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Abstract Background Respiratory diseases impose an immense health burden worldwide. Epidemiological studies have revealed extensive disparities in the incidence and severity of respiratory tract infections between men and women. It has been hypothesized that there might also be a nasal microbiome axis contributing to the observed sex disparities. Results Here, we study the nasal microbiome of healthy young adults in the largest cohort to date with 1593 individuals, using shotgun metagenomic sequencing. We compile the most comprehensive reference catalog for the nasal bacterial community containing 4197 metagenome-assembled genomes and integrate the mycobiome, to provide a valuable resource and a more holistic perspective for the understudied human nasal microbiome. We systematically evaluate sex differences and reveal extensive sex-specific features in both taxonomic and functional levels in the nasal microbiome. Through network analyses, we capture markedly higher ecological stability and antagonistic potentials in the female nasal microbiome compared to the male’s. The analysis of the keystone bacteria reveals that the sex-dependent evolutionary characteristics might have contributed to these differences. Conclusions In summary, we construct the most comprehensive catalog of metagenome-assembled-genomes for the nasal bacterial community to provide a valuable resource for the understudied human nasal microbiome. On top of that, comparative analysis in relative abundance and microbial co-occurrence networks identify extensive sex differences in the respiratory tract community, which may help to further our understanding of the observed sex disparities in the respiratory diseases.

Abstract The first-order antisymmetric (A1) mode lamb wave resonator (LWR) based on Z-cut LiNbO3 thin films has attracted significant attention and is widely believed to be a candidate for next-generation reconfigurable filters with high frequency and large bandwidth (BW). However, it is challenging for traditional interdigitated electrodes (IDTs) based LWR filters to meet the requirement of a clean frequency spectrum response and enough out-of-band (OoB) rejection. To solve the problem, we propose LWRs with checker-shaped IDTs for the design of filters that meet the Wi-Fi 6E standard. By taking advantage of checker-shaped IDTs with unparalleled boundaries, the fabricated 6-GHz resonators successfully suppress higher-order A1 spurious modes, demonstrating a spurious-free impedance response and a high figure-of-merit (FOM) up to 104. Based on the demonstrated checker-shaped electrode design, the filter features a center frequency (f 0 ) of more than 6 GHz, a 3 dB BW exceeding 620 MHz, and an excellent OoB rejection >25 dB, consistent with the acoustic-electric-electromagnetic (EM) multi-physics simulations. Furthermore, through the capacitance-inductance matching network technology, the filter’s voltage standing wave ratio (VSWR) is successfully reduced below 2, showing an excellent 50 Ω impedance matching. This study lays a foundation for ultra-high-frequency and ultra-wideband filters for the Wi-Fi 6/6E application.

Clavulina possesses important ecological and economic value and has attracted extensive attention from mycologists. Macrofungal diversity is high in China, but Clavulina species have not been thoroughly studied. In this study, based on morphological evidence and phylogenetic analyses of the nucleotide sequences of three loci (nrITS, nrLSU, and rpb2), three new species of Clavulina from North China were identified. Morphologically, Clavulina chengdeensis is characterized by its white to dirty white basidiomata with somewhat pale orange tips and somewhat wrinkled hymenium. Clavulina griseoviolacea is characterized by its gray to dark grayish violet basidiomata, with a sometimes-white stipe base, monopodial or irregularly polychotomous toward branch apices. Clavulina pallida is characterized by its white to pale cream white basidiomata with somewhat orange tips. Phylogenetically, the three new species form three independent branches with high support values in the phylogenetic tree.

Abstract The mismanagement of waste is jeopardizing urban sustainability. Although polycentric waste governance (PWG) has been introduced, characterizing the PWG remains challenging. This paper employs game theory to illustrate polycentricity by investigating the equilibrium state from the stakeholders’ perspective. Shanghai, Tokyo, and Hong Kong are selected as target cities for comparative analysis. The findings reveal the heterogeneous characteristics in three megacities’ PWG—the collaboration by principal stakeholders (formal recyclers, informal recyclers, households) in Shanghai, the exclusion of informal recyclers in Tokyo, and the limited contribution provided by the formal recyclers in Hong Kong. The divergent PWG characteristics can be attributed to variations in governance patterns, socioeconomic factors, and policy formulation. Regarding urban sustainability, Tokyo and Shanghai’s PWG contribute to the circular economy’s expansion, while Hong Kong’ potential, in this regard, is undervalued. Despite Tokyo’s improved social recognition to practitioners, this PWG mode, primarily driven by formal recyclers and households, presents limited inclusion of low-income groups. Additionally, it is crucial for the authorities in Shanghai and Hong Kong to acknowledge the potential pollution of informal recyclers’ non-environmental behavior. This paper offers a valuable model for characterizing and analyzing PWG across different cities, facilitating knowledge aggregation and the implementation of PWG practice.

Abstract BUB1 mitotic checkpoint serine/threonine kinase B (BUB1b) has been unequivocally identified as an oncogene in various cancers. However, the potential mechanism by which BUB1b orchestrates the progression of lung adenocarcinoma (LUAD) remains unclear. Here we found that both the transcript and protein levels of BUB1b were dramatically upregulated in tumor tissues and contributed to the dismal prognosis of LUAD patients. Moreover, gain- and loss-of-function assays, conducted both in vitro and in vivo, confirmed that BUB1b enhanced the viability of LUAD cells. Mechanistically, BUB1b forms a complex with OTUD3 and NRF2 and stabilizes the downstream NRF2 signaling pathway to facilitate insensitivity to ferroptosis and chemotherapy. In BALB/c nude mice bearing subcutaneous tumors that overexpress BUB1b, a combined strategy of ML385 targeting and chemotherapy achieved synergistic effects, inhibiting tumor growth and obviously improving survival. Taken together our study uncovered the underlying mechanism by which BUB1b promotes the progression of LUAD and proposed a novel strategy to enhance the efficacy of chemotherapy.

Abstract Background Subarachnoid hemorrhage (SAH) is a severe stroke subtype that lacks effective treatment. Exosomes derived from human dental pulp stem cells (DPSCs) are a promising acellular therapeutic strategy for neurological diseases. However, the therapeutic effects of DPSC-derived exosomes (DPSC-Exos) on SAH remain unknown. In this study, we investigated the therapeutic effects and mechanisms of action of DPSC-Exos in SAH. Materials and methods SAH was established using 120 male Sprague-Dawley rats. One hour after SAH induction, DPSC-Exos were administered via tail vein injection. To investigate the effect of DPSC-Exos, SAH grading, short-term and long-term neurobehavioral assessments, brain water content, western blot (WB), immunofluorescence staining, Nissl staining, and HE staining were performed. The role of miR-197-3p/FOXO3 in regulating pyroptosis was demonstrated through miRNA sequencing, bioinformatics analysis, and rescue experiments. The SAH model in vitro was established by stimulating BV2 cells with hemoglobin (Hb) and the underlying mechanism of DPSC-Exos was investigated through WB and Hoechst/PI staining. Results The expressions of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) were increased after SAH. DPSC-Exos alleviated brain edema and neuroinflammation by inhibiting the expression of FOXO3 and reducing NLRP3 inflammasome activation, leading to improved neurobehavioral functions at 24 h after SAH. In vitro, the expression of the NLRP3 inflammasome components (NLRP3 and caspase1-p20), GSDMD-N, and IL-18 was inhibited in BV2 cells pretreated with DPSC-Exos. Importantly, DPSC-Exos overexpressing miR-197-3p had a more obvious protective effect than those from NC-transfected DPSCs, while those from DPSCs transfected with the miR-197-3p inhibitor had a weaker protective effect. Functional studies indicated that miR-197-3p bound to the 3ʹ-untranslated region of FOXO3, inhibiting its transcription. Furthermore, the overexpression of FOXO3 reversed the protective effects of miR-197-3p. Conclusions DPSC-Exos inhibited activation of the NLRP3 inflammasome and related cytokine release via the miR-197-3p/FOXO3 pathway, alleviated neuroinflammation, and inhibited microglial pyroptosis. These findings suggest that using DPSC-Exos is a promising therapeutic strategy for SAH. Graphical Abstract

Abstract Tumour metabolic reprogramming is pivotal for tumour survival and proliferation. Investigating potential molecular mechanisms within the heterogeneous and clinically aggressive triple-negative breast cancer (TNBC) subtype is essential to identifying novel therapeutic targets. Accordingly, we investigated the role of branched-chain α-keto acid dehydrogenase kinase (BCKDK) in promoting tumorigenesis in TNBC. We analysed The Cancer Genome Atlas dataset and immunohistochemically stained surgical specimens to investigate BCKDK expression and its prognostic implications in TNBC. The effects of BCKDK on tumorigenesis were assessed using cell viability, colony formation, apoptosis, and cell cycle assays, and subsequently validated in vivo. Metabolomic screening was performed via isotope tracer studies. The downstream target was confirmed using mass spectrometry and a co-immunoprecipitation experiment coupled with immunofluorescence analysis. Upstream transcription factors were also examined using chromatin immunoprecipitation and luciferase assays. BCKDK was upregulated in TNBC tumour tissues and associated with poor prognosis. BCKDK depletion led to reduced cell proliferation both in vitro and vivo. MYC-associated zinc finger protein (MAZ) was confirmed as the major transcription factor directly regulating BCKDK expression in TNBC. Mechanistically, BCKDK interacted with glucose-6-phosphate dehydrogenase (G6PD), leading to increased flux in the pentose phosphate pathway for macromolecule synthesis and detoxification of reactive oxygen species. Forced expression of G6PD rescued the growth defect in BCKDK-deficient cells. Notably, the small-molecule inhibitor of BCKDK, 3,6-dichlorobenzo(b)thiophene-2-carboxylic acid, exhibited anti-tumour effects in a patient-derived tumour xenograft model. Our findings hold significant promise for developing targeted therapies aimed at disrupting the MAZ/BCKDK/G6PD signalling pathway, offering potential advancements in treating TNBC through metabolic reprogramming.

Abstract Molecular weight (MW) of organics was one of the important factors influencing membrane fouling propensity. This study identified critical foulants of reverse osmosis (RO) membranes in reclaimed water by MW fractionation. MW > 10 kDa component was identified as the critical fouling contributor (CFC) in secondary effluent (SE), which accounted for only 13 ± 5% of dissolved organic carbon (DOC) but contributed to 86 ± 11% of flux decline. Throughout 12-month monitoring, SE and MW > 10 kDa component showed a similar fouling variation tendency: apparently higher fouling potential in winter and lower in summer, while MW 10 kDa component and glean valuable insights into RO fouling mechanisms of reclaimed water in practical application.

Abstract Objective This study aimed to investigate the critical role of MDSCs in CRC immune suppression, focusing on the CSF1R and JAK/STAT3 signaling axis. Additionally, it assessed the therapeutic efficacy of LNCs@CSF1R siRNA and anti-PD-1 in combination. Methods Single-cell transcriptome sequencing data from CRC and adjacent normal tissues identified MDSC-related differentially expressed genes. RNA-seq analysis comprehensively profiled MDSC gene expression in murine CRC tumors. LNCs@CSF1R siRNA nanocarriers effectively targeted and inhibited CSF1R. Flow cytometry quantified changes in MDSC surface markers post-CSF1R inhibition. RNA-seq and pathway enrichment analyses revealed the impact of CSF1R on MDSC metabolism and signaling. The effect of CSF1R inhibition on the JAK/STAT3 signaling axis was validated using Colivelin and metabolic assessments. Glucose and fatty acid uptake were measured via fluorescence-based flow cytometry. The efficacy of LNCs@CSF1R siRNA and anti-PD-1, alone and in combination, was evaluated in a murine CRC model with extensive tumor section analyses. Results CSF1R played a significant role in MDSC-mediated immune suppression. LNCs@CSF1R siRNA nanocarriers effectively targeted MDSCs and inhibited CSF1R. CSF1R regulated MDSC fatty acid metabolism and immune suppression through the JAK/STAT3 signaling axis. Inhibition of CSF1R reduced STAT3 activation and target gene expression, which was rescued by Colivelin. Combined treatment with LNCs@CSF1R siRNA and anti-PD-1 significantly slowed tumor growth and reduced MDSC abundance within CRC tumors. Conclusion CSF1R via the JAK/STAT3 axis critically regulates MDSCs, particularly in fatty acid metabolism and immune suppression. Combined therapy with LNCs@CSF1R siRNA and anti-PD-1 enhances therapeutic efficacy in a murine CRC model, providing a strong foundation for future clinical applications.

Microbial phospholipase D (PLD) showed a more competent potential for phospholipids production due to its higher catalytic activity and broader substrate specificity. In this study, the PLD from Acinetobacter sp. DUT-2 (ADPLD) was used as the research object. Firstly, bioinformatics was used to examine the protein sequence characteristics. Then, the recombinant plasmid was generated and heterologously expressed in Escherichia coli. The enzyme protein was purified further, and the substrate selectivity of ADPLD to phosphatidylcholine (PC) with various acyl chains was investigated. Finally, the substrate recognition mechanism of ADPLD was investigated using molecular docking and molecular dynamics simulation. Multiple sequence alignment and phylogenetic tree analysis of ADPLD and other microbial-derived PLDs revealed that the sequence similarity between ADPLD and Streptomyces-derived PLDs was less than 30%, and there was only one conserved HKD motif, indicating that the catalytic mechanism of ADPLD might differ from the reaction mechanism in traditional cognition, which required two HKD motifs to complete the PLD catalytic process. ADPLD was mostly produced as a soluble protein, and a relatively uniform protein could be purified using Ni2+ affinity chromatography at a low concentration of 50 mmol/L imidazole. When soybean PC was utilized as a substrate, the specific activity of ADPLD was about 4.09 U/mg. ADPLD showed relatively high activity in neutralizing short-chain PC (C6~C14), with a specific activity of 13.2 U/mg for 8:0/8:0-PC, which was higher than that of other PC substrates with long acyl chains. The activity of ADPLD on PC reduced dramatically when the acyl chain length of PC grew from C14 to C16. Molecular dynamics simulation and molecular docking experiments revealed that the ADPLD amino acid residues Thr205, Pro209, Phe293, Ala324, Lys329, and Phe453 might form hydrophobic interactions with PC. Arg383 and Gly326 could form hydrogen bonds with PC when the distance between Arg383 (N), Gly326 (N), and PC (P) was

Abstract In virtual reality, due to factors such as light sources and surface materials of objects, the details of the scene exhibit extremely complex changes, making it difficult to capture environmental modeling relationships and reducing the quality of scene details. Therefore, a VR scene detail enhancement method based on deep reinforcement learning algorithm is proposed. Using the Total Variation (TV) denoising algorithm to decompose the VR scene, the VR scene is divided into two parts: noisy and non-noisy, to complete the noise removal. Based on the denoised VR scene, a Hessian matrix is constructed to extract VR scene features using the SURF algorithm. Using deep reinforcement learning algorithms to train and process the extracted VR visual features, introducing meta-learning within the gradient descent method, updating the parameters of the deep reinforcement learning Expose framework, and accelerating the training speed of the deep reinforcement learning Expose framework. By designing L1 loss, structural similarity loss, content perception loss, and sharpness loss functions, the enhancement effect of VR visual details can be improved. The experimental results show that the proposed method enhances the gray-scale values and distribution of VR scene detail images to be higher and more uniform. When the magnification is different, the studied method can effectively enhance the signal-to-noise ratio of VR scenes. Therefore, it indicates that the VR scene detail enhancement effect of the method proposed in this article is good.

Abstract Background The association of hepatitis B virus (HBV) DNA levels and liver fibrosis in chronic hepatitis B (CHB) patients with immune-tolerant phase remains unclear. We explored the association between liver fibrosis and HBV DNA levels in HBeAg-positive CHB patients with normal alanine transaminase (ALT) with relatively high HBV DNA. Methods Six hundred and twenty-two HBeAg-positive CHB patients with normal ALT were included. Patients were divided into three categories: low (6 log10 IU/mL ≤ HBV DNA

The zinc finger protein CTCF is ubiquitously expressed and is integral to the regulation of chromatin architecture through its interaction with cohesin. Conversely, CTCFL expression is predominantly restricted to the adult male testis but is aberrantly expressed in certain cancers. Despite their distinct expression patterns, the cooperative and competitive mechanisms by which CTCF and CTCFL regulate target gene expression in spermatocytes and cancer cells remain inadequately understood. In this review, we comprehensively examine the literature on the divergent amino acid sequences, target sites, expression profiles and functions of CTCF and CTCFL in normal tissues and cancers. We further elucidate the mechanisms by which CTCFL competitively or cooperatively binds to CTCF target sites during spermatogenesis and carcinogenesis to modulate chromatin architecture. We mainly focus on the role of CTCFL in testicular and cancer development, highlighting its interaction with CTCF at CTCF binding sites to regulate target genes. In the testis, CTCF and CTCFL cooperate to regulate the expression of testis-specific genes, essential for proper germ cell progression. In cancers, CTCFL overexpression competes with CTCF for DNA binding, leading to aberrant gene expression, a more relaxed chromatin state, and altered chromatin loops. By uncovering the roles of CTCF and CTCFL in spermatogenesis and carcinogenesis, we can better understand the implications of aberrant CTCFL expression in altering chromatin loops and its contribution to disease pathogenesis.

Background: Inequities in stroke outcomes have existed for decades, and the COVID-19 pandemic amplified these inequities. Objectives: This study examined the association between social vulnerability and all-cause mortality among Medicare beneficiaries hospitalized with acute ischemic stroke (AIS) during COVID-19 pandemic periods. Methods: We analyzed data on Medicare fee-for-service beneficiaries aged ≥65 years hospitalized with AIS between April 1, 2020, and December 31, 2021 (followed until December 31, 2023) merged with county-level data from the 2020 Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry’s Social Vulnerability Index (SVI). We used a Cox proportional hazard model to examine the association between SVI quartile and all-cause mortality. Results: Among 176,123 Medicare fee-for-service beneficiaries with AIS, 29.9% resided in the most vulnerable counties (SVI quartile 4), while 14.9% resided in counties with least social vulnerability (SVI quartile 1). AIS Medicare beneficiaries living in the most vulnerable counties had the highest proportions of adults aged 65 to 74 years, non-Hispanic Black or Hispanic, severe stroke at admission, a history of COVID-19, and more prevalent comorbidities. Compared to those living in least vulnerable counties, AIS Medicare beneficiaries living in most vulnerable counties had significantly higher all-cause mortality (adjusted HR: 1.11, 95% CI: 1.08-1.14). The pattern of association was largely consistent in subgroup analyses by age group, sex, and race and ethnicity. Conclusions: Higher social vulnerability levels were associated with increased all-cause mortality among AIS Medicare beneficiaries. To improve outcomes and address disparities, it may be important to focus efforts toward addressing social vulnerability.

Regarding the issue of low granulation qualification rates during the granulation coating of red clover seeds, this study theoretically analyzed the force conditions of seeds and powder particles under the action of liquid to obtain the main factors affecting seed coating quality. During the seed granulation coating process, an intermittent powder supply method combined with continuous liquid supply was utilized to control the ratio of powder to liquid. Using the granulation qualification rate as the evaluation index, single-factor experiments were conducted to investigate the effects of coating pan fill ratio, single powder supply amount, powder supply interval, and liquid supply amount on the quality of red clover seed granulation coating. Based on the results of the single-factor experiments, orthogonal experiments were conducted, revealing that the interaction of factors would influence the experimental results. To further optimize the quality of seed granulation coating, the mechanisms of powder and liquid in the adhesion process on granulation coating were explored. Orthogonal experiments were conducted on the process parameters of the granulation coating machine, and the GA-BP model was employed for optimization and solution. The optimal process parameter combination obtained was a coating pan fill ratio of 33.78 %, a single powder supply amount of 5.17 g, a powder supply interval of 7.7 s, and a liquid supply amount of 0.42 mL/s. Under this optimal parameter combination, granulation coating experiments with red clover seeds were performed, and the seed granulation coating quality was relatively high, with a granulation qualification rate of 97.7 %. The research results can provide a reference for optimization experiments on coating irregular seeds.

Summary: Antibodies represent a primary mediator of protection against respiratory viruses. Serum neutralizing antibodies (NAbs) are often considered a primary correlate of protection. However, detailed antibody profiles including characterization of antibody functions in different anatomic compartments are poorly understood. Here we show that antibody correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge are different in systemic versus mucosal compartments in rhesus macaques. In serum, NAbs were the strongest correlate of protection and linked to spike-specific binding antibodies and other extra-NAb functions that create a larger protective network. In bronchiolar lavage (BAL), antibody-dependent cellular phagocytosis (ADCP) proved the strongest correlate of protection rather than NAbs. Within BAL, ADCP was linked to mucosal spike-specific immunoglobulin (Ig)G, IgA/secretory IgA, and Fcγ-receptor binding antibodies. Our results support a model in which antibodies with different functions mediate protection at different anatomic sites.

Introduction We aim to assess the association between smoking behavior and intracranial aneurysms (IAs) and the effect of smoking cessation medications on IAs at the genetic level. Methods Causal effects of four phenotypes: 1) age at initiation of regular smoking, 2) cigarettes smoked per day, 3) smoking cessation, and 4) smoking initiation on IAs, were analyzed using two-sample inverse-variance weighted Mendelian randomization analyses. The effects of genes interacting with the smoking cessation medications were analyzed using cis-expression quantitative trait loci genetic instruments on IAs using summary statistics-based Mendelian randomization analyses. Colocalization analyses were then used to test whether the genes shared causal variants with IAs. The role of confounding phenotypes as potential causative mechanisms of IAs at these gene loci was tested. Results Cigarettes smoked per day (OR=2.89; 95% CI:1.85–4.51) and smoking initiation on IAs (OR=4.64; 95% CI: 2.64–8.15) were significantly associated with IA risk. However, age at initiation of regular smoking (OR=0.54; 95% CI: 0.10–2.8) and smoking cessation (OR=6.80; 95% CI: 0.01–4812) had no overall effect on IAs. Of 88 genes that interacted with smoking cessation medications, two had a causal effect on IA risk. Genetic variants affecting HYKK levels showed strong evidence of colocalization with IA risk. Higher HYKK levels in the blood were associated with a lower IA risk. Gene target analyses revealed that cigarettes/ day could be a main mediator of HYKK’s effect on IA risk. Conclusions This study provides evidence supporting that smoking initiation on IAs and cigarettes/day may increase IA risk. Increased HYKK gene expression may reduce IA risk. This can be explained by the increased number of cigarettes consumed daily. HYKK could also reduce IA risk due to the positive effect of continuous abstinence and varenicline therapy on smoking cessation.

Abstract The incidence of young-onset colorectal cancer (yCRC) has been increasing in recent decades, but little is known about the gut microbiome of these patients. Most studies have focused on old-onset CRC (oCRC), and it remains unclear whether CRC signatures derived from old patients are valid in young patients. To address this, we assembled the largest yCRC gut metagenomes to date from two independent cohorts and found that the CRC microbiome had limited association with age across adulthood. Differential analysis revealed that well-known CRC-associated taxa, such as Clostridium symbiosum, Peptostreptococcus stomatis, Parvimonas micra and Hungatella hathewayi were significantly enriched (false discovery rate

Abstract Aims Hepatitis B virus (HBV) is an enveloped DNA virus belonging to the Hepadnaviridae family. It is a significant contributor to the prevalence of chronic liver disease on a global scale. Mutations in HBV DNA can affect the diagnosis, treatment, and prognosis of patients with chronic hepatitis B. Although numerous studies on HBV DNA mutations have been conducted, few bibliometric studies have been performed to date. This study aimed to analyze changes in scientific output to gain a better understanding of the current research status and identify potential new research directions in the field of HBV DNA mutation. Methods Relevant studies published between 2003 and 2022 were retrieved from the Web of Science Core Collection database. CiteSpace version 6.1.R6 was used to construct network maps to evaluate collaborations among countries, institutions, authors, journals, and keywords. Results In total, 1508 publications over the past 20 years were obtained, mainly from China, the United States, and Japan. The major research institutions in China included the University of Hong Kong, Fudan University, and Peking University. Lai Ching Lung was the most productive author, whereas Anna Suk‐Fong Lok was the most frequently co‐cited author. The keyword “HBsAg” was the strongest burst keyword in recent years, indicating possible future study trends. Conclusions This bibliometric analysis intuitively revealed the overall research status of HBV DNA mutations, providing valuable information for researchers, funding agencies, and policymakers to explore the current research status, research hotspots, and new directions for future research.

Abstract While phonon anharmonicity affects lattice thermal conductivity intrinsically and is difficult to be modified, controllable lattice defects routinely function only by scattering phonons extrinsically. Here, through a comprehensive study of crystal structure and lattice dynamics of Zintl-type Sr(Cu,Ag,Zn)Sb thermoelectric compounds using neutron scattering techniques and theoretical simulations, we show that the role of vacancies in suppressing lattice thermal conductivity could extend beyond defect scattering. The vacancies in Sr2ZnSb2 significantly enhance lattice anharmonicity, causing a giant softening and broadening of the entire phonon spectrum and, together with defect scattering, leading to a ~ 86% decrease in the maximum lattice thermal conductivity compared to SrCuSb. We show that this huge lattice change arises from charge density reconstruction, which undermines both interlayer and intralayer atomic bonding strength in the hierarchical structure. These microscopic insights demonstrate a promise of artificially tailoring phonon anharmonicity through lattice defect engineering to manipulate lattice thermal conductivity in the design of energy conversion materials.

The increasing amount of massive data generated by commercial spacecraft in orbit puts forward higher and higher requirements for the stability, reliability, and computing power of computer systems for commercial aerospace data center. Data center computer systems are gradually transforming from X86 architecture and IP network model to a platform model with cloud computing and software-defined network (SDN) technology. This article proposes a new network architecture based on a unicast/multicast protocol for data interaction between the SDN and IP network. There are three main contributions of this article. The first is that the architecture proposed in this article aims to reduce end-to-end transmission latency and packet loss. The second is to improve the flexibility of system configuration and precise control when the SND controller state changes. The third is to verify the feasibility of deploying network architecture in a real data center environment.

ABSTRACTSerum hepatitis B surface antigen (HBsAg) level < 100 IU/ml and undetectable hepatitis B virus (HBV) DNA have been recently proposed as an alternate endpoint of “partial cure” in chronic hepatitis B (CHB). We investigated clinical outcomes of hepatitis B e antigen (HBeAg)-negative CHB patients with HBsAg

Abstract Combinatorial optimization (CO) has a broad range of applications in various fields, including operations research, computer science, and artificial intelligence. However, many of these problems are classified as nondeterministic polynomial‐time (NP)‐complete or NP‐hard problems, which are known for their computational complexity and cannot be solved in polynomial time on traditional digital computers. To address this challenge, continuous‐time Ising machine solvers have been developed, utilizing different physical principles to map CO problems to ground state finding. However, most Ising machine prototypes operate at speeds comparable to digital hardware and rely on binarizing node states, resulting in increased system complexity and further limiting operating speed. To tackle these issues, a novel device‐algorithm co‐design method is proposed for fast sub‐optimal solution finding with low hardware complexity. On the device side, a piezoelectric lithium niobate (LiNbO3) microelectromechanical system (MEMS) oscillator network‐based Ising machine without second‐harmonic injection locking (SHIL) is devised to solve Max‐cut and graph coloring problems. The LiNbO3 oscillator operates at speeds greater than 9 GHz, making it one of the fastest oscillatory Ising machines. System‐wise, an innovative grouping method is used that achieves a performance guarantee of 0.878 for Max‐cut and 0.658 for graph coloring problems, which is comparable to Ising machines that utilize binarization.

Objectives: Compromised hepatic fatty acid oxidation (FAO) has been observed in human MASH patients and animal models of MASLD/MASH. It remains poorly understood how and when the hepatic FAO pathway is suppressed during the progression of MASLD towards MASH. Hepatic ChREBP⍺ is a classical lipogenic transcription factor that responds to the intake of dietary sugars. Methods: We examined its role in regulating hepatocyte fatty acid oxidation (FAO) and the impact of hepatic Chrebpa deficiency on sensitivity to diet-induced MASLD/MASH in mice. Results: We discovered that hepatocyte ChREBP⍺ is both necessary and sufficient to maintain FAO in a cell-autonomous manner independently of its DNA-binding activity. Supplementation of synthetic PPAR⍺/δ agonist is sufficient to restore FAO in Chrebp−/− primary mouse hepatocytes. Hepatic ChREBP⍺ was decreased in mouse models of diet-induced MAFSLD/MASH and in patients with MASH. Hepatocyte-specific Chrebp⍺ knockout impaired FAO, aggravated liver steatosis and inflammation, leading to early-onset fibrosis in response to diet-induced MASH. Conversely, liver overexpression of ChREBP⍺-WT or its non-lipogenic mutant enhanced FAO, reduced lipid deposition, and alleviated liver injury, inflammation, and fibrosis. RNA-seq analysis identified the CYP450 epoxygenase (CYP2C50) pathway of arachidonic acid metabolism as a novel target of ChREBP⍺. Over-expression of CYP2C50 partially restores hepatic FAO in primary hepatocytes with Chrebp⍺ deficiency and attenuates preexisting MASH in the livers of hepatocyte-specific Chrebp⍺-deleted mice. Conclusions: Our findings support the protective role of hepatocyte ChREBPa against diet-induced MASLD/MASH in mouse models in part via promoting CYP2C50-driven FAO.

Abstract Dipterocarpoideae species form the emergent layer of Asian rainforests. They are the indicator species for Asian rainforest distribution, but they are severely threatened. Here, to understand their adaptation and population decline, we assemble high-quality genomes of seven Dipterocarpoideae species including two autotetraploid species. We estimate the divergence time between Dipterocarpoideae and Malvaceae and within Dipterocarpoideae to be 108.2 (97.8‒118.2) and 88.4 (77.7‒102.9) million years ago, and we identify a whole genome duplication event preceding dipterocarp lineage diversification. We find several genes that showed a signature of selection, likely associated with the adaptation to Asian rainforests. By resequencing of two endangered species, we detect an expansion of effective population size after the last glacial period and a recent sharp decline coinciding with the history of local human activities. Our findings contribute to understanding the diversification and adaptation of dipterocarps and highlight anthropogenic disturbances as a major factor in their endangered status.

Abstract Background Triosephosphate isomerase 1 (TPI1), as a widely involved glycolytic enzyme, plays a significant role in glucose metabolism and is highly expressed in various tumors. However, its role in lung adenocarcinoma (LUAD) remains incompletely understood. Methods Through bioinformatic analysis, we identified a positive association between high expression of TPI1 and metastasis in LUAD. Western blot, RT‐qPCR, wound healing assays and transwell experiments, were employed to investigate potential mechanisms. Results In this study, bioinformatic analysis showed that high expression of TPI1 was associated with poor prognosis in LUAD patients. We examined the expression of TPI1 in 29 paired LUAD tissues and found that TPI1 expression was higher in LUAD tissues than in paired adjacent noncancerous tissues. Meanwhile, overexpression of TPI1 promoted the epithelial‐mesenchymal transition (EMT) process in LUAD cells, while silencing TPI1 weakened the EMT process. Furthermore, TPI1 was shown to regulate EMT through the MAPK/ERK signaling pathway. Conclusion TPI1 promotes LUAD metastasis by activating the MAPK/ERK signaling pathway.

Abstract The nasal cavity harbors diverse microbiota that contributes to human health and respiratory diseases. However, whether and to what extent the host genome shapes the nasal microbiome remains largely unknown. Here, by dissecting the human genome and nasal metagenome data from 1401 healthy individuals, we demonstrated that the top three host genetic principal components strongly correlated with the nasal microbiota diversity and composition. The genetic association analyses identified 63 genome-wide significant loci affecting the nasal microbial taxa and functions, of which 2 loci reached study-wide significance (p

Coarse grain and poor thermal stability of Mg17Al12 are usually present in the as-cast Mg–Al alloys, which are detrimental to the mechanical properties. In this work, the microstructure evolution, and mechanical properties of as-cast AZ31-1Y alloy with different cooling rates (4.0–29.9 °C/s) were systematically investigated by thermal analysis and microstructure characterization. The results show that the addition of Y to AZ31 alloy results in the formation of primary Al2Y and eutectic Al2Y, while suppressing the formation of β-Mg17Al12. The AZ31-1Y alloy with a cooling rate of 29.9 °C/s exhibits the finest grain, with a grain refinement efficiency 40.9 % higher than that of AZ31 alloy with a cooling rate of 4.0 °C/s. After heat treatment, the acicular eutectic Al2Y is modified into a granular shape and numerous nano-sized Al2Y precipitates are observed within the α-Mg matrix. The addition of Y can effectively improve the mechanical properties of AZ31 alloy under high cooling rates, but the mechanical properties deteriorate at slower cooling rates due to stress concentration caused by the agglomeration of large-sized Al2Y particles. The optimal mechanical properties of the AZ31-1Y alloy are achieved at a cooling rate of 29.9 °C/s combined with subsequent heat treatment, and its YS, UTS, and EL reached up to 69 MPa, 293 MPa, and 14.5 %, respectively. Moreover, the related strengthening mechanisms are quantified. It is believed that this work can provide guidance for controlling the microstructure and optimizing the mechanical properties of as-cast Mg–Al alloys.

Abstract Background Studies evaluating the association between monocyte chemoattractant protein-1 (MCP-1) -2518 A > G (rs1024611) polymorphism and type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) are contradictory. The present study aims to provide a comprehensive assessment and more reliable estimation of the relationship between the MCP-1 rs1024611 polymorphism and T2DM and DN risk. Methods Eligible articles were retrieved from the PubMed, Web of Science, EMBASE, Cochrane, and China National Knowledge Infrastructure databases. The effect summary odds ratios (ORs) and 95% confidence intervals (CIs) were obtained to calculate the summary effect size. Heterogeneity was analyzed by subgroup analysis and meta-regression. Publication bias was tested using funnel plots and Egger’s test. Results In total, sixteen studies were included. Thirteen studies involving 2,363 patients with T2DM and 4,650 healthy controls found no significant association between the MCP-1 rs1024611 polymorphism and T2DM in the overall population. Ethnicity stratification found an association between the GG + GA genotype and decreased T2DM risk in Caucasians (OR = 0.79, 95% CI: 0.66–0.93, P = 0.006; P Q = 0.372). No significant risks were found in the Asian population for any genetic models. Seven studies found an association between the GG + GA genotype and DN risk in the Asian population (OR = 1.37, 95% CI: 1.11–1.71, P = 0.004, P Q = 0.222). No significant risks were found in the Caucasian population with any genetic models. There were no statistically significant differences in genotype distribution between patients with T2DM and DN in Asians or Caucasians. Meta-regression revealed that genotyping method was a major driver of heterogeneity in five genetic models (GG + GA vs. AA: P = 0.032; GG vs. GA + AA: P = 0.028; GG vs. AA: P = 0.035; GG vs. GA: P = 0.041; G vs. A: P = 0.041). Conclusion The MCP-1 rs1024611 polymorphism is associated with susceptibility to T2DM in Caucasians and DN in Asians. Larger, well-designed cohort studies are needed in the future to verify this association.

ABSTRACTThe inactivated whole-virion vaccine, CoronaVac, is one of the most widely used coronavirus disease 2019 (COVID-19) vaccines worldwide. There is a paucity of data indicating the durability of the immune response and the impact of immune imprinting induced by CoronaVac upon Omicron infection. In this prospective cohort study, 41 recipients of triple-dose CoronaVac and 14 unvaccinated individuals were recruited. We comprehensively profiled adaptive immune parameters in both groups, including spike-specific immunoglobulin (Ig) G and IgA titers, neutralizing activity, B cells, circulating follicular helper T (cTfh) cells, CD4+ and CD8+ T cells, and their memory subpopulations at 12 months after the third booster dose and at 4 and 20 weeks after Omicron BA.5 infection. Twelve months after the third CoronaVac vaccination, spike-specific antibodies and cellular responses were detectable in most vaccinated individuals. BA.5 infection significantly augmented the magnitude, cross-reactivity, and durability of serum neutralization activities, Fc-mediated phagocytosis, nasal spike-specific IgA responses, memory B cells, activated cTfh cells, memory CD4+ T cells, and memory CD8+ T cells for both the ancestral strain and Omicron subvariants, compared to unvaccinated individuals. Notably, the increase in BA.5-specific immunity after breakthrough infection was consistently comparable to or higher than that of the ancestral strain, suggesting no evidence of immune imprinting. Immune landscape analyses showed that vaccinated individuals have better synchronization of multiple immune components than unvaccinated individuals upon heterologous infection. Our data provide detailed insight into the protective role of the inactivated COVID-19 vaccine in shaping humoral and cellular immunity to Omicron infection.IMPORTANCEThere is a paucity of data indicating the durability of the immune response and the impact of immune imprinting induced by CoronaVac upon Omicron breakthrough infection. In this prospective cohort study, the anti-severe acute respiratory syndrome coronavirus 2 adaptive responses were analyzed before and after the Omicron BA.5 infection. Our data provide detailed insight into the protective role of the inactivated COVID-19 vaccine in shaping humoral and cellular immune responses to heterologous Omicron infection.CLINICAL TRIALThis study is registered with ClinicalTrials.gov as NCT05680896.

This research explores the role of extended producer responsibility (EPR) as an enabler of circular value chain in the Chinese context. The driven forces and key stakeholders were identified to extend producer responsibility in developing the national-circular-economy strategies. An evaluation system was established to link the eco-design strategy of the producer with the downstream-recycling performance of products. The eco-design information was retrieved from the self-disclosure information in the sustainable development report of producers. The downstream-waste-flow information comes from multiple platforms of reuse and recycling companies. The aim of reforming the EPR system is to establish an open forum for competition and cooperation among different stakeholders to achieve a continuously-improving target of circularity and life cycle environmental performance of the products. With the evaluation results, the producers are encouraged to fully explore all opportunities in the circular value chain instead of focusing only on the final disposal or disassembly of waste. The conclusion suggests that EPR policies should break the restrictions on eco-design and innovation in business models by creating and capturing values of circularity along with the world's collective climate change mitigation efforts.

Rationale and objectives: The off-label use of flow diverters (FDs) has broadened to include treating aneurysms in posterior circulation (PC). A novel flow diverter, the Tubridge flow diverter (TFD), has been created in China specifically for treating PC aneurysms. However, studies comparing between pipeline embolization device (PED) and TFD are rare. Thus, our study aimed to explore the effectiveness of PED and TFD in the treatment of PC aneurysms using a propensity score matched cohort design. Methods: Retrospective data collection was conducted on patients who underwent treatment with either PED or TFD over the period from 2015 through 2020. Propensity score matching (PSM) was employed to calibrate for patient age; history of ischemic stroke; aneurysm size; morphology; location and neck; number of FDs; parent vessel diameter; and the employment of assisted coiling and balloon techniques. Data on previously ruptured aneurysms was not included in the analysis. A comparison was conducted between the two devices to assess perioperative complications, aneurysm occlusion rates, and functional outcomes. Results: A total of 252 PC aneurysms were treated in 248 patients. Clinical and imaging follow-ups were lost in 26 and 47 patients, respectively. Major perioperative complications occurred in 7.5% of the cases, with favorable clinical outcomes in 91.0% and complete occlusion in 79.1%. Eighty-two (32.5%) aneurysms were treated with TFD, while 170 (67.5%) aneurysms were treated with PED. PSM was used to account for these significant variations, producing 82 matched pairs of unruptured aneurysms treated with PED or TFD. In terms of functional and angiographic outcomes, no significant differences were found between PED and TFD (functional outcome, p = 0.594 and angiographic outcome, p = 0.415). However, more perioperative major complications were found in patients treated with TFD (p = 0.005) compared with those receiving PED. Conclusion: The comparative study of PED and TFD in the treatment of PC aneurysms resulted in positive clinical results and sustained occlusion rates, with acceptable perioperative complications. However, higher quality studies are needed to enhance our understanding of the use of FDs for treating of PC aneurysms.

Balancing strength and ductility proves challenging in high-strength wrought Al-Cu-Li alloys, particularly in extruded rods. The abundance of subgrain structures hinders dislocation movement, inevitably sacrificing the ductility. Herein, an effective strategy for enhancing the strength-ductility synergy in an extruded Al-3.7Cu-1Li-0.40Mg-0.75Ag alloy was reported by developing a novel combinatorial pretreatment (CPT), including pre-ageing after solution treatment, followed by pre-stretching. Subsequently, the CPT alloys undergo artificial ageing at 150 °C. Desirable comprehensive mechanical properties (YS = 668 MPa, UTS = 700 MPa, and EL = 12.5 %) were obtained through pre-ageing at 110 °C before 4 % pre-stretching. Notably, the elongation showed a remarkable improvement of 60.3 % compared to the non-CPT sample, without sacrificing the yield strength. Microstructure analysis indicates that the interactions between the GP zones and dislocations facilitated energy dissipation during pre-stretching, effectively mitigating local stress concentration. Consequently, promoted ductility was realized through a more uniform dislocation distribution. Furthermore, the dense GP zones formed during pre-ageing served as the heterogeneous nucleation sites for precipitates, increasing the volume fraction of θ′ phases. This adjustment in dislocation motion further contributed to ductility improvements. Our approach offers new insights into developing high-performance extruded Al-Cu-Li alloys with both high strength and desirable ductility.

High-performance cast magnesium rare-earth (Mg-RE) alloys are one of the most important materials among all developed Mg alloy families, and have shown great potential in military and weapons, aerospace and aviation, orthopedic implants, etc. Controlling grain size and distribution of it is key to the promising mechanical performance of Mg-RE alloy casting components. During the casting of a real component, nearly every procedure in the fabrication process will influence the grain refinement effect. The procedure may include and may not be limited to the chemical inoculations, possibly applied physical fields, the interfere between grain refiner and purifications, and the casting techniques with different processing parameters. This paper reviews the recent advances and proposed future developments in these categories on grain refinement of cast Mg-RE alloys. The review will provide insights for the future design of grain refinement techniques, the choosing of processing parameters, and coping strategies for the failure of coarsening for cast Mg-RE components with high quality and good performance.

Background: We conducted a comprehensive systematic review and meta-analysis to evaluate the diverse impacts of combining aspirin with prednisone or prednisolone on patients undergoing in vitro fertilization (IVF) or experiencing recurrent implantation failure (RIF). Our analysis encompassed parameters such as clinical pregnancy rate, implantation rate, live birth rate, miscarriage rate, and fertilization rate. Our primary objective was to resolve the debate regarding the comparative efficacy of prednisone versus prednisolone when administered alongside aspirin in women undergoing assisted reproduction. Methods: A variety of electronic databases were searched between 1984 and December 2023, including PubMed, Web of Science, Embase, the China National Knowledge Infrastructure (CNKI), the China Biology Medicine Disc (CBM), and the CQVIP Database. We employed the Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool for the quality evaluation. We used Stata 12.0 and Revman 5.4 to pool the data. Results: In this meta-analysis, 10 trials, including 2902 individuals, were considered. Aspirin plus prednisone or prednisolone might improve clinical pregnancy rates (relative risk (RR) = 1.13; 95% confidence interval (95% CI) = 1.03–1.23) and implantation rates (RR = 1.27; 95% CI = 1.01–1.60) compared with the placebo or no treatment group. Conclusions: Our findings suggest that aspirin plus prednisone or prednisolone may improve clinical pregnancy rates and implantation rates in patients with IVF or RIF, and in the subgroup of ANA-positive patients, it may also improve implantation rates. Further design of larger randomized controlled trials is required to determine whether aspirin in combination with prednisone or prednisolone may improve assisted reproductive outcomes in patients undergoing IVF or RIF, considering the limits of study enrollment.

Protection suits are vital for firefighters’ safety. Traditional protection suits physically protect firemen from burns, but cannot locate the position of bodily injuries caused by impact debris. Herein, we present a wearable impact debris positioning system for firefighter protection suits based on an accelerometer array. Wearable piezoelectric accelerometers are distributed regularly on the suit to detect the vibration on different body parts, which is conducive to determining the position of injured body parts. In addition, the injured parts can be displayed on a dummy body model on the upper computer with a higher localization accuracy of 4 cm. The positioning alarm system has a rapid response time of 0.11 ms, attributed to the smart signal processing method. This work provides a reliable and smart method for locating and assessing the position of bodily injuries caused by impact debris, which is significant because it enables fire commanders to rescue injured firefighters in time.

Implantable drug delivery systems formed upon injection offer a host of advantages, including localized drug administration, sustained release, minimized side effects, and enhanced patient compliance. Among the various techniques utilized for the development of in situ forming drug implants, solvent-induced phase inversion emerges as a particularly promising approach. However, synthetic polymer-based implants have been associated with undesirable effects arising from polymer degradation. In response to this challenge, a novel category of drug delivery systems, known as phospholipids-based phase separation gels (PPSGs), has emerged. These gels, characterized by their low initial viscosity, exhibit injectability and undergo rapid transformation into in situ implants when exposed to an aqueous environment. A typical PPSG formulation comprises biodegradable components, such as phospholipids, pharmaceutical oil, and a minimal amount of ethanol. The minimized organic solvents in the composition show good biocompatibility. And the relatively simple composition holds promise for industrial-scale manufacturing. This comprehensive review provides an overview of the principles and advancements in PPSG systems, with specific emphasis on their suitability as drug delivery systems for a wide range of active pharmaceutical ingredients (APIs), spanning from small molecules to peptides and proteins. Additionally, we explore the critical parameters and underlying principles governing the formulation of PPSG-based drug delivery strategies, offering valuable insights on optimization strategies.

Abstract Background The association between the timing of administration of multiple vasopressors and patient outcomes has not been investigated. Methods This study used data from the MIMIC-IV database. Patients with sepsis who were administered two or more vasopressors were included. The principal exposure was the last norepinephrine dose when adding a second vasopressor. The cohort was divided into early (last norepinephrine dose

Abstract Recognizing 3D part instances from a 3D point cloud is crucial for 3D structure and scene understanding. Several learning-based approaches use semantic segmentation and instance center prediction as training tasks and fail to further exploit the inherent relationship between shape semantics and part instances. In this paper, we present a new method for 3D part instance segmentation. Our method exploits semantic segmentation to fuse nonlocal instance features, such as center prediction, and further enhances the fusion scheme in a multi- and cross-level way. We also propose a semantic region center prediction task to train and leverage the prediction results to improve the clustering of instance points. Our method outperforms existing methods with a large-margin improvement in the PartNet benchmark. We also demonstrate that our feature fusion scheme can be applied to other existing methods to improve their performance in indoor scene instance segmentation tasks.

With the rise of multi-modal methods, multi-modal knowledge graphs have become a better choice for storing human knowledge. However, knowledge graphs often suffer from the problem of incompleteness due to the infinite and constantly updating nature of knowledge, and thus the task of knowledge graph completion has been proposed. Existing multi-modal knowledge graph completion methods mostly rely on either embedding-based representations or graph neural networks, and there is still room for improvement in terms of interpretability and the ability to handle multi-hop tasks. Therefore, we propose a new method for multi-modal knowledge graph completion. Our method aims to learn multi-level graph structural features to fully explore hidden relationships within the knowledge graph and to improve reasoning accuracy. Specifically, we first use a Transformer architecture to separately learn about data representations for both the image and text modalities. Then, with the help of multimodal gating units, we filter out irrelevant information and perform feature fusion to obtain a unified encoding of knowledge representations. Furthermore, we extract multi-level path features using a width-adjustable sliding window and learn about structural feature information in the knowledge graph using graph convolutional operations. Finally, we use a scoring function to evaluate the probability of the truthfulness of encoded triplets and to complete the prediction task. To demonstrate the effectiveness of the model, we conduct experiments on two publicly available datasets, FB15K-237-IMG and WN18-IMG, and achieve improvements of 1.8 and 0.7%, respectively, in the Hits@1 metric.

Abstract Selective autophagy is a double-edged sword in antiviral immunity and regulated by various autophagy receptors. However, it remains unclear how to balance the opposite roles by one autophagy receptor. We previously identified a virus-induced small peptide called VISP1 as a selective autophagy receptor that facilitates virus infections by targeting components of antiviral RNA silencing. However, we show here that VISP1 can also inhibit virus infections by mediating autophagic degradation of viral suppressors of RNA silencing (VSRs). VISP1 targets the cucumber mosaic virus (CMV) 2b protein for degradation and attenuates its suppression activity on RNA silencing. Knockout and overexpression of VISP1 exhibit compromised and enhanced resistance against late infection of CMV, respectively. Consequently, VISP1 induces symptom recovery from CMV infection by triggering 2b turnover. VISP1 also targets the C2/AC2 VSRs of two geminiviruses and enhances antiviral immunity. Together, VISP1 induces symptom recovery from severe infections of plant viruses through controlling VSR accumulation.

To validate range shifts in proton therapy, we investigated the potential of using the temporal information of prompt gamma rays as an indicator. We simulated the proton transport process using Monte Carlo simulations and used a geometric scorer to obtain the location and timing of prompt gamma ray production. By using a homogeneous target material in the simulation model, we established a fitted relationship between the range of 90–210 MeV protons and the corresponding temporal spectral width. Additionally, by introducing air cavities of 2–20 mm in simulations of inhomogeneous target materials, we observed significant correlations between the range offsets and the temporal spectral widths. These correlations were fitted to derive a functional relationship between the two variables.

BackgroundSARS-CoV2, the virus that causes coronavirus disease 2019 (COVID-19), can affect multiple human organs structurally and functionally, including the cardiovascular system and brain. Many studies focused on the acute effects of COVID-19 on risk of cardiovascular disease (CVD) and stroke especially among hospitalized patients with limited follow-up time. This study examined long-term mortality, hospitalization, CVD and stroke outcomes after non-hospitalized COVID-19 among Medicare fee-for-service (FFS) beneficiaries in the United States.MethodsThis retrospective matched cohort study included 944,371 FFS beneficiaries aged ≥66 years diagnosed with non-hospitalized COVID-19 from April 1, 2020, to April 30, 2021, and followed-up to May 31, 2022, and 944,371 propensity score matched FFS beneficiaries without COVID-19. Primary outcomes were all-cause mortality, hospitalization, and incidence of 15 CVD and stroke. Because most outcomes violated the proportional hazards assumption, we used restricted cubic splines to model non-proportional hazards in Cox models and presented time-varying hazard ratios (HRs) and Bonferroni corrected 95% confidence intervals (CI).ResultsThe mean age was 75.3 years; 58.0% women and 82.6% non-Hispanic White. The median follow-up was 18.5 months (interquartile range 16.5 to 20.5). COVID-19 showed initial stronger effects on all-cause mortality, hospitalization and 12 incident CVD outcomes with adjusted HRs in 0-3 months ranging from 1.05 (95% CI 1.01-1.09) for mortality to 2.55 (2.26-2.87) for pulmonary embolism. The effects of COVID-19 on outcomes reduced significantly after 3-month follow-up. Risk of mortality, acute myocardial infarction, cardiomyopathy, deep vein thrombosis, and pulmonary embolism returned to baseline after 6-month follow-up. Patterns of initial stronger effects of COVID-19 were largely consistent across age groups, sex, and race/ethnicity.ConclusionsOur results showed a consistent time-varying effects of COVID-19 on mortality, hospitalization, and incident CVD among non-hospitalized COVID-19 survivors.

Background Sensorimotor communication is frequently observed in complex joint actions and social interactions. However, it remains challenging to explore the cognitive foundations behind sensorimotor communication. Methods The present study extends previous research by introducing a single-person baseline condition and formulates two distinct categories of asymmetric joint action tasks: distance tasks and orientation tasks. This research investigates the action performance of 65 participants under various experimental conditions utilizing a 2 (cooperative intention: Coop, No-coop) × 2 (task characteristic: distance, orientation) × 4 (target: T1, T2, T3, T4) repeated-measures experimental design to investigate the cognitive mechanisms underlying sensorimotor communication between individuals. Results The results showed that (1) target key dwell time, motion time, total motion time, and maximum motion height in the Coop condition are more than in the No-coop condition. (2) In the distance task without cooperative intention, the dwell time of T4 is smaller than T1, T2, T3, and its variability of T1, T2, T3, and T4 were no different. In the distance task with cooperative intention, the dwell time and its variability of T1, T2, T3, and T4 displayed an increasing trend. (3) In the orientation task without cooperative intention, the dwell time of T1 is smaller than T2, T3, T4, and variability of the target keys T1, T2, T3, and T4 had no difference. In the orientation task with cooperative intention, the dwell time and variability of the target keys T1, T2, T3, and T4 had increasing trends. Conclusions Those findings underscore the importance of cooperative intention for sensorimotor communication. In the distance task with cooperative intention, message senders establish a mapping relationship characterized by “near-small, far-large” between the task distance and the individual’s action characteristics through sensorimotor experience. In the orientation task with cooperative intention, message senders combined sensorimotor experience and verbal metaphors to establish a mapping relationship between task orientation and action characteristics, following the sequence of “left-up, right-up, left-down, right-down” to transmit the message to others.

Objective: To explore the mechanism by which the Wnt/β-catenin pathway induces osteogenic differentiation of bone marrow-derived stem cells (BMSCs) in anhidrotic ectodermal dysplasia (AED) with an Ectodysplasin A (EDA)/EDA receptor (EDAR)/EDARADD mutation. Methods: An AED patient served as the AED group, whereas the other patients without AED were included in the normal group. Peripheral venous blood collected from the AED patient was subjected to whole-genome resequencing. BMSCs from the mandible of patients with AED and normal individuals were isolated and cultured in vitro. Cell proliferation assay was performed to compare the growth speed of BMSCs between the AED and normal groups. CHIR-99021, an activator of the Wnt/β-catenin pathway and XAV-939, an inhibitor, was used to manage BMSCs in an osteogenic environment in both groups. The expression of β-catenin was detected by quantitative polymerase chain reaction, while that of RUNX2 was detected by western blotting. Alizarin red was used for staining. Results: A novel mutation (c.152T > A in EDA) and two known mutations (c.1109T > C in EDAR and c.27G > A in EDARADD) were identified. The growth rate in the normal group was higher than that in the AED group. In the normal group, the number and size of calcified nodes and the expression of RUNX-2 increased with CHIR-99021 treatment, which could be inhibited by XAV-939. In contrast, CHIR-99021 inhibited osteogenesis in the AED group and this effect was promoted by XAV-939. Conclusion: Activation of the Wnt/β-catenin pathway downregulates osteogenesis of BMSCs in AED patients with EDA/EDAR/EDARADD gene mutations. Further investigation in more AED patients is required, given the wide range of mutations involved in AED.

Introduction and Objectives: Chronic hepatitis B (CHB) may progress to more serious liver diseases and it is often accompanied by non-alcoholic fatty liver disease (NAFLD). NAFLD and CHB share risk factors for liver fibrosis and cirrhosis, but the influence of NAFLD on fibrosis progression is controversial. This retrospective study evaluated the prevalence of NAFLD in patients with CHB and investigated associations between NAFLD and liver fibrosis in a large multi-center cohort of hepatitis B patients submitted to liver biopsy. Patients and Methods: Treatment-naïve patients with CHB who underwent liver biopsy were analyzed. Propensity score matching (PSM) was performed to adjust the confounders between patients with and without NAFLD. Results: A total of 1496 CHB patients were included. Two hundred and ninety (19.4%) patients were diagnosed with NAFLD by liver biopsy. The proportions of significant liver fibrosis (52.8% vs. 63.9%, P

Background: Patients with autoimmune hepatitis-primary biliary cholangitis (AIH-PBC) overlap syndrome have a worse prognosis compared to AIH or PBC alone and accurately predicting the severity and dynamically monitoring the progression of disease are therefore essential. We aimed to develop a nomogram-based model to predict advanced liver fibrosis in patients with AIH-PBC overlap syndrome. Methods: A total of 121 patients with AIH-PBC overlap syndrome were retrospectively included and randomly assigned to a development set and a validation set. Backward stepwise regression's best model with the lowest AIC was employed to create a nomogram. Diagnose accuracy was evaluated using the area under the receiver operator characteristic curve (AUROC), calibration analysis, and decision curve analysis (DCA) and was compared with aspartate aminotransferase-to-platelet ratio (APRI) and fibrosis index based on four factors-4 (FIB-4) score. Results: The median age of patients was 53.0 years (IQR: 46.0–63.0), and female patients accounted for 95.0 %. Platelets, globulin, total bilirubin, and prothrombin time were associated with advanced fibrosis (≥S3) and used to construct an AIH-PBC overlap syndrome fibrosis (APOSF)-nomogram (available online at https://ndth-zzy.shinyapps.io/APOSF-nomogram/). The AUROCs of APOSF-nomogram were 0.845 (95 % CI: 0.754–0.936) and 0.843 (95 % CI: 0.705–0.982) in development set and validation set respectively, which was significantly better than APRI and FIB-4. Calibration revealed that the estimated risk fits well with biopsy-proven observation. DCA outperformed APRI and FIB4 in terms of net benefit, demonstrating clinical utility. Conclusion: This novel non-invasive web-based online APOSF-nomogram provided a convenient tool for identifying advanced fibrosis in patients with AIH-PBC overlap syndrome. Further prospective, multicenter studies with large sample size are necessary to validate the applicability of APOSF-nomogram.

In this paper, field spectroradiometer and aboveground biomass (AGB) data were acquired at the harvest stage at two sites in semiarid grasslands in Inner Mongolia, China. Four forms of commonly used vegetation indices (VIs) using all possible combinations of narrow-band first derivative (FDR) and raw reflectance (RR) were calculated, and the best FDR-VIs and RR-VIs were chosen by a linear regression analysis against AGB. The stepwise multiple linear regression (SMLR) models using the optimal FDR-VIs, RR-VIs, and both FDR-VIs and RR-VIs as input variables were developed for estimating the AGB. Results demonstrated that the estimation performance using the best FDR-VIs were comparable with the best RR-VIs, while the accuracy has been further improved by combining the best FDR-VIs and RR-VIs (maximum decrease in RMSE of 44% and minimum RMAE of 4.7%). The approach was found to be an important step for more accurate and effective grassland AGB estimation.