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Abstract Background Invertases (INVs) are key enzymes in sugar metabolism, cleaving sucrose into glucose and fructose and playing an important role in plant development and the stress response, however, the INV gene family in passion fruit has not been systematically reported. Results In this study, a total of 16 PeINV genes were identified from the passion fruit genome and named according to their subcellular location and chromosome position. These include six cell wall invertase (CWINV) genes, two vacuolar invertase (VINV) genes, and eight neutral/alkaline invertase (N/AINV) genes. The gene structures, phylogenetic tree, and cis-acting elements of PeINV gene family were predicted using bioinformatics methods. Results showed that the upstream promoter region of the PeINV genes contained various response elements; particularly, PeVINV2, PeN/AINV3, PeN/AINV5, PeN/AINV6, PeN/AINV7, and PeN/AINV8 had more response elements. Additionally, the expression profiles of PeINV genes under different abiotic stresses (drought, salt, cold temperature, and high temperature) indicated that PeCWINV5, PeCWINV6, PeVINV1, PeVINV2, PeN/AINV2, PeN/AINV3, PeN/AINV6, and PeN/AINV7 responded significantly to these abiotic stresses, which was consistent with cis-acting element prediction results. Sucrose, glucose, and fructose are main soluble components in passion fruit pulp. The contents of total soluble sugar, hexoses, and sweetness index increased significantly at early stages during fruit ripening. Transcriptome data showed that with an increase in fruit development and maturity, the expression levels of PeCWINV2, PeCWINV5, and PeN/AINV3 exhibited an up-regulated trend, especially for PeCWINV5 which showed highest abundance, this correlated with the accumulation of soluble sugar and sweetness index. Transient overexpression results demonstrated that the contents of fructose, glucose and sucrose increased in the pulp of PeCWINV5 overexpressing fruit. It is speculated that this cell wall invertase gene, PeCWINV5, may play an important role in sucrose unloading and hexose accumulation. Conclusion In this study, we systematically identified INV genes in passion fruit for the first time and further investigated their physicochemical properties, evolution, and expression patterns. Furthermore, we screened out a key candidate gene involved in hexose accumulation. This study lays a foundation for further study on INV genes and will be beneficial on the genetic improvement of passion fruit breeding.

Abstract Meningitis induced by Pasteurella multocida has been substantially described in clinical practice in both human and veterinary medicine, but the underlying mechanisms have not been previously reported. In this study, we investigated the influence of P. multocida infection on the permeability of the blood–brain barrier (BBB) using different models. Our in vivo tests in a mouse model and in vitro tests using human brain microvascular endothelial cell (hBMEC) model showed that P. multocida infection increased murine BBB permeability in mice and hBMEC monolayer permeability. Furthermore, we observed that P. multocida infection resulted in decreased expression of tight junctions (ZO1, claudin-5, occludin) and adherens junctions (E-cadherin) between neighboring hBMECs. Subsequent experiments revealed that P. multocida infection promoted the activation of hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor A (VEGFA) signaling and NF-κB signaling, and suppressed the HIF-1α/VEGFA significantly remitted the decrease in ZO1/E-cadherin induced by P. multocida infection (P

Abstract The present study investigated the associations of serum gamma-glutamyl transferase (GGT), a marker of fatty liver and oxidative stress, and ALT/AST, a marker of fatty liver, with percentage trunk fat and postload glucose, insulin resistance, and β-cell function in middle-aged Japanese individuals, whose BMI averaged

Abstract The relationship of adipose tissue insulin resistance (AT-IR, a product of fasting insulin and free fatty acids) and homeostasis-model assessment-insulin resistance (HOMA-IR) to β-cell function was studied cross-sectionally in the setting of subtle glucose dysregulation. Associations of AT-IR and HOMA-IR with fasting and post-glucose glycemia and β-cell function inferred from serum insulin kinetics during a 75 g oral glucose tolerance test were studied in 168 young female Japanese students. β-cell function was evaluated by disposition index calculated as a product of the insulinogenic index (IGI) and Matsuda index. AT-IR, not HOMA-IR, showed positive associations with post-glucose glycemia and area under the glucose response curve although both indices were associated with fasting glycemia. HOMA-IR, not AT-IR, was associated positively with log IGI whereas both indices were inversely associated with Matsuda index. AT-IR, not HOMA-IR, showed inverse associations with log disposition index. Associations of adipose tissue insulin resistance with β-cell function (inverse) and glucose excursion in young Japanese women may suggest that lipotoxicity to pancreatic β-cells for decades may be associated with β cell dysfunction found in Japanese patients with type 2 diabetes. Positive association of HOMA-IR with insulinogenic index may be associated with compensatory increased insulin secretion.

According to previous studies, D-dimer levels are associated with the prognosis of patients with pancreatic cancer (PC). However, the results of current studies are limited and controversial. Therefore, we performed this meta-analysis to assess the relationship between D-dimer levels and prognostic and pathological characteristics of PC patients. We first searched the databases of PubMed, Embase, The Cochrane Library, Web Of Science, CBM, VIP, CNKI and Wanfang to identify available studies. The relationship between pretreatment d-dimer levels and prognosis in PC patients was assessed using the combined hazard ratio (HR) and 95% confidence interval (CI). The combined odds ratio (OR) and 95% confidence interval (CI) were used in assessing the relationship between pathological characteristics and d-dimer levels in PC patients. Stata 12.0 software was used for all statistical analyses. In total, we included 13 studies involving 2777 patients. The results showed that elevated pre-treatment d -dimer levels were significantly associated with OS deterioration (HR = 1.46 95% CI: 1.34–1.59; p

To enhance the sensitivity, signal-to-noise ratio and durance of electrospray mass spectrometer, an off-axis ion guide combining a traveling-wave (TW) stacked-ring and a shaped ion funnel has been designed, which is capable of filtering out the neutral contaminants and charged droplets entrained in the electrospray plume. According to its structural characteristics, the corresponding TW and radio frequency (RF) coupling power supply and measurement as well as control system were designed. Customizable Ethernet communication protocol was used to control the field-programmable logic gate array (FPGA) for full-circuit signal control and generation, and an 8-channel traveling-wave amplitude monitoring was achieved through a 12-bit analog-to-digital converter (ADC) and a 16-bit digital-to-analog converter (DAC). In addition, dual-plane transformer coupling circuit was designed. The use of traveling wave changed the central reference frame of the RF, achieving the purpose of programmed RF and the effect of TW in the stacked-ring to provide axial kinetic energy. The stability and accuracy of the electrical parameters of the hardware system on the off-axis transmission structure were tested. The results showed that the controllable voltage range of TW power supply is 0.1-100 V and the controlled DC power supply’s full range detection and control absolute error are less than 0.04 V. The frequency of TW up to 400 kHz, both rising edge and falling edge are less than 30 ns. Furthermore, the waveforms of TW, RF and post-coupling waveform are sufficiently smooth. The test results also showed that the performance of the power supply and measurement and control system are stable and reliable, and their accuracy and range can satisfy the design requirements. Then, the performance of off-axis structure was tested under rough vacuum using reserpine ions. It was found that the reference voltage difference between the upper and lower traveling-waves (the voltage which the ions were extracted), the voltage of the upper traveling-waves, and the traveling-wave duty cycle of the off-axis ion transmitter have more significant effects on the off-axis transmission of ions than other electrical parameters. The experimental results provide a fundamental understanding of ion transport and off-axis separation of traveling-wave stacked-ring structures, which is valuable for the development of high signal-to-noise mass spectrometry system. In the future, this novel traveling-wave off-axis transmitter and its coupling power supply system will be applied to homemade mass spectrometry instruments. Besides, we will compare the developed device with the mainstream ion transmission devices in the market so as to further improve the device structure and power supply parameters, and deeply explore the role of traveling-wave off-axis transmitter in different ionization sources and different detectors.

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.

Objective(s): Neuroinflammation is considered an important step in the progression of secondary brain injury (SBI) induced by cerebral hemorrhage (ICH). The nucleotide-binding and oligomerization structural domain-like receptor family of pyridine structural domain-containing 3 (NLRP3) inflammasomes play an important role in the immune pathophysiology of SBI. Febuxostat (Feb) is a xanthine oxidase inhibitor that is approved for the treatment of gout and has been found to have potent anti-inflammatory effects. However, it has been less studied after ICH and we aimed to explore its protective role in ICH.Materials and Methods: We established an autologous blood-brain hemorrhage model in C57BL/6 mice. Functions of co-expressed genes were analyzed by trend analysis and bioinformatics analysis. Enzyme-linked immunosorbent assay were used to assess the inflammatory factor levels. Fluoro-Jade B histochemistry and TUNEL staining were used to detect neuronal apoptosis. Immunofluorescence staining and western blotting were used to detect the expression of NLRP3 inflammasomes.Results: Pretreatment with Feb reduced neuronal cell death and degeneration and alleviated neurobehavioral disorders in vivo. Feb was found to modulate inflammation-related pathways by trend analysis and bioinformatics analysis. In addition, Feb inhibited microglia activation and elevated cytokine levels after ICH. Furthermore, double immunofluorescence staining showed that co-localization of NLRP3 with Iba1 positive cells was reduced after treatment with Feb. Finally, we found that Feb inhibited the activation of the NLRP3/ASC/caspase-1 pathway after ICH. Conclusion: By inhibiting the NLRP3 inflammasome, preconditioning Feb attenuates inflammatory injury after ICH. Our findings may provide new insights into the role of Feb in neuroprotection.

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.

The three-dimensional (3D) geometry of carotid atherosclerotic plaques is associated with multiple cardiovascular diseases. However, it is unknown if carotid plaques of different sizes are consistent in 3D geometry, with a lack of quantitative observation. We aim to evaluate the geometric consistency of carotid plaques using the correlations between multidimensional parameters.42 cases with asymptomatic stenosis caused by atherosclerotic plaque in the carotid artery were included. Carotid plaques and calcifications were identified on computed tomography angiography images and 3D reconstructed. Multidimensional geometric parameters (length, surface area, volume, etc.) were measured on the reconstructed 3D structures. Linear and non-linear (power function) fittings were used to investigate the relationships between multidimensional parameters. The analysis was performed based on cases and plaques, respectively. Spearman rank correlation analysis, R-squared, and p-values were used to evaluate the significance of the relationship. Significant relationship was defined as R-squared >0.25 and p

Aim: We tested whether skeletal muscle mass is associated with insulin sensitivity, pancreatic β-cell function, and postglucose glycemia. Methods: Appendicular skeletal muscle mass (ASM) (relative to body size, %ASM) by DXA, surrogate measures of insulin sensitivity, insulin secretion and the disposition index (insulin sensitivity adjusted insulin secretion: a product of the insulinogenic index and Matsuda insulin sensitivity index) inferred from serum insulin kinetics during a 75 g oral glucose tolerance test (OGTT) were evaluated in 168 young and 65 middle-aged women, whose BMI averaged

Energy systems are currently undergoing a transformation towards new paradigms characterized by decarbonization, decentralization, democratization, and digitalization. In this evolving context, energy blockchain, aiming to enhance efficiency, transparency, and security, emerges as an integrated technological solution designed to address the diverse challenges in this field. Data security is essential for the reliable and efficient functioning of energy blockchain. The pressing need to address challenges related to secure data storage, effective data management, and efficient data utilization is increasingly vital. This paper offers a comprehensive survey of academic discourse on energy blockchain data security over the past five years, adopting an all-encompassing perspective that spans data storage, management, and utilization. Our work systematically evaluates and contrasts the strengths and weaknesses of various research methodologies. Additionally, this paper proposes an integrated hierarchical on-chain and off-chain security energy blockchain architecture, specifically designed to meet the complex security requirements of multi-blockchain business environments. Concludingly, this paper identifies key directions for future research, particularly in advancing the integration of storage, management, and utilization of energy blockchain data security.

Introduction and Objectives: Assessing fibrosis risk noninvasively is essential. The steatosis-associated fibrosis estimator (SAFE) score shows promise but needs validation. Patients and Methods: This was a three-part study. In part 1, we compared the SAFE score with the Fibrosis-4 (FIB-4) and NAFLD fibrosis score (NFS) in the National Health and Nutrition Examination Survey (NHANES) cohort (2017–2020), using transient elastography (TE) as screening reference. In part 2, we examined patients who underwent liver biopsies at an Asian center between 2018 and 2020 to assess these models in various liver diseases. In part 3, the SAFE score was applied to adults in the NHANES cohort (1999–2016) to assess the correlation with mortality. Results: In part 1, we studied 6,677 patients, comprising 595 screening positive (TE ≥8 kPa). SAFE (cutoff 100) displayed a lower proportion of false positives (10.4 %) than FIB-4 (cutoff 1.3) and NFS (cutoff -1.455) (22.1 % and 43.6 %) while retaining a low proportion of false negatives (5.5 %). In part 2, SAFE outperformed FIB-4 (P = 0.04) and NFS (P = 0.04) in staging significant fibrosis (≥S2) in NAFLD and had similar accuracies in other etiologies. In part 3, the FIB-4, NFS, and SAFE score were associated with all-cause mortality in the general population, with c-statistics of 0.738, 0.736, and 0.759, respectively. Conclusions: The SAFE score reduced futile referrals more effectively than FIB-4 without raising the missed TE ≥ 8 kPa rate. It correlated with all-cause mortality in the general population and excelled in staging significant fibrosis in NAFLD.

Zero Valent Iron (ZVI), an ideal reductant treating persistent pollutants, is hampered by issues like corrosion, passivation, and suboptimal utilization. Recent advancements in nonmetallic modified ZVI (NM-ZVI) show promising potential in circumventing these challenges by modifying ZVI's surface and internal physicochemical properties. Despite its promise, a thorough synthesis of research advancements in this domain remains elusive. Here we review the innovative methodologies, regulatory principles, and reduction-centric mechanisms underpinning NM-ZVI's effectiveness against two prevalent persistent pollutants: halogenated organic compounds and heavy metals. We start by evaluating different nonmetallic modification techniques, such as liquid-phase reduction, mechanical ball milling, and pyrolysis, and their respective advantages. The discussion progresses towards a critical analysis of current strategies and mechanisms used for NM-ZVI to enhance its reactivity, electron selectivity, and electron utilization efficiency. This is achieved by optimizing the elemental compositions, content ratios, lattice constants, hydrophobicity, and conductivity. Furthermore, we propose novel approaches for augmenting NM-ZVI's capability to address complex pollution challenges. This review highlights NM-ZVI's potential as an alternative to remediate water environments contaminated with halogenated organic compounds or heavy metals, contributing to the broader discourse on green remediation technologies.

ObjectivesTo investigate the effect of aripiprazole on prolactin levels in patients with schizophrenia and analyze whether varying baseline prolactin levels affect the effectiveness and safety of aripiprazole, in a real-life diagnostic and therapeutic setting in a post-hoc analysis.MethodsIn this post-hoc analysis, patients with schizophrenia in the acute phase were divided into an elevated-prolactin group and a normal-prolactin group. After 8 weeks of aripiprazole treatment, changes in the proportion of patients with an abnormal prolactin level were analyzed in both groups, and the efficacy and safety of aripiprazole were compared between the two groups.ResultsThe elevated-prolactin group had more women, a longer duration of disease, and lower Positive and Negative Syndrome Scale (PANSS) total and subscale scores at baseline compared with the normal-prolactin group (all P < 0.05), and there was no significant difference in the proportion of patients with prior use of antipsychotic medication between the two groups. Regardless of previous antipsychotic use, patients in both groups developed hyperprolactinemia (23/168 [13.7%] in those who had taken antipsychotics vs. 43/375 [11.4%] in those who had not). After 8 weeks of aripiprazole treatment, the proportion of patients with abnormal prolactin in the elevated-prolactin group significantly decreased with prolonged treatment (P < 0.001), and aripiprazole had no significant effect on the normal-prolactin group (P = 0.250). Normal-prolactin group showed better efficacy than the elevated-prolactin group, and the differences in efficacy between the two groups was observed from week 4 to the endpoint (all p

ABSTRACT Interaction between viruses and bacteria during the development of infectious diseases is a complex question that requires continuous study. In this study, we explored the interactions between pseudorabies virus (PRV) and Pasteurella multocida (PM), which are recognized as the primary and secondary agents of porcine respiratory disease complex (PRDC), respectively. In vivo tests using mouse models demonstrated that intranasal inoculation with PRV at a sublethal dose induced disruption of murine respiratory barrier and promoted the invasion and damages caused by PM through respiratory infection. Inoculation with PRV also disrupted the barrier function of murine and porcine respiratory epithelial cells, and accelerated the adherence and invasion of PM to the cells. In mechanism, PRV infection resulted in decreased expression of tight junction proteins (ZO-1, occludin) and adherens junction proteins (β-catenin, E-cadherin) between neighboring respiratory epithelial cells. Additionally, PRV inoculation at an early stage downregulated multiple biological processes contributing to epithelial adhesion and barrier functions while upregulating signals beneficial for respiratory barrier disruption (e.g., the HIF-1α signaling). Furthermore, PRV infection also stimulated the upregulation of cellular receptors (CAM5, ICAM2, ACAN, and DSCAM) that promote bacterial adherence. The data presented in this study provide insights into the understanding of virus-bacteria interactions in PRDC and may also contribute to understanding the mechanisms of secondary infections caused by different respiratory viruses (e.g., influenza virus and SARS-CoV-2) in both medical and veterinary medicine.IMPORTANCECo-infections caused by viral and bacterial agents are common in both medical and veterinary medicine, but the related mechanisms are not fully understood. This study investigated the interactions between the zoonotic pathogens PRV and PM during the development of respiratory infections in both cell and mouse models, and reported the possible mechanisms which included: (i) the primary infection of PRV may induce the disruption and/or damage of mammal respiratory barrier, thereby contributing to the invasion of PM; (ii) PRV infection at early stage accelerates the transcription and/or expression of several cellular receptors that are beneficial for bacterial adherence. This study may shed a light on understanding the mechanisms on the secondary infection of PM promoted by different respiratory viruses (e.g., influenza virus and SARS-CoV-2) in both medical and veterinary medicine.

Background: The significance of CXCL5 in pancreatic cancer is unclear, although it has been implicated in the malignant process of many different types of cancer. Research on the impact of CXCL5 on immune cell infiltration and the malignant phenotype of pancreatic cancer is needed. This study aimed to examine the connection between CXCL5 expression and immune cell infiltration and the malignant phenotype of pancreatic cancer. Methods: Tissue samples and clinical information were collected from 90 patients with pancreatic cancer. Tumour tissues and adjacent tissues were made into a tissue microarray and stained for immunohistochemistry analysis. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were performed to measure the expression level of CXCL5. CXCL5-overexpressing/CXCL5-knockdown cell lines were constructed via transfection for cytological experiments. CCK-8, cell apoptosis, cell cycle, cell invasion, and cell colony formation assays were used to detect the effect of CXCL5 on the malignant phenotype of pancreatic cancer cells. Finally, a mouse model of pancreatic cancer was constructed for in vivo verification. Results: Compared with control cells, pancreatic cancer cells overexpressing CXCL5 exhibited increased proliferation, migration, and invasion but decreased apoptosis. Conversely, knockdown of CXCL5 did not enhance the malignant phenotype of pancreatic cancer cells. Spearman correlation analysis indicated that there was a significant negative correlation between CXCL5 levels and the CD8 IRS. However, there was a significant positive correlation between FOXP3 IRS and CXCL5 levels. Conclusions: CXCL5 is highly expressed in pancreatic cancer and promotes the malignant phenotype of pancreatic cancer cells. CXCL5 is associated with immunosuppressive FOXP3 + T-cell infiltration, which facilitates the formation of an immunosuppressive microenvironment (with low CD8 + T-cell infiltration).

Hepatic ischemia‒reperfusion injury is a common injury in liver surgery and liver transplantation that can lead to liver function damage, including oxidative stress, apoptosis, autophagy and inflammatory reactions. Pyroptosis is a type of inflammatory programmed cell death that has been implicated in ischemia‒reperfusion injury-associated inflammatory reactions. Although circular RNAs can regulate cell death in hepatic ischemia‒reperfusion injury, their relationship with pyroptosis remains unclear. Therefore, this study aimed to investigate the effect of circular RNA on pyroptosis in hepatic ischemia‒reperfusion injury. We constructed a mouse hepatic ischemia‒reperfusion injury model for circular RNA sequencing and obtained 40 circular RNAs with significant differential expression, of which 39 were upregulated and 1 was downregulated. Subsequently, the endogenous competitive RNA network was constructed using TarBase, miRTarBase, TargetScan, RNAhybrid, and miRanda. Gene Set Enrichment Analysis, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology functional analyses of downstream target genes revealed that circRNA-Phf21a_0002 might affect pyroptosis by regulating the mTOR signaling pathway and Bach1 by sponging let-7b-5p. The overexpression plasmid upregulated the expression of circRNA-Phf21a_0002 in a hypoxia/reoxygenation model, which aggravated pyroptosis in AML12 cells and apoptosis and necrosis of hepatocytes. Next, we investigated the underlying mechanism and found that circRNA-Phf21a_0002 enabled the expression of Bach1 through sponging of let-7b-5p. The aggravation of pyroptosis via overexpression of circRNA-Phf21a_0002 was reversed by let-7b-5p mimics in hypoxia/reoxygenation-subjected AML12 cells. Collectively, our study clarifies that circRNA-Phf21a_0002 aggravates the pyroptosis of hepatocytes related to ischemia-reperfusion by sponging let-7b-5p. These findings provide new molecular mechanisms and novel biomarkers for follow-up treatment.

Circular RNA (circRNA) has been widely studied as a competitive endogenous RNA targeting microRNA (miRNA)/messenger RNA to regulate cancer progression. However, the regulatory mechanism of circ_0023179 in non-small cell lung cancer (NSCLC) remains unclear. The expression levels of circ_0023179, miR-615-5p and Cadherin 3 (CDH3) in NSCLC were detected using quantitative real-time polymerase chain reaction. The stability of circ_0023179 was verified using ribonuclease R enzyme, Actinomycin D and agarose gel electrophoresis. Colony formation and thymidine analog 5-ethynyl-2’-deoxyuridine assays were performed to examine proliferation changes in NSCLC cells. Western blot was used to assess the levels of CDH3 and epithelial-mesenchymal transition (EMT)–related marker proteins to evaluate EMT. Dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays were performed to explore the potential mechanisms of circ_0023179 in regulating NSCLC progression. Finally, the effects of circ_0023179 on NSCLC tumour growth in vivo were explored using a nude mouse subcutaneous tumour model. The results showed that the expression of circ_0023179 was remarkably higher in NSCLC tissues and cells, and it had a significant effect on NSCLC cell proliferation. Additionally, the knockdown of circ_0023179 significantly inhibited tumour growth in NSCLC mice. Mechanistically, circ_0023179 alleviated its inhibition of downstream CDH3 through the sponge-like adsorption of miR-615-5p. The downregulation of miR-615-5p and the upregulation of CDH3 mitigated the inhibitory effect of silencing circ_0023179 on NSCLC cell proliferation. In conclusion, silencing circ_0023179 inhibited NSCLC cell proliferation by targeting the miR-615-5p/CDH3 axis involved in NSCLC progression.

Background: This study was conducted to investigate whether baseline creatinine–cystatin C ratio is associated with all-cause mortality in adult Chinese patients hospitalized with coronavirus disease 2019. Methods: This study included 933 patients with coronavirus disease 2019 who were admitted to The Affiliated Hospital of Guangdong Medical University between December 2022 and March 2023. All-cause mortality was determined by telephone follow-up after 28 days. Multivariate Cox proportional risk models were used to investigate the relationship between baseline creatinine–cystatin C ratio and all-cause mortality. Restricted cubic spline and two-piecewise Cox proportional hazards risk models were used to identify non-linear correlations. Results: Of the 933 patients, 128 died during the 28 days follow-up. The restricted cubic spline analysis of hospitalized patients with coronavirus disease 2019 revealed an L-shaped association between baseline creatinine–cystatin C ratio and all-cause mortality, with a threshold creatinine–cystatin C ratio of ≤0.93 predicting all-cause mortality. Specifically, a baseline creatinine–cystatin C ratio below this threshold value was negatively correlated with mortality (hazard ratio 0.12, 95 % confidence interval 0.03–0.48), but a creatinine–cystatin C ratio >0.93 was not correlated with mortality (hazard ratio 1.29, 95 % confidence interval 0.65–2.55). Conclusions: In Chinese adult patients hospitalized with coronavirus disease 2019, an L-shaped relationship was observed between the baseline creatinine–cystatin C ratio and all-cause mortality.

BackgroundThe Centre for Disease Control and Prevention in Yangquan, China, has taken a series of preventive and control measures in response to the increasing trend of Kala-Azar. In response, we propose a new model to more scientifically evaluate the effectiveness of these interventions.MethodsWe obtained the incidence data of Kala-Azar from 2017 to 2021 from the Centre for Disease Control and Prevention (CDC) in Yangquan. We constructed Poisson segmented regression model, harmonic Poisson segmental regression model, and improved harmonic Poisson segmented regression model, and used the three models to explain the intervention effect, respectively. Finally, we selected the optimal model by comparing the fitting effects of the three models.ResultsThe primary analysis showed an underlying upward trend of Kala-Azar before intervention [incidence rate ratio (IRR): 1.045, 95% confidence interval (CI): 1.027–1.063, p

Intraglandular dissemination is an important pathological feature of thyroid cancer, yet the biological characteristics of this phenomenon remain relatively underexplored. This paper aims to provide a comprehensive overview of its biological behaviors, protein expressions, and identification methods. Several retrospective studies have found that thyroid cancers with intraglandular dissemination have higher rates of lymph node metastasis, capsule invasion, and vascular invasion, exhibiting more aggressive biological behavior. Immunohistochemistry results show abnormal expression of proteins such as FKBP5, CENPF, CX26, KIF11, PTK7, which are associated with poor prognosis in thyroid cancers with intraglandular dissemination, offering potential guidance for specific targeted therapy in the future. Moreover, adjunctive techniques including ultrasound, fine-needle aspiration, and genetic testing offer valuable support in accurately identifying these cases, facilitating moreproactive treatment and closer follow-up.

BackgroundThrough an analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS), we explored the signal strength of adverse reactions (ADRs) related to myopathy caused by the combination of colchicine and statins and gained insight into the characteristics of these myopathy related ADRs.MethodsWe extracted data from the FAERS database about ADRs in individuals with myopathy resulting from the combination of colchicine and statins. The analysis was conducted for the period spanning from January 2004 to December 2023 using the reported odds ratio (ROR) and information component (IC) methods to assess muscle-related ADR signals.ResultsA total of 18,386 reports of statin myopathy-associated adverse reactions, 348 colchicine myopathy-associated adverse reactions, and 461 muscle-associated adverse reactions due to the combination of the two were collected; the strongest signals of statin myotoxicity events were for necrotizing myositis (ROR 50.47, 95% CL 41.74–61.01; IC 3.70 95% CL 3.25–4.08); the strongest signal for colchicine myotoxicity events was toxic myopathy (ROR 32.50, 95% CL 19.74–53.51; IC 4.97 95% CL 1.89–5.10), and the strongest signal for statins combined with colchicine was toxic myopathy (ROR 159.85, 95% CL 111.60–228.98; IC 7.22 95% CL 3.59–5.9); muscle-related adverse reactions signals were meaningful when the two drugs were combined in the order of colchicine combined with fluvastatin (ROR 187.38, 95% CL 96.68–363.17; IC 6.99 95% CL 1.65–5.68); colchicine combined with simvastatin in 135 cases (ROR 30.08. 95% CL 25.25–35.85; IC 4.80 95% CL 3.96–5.12); and colchicine combined with rosuvastatin (ROR 25.73, 95% CL 20.16–32.83; IC 4.59 95% CL 3.38–4.98) versus colchicine combined with atorvastatin (ROR 25.73, 95% CL 22.33–29.66; IC 4.59 95% CL 3.97–4.91) with almost identical signal intensity, followed by colchicine combined with pravastatin (ROR 13.67, 95% CL 9.17–20.37; IC 3.73 95% CL 1.87–4.47), whereas no signals were generated for lovastatin or pitavastatin.ConclusionSimilar ADRs can occur when colchicine and statins are used individually or in combination; however, the strength of these reactions may differ. To minimize the risk of drug interactions, statins with less potential interactions, such as lovastatin, pitavastatin, and pravastatin, should be chosen, and myopathy-related indices and symptoms should be closely monitored during use.

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.

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

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