylation modification, ubiquitination modification, SUMOylation modification, etc., which regulate the formation of phase separation and the stability of phase separation structure through multivalent interactions. This regulatory role is closely related to the development of neurodegenerative diseases, tumors, viral infections, and other diseases, and also plays essential functions in environmental stress, DNA damage repair, transcriptional regulation, signal transduction, and cell homeostasis of living organisms, which provides an idea to explore the interaction between novel protein post-translational modifications and phase separation. Video Abstract

Abstract Progressive cerebral infarction (PCI) is a common complication in patients with ischemic stroke that leads to poor prognosis. Blood pressure (BP) can indicate post‐stroke hemodynamic changes which play a key role in the development of PCI. The authors aim to investigate the association between BP‐derived hemodynamic parameters and PCI. Clinical data and BP recordings were collected from 80 patients with cerebral infarction, including 40 patients with PCI and 40 patients with non‐progressive cerebral infarction (NPCI). Hemodynamic parameters were calculated from the BP recordings of the first 7 days after admission, including systolic and diastolic BP, mean arterial pressure, and pulse pressure (PP), with the mean values of each group calculated and compared between daytime and nighttime, and between different days. Hemodynamic parameters and circadian BP rhythm patterns were compared between PCI and NPCI groups using t‐test or non‐parametric equivalent for continuous variables, Chi‐squared test or Fisher's exact test for categorical variables, Cox proportional hazards regression analysis and binary logistic regression analysis for potential risk factors. In PCI and NPCI groups, significant decrease of daytime systolic BP appeared on the second and sixth days, respectively. Systolic BP and fibrinogen at admission, daytime systolic BP of the first day, nighttime systolic BP of the third day, PP, and the ratio of abnormal BP circadian rhythms were all higher in the PCI group. PCI and NPCI groups were significantly different in BP circadian rhythm pattern. PCI is associated with higher systolic BP, PP and more abnormal circadian rhythms of BP.

Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3′-untranslated region (3′ UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

AIM: To observe the retinal and choroidal circulations in patients with non-arteritic permanent central retinal artery occlusion (NA-CRAO) via optical coherence tomography angiography (OCTA) and analyze their correlation with visual acuity. METHODS: Sixty-two eyes with clinically confirmed acute NA-CRAO were included in the study and divided into: A type (mild n=29), B type (moderate n=27) and C type (severe n=6) based on the degree of visual loss, retinal edema, and arterial blood flow delay in fundus fluorescence angiography (FFA). Contralateral healthy eyes were used as the control group. Best-corrected visual acuity (BCVA), slit lamp microscopy, indirect ophthalmoscopy, fundus color photography, OCTA, and FFA were performed. Spearman's correlation analysis was used to determine the correlations between retinal and choroidal vessels and visual acuity. RESULTS: There were no statistically significant differences in age, gender, and intraocular pressure among the three types and the control group (P>0.05). Vessel density in deep capillary plexus (VD-DCP) significantly decreased (P

Summary: A DNA double-strand break (DSB) jeopardizes genome integrity and endangers cell viability. Actively transcribed genes are particularly detrimental if broken and need to be repressed. However, it remains elusive how fast the repression is initiated and how far it influences the neighboring genes on the chromosome. We adopt a recently developed, very fast CRISPR to generate a DSB at a specific genomic locus with precise timing, visualize transcription in live cells, and measure the RNA polymerase II (RNAPII) occupancy near the broken site. We observe that a single DSB represses the transcription of the damaged gene in minutes, which coincides with the recruitment of a damage repair protein. Transcription repression propagates bi-directionally along the chromosome from the DSB for hundreds of kilobases, and proteasome is evoked to remove RNAPII in this process. Our method builds a foundation to measure the rapid kinetic events around a single DSB and elucidate the molecular mechanism.

Summary: ADAR1-mediated RNA editing establishes immune tolerance to endogenous double-stranded RNA (dsRNA) by preventing its sensing, primarily by MDA5. Although deleting Ifih1 (encoding MDA5) rescues embryonic lethality in ADAR1-deficient mice, they still experience early postnatal death, and removing other MDA5 signaling proteins does not yield the same rescue. Here, we show that ablation of MDA5 in a liver-specific Adar knockout (KO) murine model fails to rescue hepatic abnormalities caused by ADAR1 loss. Ifih1;Adar double KO (dKO) hepatocytes accumulate endogenous dsRNAs, leading to aberrant transition to a highly inflammatory state and recruitment of macrophages into dKO livers. Mechanistically, progranulin (PGRN) appears to mediate ADAR1 deficiency-induced liver pathology, promoting interferon signaling and attracting epidermal growth factor receptor (EGFR)+ macrophages into dKO liver, exacerbating hepatic inflammation. Notably, the PGRN-EGFR crosstalk communication and consequent immune responses are significantly repressed in ADAR1high tumors, revealing that pre-neoplastic or neoplastic cells can exploit ADAR1-dependent immune tolerance to facilitate immune evasion.

BackgroundStatins were regarded as a main medication for managing hypercholesterolemia. Administration of statin therapy could reduce the incidence of cardiovascular disease in individuals diagnosed with type 2 diabetes mellitus (DM), which was recognized by multipal clinical guidelines. But previous studies had conflicting results on whether the long-term use of statins could benefit the renal function in diabetic patients.AimTo evaluate the association between statin treatment and Chronic Kidney Disease in DM patients.MethodsThis is a retrospective disproportionality analysis and cohort study based on real-world data. All DM cases reported in US Food and Drug Administration adverse event reporting system (FAERS) between the first quarter of 2004 and the fourth quarter of 2022 were included. Disproportionality analyses were conducted by estimating the reporting odds ratio (ROR) and the information component (IC). We further compared the CKD odds ratio (OR) between the statins group and the other primary suspected drug group among the included diabetes mellitus cases.ResultsWe finally included 593647 DM cases from FAERS, 5113 (5.31%) CKD cases in the statins group and 8810 (1.77%) CKD cases in the control group. Data analysis showed that the statins group showed a significant CKD signal (ROR: 3.11, 95% CI: 3.00–3.22; IC: 1.18, 95% CI: 1.07–1.29). In case group with two or more statins treatment history, the CKD signal was even stronger (ROR: 19.56, 95% CI: 18.10–21.13; IC: 3.70, 95% CI:3.44–3.93) compared with cases with one statin treatment history.ConclusionThe impact of statin therapy on the progression of renal disease in individuals diagnosed with type 2 diabetes mellitus (DM) remains inconclusive. After data mining on the current FAERS dataset, we discovered significant signals between statin treatment and CKD in diabetic patients. Furthermore, the incidence rate of CKD was higher among DM patients who used statins compared to those who did not.

BackgroundNecrotizing enterocolitis (NEC) is a severe neonatal intestinal disease, often occurring in preterm infants following the administration of hyperosmolar formula. It is one of the leading causes of neonatal mortality in the NICU, and currently, there are no clear standards for surgical intervention, which typically depends on the joint discretion of surgeons and neonatologists. In recent years, deep learning has been extensively applied in areas such as image segmentation, fracture and pneumonia classification, drug development, and pathological diagnosis.ObjectiveInvestigating deep learning applications using bedside x-rays to help optimizing surgical decision-making in neonatal NEC.MethodsThrough a retrospective analysis of anteroposterior bedside chest and abdominal x-rays from 263 infants diagnosed with NEC between January 2015 and April 2023, including a surgery group (94 cases) and a non-surgery group (169 cases), the infants were divided into a training set and a validation set in a 7:3 ratio. Models were built based on Resnet18, Densenet121, and SimpleViT to predict whether NEC patients required surgical intervention. Finally, the model's performance was tested using an additional 40 cases, including both surgical and non-surgical NEC cases, as a test group. To enhance the interpretability of the models, the study employed 2D-Grad-CAM technology to describe the models’ focus on significant areas within the x-ray images.ResultsResnet18 demonstrated outstanding performance in binary diagnostic capability, achieving an accuracy of 0.919 with its precise lesion imaging and interpretability particularly highlighted. Its precision, specificity, sensitivity, and F1 score were significantly high, proving its advantages in optimizing surgical decision-making for neonatal NEC.ConclusionThe Resnet18 deep learning model, constructed using bedside chest and abdominal imaging, effectively assists clinical physicians in determining whether infants with NEC require surgical intervention.

Aim: Associations of the adipose tissue insulin resistance index (AT-IR, a product of fasting insulin and free fatty acid) with body fat distribution and the ratio of alanine to aspartate aminotransferase (ALT/AST), a marker of hepatosteatosis, were examined in the context of the metabolic syndrome. Methods: Legs, the trunk and body fat by DXA, blood pressure (BP) and blood chemistry were measured in 284 young Japanese female university students and 148 middle-aged biological mothers whose BMI averaged

Citri Reticulatae Pericarpium(CRP) and Polygalae Radix (PR) are traditional Chinese medicinal herbs and dietary supplements, and they are commonly included in most prescriptions. Fungal contamination in CRP and PR has long been a concern for the public. Thus, in this study, the fungal diversity and abundance in CRP and PR were investigated via high-throughput sequencing technology. Analysis was conducted to determine the differences in dominant fungal microbiomes between mouldy and nonmouldy samples, and the correlation between the total number of fungi and fungal diversity in medicinal herbs at different altitudes and latitudes with other research was explored. Results show the fungal contamination of all 12 samples. At the phylum level, Ascomycota prevailed the most in CRP and PR with relative abundances of 56.96%–99.26% and 23.28%–76.06%, respectively. The dominant genera in CRP comprised Xeromyces (2.57%–53.21%), Aspergillus (0.18%–23.04%), Cystofilobasidium (0.032%–28.03) and Xerochrysium (0.31%–34.41%). The dominant genera in PR included Wallemia (0.27%–56.20%), Aspergillus (2.03%–48.06%), Xeromyces (0.20%–48.28%) and Xerochrysium (0.093%–43.95%). Two potential toxigenic fungi were detected: Alternaria alternata and Aspergillus versicolor. In addition, combined with the results of previous studies, the findings reveal the possible relation of diversity and abundance of fungal species to altitude and latitude: As the altitude and latitude decrease, the diversity and abundance of fungal species may increase. In conclusion, for the first time, this study focused on altitude and latitude as indicators and integrated multiple research findings to explore the correlation between the total amount and diversity of fungal species in the two edible herbs. Results reveal the fungal contamination of the surfaces of CRP and PR and provide a theoretical basis for the prevention and control of their fungal contamination.

The phase transition has always been a major focus in the study of black hole thermodynamics. This study employs the Kramer escape rate from stochastic processes to investigate the first-order phase transition strength between the large and small black hole states. The results indicate that the phase transition of the third-order Lovelock black holes exhibits significant asymmetric characteristics in diverse dimensions both in the hyperbolic and spherical topology, with an overall trend of the transition from large black holes to small black holes. Especially for the spherical topology, when the dimension is higher than seven, there exists a certain temperature beyond which a dynamic equilibrium is established for the phase transition. This study provides valuable insights into the first-order phase transition rate of black holes and enriches the understanding of black hole phase transitions.

To solve the current situation of low vehicle-to-pile ratio, charging pile (CP) operators incorporate private CPs into the shared charging system. However, the introduction of private CP has brought about the problem of poor service quality. Reputation is a common service evaluation scheme, in which the third-party reputation scheme has the issue of single point of failure; although the blockchain-based reputation scheme solves the single point of failure issue, it also brings the challenges of storage and query efficiency. It is a feasible solution to classify and store information on multiple chains, and at this time, reputation needs to be calculated in a cross-chain mode. Crosschain reputation calculation faces the problems of correctness verification, integrity verification and efficiency. Therefore, this paper proposes a verifiable and efficient cross-chain calculation model for CP reputation. Specially, in this model, we propose a verifiable cross-chain contract calculation scheme that adopts polynomial commitment to solve the problems of polynomial damage and tampering that may be encountered in the crosschain process of outsourced polynomials, so as to ensure the integrity and correctness of polynomial calculations. In addition, the miner selection and incentive mechanism algorithm in this scheme ensures the correctness of extracted information when the outsourced polynomial is calculated on the blockchain. The security analysis and experimental results demonstrate that this scheme is feasible in practice.

BackgroundPrevious observational epidemiological studies have suggested a potential association between thyroid function and inflammatory bowel disease (IBD). However, the findings remain inconclusive, and whether this association is causal remains uncertain. The objective of this study is to investigate the causal association between thyroid function and IBD.MethodsGenome-wide association studies (GWAS) involving seven indicators of thyroid function, IBD, and 41 cytokines were analyzed. Bidirectional two-sample Mendelian randomization (MR) and multivariable MR were conducted to examine the causal relationship between thyroid function and IBD and to explore the potential mechanisms underlying the associations.ResultsGenetically determined hypothyroidism significantly reduced the risk of CD (odds ratio [OR] = 0.761, 95% CI: 0.655–0.882, p < 0.001). Genetically determined reference-range TSH was found to have a suggestive causal effect on IBD (OR = 0.931, 95% CI: 0.888–0.976, p = 0.003), (Crohn disease) CD (OR = 0.915, 95% CI: 0.857–0.977, p = 0.008), and ulcerative colitis (UC) (OR =0.910, 95% CI: 0.830–0.997, p = 0.043). In reverse MR analysis, both IBD and CD appeared to have a suggestive causal effect on the fT3/fT4 ratio (OR = 1.002, p = 0.013 and OR = 1.001, p = 0.015, respectively). Among 41 cytokines, hypothyroidism had a significant impact on interferon-inducible protein-10 (IP-10) (OR = 1.465, 95% CI: 1.094–1.962, p = 0.010). The results of multivariable MR showed that IP-10 may mediate the causal effects of hypothyroidism with CD.ConclusionOur results suggest that an elevated TSH level reduces the risk of CD, with IP-10 potentially mediating this association. This highlights the pituitary-thyroid axis could serve as a potential therapeutic strategy for CD.

BackgroundSpinal cord injury (SCI) is a nervous system disease leading to motor and sensory dysfunction below the injury level, and can result in paralysis. MicroRNAs (miRNAs) play a key role in SCI treatment, and related research provides insights for SCI diagnosis and treatment. Bibliometrics is an important tool for literature statistics and evaluation, objectively summarizing multidimensional information. This study comprehensively overviews the field through bibliometric analysis of miRNA and SCI research, providing contemporary resources for future collaboration and clinical treatment.Materials and methodsIn this study, we searched the Web of Science Core Collection (WOSCC) database. After careful screening and data import, we extracted annual publications, citation counts, countries, institutions, authors, journals, highly cited articles, co-cited articles, keywords, and H-index. Bibliometrics and visualization analyses employed VOSviewer, CiteSpace, the R package “bibliometrix,” and online analytic platforms. Using Arrowsmith,1 we determined miRNA-SCI relationships and discussed potential miRNA mechanisms in SCI.ResultsFrom 2008 to 2024, the number of related papers increased annually, reaching 754. The number of yearly publications remained high and entered a period of rapid development. Researchers from 50 countries/regions, 802 institutions, 278 journals, and 3,867 authors participated in the field. Currently, China has advantages in the number of national papers, citations, institutions, and authors. However, it is necessary to strengthen cooperation among different authors, institutions, and countries to promote the production of important academic achievements. The research in the field currently focuses on nerve injury, apoptosis, and gene expression. Future research directions mainly involve molecular mechanisms, clinical trials, exosomes, and inflammatory reactions.ConclusionOverall, this study comprehensively analyzes the research status and frontier of miRNAs in SCI. A systematic summary provides a complete and intuitive understanding of the relationship between SCI and miRNAs. The presented findings establish a basis for future research and clinical application in this field.

Rapid reduction of plasma triglycerides (TG) is believed to improve the outcome of pancreatitis in the context of hypertriglyceridaemia (HTG)-induced acute pancreatitis (HTG-AP). Previous studies have suggested that haemoperfusion (HP) with the Jafron cartridge series could be effective for reducing TG concentrations in patients with HTG-AP. However, the clearance capacity (CC) for TG removal has not been reported. This case series reports on data from three patients with HTG-AP who underwent HP with HA230 or HA330 cartridges. Blood samples were collected from both before and after the cartridge circuit every 30 min and the CC was calculated. Twelve pairs of blood samples were collected for each type of HP cartridge. The mean ± SD CC of the HA230 cartridge for TG removal in this case series was 0.009781 ± 1.117235 ml/min (95% confidence interval [CI], –0.7000762, 0.7196384 ml). The mean ± SD CC of the HA330 cartridge for TG removal in this case series was 0.344914 ± 1.412183 ml/min (95% CI, –0.5523448, 1.2421721 ml). Based on the findings of this small case series, special caution is advised when considering the use of the HA230 and HA330 cartridges for reducing blood TG concentration pending further conclusive evidence from larger studies.

Managing severe chronic pain is a challenging task, given the limited effectiveness of available pharmacological and non-pharmacological treatments. This issue continues to be a significant public health concern, requiring a substantial therapeutic response. Ziconotide, a synthetic peptide initially isolated from Conus magus in 1982 and approved by the US Food and Drug Administration and the European Medicines Agency in 2004, is the first-line intrathecal method for individuals experiencing severe chronic pain refractory to other therapeutic measures. Ziconotide produces powerful analgesia by blocking N-type calcium channels in the spinal cord, which inhibits the release of pain-relevant neurotransmitters from the central terminals of primary afferent neurons. However, despite possessing many favorable qualities, including the absence of tolerance development, respiratory depression, and withdrawal symptoms (largely due to the absence of a G-protein mediation mechanism), ziconotide's application is limited due to factors such as intrathecal administration and a narrow therapeutic window resulting from significant dose-related undesired effects of the central nervous system. This review aims to provide a comprehensive and clinically relevant summary of the literatures concerning the pharmacokinetics and metabolism of intrathecal ziconotide. It will also describe strategies intended to enhance clinical efficacy while reducing the incidence of side effects. Additionally, the review will explore the current efforts to refine the structure of ziconotide for better clinical outcomes. Lastly, it will prospect potential developments in the new class of selective N-type voltage-sensitive calcium-channel blockers.

Background: Antidepressants are widely used to manage depression and other psychiatric diseases. A previous study revealed that hepatotoxicity was the main adverse event related to antidepressants. Therefore, drug-induced liver injury (DILI) caused by antidepressants deserves more attention. Objectives: To investigate DILI adverse events reported due to antidepressant use in the United States Food and Drug Administration Adverse Events Reporting System (FAERS) database. Research design: A disproportionality analysis of spontaneously reported adverse events was conducted to assess the association between antidepressant drugs and DILI. Methods: FAERS data from 1 January 2004 to 31 December 2021 were compiled and analyzed using the reporting odds ratio (ROR) and information component (IC). Results: As per the FAERS database, of the 324,588 cases that were administered antidepressants, 10,355 were identified as cases with DILI. Among the identified 42 antidepressants, nefazodone ( n = 47, ROR = 7.79, IC = 2.91), fluvoxamine ( n = 29, ROR = 4.69, IC = 2.20), and clomipramine ( n = 24, ROR = 3.97, IC = 1.96) had the highest ROR for cholestatic injury; mianserin ( n = 3, ROR = 21.46, IC = 3.99), nefazodone ( n = 264, ROR = 18.67, IC = 3.84), and maprotiline ( n = 15, ROR = 5.65, IC = 2.39) for hepatocellular injury; and nefazodone ( n = 187, ROR = 12.71, IC = 0.48), clomipramine ( n = 35, ROR = 2.07, IC = 0.26), and mirtazapine ( n = 483, ROR = 1.96, IC = 0.94) for severe drug-related hepatic disorders. Only nefazodone elicited hepatic failure signals ( n = 48, ROR = 18.64, IC = 4.16). There are limited reports on the adverse reactions of relatively new antidepressant drugs, such as milnacipran, viloxazine, esketamine, and tianeptine, and those not approved by the Food and Drugs Administration, such as reboxetine and agomelatine. Conclusion: A significant association was observed between DILI and nefazodone. Duloxetine and clomipramine were associated with three DILI categories, except hepatic failure. The disproportionality analysis cannot conclude on a definite causal link between antidepressants and DILI. Additional research is required to assess new-generation antidepressants for their propensity to cause DILI.

BackgroundDue to the expanding coverage of medical insurance and the growth of medical expenses, the ability to assess the performance of designated medical institutions (DMIs) in supporting the delivery of high-quality patient care and the standardized use of funds represents a priority in China. Despite such interest, there has yet to be an operable standard and labor-saving method for assessing DMIs in China.ObjectiveThe main objectives include two aspects: (1) establishing an evaluation index system for DMIs based on contracts; (2) designing and developing an online evaluation platform.MethodsA group of 20 experts with theoretical and practical expertise in medical insurance regulation and performance evaluation were invited to select available indicators. A combination weighting method based on analytic hierarchy process and entropy method was used to determine the weight coefficient. Shanghai was taken as the sample area, and 760 DMIs were included in the empirical research. The test-retest reliability method and criterion-related validity method was used to test the reliability and the validity of the evaluation result.ResultsAn assessment index system that included 6 domains and 56 indicators was established in this study. Furthermore, we developed an online platform to assist in the implementation of the assessment. The results showed that the average score of assessment was 94.39, the median was 96.92. The test-retest reliability value was 0.96 (P ≤ 0.01), which indicated high stability of the assessment. In addition, there was a significant negative relationship between assessment score and the penalty amount of DMIs (R = −0.133, P < 0.001). After adjusting for the basic characteristics of medical institutions, the number of visits and revenue, the negative relationship was still significant (B = −0.080, P < 0.05). These results are consistent with expectations, indicating that the assessment had good criterion-related validity.ConclusionsThis study established an operable assessment measure and developed an online platform to assess the performance of DMIs. The results showed good feasibility and reliability in empirical research. Our research findings provided an operable Chinese solution for DMI assessment that saves manpower and time, which would have good enlightening significance in other regions of China and in low-income and middle-income countries internationally.

In this article, we analyze the electromagnetic form factors of the vector heavy-light mesons to the pseudoscalar heavy-light mesons in the framework of three-point QCD sum rules, where the contributions of vacuum condensate terms 〈q‾q〉, 〈q‾gsσGq〉, 〈gs2G2〉, 〈f3G3〉 and 〈q‾q〉〈gs2G2〉 are considered. With these results, we also obtain the radiative decay widths of the vector heavy-light mesons and then compare our results with those of other collaboration's. The final results about the radiative decay widths are Γ(D⁎0→D0γ)=1.74−0.37+0.40 keV, Γ(D⁎+→D+γ)=0.17−0.07+0.08 keV, Γ(Ds⁎→Dsγ)=0.029−0.008+0.009 keV, Γ(B⁎0→B0γ)=0.018−0.005+0.006 keV, Γ(B⁎+→B+γ)=0.015−0.007+0.007 keV and Γ(Bs⁎→Bsγ)=0.016−0.005+0.003 keV.

Vascular cognitive impairment (VCI) encompasses a range of cognitive deficits arising from vascular pathology. The pathophysiological mechanisms underlying VCI remain incompletely understood; however, chronic cerebral hypoperfusion (CCH) is widely acknowledged as a principal pathological contributor. Mitochondria, crucial for cellular energy production and intracellular signaling, can lead to numerous neurological impairments when dysfunctional. Recent evidence indicates that mitochondrial dysfunction—marked by oxidative stress, disturbed calcium homeostasis, compromised mitophagy, and anomalies in mitochondrial dynamics—plays a pivotal role in VCI pathogenesis. This review offers a detailed examination of the latest insights into mitochondrial dysfunction within the VCI context, focusing on both the origins and consequences of compromised mitochondrial health. It aims to lay a robust scientific groundwork for guiding the development and refinement of mitochondrial-targeted interventions for VCI.

Gas explosion accidents are the most serious type of accidents that cause losses in coal mines. In order to explore the pattern of unsafe actions related to such accidents and to regulate the behaviors of relevant work types in the operation process of underground coal mines, 116 serious gas explosion accidents in coal mines from 2005 to 2022 were statistically analyzed to explore the distribution characteristics of unsafe actions in different dimensions of gas explosion accidents in coal mines, to discuss the reasons for their occurrence, and to put forward targeted measures. The results show that: from the aspect of the coupling of work type and accident location, blasting operators and tile inspection operators have the highest number of unsafe actions in the face of digging and coal mining, respectively; from the aspect of the coupling of work type and laws and regulations, blasting operators are the operators with the highest frequency of violating the regulations, and the most violated regulations is the Coal Mine Safety Regulations.

To at the low robustness of the existing model for occluded object detection, an occluded object detection algorithm based on fuzzy sample anchor box IoU Matching degree Deviation Aware(IoU_MDA)is proposed. Firstly, fuzzy samples are defined based on Anchor-based, which reflects the degree of object occlusion. Secondly, IoU_MDA is proposed to quantify the degree of interference experienced by fuzzy samples. Then, IoU_MDA_Loss is constructed based on IoU_MDA, combined with IoU and the balance parameter $\Phi$ . To address class imbalance issues and enhance model generality, intra-class and inter-class fuzzy weights, and fuzzy sample focusing parameters are designed on the basis of the initial IoU_MDA_Loss. An occluded object training scheme is designed based on IoU perception, and non-fuzzy sample weight balancing parameters are constructed. Finally, IoU_MDA_Loss is merged with Focal Loss to obtain IoU_MDA_Focal Loss, simultaneously enhancing the detection performance of fuzzy samples and difficult-to-distinguish samples. The experimental results on the WiderPerson and VOC2007 datasets show that the mAP of IoU_MDA_Loss has increased by 2.04%, 2.36%, and IoU_MDA_Focal Loss has increased by 1.82%, 2.65%, respectively, compared to the baseline model. The detection performance surpasses current mainstream algorithms.

Abstract Purpose To explore the predictive value of radiomics in predicting stroke-associated pneumonia (SAP) in acute ischemic stroke (AIS) patients and construct a prediction model based on clinical features and DWI-MRI radiomics features. Methods Univariate and multivariate logistic regression analyses were used to identify the independent clinical predictors for SAP. Pearson correlation analysis and the least absolute shrinkage and selection operator with ten-fold cross-validation were used to calculate the radiomics score for each feature and identify the predictive radiomics features for SAP. Multivariate logistic regression was used to combine the predictive radiomics features with the independent clinical predictors. The prediction performance of the SAP models was evaluated using receiver operating characteristics (ROC), calibration curves, decision curve analysis, and subgroup analyses. Results Triglycerides, the neutrophil-to-lymphocyte ratio, dysphagia, the National Institutes of Health Stroke Scale (NIHSS) score, and internal carotid artery stenosis were identified as clinically independent risk factors for SAP. The radiomics scores in patients with SAP were generally higher than in patients without SAP (P

Current groundwater prediction models often exhibit low accuracy and complex parameter adjustment. To tackle these limitations, a novel prediction model, called improved Aquila optimizer bi-directional long-term and short-term memory (IAO-BiLSTM) network, is proposed. IAO-BiLSTM optimizes the hyperparameters of the BiLSTM network using an IAO algorithm. IAO incorporates three novel enhancements, including population initialization, population updating, and global best individual updating, to overcome the drawbacks of current optimization algorithms. Before making predictions, the challenge posed by the highly nonlinear and non-stationary characteristics of groundwater level signals was addressed through the application of a wavelet multi-scale analysis method. Using a landslide site in Zhejiang Province as an example, a monitoring system is established, and continuous wavelet transform, cross-wavelet transform, and wavelet coherence analysis are employed to perform multi-scale feature analysis on a 2-year dataset of rainfall and groundwater depth. The findings reveal that the groundwater depth of monitoring holes exhibits similar high energy resonating periods and phase relationships, strongly correlating with rainfall. Subsequently, IAO-BiLSTM is employed to predict groundwater depth, and its results are compared with seven popular machine learning regression models. The results demonstrate that IAO-BiLSTM achieves the highest accuracy, as evidenced by its root mean squared error of 0.25. HIGHLIGHTS The wavelet multi-scale analysis method overcomes the limitation of the traditional qualitative analysis method.; The wavelet multi-scale analysis method successfully reveals the multi-scale characteristics and the most significant influencing factors.; An improved Aquila optimizer bi-directional long-term and short-term memory (IAO-BiLSTM) network can predict groundwater level reliably and effectively.; IAO-BiLSTM beats the current seven hot prediction models and showed good performance.;

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a devastating chronic lung disease characterized by irreversible scarring of the lung parenchyma. Despite various interventions aimed at mitigating several different molecular aspects of the disease, only two drugs with limited clinical efficacy have so far been approved for IPF therapy. Objective We investigated the therapeutic efficacy of amifostine, a detoxifying drug clinically used for radiation-caused cytotoxicity, in bleomycin-induced murine pulmonary fibrosis. Methods C57BL6/J mice were intratracheally instilled with 3 U/kg of bleomycin. Three doses of amifostine (WR-2721, 200 mg/kg) were administered intraperitoneally on days 1, 3, and 5 after the bleomycin challenge. Bronchoalveolar lavage fluid (BALF) was collected on day 7 and day 21 for the assessment of lung inflammation, metabolites, and fibrotic injury. Human fibroblasts were treated in vitro with transforming growth factor beta 1 (TGF-β1), followed by amifostine (WR-1065, 1–4 µg/mL) treatment. The effects of TGF-β1 and amifostine on the mitochondrial production of reactive oxygen species (ROS) were assessed by live cell imaging of MitoSOX. Cellular metabolism was assessed by the extracellular acidification rate (ECAR), the oxygen consumption rate (OCR), and the concentrations of various energy-related metabolites as measured by mass spectrum (MS). Western blot analysis was performed to investigate the effect of amifostine on sirtuin 1 (SIRT1) and adenosine monophosphate activated kinase (AMPK). Results Three doses of amifostine significantly attenuated lung inflammation and pulmonary fibrosis. Pretreatment and post-treatment of human fibroblast cells with amifostine blocked TGF-β1-induced mitochondrial ROS production and mitochondrial dysfunction in human fibroblast cells. Further, treatment of fibroblasts with TGF-β1 shifted energy metabolism away from mitochondrial oxidative phosphorylation (OXPHOS) and towards glycolysis, as observed by an altered metabolite profile including a decreased ratio of NAD + /NADH and increased lactate concentration. Treatment with amifostine significantly restored energy metabolism and activated SIRT1, which in turn activated AMPK. The activation of AMPK was required to mediate the effects of amifostine on mitochondrial homeostasis and pulmonary fibrosis. This study provides evidence that repurposing of the clinically used drug amifostine may have therapeutic applications for IPF treatment. Conclusion Amifostine inhibits bleomycin-induced pulmonary fibrosis by restoring mitochondrial function and cellular metabolism.

Abstract Liver fibrosis is a reparative response to injury that arises from various etiologies, characterized by activation of hepatic stellate cells (HSCs). Periostin, a secreted matricellular protein, has been reported to participate in tissue development and regeneration. However, its involvement in liver fibrosis remains unknown. This study investigated the roles and mechanisms of Periostin in phenotypic transition of HSCs and relevant abnormal cellular crosstalk during liver fibrosis. The fate of hepatic stellate cells (HSCs) during liver fibrogenesis was investigated using single-cell and bulk RNA sequencing profiles, which revealed a significant proliferation of activated HSCs (aHSCs) in fibrotic livers of both humans and mice. αSMA-TK mice were used to demonstrate that depletion of proliferative aHSCs attenuates liver fibrosis induced by carbon tetrachloride and 3,5-diethoxycarbonyl-1,4-dihydrocollidine. Through integrating data from single-cell and bulk sequencing, Periostin was identified as a distinctive hallmark of proliferative aHSC subpopulation. Elevated levels of Periostin were detected in fibrotic livers of both humans and mice, primarily within aHSCs. However, hepatic Periostin levels were decreased along with depletion of proliferative aHSCs. Deficiency of Periostin led to reduced liver fibrosis and suppressed hepatocyte epithelial-mesenchymal transition (EMT). Periostin-overexpressing HSCs, exhibiting a proliferative aHSC phenotype, release bone morphogenetic protein-1 (Bmp-1), which activates EGFR signaling, inducing hepatocyte EMT and contributing to liver fibrosis. In conclusion, Periostin in aHSCs drives their acquisition of a proliferative phenotype and the release of Bmp-1. Proliferative aHSC subpopulation-derived Bmp-1 induces hepatocyte EMT via EGFR signaling, promoting liver fibrogenesis. Bmp-1 and Periostin should be potential therapeutic targets for liver fibrosis.

Objective Ankle joint fractures are often accompanied by medial deltoid ligament rupture. There is controversy over whether or how to treat deltoid ligament rupture. This study was aimed to explore the feasibility of repairing the medial deltoid ligament using Kirschner wire internal fixation of the medial tibiotalar joint combined with external fixation. Methods Forty‐six patients with ankle fractures involving deltoid ligament rupture, treated between October 2012 and February 2021, were retrospectively evaluated. Twenty‐five patients were treated with a Kirschner wire to fix the tibiotalar joint and indirectly repair the deltoid ligament as the repaired group. Twenty‐one patients underwent reduction and fixation of internal and external malleolus fractures, and the deltoid ligament was not repaired in the unrepaired group. The American Orthopaedic Foot and Ankle Society (AOFAS) ankle‐hindfoot score, visual analog scale (VAS), Medical Outcomes Short Form 36‐item questionnaire score (SF‐36), and Medial clear space perpendicular (preoperative, postoperative, final follow‐up) were used for functional evaluations and reduction assessments. Mann–Whitney test were used to compare the differences between the groups. Results The follow‐up time was 13–112 months with a mean of 59.32 months for the repaired group and 11–94 months with a mean of 53.43 months for the unrepaired group. There was no significant difference in the operative time or intraoperative blood loss between the two groups (p > 0.05). At the last follow‐up, the AOFAS ankle‐hindfoot and SF‐36 scores of the repaired group were significantly higher than those of the non‐repaired group (p

Currently, convolutional neural networks (CNNs) and vision transformers (ViTs) are widely adopted as the predominant neural network architectures for remote sensing image scene classification. Although CNNs have lower computational complexity, ViTs have a higher performance ceiling, making both suitable as backbone networks for remote sensing scene classification tasks. However, remote sensing imagery has high intraclass variation and interclass similarity, which poses a challenge for existing methods. To address this issue, we propose the class-aware self-distillation (CASD) framework. This framework uses an end-to-end distillation mechanism to mine class-aware knowledge, effectively reducing the impact of significant intraclass variation and interclass similarity in remote sensing imagery. Specifically, our approach involves constructing pairs of images: similar pairs consisting of images belonging to the same class, and dissimilar pairs consisting of images from different classes. We then apply a distillation loss that we designed, which distills the corresponding probability distributions to ensure that the distributions of similar pairs become more consistent, and those of dissimilar pairs become more distinct. In addition, the enforced learnable $\alpha$ added to the distillation loss further amplifies the network's ability to comprehend class-aware knowledge. The experiment section demonstrates that our method CASD outperforms other methods on four publicly available datasets. And the ablation experiments demonstrate the effectiveness of the method.

Abstract The skeleton is a highly innervated organ in which nerve fibers interact with various skeletal cells. Peripheral nerve endings release neurogenic factors and sense skeletal signals, which mediate bone metabolism and skeletal pain. In recent years, bone tissue engineering has increasingly focused on the effects of the nervous system on bone regeneration. Simultaneous regeneration of bone and nerves through the use of materials or by the enhancement of endogenous neurogenic repair signals has been proven to promote functional bone regeneration. Additionally, emerging information on the mechanisms of skeletal interoception and the central nervous system regulation of bone homeostasis provide an opportunity for advancing biomaterials. However, comprehensive reviews of this topic are lacking. Therefore, this review provides an overview of the relationship between nerves and bone regeneration, focusing on tissue engineering applications. We discuss novel regulatory mechanisms and explore innovative approaches based on nerve–bone interactions for bone regeneration. Finally, the challenges and future prospects of this field are briefly discussed.