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Abstract Background Mesenchymal stem cells (MSCs) demonstrate a wide range of therapeutic capabilities in the treatment of inflammatory bowel disease (IBD). The intraperitoneal injection of MSCs has exhibited superior therapeutic efficacy on IBD than intravenous injection. Nevertheless, the precise in vivo distribution of MSCs and their biological consequences following intraperitoneal injection remain inadequately understood. Additional studies are required to explore the correlation between MSCs distribution and their biological effects. Methods First, the distribution of human umbilical cord MSCs (hUC-MSCs) and the numbers of Treg and Th17 cells in mesenteric lymph nodes (MLNs) were analyzed after intraperitoneal injection of hUC-MSCs. Subsequently, the investigation focused on the levels of transforming growth factor beta1 (TGF-β1), a key cytokine to the biology of both Treg and Th17 cells, in tissues of mice with colitis, particularly in MLNs. The study also delved into the impact of hUC-MSCs therapy on Treg cell counts in MLNs, as well as the consequence of TGFB1 knockdown hUC-MSCs on the differentiation of Treg cells and the treatment of IBD. Results The therapeutic effectiveness of intraperitoneally administered hUC-MSCs in the treatment of colitis was found to be significant, which was closely related to their quick migration to MLNs and secretion of TGF-β1. The abundance of hUC-MSCs in MLNs of colitis mice is much higher than that in other organs even the inflamed sites of colon. Intraperitoneal injection of hUC-MSCs led to a significant increase in the number of Treg cells and a decrease in Th17 cells especially in MLNs. Furthermore, the concentration of TGF-β1, the key cytokine for Treg differentiation, were also found to be significantly elevated in MLNs after hUC-MSCs treatment. Knockdown of TGFB1 in hUC-MSCs resulted in a noticeable reduction of Treg cells in MLNs and the eventually failure of hUC-MSCs therapy in colitis. Conclusions MLNs may be a critical site for the regulatory effect of hUC-MSCs on Treg/Th17 cells and the therapeutic effect on colitis. TGF-β1 derived from hUC-MSCs promotes local Treg differentiation in MLNs. This study will provide new ideas for the development of MSC-based therapeutic strategies in IBD patients.

Abstract Retinoblastoma is one of the most common ocular malignancies in children. Bmi-1, a member of the Polycomb group family of transcriptional repressors, is expressed in a variety of tumors. The purpose of our study was to explore the role of Bmi-1 in retinoblastoma. RT-qPCR and western blot were used for calculating the mRNA and protein levels of Bmi-1 and RKIP. MTT, Wound healing and Transwell assays were performed to measure the proliferation, migration and invasion in retinoblastoma cells. Cell apoptosis was detected by flow cytometry. The volume and mass of transplanted tumors were detected in nude mice. Bmi-1 was over expressed, and RKIP was low expressed in retinoblastoma cells. Bmi-1 promoted cell proliferation, migration and invasion and suppressed cell apoptosis of Y79 and SO-RB50 cells. Downregulation of Bmi-1 and overexpression of RKIP inhibited cell proliferation, migration and invasion, and increased cell apoptosis. The functions of Bmi-1 knockdown on retinoblastoma cells were blocked by RKIP knockdown, but promoted by RKIP. Down-regulated Bmi-1 inhibited xenograft tumor growth, and RKIP exacerbated this inhibitory effect. Bmi-1 served as a potential therapeutic target for improving the efficacy of clinical treatment in retinoblastoma. All the findings revealed the functions of Bmi-1/RKIP axis in retinoblastoma tumorigenesis.

Abstract Background The lack of professional identity can impede the transition from nursing students to qualified nurses and exacerbate the shortage of health care professionals. Personality is important to resilience-building and professional identity development in nursing students. However, the associations among personality, resilience, and professional identity are less explored. The study aims to identify latent subtypes of personality, to evaluate the mediating role of resilience between personality and professional identity in nursing students, and to provide practical guidance for educators’ subsequent interventions with nursing students’ professional identity. Methods 1397 nursing students were recruited from Be Resilient to Nursing Career (BRNC) between October 2020 and April 2022 by cluster sampling from 4 universities in China. NEO Five-Factor Inventory, 10-item Connor-Davidson Resilience Scale, and Professional Identity Questionnaire for Undergraduate Students were administered. Analyses of latent profiles and mediations were performed. Results Three latent personality types were identified: Over-sensitivity (35.4%), Ordinary (53.8%), and Flexibility (10.8%). Nursing role model was found to be a significant indicator of personality (Ordinary as ref, Over-sensitivity: OR = 0.73, 95% CI: 0.57–0.93, P = 0.010; Flexibility: OR = 1.85, 95% CI: 1.29–2.65, P = 0.001). The association between personality portraits and professional identity were significantly mediated by resilience (P

Abstract Intron retention (IR) is the most common alternative splicing event in Arabidopsis. An increasing number of studies have demonstrated the major role of IR in gene expression regulation. The impacts of IR on plant growth and development and response to environments remain underexplored. Here, we found that IR functions directly in gene expression regulation on a genome-wide scale through the detainment of intron-retained transcripts (IRTs) in the nucleus. Nuclear-retained IRTs can be kept away from translation through this mechanism. COP1-dependent light modulation of the IRTs of light signaling genes, such as PIF4, RVE1, and ABA3, contribute to seedling morphological development in response to changing light conditions. Furthermore, light-induced IR changes are under the control of the spliceosome, and in part through COP1-dependent ubiquitination and degradation of DCS1, a plant-specific spliceosomal component. Our data suggest that light regulates the activity of the spliceosome and the consequent IRT nucleus detainment to modulate photomorphogenesis through COP1.

Abstract In next‐generation wireless communications, reconfigurable intelligent surface (RIS) has emerged as a cost‐effective technique for enhancing physical layer security (PLS) in millimeter‐wave (mmWave) communications, especially under challenging scenarios with adversarial entities and obstructions. However, the primary studies for RIS incorporation in mmWave communication systems utilized static deployments, lacking adaptability and efficiency in complex environments. To address this problem, a dynamic RIS deployment design framework is introduced for PLS enhancement in mmWave systems against jamming and eavesdropping attacks. For the design, it is aimed to maximize the secrecy rate by jointly optimizing the RIS selection with the beamforming design. The resulting optimization problem is challenging to solve due to the coupling of the RIS control factor, joint beamforming design, and non‐convex constraints. To tackle these issues, an efficient multi‐RIS‐aided PLS enhancement algorithm is proposed. It transforms the objective into a series of subproblems and employs the fractional programming technique and prox‐linear block coordinate descent updating method to solve them alternatively and obtain the optimal solution. The simulations demonstrate the advantage of the dynamic deployment, which exhibits enhanced security performance with reduced complexity compared with benchmarks. Further examinations also provide insight into optimal RIS activation configurations, achieving optimal balance for securing mmWave communications against emerging threats while maintaining system efficiency.

BackgroundInternet hospitals have become an important way to improve the accessibility of medical services and promote medical equity in China. However, there is still lack of research on the behavior of medical personnel during the process of using Internet medical services, and the elements of behavior that motivate doctors to actively use or resist the use of Internet hospitals are still not fully analyzed. The study applied the Theoretical Domains Framework to examine the factors affecting the engagement of medical personnel in Internet hospitals, with the aim of guiding the design of intervention to enhance Internet hospital participation.MethodsThis study utilized qualitative analysis. Semi-structured questionnaires based on the Theoretical Domains Framework (TDF) and Capability-Opportunity-Motivation-Behavior (COM-B) model was developed and administered to 40 doctors and nurses at a Grade A tertiary hospital in Guangdong Province. Data was coded and analyzed using qualitative methods including Nvivo software.ResultsThe research displayed 19 barriers and 7 enablers for the implementation of Internet hospitals, all 14 TDF domains impacted participation with motivation cited most frequently. Despite challenges, medical personnel exhibited a generally optimistic stance towards utilization of the Internet hospital. Major barriers include the higher requirement of diagnostic ability, objective difficulties brought by online consultation to the decision-making process, limitation of time and other resources, not ideal technological and institutional environment, lack of self-efficacy and negative expectation of results in online consultation. Key enablers include patient needs and the positive impact of online care on the medical process and patient experience.DiscussionThis qualitative study identified a range of barriers and enablers to Internet hospital participation according to medical personnel, providing an conceptual framework to guide further research evaluating implementation strategies. Expanded research and targeted interventions design can help optimize participation in this evolving healthcare delivery model.

The cloud boundary network environment is characterized by a passive defense strategy, discrete defense actions, and delayed defense feedback in the face of network attacks, ignoring the influence of the external environment on defense decisions, thus resulting in poor defense effectiveness. Therefore, this paper proposes a cloud boundary network active defense model and decision method based on the reinforcement learning of intelligent agent, designs the network structure of the intelligent agent attack and defense game, and depicts the attack and defense game process of cloud boundary network; constructs the observation space and action space of reinforcement learning of intelligent agent in the non-complete information environment, and portrays the interaction process between intelligent agent and environment; establishes the reward mechanism based on the attack and defense gain, and encourage intelligent agents to learn more effective defense strategies. the designed active defense decision intelligent agent based on deep reinforcement learning can solve the problems of border dynamics, interaction lag, and control dispersion in the defense decision process of cloud boundary networks, and improve the autonomy and continuity of defense decisions.

The nanoscale confinement is of great important for the industrial applications of molecular sieve, desalination, and also essential in biological transport systems. Massive efforts have been devoted to the influence of restricted spaces on the properties of confined fluids. However, the situation of channel-wall is crucial but attracts less attention and remains unknown. To fundamentally understand the mechanism of channel-walls in nanoconfinement, we investigated the interaction between the counter-force of the liquid and interlamellar spacing of nanochannel walls by considering the effect of both spatial confinement and surface wettability. The results reveal that the nanochannel stables at only a few discrete spacing states when its confinement is within 1.4 nm. The quantized interlayer spacing is attributed to water molecules becoming laminated structures, and the stable states are corresponding to the monolayer, bilayer and trilayer water configurations, respectively. The results can potentially help to understand the characterized interlayers spacing of graphene oxide membrane in water. Our findings are hold great promise in design of ion filtration membrane and artificial water/ion channels.

Objective Circadian rhythm disruption (CRD) has been associated with inflammation and immune disorders, but its role in SLE progression is unclear. We aimed to investigate the impact of circadian rhythms on immune function and inflammation and their contribution to SLE progression to lupus nephritis (LN).Methods This study retrospectively analysed the clinical characteristics and transcriptional profiles of 373 samples using bioinformatics and machine-learning methods. A flare risk score (FRS) was established to predict overall disease progression for patients with lupus. Mendelian randomisation was used to analyse the causal relationship between CRD and SLE progression.Results Abnormalities in the circadian pathway were detected in patients with SLE, and lower enrichment levels suggested a disease state (normalised enrichment score=0.6714, p=0.0062). The disruption of circadian rhythms was found to be closely linked to lupus flares, with the FRS showing a strong ability to predict disease progression (area under the curve (AUC) of 5-year prediction: 0.76). The accuracy of disease prediction was improved by using a prognostic nomogram based on FRS (AUC=0.77). Additionally, Mendelian randomisation analysis revealed an inverse causal relationship between CRD and SLE (OR 0.6284 (95% CI 0.3630 to 1.0881), p=0.0485) and a positive causal relationship with glomerular disorders (OR 0.0337 (95% CI 1.634e-3 to 6.934e-1), p=0.0280).Conclusion Our study reveals that genetic characteristics arising from CRD can serve as biomarkers for predicting the exacerbation of SLE. This highlights the crucial impact of CRD on the progression of lupus.

Abstract The increasing demand for high‐performance devices on heat dissipation makes it approach the bottleneck even for metals with high thermal conductivities. The coating of only one layer of graphene, the heat dissipation performances of Cu, Ag, and Al can be further enhanced, e.g., with a maximum temperature reduction by ≈9% for a Cu foil is demonstrated. Molecular dynamics (MD) analysis of spectral phonon transmission reveals that low‐frequency phonons play a significant role in the thermal transport within the Cu/single‐layer graphene (SLG) system, and the high‐frequency phonons exhibit substantial mismatch. It suggests that the thermal anisotropy of graphene enables a rapid heat dispersion in the in‐plane direction and provides an effective thermal insulation in the out‐of‐plane direction. The thermal conductivity calculations demonstrate an enhanced participation of phonons in heat conduction by the graphene layer, indicating a novel heat conduction mechanism in the Cu/single‐layer graphene system. These findings highlight the positive impact of graphene on the heat conduction of metals, and they will hold crucial implications for the design and application of graphene‐based thermal devices is believed.

BackgroundIn patients with pulmonary nodules undergoing computed tomography (CT)-guided localization procedures, a range of liquid-based materials have been employed to date in an effort to guide video-assisted thoracoscopic surgery (VATS) procedures to resect target nodules. However, the relative performance of these different liquid-based localization strategies has yet to be systematically evaluated. Accordingly, this study was developed with the aim of examining the relative safety and efficacy of CT-guided indocyanine green (IG) and blue-stained glue (BSG) PN localization.MethodsConsecutive patients with PNs undergoing CT-guided localization prior to VATS from November 2021 - April 2022 were enrolled in this study. Safety and efficacy outcomes were compared between patients in which different localization materials were used.ResultsIn total, localization procedures were performed with IG for 121 patients (140 PNs), while BSG was used for localization procedures for 113 patients (153 PNs). Both of these materials achieved 100% technical success rates for localization, with no significant differences between groups with respect to the duration of localization (P = 0.074) or visual analog scale scores (P = 0.787). Pneumothorax affected 8 (6.6%) and 8 (7.1%) patients in the respective IG and BSG groups (P = 0.887), while 12 (9.9%) and 10 (8.8%) patients of these patients experienced pulmonary hemorrhage. IG was less expensive than BSG ($17.2 vs. $165). VATS sublobar resection procedure technical success rates were also 100% in both groups, with no instances of conversion to thoracotomy.ConclusionsIG and BSG both offer similarly high levels of clinical safety and efficacy when applied for preoperative CT-guided PN localization, with IG being less expensive than BSG.

Objectives: Left-sided portal hypertension (LSPH) leads to life-threatening gastrointestinal (GI) bleeding. There are no recommendations or consensus about the management of GI bleeding caused by LSPH. This systematic review and meta-analysis were conducted to evaluate the incidence of GI bleeding and the mortality of patients with LSPH receiving different therapeutic strategies. Design: A systematic review and meta-analysis were performed to determine the efficacy of different therapeutic strategies for GI bleeding caused by LSPH. Data sources and methods: All relevant studies were searched from PubMed, Embase, Web of Science, Cochrane Library, Scopus, ScienceDirect, MEDLINE, Google Scholar, CNKI, and Wanfang Data without language restriction through 15 November 2023. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated through RevMan5.3 software. (The Cochrane Collaboration, Copenhagen, Denmark). Results: Seventeen retrospective studies and one prospective study involving 624 patients were included. This systematic review and meta-analysis found that: (1) splenectomy was more effective than non-splenectomy therapeutic strategies in reducing the incidence of GI bleeding caused by LSPH (OR: 0.12; 95% CI: 0.06–0.27); (2) splenectomy was superior to partial splenic artery embolism (PSAE) (OR: 0.06; 95% CI: 0.01–0.62) or endoscopic interventions (OR: 0.04; 95% CI: 0.01–0.19) in the prevention of GI bleeding, respectively; (3) no significant difference in the mortality was observed between splenectomy and non-splenectomy therapeutic strategies (OR: 0.46; 95% CI: 0.20–1.08); and (4) patients receiving preoperative PSAE followed by splenectomy had less intraoperative bleeding and shorter operative time than those receiving splenectomy. Conclusion: This meta-analysis demonstrated that splenectomy is superior to non-splenectomy therapeutic strategies in reducing the incidence of GI bleeding from LSPH, which revealed that splenectomy should be recommended in the management of these patients. Trial registration: This study has been registered on the PROSPERO database with the registration number CRD42023483764.

Perovskite oxides with unique crystal structures and high defect tolerance are promising as atomic surface passivation layers for photoelectrodes for efficient and stable water splitting. However, controllably depositing and crystalizing perovskite-type metal oxides at the atomic level remains challenging, as they usually crystalize at higher temperatures than regular metal oxides. Here, we report a mild solution chemistry approach for the quasi-epitaxial growth of an atomic CaTiO3 perovskite layer on rutile TiO2 nanorod arrays. The high-temperature crystallization of CaTiO3 perovskite is overcome by a sequential hydrothermal conversion of the atomic amorphous TiOx layer to CaTiO3 perovskite. The atomic quasi-epitaxial CaTiO3 layer passivated TiO2 nanorod arrays exhibit more efficient interface charge transfer and high photoelectrochemical performance for water splitting. Such a mild solution-based approach for the quasi-epitaxial growth of atomic metal oxide perovskite layers could be a promising strategy for both fabricating atomic perovskite layers and improving their photoelectrochemical properties.

Background: West Nile virus is a severe zoonotic pathogen that can cause severe central nervous system symptoms in humans and horses, and is fatal for birds, chickens and other poultry. With no specific drugs or vaccines available, antibody-based therapy is a promising treatment. This study aims to develop neutralizing antibodies against West Nile virus and assess their cross-protective potential against Japanese encephalitis virus. Methods: Monoclonal antibodies against WNV and JEV were isolated by hybridoma technology. The therapeutic efficacy of these antibodies was evaluated using a mouse model, and a humanized version of the monoclonal antibody was generated for potential human application. Results: In this study, we generated eight monoclonal antibodies that exhibit neutralizing activity against WNV. Their therapeutic effects against WNV were validated both in vivo and in vitro. Among these antibodies, C9-G11-F3 also exhibited cross-protective activity against JEV. We also humanized the antibody to ensure that it could be used for WNV infection treatment in humans. Conclusion: This study highlights the importance of neutralizing antibodies as a promising approach for protection against West Nile virus infection and suggests their potential utility in the development of therapeutic interventions.

Lettuce is an annual plant of the family Asteraceae. It is most often grown as a leaf vegetable, but sometimes for its stem and seeds, and its growth status and quality are evaluated based on its morphological phenotypic traits. However, traditional measurement methods are often labor-intensive and time-consuming due to manual measurements and may result in less accuracy. In this study, we proposed a new method utilizing RGB images and Mask R-Convolutional Neural Network (CNN) for estimating lettuce critical phenotypic traits. Leveraging publicly available datasets, we employed an improved Mask R-CNN model to perform a phenotypic analysis of lettuce images. This allowed us to estimate five phenotypic traits simultaneously, which include fresh weight, dry weight, plant height, canopy diameter, and leaf area. The enhanced Mask R-CNN model involved two key aspects: (1) replacing the backbone network from ResNet to RepVGG to enhance computational efficiency and performance; (2) adding phenotypic branches and constructing a multi-task regression model to achieve end-to-end estimation of lettuce phenotypic traits. Experimental results demonstrated that the present method achieved high accuracy and stable results in lettuce image segmentation, detection, and phenotypic estimation tasks, with APs for detection and segmentation being 0.8684 and 0.8803, respectively. Additionally, the R2 values for the five phenotypic traits are 0.96, 0.9596, 0.9329, 0.9136, and 0.9592, with corresponding mean absolute percentage errors (MAPEs) of 0.1072, 0.1522, 0.0757, 0.0548, and 0.0899, respectively. This study presents a novel technical advancement based on digital knowledge for phenotypic analysis and evaluation of lettuce quality, which could lay the foundation for artificial intelligence expiation in fresh vegetable production.

Background: In the era characterized by global environmental and climatic changes, understanding the effects of PM2.5 components and heatwaves on schizophrenia (SCZ) is essential for implementing environmental interventions at the population level. However, research in this area remains limited, which highlights the need for further research and effort. We aim to assess the association between exposure to PM2.5 components and hospitalizations for SCZ under different heatwave characteristics. Methods: We conducted a 16 municipalities-wide, individual exposure-based, time-stratified, case-crossover study from January 1, 2017, to December 31, 2020, encompassing 160736 hospitalizations in Anhui Province, China. Daily concentrations of PM2.5 components were obtained from the Tracking Air Pollution in China dataset. Conditional logistic regression models were used to investigate the association between PM2.5 components and hospitalizations. Additionally, restricted cubic spline models were used to identify protective thresholds of residential environment in response to environmental and climate change. Results: Our findings indicate a positive correlation between PM2.5 and its components and hospitalizations. Significantly, a 1 μg/m3 increase in black carbon (BC) was associated with the highest risk, at 1.58% (95%CI: 0.95–2.25). Exposure to heatwaves synergistically enhanced the impact of PM2.5 components on hospitalization risks, and the interaction varied with the intensity and duration of heatwaves. Under the 99th percentile heatwave events, the impact of PM2.5 and its components on hospitalizations was most pronounced, which were PM2.5 (2–4d: 4.59%, 5.09%, and 5.09%), sulfate (2–4d: 21.73%, 23.23%, and 25.25%), nitrate (2–4d: 17.51%, 16.93%, and 20.31%), ammonium (2–4d: 27.49%, 31.03%, and 32.41%), organic matter (2–4d: 32.07%, 25.42%, and 24.48%), and BC (2–4d: 259.36%, 288.21%, and 152.52%), respectively. Encouragingly, a protective effect was observed when green and blue spaces comprised more than 17.6% of the residential environment. Discussion: PM2.5 components and heatwave exposure were positively associated with an increased risk of hospitalizations, although green and blue spaces provided a mitigating effect.

Summary: Functions of the SKP1-CUL1-F box (SCF) ubiquitin E3 ligases are essential in plants. The F box proteins (FBPs) are substrate receptors that recruit substrates and assemble an active SCF complex, but the regulatory mechanism underlying the FBPs binding to CUL1 to activate the SCF cycle is not fully understood. We show that Arabidopsis csn1-10 is defective in SCFEBF1-mediated PIF3 degradation during de-etiolation, due to impaired association of EBF1 with CUL1 in csn1-10. EBF1 preferentially associates with un-neddylated CUL1 that is deficient in csn1-10 and the EBF1-CUL1 binding is rescued by the neddylation inhibitor MLN4924. Furthermore, we identify a subset of FBPs with impaired binding to CUL1 in csn1-10, indicating their assembly to form SCF complexes may depend on COP9 signalosome (CSN)-mediated deneddylation of CUL1. This study reports that a key role of CSN-mediated CULLIN deneddylation is to gate the binding of the FBP-substrate module to CUL1, thus initiating the SCF cycle of substrate ubiquitination.

Aurora kinase A (Aurora-A), a serine/threonine kinase, plays a pivotal role in various cellular processes, including mitotic entry, centrosome maturation and spindle formation. Overexpression or gene-amplification/mutation of Aurora-A kinase occurs in different types of cancer, including lung cancer, colorectal cancer, and breast cancer. Alteration of Aurora-A impacts multiple cancer hallmarks, especially, immortalization, energy metabolism, immune escape and cell death resistance which are involved in cancer progression and resistance. This review highlights the most recent advances in the oncogenic roles and related multiple cancer hallmarks of Aurora-A kinase-driving cancer therapy resistance, including chemoresistance (taxanes, cisplatin, cyclophosphamide), targeted therapy resistance (osimertinib, imatinib, sorafenib, etc.), endocrine therapy resistance (tamoxifen, fulvestrant) and radioresistance. Specifically, the mechanisms of Aurora-A kinase promote acquired resistance through modulating DNA damage repair, feedback activation bypass pathways, resistance to apoptosis, necroptosis and autophagy, metastasis, and stemness. Noticeably, our review also summarizes the promising synthetic lethality strategy for Aurora-A inhibitors in RB1, ARID1A and MYC gene mutation tumors, and potential synergistic strategy for mTOR, PAK1, MDM2, MEK inhibitors or PD-L1 antibodies combined with targeting Aurora-A kinase. In addition, we discuss the design and development of the novel class of Aurora-A inhibitors in precision medicine for cancer treatment.

Abstract This paper, taking the middle-aged and elderly parents in rural families of China as the subject, studies the impact of children’s education on parents’ dietary nutrient intake. After analyzing the data in China Health and Nutrition Survey (CHNS) 2011, this study discovers that China’s rural children’s higher educational level exerts a significant positive impact on the improvement of parents’ food consumption, nutrient intake and diet quality. This indicates that the improvement of rural education can be an effective approach to increase dietary nutrient intake of China’s rural population. The policy implication of this study is to further develop rural basic education, consolidate the coverage of compulsory education, and incorporate nutrition education into national education system.

The transcription and replication of the Newcastle disease virus (NDV) strictly rely on the viral ribonucleoprotein (RNP) complex, which is composed of viral NP, P, L and RNA. However, it is not known whether other viral non-RNP proteins participate in this process for viral self-regulation. In this study, we used a minigenome (MG) system to identify the regulatory role of the viral non-RNP proteins V, M, W, F and HN. Among them, V significantly reduced MG-encoded reporter activity compared with the other proteins and inhibited the synthesis of viral mRNA and cRNA. Further, V interacted with NP. A mutation in residue W195 of V diminished V–NP interaction and inhibited inclusion body (IB) formation in NP-P-L-cotransfected cells. Furthermore, a reverse-genetics system for the highly virulent strain F48E9 was established. The mutant rF48E9-VW195R increased viral replication and apparently enhanced IB formation. In vivo experiments demonstrated that rF48E9-VW195R decreased virulence and retarded time of death. Overall, the results indicate that the V–NP interaction of the W195 mutant V decreased, which regulated viral RNA synthesis, IB formation, viral replication and pathogenicity. This study provides insight into the self-regulation of non-RNP proteins in paramyxoviruses.

Path hopping serves as an active defense mechanism in network security, yet it encounters challenges like a restricted path switching space, the recurrent use of similar paths and vital nodes, a singular triggering mechanism for path switching, and fixed hopping intervals. This paper introduces an active defense method employing multiple constraints and strategies for path hopping. A depth-first search (DFS) traversal is utilized to compute all possible paths between nodes, thereby broadening the path switching space while simplifying path generation complexity. Subsequently, constraints are imposed on residual bandwidth, selection periods, path similitude, and critical nodes to reduce the likelihood of reusing similar paths and crucial nodes. Moreover, two path switching strategies are formulated based on the weights of residual bandwidth and critical nodes, along with the calculation of path switching periods. This facilitates adaptive switching of path hopping paths and intervals, contingent on the network’s residual bandwidth threshold, in response to diverse attack scenarios. Simulation outcomes illustrate that this method, while maintaining normal communication performance, expands the path switching space effectively, safeguards against eavesdropping and link-flooding attacks, enhances path switching diversity and unpredictability, and fortifies the network’s resilience against malicious attacks.

A porous 3D cross-linked conductive network pierced by multi-wall carbon nanotubes (MWCNTs) was successfully designed from zeolitic imidazolate framework-8 (ZIF-8). Zn@NPC@MWCNTs composites were tailored by the facile regulating the mass ratios and thermal annealing treatment. Due to the combination of less eddy current loss and dielectric loss together with multiple reflection attenuation caused by a unique structure. With a 10 wt% filler loading, the Zn@NPC@MWCNTs composites carbonized at 800 °C show two high reflection loss (RL) values with different thicknesses. An RL value is −53.18 dB with 4.09 mm thickness in the C-Band (4–8 GHz), and a minimum RL can reach −74.83 dB (10.8 GHz) with a matching thickness of 2.749 mm. The effective absorption bandwidth is 4 GHz (from 8 to 12 GHz, RL ≤ −10 dB), which just covers the full X-band. Low cost and easy preparation can also provide advantages to develop MOF-based materials as effective EMW absorbents.

Researchers have begun to investigate the relationship between eye movement characteristics of gaze patterns and cognitive abilities, and have attempted to use eye-tracking technology as a new method to evaluate cognitive abilities. Traditional eye movement analysis methods typically separate spatial and temporal information of eye movements, mostly analyze averaged data, and consider individual differences as noise. In addition, current eye movement studies on gaze patterns mostly involve adults, while research on infants and toddlers is limited with small sample sizes and narrow age ranges. It is still unknown whether the conclusions drawn from adult-based research can be applied to children. Consequently, eye movement research on gaze patterns in children is necessary. To address the concerns stated above, this study used the Hidden Markov machine learning method to model gaze patterns of 330 children aged 1–6 years while observing faces freely, and analyzed characteristics of eye movement gaze patterns. Additionally, we analyzed the correlation between gaze patterns of 31 toddlers aged 1–3 years and 37 preschoolers aged 4–6 years, and the different dimensions of cognitive abilities. The findings indicated that children exhibited holistic and analytic gaze patterns while observing different faces freely. More children adopted a holistic gaze pattern, and there were age-specific gaze pattern characteristics and regularities. Gaze patterns of toddlers may be correlated with their adaptive abilities and gaze patterns of preschoolers may be correlated with their visual space abilities. Specifically, toddlers aged 1–3 years showed a moderate negative correlation between the H-A scale and the adaptive dimension, while preschoolers aged 4–6 years showed a low negative correlation between the H-A scale and the visual space dimension. This study may provide new insights into the characteristics of children’s eye-movement gaze patterns during face observation, and potentially offer objective evidence for future research aimed at promoting the use of eye-tracking technology in the assessment of toddlers’ adaptive abilities and preschoolers’ visual space abilities in the field of face perception.

Background: Epidemiological studies show that outdoor artificial light at night (ALAN) is linked to metabolic hazards, but its association with metabolic syndrome (MetS) remains unclear. We aimed to investigate the association of outdoor ALAN with MetS in middle-aged and elderly Chinese. Methods: From 2017–2020, we conducted a cross-sectional study in a total of 109,452 participants living in ten cities of eastern China. MetS was defined by fasting blood glucose (FG), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), blood pressure (BP), and waist circumference (WC). In 2021, we followed up 4395 participants without MetS at the baseline. Each participant's five-year average exposure to outdoor ALAN, as well as their exposure to green space type, were measured through matching to their address. Generalized linear models were used to assess the associations of outdoor ALAN with MetS. Stratified analyses were performed by sex, age, region, physical activity, and exposure to green space. Results: In the cross-sectional study, compared to the first quantile (Q1) of outdoor ALAN exposure, the odds ratios (ORs) of MetS were 1.156 [95 % confidence interval (CI): 1.111–1.203] and 1.073 (95 %CI: 1.021–1.128) respectively in the third and fourth quantiles (Q3, Q4) of outdoor ALAN exposure. The follow-up study found that, compared to the first quantile (Q1) of outdoor ALAN exposure, the OR of MetS in Q4 of ALAN exposure was 1.204 (95 %CI: 1.019–1.422). Adverse associations of ALAN with MetS components, including high FG, high TG, and obesity, were also found. Greater associations of ALAN with MetS were found in males, the elderly, urban residents, those with low frequency of physical activity, and those living in areas with low levels of grass cover and tree cover. Conclusions: Outdoor ALAN exposure is associated with an increased MetS risk, especially in males, the elderly, urban residents, those lacking physical activity, and those living in lower levels of grass cover and tree cover.

Background and aimsEndoscopic ultrasonography (EUS) is commonly utilized in the diagnosis of pancreatic tumors, although as this modality relies primarily on the practitioner’s visual judgment, it is prone to result in a missed diagnosis or misdiagnosis due to inexperience, fatigue, or distraction. Deep learning (DL) techniques, which can be used to automatically extract detailed imaging features from images, have been increasingly beneficial in the field of medical image-based assisted diagnosis. The present systematic review included a meta-analysis aimed at evaluating the accuracy of DL-assisted EUS for the diagnosis of pancreatic tumors diagnosis.MethodsWe performed a comprehensive search for all studies relevant to EUS and DL in the following four databases, from their inception through February 2023: PubMed, Embase, Web of Science, and the Cochrane Library. Target studies were strictly screened based on specific inclusion and exclusion criteria, after which we performed a meta-analysis using Stata 16.0 to assess the diagnostic ability of DL and compare it with that of EUS practitioners. Any sources of heterogeneity were explored using subgroup and meta-regression analyses.ResultsA total of 10 studies, involving 3,529 patients and 34,773 training images, were included in the present meta-analysis. The pooled sensitivity was 93% (95% confidence interval [CI], 87–96%), the pooled specificity was 95% (95% CI, 89–98%), and the area under the summary receiver operating characteristic curve (AUC) was 0.98 (95% CI, 0.96–0.99).ConclusionDL-assisted EUS has a high accuracy and clinical applicability for diagnosing pancreatic tumors.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023391853, identifier CRD42023391853.

This study presents a method to develop a series of unique deliverability smart models for underground natural gas storage (UNGS) in different types of target formations. The natural gas supply loop is defined by periodic mismatches between demand and supply. Efficient and faster approaches for forecasting UNGS deliverability may not only assist stakeholders but also the competitive natural gas industry. Due to this fact, this article suggests a series of robust deliverability estimation models for 387 UNGS sites in depleted fields, aquifers, and salt domes based on rigorous machine learning (ML) techniques. To this end, the potential of three ML algorithms, including Gaussian Process Regression (GPR), Least Squares Support Vector Machine (LSSVM), and Extra Tree (ET), is employed. To assess and compare the proposed models, statistical parameters including coefficient of determination (R2), root mean square error (RMSE), mean absolute error (MAE), and standard deviation (SD) were employed. Accordingly, in the case of depleted fields, the GPR, LSSVM, and ET paradigms show overall R2, RMSE, and MAE of 0.999999998, 4.75E−06, 0.00021, and 0.00021. For salt domes, the GPR, LSSVM, and ET models indicate overall R2, RMSE, and MAE of 0.987, 0.0046, and 0.11. Finally, for aquifers, the GPR, LSSVM, and ET algorithms represent overall R2, RMSE, and MAE of 0.999999997, 7.1094E−06, and 0.0002102. The prediction performance reveals that the GPR model is superior to the LSSVM and ET models. This study found that the proposed intelligent models could be utilized as a template for fast estimating the deliverability of UNGS in depleted fields, aquifers, and salt domes with high accuracy. In the end, the outcomes of this study contribute to a deeper understanding of the critical role of machine learning in resolving the difficulty of forecasting the UNSG on cleaner production and sustainable development strategies.

Abstract Tacrolimus (Tac) is a common immunosuppressant that used in organ transplantation. However, its therapeutic index is narrow, and it is prone to adverse side effects, along with an increased risk of toxicity, namely, cardio-, nephro-, hepato-, and neurotoxicity. Prior metabolomic investigations involving Tac-driven toxicity primarily focused on changes in individual organs. However, extensive research on multiple matrices is uncommon. Hence, in this research, the authors systemically evaluated Tac-mediated toxicity in major organs, namely, serum, brain, heart, liver, lung, kidney, and intestines, using gas chromatography−mass spectrometry (GC-MS). The authors also employed multivariate analyses, including orthogonal projections to the latent structure (OPLS) and t-test, to screen 8 serum metabolites, namely, D-proline, glycerol, D-fructose, D-glucitol, sulfurous acid, 1-monopalmitin (MG (16:0/0:0/0:0)), glycerol monostearate (MG (0:0/18:0/0:0)), and cholesterol. Metabolic changes within the brain involved alterations in the levels of butanamide, tartronic acid, aminomalonic acid, scyllo-inositol, dihydromorphine, myo-inositol, and 11-octadecenoic acid. Within the heart, the acetone and D-fructose metabolites were altered. In the liver, D-glucitol, L-sorbose, palmitic acid, myo-inositol, and uridine were altered. In the lung, L-lactic acid, L-5-oxoproline, L-threonine, phosphoric acid, phosphorylethanolamine, D-allose, and cholesterol were altered. Lastly, in the kidney, L-valine and D-glucose were altered. Our findings will provide a systematic evaluation of the metabolic alterations in target organs within a Tac-driven toxicity mouse model.

Objectives: The aim of this research was to establish standard norms for posterior smile-related characteristics including posterior smile line (PSL), the most posterior teeth displayed, buccal corridor ratio (BCR), and buccal corridor symmetry (BCS) and investigate its aesthetic contributions to smile attractiveness in a Chinese population. Materials and methods: From digitally recorded dynamic smile videos of young Chinese participants, 188 standardised full-smile images were captured and then aesthetically evaluated by 22 laypersons using a visual analog scale (VAS). Four smile-related variables in the posterior region were analysed. VAS data were compared between subgroups to test the influence of these variables on smile aesthetics with significance level of P < .05. Results: The VAS scores of participants with high PSL were significantly lower than those with average or low PSL (P < .01), especially when they display average or low anterior smile line (P < .05). Smiles with the second premolar displayed obtained the highest VAS amongst the 3 subgroups (P < .05). No significant differences were found between the VAS scores of BCR and BCS (P > .05). Conclusions: Maxillary posterior gingiva and teeth displayed influence smile attractiveness evaluated by laypersons, which should be given attention when treating patients with compromised aesthetics, especially those displaying average or low anterior smile lines.

Abstract Leaf area index (LAI) is a fundamental indicator of crop growth status, timely and non-destructive estimation of LAI is of significant importance for precision agriculture. In this study, a multi-rotor UAV platform equipped with CMOS image sensors was used to capture maize canopy information, simultaneously, a total of 264 ground‐measured LAI data were collected during a 2-year field experiment. Linear regression (LR), backpropagation neural network (BPNN), and random forest (RF) algorithms were used to establish LAI estimation models, and their performances were evaluated through 500 repetitions of random sub-sampling, training, and testing. The results showed that RGB-based VIs derived from UAV digital images were strongly related to LAI, and the grain-filling stage (GS) of maize was identified as the optimal period for LAI estimation. The RF model performed best at both whole period and individual growth stages, with the highest R2 (0.71–0.88) and the lowest RMSE (0.12–0.25) on test datasets, followed by the BPNN model and LR models. In addition, a smaller 5–95% interval range of R2 and RMSE was observed in the RF model, which indicated that the RF model has good generalization ability and is able to produce reliable estimation results.

Abstract Background Direct localization of small and deep pulmonary nodules before thoracoscopic surgery using the hookwire or methylene blue techniques has been recently attempted for better surgical outcomes. In this study, we compare the outcomes of the above two techniques. Methods Two hundred and nineteen patients undergoing 135 hookwire and 151 methylene blue techniques in our University Hospital between July 2020 and January 2022 were compared for localization and hospitalization durations, and the complication risk. Other confounders included patients’ age, gender, localization position, nodules location, count, diameter, and depth. Results After adjustment of all predictors, the methylene blue technique was associated with a significant 0.6-min (parameter estimate (PE) = −0.568, p value = 0.0173) and an 0.7-day shorter localization and hospitalization time (PE = −0.713, p value =

AIM: To explore the etiology classification and clinical characteristics of infants with moderate-severe visual impairment aged 0-2 years old, and preliminarily formulate a set of process for grass-roots health-care institutions to carry out the screening and management of children visual impairment.METHODS: There were 245 cases of children aged 0-2 years with moderate-severe visual impairment who were admitted to the Children Eye Care Specialist Clinic in Nanjing Maternal and Child Health Hospital from January 2009 to December 2020 were retrospectively analyzed. A complete profile of visual development was established, including age, sex, medical history, vision, eye position and movement, anterior segment examination, fundus examination, refractive examination under cycloplegia with 1% atropine ophthalmic gel, if necessary, some special eye examinations such as fundus photography, eye A/B ultrasound and visual electrophysiology were received.RESULTS: The average visit age of 245 cases of infants was 1.82±0.79 years, including refraction error of 128 cases(52.2%), among them, 100 cases(40.8%)were high refraction error; 79 cases(32.2%)were eye diseases, most of which were congenital cataract(33 cases); and 38 cases(15.5%)were cerebral visual impairment(CVI)(15.5%).CONCLUSION: It is necessary to proceed classified managements according to the etiology and clinical characteristics of infant visual impairment to find early and diagnose and treat multidisciplinary,including drawing up screening plans for remediable eye diseases, carrying out necessary refractive correction and training children to use residual visual function.

Abstract Significant land greening since the 1980s has been detected through satellite observation, forest inventory, and Earth system modeling. However, whether and to what extent global land greening enhances ecosystem carbon stock remains uncertain. Here, using 40 global models, we first detected a positive correlation between the terrestrial ecosystem carbon stock and leaf area index (LAI) over time. Then, we diagnose the source of uncertainty of simulated the sensitivities of ecosystem carbon stock to LAI based on a traceability analysis. We found that the sensitivity of gross primary productivity (GPP) to LAI is the largest contributor to the model uncertainty in more than 60% of the vegetated grids. Using the ensemble of four long‐term global data sets of GPP and three satellite LAI products from 1982 to 2014, we provided an emergent constraint on the ecosystem carbon stock increase as 0.75 ± 0.46 kg C m−2 per unit LAI over global land areas. Furthermore, the biome‐based results reveal that the tropical forest regions have the highest inter‐model variation and model bias. Overall, this study identifies the uncertainty source and provides constrained estimates of the greening effect on ecosystem carbon stock at the global scale.

Background and aimsThe diagnosis of chronic atrophic gastritis (CAG) under normal white-light endoscopy depends on the endoscopist's experience and is not ideal. Artificial intelligence (AI) is increasingly used to diagnose diseases with good results. This review aimed to evaluate the accuracy of AI-assisted diagnosis of CAG through a meta-analysis.MethodsWe conducted a comprehensive literature search of four databases: PubMed, Embase, Web of Science, and the Cochrane Library. Studies published by November 21, 2022, on AI diagnosis CAG with endoscopic images or videos were included. We assessed the diagnostic performance of AI using meta-analysis, explored the sources of heterogeneity through subgroup analysis and meta-regression, and compared the accuracy of AI and endoscopists in diagnosing CAG.ResultsEight studies that included a total of 25,216 patients of interest, 84,678 image training set images, and 10,937 test set images/videos were included. The results of the meta-analysis showed that the sensitivity of AI in identifying CAG was 94% (95% confidence interval [CI]: 0.88–0.97, I2 = 96.2%), the specificity was 96% (95% CI: 0.88–0.98, I2 = 98.04%), and the area under the summary receiver operating characteristic curve was 0.98 (95% CI: 0.96–0.99). The accuracy of AI in diagnosing CAG was significantly higher than that of endoscopists.ConclusionsAI-assisted diagnosis of CAG in endoscopy has high accuracy and clinical diagnostic value.Systematic review registrationhttp://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42023391853.

BackgroundChronic atrophic gastritis (CAG) is a precancerous condition. It is not easy to detect CAG in endoscopy. Improving the detection rate of CAG under endoscopy is essential to reduce or interrupt the occurrence of gastric cancer. This study aimed to construct a deep learning (DL) model for CAG recognition based on endoscopic images to improve the CAG detection rate during endoscopy.MethodsWe collected 10,961 endoscopic images and 118 video clips from 4,050 patients. For model training and testing, we divided them into two groups based on the pathological results: CAG and chronic non-atrophic gastritis (CNAG). We compared the performance of four state-of-the-art (SOTA) DL networks for CAG recognition and selected one of them for further improvement. The improved network was called GAM-EfficientNet. Finally, we compared GAM-EfficientNet with three endoscopists and analyzed the decision basis of the network in the form of heatmaps.ResultsAfter fine-tuning and transfer learning, the sensitivity, specificity, and accuracy of GAM-EfficientNet reached 93%, 94%, and 93.5% in the external test set and 96.23%, 89.23%, and 92.37% in the video test set, respectively, which were higher than those of the three endoscopists.ConclusionsThe CAG recognition model based on deep learning has high sensitivity and accuracy, and its performance is higher than that of endoscopists.

Abstract Data-driven based deep learing has become a key research direction in the field of artificial intelligence. Abundant training data is a guarantee for building efficient and accurate models. However, due to the privacy protection policy, research institutions are often limited to obtain a large number of training data, which would lead to a lack of training sets circumstance. In this paper, a mixed-type data generation model based on generative adversarial networks is proposed to synthesize fake data that have the same distribution with the real data, so as to supplement the real data and increase the number of available samples. The model first pre-trains the autoencoder which maps given dataset into a low-dimensional continuous space. Then, the generator constructed in the low-dimension space is obtained by training it adversarially with discriminator constructed in the original space. Since the constructed discriminator not only consider the loss of the continuous attributes but also the labeled attributes, the generator nets formed by the generator and the decoder can effectively learn the intrinsic distribution of the mixed data. We evaluate the proposed method both in the independent distribution of the attribute and in the relationship of the attributes, and the experiment results show that the proposed generate method has a better performance in preserve the intrinsic distribution compared with other generation algorithms based on deep learning.

Artemisia annua is the main natural source of artemisinin production. In A. annua, extended drought stress severely reduces its biomass and artemisinin production while short-term water-withholding or abscisic acid (ABA) treatment can increase artemisinin biosynthesis. ABA-responsive transcription factor AabZIP1 and JA signaling AaMYC2 have been shown in separate studies to promote artemisinin production by targeting several artemisinin biosynthesis genes. Here, we found AabZIP1 promote the expression of multiple artemisinin biosynthesis genes including AaDBR2 and AaALDH1, which AabZIP1 does not directly activate. Subsequently, it was found that AabZIP1 up-regulates AaMYC2 expression through direct binding to its promoter, and that AaMYC2 binds to the promoter of AaALDH1 to activate its transcription. In addition, AabZIP1 directly transactivates wax biosynthesis genes AaCER1 and AaCYP86A1. The biosynthesis of artemisinin and cuticular wax and the tolerance of drought stress were significantly increased by AabZIP1 overexpression, whereas they were significantly decreased in RNAi-AabZIP1 plants. Collectively, we have uncovered the AabZIP1-AaMYC2 transcriptional module as a point of cross-talk between ABA and JA signaling in artemisinin biosynthesis, which may have general implications. We have also identified AabZIP1 as a promising candidate gene for the development of A. annua plants with high artemisinin content and drought tolerance in metabolic engineering breeding.

Objective. To investigate the clinical characteristics and pathogenic genetic mutations of a Chinese family with anterior segment mesenchymal dysgenesis and congenital posterior polar cataract. Methods. Through family investigation, the family members were examined via slit lamp anterior segment imaging and screened for eye and other diseases by eye B-ultrasound. Genetic test was performed on the blood samples of the fourth family generation (23 people) via whole exome sequencing (trio-WES) and Sanger sequencing. Results. Among the 36 members in four family generations, there were 11 living cases with different degrees of ocular abnormalities, such as cataracts, leukoplakia, and small cornea. All patients who received the genetic test had the heterozygous frameshift mutation c.640_656dup (p.G220Pfs∗95) on exon 4 of the PITX3 gene. This mutation was cosegregated with the clinical phenotypes in the family and thus might be one of the genetic factors that cause the corresponding ocular abnormalities in this family. Conclusion. The congenital posterior polar cataract with or without anterior interstitial dysplasia (ASMD) of this family was inherited in an autosomal dominant manner, and the frameshift mutation (c.640_656dup) in the PITX3 gene was the cause of ocular abnormalities observed in this family. This study is of great significance for guiding prenatal diagnosis and disease treatment.

ObjectivesThis study aims to quantitatively evaluate the femoral–tibial contact pressure on the knee under certain malrotaional degrees.MethodsFemoral–tibial contact pressure was carried out on 14 fixed rotational knee models under 200/400/600 N vertical load using ultra-low-pressure sensitive film technology, rotation angles including neutral position (0°, anatomically reduced), 5°, 10°, and 15° internally and externally. Data were collected and analyzed with SPSS software.ResultsThere are significant statistical differences between the medial contact pressure among rotational deformities (including neutral position) (P 0.05). In the comparison of medial to lateral contact pressures, no statistically significant differences were found in neutral and 5° internal rotation under 200/400 N, neutral, 5° internal rotation, and 15° external rotation under 600 N. In contrast, medial contact pressures were higher than lateral at other angles (P

Summary: Carbon capture, utilization and storage (CCUS) technology is critical to global net-zero emission goal, whereas actual deployment is well below expectations. This study constructs a comprehensive framework, integrating nonlinear dynamic optimization, real option and technology learning curve, to explore optimal CCUS deployment for China’s coal-fired power plant toward carbon neutrality. The commercialization application will occur in 2030–2035, with the optimal potential ranging between 248.54 GW and 564.90 GW. East China has the greatest potential, reaching 196.85 GW, followed by North China with the potential of 116.29 GW. The cost of second-generation capture technology will decrease from 219 CNY/ton CO2 to 165 CNY/ton CO2 during 2030–2031.The annual corporate expenditure (R&D investment and capture cost) and government expenditure (subsidy) will peak at 23.92 billion CNY in 2035 and 63.71 billion CNY in 2044, respectively. The financial burden can be lessened by carbon trading market and third-party intervention in the later period.

Graphene is a two-dimensional material that can be folded into diverse and yet interesting nanostructures like macro-scale paper origami. Folding of graphene not only makes different morphological configurations but also modifies their mechanical and thermal properties. Inspired by paper origami, herein we studied systemically the effects of creases, where sp2 to sp3 bond transformation occurs, on the thermal properties of graphene origami using molecular dynamics (MD) simulations. Our MD simulation results show that tensile strain reduces (not increases) the interfacial thermal resistance owing to the presence of the crease. This unusual phenomenon is explained by the micro-heat flux migration and stress distribution. Our findings on the graphene origami enable the design of the next-generation thermal management devices and flexible electronics with tuneable properties.

Abstract The fusion (F) and haemagglutinin-neuraminidase (HN) proteins of Newcastle disease virus (NDV) are viral entry proteins and are recognized as the major virulence determinants. Previously, a lentogenic NDV virus (CE16) was derived from a mesogenic strain (CI10) through sequential passages in chick embryos. Whole-genome sequence analysis revealed that the two homologous strains shared the same F protein but differed in HN with two amino acid (aa) substitutions (A215G and T430A). To elucidate the molecular reasons for virulence attenuation, two original plasmids (HN-CI10 and HN-CE16) and two single-point mutants (G215A and A430T) reverse-mutated from HN-CE16 were constructed to analyse the known biological functions of HN. The results showed that the A430T substitution significantly weakened the haemadsorption (HAd) activity, increased the neuraminidase (NA) activity, improved the fusion-promoting activity, and enhanced the cleavage-promoting activity of HN-CE16. However, G215A failed to induce obvious functional changes. Therefore, the aa residue HN430 may play a key role in determining virulence. To test this hypothesis, further studies on A430T were conducted through reverse genetics using an infectious cDNA clone. At the viral level, the A430T-mutated virus showed dramatic promotion of viral plaque formation, propagation, and pathogenicity in vitro and in vivo. This study demonstrates a new virulence site associated with HN protein functions, viral propagation, and pathogenicity. All these findings could lay a foundation for illuminating the molecular mechanism of NDV virulence.

Agricultural soils originating from carbonate rocks within karst regions exhibit inherent high concentrations of potentially toxic elements (PTEs) due to geogenic processes. However, the influencing factors of the elevated levels of PTEs in the naturally contaminated karst regions remain inadequately comprehended. This research investigates the chemical compositions of 278 soils derived from carbonate rocks. Descriptive statistics, stepwise multiple regression, and the random forest (RF) method were applied to screen the significant factors that affect the distribution, migration, and enrichment of the PTEs in soils. Cadmium (Cd) and arsenic (As) are the most highly contaminated PTEs in the soils of the study area, and the average contents of Cd and As in soils are 11.5 and 2.92 times the national soil background value, respectively. The pollution risk ranking of PTEs is Cd > As > Cr > Zn > Pb > Cu > Ni > Hg, using the proportion exceeding the risk screening thresholds of agricultural land as the standard. Soil Fe2O3 and Mn contents, soil pH and total organic carbon (TOC) values, and weathering intensity (characterized using the chemical index of alternation, CIA) are the most important factors influencing the PTE levels in agricultural soils.

Colorectal cancer (CRC) is a heterogeneous disease with a myriad of alterations at the cellular and molecular levels. Kristen rat sarcoma (KRAS) mutations occur in up to 40% of CRCs and serve as both a prognostic and predictive biomarker. Oncogenic mutations in the KRAS protein affect cellular proliferation and survival, leading to tumorigenesis through RAS/MAPK pathways. Until recently, only indirect targeting of the pathway had been investigated. There are now several KRAS allele-specific inhibitors in late-phase clinical trials, and many newer agents and targeting strategies undergoing preclinical and early-phase clinical testing. The adequate treatment of KRAS-mutated CRC will inevitably involve combination therapies due to the existence of robust adaptive resistance mechanisms in these tumors. In this article, we review the most recent understanding and findings related to targeting KRAS mutations in CRC, mechanisms of resistance to KRAS inhibitors, as well as evolving treatment strategies for KRAS-mutated CRC patients.

Phosphate is one of the essential mineral nutrients. Phosphate transporter genes (PHTs) play an important role in Pi acquisition and homeostasis in tomato plants. However, basic biological information on PHT genes and their responses of symbiosis with arbuscular mycorrhizal in the genome remains largely unknown. We analyzed the physiological changes and PHT gene expression in tomatoes (Micro-Tom) inoculated with arbuscular mycorrhizal (AM) fungi (Funneliformis mosseae) under different phosphate conditions (P1: 0 µM, P2: 25 µM, and P3: 200 µM Pi). Twenty-three PHT genes were identified in the tomato genomics database. Protein sequence alignment further divided the 23 PHT genes into three groups, with similar classifications of exons and introns. Good colonization of plants was observed under low phosphate conditions (25 µM Pi), and Pi stress and AM fungi significantly affected P and N accumulation and root morphological plasticity. Moreover, gene expression data showed that genes in the SlPHT1 (SlPT3, SlPT4, and SlPT5) gene family were upregulated by Funneliformis mosseae under all conditions, which indicated that these gene levels were significantly increased with AM fungi inoculation. None of the analyzed SlPHT genes in the SlPH2, SlPHT3, SlPHT4, and SlPHO gene families were changed at any Pi concentration. Our results indicate that inoculation with AM fungi mainly altered the expression of the PHT1 gene family. These results will lay a foundation for better understanding the molecular mechanisms of inorganic phosphate transport under AM fungi inoculation.

The efficiency and stability of typical three-dimensional (3D) MAPbI3 perovskite-based solar cells are highly restricted, due to the weak interaction between methylammonium (MA+) and [PbI6]4-octahedra in the 3D structure, which can cause the ion migration and the related defects. Here, we found that the in situ-grown perovskitoid TEAPbI3 layer on 3D MAPbI3 can inhibit the MA+ migration in a polar solvent, thus enhancing the thermal and moisture stability of perovskite films. The crystal structure and orientation of TEAPbI3 are reported for the first time by single crystal and synchrotron radiation analysis. The ultra-thin perovskitoid layer can reduce the trap states and accelerate photo-carrier diffusion in perovskite solar cells, as confirmed by ultra-fast spectroscopy. The power conversion efficiency of TEAPbI3-MAPbI3 based solar cells increases from 18.87% to 21.79% with enhanced stability. This work suggests that passivation and stabilization by in situ-grown perovskitoid can be a promising strategy for efficient and stable perovskite solar cells.

Abstract Epidemiological studies have demonstrated that the genetic factors partly influence the development of same-sex sexual behavior, but most genetic studies have focused on people of primarily European ancestry, potentially missing important biological insights. Here, we performed a two-stage genome-wide association study (GWAS) with a total sample of 1478 homosexual males and 3313 heterosexual males in Han Chinese populations and identified two genetic loci (rs17320865, Xq27.3, FMR1NB, P meta = 8.36 × 10−8, OR = 1.29; rs7259428, 19q12, ZNF536, P meta = 7.58 × 10−8, OR = 0.75) showing consistent association with male sexual orientation. A fixed-effect meta-analysis including individuals of Han Chinese (n = 4791) and European ancestries (n = 408,995) revealed 3 genome-wide significant loci of same-sex sexual behavior (rs9677294, 2p22.1, SLC8A1, P meta = 1.95 × 10−8; rs2414487, 15q21.3, LOC145783, P meta = 4.53 × 10−9; rs2106525, 7q31.1, MDFIC, P meta = 6.24 × 10−9). These findings may provide new insights into the genetic basis of male sexual orientation from a wider population scope. Furthermore, we defined the average ZNF536-immunoreactivity (ZNF536-ir) concentration in the suprachiasmatic nucleus (SCN) as lower in homosexual individuals than in heterosexual individuals (0.011 ± 0.001 vs 0.021 ± 0.004, P = 0.013) in a postmortem study. In addition, compared with heterosexuals, the percentage of ZNF536 stained area in the SCN was also smaller in the homosexuals (0.075 ± 0.040 vs 0.137 ± 0.103, P = 0.043). More homosexual preference was observed in FMR1NB-knockout mice and we also found significant differences in the expression of serotonin, dopamine, and inflammation pathways that were reported to be related to sexual orientation when comparing CRISPR-mediated FMR1NB knockout mice to matched wild-type target C57 male mice.

ObjectivesIn this study, the effect of WeChat use on the subjective health of older adults was examined.MethodsUsing 2018 China Health and Retirement Longitudinal Study (CHARLS) survey data, we attempted to rule out potential endogeneity bias by employing instrumental variable regression to estimate the effects of WeChat use on the health of older individuals. Mobile phone price was chosen as the instrumental variable, and the health of older adults was measured from two aspects: self-rated health and the Center for Epidemiological Studies of Depression Scale (CES-D10).ResultsWeChat use has a significant positive impact on the subjective health of older adults and can significantly improve their self-rated health and mental health status. WeChat use has significant positive effects on the subjective health of both older men and women, but relatively younger older adults obtain more health benefits from WeChat use.ConclusionThe virtual social participation prompted by WeChat use affects the health of older adults. This finding provides a reference for promoting the active integration of older adults into digital life.

Background: Diabetic retinopathy (DR) is a common problem in the diabetic patients due to the high blood glucose level. DR affects more number of diabetic patients worldwide with irreversible vision loss. Objective: The current investigation was focused to reveal the therapeutic actions of nimbolide against the streptozotocin (STZ)-provoked DR in rats through inhibition of TLR4/NF-κB pathway. Methodology: DR was provoked to the rats through administering a single dose of STZ (60 mg/kg) intraperitoneally. The DR rats were then supplemented with the 50 mg/kg of nimbolide for 60 days. The bodyweight and blood glucose level was measured using standard methods. The lipid profiles (cholesterol, TG, LDL, and HDL), inflammatory markers, and antioxidants level was detected using respective kits. The level of MCP-1, VEGF, and MMP-9 was quantified using kits. The morphometric analysis of retinal tissues were done. The mRNA expressions of target genes were studied using RT-PCR assay. Results: Nimbolide treatment effective decreased the food intake and blood glucose, and improved the bodyweight of STZ-provoked animals. The levels of pro-inflammatory mediators, cholesterol, TG, LDL, and HDL, MCP-1, VEGF, and MMP-9 was remarkably suppressed by the nimbolide treatment. Nimbolide also improved the antioxidants, retinal thickness and cell numbers. The TLR4/NF-κB pathway was appreciably inhibited by the nimbolide. Conclusion: Overall, our findings demonstrated that the nimbolide attenuated the STZ-provoked DR in rats through inhibiting the TLR4/NF-κB pathway.