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Abstract Acetylcholine regulates various cognitive functions through broad cholinergic innervation. However, specific cholinergic subpopulations, circuits and molecular mechanisms underlying recognition memory remain largely unknown. Here we show that Ngfr + cholinergic neurons in the substantia innominate (SI)/nucleus basalis of Meynert (nBM)-medial prefrontal cortex (mPFC) circuit selectively underlies recency judgements. Loss of nerve growth factor receptor (Ngfr −/− mice) reduced the excitability of cholinergic neurons in the SI/nBM-mPFC circuit but not in the medial septum (MS)-hippocampus pathway, and impaired temporal order memory but not novel object and object location recognition. Expression of Ngfr in Ngfr −/− SI/nBM restored defected temporal order memory. Fiber photometry revealed that acetylcholine release in mPFC not only predicted object encounters but also mediated recency judgments of objects, and such acetylcholine release was absent in Ngfr −/− mPFC. Chemogenetic and optogenetic inhibition of SI/nBM projection to mPFC in ChAT-Cre mice diminished mPFC acetylcholine release and deteriorated temporal order recognition. Impaired cholinergic activity led to a depolarizing shift of GABAergic inputs to mPFC pyramidal neurons, due to disturbed KCC2-mediated chloride gradients. Finally, potentiation of acetylcholine signaling upregulated KCC2 levels, restored GABAergic driving force and rescued temporal order recognition deficits in Ngfr −/− mice. Thus, NGFR-dependent SI/nBM-mPFC cholinergic circuit underlies temporal order recognition memory.

Abstract CD4+ chronic lymphocytic leukemia (CLL) represents an extremely rare example of phenotypic aberrancy within CLL. We present a case of an 86‐year‐old male veteran with a history of multiple comorbidities who was incidentally diagnosed with CD4+ CLL during a routine peripheral blood workup. This case highlights the diagnostic challenges and characteristic features of CD4+ CLL, including flow cytometric analysis, molecular, and fluorescence in situ hybridization findings. The patient was classified as asymptomatic CLL Rai stage 0, warranting regular monitoring without a need for treatment intervention.

Abstract To explore the clinical characteristics of patients infected with SARS-CoV-2 nationwide, especially the effect factors of asymptomatic infection and disappearance of clinical symptoms. A total of 66,448 COVID-19 patients in China who have been diagnosed by nucleic acid test or rapid antigen test were surveyed online (December 24, 2022 to January 16, 2023). Our cross-sectional study used descriptive analyses and binary Logistics regression model to assess the correlation between the clinical characteristics and relative factors, including age, gender, pre-existing conditions, reinfection, vaccination and treatment. A total of 64,515 valid questionnaires were collected. Among included participants, 5969 of which were asymptomatic. The symptoms were mainly upper respiratory symptoms, including dry and itchy throat (64.16%), sore throat (59.95%), hoarseness (57.90%), nasal congestion (53.39%). In binary Logistics regression model, we found that male, no pre-existing conditions, reinfection and vaccination have positive correlations with the appearance of asymptomatic COVID-19 patients. In Cox proportional-hazards regression model, considering all clinical symptoms disappeared in 14 days as outcome, we found that ≤ 60 years old, male, no pre-existing conditions, vaccination and adopted treatment have positive correlations with rapid amelioration of clinical symptoms in COVID-19 patients. The clinical symptoms of the participants were mainly upper respiratory symptoms which were according with the infection of Omicron variant. Factors including age, gender, pre-existing conditions and reinfection could influence the clinical characteristics and prognosis of COVID-19 patients. Importantly, vaccination has positive significance for the prevention and treatment of COVID-19. Lastly, the use of Chinese medicine maybe beneficial to COVID-19 patients, however, reasonable guidance is necessary.

Abstract With increases in life expectancy, the number of patients requiring joint replacement therapy and experiencing periprosthetic osteolysis, the most common complication leading to implant failure, is growing or underestimated. In this study, we found that osteolysis progression and osteoclast differentiation in the surface of the skull bone of adult mice were accompanied by significant expansion of lymphatic vessels within bones. Using recombinant VEGF-C protein to activate VEGFR3 and promote proliferation of lymphatic vessels in bone, we counteracted excessive differentiation of osteoclasts and osteolysis caused by titanium alloy particles or inflammatory cytokines LPS/TNF-α. However, this effect was not observed in aged mice because adipogenically differentiated mesenchymal stem cells (MSCs) inhibited the response of lymphatic endothelial cells to agonist proteins. The addition of the JAK inhibitor ruxolitinib restored the response of lymphatic vessels to external stimuli in aged mice to protect against osteolysis progression. These findings suggest that inhibiting SASP secretion by adipogenically differentiated MSCs while activating lymphatic vessels in bone offers a new method to prevent periprosthetic osteolysis during joint replacement follow-up.

Introduction: Treating orthopedic implant-associated infections, especially those caused by Staphylococcus aureus (S. aureus), remains a significant challenge. S. aureus has the ability to invade host cells, enabling it to evade both antibiotics and immune responses during infection, which may result in clinical treatment failures. Therefore, it is critical to identify the host cell type of implant-associated intracellular S. aureus infections and to develop a strategy for highly targeted delivery of antibiotics to the host cells. Objectives: Introduced an antibody-antibiotic conjugate (AAC) for the targeted elimination of intracellular S. aureus. Methods: The AAC comprises of a human monoclonal antibody (M0662) directly recognizes the surface antigen of S. aureus, Staphylococcus protein A, which is conjugated with vancomycin through cathepsin-sensitive linkers that are cleavable in the proteolytic environment of the intracellular phagolysosome. AAC, vancomycin and vancomycin combined with AAC were used in vitro intracellular infection and mice implant infection models. We then tested the effect of AAC in vivo and in vivo by fluorescence imaging, in vivo imaging, bacterial quantitative analysis and bacterial biofilm imaging. Results: In vitro, it was observed that AAC captured extracellular S. aureus and co-entered the cells, and subsequently released vancomycin to induce rapid elimination of intracellular S. aureus. In the implant infection model, AAC significantly improved the bactericidal effect of vancomycin. Scanning electron microscopy showed that the application of AAC effectively blocked the formation of bacterial biofilm. Further histochemical and micro-CT analysis showed AAC significantly reduced the level of bone marrow density (BMD) and bone volume fraction (BV/TV) reduction caused by bacterial infection in the distal femur of mice compared to vancomycin treatment alone. Conclusions: The application of AAC in an implant infection model showed that it significantly improved the bactericidal effects of vancomycin and effectively blocked the formation of bacterial biofilms, without apparent toxicity to the host.

Abstract The transformative role of artificial intelligence (AI) in various fields highlights the need for it to be both accurate and fair. Biased medical AI systems pose significant potential risks to achieving fair and equitable healthcare. Here, we show an implicit fairness learning approach to build a fairer ophthalmology AI (called FairerOPTH) that mitigates sex (biological attribute) and age biases in AI diagnosis of eye diseases. Specifically, FairerOPTH incorporates the causal relationship between fundus features and eye diseases, which is relatively independent of sensitive attributes such as race, sex, and age. We demonstrate on a large and diverse collected dataset that FairerOPTH significantly outperforms several state-of-the-art approaches in terms of diagnostic accuracy and fairness for 38 eye diseases in ultra-widefield imaging and 16 eye diseases in narrow-angle imaging. This work demonstrates the significant potential of implicit fairness learning in promoting equitable treatment for patients regardless of their sex or age.

Coalbed methane (CBM) development and underground coal gasification (UCG) are important sources for coal-based natural gas production in China, and coal and CBM resources are abundant in the inclined coalbed development area of the Xinjiang foreland thrust belt. To deeply analyze the feasibility of coordinated development of CBM and UCG in inclined coal seams, the existing key technologies of CBM and UCG and their significances for coordinated development of CBM- UCG was systematically analyzed, the advantages, the technical routes, major problems and future research directions of coordinated development of CBM and UCG in inclined coal seams were also elaborated, the major problems faced and the direction of future research were proposed, and the following understanding was obtained. ① The coordinated development of CBM-UCG under the “CBM development dredging effect”, “UCG thermal desorption effect”, and “UCG mining pressure releasing effect” can form a virtuous cycle of mutual promotion. ② The coordinated development technology routes was proposed, such as vertical wells + inclined well along coal seam with “first drainage and then gasification”, multiple inclined wells along the coal seam with “simultaneous drainage and gasification”, directional L-typed CBM wells + UCG wells along the coal seam direction with “simultaneous gasification and drainage”, UCG wells along inclined wells in the lower coal + directional L-typed CBM wells in the upper coal seam with “first drainage, then gasification, and then drainage again”, and the “well factory” arrangement of complex well type. ③ The coordinated development of CBM and UCG faces theoretical issues such as weak theoretical foundation research on geological constituency evaluation, unclear expansion range of UCG thermal action under the condition of fracture network, and the undetermined range of rock movement and pressure relief in the UCG process of inclined coal seams. It also faces the engineering issues such as coordinated development of CBM-UCG “well factory” drilling technology, coordinated development of CBM wells and UCG wells production system, coordinated development of CBM and UCG wells geodynamic measurement and control, and the sealing and high-temperature-resistant protection of CBM wells. ④ It is necessary to strengthen the study on the evaluation of geological site selection for the coordinated development of CBM and UCG in inclined coal seams, the theoretical research on the development dynamics, and the pioneering experimental study on engineering coordination technology, so as to ensure that the coordinated development is safe, orderly, controllable and efficient.

Abstract Chimeric antigen receptor T (CAR-T) cells have been proposed for HIV-1 treatment but have not yet demonstrated desirable therapeutic efficacy. Here, we report newly developed anti-HIV-1 CAR-T cells armed with endogenic broadly neutralizing antibodies (bNAbs) and the follicle-homing receptor CXCR5, termed M10 cells. M10 cells were designed to exercise three-fold biological functions, including broad cytotoxic effects on HIV-infected cells, neutralization of cell-free viruses produced after latency reversal, and B-cell follicle homing. After demonstrating the three-fold biological activities, M10 cells were administered to treat 18 HIV-1 patients via a regimen of two allogenic M10 cell infusions with an interval of 30 days, with each M10 cell infusion followed by two chidamide stimulations for HIV-1 reservoir activation. Consequently, 74.3% of M10 cell infusions resulted in significant suppression of viral rebound, with viral loads declining by an average of 67.1%, and 10 patients showed persistently reduced cell-associated HIV-1 RNA levels (average decrease of 1.15 log10) over the 150-day observation period. M10 cells were also found to impose selective pressure on the latent viral reservoir. No significant treatment-related adverse effects were observed. Overall, our study supported the potential of M10 CAR-T cells as a novel, safe, and effective therapeutic option for the functional cure of HIV-1/AIDS.

Abstract Osteomyelitis is a devastating disease caused by microbial infection in deep bone tissue. Its high recurrence rate and impaired restoration of bone deficiencies are major challenges in treatment. Microbes have evolved numerous mechanisms to effectively evade host intrinsic and adaptive immune attacks to persistently localize in the host, such as drug-resistant bacteria, biofilms, persister cells, intracellular bacteria, and small colony variants (SCVs). Moreover, microbial-mediated dysregulation of the bone immune microenvironment impedes the bone regeneration process, leading to impaired bone defect repair. Despite advances in surgical strategies and drug applications for the treatment of bone infections within the last decade, challenges remain in clinical management. The development and application of tissue engineering materials have provided new strategies for the treatment of bone infections, but a comprehensive review of their research progress is lacking. This review discusses the critical pathogenic mechanisms of microbes in the skeletal system and their immunomodulatory effects on bone regeneration, and highlights the prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections. It will inform the development and translation of antimicrobial and bone repair tissue engineering materials for the management of bone infections.

Abstract This study aimed to investigate the effects of exercise on excessive mitochondrial fission, insulin resistance, and inflammation in the muscles of diabetic rats. The role of the irisin/AMPK pathway in regulating exercise effects was also determined. Thirty-two 8-week-old male Wistar rats were randomly divided into four groups (n = 8 per group): one control group (Con) and three experimental groups. Type 2 diabetes mellitus (T2DM) was induced in the experimental groups via a high-fat diet followed by a single intraperitoneal injection of streptozotocin (STZ) at a dosage of 30 mg/kg body weight. After T2DM induction, groups were assigned as sedentary (DM), subjected to 8 weeks of treadmill exercise training (Ex), or exercise training combined with 8-week cycloRGDyk treatment (ExRg). Upon completion of the last training session, all rats were euthanized and samples of fasting blood and soleus muscle were collected for analysis using ELISA, immunofluorescence, RT-qPCR, and Western blotting. Statistical differences between groups were analyzed using one-way ANOVA, and differences between two groups were assessed using t-tests. Our findings demonstrate that exercise training markedly ameliorated hyperglycaemia, hyperlipidaemia, and insulin resistance in diabetic rats (p

ABSTRACT: The purpose of this study was to investigate the effects of early castration and eucalyptus oil (EUC) supplementation on dry matter intake (DMI), growth performance, and immune response of Holstein calves. Fifty-six male Holstein calves 52 d old and with an initial body weight (BW) of 63.5 ± 5.27 kg were used. The animals were blocked by BW and randomly assigned into 1 of the 4 treatment groups in a randomized complete block design with a 2 (no castration vs. castration) × 2 (without vs. with EUC) factorial arrangement of treatments. The treatments were (1) uncastrated calves fed without EUC, (2) uncastrated calves fed 0.5 g/d EUC (EUC group), (3) castrated calves (steers) fed without EUC (castrated group), and (4) steers fed with 0.5 g/d EUC (castrated + EUC). The experiment was 8 wk long, including pre- and postweaning (weaned at 72 d). The EUC × castrated interactions were not significant for DMI, growth performance, nutrient digestibility, and immune response. Castration did not affect the DMI, final BW, average daily gain (ADG), or feed efficiency, except that the ADG was greater for bull calves than for steers at postweaning. Supplementation with EUC increased DMI pre- and postweaning and increased the ADG of weaned calves. Digestibility in the total digestive tract was not affected by castration (except for organic matter digestibility), whereas adding EUC improved the digestibility of dry matter, acid detergent fiber, and crude protein. Blood concentration of IL-6 at d 94 was decreased by feeding EUC. These results indicate that the EUC could be fed to either intact or castrated dairy calves to promote growth and health postweaning; castration before weaning may reduce ADG and cause inflammatory stress without affecting feed intake or feed efficiency.

Abstract Black carbon (BC) is a highly persistent yet poorly understood component of forest soil carbon reservoirs, while its inventory, distribution, and determining factors in forest soils on a large geographic scale remain unclear. Here, we characterized soil BC across 68 Chinese forest sites using benzene polycarboxylic acid method and developed machine learning (ML) models to predict and interpret potential impacts of soil organic matter (SOM) properties, soil physiochemical properties, meteorological conditions, wildfire history, and microbial diversity on BC. Results revealed that SOM properties were the most critical in predicting BC, complemented by the negative impact of mean annual temperature and alkaline mineral composition. The superior prediction accuracy for BC with higher condensed aromaticity (more benzene hexa‐ and penta‐carboxylic acid monomers) likely results from its simpler sources and greater resistance to transformation. This study introduces an effective ML model for predicting and interpreting soil BC inventory to better understand BC cycling.

Reduction of the driving range under either cold temperature or real-world running condition has become the biggest challenge for battery electric vehicle (BEV). In this paper, a simulation platform that combines a kinematics model, a thermal management model, and extracted typical running conditions has been established to estimate the energy flows inside the electric vehicle under cold temperature and real-world running condition. Three vehicles have been selected to validate the accuracy of the simulation platform, giving an accuracy between 90.6% and 96.6% according to different running conditions. Under highway running condition, the driving range could be reduced by 54%. Under urban running condition, when the environment temperature drops down to −20°C, the driving range is only 49.1% of that under 20°C. In addition, there could be a 4.4% increase in driving range if the target cabin temperature could be decreased from 28°C to 20°C. According to simulation, the application of motor waste heat recovery, internal gas recirculation, and heat pump, could increase the driving range at −7°C under urban running condition by 3.5%, 2.9%, and 3.9%, indicating a 10.3% improvement in total. This has been validated via experimental test after implementing these three approaches onto the test vehicle.

Two-dimensional (2D) hybrid organic–inorganic perovskites (HOIPs) have garnered plentiful attention as a result of their exceptional structural flexibility and multiple applications. In this study, we present a 2D HOIP (CHA)2PbBr4 (CHA = cyclohexylamine), for its potential applications in piezoelectricity, such as strain energy sensing and harvesting. Flexible composite films of (CHA)2PbBr4/PDMS (PDMS = polydimethylsiloxane) with a sequence of weight ratios (0, 5, 10, 15, 20 wt %) of (CHA)2PbBr4 were fabricated to analyze the energy harvesting properties. Experimental results demonstrated that a device with 15% composition exhibited the most optimized performance in energy harvesting, producing a peak magnitude of output voltage of 11.6 V, a short-circuit current of 0.38 µA, and a power density of 6.77 µW/cm2, along with notable stability exceeding 4000 cycles. Furthermore, this device exhibited high sensitivity in monitoring many varieties of human movements, such as finger bending and tapping, elbow bending, and gentle foot stamping. The findings of this study indicate that this 2D HOIP holds significant potential for use in flexible sensing and intelligent wearable devices.

Abstract The Ice Sheet Model Intercomparison Project for CMIP6 (ISMIP6) is the primary effort of CMIP6 (Coupled Model Intercomparison Project–Phase 6) focusing on ice sheets, designed to provide an ensemble of process‐based projections of the ice‐sheet contribution to sea‐level rise over the twenty‐first century. However, the behavior of the Antarctic Ice Sheet beyond 2100 remains largely unknown: several instability mechanisms can develop on longer time scales, potentially destabilizing large parts of Antarctica. Projections of Antarctic Ice Sheet evolution until 2300 are presented here, using an ensemble of 16 ice‐flow models and forcing from global climate models. Under high‐emission scenarios, the Antarctic sea‐level contribution is limited to less than 30 cm sea‐level equivalent (SLE) by 2100, but increases rapidly thereafter to reach up to 4.4 m SLE by 2300. Simulations including ice‐shelf collapse lead to an additional 1.1 m SLE on average by 2300, and can reach 6.9 m SLE. Widespread retreat is observed on that timescale in most West Antarctic basins, leading to a collapse of large sectors of West Antarctica by 2300 in 30%–40% of the ensemble. While the onset date of retreat varies among ice models, the rate of upstream propagation is highly consistent once retreat begins. Calculations of sea‐level contribution including water density corrections lead to an additional ∼10% sea level and up to 50% for contributions accounting for bedrock uplift in response to ice loading. Overall, these results highlight large sea‐level contributions from Antarctica and suggest that the choice of ice sheet model remains the leading source of uncertainty in multi‐century projections.

The β-catenin-dependent canonical Wnt signaling is pivotal in organ development, tissue homeostasis, and cancer. Here, we identified an upstream enhancer of Ctnnb1 – the coding gene for β-catenin, named ieCtnnb1 (intestinal enhancer of Ctnnb1), which is crucial for intestinal homeostasis. ieCtnnb1 is predominantly active in the base of small intestinal crypts and throughout the epithelia of large intestine. Knockout of ieCtnnb1 led to a reduction in Ctnnb1 transcription, compromising the canonical Wnt signaling in intestinal crypts. Single-cell sequencing revealed that ieCtnnb1 knockout altered epithelial compositions and potentially compromised functions of small intestinal crypts. While deletion of ieCtnnb1 hampered epithelial turnovers in physiologic conditions, it prevented occurrence and progression of Wnt/β-catenin-driven colorectal cancers. Human ieCTNNB1 drove reporter gene expression in a pattern highly similar to mouse ieCtnnb1. ieCTNNB1 contains a single-nucleotide polymorphism associated with CTNNB1 expression levels in human gastrointestinal epithelia. The enhancer activity of ieCTNNB1 in colorectal cancer tissues was stronger than that in adjacent normal tissues. HNF4α and phosphorylated CREB1 were identified as key trans-factors binding to ieCTNNB1 and regulating CTNNB1 transcription. Together, these findings unveil an enhancer-dependent mechanism controlling the dosage of Wnt signaling and homeostasis in intestinal epithelia.

Hip fractures present a significant healthcare challenge, especially within aging populations, where they are often caused by falls. These fractures lead to substantial morbidity and mortality, emphasizing the need for timely surgical intervention. Despite advancements in medical care, hip fractures impose a significant burden on individuals and healthcare systems. This paper focuses on the prediction of hip fracture risk in older and middle-aged adults, where falls and compromised bone quality are predominant factors.The study cohort included 547 patients, with 94 experiencing hip fracture. To assess the risk of hip fracture, clinical variables and clinical variables combined with hip DXA imaging features were evaluated as predictors, followed by a novel staged approach. Hip DXA imaging features included those extracted by convolutional neural networks (CNNs), shape measurements, and texture features. Two ensemble machine learning models were evaluated: Ensemble 1 (clinical variables only) and Ensemble 2 (clinical variables and imaging features) using the logistic regression as the base classifier and bootstrapping for ensemble learning. The staged approach was developed using uncertainty quantification from Ensemble 1 which was used to decide if hip DXA imaging features were necessary to improve prediction for each subject. Ensemble 2 exhibited the highest performance, achieving an Area Under the Curve (AUC) of 0.95, an accuracy of 0.92, a sensitivity of 0.81, and a specificity of 0.94. The staged model also performed well, with an AUC of 0.85, an accuracy of 0.86, a sensitivity of 0.56, and a specificity of 0.92, outperforming Ensemble 1, which had an AUC of 0.55, an accuracy of 0.73, a sensitivity of 0.20, and a specificity of 0.83. Furthermore, the staged model suggested that 54.49 % of patients did not require DXA scanning, effectively balancing accuracy and specificity, while offering a robust solution when DXA data acquisition is not feasible. Statistical tests confirmed significant differences between the models, highlighting the advantages of advanced modeling strategies.Our staged approach offers a cost-effective holistic view of patient health. It can identify individuals at risk of hip fracture with a high accuracy while reducing unnecessary DXA scans. This approach has great promise to guide the need for interventions to prevent hip fracture while reducing diagnostic cost and exposure to radiation.

Background and objectivesGeographical variation existed in the incidences of Guillain-Barré syndrome (GBS), but no national population-based study has evaluated the incidences of GBS in China. This study aimed to estimate the incidence of GBS in urban China and evaluate the worldwide variation in the incidence of GBS.MethodsFirstly, we did a population-based study to calculate the incidence of GBS in urban China based on the National Urban Medical Insurance database from 2013 to 2017. To identify GBS cases, natural language processing was used first for handling the lengthy and unstructured diagnostic information and then checked by prestigious neurologists. Secondly, a systematic review and meta-analysis were performed to analyze the incidence of GBS worldwide. Up to July 4, 2022, Medline, Embase, and Web of Science were retrieved to identify the population-based studies regarding the incidence of GBS. The basic information and the statistics regarding incidence were extracted. Quality assessment considered sample representativeness, condition assessment, and statistical methods.ResultsA total of 1.44 billion person-years in insurance data was covered, with 3,534 GBS cases identified. The annual incidences of GBS in urban China between 2013 and 2017 ranged from 0.41 (95% CI: 0.27 to 0.58) to 0.58 (95% CI: 0.38 to 0.82) per 100,000 person-years. The incidence was the highest in Northwest China and the lowest in Northeast China. The meta-analysis included 122 articles. The quality assessment showed that the quality scores of 43.3% of studies were ≥ 0.75 (the total score is 1). The global incidence of GBS was 1.12 (95% CI: 0.98 to 1.27) per 100,000 person-years. The incidences in West Europe, South Asia, and North Europe were higher, while the incidences in Australia and New Zealand, Southeast Asia, and North Africa were lower. The incidence of enteric infections was positively associated with the incidence of GBS (coefficient=0.0000185, P=0.007). The incidence in Europe, Australia, and America rose significantly from 1960 to 2020 (coefficient=0.01, t=2.52, P=0.015).DiscussionThere is a clear regional variation of the GBS incidence at both national and global levels. Careful control of enteric infections should be conducted to reduce the disease burden.

Abstract The lack of a cure for osteoarthritis (OA), a prevalent joint disease among older individuals, remains an ongoing challenge. Obesity is a common risk factor for OA. Chondrocyte autophagy plays a crucial role in delaying the onset of OA. Our previous studies have demonstrated a significant elevation in the levels of oleic acid (OLA) and linoleic acid (LA) in the synovial fluid (SF) of patients with OA and obesity compared to those with OA alone, and an inhibitory effect of these molecules on the activation of autophagy. Accumulating evidence indicates a reciprocal regulatory relationship between autophagy and ciliogenesis; however, whether autophagy‐mediated ciliogenesis plays a significant role in the pathogenesis of OA remains unclear. In this study, we aimed to determine whether OLA and LA affect OA development via the regulation of chondrocyte autophagy‐mediated ciliogenesis. We found that both molecules inhibited this process in chondrocytes. Moreover, intracellular calcium and reactive oxygen species (ROS) levels increased simultaneously. Further, we explored the relationship between autophagy and ciliogenesis in chondrocytes. Activation of autophagy by rapamycin significantly attenuated the ciliogenesis inhibition caused by OLA and LA. Importantly, the downregulation of AKT and mTOR expression in chondrocytes reversed the autophagy‐mediated inhibition of ciliogenesis and the ROS‐accumulation‐mediated inflammation induced by OLA and LA. Taken together, our results suggest that OLA and LA induce calcium‐overload‐driven ROS accumulation via autophagy‐mediated ciliogenic disorders during OA pathogenesis. These findings demonstrate that targeting autophagy and ciliogenesis in chondrocytes is a protective strategy in the OA pathogenesis induced by OLA and LA.

In this study, the dried biomass of four marine algae, namely Porphyra sp., Gracilaria bursa-pastoris, Undaria pinnatifida and Laminaria sp., were screened for their ability to remove methylene blue (MB) dye from aqueous solutions. Statistical approaches of the Plackett-Burman Design (PBD) and Box-Behnken Design (BBD) were applied to optimize different environmental conditions in order to achieve the maximum MB removal percentage by Gracilaria bursa-pastoris. The biosorbent was characterized before and after adsorption process using FTIR, XRD and SEM analysis. Additionally, isotherms, kinetics and thermodynamics studies were conducted to investigate the adsorption behavior of the adsorbent. The results showed that Gracilaria bursa-pastoris achieved the highest dye removal efficiency (98.5 %) compared to 96.5 %, 93.5 % and 93.9 % for Undaria pinnatifida, Porphyra sp. and Laminaria sp., respectively. PBD analysis revealed that the agitation speed, pH, and biomass dose were found to be the significant parameters affecting MB removal onto Gracilaria dried biomass. According to the BBD results, the maximum dye removal percentage (99.68 %) was obtained at agitation speed of 132 rpm, pH 7 and biomass dose of 7.5 g/L. FTIR, XRD and SEM analysis demonstrated the participation of several functional groups in the adsorption process and changes in the cell surface morphology of the adsorbent following the dye adsorption. The adsorption isotherms showed better fit to Freundlich model (R2 = 0.9891) than the Langmuir, Temkin, and Dubinin-Radushkevich models. The adsorption kinetics were best described by the pseudo-second-order model (R2 = 0.9999), suggesting the chemical interactions between dye ions and the algal biomass. The thermodynamic parameters indicated that the adsorption of MB onto Gracilaria dried biomass was spontaneous, feasible, endothermic and random. These results indicate that dried biomass of Gracilaria bursa-pastoris is an attractive, environmentally friendly, cheap and effective agent for MB dye removal from environmental discharges.

The question of which specific tectonic regimes played an essential role in shaping the Neoarchean evolution of the North China Craton (NCC) has been a contentious and controversial topic. Mafic rocks, containing valuable geochemical information from the mantle and deep crust, serve as an important source of data to provide essential constraints on above issue. This study presents bulk-rock geochemistry, zircon U-Pb geochronology and Hf-Nd isotopes for the Neoarchean mafic rocks in the core area of the Longgang Block of the NCC. Petrographically, these mafic rocks are composed of the amphibolite and metadiabase. Zircon U-Pb dating results revealed that they were synchronously emplaced at ca. 2.5 Ga. Geochemically, the amphibolites belong to subalkaline tholeiite series, exhibiting enrichment in light rare earth elements (LREEs), intensely negative Nb, Ta and Ti anomalies, and slightly enriched Nd and relatively variable zircon Hf isotopic compositions. These geochemical and isotopic features show large affinity to arc-like magmatism, implying that they were derived from subduction-related metasomatized lithospheric mantle. In contrast, the metadiabases exhibit high-Ti alkaline basalt affinities, OIB-like REE, and trace element patterns. They also show clearly positive Nb, Ta and Ti anomalies, indicating that they originated from a mantle plume-related tectonic environment. The new geochemical and isotopic data reveal that these Neoarchean mafic rocks could have resulted from coexisting mantle plume and subduction processes. Combined with available regional structural, geochemical, and metamorphic data, it is likely that during the Neoarchean, both a mantle plume and subduction jointly controlled the crustal growth and tectonic evolution of the Longgang Block in the eastern NCC.

Abstract Lignocellulose was directly used in itaconic acid production by a model filamentous fungus Neurospora crassa. The promoters of two clock control genes and cellobiohydrolase 1 gene were selected for heterologous genes expression by evaluating different types of promoters. The effect of overexpression of different cellulase was compared, and it was found that expression of cellobiohydrolase 2 from Trichoderma reesei increased the filter paper activity by 2 times, the cellobiohydrolase activity by 4.5 times, and that the itaconic acid titer was also significantly improved. A bidirectional cis-aconitic acid accumulation strategy was established by constructing the reverse glyoxylate shunt and expressing the transporter MTTA, which increased itaconic acid production to 637.2 mg/L. The simultaneous optimization of cellulase and metabolic pathway was more conducive to the improvement of cellulase activity than that of cellulase alone, so as to further increase itaconic acid production. Finally, through the combination of fermentation by optimized strains and medium optimization, the titers of itaconic acid using Avicel and corn stover as substrate were 1165.1 mg/L and 871.3 mg/L, respectively. The results prove the potential of the consolidated bioprocessing that directly converts lignocellulose to itaconic acid by a model cellulase synthesizing strain.

Abstract Aim This study aimed to verify the accuracy of intraoperative femurofibular angle combined with tibiofibular angle (FFA–TFA) measurement and compare it with traditional alignment line methods in open-wedge high tibial osteotomy (OWHTO). Methods A total of 174 knees of 122 patients undergoing OWHTO and using an alignment line or FFA–TFA measurement as an index of optimal correction were included in this retrospective study. The intraoperative alignment line passed through the targeted weight-bearing line (WBL) of the tibial plateau in the alignment line group. The intraoperative FFA–TFA aligned to the preplanned FFA–TFA angle in the FFA–TFA group. WBL, FFA, TFA, and knee joint-line convergence angle of the femur and tibia were assessed as radiological results preoperatively and one year after surgery. The Knee Society Score and the Western Ontario and McMaster Universities were assessed as objective clinical results. Results Postoperative WBL in the FFA–TFA group was closer to the target WBL than in the alignment line group (FFA–TFA vs alignment line group: 1.43 ± 1.20% vs 3.82 ± 3.29%; P 0.05). Conclusions The intraoperative measurement of FFA–TFA had fewer complications in terms of under-correction and over-correction compared with the alignment line measurement. No significant differences between the two methods were observed in clinical results one year after surgery.

Abstract Background Solid nodules (SN) had more aggressive features and a poorer prognosis than part-solid nodules (PSN). This study aimed to evaluate the specific impacts of nodule radiological appearance (SN vs. PSN) on lymph node metastasis and prognosis based on solid size in cT1 non-small cell lung cancer (NSCLC). Methods Patients with cT1 NSCLC who underwent anatomical resection between 2010 and 2019 were retrospectively screened. Univariable and multivariable logistic regression analyses were adopted to evaluate the associations between nodule radiological appearance and lymph node metastasis. The log-rank test and Cox regression analyses were applied for prognostic evaluation. The cumulative recurrence risk was evaluated by the competing risk model. Results There were 958 and 665 NSCLC patients with PSN and SN. Compared to the PSN group, the SN arm had a higher overall lymph node metastasis rate (21.7% vs. 2.7%, P

Drought stress limits agricultural productivity worldwide. Identifying and characterizing genetic components of drought stress-tolerance networks may improve crop resistance to drought stress. We show that the regulatory module formed by miR166 and its target gene, ATHB14-LIKE, functions in the regulation of drought tolerance in soybean (Glycine max). Drought stress represses the accumulation of miR166, leading to upregulation of its target genes. Optimal knockdown of miR166 in the stable transgenic line GmSTTM166 conferred drought tolerance without affecting yield. Expression of ABA signaling pathway genes was regulated by the miR166-mediated regulatory pathway, and ATHB14-LIKE directly activates some of these genes. There is a feedback regulation between ATHB14-LIKE and MIR166 genes, and ATHB14-LIKE inhibits MIR166 expression. These findings reveal that drought-triggered regulation of the miR166-mediated regulatory pathway increases plants drought resistance, providing new insights into drought stress regulatory network in soybean.

Undergraduate medical education in China has shifted from educator-centered learning to self-directed learning (SDL) over the past few decades. Careful design of public engagement activities can enable SDL and empower medical students to pioneer public health and patient safety education. In this study, we aimed to innovate nervous system education by implementing a public engagement model that empowers students to learn about the nervous system by teaching the public. Our goal was to generate greater interest in the nervous system at the undergraduate stage, inspire students’ enthusiasm to pursue a career in neurology, and ultimately, contribute to health promotion. During the nervous system module of the second year of the undergraduate curriculum, students were given the option to participate in the public engagement model. Participants were tasked with the creation of educational videos focusing on knowledge, attitudes, and behaviors associated with the prevention and management of neurological diseases and their complications. The videos were made accessible to the general public through the university’s official channel at the end of the semester. A total of 117 students (67.24% of all students) chose to participate in the public engagement model. Female students and those with higher Grade Point Averages in the present semester were more likely to participate. The model received strong positive feedback from participants, as students found the public engagement task helpful in learning about the nervous system module as well as in enhancing their public engagement skills. Despite the time and effort consumption, participating in the public engagement task did not affect students’ exam scores. The public engagement task is an innovative model in the nervous system curriculum and has the potential to be integrated into a broader range of undergraduate courses. It empowers medical students to pioneer public health and patient safety education.

Bipolar plates perform multiple functions for the proton exchange membrane fuel cell (PEMFC). This study focuses on optimizing cathode channels to leverage a local loss mechanism to enhance gas transfer and diffusion efficiency. Through the investigation of 3D simulations, this research delves into the effects of curvature of cathode channels on both reactant transfer and diffusion. The results illustrated that compared with straight channels, the cell performance improves as the bending angle ([Formula: see text]) of 2.5° and 5° at different current densities. Specifically, at a bending angle of 5°, a 5.5% higher current density than the channel of 0° is obtained. This suggests that moderate curvature can effectively promote efficient mass transport and diffusion, ultimately contributing to enhanced cell performance. Furthermore, the analysis of local mass transfer and diffusion around the bends of channels underscores the importance of the balance between these factors. While bending angles within the range of 2.5° to 5° offer optimal performance gains, excessive curvature, such as a 10° angle, may lead to diminished cell performance. By identifying the optimal bending angle range and elucidating the underlying mechanisms driving performance improvements, this study provides insights into the design and optimization of cathode flow fields in AO-PEMFC.

Background Elderly hemodialysis (HD) patients have a high risk of death. The effect of different types of HD membranes on survival is still controversial. The purpose of this study was to determine the relationship between the use of low-flux or high-flux membranes and all-cause and cardiovascular mortality in elderly hemodialysis patients.Methods This was a retrospective clinical study involving maintenance hemodialysis patients which were categorized into low-flux and high-flux groups according to the dialyzer they were using. Propensity score matching was used to balance the baseline data of the two groups. Survival rates were compared between the two groups, and the risk factors for death were analyzed by multivariate Cox regression.Results Kaplan–Meier survival analysis revealed no significant difference in all-cause mortality between the low-flux group and the high-flux group (log-rank test, p = 0.559). Cardiovascular mortality was significantly greater in the low-flux group than in the high-flux group (log-rank test, p = 0.049). After adjustment through three different multivariate models, we detected no significant difference in all-cause mortality. Patients in the high-flux group had a lower risk of cardiovascular death than did those in the low-flux group (HR = 0.79, 95% CI, 0.54–1.16, p = 0.222; HR = 0.58, 95% CI, 0.37–0.91, p = 0.019).Conclusions High-flux hemodialysis was associated with a lower relative risk of cardiovascular mortality in elderly MHD patients. High-flux hemodialysis did not improve all-cause mortality rate. Differences in urea distribution volume, blood flow, and systemic differences in solute clearance by dialyzers were not further analyzed, which are the limitations of this study.

IntroductionThe influence of excess weight on the development of children's feet remains a subject of debate. To further elucidate whether this relation occurs, this study compared arch morphology and flexibility in three groups of children: underweight, normal, and overweight.MethodsIn total, 1,532 children (807 boys, 725 girls; age range 7–11 years) participated in the study. The researchers measured the participants’ height and weight, calculated their body mass index, and categorized their weight status as underweight, normal weight, or overweight. A three-dimensional foot model was taken using a three-dimensional plantar scanner under non-weight-bearing and weight-bearing conditions to obtain arch morphometric indices (arch index and arch volume) and arch flexibility index (arch volume index).ResultsAnalysis of the data showed that the arch index was higher in overweight children compared to underweight and normal weight children (p 0.05). All children were divided into flatfoot, normal, and pes cavus groups according to arch index, and the arch volume index was statistically significant (p

Purpose: To evaluate the performance of four large language models (LLMs)—GPT-4, PaLM 2, Qwen, and Baichuan 2—in generating responses to inquiries from Chinese patients about dry eye disease (DED). Design: Two-phase study, including a cross-sectional test in the first phase and a real-world clinical assessment in the second phase. Subjects: Eight board-certified ophthalmologists and 46 patients with DED. Methods: The chatbots' responses to Chinese patients' inquiries about DED were assessed by the evaluation. In the first phase, six senior ophthalmologists subjectively rated the chatbots’ responses using a 5-point Likert scale across five domains: correctness, completeness, readability, helpfulness, and safety. Objective readability analysis was performed using a Chinese readability analysis platform. In the second phase, 46 representative patients with DED asked the two language models (GPT-4 and Baichuan 2) that performed best in the in the first phase questions and then rated the answers for satisfaction and readability. Two senior ophthalmologists then assessed the responses across the five domains. Main outcome measures: Subjective scores for the five domains and objective readability scores in the first phase. The patient satisfaction, readability scores, and subjective scores for the five-domains in the second phase. Results: In the first phase, GPT-4 exhibited superior performance across the five domains (correctness: 4.47; completeness: 4.39; readability: 4.47; helpfulness: 4.49; safety: 4.47, p

IntroductionSepsis is a syndrome of organ dysfunction caused by a dysregulated host response to infection and septic shock. Currently, antibiotic therapy is the standard treatment for sepsis, but it can lead to drug resistance. The disturbance of the gut microbiota which is affected by sepsis could lead to the development of organ failure. It is reported that probiotics could shape the gut microbiota, potentially controlling a variety of intestinal diseases and promoting whole-body health.MethodsIn this study, we evaluated the preventive effects of intra- and extracellular products of probiotics on sepsis. The extracellular products of Lactococcus lactis (L. lactis) were identified through the in vivo cell experiments. The preventive effect and mechanism of L. lactis extracellular products on mouse sepsis were further explored through HE staining, mouse survival rate measurement, chip analysis, etc.ResultsL. lactis extracellular products increase cell survival and significantly reduce inflammatory factors secreted in a cellular sepsis model. In in vivo experiments in mice, our samples attenuated sepsis-induced pulmonary edema and inflammatory infiltrates in the lungs of mice, and reduced mortality and inflammatory factor levels within the serum of mice. Finally, the mechanism of sepsis prevention by lactic acid bacteria is suggested. Extracellular products of L. lactis could effectively prevent sepsis episodes.DiscussionIn animal experiments, we reported that extracellular products of L. lactis can effectively prevent sepsis, and preliminarily discussed the pathological mechanism, which provides more ideas for the prevention of sepsis. In the future, probiotics may be considered a new way to prevent sepsis.

Summary: Natural silks are renewable proteins with impressive mechanical properties and biocompatibility that are useful in various fields. However, the cellular and spatial organization of silk-secreting organs remains unclear. Here, we combined single-nucleus and spatially resolved transcriptomics to systematically map the cellular and spatial composition of the silk glands (SGs) of mulberry silkworms late in larval development. This approach allowed us to profile SG cell types and cell state dynamics and identify regulatory networks and cell-cell communication related to efficient silk protein synthesis; key markers were validated via transgenic approaches. Notably, we demonstrated the indispensable role of the ecdysone receptor (ultraspiracle) in regulating endoreplication in SG cells. Our atlas presents the results of spatiotemporal analysis of silk-secreting organ architecture late in larval development; this atlas provides a valuable reference for elucidating the mechanism of efficient silk protein synthesis and developing sustainable products made from natural silk.

Ischemic stroke, a significant threat to human life and health, refers to a class of conditions where brain tissue damage is induced following decreased cerebral blood flow. The incidence of ischemic stroke has been steadily increasing globally, and its disease mechanisms are highly complex and involve a multitude of biological mechanisms at various scales from genes all the way to the human body system that can affect the stroke onset, progression, treatment, and prognosis. To complement conventional experimental research methods, computational systems biology modeling can integrate and describe the pathogenic mechanisms of ischemic stroke across multiple biological scales and help identify emergent modulatory principles that drive disease progression and recovery. In addition, by running virtual experiments and trials in computers, these models can efficiently predict and evaluate outcomes of different treatment methods and thereby assist clinical decision-making. In this review, we summarize the current research and application of systems-level computational modeling in the field of ischemic stroke from the multiscale mechanism-based, physics-based and omics-based perspectives and discuss how modeling-driven research frameworks can deliver insights for future stroke research and drug development.

ObjectiveThis study revealed a core regulator and common upstream mechanisms for the multifaceted pathological processes of age-related macular degeneration (AMD) and provided proof-of-concept for this new therapeutic target.MethodsComprehensive gene expression analysis was performed using RNA sequencing of eye cup from old mice as well as laser-induced choroidal neovascularization (CNV) mouse model. Through integrative analysis and protein-protein interaction (PPI) analysis, common pathways and key transcription factor was identified simultaneously engaged in age-related retinal degeneration and CNV, the two typical pathological process of AMD. Subsequently, the expression changes of Spi1, the key regulator, as well as the alternation of the downstream mechanisms were validated in both models through qRT-PCR, Elisa, flow cytometry and immunofluorescence. Further, we assessed the impact of Spi1 knockdown in vitro and in vivo using gene intervention vectors carried by adeno-associated virus or lentivirus to test its potential as a therapeutic target.ResultsCompared to corresponding controls, we found 1,939 and 1,319 genes differentially expressed in eye cups of old and CNV mice respectively. The integrative analysis identified a total of 275 overlapping DEGs, of which 150 genes were co-upregulated. PPI analysis verified a central transcription factor, SPI1. The significant upregulation of Spi1 expression was then validated in both models, accompanied by macrophage polarization towards the M1 phenotype. Finally, SPI1 suppression significantly inhibited M1 polarization of BMDMs and attenuated neovascularization in CNV mice.ConclusionThis study demonstrates that SPI1 exerts a pivotal role in AMD by regulation of macrophage polarization and innate immune response, offering promise as an innovative target for treating AMD.

To address the efficiency bottleneck encountered in reactor design calculations for the newly developed lead-based reactor neutronics analysis code system MOSASAUR, we recently developed acceleration functions based on various coarse-mesh finite difference (CMFD) methods and spatial domain decomposition parallel algorithm. However, the applicability of these improvements to different lead-based reactors remains to be analyzed. This work collected and established core models for various types of lead-based reactor. Based on different SN nodal transport solvers, we analyzed the acceleration performance of different CMFD methods, different CPU cores, and the combination of CMFD and parallel calculation. The results indicated that the impact of different CMFD acceleration or parallel acceleration on the calculation accuracy was negligible; the rCMFD method had good stability and convergence rate, achieving speedup of several to dozens; parallel efficiency was related to the number of meshes, and for large reactor cores, superlinear speedup was achieved with 200 CPU cores; rCMFD and parallel computing could achieve combined speedup, with 200 cores achieving speedup of hundreds to thousands, typically completing a reactor core transport calculation in 1 min.

The persistence of neuronal degeneration and damage is a major obstacle in ageing medicine. Nucleotide-binding oligomerization domain (NOD)-like receptors detect environmental stressors and trigger the maturation and secretion of pro-inflammatory cytokines that can cause neuronal damage and accelerate cell death. NLR (NOD-like receptors) inflammasomes are protein complexes that contain NOD-like receptors. Studying the role of NLR inflammasomes in ageing-related neurological disorders can provide valuable insights into the mechanisms of neurodegeneration. This includes investigating their activation of inflammasomes, transcription, and capacity to promote or inhibit inflammatory signaling, as well as exploring strategies to regulate NLR inflammasomes levels. This review summarizes the use of NLR inflammasomes in guiding neuronal degeneration and injury during the ageing process, covering several neurological disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke, and peripheral neuropathies. To improve the quality of life and slow the progression of neurological damage, NLR-based treatment strategies, including inhibitor-related therapies and physical therapy, are presented. Additionally, important connections between age-related neurological disorders and NLR inflammasomes are highlighted to guide future research and facilitate the development of new treatment options.

Ovarian aging is a complex process characterized by a decline in oocyte quantity and quality, directly impacting fertility and overall well-being. Recent researches have identified mitochondria as pivotal players in the aging of ovaries, influencing various hallmarks and pathways governing this intricate process. In this review, we discuss the multifaceted role of mitochondria in determining ovarian fate, and outline the pivotal mechanisms through which mitochondria contribute to ovarian aging. Specifically, we emphasize the potential of targeting mitochondrial dysfunction through innovative therapeutic approaches, including antioxidants, metabolic improvement, biogenesis promotion, mitophagy enhancement, mitochondrial transfer, and traditional Chinese medicine. These strategies hold promise as effective means to mitigate age-related fertility decline and preserve ovarian health. Drawing insights from advanced researches in the field, this review provides a deeper understanding of the intricate interplay between mitochondrial function and ovarian aging, offering valuable perspectives for the development of novel therapeutic interventions aimed at preserving fertility and enhancing overall reproductive health.

Abstract Reservoirs exert a profound influence on the cycling of dissolved organic matter (DOM) in inland waters by altering flow regimes. Biological incubations can help to disentangle the role that microbial processing plays in the DOM cycling within reservoirs. However, the complex DOM composition poses a great challenge to the analysis of such data. Here we tested if the interpretable machine learning (ML) methodologies can contribute to capturing the relationships between molecular reactivity and composition. We developed time‐specific ML models based on 7‐day and 30‐day incubations to simulate the biogeochemical processes in the Three Gorges Reservoir over shorter and longer water retention periods, respectively. Results showed that the extended water retention time likely allows the successive microbial degradation of molecules, with stochasticity exerting a non‐negligible effect on the molecular composition at the initial stage of the incubation. This study highlights the potential of ML in enhancing our interpretation of DOM dynamics over time.

Our recent multi-omics studies have revealed rich sources of novel bioactive proteins and polypeptides from marine organisms including cnidarians. In the present study, we initially conducted a transcriptomic analysis to review the composition profile of polypeptides from Zoanthus sociatus. Then, a newly discovered NPY-like polypeptide-ZoaNPY was selected for further in silico structural, binding and virtually pharmacological studies. To evaluate the pro-angiogenic effects of ZoaNPY, we employed an in vitro HUVECs model and an in vivo zebrafish model. Our results indicate that ZoaNPY, at 1–100 pmol, enhances cell survival, migration and tube formation in the endothelial cells. Besides, treatment with ZoaNPY could restore a chemically-induced vascular insufficiency in zebrafish embryos. Western blot results demonstrated the application of ZoaNPY could increase the phosphorylation of proteins related to angiogenesis signaling including PKC, PLC, FAK, Src, Akt, mTOR, MEK, and ERK1/2. Furthermore, through molecular docking and surface plasmon resonance (SPR) verification, ZoaNPY was shown to directly and physically interact with NPY Y2 receptor. In view of this, all evidence showed that the pro-angiogenic effects of ZoaNPY involve the activation of NPY Y2 receptor, thereby activating the Akt/mTOR, PLC/PKC, ERK/MEK and Src- FAK-dependent signaling pathways. Furthermore, in an excision wound model, the treatment with ZoaNPY was shown to accelerate the wound healing process in mice. Our findings provide new insights into the discovery and development of novel pro-angiogenic drugs derived from NPY-like polypeptides in the future.

Cylindrospermopsin (CYN), a cyanobacterial toxin, has been detected in the global water environment. However, information concerning the potential environmental risk of CYN is limited, since the majority of previous studies have mainly focused on the adverse health effects of CYN through contaminated drinking water. The present study reported that CYN at environmentally relevant levels (0.1–100 μg/L) can significantly enhance the conjugative transfer of RP4 plasmid in Escherichia coli genera, wherein application of 10 μg/L of CYN led to maximum fold change of ∼6.5- fold at 16 h of exposure. Meanwhile, evaluation of underlying mechanisms revealed that environmental concentration of CYN exposure could increase oxidative stress in the bacterial cells, resulting in ROS overproduction. In turn, this led to an upregulation of antioxidant enzyme-related genes to avoid ROS attack. Further, inhibition of the synthesis of glutathione (GSH) was also detected, which led to the rapid depletion of GSH in cells and thus triggered the SOS response and promoted the conjugative transfer process. Increase in cell membrane permeability, upregulation of expression of genes related to pilus generation, ATP synthesis, and RP4 gene expression were also observed. These results highlight the potential impact on the spread of antimicrobial resistance in water environments.

Abstract Objective The aim of this study was to assess the accuracy and test-retest reliability of a wearable inertial measurement unit (IMU) system for gait analysis in healthy female compared to a gold-standard optoelectronic motion capture (OMC) system. Methods In our study, we collected data from 5 healthy young females. Participants were attached with markers from both the OMC system and the IMU system simultaneously. Data was collected when participants walked on a 7 m walking path. Each participant performed 50 repetitions of walking on the path. To ensure the collection of complete gait cycle data, a gait cycle was considered valid only if the participant passed through the center of the walking path at the same time that the OMC system detected a valid marker signal. As a result, 5 gait cycles that met the standards of the OMC system were included in the final analysis. The stride length, cadence, velocity, stance phase and swing phase of the spatio-temporal parameters were included in the analysis. A generalized linear mixture model was used to assess the repeatability of the two systems. The Wilcoxon rank-sum test for continuous variables was used to compare the mean differences between the two systems. For evaluating the reliability of the IMU system, we calculated the Intra-class Correlation Coefficient (ICC). Additionally, Bland-Altman plots were used to compare the levels of agreement between the two systems. Results The measurements of Spatio-temporal parameters, including the stance phase (P = 0.78, 0.13, L-R), swing phase (P = 0.78, 0.13, L-R), velocity (P = 0.14, 0.13, L-R), cadence (P = 0.53, 0.22, L-R), stride length (P = 0.05, 0.19, L-R), by the IMU system and OMC system were similar. Which suggested that IMU and OMC systems could be used interchangeably for gait measurements. The intra-rater reliability showed an excellent correlation for the stance phase, swing phase, velocity and cadence (Intraclass Correlation Coefficient, ICC > 0.9) for both systems. However, the correlation of stride length was poor (ICC = 0.36, P = 0.34, L) to medium (ICC = 0.56, P = 0.22, R). Additionally, the measurements of IMU systems were repeatable. Conclusions The results of IMU system and OMC system shown good repeatability. Wearable IMU system could analyze gait data accurately. In particular, the measurement of stance phase, swing phase, velocity and cadence showed excellent reliability. IMU system provided an alternative measurement to OMC for gait analysis. However, the measurement of stride length by IMU needs further consideration.

Coherent microwave radar utilizes the direct relationship between the orbital wave velocity and the wave height spectrum to retrieve wave parameters. However, due to the broken wave and its evolution, “Group-Line” is introduced in the radar-obtained wavenumber–frequency spectrum, and the dominant wave energy is reduced. Many methods have proposed to remove “Group-Line” in the wavenumber–frequency spectrum, but these methods can only remove low-frequency energy and fail to compensate for the dominant wave energy. To solve this problem, a method for wave parameter inversion using quasi-binary variational mode decomposition (QB-VMD) is proposed. First, QB-VMD decomposes the spatial–temporal radial velocity series, and a series of modes is obtained, including “Group-Line” and dominant wave modes. Second, the “Group-Line” mode is discarded, and the dominant wave mode is compensated appropriately to reconstruct the spatial–temporal radial velocity series. Finally, the wave parameters are retrieved according to the reconstructed spatial–temporal radial velocity series. The proposed method is verified by simulation. In addition, this article uses an eight-day dataset collected by the coherent $S$-band radar deployed at Beishuang island for analysis. The significant wave height and mean wave period are retrieved from the dataset. The wave parameters estimated by the proposed method are compared with the buoy results. The correlation coefficients are 0.97 and 0.80, and the root-mean-square errors are 0.12 m and 0.49 s, respectively. The results show that the proposed method can invert wave parameters using the coherent $S$-band radar with reasonable performance.

In modern cities, consumers with distributed energy resources (DERs) can trade energy by managing their consumption and supply. Blockchain is considered to provide technical support for establishing a distributed energy market, while the current mainstream blockchain technology cannot meet the requirement of efficiency and scalability under such a transaction scenario. In addition, the potential defaults of market players also hinder market implementation. Therefore, a reputation-based distributed energy trading mechanism and the corresponding blockchain consensus method considering reputation management are proposed in this paper. Firstly, a distributed reputation management mechanism is designed to systematically evaluate the user’s behavior in the market. Secondly, to address the limitations of traditional consensus methods in the distributed energy market distributed reputation control is introduced into the node model of blockchain, and a new energy blockchain consensus method named DPoR is proposed to solve the technical bottleneck under the distributed energy trading scenario. We also present a corresponding transaction mechanism to encourage market participants to maintain their reputations. Finally, the simulation results verify the effectiveness of the proposed transaction mechanism in this paper, and the presented blockchain consensus mechanism can meet the performance requirements under distributed energy trading scenarios in terms of high efficiency, low consumption, and openness.

Abstract The enhancement of the photocatalytic performance of pristine WO3 was systematically adjusted due to its fast recombination rate and low reduction potential. A designed heterostructure photocatalyst was necessarily synthesised by Fe3+ metal ions doping into WO3 structure with and composition modification. In this study, we synthesised a retrievable Fe-doped WO3/SiO2 heterostructure using a surfactant-assisted hydrothermal method. This heterostructure was then employed as an effective photocatalyst for the removal of Cr(VI) under visible light irradiation. Enlarged photocatalytic reduction was observed over a synergetic 7.5 mol% Fe-doped WO3/SiO2-20 nanocomposite, resulting in dramatically increased activity compared with undoped WO3 and SiO2 nanomaterials under visible light illumination within 90 min. The presence of 7.5 mol% Fe3+ ion dopant in WO3 optimised electron–hole recombination, consequently reducing WO3 photocorrosion. After adding SiO2 nanoparticles, the binary WO3-SiO2 nanocomposite played roles as both adsorbent and photocatalyst to increase specific surface area. Thus, the 7.5 mol% Fe-doped WO3/SiO2-20 nanocomposite catalyst had more active sites on the surface of catalyst, and enhanced photocatalytic reduction was significantly achieved. The results showed 91.1% photocatalytic reduction over the optimum photocatalyst, with a photoreduction kinetic rate of 21.1 × 10–3 min−1, which was approximately four times faster than pristine WO3. Therefore, the superior optimal photocatalyst demonstrated reusability, with activities decreasing by only 9.8% after five cycles. The high photocatalytic performance and excellent stability of our photocatalyst indicate great potential for water pollution treatments.

Abstract Developing functional additive resistant to space atomic oxygen (AO) irradiation through simple molecular design and chemical synthesis to enhance the lubricating performance of multialkylated cyclopentanes (MACs) oil is a significant challenge. Herein, sulfur-containing polyhedral oligomere silsesquioxane (POSS) were synthesize via a click-chemistry reaction of octavinyl polyhedral oligomeric with alkyl sulfide. The reduce-friction (RF), anti-wear (AW) properties and anti-AO irradiation of POSS-S-R as MACs base oil additives in atmospheric and simulated space environments were systematically investigated for the first time. Results demonstrate that POSS-S-R not only possesses outstanding anti-AO irradiation capacity but also effectively improves the RF and AW of MACs in atmospheric or simulated space surroundings. This improvement is due to the excellent anti-AO irradiation properties of the POSS structure itself and the high load-carrying ability of silicon-containing and sulfur-containing compounds generated by tribo-chemical reactions, which effectively separates the direct contact of the friction interface. We believe that this synthesized POSS-S-R is a promising additive for space lubricants.

This study evaluates petrophysical properties (especially porosity, permeability, tortuosity, and diffusivity) of representative geological rocks in the context of injectivity, storage space, and caprock integrity for effective utilization and long-term storage of carbon dioxide. A total of 10 geological rocks were selected as representative storage media for consideration as saline aquifers & depleted oil and gas reservoirs (sandstones and carbonates), basalts, and cap rocks, as well as utilization in organic-rich shale and coal seams. An integrated suite of laboratory tests, including liquid immersion porosimetry, gas expansion porosimetry, grain size distribution, mercury intrusion porosimetry, and gas diffusion, were performed on these various rock samples. The results exhibit a disparity of petrophysical properties among two broad groups of rocks: rocks selected for possible storage of CO2have porosities of ∼10-25%, permeabilities of ∼10−16-10−13m2, μm-sized pore-throat size distribution, and mostly good pore connectivity; in contrast, the potential caprocks have porosities of ∼0.5-5%, permeabilities of ∼10−20-10−18m2, pore throat sizes of

For missile-borne platforms, traditional SAR technology consistently encounters two significant shortcomings: geometric distortion of 2D images and the inability to achieve forward-looking imaging. To address these issues, this paper explores the feasibility of using a maneuvering trajectory to enable forward-looking and three-dimensional imaging by analyzing the maneuvering characteristics of an actual missile-borne platform. Additionally, it derives the corresponding resolution characterization model, which lays a theoretical foundation for future applications. Building on this, the paper proposes a three-dimensional super-resolution imaging algorithm that combines axis rotation with compressed sensing. The axis rotation not only realizes the dimensionality reduction of data, but also can expand the observation scenario in the cross-track dimension. The proposed algorithm first focuses on the track-vertical plane to extract 2D position parameters. Then, a compressed sensing-based process is applied to extract reflection coefficients and super-resolution cross-track position parameters, thereby achieving precise 3D imaging reconstruction. Finally, numerical simulation results confirm the effectiveness and accuracy of the proposed algorithm.

Exposure to Pb2+ in the environment, especially in water, poses a significant threat to human health and urgently necessitates the development of highly sensitive Pb2+ detection methods. In this study, we have integrated the high sensitivity of electrochemical techniques with allosteric transcription factors (aTFs) to develop an innovative electrochemical biosensing platform. This biosensors leverage the specific binding and dissociation of DNA to the aTFs (PbrR) on electrode surfaces to detect Pb2+. Under the optimal conditions, the platform has a broad linear detection range from 1 pM to 10 nM and an exceptionally low detection threshold of 1 pM, coupled with excellent selectivity for Pb2+. Notably, the biosensor demonstrates regenerative capabilities, enabling up to five effective Pb2+ measurements. After one week of storage at 4 °C, effective lead ion detection was still possible, demonstrating the biosensor’s excellent stability, this can effectively save the cost of detection. The biosensor also achieves a recovery rate of 93.3% to 106.6% in real water samples. The biosensor shows its potential as a robust tool for the ultrasensitive detection of Pb2+ in environmental monitoring. Moreover, this research provides new insights into the future applications of aTFs in electrochemical sensing.

To analyze the impact of volcanic rocks in the Offshore Indus Basin on hydrocarbon reservoir formation, seismic data interpretation, seismic data inversion, and sea–land correlation analysis were carried out. The results show that, longitudinally, volcanic rocks are mainly distributed at the top of the Cretaceous system or at the bottom of the Paleocene, and carbonate rock platforms or reefs of the Paleocene–Eocene are usually developed on them. On the plane, volcanic rocks are mainly distributed on the Saurashtra High in the southeastern part of the basin. In terms of thickness, the volcanic rocks revealed by drilling in Karachi nearshore are about 70 m thick. We conducted sparse spike inversion for acoustic impedance in the volcanic rock area. The results show that the thickness of the Deccan volcanic rocks in the study area is between 250 and 750 m which is thinning from southeast to northwest. Based on sea–land comparison and comprehensive research, the distribution of volcanic rocks in the Indian Fan Offshore Basin played a constructive role in the Mesozoic oil and gas accumulation in the Indus offshore. Therefore, in the Indian Fan Offshore Basin, attention should be paid to finding Mesozoic self-generated and self-stored hydrocarbon reservoirs and Cenozoic lower-generated and upper-stored hydrocarbon reservoirs.