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Abstract Peritumoral hepatocytes are critical components of the liver cancer microenvironment, However, the role of peritumoral hepatocytes in the local tumor immune interface and the underlying molecular mechanisms have not been elucidated. YTHDF2, an RNA N 6 -methyladenosine (m6A) reader, is critical for liver tumor progression. The function and regulatory roles of YTHDF2 in peritumoral hepatocytes are unknown. This study demonstrated that oxaliplatin (OXA) upregulated m6A modification and YTHDF2 expression in hepatocytes. Studies using tumor-bearing liver-specific Ythdf2 knockout mice revealed that hepatocyte YTHDF2 suppresses liver tumor growth through CD8+ T cell recruitment and activation. Additionally, YTHDF2 mediated the response to immunotherapy. Mechanistically, OXA upregulated YTHDF2 expression by activating the cGAS-STING signaling pathway and consequently enhanced the therapeutic outcomes of immunotherapeutic interventions. Ythdf2 stabilized Cx3cl1 transcripts in an m6A-dependent manner, regulating the interplay between CD8+ T cells and the progression of liver malignancies. Thus, this study elucidated the novel role of hepatocyte YTHDF2, which promotes therapy-induced antitumor immune responses in the liver. The findings of this study provide valuable insights into the mechanism underlying the therapeutic benefits of targeting YTHDF2.

Abstract Transcranial temporal interference stimulation (tTIS) is a promising brain stimulation method that can target deep brain regions by delivering an interfering current from surface electrodes. Most instances of tTIS stimulate the brain with a single-frequency sinusoidal waveform generated by wave interference. Theta burst stimulation is an effective stimulation scheme that can modulate neuroplasticity by generating long-term potentiation- or depression-like effects. To broaden tTIS application, we developed a theta burst protocol using tTIS technique to modulate neuroplasticity in rats. Two cannula electrodes were unilaterally implanted into the intact skull over the primary motor cortex. Electrical field of temporal interference envelopes generated by tTIS through cannula electrodes were recorded from primary motor cortex. Theta burst schemes were characterized, and motor activation induced by the stimulation was also evaluated simultaneously by observing electromyographic signals from the corresponding brachioradialis muscle. After validating the stimulation scheme, we further tested the modulatory effects of theta burst stimulation delivered by tTIS and by conventional transcranial electrical stimulation on primary motor cortex excitability. Changes in the amplitude of motor evoked potentials, elicited when the primary motor cortex was activated by electrical pulses, were measured before and after theta burst stimulation by both techniques. Significant potentiation and suppression were found at 15 to 30 min after the intermittent and continuous theta burst stimulation delivered using tTIS, respectively. However, comparing to theta burst stimulations delivered using conventional form of transcranial electrical stimulation, using tTIS expressed no significant difference in modulating motor evoked potential amplitudes. Sham treatment from both methods had no effect on changing the motor evoked potential amplitude. The present study demonstrated the feasibility of using tTIS to achieve a theta burst stimulation scheme for motor cortical neuromodulation. These findings also indicated the future potential of using tTIS to carry out theta burst stimulation protocols in deep-brain networks for modulating neuroplasticity.

Abstract Physical exercise is recognized for its beneficial effects on brain health and executive function, particularly through the careful manipulation of key exercise parameters, including type, intensity, and duration. The aim of this systematic review and meta-analysis was to delineate the optimal types, intensities, and durations of exercise that improve cognitive functions in older adults with mild cognitive impairment (MCI) or dementia. A comprehensive search was conducted in Scopus, Web of Science, and PubMed from their inception until December 2023. The methodological quality and publication bias of the included studies were assessed using the PEDro scale and Egger’s regression test, respectively. Separate meta-analyses were performed to assess the overall impact of exercise on cognitive assessments and to explore the effects of different exercise types (i.e., aerobic, resistance, dual-task, mind-body, and multi-component exercises) and intensities (i.e., low, moderate, and high) on executive function. Results were presented as standardized mean differences (SMD) and 95% confidence intervals (95% CI). A meta-regression analysis was conducted to examine the correlation between exercise duration and mean effects. In total, 15,087 articles were retrieved from three databases, of which 35 studies were included in our final analyses. The results indicated high overall methodological quality (PEDro score = 8) but a potential for publication bias (t = 2.08, p = 0.045). Meta-analyses revealed that all types of exercise (SMD = 0.691, CI [0.498 to 0.885], p

Abstract Objective To study the effects of selective serotonin reuptake inhibitors (SSRIs) on cognitive functions, mental improvements, and adverse effects in patients with Alzheimer’s disease (AD). Methods Registered in INPLASY (INPLASY202450004), five drugs (citalopram, s-citalopram, quetiapine, olanzapine, and sertraline) were selected as representatives. A comprehensive search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library up to May 15, 2024. Search terms were combined using Boolean operators, specifically ‘AND’ between different categories (e.g., ‘Alzheimer’s Disease’ AND ‘SSRIs’) and ‘OR’ within the same category (e.g., ‘citalopram OR s-citalopram OR quetiapine OR olanzapine OR sertraline’), to ensure a thorough retrieval of relevant studies. The selection followed rigorous inclusion and exclusion criteria for meta-analysis. Results Fourteen articles from 1118 were selected for meta-analysis. The indicators, including Neuropsychiatric Inventory (NPI), Mini-Mental State Examination (MMSE), Brief Psychiatric Rating Scale (BPRS), and Cornell Scale for Depression in Dementia (CSDD), were used to assess the effects of the drugs on AD treatment. According to the results of NPI, CSDD, BPRS, MMSE, and security assessments, the five antidepressants have significant advantages in AD treatment compared with placebo, while the MMSE of the patient treated with the antidepressants did not show notable changes compared with patients treated only with placebo. Statistical analyses were conducted using Review Manager 5.3, employing random-effects models to account for study heterogeneity and sensitivity analyses to test the robustness of our findings. Conclusion This study suggests that SSRI-related antidepressants have great potential values in AD treatment, and further research on the application of SSRI-related antidepressants in AD treatment is necessary.

ObjectivesThe purpose of this paper is to investigate the control and optimization of the power output system for a multi-body floating wave energy converter (MBFWEC) with wave protection effects.MethodsTo study the interaction of the multi-body floating WEC with waves, a numerical wave flume is constructed using OpenFOAM software. The experiment simulates the interaction between the WEC and waves under different power take-off (PTO) strategies, namely linear, constant, linear spring, velocity-squared and snap through PTO systems, then compares the energy capture efficiency and wave dissipation performance of the WEC under each.ResultsThe results show that the wave energy capture efficiency of the MBFWEC can reach up to 52.6%. The linear spring and snap through PTO systems, which are based on the optimization of linear PTO, have a certain degree of influence on the WEC and its wave dissipation effects. However, linear PTO is more advantageous than linear spring and snap through when considering both wave energy capture and wave dissipation effects.ConclusionsThis study identifies the advantageous wave intervals of PTO systems such as constant damping and velocity-squared damping, and can provide useful references for optimizing PTO system settings for MBFWECs.

Abstract Circular RNAs (circRNAs) are unique noncoding RNAs that have a closed and stable loop structure generated through backsplicing. Due to their conservation, stability and tissue specificity, circRNAs can potentially be used as diagnostic indicators and therapeutic targets for certain tumors. Many studies have shown that circRNAs can act as microRNA (miRNA) sponges, and engage in interactions with proteins and translation templates to regulate gene expression and signal transduction, thereby participating in the occurrence and development of a variety of malignant tumors. Immunotherapy has revolutionized the treatment of cancer. Early researches have indicated that circRNAs are involved in regulating tumor immune microenvironment and antitumor immunity. CircRNAs may have the potential to be important targets for increasing sensitivity to immunotherapy and expanding the population of patients who benefit from cancer immunotherapy. However, few studies have investigated the correlation between circRNAs and tumor immunity. In this review, we summarize the current researches on circRNAs involved in antitumor immune regulation through different mechanisms and their potential value in increasing immunotherapy efficacy with the goal of providing new targets for cancer immunotherapy.

Abstract Identification of high consequence areas is an important task in pipeline integrity management. However, traditional identification methods are generally characterized by low efficiency, high cost and low accuracy. For this reason, this paper proposes a recognition method based on the improved algorithm Mask Region-based Convolutional Neural Network. Coordinate attention mechanism module is introduced into the traditional Mask R-CNN algorithm to improve the recognition accuracy and reduce the training time. For the identification results, GIS tools are utilized to establish high consequence zones along both sides of the pipeline, and the grade and scope of the high consequence zones are determined according to relevant specifications.In this paper, this method is used to identify the high-consequence area of a pipeline section in Guangdong Province, the results show that: 1, the improved algorithm in the identification of densely populated, geologic hazards, flammable and explosive high consequence zones of the average accuracy of the identification of 1.7%, 3.4%, 3.9%. 2, The method in this paper identifies 8 more building elements and 0.311 more kilometers of pipeline mileage compared to traditional identification methods. The method of this paper can provide a reference for the early identification of high consequence areas of pipelines.

Abstract Vermicomposting utilizes the synergistic effect of earthworms with microorganisms to accelerate the stabilization of organic matter in biowastes. Nevertheless, the exact mechanism behind the maturity of vermicompost and the growth of earthworms exposed to biochar of varying particle sizes remains unclear. This study presents an investigation of the effect of biochar particle size on earthworm (Eisenia fetida) survival, microbial diversity, and the quality of vermicompost products. To address these issues, pelletized dewatered sludge samples from a municipal sewage treatment plant were amended with pine-based biochar with particle sizes of 1–2 mm, 25–75 μm, 200 nm, and 60 nm as the substrate for vermicomposting. This study revealed that the addition of millimeter-scale biochar and micron-scale biochar significantly promoted the degradation of organic matter since the organic matter in the treatment with 1–2 mm biochar at the end of the vermicomposting experiment decreased by 12.6%, which was equivalent to a 1.9-fold increase compared with that of the control. Excessive nanopowdering of nanobiochar significantly affected the survival of earthworms and led to 24.4–33.3% cumulative mortality, while millimeter-scale (mm) biochar and micron-scale (μm) biochar achieved zero mortality. The findings of this study could be used for evaluating the potential impact of nanoscale biochar to earthworms and guiding biochar-augmented vermicomposting. Graphical Abstract

Abstract Objectives Epilepsy and migraine are common chronic neurological disease. Epidemiologic studies and shared pathophysiology and treatment suggest that these two diseases overlap. However, migraine is often underestimated among patients with epilepsy. This study aimed to evaluate the prevalence of migraine and identify the related influencing factors among adult patients with epilepsy. Methods Adult patients with epilepsy were recruited at the outpatient epilepsy clinic of 13 tertiary hospitals in China from February to September 2022. ID Migraine questionnaire was applied to evaluate for migraine. Both univariable and multivariable logistic regression models were used to explore the influencing factors of migraine. Results A total of 1326 patients with epilepsy were enrolled in this study. The prevalence of migraine among patients with epilepsy was 19.2% (254/1326). In the multivariable analysis, being female (OR = 1.451, 95% CI: 1.068–1.975; p = 0.018), focal and focal to bilateral tonic–clonic seizures (OR = 1.583, 95% CI: 1.090–2.281; p = 0.015), and current seizure attack in the last 3 months (OR = 1.967, 95% CI: 1.282–3.063; p = 0.002) were the influencing factors for migraine. However,

To explore the mechanical response of composites under fire conditions，a thermal-tensile response model for polymer composites considering matrix pyrolysis and fiber softening effects was developed. Nonlinear equations were solved using multidimensional array operations to research the variation of tensile performance of glass fiber/vinyl ester composites at high temperature and to predict the failure time under different tensile loads and one-sided heat flux conditions.The results indicate that the developed nonlinear thermal-tensile response model can effectively predict the tensile behaviour of vinyl ester and glass fiber/vinyl ester composites under unilateral steady heat flux. The results calculated using the model show that there are two distinct phases during the decrease of the tensile strength of glass fiber/vinyl ester composites with temperature decreasing： the first phase features a rapid decrease near the glass transition temperature，while the second phase shows a gradual decline following the complete glassy transition of the matrix. Furthermore，the failure time of the glass fiber/vinyl ester composites significantly decreases with increasing tensile load，displaying a consistent trend across different heat flux densities. Under constant tensile stress，the reduction in heat flux density can extend failure time of composites. Specifically，at the tensile stress of 80% of room temperature strength，the failure time of the laminate at 10 kW/m² is extended by 300 seconds compared to 75 kW/m2. Additionally，at 10 kW/m2，when the tensile stress is less than 50% of the room temperature strength，the laminate will not fail for a long time.

Popularization of medical knowledge plays an important role in promoting effective communication and understanding between doctors and patients. Based on the shortcomings of the model of popularization of traditional medical knowledge, such as unidirectional dissemination, insufficient depth of information and difficulty in understanding, this paper explores the types and advantages of innovative models of popularization of medical knowledge by searching the literature. Currently, the main models of community-based popularization of medical knowledge include traditional media (TV, radio, newspapers), lectures, special report, books, brochures, etc., which are limited in terms of the effectiveness of information dissemination, lack of interaction and personalization, as well as continuity and traceability. In this paper, an in-depth discussion was conducted on the innovative model of popularizing the knowledge of critical care medicine in the community, and many new models of popularizing knowledge, including cartoons, animation, virtual reality, augmented reality, and Internet platforms were proposed, and useful community practice was carried out. The results of the practice showed that the number of reading hits and the satisfaction with popularizing science were significantly increased under the innovative models of popularization of knowledge. The innovative model of popularization of knowledge can improve the efficiency of medical knowledge popularization, enhance patient participation, bridge the gap of medical knowledge, and provide customized health management solutions, which is of a significant advantage, however, it also has limitations such as higher dependence on technology and equipment, and the model of popularization of knowledge still needs to be continuously innovated and explored.

Objective The good oil test results of Taiye 1 and Xingye L1 wells in the Jurassic Lianggaoshan Formation shale indicate the breakthrough of shale oil/gas exploration in the Jurassic continental shale in the Fuxing area of the eastern Sichuan Basin. To further clarify the oil/gas exploration potential and the organic matter enrichment mechanism of the Jurassic Lianggaoshan Formation shale, utilizing logging and core data of two typical wells Xingye X and Xingye Y, the whole-rock X-ray diffraction, organic carbon, major and trace elements were analyzed. Methods The Liang-2 lower submember was deposited in the environment of warm-wet (moderate weathering conditions) and freshwater, and there was no obvious difference in palaeoclimates of different unit formations. The La-Co data suggests a semi-deep to deep lake environment with a palaeowater depth ranging from 10.9 to 56.1 m; the anoxic reducing environment persisted on the lake floor despite the lake level fluctuation, but the palaeoproductivity was vertically increased. The shale interval is rich in sandy laminae, but the deposition rate of the shale layer is lower than that of the sandstone layer. Results According to the correlation analysis between sedimentary environment parameters and organic carbon content (TOC), the organic matter enrichment in the Liang-2 lower submember shale was mainly controlled by factors of palaeowater depth, palaeoredox environment, deposition rate, and palaeoproductivity, and slightly affected by the palaeosalinity and palaeoclimate conditions. The variation in the deposition environment resulted in the vertical heterogeneity of shale. Conclusion The shale facies of Unit 6, formed in the good conditions for the organic matter enrichment referring to an anoxic environment in deep water, with a low deposition rate, a high palaeoproductivity, and the slight influence of terrigenous sources, was a favorable target layer for exploration.

BackgroundBacteria are the most diverse and widely sourced microorganisms in the indoor air of subway stations, where pathogenic bacteria can spread through the air, leading to increased health risks. ObjectiveTo understand the status and distribution characteristics of indoor air bacterial pollution in subway stations and compartments in a city of Central South China, and to provide a scientific basis for formulating intervention measures to address indoor air bacteria pollution in subways. MethodsThree subway stations and the compartments of trains parking there in a city in Central South China were selected according to passenger flow for synchronous air sampling and monitoring. Temperature, humidity, wind speed, carbon dioxide (CO2), fine particulate matter (PM2.5), and inhalable particulate matter (PM10) were measured by direct reading method. In accordance with the requirements of Examination methods for public places-Part 3: Airborne microorganisms (GB/T 18204.3-2013), air samples were collected at a flow rate of 28.3 L·min−1, and total bacterial count was estimated. Bacterial microbial species were identified with a mass spectrometer and pathogenic bacteria were distinguished from non-pathogenic bacteria according to the Catalogue of pathogenic microorganisms transmitted to human beings issued by National Health Commission. Kruskal-Wallis H test was used to compare the subway hygiene indicators in different regions and time periods, and Bonferroni test was used for pairwise comparison. Spearman correlation test was used to evaluate the correlation between CO2 concentration and total bacterial count. ResultsThe pass rates were 100.0% for airborne total bacteria count, PM2.5, and PM10 in the subway stations and train compartments, 94.4% for temperature and wind speed, 98.6% for CO2, but 0% for humidity. The overall median (P25, P75) total bacteria count was 177 (138,262) CFU·m−3. Specifically, the total bacteria count was higher in station halls than in platforms, and higher during morning peak hours than during evening peak hours (P

Abstract Background Cervical spondylosis (CS), including myelopathy and radiculopathy, is the most common degenerative cervical spine disease. This study aims to evaluate the clinical outcomes of unilateral biportal endoscopy (UBE) compared to those of conventional anterior cervical decompression and fusion (ACDF) for treating unilateral cervical radiculopathy or coexisting cervical myelopathy induced by unilateral cervical herniated discs. Methods A prospective, randomized, controlled, noninferiority trial was conducted. The sample consisted of 131 patients who underwent UBE or ACDF was conducted between September 2021 and September 2022. Patients with cervical nerve roots or coexisting spinal cord compression symptoms and imaging-defined unilateral cervical radiculopathy or coexisting cervical myelopathy induced by unilateral cervical herniated discs were randomized into two groups: a UBE group (n = 63) and an ACDF group (n = 68). The operative time, blood loss, length of hospital stay after surgery, and perioperative complications were recorded. Preoperative and postoperative modified Japanese Orthopaedic Association (mJOA) scale scores, visual analog scale (VAS) scores, neck disability index (NDI) scores, and recovery rate (RR) of the mJOA were utilized to evaluate clinical outcomes. Results The hospital stay after surgery was significantly shorter in patients treated with UBE than in those treated with ACDF (p

Abstract Background The high recurrence rate after liver resection emphasizes the urgent need for neoadjuvant therapy in hepatocellular carcinoma (HCC) to enhance the overall prognosis for patients. Immune checkpoint inhibitors, camrelizumab combined with an anti-angiogenic tyrosine kinase inhibitor (TKI) apatinib, have emerged as a first-line treatment option for patients with unresectable HCC, yet its neoadjuvant application in combination with transarterial chemoembolization (TACE) in HCC remains unexplored. Therefore, this study aims to investigate the efficacy and safety of sequential TACE, camrelizumab, and apatinib as a neoadjuvant therapy for single, huge HCC. Methods This multi-center, open-label randomized phase 3 trial will be conducted at 7 tertiary hospitals. Patients with single huge (≥ 10 cm in diameter), resectable HCC will be randomly assigned in a 1:1 ratio to arm of surgery alone or arm of neoadjuvant therapy followed by surgery. In the neoadjuvant therapy group, patients will receive TACE within 1 week after randomization, followed by camrelizumab (200 mg q2w, 4 cycles), along with apatinib (250 mg qd, 2 months). Patients will receive liver resection after neoadjuvant therapy unless the disease is assessed as progressive. The primary outcome is recurrence-free survival (RFS) at 1 year. The planned sample size of 60 patients will be calculated to permit the accumulation of sufficient RFS events in 1 year to achieve 80% power for the RFS primary endpoint. Discussion Synergistic effects provided by multimodality therapy of locoregional treatment, TKI, and anti-programmed cell death 1 inhibitor significantly improved overall survival for patients with unresectable HCC. Our trial will investigate the efficacy and safety of the triple combination of TACE, camrelizumab, and apatinib as a neoadjuvant strategy for huge, resectable HCC. Trial registration www.chitr.org.cn ChiCTR2300078086. Registered on November 28, 2023. Start recruitment: 1st January 2024. Expected completion of recruitment: 15th June 2025.

Abstract Solid-state infrared-to-visible photon up-conversion is important for spectral-tailoring applications. However, existing up-conversion systems not only suffer from low efficiencies and a need for high excitation intensity, but also exhibit a limited selection of materials and complex fabrication processes. Herein, we propose a sensitizer with a bulk-heterojunction structure, comprising both an energy donor and an energy acceptor, for triplet-triplet annihilation up-conversion devices. The up-conversion occurs through charge separation at the donor-acceptor interface, followed by the formation of charge transfer state between the energy donor and annihilator following the spin statistics. The bulk-heterojunction sensitizer ensures efficient charge generation and low charge recombination. Hence, we achieve a highly efficient solid-state up-conversion device with 2.20% efficiency and low excitation intensity (10 mW cm−2) through a one-step solution method. We also demonstrate bright up-conversion devices on highly-flexible large-area substrates. This study introduces a simple and scalable platform strategy for fabricating efficient up-conversion devices.

Objective: To investigate the characteristics of three-dimensional distribution of subchondral fracture lines on the surface of the osteonecrosis femoral head, and to discuss the underlying mechanisms that contribute to its collapse. Methods: We retrospectively analyzed computed tomography (CT) images from 75 patients (comprising a total of 77 femoral heads) diagnosed with Association Research Circulation Osseous (ARCO) stage IIIA or IIIB femoral head necrosis. The three-dimensional structures of both the femoral head and the subchondral fracture line were reconstructed and subsequently fitted into normal femoral head model. A heat map of fracture line was generated to visualize its spatial distribution across the femoral heads surface.to observe its distribution. In addition to that, the femoral head was partitioned into four zones, and the frequency of each fracture line traversing different zones was calculated and analysed. Results: Highest and lowest density of subchondral fracture lines was demonstrated in anterolateral and posterolateral zone respectively. and most sparse in posterolateral. Furthermore, the three-dimensional heat map of fracture lines highlighted their most frequent occurrence in the anterolateral area, particularly near the junction of the femoral head and neck. One fracture line may pass through multiple areas, passage frequencies for fracture lines was observed in zones I, II, III and IV for 66 times (85.7 %), 52 times (67.5 %), 25 times (32.5 %) and 46 times (59.7 %), respectively, with a significant difference between zone I and other zones (P

In this study, the effect of component migration and interaction with concomitant saponins on the composition and functional properties of the seed storage proteins from Camellia oleifera Abel., a typical woody oil crop in China, was investigated using proteomics and molecular docking. The results showed that the optimal parameters for alkaline extraction were solid/liquid ratio 1:10 (g/mL) and pH 8.0, which resulted in an extraction rate of 75.8%, and a saponin-to-protein ratio of 2.60. The 11S globulins were precipitated at pH 4.5 with a saponin-to-protein ratio of 0.36. Albumin accounted for 69% of the total storage proteins, and coexisted with saponin during the extraction process, thus resulting in a high saponin-to-protein ratio of 3.73. The foaming properties of albumin and globulin from C. oleifera Abel. seeds were larger than 200%, and the emulsifying activity index was 16.7 m2/g. The interaction between saponins and proteins significantly improved the emulsion stability. This study provides theoretical support for the high-value utilization of proteins from C. oleifera Abel. and the development of functional food ingredients.

Abstract Background By complexing poly (ADP-ribose) (PAR) in reaction to broke strand, PAR polymerase1 (PARP1) acts as the key enzyme participated in DNA repair. However, recent studies suggest that unrepaired DNA breaks results in persistent PARP1 activation, which leads to a progressively reduce in hexokinase1 (HK1) activity and cell death. PARP-1 is TCF-4/β-A novel co activator of gene transactivation induced by catenin may play a role in the development of colorectal cancer. The molecular mechanism of PARP1 remains elusive. Methods 212 colorectal cancer (CRC) patients who had the operation at our hospital were recruited. PARP1 expression was evaluated by immunohistochemistry. Stable CRC cell lines with low or high PARP1 expression were constructed. Survival analysis was computed based on PARP1 expression. The cell proliferation was tested by CCK-8 and Colony formation assay. The interaction of PARP1 and XRCC2 was detected by immunoprecipitation (IP) analysis. Results Compared with matching adjacent noncancerous tissue, PARP1 was upregulated in CRC tissue which was correlated with the degree of differentiation, TNM stage, depth of invasion, metastasis, and survival. In addition, after constructing CRC stable cell lines with abnormal expression of PARP1, we found that overexpression of PARP1 promoted proliferation, and demonstrated the interaction between PARP1 and XRCC2 in CRC cells through immunoprecipitation (IP) analysis. Moreover, the inhibitor of XRCC2 can suppress the in vitro proliferation arousing by upregulation of PARP1. Conclusions PARP1 was upregulated in CRC cells and promoted cell proliferation. Furthermore, the expression status of PARP1 was significantly correlated with some clinicopathological features and 5-year survival.

Abstract Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in young children and the elderly. There are currently no approved RSV-specific therapeutic small molecules available. Using high-throughput antiviral screening, we identified an oral drug, the prenylation inhibitor lonafarnib, which showed potent inhibition of the RSV fusion process. Lonafarnib exhibited antiviral activity against both the RSV A and B genotypes and showed low cytotoxicity in HEp-2 and human primary bronchial epithelial cells (HBEC). Time-of-addition and pseudovirus assays demonstrated that lonafarnib inhibits RSV entry, but has farnesyltransferase-independent antiviral efficacy. Cryo-electron microscopy revealed that lonafarnib binds to a triple-symmetric pocket within the central cavity of the RSV F metastable pre-fusion conformation. Mutants at the RSV F sites interacting with lonafarnib showed resistance to lonafarnib but remained fully sensitive to the neutralizing monoclonal antibody palivizumab. Furthermore, lonafarnib dose-dependently reduced the replication of RSV in BALB/c mice. Collectively, lonafarnib could be a potential fusion inhibitor for RSV infection.

Abstract Objective Our study aimed to determine whether there exists an association between low-grade systemic inflammation, as measured by serum C-reactive protein (CRP), and the risk of lower-extremity deep venous thrombosis (LEDVT) in patients with primary intracerebral hemorrhage (ICH). Methods This observational study was retrospectively conducted on patients with primary ICH who were presented to two tertiary medical centers between January 2021 and August 2022. The primary outcome was detecting LEDVT occurrence within 14 days from the onset of the acute ICH episode. Weighted logistic regression and restricted cubic spline models were employed to estimate the association between CRP and LEDVT following 1:1 propensity score matching (PSM). Results Of the 538 patients with primary ICH who met the inclusion criteria, 76 (14.13%) experienced LEDVT. Based on the cut-off levels of CRP measured upon admission from the receiver operating characteristic (ROC) curve, patients with primary ICH were categorized into two groups: (i) CRP

Background Current research on the physical fitness test scores of high school students is more localized within provinces and cities, with few multicenter, large-sample-size, domain-wide research results. The prevalence of blended online and offline teaching in schools of all types has inevitably prolonged the already long sedentary time of high school students. Whether this trend has some impact on the physical health of high school students is an urgent need for a region-wide study. Objective To investigate and analyze the levels of physical fitness test scores and related influencing factors of urban and rural high school first- and second-year students in seven regions of China, and to explore the empowering paths for the balanced improvement of physical fitness levels of first- and second-year high school students. Methods Stratified randomized cluster sampling method was used to conduct stratified sampling according to urban counties and townships and villages in high school schools in seven regions (East China, South China, North China, Central China, Northwest China, Southwest China, Northeast China) of 31 provinces (municipalities directly under the central government and autonomous regions) of China from January to March 2019, and then randomized clusters of 1 high school school in urban counties and 1 high school school in townships and villages in total of 62 schools were selected respectively. A total of 42 523 freshmen and sophomores in high schools were randomly selected to conduct the research, and the data on students' physical fitness test scores were collected at the same time (BMI reflects the level of physical development; lung capacity reflects the level of physical function; sit-and-reach reflects the level of flexibility; pull-up, 50 m run, standing long jump reflects the level of explosive strength of upper and lower limbs; 1 min sit-up reflects the level of core strength of the torso; 800 m run, 1 000 m run reflects the level of cardiorespiratory endurance), and non-parametric tests and multiple linear regression analysis were used to explore the influencing factors of the level of physical fitness test scores. Results The age distribution of 42 523 high school students was 16.0 (16.0, 17.0) years; 20 074 (47.2%) boys and 22 449 (52.8%) girls, 21 725 (51.1%) in cities, counties and districts, and 20 798 (48.9%) in towns and villages. Comparison of the gender and urban-rural distribution of high school students in the seven regions showed statistically significant differences (PNortheast China>Central China), body mass (Northeast China>North China>Central China), BMI (Central China>Northeast China>North China), lung capacity (Northeast China>Central China>South China), 50 m run (South China>Central China>East China), standing long jump (South China>North China>Northwest China), sit-and-reach (South China>Southwest China>Central China), pull-up (South China>Southwest China>Northwest China), and 1 000 m run (South China>Central China>Southwest China). High school boys in the city, county and districts had higher lung capacity scores than those in the town and country, and lower scores than those in the town and country in the 50 m run, standing long jump, sit-and-reach, pull-up, and 1 000 m run (P0.05). The differences in the scores of high school girls in each physical fitness test in the seven regions are statistically significant (PNortheast China>Northwest China), body mass (Northeast China>North China>Northwest China), BMI (Northeast China>North China>Northwest China), lung capacity (Northeast China>South China>Central China), 50 m run (South China>Central China>East China), standing long jump (South China>North China>Central China), sit-and-reach (Northeast China>Central China>South China), 1 min sit-up (North China>Central China>East China=Southwest China), 800 m run (Northeast>Central China>South China). High school girls in the city and county districts had higher height, body mass, and BMI scores than those in the town and country, and lower scores than those in the town and country in lung capacity, 50 m run, standing long jump, sit-and-reach, 1 min sit-up, and 800 m run (P

Abstract As potent approaches for addressing computationally expensive optimization problems, surrogate-assisted evolutionary algorithms (SAEAs) have garnered increasing attention. Prevailing endeavors in evolutionary computation predominantly concentrate on expensive continuous optimization problems, with a notable scarcity of investigations directed toward expensive combinatorial optimization problems (ECOPs). Nevertheless, numerous ECOPs persist in practical applications. The widespread prevalence of such problems starkly contrasts the limited development of relevant research. Motivated by this disparity, this paper conducts a comprehensive survey on SAEAs tailored to address ECOPs. This survey comprises two primary segments. The first segment synthesizes prevalent global, local, hybrid, and learning search strategies, elucidating their respective strengths and weaknesses. Subsequently, the second segment furnishes an overview of surrogate-based evaluation technologies, delving into three pivotal facets: model selection, construction, and management. The paper also discusses several potential future directions for SAEAs with a focus towards expensive combinatorial optimization.

Abstract GDM, as a metabolic disease during pregnancy, regulates GLUT3 translocation by AMPK, thereby affecting glucose uptake in trophoblasts. It provides a new research idea and therapeutic target for alleviating intrauterine hyperglycemia in GDM. STZ was used to construct GDM mice, inject AICAR into pregnant mice, and observe fetal and placental weight; flow cytometry was employed for the detection of glucose uptake by primary trophoblast cells; immunofluorescence was applied to detect the localization of GLUT3 and AMPK in placental tissue; Cocofal microscope was used to detect the localization of GLUT3 in trophoblast cells;qRT-PCR and Western blot experiments were carried out to detect the expression levels of GLUT3 and AMPK in placental tissue; CO-IP was utilized to detect the interaction of GLUT3 and AMPK. Compared with the normal pregnancy group, the weight of the fetus and placenta of GDM mice increased (P

Abstract Federated learning is a distributed machine learning paradigm where the goal is to collaboratively train a high quality global model while private training data remains local over distributed clients. However, heterogenous data distribution over clients is severely challenging for federated learning system, which severely damage the quality of model. In order to address this challenge, we propose global prototype distillation (FedGPD) for heterogenous federated learning to improve performance of global model. The intuition is to use global class prototypes as knowledge to instruct local training on client side. Eventually, local objectives will be consistent with the global optima so that FedGPD learns an improved global model. Experiments show that FedGPD outperforms previous state-of-art methods by 0.22% ~1.28% in terms of average accuracy on representative benchmark datasets.

Abstract Since the discovery of the extraordinary optical transmission phenomenon, nanohole arrays have attracted much attention and been widely applied in sensing. However, their typical fabrication process, utilizing photolithographic top-down manufacturing technologies, has intrinsic drawbacks including the high costs, time consumption, small footprint, and low throughput. This study presented a low-cost, high-throughput, and scalable method for fabricating centimeter-scale (1×2 cm2) nanohole arrays using the improved nanosphere lithography. The large-scale close-packed polystyrene monolayers obtained by the hemispherical-depression-assisted self-assembly method were employed as colloidal masks for the nanosphere lithography, and the nanohole diameter was tuned from 233 nm to 346 nm with a fixed period of 420 nm via plasma etching. The optical properties and sensing performance of the nanohole arrays were investigated, and two transmission dips were observed due to the resonant coupling of plasmonic modes. Both dips were found to be sensitive to the surrounding environment, and the maximum bulk refractive index sensitivity was up to 162.1 nm/RIU with a 233 nm hole diameter. This study offered a promising approach for fabricating large-scale highly ordered nanohole arrays with various periods and nanohole diameters that could be used for the development of low-cost and high-throughput on-chip plasmonic sensors.

Abstract Parkinson’s disease is a progressive neurodegenerative disorder in which loss of dopaminergic neurons in the substantia nigra results in a clinically heterogeneous group with variable motor and non-motor symptoms with a degree of misdiagnosis. Only 3–25% of sporadic Parkinson’s patients present with genetic abnormalities that could represent a risk factor, thus environmental, metabolic, and other unknown causes contribute to the pathogenesis of Parkinson’s disease, which highlights the critical need for biomarkers. In the present study, we prospectively collected and analyzed plasma samples from 194 Parkinson’s disease patients and 197 age-matched non-diseased controls. N-acetyl putrescine (NAP) in combination with sense of smell (B-SIT), depression/anxiety (HADS), and acting out dreams (RBD1Q) clinical measurements demonstrated combined diagnostic utility. NAP was increased by 28% in Parkinsons disease patients and exhibited an AUC of 0.72 as well as an OR of 4.79. The clinical and NAP panel demonstrated an area under the curve, AUC = 0.9 and an OR of 20.4. The assessed diagnostic panel demonstrates combinatorial utility in diagnosing Parkinson’s disease, allowing for an integrated interpretation of disease pathophysiology and highlighting the use of multi-tiered panels in neurological disease diagnosis.

Abstract Objective This study aimed to compare the per OPU clinical outcomes for transfer of Day 3 double cleavage-stage embryos (DET) and Day 5 single blastocyst-stage (SBT) in patients with five or fewer good quality embryos on day 3 per occyte pick-up cycle (OPU) in antagonist cycles with consideration of blastocyst formation failure. Methods This was a retrospective, observational cohort study of 2,116 cases of OPU treated with antagonist protocol in the affiliated Chenggong Hospital of Xiamen University between January 2013 and December 2020. DET was performed in 1,811cycles and SBT was performed in 305 cycles. The DET group was matched to the SBT group by propensity score (PS) matching according to multiple maternal baseline covariates. After PS matching, there were 303 ET cycles in each group. The primary outcomes were the cumulative live birth rate (CLBR), cumulative multiple pregnancy rate(CMPR)per OPU and the number of ET to achieve live birth per OPU. Secondary outcomes were the percentage of clinical pregnancy(CPR), live birth rate(LBR), multiple pregnancy rate(MPR). Results Following PS mating, the CLBR was slightly higher (48.8% versus 40.3% ; P = 0.041) and the CMPR was significantly higher in the DET group compared to SBT group(44.2% versus 7.9%, P

Objective We explored risk factors for cognitive frailty in older patients with chronic obstructive pulmonary disease (COPD) and diabetes mellitus to develop and verify a risk prediction model for cognitive frailty. Methods This was a cross-sectional study. Convenience sampling was used to randomly select 378 patients hospitalized between February 2022 and December 2023. We allocated 265 patients who visited between February 2022 and February 2023 to a modeling group to analyze risk factors for cognitive frailty and create a logistic regression model for risk prediction. Another 113 patients who visited between March 2023 and December 2023 were included in a validation group for model verification. Results The cognitive frailty incidence in the 265 patients was 35.09% (93/265). Regression analysis showed that age >80 years (odds ratio [OR] = 4.576), regular exercise (OR = 0.390, polypharmacy (OR = 3.074), depression (OR = 2.395) duration of COPD combined with diabetes (OR = 1.902), Family APGAR index score (OR = 0.428), and chronic pain (OR = 2.156) were factors influencing the occurrence of cognitive frailty in older patients with COPD accompanied by diabetes. Conclusions The constructed risk prediction model for cognitive frailty in older patients with COPD and diabetes showed good predictive value, aiding in the clinical identification of high-risk patients and facilitating timely intervention and guidance.

Nonlinear resonators of superconducting thin-film kinetic inductance have attracted considerable research interest in the fields of detectors, qubits, parametric amplifiers, and more. By tuning the deposition parameters, niobium titanium nitride (NbTiN) films (∼12 nm in thickness) present high resistivity(∼2000 μΩ cm) and large sheet kinetic inductance (∼0.7 nH/□). We designed resonators with NbTiN micronwire as the inductor and aluminum as the capacitor, which result in a high internal quality factor and a Kerr nonlinearity of a few hertz. The radio frequency response of the resonators demonstrates nonlinear behavior similar to that of the cubic Duffing oscillator, including frequency shift and hysteresis region. The kinetic inductance resonator is a promising candidate for high saturation power parametric amplifiers.

Abstract Background The safety of medication use among older adults is a growing concern, given the aging population. Despite widespread attention, the exploration of medication literacy in older adults, particularly from the perspective of information literacy, is in its nascent stages. Methods This study utilized the existing literature to define medication information literacy (MIL) as a theoretical framework. A two‐round Delphi survey was conducted to identify the essential components of a MIL indicator system for older adults. The analytic hierarchy process (AHP) was then used to assign weights to each indicator. Results The study observed relatively high response rates in both rounds of the questionnaire, which, along with expert authority coefficients (Cr) of 0.86 and 0.89, underscores the credibility and expertise of the panellists. Additionally, Kendall's coefficient of concordance (Kendall's W) ranging from 0.157 to 0.33 (p

Ontologies play a pivotal role in knowledge representation across various artificial intelligence domains, serving as foundational frameworks for organizing data and concepts. However, the construction and evolution of ontologies frequently lead to logical contradictions that undermine their utility and accuracy. Typically, these contradictions are addressed using an Integer Linear Programming (ILP) model, which traditionally treats all formulas with equal importance, thereby neglecting the distinct impacts of individual formulas within minimal conflict sets. To advance this method, we integrate cooperative game theory to compute the Shapley value for each formula, reflecting its marginal contribution towards resolving logical contradictions. We further construct a graph-based representation of the ontology, enabling the extension of Shapley values to Myerson values. Subsequently, we introduce a Myerson-weighted ILP model that employs a lexicographic approach to eliminate logical contradictions in ontologies. The model ensures the minimum number of formula deletions, subsequently applying Myerson values to guide the prioritization of deletions. Our comparative analysis across 18 ontologies confirms that our approach not only preserves more graph edges than traditional ILP models but also quantifies formula contributions and establishes deletion priorities, presenting a novel approach to ILP-based contradiction resolution.

Abstract Extremely low‐frequency (ELF) electromagnetic (EM) waves adeptly propagate in harsh cross‐medium environments, overcoming rapid decay that hinders high‐frequency counterparts. Traditional antennas, however, encounter challenges concerning size, efficiency, and power. Here, drawing inspiration from nature, we present a groundbreaking piezo‐actuated, bionic flapping‐wing magnetic‐dipole resonator (BFW‐MDR), operating in the electro‐mechano‐magnetic coupling mechanism, designed for efficient ELF EM wave transmission. The unique rigid‐flexible hybrid flapping‐wing structure magnifies rotation angles of anti‐phase magnetic dipoles by tenfold, leading to constructive superposition of emitted magnetic fields. Consequently, the BFW‐MDR exhibits a remarkable quality factor of 288 and an enhanced magnetic field emission of 514 fT at 100 meters with only 6.9 mW power consumption, surpassing traditional coil antennas by three orders of magnitude. The communication rate is doubled by the ASK+PSK modulation method. Its robust performance in cross‐medium communication, even amidst various interferences, underscores its potential as a highly efficient antenna for underwater and underground applications.

The cylindrical-perfect-conductors (CPC) theory, which assumes an infinite and homogeneous soil medium, can be used to analyze heat pulse (HP) measurements to estimate soil thermal property values. However, when a HP sensor is positioned near the soil surface, the CPC theory is not valid because of the change in media properties at the soil-atmosphere interface. In this study, a CPC solution considering an adiabatic boundary condition (CPC-ABC) is presented to account for the soil-atmosphere interface effect. Compared with the results from numerical simulations, the CPC-ABC solution gave more accurate soil temperature values at the sensing probe than did a CPC model. When a HP sensor was positioned horizontally at a depth of 1 mm below a sand soil surface, the relative errors (RE) of CPC estimated thermal property values were as large as 52%, while the RE values based on the CPC-ABC solution were about 8%. Results from numerical simulations and laboratory experiments both showed that the CPC model worked well for horizontally positioned HP sensors with probe lengths of 70-mm at burial depths greater than 15 mm. Soil-atmosphere interface effect was largely dependent on HP sensor dimensions and measurement volumes. Overall, the extended CPC-ABC theory provided accurate soil thermal property estimates by considering the effects of finite probe properties and the presence of the soil-atmosphere interface.

Objective: This study aimed to analyze research on anxiety disorders using VOSviewer and CiteSpace to identify research hotspots and future directions. Methods: We conduct ed a comprehensive search on the Web of Science Core Collection (WoSCC) for relevant studies about anxiety disorders published within the past two decades (from 2004 to 2024). VOSviewer and CiteSpace were mainly used to analyze the authors, institutions, countries, publishing journals, reference co-citation patterns, keyword co-occurrence, keyword clustering, and other aspects to construct a knowledge atlas. Results: A total of 22,267 publications related to anxiety disorders were retrieved. The number of publications about anxiety disorders has generally increased over time, with some fluctuations. The United States emerged as the most productive country, with Harvard University identified as the most prolific institution and Brenda W. J. H. Penninx as the most prolific author in the field. Conclusion: This research identified the most influential publications, authors, journals, institutions, and countries in the field of anxiety research. Future research directions are involved advanced treatments based on pharmacotherapy, psychotherapy and digital interventions, mechanism exploration to anxiety disorders based on neurobiological and genetic basis, influence of social and environmental factors on the onset of anxiety disorders.

Genomic instability stands out as a pivotal hallmark of cancer, and PARP inhibitors (PARPi) emerging as a groundbreaking class of targeted therapy drugs meticulously crafted to inhibit the repair of DNA single-strand breaks(SSB) in tumor cells. Currently, PARPi have been approved for the treatment of ovarian cancer, pancreatic cancer, breast cancer, and prostate cancer characterized by homologous recombination(HR) repair deficiencies due to mutations in BRCA1/2 or other DNA repair associated genes and acquiring the designation of breakthrough therapy. Nonetheless, PARPi exhibit limited efficacy in the majority of HR-proficient BRCA1/2 wild-type cancers. At present, the synergistic approach of combining PARPi with agents that induce HR defects, or with chemotherapy and radiotherapy to induce substantial DNA damage, significantly enhances the efficacy of PARPi in BRCA wild-type or HR-proficient patients, supporting extension the use of PARPi in HR proficient patients. Therefore, we have summarized the effects and mechanisms of the combined use of drugs with PARPi, including the combination of PARPi with HR defect-inducing drugs such as ATRi, CHKi, HR indirectly inducing drugs like VEGFRi, CDKi, immune checkpoint inhibitors and drugs instigating DNA damage such as chemotherapy or radiotherapy. In addition, this review discusses several ongoing clinical trials aimed at analyzing the clinical application potential of these combined treatment strategies.

Background: Observational studies and clinical trials suggest associations between immune cells, inflammatory factors, serum metabolites, and hepatic cancer. However, the causal relationships between these factors and hepatic cancer remain to be established. Objective: To explore the causal relationships between immune cells, inflammatory factors, serum metabolites, and hepatic cancer. Methods: This study employed comprehensive two-sample Mendelian randomization (MR) utilizing publicly available genetic data (GWAS) to analyze causal relationships between 731 immune cell traits, 91 inflammatory factors, 1400 serum metabolites, and hepatic cancer. The primary analysis used inverse variance-weighted (IVW) MR, with additional sensitivity tests to assess the validity of causal relationships. Results: After correction for heterogeneity and horizontal pleiotropy, in exploring the causal relationships between immune cell groups and hepatic cancer, we found that Terminally Differentiated CD4−CD8− T cell %T cell was negatively associated with hepatic cancer, serving as a protective factor, while Effector Memory CD4−CD8− T cell %CD4−CD8− T cell was positively associated with hepatic cancer, acting as a risk factor. In investigating the causal relationships between inflammatory factors and hepatic cancer, C–C motif chemokine 19 levels were positively associated with hepatic cancer, representing a risk factor, while Interleukin-10 levels were negatively associated with hepatic cancer, acting as a protective factor. Regarding the causal relationships between serum metabolites and hepatic cancer, (N(1) + N(8))-acetylspermidine levels were negatively associated with hepatic cancer, serving as a protective factor, while 1-(1-enyl-palmitoyl)-GPC (p-16:0) levels were positively associated with hepatic cancer, acting as a risk factor. Conclusion: Our MR analysis indicates causal relationships between immune cells, inflammatory factors, serum metabolites, and hepatic cancer. However, further validation is needed to assess the potential of these immune cells, inflammatory factors, and serum metabolites as preventive or therapeutic targets for hepatic cancer.

Coronary heart disease (CHD) is a serious cardiovascular illness, for which an elevated uric acid (UA) level presents as a considerable risk factor. This can be treated with UA-lowering drugs such as allopurinol and benzbromarone, which can reduce UA levels by the inhibition of UA production or by promoting its excretion. Such drugs can also be beneficial to CHD in other ways, such as reducing the degree of coronary arteriosclerosis, improving myocardial blood supply and alleviating ventricular remodeling. Different UA-lowering drugs are used in different ways: allopurinol is preferred as a single agent in clinical application, but in absence of the desired response, a combination of drugs such as benzbromarone with ACE inhibitors may be used. Patients must be monitored regularly to adjust the medication regimen. Appropriate use of UA-lowering drugs has great significance for the prevention and treatment of CHD. However, the specific mechanisms of the drugs and individualized drug use need further research. This review article expounds the mechanisms of UA-lowering drugs on CHD and their clinical application strategy, thereby providing a reference for further optimization of treatment.

Study region: The Daliang Mountain region, characterized by its widespread debris flow-pone catchments, is the primary sediment source area for the upper reaches of the Yangtze River, and has experienced intensive human activity over the past half-century. Study focus: Here, we combined lake deposits with sediment source areas to quantify the sediment source and corresponding sediment yield (SY) in response to recent human impacts in a typical debris flow-prone catchment located in the Daliang Mountain region, Southwest China. The fingerprinting techniques, incorporating geochemical elements and their specific ratios, were used to characterize the sediment provenances and corresponding SY. New hydrological insight for the region: The results indicated that gully erosion was the major sediment provenance (90.10 %) in the catchment, followed by cultivated land (6.76 %) and forested land (3.14 %) for the studied period. The temporal variations of SY showed two distinctive erosional stages in response to different human activities over the past 70 years, namely 1950−2004 and 2004−2020. Greater SY values, dominated by gully erosion, occurred from 1950 to 2004, implying that both critical national activities and revegetation projects have limited effects on surface sediment generation. In contrast, gully activity and resulting SY have sharply decreased since 2004 following the implementation of check dams. These comparisons indicate a central role of the check dam in reducing gully activity. The findings have important implications for policymakers to optimize the spatial layout of future soil conservation strategies in the region.

Heat pulse (HP) method has been widely applied for measuring thermal properties, heat fluxes, and soil–water evaporation for near-surface soil layers. In topsoil layers, the presence of roots violates the underlying assumption of HP method that the soil under test is homogeneous. In this study, numerical and laboratory experiments were conducted to test the influence of root fragments on soil thermal property measurement with HP sensors. Soybean root fragments, with a water content of about 0.74 m3 m−3 and diameters ranging from 0.5 to 4 mm, were carefully repacked into soil samples that were used for HP measurements. Results showed that the effects of roots on soil thermal property measurements depended on root size, root location and directions relative to the heater probe, and the thermal property differences between soil sample and root. Roots showed negligible influence on heat pulse data when the root fragments were positioned outside the HP measurement region (more than probe space away from heater probe), or root diameters (d) were less than 1 mm, or in oven-dried soil samples. On relatively wet soils (i.e., with water content of 0.05–0.25 m3 m−3), when root fragments were located in between the heater and sensing probes (parallel to the probe planes), (1) the heat capacity (C) and thermal conductivity (λ) differences between root-free soil and root-soil mixture increased proportionally with d increased from 1 mm to 4 mm; (2) the differences in absolute values of C and λ between the root-free soil and soil-root mixture were highly dependent on soil water content. The errors in soil C and λ estimates were larger when the root fragment was parallel with than perpendicular to or inclined 45 degrees to the probe plane, and the error overall decreased with a smaller ρb and sand fraction. When the root fragments were positioned within the HP measurement region, or d were larger than 1 mm, or in relatively wet soil samples, it is important to consider root effect when interpreting HP signals.

ABSTRACT Klebsiella pneumoniae is an important opportunistic pathogen that causes a variety of infections. It is critical for bacteria to maintain metal homeostasis during infection. By using an isogenic mntP deletion mutant of K. pneumoniae strain NTUH-K2044, we found that MntP was a manganese efflux pump. Manganese increased the tolerance to oxidative stress, and oxidative stress could increase the intracellular manganese concentration. In oxidative stress, the mntP deletion mutant exhibited significantly higher sensitivity to manganese. Furthermore, iron could increase the tolerance of the mntP deletion mutant to manganese. Inductively coupled plasma mass spectrometry analysis revealed that the mntP deletion mutant had higher intracellular manganese and iron concentrations than wild-type and complementary strains. These findings suggested that iron could increase manganese tolerance in K. pneumoniae. This work elucidated the role of MntP in manganese detoxification and Mn/Fe homeostasis in K. pneumoniae.IMPORTANCEMetal homeostasis plays an important role during the process of bacterial infection. Herein, we revealed that MntP was involved in intracellular manganese homeostasis. Manganese promoted resistance to oxidative stress in Klebsiella pneumoniae. Furthermore, we demonstrated that the mntP deletion mutant exhibited significantly lower survival under manganese and H2O2 conditions. Oxidative stress increased the intracellular manganese content of the mntP deletion mutant. MntP played a critical role in maintaining intracellular manganese and iron concentrations. MntP contributed to manganese detoxification and Mn/Fe homeostasis in K. pneumoniae.

Abstract Introduction Lung adenocarcinoma (LUAD) is the most common malignant tumor in respiratory system. Methyltransferase‐like 1 (METTL1) is a driver of m7G modification in mRNA. This study aimed to demonstrate the role of METTL1 in the proliferation, invasion and Gefitinib‐resistance of LUAD. Methods Public datasets were downloaded from the Gene Expression Profiling Interactive Analysis (GEPIA) and GSE31210 datasets. Malignant tumor phenotypes were tested in vitro and in vivo through biological function assays and nude mouse with xenograft tumors. RNA immunoprecipitation assays were conducted to determine the interaction between METTL1 protein and FOXM1 mRNA. Public transcriptional database, Chromatin immunoprecipitation and luciferase report assays were conducted to detect the downstream target of a transcriptional factor FOXM1. Half maximal inhibitory concentration (IC50) was calculated to evaluate the sensitivity to Gefitinib in LUAD cells. Results The results showed that METTL1 was upregulated in LUAD, and the high expression of METTL1 was associated with unfavorable prognosis. Through the m7G‐dependent manner, METTL1 improved the RNA stability of FOXM1, leading to the up‐regulation of FOXM1. FOXM1 transcriptionally suppressed PTPN13 expression. The METTL1/FOXM1/PTPN13 axis reduced the sensitivity of LUAD cells to Gefitinib. Taken together, our data suggested that METTL1 plays oncogenic role in LUAD through inducing the m7G modification of FOXM1, therefore METTL1 probably is a new potential therapeutic target to counteract Gefitinib resistance in LUAD.

C32H48O5, orthorhombic, P212121 (no. 19), a = 7.1564(10) Å, b = 17.542(3) Å, c = 23.134(4) Å, V = 2904.2(8) Å3, Z = 4, Rgt(F) = 0.0555, wRref(F2) = 0.1343, T = 273(2) K.

Abstract The express/local mode of municipal rail transit provides passengers with multiple alternatives to achieve more efficient and superior travel, in contrast to the conventional all-stop operation mode. However, the various route choices (including direct express trains, direct local trains, or transfers) covering different passenger groups pose a significant challenge to passenger flow assignment. To understand route choice behavior, it is crucial to measure the passenger heterogeneity (variability in individual and trip attributes) in order to propose targeted solutions for operation schemes and service planning. This paper proposes a hybrid model by integrating structural equation modeling and the mixed logit model under express/local mode to estimate the impact of passenger heterogeneity on route choice. An empirical study with revealed preference and stated preference surveys carried out in Shanghai revealed how individual and trip attributes quantitatively impact the sensitivity of factors in route choice. The results show that age and trip purpose are more significant factors. Compared to the control group, the probability of express trains is reduced by 10.22% for the elderly and by 11.36% for non-commuters. Our findings can provide support for more reasonable operation schemes and more targeted services.

Objective After the exploration break through of the Well Fuye 10 in the Fuxing area of the Sichuan Basin, shale oil and gas from the Dongyuemiao section of the Jurassic Ziliujing Formation showed good exploration potential. The Dongyuemiao shale is characterized by unique shell limestone interlayers, high clay mineral content (up to 60%), various reservoir pore types, and strong vertical heterogeneity. Methods Taking the Well Xingye X as an example, combined with logging data, core observation, argon ion polishing scanning electron microscopy (SPE), and other technical means, the lithofacies characteristics and pore development characteristics of continental shale in the Dongyuemiao section were emphatically analysed. Results In this study, the principle of continental shale lithofacies division of "interlayer+mineral three-terminalelements" was established, and the continental shale of the Dongyuemiao section was vertically divided into 6 lithofacies: shell rhythmic mixed shale facies, silt shell interbedded clay shale facies, silt lithic interbedded mixed shale facies, lithic limestone facies, lithic interbedded mixed shale facies, and lithic interbedded clay shale facies. Through argon ion polishing and scanning electron microscopy (SEM), it was found that this set of continental shale mainly develops special complex organic clay pores, of which the lithic interbedded clay shale facies was the most developed type of organic pore, while the lithic limestone facies organic pores were not developed, mainly develop intragranular dissolved pores. The mercury intrusion nitrogen adsorption joint measurement results revealed that there was no significant difference in the pore size distribution of the six lithofacies shales. Conclusion Comprehensive analysis revealed that the interaction between organic matter and clay minerals during the diagenetic evolution process was the main factor influencing the pore development of continental shale in the Dongyuemiao section.

Abstract Localized surface plasmon resonance (LSPR) biosensors, which enable nanoscale confinement and manipulation of light, offer the enhanced sensitivity and electromagnetic energy localization. The integration of LSPR with the fiber-optic technology has led to the development of compact and versatile sensors for miniaturization and remote sensing. This comprehensive review explores various sensor configurations, fiber types, and geometric shapes, highlighting their benefits in terms of sensitivity, integration, and performance improvement. Fabrication techniques such as focused non-chemical bonding strategies and self-assembly of nanoparticles are discussed, providing control over nanostructure morphology and enhancing sensor performance. Bio-applications of fiber-optic LSPR (FOLSPR) sensors are detailed, specifically in biomolecular interactions and analysis of proteins, pathogens and cells, nucleic acids (DNA and RNA), and other small molecules (organic compounds and heavy metal ions). Surface modification and detection schemes are emphasized for their potential for label-free and real-time biosensing. The challenges and prospects of FOLSPR sensors are addressed, including the developments in sensitivity, fabrication techniques, and measurement reliability. Integration with emerging technologies such as nanomaterials is highlighted as a promising direction for future research. Overall, this review provides insights into the advancements and potential applications of FOLSPR sensors, paving the way for sensitive and versatile optical biosensing platforms in various fields.

Abstract Background The recurrence rate and mortality rate among postoperative pancreatic cancer patients remain elevated. This study aims to develop and validate the cancer-specific survival period for individuals who have undergone pancreatic cancer surgery. Methods We extracted eligible data from the Surveillance, Epidemiology, and End Results database and randomly divided all patients into a training cohort and an internal validation cohort. External validation was performed using a separate Chinese cohort. The nomogram was developed using significant risk factors identified through univariate and multivariate Cox proportional hazards regression. The effectiveness of the nomogram was assessed using the area under the time-dependent curve, calibration plots, and decision curve analysis. Kaplan–Meier survival curves were utilized to visualize the risk stratification of nomogram and AJCC stage. Results Seven variables were identified through univariate and multivariate analysis to construct the nomogram. The consistency index of the nomogram for predicting overall survival was 0.683 (95% CI: 0.675–0.690), 0.689 (95% CI: 0.677–0.701), and 0.823 (95% CI: 0.786–0.860). The AUC values for the 1- and 2-year time-ROC curves were 0.751 and 0.721 for the training cohort, 0.731 and 0.7554 for the internal validation cohort, and 0.901 and 0.830 for the external validation cohorts, respectively. Calibration plots demonstrated favorable consistency between the predictions of the nomogram and actual observations. Moreover, the decision curve analysis indicated the clinical utility of the nomogram, and the risk stratification of the nomogram effectively identified high-risk patients. Conclusion The nomogram guides clinicians in assessing the survival period of postoperative pancreatic cancer patients, identifying high-risk groups, and devising tailored follow-up strategies.

Background: The changes in risk scores of inflammatory markers among patients diagnosed with hepatocellular carcinoma (HCC) remain unknown. Aims: To investigate the relationship between the inflammation risk score and other contributing factors and the prognostic outcomes in patients with moderate and advanced hepatitis B virus (HBV)-related HCC. Study Design: A retrospective cohort study. Methods: A total of 174 patients with moderate and advanced HBV related HCC were recruited to investigate the impact of stratified inflammatory risk scores and other associated risk factors on disease prognosis. Based on the optimal cut-off values calculated by the Youden index, the patients were divided into high-risk and low-risk groups based on their inflammation risk scores. Results: The study found a significant difference in median survival time between the low-risk and high-risk groups based on the inflammation risk score. Furthermore, the inflammation risk score, alpha-fetoprotein levels, transarterial chemoembolization treatment, and Barcelona Clinic Liver Cancer stage were identified as independent prognostic factors. The four variables were used to construct a prognostic nomogram for HCC. Subsequent evaluations using time-dependent receiver operating characteristic analysis and calibration curve tests revealed the nomogram’s commendable discriminatory ability. As a result, the nomogram proved to be an effective tool for predicting survival at 2- to 4-years. Conclusion: The inflammation risk score has been identified as a significant prognostic factor for HBV-related HCC. The development of nomogram models has provided a practical and effective tool for determining the prognosis of patients affected by HBV-related HCC.