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【Objective】This study aimed to explore the downstream response genes of Dendrobium catenatum Lindl. DcCIPK24, and provided guidance for studying the molecular regulatory pathway of DcCIPK24 to improve salt tolerance.【Method】The DcCIPK24 transgenic Arabidopsis thaliana and wild type plants under 200 mmol/L NaCl treatment and normal conditions were used for RNA-seq on the illumina NovaSeq 6000 sequencing platform. The enrichment pathway of differentially expressed genes (DEGs) was analyzed, and their expression patterns were verified by quantitative real-time PCR.【Result】A total of 96 DEGs were identified from transgenic A. thaliana and wild type plants under salt stress. GO annotation analysis showed that 96 DEGs were mainly enriched in molecular function pathways. KEGG enrichment analysis found that DEGs enriched in amino sugar and nucleotide sugar metabolism, plant MAPK signaling pathway and glycerolipid metabolism. The DEGs including four upregulated genes (AtGPAT5, AtSIRK, AtMEE25, and AtUGE5) and four downregulated genes (AtAMT1-2, AtATTI3, AtCYP71A25, and AtLHCB4.3) were selected for qRT-PCR validation. The results showed that the trends of 8 DEGs' expression were basically consistent with the RNA-seq data.【Conclusion】DcCIPK24 responded to salt tolerance mainly through amino sugar and nucleotide sugar metabolism, plant MAPK signaling pathway, and glycerolipid metabolism.

Abstract Metastasis is the leading cause of cancer-related death, where TGFβ-induced epithelial-mesenchymal transition (EMT) process confers on cancer cells increased metastatic potential. However, the involvement of circRNAs in this process is still obscure. Here, we identify a TGFβ-induced circRNA called circITGB6 as an indispensable factor during the TGFβ-mediated EMT process. circITGB6 is significantly upregulated in metastatic cancer samples and its higher abundance is closely correlated to worse prognosis of colorectal cancer (CRC) patients. Through gain- and loss-of-function assays, circITGB6 is found to potently promote EMT process and tumor metastasis in various models in vitro and in vivo. Mechanistically, circITGB6 enhances the mRNA stability of PDPN, an EMT-promoting gene, by directly interacting with IGF2BP3. Notably, interfering circITGB6 with PEI-coated specific siRNA effectively represses liver metastasis. Therefore, our study reveals the function of a TGFβ-regulated circRNA in tumor metastasis and suggests that targeting circITGB6 is a promising strategy for cancer therapy.

Abstract Background During the early “containment” phase of the COVID-19 response in England (January-March 2020), contact tracing was managed by Public Health England (PHE). Adherence to self-isolation during this phase and how people were making those decisions has not previously been determined. The aim of this study was to gain a better understanding of decisions around adherence to self-isolation during the first phase of the COVID-19 response in England. Methods A mixed-methods cross sectional study was conducted, including an online survey and qualitative interviews. The overall pattern of adherence was described as never leaving home, leaving home for lower-contact reasons and leaving home for higher-contact reasons. Fisher’s exact test was used to test associations between adherence and potentially predictive binary factors. Factors showing evidence of association overall were then considered in relation to the three aspects of adherence individually. Qualitative data were analysed using inductive thematic analysis. Results Of 250 respondents who were advised to self-isolate, 63% reported not leaving home at all during their isolation period, 20% reported leaving only for lower-contact activities (dog walking or exercise) and 16% reported leaving for higher-contact, and therefore higher-risk, reasons. Factors associated with adherence to never going out included: the belief that following isolation advice would save lives, experiencing COVID-19 symptoms, being advised to stay in their room, having help from outside and having regular contact by text message from PHE. Factors associated with non-adherence included being angry about the advice to isolate, being unable to get groceries delivered and concerns about losing touch with friends and family. Interviews highlighted that a sense of duty motivated people to adhere to isolation guidance and where people did leave their homes, these decisions were based on rational calculations of the risk of transmission – people would only leave their homes when they thought they were unlikely to come into contact with others. Conclusions Understanding adherence to isolation and associated reasoning during the early stages of the pandemic is essential to pandemic preparedness for future emerging infectious disease outbreaks. Individuals make complex decisions around adherence by calibrating transmission risks, therefore treating adherence as binary should be avoided.

Abstract The role of follicular T helper (Tfh) cells in humoral response has been considered essential in recent years. Understanding how Tfh cells control complex humoral immunity is critical to developing strategies to improve the efficacy of vaccines against SARS-CoV-2 and other emerging pathogens. However, the immunologic mechanism of Tfh cells in SARS-CoV-2 receptor binding domain (RBD) vaccine strategy is limited. In this study, we expressed and purified recombinant SARS-CoV-2 RBD protein in Drosophila S2 cells for the first time and explored the mechanism of Tfh cells induced by RBD vaccine in humoral immune response. We mapped the dynamic of Tfh cell in lymph node and spleen following RBD vaccination and revealed the relationship between Tfh cells and humoral immune response induced by SARS-CoV-2 RBD vaccine through correlation analysis, blocking of IL-21 signaling pathway, and co-culture of Tfh with memory B cells. Recombinant RBD protein elicited a predominant Tfh1 and Tfh1-17 subset response and strong GC responses in spleen and lymph nodes, especially to enhanced vaccination. IL-21 secreted by Tfh cells affected the development and differentiation of B cells and played a key role in the humoral immune response. These observations will help us further understand the mechanism of protective immune response induced by COVID-19 vaccine and has guiding significance for the development of vaccines against newly emerging mutants.

Abstract Background Osseous changes of the temporomandibular joint (TMJ) are related to the progression of temporomandibular disorders (TMD), and computed tomography (CT) plays a vital role in disease evaluation. Objective The aims of this study were to evaluate the image quality and diagnostic value of ultra-high-resolution CT (U-HRCT) in TMD compared to cone-beam CT (CBCT). Methods TMD patients who underwent both CBCT and U-HRCT between November 2021 and September 2022 were retrospectively included. Image quality scores were assigned for four osseous structures (the cortical and trabecular bones of the condyle, articular eminence, and glenoid fossa) by two independent observers from Score 1 (unacceptable) to Score 5 (excellent). Diagnostic classification of TMD was categorized as follows: Class A (no evident lesion), Class B (indeterminate condition) and Class C (definitive lesion). Image quality scores and diagnostic classifications were compared between CBCT and U-HRCT. The Cohen’s Kappa test, Wilcoxon signed-rank test, Chi-square test and Fisher’s exact test were conducted for statistical analysis. Results Thirty TMD patients (median age, 30 years; interquartile range, 26–43 years; 25 females) with 60 TMJs were enrolled. Image quality scores were higher for U-HRCT than for CBCT by both observers (all Ps

Abstract Background Antibiotics are over-used for patients with respiratory tract infections (RTIs) in primary care, especially in the rural areas of China. Methods A cluster randomized controlled trial (RCT) will be carried out to estimate the effectiveness of a tailored message package for educating patients to reduce antibiotic use for symptomatic respiratory tract infections (RTIs). In the intervention group, patients will receive 12 short messages in 12 consecutive days. The whole process of the message design, modification, translation (of substitution variables), and sending will be facilitated by a user-friendly mini-computer program. The primary measure for assessment is the reduction in number of days in which antibiotics are used by patients with symptomatic RTIs. The secondary measures include (1) patients’ knowledge about and attitude toward antibiotics; (2) patients’ quality of life (EQ-5D-5L) and symptom severity and duration; (3) times of re-visits to clinics and antibiotics re-prescription for the same RTI episode; and (4) times of re-occurrence of RTIs and related health service seeking and antibiotics consumption. Discussion This study will determine the efficacy of a 12-message intervention to educate patients to reduce excessive antibiotic use in rural China. Trial registration ISRCTN29801086 . Registered on 23 September 2022.

In this study, a global agricultural trade network was constructed, and its topological characteristics from 1991 to 2021 were analysed. The influences of nine variables were empirically tested, including factor endowments and economic, geographical, and institutional factors. The research results show that the scale of trade networks is constantly expanding, and trade relations are becoming increasingly concentrated. Further, global agricultural trade patterns are gradually being reshaped. However, European economies and the United States still dominate the power of network control, with a clear 'core-edge' hierarchy. Among the factors influencing the global agricultural trade network, differences in arable land areas, agricultural product prices, geographical distances, and financial institutions have proven important. However, their influence varies. Compared to the differences in the endowments of other factors, the comparative advantage of agricultural trade in various nodes worldwide comes more from the arable land areas. The greater the difference in agricultural prices, the closer are the trade ties between nodes. Differences in geographical distance have proven conducive to establishing agricultural trade relations. Finally, the greater the difference in financial systems, the greater the likelihood that agricultural trade links will occur.

Abstract CSCs (Cancer stem cells) with distinct metabolic features are considered to cause HCC (hepatocellular carcinoma) initiation, metastasis and therapeutic resistance. Here, we perform a metabolic gene CRISPR/Cas9 knockout library screen in tumorspheres derived from HCC cells and find that deletion of SCARB2 suppresses the cancer stem cell-like properties of HCC cells. Knockout of Scarb2 in hepatocytes attenuates HCC initiation and progression in both MYC-driven and DEN (diethylnitrosamine)-induced HCC mouse models. Mechanistically, binding of SCARB2 with MYC promotes MYC acetylation by interfering with HDCA3-mediated MYC deacetylation on lysine 148 and subsequently enhances MYC transcriptional activity. Screening of a database of FDA (Food and Drug Administration)-approved drugs shows Polymyxin B displays high binding affinity for SCARB2 protein, disrupts the SCARB2-MYC interaction, decreases MYC activity, and reduces the tumor burden. Our study identifies SCARB2 as a functional driver of HCC and suggests Polymyxin B-based treatment as a targeted therapeutic option for HCC.

Abstract Background Antibiotic resistance rates remain high in China where antibiotics are widely used for common illnesses. This study aimed to investigate the influences on people’s decisions on treatment and antibiotic use for common illnesses in eastern China. Methods Semi-structured interviews were conducted with 29 patients recruited through convenience sampling between July 2020 and January 2021 in one hospital in County A in Zhejiang Province, and one hospital and one village clinic in County B in Jiangsu Province, respectively. All interviews were audio-recorded, transcribed verbatim and thematically analysed. This study is nested in a larger interdisciplinary mixed method project and we also compared our qualitative findings with quantitative results from a household survey conducted as part of this wider project. Results Participants’ decisions about treatment-seeking and antibiotic use for common illnesses were found to be influenced by four interactive domains. (i) Self-evaluation of illness severity: Participants tend to self-treat minor conditions with ordinary medicines first and do not resort to antibiotics unless the condition worsens or is considered inflammation- related. Visiting healthcare facilities is seen as the final option. (ii) Access to and trust in care: These treatment-seeking practices are also associated with the perception, in contrast with retail pharmacies, hospitals provide professional and trustworthy care but are difficult to access, and hence require visiting only for severe illness. (iii) Prior experience: previous medical treatment and experiences of self-medication also influence participants’ treatment decisions including the use of antibiotics. (iv) Medication characteristics: Participants view antibiotics as powerful medicines with harms and risks, requiring consumers to carefully trade off benefits and harms before use. Conclusions People’s treatment decisions in relation to antibiotic use in eastern China are influenced by an interplay of lay conceptual models of illnesses and antibiotics and broader organisational, social, and contextual factors. Interventions focusing on individual education to incorporate biomedical knowledge into lay understandings, and reducing situational and social incentives for self-medicating with antibiotics by strengthening access to quality professional care, would be helpful in promoting antibiotic stewardship.

ABSTRACT: Objectives: Emergence of carbapenemase and tigecycline resistance genes in pathogens threatens the efficacy of last-resort antibiotics. High attention should be paid to the spread and convergence of such resistance genes. This study reports an extensively drug-resistant (XDR) Providencia rettgeri clinical strain co-harbouring carbapenemase genes blaNDM-1, blaOXA-10 and the tmexCD3-toprJ1b gene cluster. Methods: The phenotype and genotype of P. rettgeri Pre20-95 were investigated by antimicrobial susceptibility testing, conjugation assay, stability testing and whole genome sequencing. Bioinformatics tools were used to uncover the genetic structures of its multidrug-resistant (MDR) plasmid pPre20-95-1 and SXT/R391 integrative and conjugative element ICEPreChn20-95. Results: P. rettgeri strain Pre20-95 was isolated from a human clinical infection and displayed an extensively drug-resistant (XDR) phenotype. Whole genome sequencing (WGS) analysis identified a pPrY2001-like MDR plasmid, namely pPre20-95-1, co-harbouring blaNDM-1 and blaOXA-10 genes in Pre20-95. The multidrug resistance region of pPre20-95-1 was composed of a Tn6625-derived module and a ∆Tn1696 structure, and blaNDM-1 and blaOXA-10 were located in a composite Tn structure consisting of insertion sequences ISCR1 and ISAba125 and an In125-like class 1 integron, respectively. Furthermore, the novel RND efflux pump gene cluster tmexCD3-toprJ1b was identified on the SXT/R391 ICE ICEPreChn20-95 of its chromosome, and reverse PCR showed that it could form a circular intermediate for transmission. Conclusion: Our findings highlight further dissemination of the tmexCD3-toprJ1b gene cluster into a clinical isolate of P. rettgeri and convergence with multiple carbapenemase genes, which increases the risk of the emergence of XDR strains and threatens the treatment of Enterobacterales bacterial infections.

Abstract Background Recently, therapeutic antibodies against programmed cell death 1 (PD-1) and its ligand (PD-L1) have exerted potent anticancer effect in a variety of tumors. However, blocking the PD-1/PD-L1 axis alone is not sufficient to restore normal immune response. Other negative regulators of antitumor immunity, like TGF-β and VEGFA, are also involved in immune escape of tumor cells and induce immunotherapy resistance. Methods We developed a novel anti-TGF-β/VEGF bispecific antibody Y332D based on the Nano-YBODY™ technology platform. The CCK-8, flow cytometry, SBE4 luciferase reporter assay, western blotting and transwell assays were used to measure the biological activities of the anti-TGF-β moiety. The NFAT luciferase reporter assay, luminescent cell viability assay and tube formation assay were used to measure the biological activities of the anti-VEGF moiety. The in vivo anticancer efficacy of Y332D alone or in combination with PD-1 blockade was evaluated in H22, EMT-6, 4T1, and AKT/Ras-driven murine hepatocellular carcinoma tumor models. Immunofluorescent staining, flow cytometry, RNA-seq and quantitative RT-PCR were adopted to analyze the alterations in the tumor microenvironment. Results Y332D could maintain specific binding affinities for TGF-β and VEGFA. Y332D almost entirely counteracted the in vitro biological functions of TGF-β and VEGFA, including immunosuppression, activated TGF-β signaling, epithelial-mesenchymal transition (EMT), activated VEGF/VEGFR signaling, HUVEC proliferation and tube formation. The in vivo experiment data demonstrated that Y332D was more effective in inhibiting tumor growth and metastasis than anti-TGF-β and anti-VEGF monotherapies. In combination therapies, Y332D plus PD-1 blockade exhibited the most potent and durable anticancer effect. Mechanistically, Y332D plus PD-1 blockade upregulated the density and function of tumor-infiltrating lymphocytes and exerted reinvigorated antitumor immunity. Conclusion Y332D could simultaneously block TGF-β and VEGF signalings. In comparison with the monotherapies, Y332D combined with PD-1 blockade exerts superior antitumor effect through improving immune microenvironment.

Abstract To date, there is no effective therapy for pathological cardiac hypertrophy, which can ultimately lead to heart failure. Bellidifolin (BEL) is an active xanthone component of Gentianella acuta (G. acuta) with a protective function for the heart. However, the role and mechanism of BEL action in cardiac hypertrophy remain unknown. In this study, the mouse model of cardiac hypertrophy was established by isoprenaline (ISO) induction with or without BEL treatment. The results showed that BEL alleviated cardiac dysfunction and pathological changes induced by ISO in the mice. The expression of cardiac hypertrophy marker genes, including ANP, BNP, and β-MHC, were inhibited by BEL both in mice and in H9C2 cells. Furthermore, BEL repressed the epigenetic regulator bromodomain-containing protein 4 (BRD4) to reduce the ISO-induced acetylation of H3K122 and phosphorylation of RNA Pol II. The Nox4/ROS/ADAM17 signalling pathway was also inhibited by BEL in a BRD4 dependent manner. Thus, BEL alleviated cardiac hypertrophy and cardiac dysfunction via the BRD4/Nox4/ROS axes during ISO-induced cardiac hypertrophy. These findings clarify the function and molecular mechanism of BEL action in the therapeutic intervention of cardiac hypertrophy.

Metasurfaces can flexibly manipulate electromagnetic waves by engineering subwavelength structures, which have attracted enormous attention in holography, cloaking, and functional multiplexing. For structures with n-fold (n > 2) rotational symmetry, they have been utilized to realize broadband and high-efficiency wavefront manipulation with generalized Pancharatnam–Berry phase, whereas spin-selective wavefront manipulation is still a challenge limited by their symmetrical spin–orbit interactions. Here, we demonstrate the spin-selective wavefront manipulations with generalized Pancharatnam–Berry phase in the range of 560–660 nm with a metal–insulator–metal metasurface consisting of the chiral C3 logarithmic spiral nanostructures. As a proof of concept, two deflectors and a bifocal metalens are designed. This configuration may provide a platform for various applications in polarimetry, polarization-selective images, and nonlinear optical responses.

Existing studies have examined unhealthy food packaging information, mainly focusing on aspects such as the content, color, and text, whilst paying less attention to the boundaries of information. This paper investigates unhealthy foods through three experiments, revealing that the presence (vs. absence) of packaging information boundaries on unhealthy foods has a negative impact on consumers’ purchasing intentions (p = 0.040) (Experiment 1). The feeling of constraint mediates this effect (β = −0.078, CI: [−0.1911, −0.0111]) (Experiment 2). Additionally, consumers with an independent self-construal exhibit reduced purchasing intentions when unhealthy food packaging information boundaries are present (vs. absent) (p < 0.001), whereas those with an interdependent self-construal show increased purchasing intentions under the same conditions (p = 0.024) (Experiment 3). This paper reveals the psychological mechanism and boundary conditions of unhealthy food packaging information boundaries affecting consumers’ purchasing intention and provides practical inspiration for government policy-making related to unhealthy food packaging.

Breast cancer is one of the most common causes of death in women. Early signs of breast cancer can be an abnormality depicted on breast images like breast ultrasonography. Unfortunately, ultrasound images contain a lot of noise, which greatly increases the difficulty for doctors to interpret them. In recent years, computer-aided diagnosis (CAD) has been widely used in medical images, reducing the workload of doctors and the probability of misdiagnosis. However, it still faces the following challenges in clinical practice: one is the lack of interpretability, and another is that the accuracy is not high enough. In this paper, we propose a classification model of breast ultrasound images that leverages tumor boundaries as prior knowledge and strengthens the model to guide classification. Furthermore, we employ the advantages of convolutional neural network (CNN) to extract local features and Transformer to extract global features to achieve information balance and complementarity between the two neural network models which increase the recognition performance of the model. Additionally, an explanation method is used to generate visual results, thereby improving the poor interpretability of deep learning models. Finally, we evaluate the model on the BUSI dataset and compare it with other CNN and Transformer models. Experimental results show that the proposed model obtains an accuracy of 0.9870 and an F1 score of 0.9872, achieving state-of-the-art performance.

To explore the effect of the photoperiod on the accumulation and distribution of dry matter in potato, a pot experiment was carried out in 2021 and 2022 with two varieties (Atlantic and Hezuo 88). The varieties were used as the main plot, and light treatments (short-day and long-day) were used as the subplot. The results showed that extended hours of light delayed tuber formation in Hezuo 88, however, the effect was not obvious for the Atlantic. Comprehensive analyses were carried out using the potato developmental process, dynamic equation fitting of the tuber and whole-plant dry matter accumulation, and the dry matter accumulation and distribution rate of each organ of the two varieties under two photoperiods. The two photoperiods had different effects on the parameters of rapid tuber and whole-plant dry matter accumulation: the starting point of the period of the rapid dry matter accumulation (t1), the duration period of the rapid dry matter accumulation (Δt), and the average growth rate of the period of the rapid dry matter accumulation (Vmean). According to comprehensive analysis, tuber dry matter accumulation in Atlantic was the highest under the short-day condition, while Hezuo 88 showed the lowest tuber dry matter accumulation under the long-day condition and was the latest to enter the rapid tuber dry matter accumulation period. The whole-plant dry matter accumulation in Atlantic was the highest under the long-day condition and lowest in Hezuo 88; meanwhile, Hezuo 88 was the latest to enter the rapid whole-plant dry matter accumulation period. In terms of the dry matter accumulation and dry matter partitioning ratio of various organs, Hezuo 88 had the lowest mean tuber dry matter accumulation and partitioning ratio under the long-day condition but the highest mean stem, leaf, root, underground stem, and stolon dry matter partitioning ratio. On the contrary, Atlantic had the highest mean tuber dry matter accumulation and portioning ratio under the short-day condition but the lowest mean stem, leaf, root, underground stem, and stolon dry matter partitioning ratio. It was concluded that different varieties of potato respond differently to the photoperiod. In the case of Hezuo 88, prolonging the photoperiod affected the dynamics and distribution of dry matter accumulation; increased the stem, leaf, root, and underground stem dry matter partitioning ratio; and decreased the tuber dry matter partitioning ratio, which resulted in a decrease in tuber dry matter accumulation and consequently delayed the emergence of the equilibrium period between the aboveground and underground dry matter.

The characteristics and responses of soil bacterial communities and potato productivity to different fertilization treatments in farmlands in the agropastoral zone of Inner Mongolia were investigated. Moreover, the diversity and structure of soil bacterial communities and potato productivity under different fertilization treatments (no fertilization, CK; phosphorus-deficient treatment, NK; conventional fertilization, NPK; and organic–inorganic combination, NPKM) were assessed using Illumina high-throughput sequencing. The results revealed that soil pH, organic matter (SOM), total nitrogen (TN), and total phosphorus (TP) content, and potato productivity were significantly increased under fertilizer treatments (NK, NPK, and NPKM) compared with those under CK, with NPKM treatment having the best enhancement effect. The application of organic fertilizers significantly increased the Shannon, evenness, Chao1, and Ace indices of soil bacterial communities and reshaped the bacterial community structure. Random forest model analysis revealed that soil pH and TP significantly affected soil bacterial diversity, whereas soil pH, SOM, TP, and TN significantly affected soil bacterial community structure. Correlation and structural equation modeling analyses revealed that soil TP and SOM indirectly affected potato productivity by changing soil bacterial diversity and community composition. The results of this study provide a scientific basis for improving the quality and productivity of farmland soil to guide the rational fertilization of farmlands in the agropastoral zone of northern China.

The low-temperature oxidation of methane gas in coal mine exhaust gas is important for reducing the greenhouse effect and protecting the environment. Unfortunately, the carbon–hydrogen bonds in methane molecules are highly stable, requiring higher reaction temperatures to achieve effective catalytic oxidation. However, metal oxide-based catalysts face the problem of easy sintering and the deactivation of active components at high temperatures, which is an important challenge that catalysts need to overcome in practical applications. In this work, a series of Mn-Co3O4 active components were grown in situ on ZSM-5 zeolite with mesoporous pore structures treated with an alkaline solution via a hydrothermal synthesis method. Due to the presence of polyethylene glycol as a structure-directing agent, manganese can be uniformly doped into the Co3O4 lattice. The large specific surface area of ZSM-5 zeolite allows the active component Mn-Co3O4 to be uniformly dispersed, effectively preventing the sintering and growth of active component particles during the catalytic reaction process. It is worth mentioning that the Mn-Co3O4/meso-ZSM-5-6.67 catalyst has a methane conversion rate of up to 90% at a space velocity of 36,000 mL·g−1·h−1 and a reaction temperature of 363 °C. This is mainly due to the mesoporous ZSM-5 carrier with a high specific surface area, which is conducive to the adsorption and mass transfer of reaction molecules. The active component has an abundance of oxygen vacancies, which is conducive to the activation of reaction molecules and enhances its catalytic activity, which is even higher than that of noble metal-based catalysts. The new ideas for the preparation of metal oxide-based low-temperature methane oxidation catalysts proposed in this work are expected to provide new solutions for low-temperature methane oxidation reactions and promote technological progress in related fields.

Unmanned surface vehicles (USVs) often operate in real-world environments with long voyage distances and complex routes. The use of a single-grid map model presents challenges, such as the high computational costs for high-resolution maps and loss of environmental information for low-resolution maps. This article proposes an environmental modeling method using a hybrid map that combines topology units and grids. The approach involves calibrating key nodes based on the watershed skeleton line, constructing a topology map using these nodes, decomposing the original map into unit maps, converting each unit map into a grid map, and creating a hybrid map environment model that comprises topology maps, unit map sets, and grid map sets. Then, the article introduces an improved genetic algorithm, called Genetic Algorithm with Feedback (FGA), to address path planning in hybrid maps. Experimental results demonstrate that FGA has better computational efficiency than other algorithms in similar experimental environments. In hybrid maps, path planning with FGA reduces the path lengths and time consumption, and the paths are more logical, smooth, and continuous. These findings contribute to enhancing the quality of path planning and the practical value of USVs.

In the early stages, uncontrolled groundwater extraction led to the Hangjiahu (HJH) Plain becoming one of the areas with the most severe land subsidence in China. Since the beginning of this century, comprehensive measures have been taken to control the continuous aggravation of large land subsidence patterns in some areas; however, urban land subsidence issues, influenced by various factors, still persist and exhibit complex geographical distribution characteristics. In this study, we utilized Sentinel-1A images and the SBAS-InSAR technique to capture surface deformation over the HJH Plain in Zhejiang from 16 March 2017 to 20 January 2023. Through a comparative analysis with geological conditions, changes in surface mass loading, rainfall and groundwater, and land use types, we discussed the contributions of natural and anthropogenic factors to land subsidence. Augmented with optical remote sensing images and field investigations, we conducted a correlation analysis of the land subsidence status. The preliminary findings suggest that changes in surface mass loading and short-term heavy rainfall under extreme weather conditions can lead to periodic land subsidence changes in the region. Additionally, extensive infrastructure construction triggered by urbanization has resulted in significant and sustained land subsidence deformation. The research findings play an important guiding role in formulating scientifically effective strategies for land subsidence prevention and control, as well as urban planning and construction.

Abstract The outbreak of coronavirus disease 2019 (COVID-19) posed an unprecedented challenge on public health systems. Despite the measures put in place to contain it, COVID-19 is likely to continue experiencing sporadic outbreaks for some time, and individuals will remain susceptible to recurrent infections. Chimeric antigen receptor (CAR)-T recipients are characterized by durable B-cell aplasia, hypogammaglobulinemia and loss of T-cell diversity, which lead to an increased proportion of severe/critical cases and a high mortality rate after COVID-19 infection. Thus, treatment decisions have become much more complex and require greater caution when considering CAR T-cell immunotherapy. Hence, we reviewed the current understanding of COVID-19 and reported clinical experience in the management of COVID-19 and CAR-T therapy. After a panel discussion, we proposed a rational procedure pertaining to CAR-T recipients with the aim of maximizing the benefit of CAR-T therapy in the post COVID-19 pandemic era.

Abstract Background Genetics evidences have long linked mosaic loss of Y-chromosome (mLOY) in peripheral leukocytes with a wide range of male age-associated diseases. However, a lack of cellular and molecular mechanistic explanations for this link has limited further investigation into the relationship between mLOY and male age-related disease. Excitingly, Sano et al. have provided the first piece of evidence directly linking mLOY to cardiac fibrosis through mLOY enriched profibrotic transforming growth factor β1 (TGF-β1) regulons in hematopoietic macrophages along with suppressed interleukin-1β (IL-1β) proinflammatory regulons. The results of this novel finding can be extrapolated to other disease related to mLOY, such as cancer, cardiac disease, and age-related macular degeneration. Results Sano et al. used a CRISPR-Cas9 gRNAs gene editing induced Y-chromosome ablation mouse model to assess results of a UK biobank prospective analysis implicating the Y-chromosome in male age-related disease. Using this in vivo model, Sano et al. showed that hematopoietic mLOY accelerated cardiac fibrosis and heart failure in male mice through profibrotic pathways. This process was linked to monocyte-macrophage differentiation during hematopoietic development. Mice confirmed to have mLOY in leukocytes, by loss of Y-chromosome genes Kdm5d, Uty, Eif2s3y, and Ddx3y, at similar percentages to the human population were shown to have accelerated rates of interstitial and perivascular fibrosis and abnormal echocardiograms. These mice also recovered poorly from the transverse aortic constriction (TAC) model of heart failure and developed left ventricular dysfunction at higher rates. This was attributed to aberrant proliferation of cardiac MEF-SK4 + fibroblasts promoted by mLOY macrophages enriched in profibrotic regulons and lacking in proinflammatory regulons. These pro-fibrotic macrophages localized to heart and eventually resulted in cardiac fibrosis via enhanced TGF-β1 and suppressed IL-1β signaling. Furthermore, treatment of mLOY mice with TGFβ1 neutralizing antibody was able to improve their cardiac function. This study by Sano et al. was able to provide a causative link between the known association between mLOY and male cardiac disease morbidity and mortality for the first time, and thereby provide a new target for improving human health. Conclusions Using a CRISPR-Cas9 induced Y-chromosome ablation mouse model, Sano et al. has proven mosaic loss of Y-chromosome in peripheral myeloid cells to have a causative effect on male mobility and mortality due to male age-related cardiac disease. They traced the mechanism of this effect to hyper-expression of the profibrotic TGF-β1 and reduced pro-inflammatory IL-1β signaling, attenuation of which could provide another potential strategy in improving outcomes against age-related diseases in men.

Abstract Background It is unclear whether dobutamine, commonly used clinically in echocardiography and short-term congestive heart failure treatment for promoting increased myocardial contractility, affects brain microcirculatory behavior. Cerebral microcirculation plays an important role in ensuring adequate oxygen transport. Therefore, we investigated the effects of dobutamine on cerebral hemodynamics. Methods Forty-eight healthy volunteers without cardiovascular or cerebrovascular disease underwent MRI to obtain cerebral blood flow (CBF) maps using 3D pseudocontinuous arterial spin labeling before and during the dobutamine stress test. Additionally, cerebrovascular morphology was obtained based on 3D-time-off-light (3D-TOF) magnetic resonance angiography (MRA). Electrocardiogram, heart rate (HR), respiration rate (RR), blood pressure, and blood oxygen were simultaneously recorded before and during dobutamine injection and during recovery (not during MRI). The anatomic features of the circle of Willis and the basilar artery (BA) diameter were assessed on MRA images by two radiologists with extensive neuroimaging experience. Binary logistic regression was used to test for the independent determinants of CBF changes. Results HR, RR, systolic (SBP), and diastolic blood pressure (DBP) significantly increased after dobutamine infusion. Blood oxygen levels remained similar. Compared to the CBF in the resting state, the CBF values exhibited significantly lower CBF levels in both grey matter and white matter. Furthermore, compared with the CBF in the resting state, that in the stress state was decreased in the anterior circulation, mainly in the frontal lobe (voxel level P

The genetic information coded in DNA leads to trait innovation via a gene regulatory network (GRN) in development. Here, we developed a conserved non-coding element interpretation method to integrate multi-omics data into gene regulatory network (CNEReg) to investigate the ruminant multi-chambered stomach innovation. We generated paired expression and chromatin accessibility data during rumen and esophagus development in sheep, and revealed 1601 active ruminant-specific conserved non-coding elements (active-RSCNEs). To interpret the function of these active-RSCNEs, we defined toolkit transcription factors (TTFs) and modeled their regulation on rumen-specific genes via batteries of active-RSCNEs during development. Our developmental GRN revealed 18 TTFs and 313 active-RSCNEs regulating 7 rumen functional modules. Notably, 6 TTFs (OTX1, SOX21, HOXC8, SOX2, TP63, and PPARG), as well as 16 active-RSCNEs, functionally distinguished the rumen from the esophagus. Our study provides a systematic approach to understanding how gene regulation evolves and shapes complex traits by putting evo-devo concepts into practice with developmental multi-omics data.

Although coronavirus disease 2019 (COVID-19) primarily affects the respiratory system, this disease can affect multiple systems, including the musculoskeletal system. However, studies regarding the effect of COVID-19 on musculoskeletal system are limited. This study analyzed the bone mineral density (BMD) and body composition of 33 patients with COVID-19 using their chest CT scans at admission, discharge, and one-year follow-up. Among the patients, 2 were asymptomatic, 8 had mild symptoms, 19 had ordinary symptoms, and 4 had severe symptoms, and no critical patients were included. The mean length of hospital stay was (29.5±9.6) days, and the mean duration to follow-up was (423.0±53.6) days. The study found no significant changes in BMD of segmental or total thoracic vertebrae at admission, discharge, and one-year follow-up. No significant changes were observed in the subcutaneous adipose tissue (SAT) area, visceral adipose tissue (VAT) area, and total adipose tissue (TAT) of the mid-slice of the T12~L1 intervertebral disc. However, the asymptomatic and mild group had a higher average BMD of the T1~T12 than that of the common and severe group at admission and one-year follow-up. The common and severe group had higher VAT and TAT area than those of the asymptomatic and mild group at admission and one-year follow-up. This study provides valuable insights into the effects of COVID-19 on the musculoskeletal system and suggests that COVID-19 does not significantly affect thoracic BMD and abdominal adipose tissue after one year of infection.

Abstract With the prevalence of Traditional Chinese Medicine (TCM), automation techniques are highly required to support the therapy and save human resources. As the fundamental of the TCM treatment, acupoint detection is attracting research attention in both academic and industrial domains, while current approaches suffer from poor accuracy even with sparse acupoints or require extra equipment. In this study, considering the decision‐making knowledge of human experts, an image‐based deep learning approach is proposed to detect facial acupoints by localising the centre of acupoints. In the proposed approach, high‐resolution networks are selected as the backbone to learn informative facial features with different resolution paths. To fuse the learnt features from the high‐resolution network, a resolution, channel, and spatial attention‐based fusion module is innovatively proposed to imitate human decision, that is, focusing on the facial features to detect required acupoints. Finally, the heatmap is designed to integrally achieve the acupoint classification and position localisation in a single step. A small‐scale real‐world dataset is constructed and annotated to evaluate the proposed approach based on the authorised face dataset. The experimental results demonstrate the proposed approach outperforms other baseline models, achieving a 2.4228% normalised mean error. Most importantly, the effectiveness and efficiency of the proposed technical improvements are also confirmed by extensive experiments. The authors believe that the proposed approach can achieve acupoint detection with considerable high performance, and further support TCM automation.

Abstract Purpose Bloodstream infection (BSI) caused by Carbapenem-Resistant Enterobacteriaceae (CRE) are associated with poor outcomes in hematological patients. The aim of this study was to identify risk factors for mortality and evaluate the value of epidemiological feature of carbapenemases in guiding antimicrobial treatment options. Methods Hematological patients with monomicrobial CRE BSI between January 2012 and April 2021 were included. The primary outcome was all-cause mortality 30 days after BSI onset. Results A total of 94 patients were documented in the study period. Escherichia coli was the most common Enterobacteriaceae, followed by Klebsiella pneumoniae. 66 CRE strains were tested for carbapenemase genes, and 81.8% (54/66) were positive, including NDM (36/54), KPC (16/54), IMP (1/54). Besides, one E. coli isolate was found to express both NDM and OXA-48-like genes. Overall, 28 patients received an antimicrobial treatment containing ceftazidime-avibactam (CAZ-AVI), of which 21 cases were combined with aztreonam. The remaining 66 patients were treated with other active antibiotics (OAAs). The 30-day mortality rate was 28.7% (27/94) for all patients, and was only 7.1% ((2/28) for patients treated with CAZ-AVI. In multivariate analysis, the presence of septic shock at BSI onset (OR 10.526, 95% CI 1.376–76.923) and pulmonary infection (OR 6.289, 95% CI 1.351–29.412) were independently risk factors for 30-day mortality. Comparing different antimicrobial regimens, CAZ-AVI showed a significant survive benefit than OAAs (OR 0.068, 95% CI 0.007–0.651). Conclusion CAZ-AVI-containing regimen is superior to OAAs for CRE BSI. As the predominance of blaNDM in our center, we recommend the combination with aztreonam when choose CAZ-AVI.

Abstract Specific emitter identification (SEI) is an emerging device authentication technology, which depends on the inherent hardware characteristics of wireless devices. By analysing the received signal, the hardware characteristics of a specific emitter can be extracted at the receiver and used for device authentication and association. Most of the existing SEI schemes focus on the identification under closed sets. In view of the explosive growth of the number of IoT devices, based on generative adversarial networks, this study proposes a method that considers the identification of unknown emitters. The reconstruction network to reconstruct the signals of the known class and fully train the feature space of the signals of the known class is designed. In the discriminator, two channels are specifically designed to perform anomaly detection for unknown signals and end‐to‐end closed‐set classification for known signals. In order to better reject unknown signals and accept known signals, Receiver operating characteristic curve and Youden index are used to determine the optimal threshold for anomaly detection. Under the given optimal threshold conditions, the identified threshold points have larger True Positive Rate. In addition, the time‐frequency feature combination vector is designed to reveal the essential characteristics of emitters. The experimental results on the real‐world datasets collected from universal software radio peripherals in short‐range communication scenario show that compared with the existing open‐set recognition methods such as C2AE, Openmax and SoftMax, the average recognition accuracy of the proposed framework improved by 0.08, 0.15, and 0.2 respectively, and the Marco‐F1 score improved by 0.05, 0.1, and 0.16, respectively, which proves the superiority of the proposed framework. In addition to identifying unknown and known Universal software radio peripherals in this article, some potential and widespread applications of the proposed framework include access user security authentication in IoT, such as Hack RF and Blue tooth devices. In addition, as a relatively general signal processing framework, the model can be used for air safety management and maritime ship identity authentication in civil aspects. In the military aspect, it can be used in electronic support and various signal reconnaissance scenarios, such as automatic signal modulation recognition in open set scenarios, individual identity determination of radar emitter and unknown working state identification of transmitters, which proves reference for subsequent research on open‐set signal recognition.

Satellite edge computing shows promise in delivering seamless, low-latency services in challenging contexts such as deserts, oceans, and during natural disasters. Previous studies focused on the selection of suitable offloading nodes for task processing and result transmission to the original node. However, for end-to-end tasks, exemplified by applications like satellite-based remote sensing and forestry monitoring, the disparity between source and destination nodes emphasizes the importance of routing selection in data transmission. This aspect substantially limits the effectiveness of traditional computation offloading methods. In this paper, we formulate a joint computation offloading, routing, and multiple resource allocation optimization problem for end-to-end tasks in satellite edge computing networks. Moreover, to reduce the complexity of this nondeterministic polynomial-time hard (NP-hard) problem, we decompose it into the multidimensional resource allocation in fixed offloading and routing condition and the computation offloading and routing selection problem. An algorithm based on binary particle swarm optimization for joint computation offloading, routing, and multiple resource allocation optimization problem is proposed. Simulation results are presented to demonstrate the performance of our scheme compared with other baseline schemes.

Abstract BRAF V600E attracts wide attention in the treatment of colorectal cancer (CRC) as stratifying and predicting a refractory classification of CRC. Recent evidence indicates that Wnt/β‐catenin signaling is broadly activated and participates in the refractoriness of BRAF V600E CRC, but the underlying molecular mechanism needs to be elucidated. Here, heat shock 70 kDa protein 8 (HSPA8), an essential regulator in chaperone‐mediated autophagy (CMA), is identified as a potential therapeutic target for advanced BRAF V600E CRC. These results show that HSPA8 is transcriptionally upregulated in BRAF V600E CRC, which promotes CMA‐dependent degradation of caveolin‐1 (CAV1) to release β‐catenin into the nucleus and thus activates the Wnt/β‐catenin pathway, contributing to metastasis and progression of BRAF V600E CRC. Of note, HSPA8 directly interacts with the KIFSN motif on CAV1, the interaction can be enhanced by p38 MAPK‐mediated CAV1 S168 phosphorylation. Furthermore, pharmacological targeting HSPA8 by VER155008 exhibits synergistic effects with BRAF inhibitors on CRC mouse models. In summary, these findings discover the important role of the HSPA8/CAV1/β‐catenin axis in the development of refractory BRAF V600E CRC and highlight HSPA8 as a predictive biomarker and therapeutic target in clinical practice.

IntroductionMalocclusion, a common oral health problem in children, is associated with several contributing factors. This study aimed to investigate the prevalence of mixed dentition stage malocclusion and its contributing factors in Chinese Zhuang children aged 7–8 years.MethodsOverall, 2,281 Zhuang children, about 7–8 years old, were randomly selected using a stratified whole-cluster sampling method from schools in counties in Northwestern Guangxi, China. The children were examined on-site for malocclusion and caries by trained dentists, and basic data on the children were collected using questionnaires, including age, sex, parental education, parental accompaniment, and children's knowledge of malocclusion and treatment needs. Data were analyzed using the chi-square test and logistic regression analysis.ResultsThe total prevalence of malocclusion in Zhuang children aged 7–8 years was 58.5%, with the highest prevalence of anterior crossbite tendency, and the prevalence of anterior crossbite and anterior edge-to-edge occlusion was 15.1% and 7.7%, respectively. This was followed by an anterior increased overjet of 13.3% and an inter-incisor spacing of 10.3%. The lowest prevalence was 2.7% for anterior open bite. Sex, parental accompaniment, parental education, and decayed, missing, and filled teeth of the first primary molar were factors that contributed to malocclusion in Zhuang children.ConclusionMalocclusion is a common oral problem among Zhuang children. Therefore, more attention must be paid to the intervention and prevention of malocclusion. The impact factors should be controlled as early as possible.

The composition of Pseudostellaria heterophylla (Tai-Zi-Shen, TZS) is greatly influenced by the growing area of the plants, making it significant to distinguish the origins of TZS. However, traditional methods for TZS origin identification are time-consuming, laborious, and destructive. To address this, two or three TZS accessions were selected from four different regions of China, with each of these resources including distinct quality grades of TZS samples. The visible near-infrared (Vis/NIR) and short-wave infrared (SWIR) hyperspectral information from these samples were then collected. Fast and high-precision methods to identify the origins of TZS were developed by combining various preprocessing algorithms, feature band extraction algorithms (CARS and SPA), traditional two-stage machine learning classifiers (PLS-DA, SVM, and RF), and an end-to-end deep learning classifier (DCNN). Specifically, SWIR hyperspectral information outperformed Vis/NIR hyperspectral information in detecting geographic origins of TZS. The SPA algorithm proved particularly effective in extracting SWIR information that was highly correlated with the origins of TZS. The corresponding FD-SPA-SVM model reduced the number of bands by 77.2% and improved the model accuracy from 97.6% to 98.1% compared to the full-band FD-SVM model. Overall, two sets of fast and high-precision models, SWIR-FD-SPA-SVM and SWIR-FD-DCNN, were established, achieving accuracies of 98.1% and 98.7% respectively. This work provides a potentially efficient alternative for rapidly detecting the origins of TZS during actual production.

PurposeRapid eye movement sleep behavior disorder (RBD) affects 30%–40% of patients with Parkinson’s disease (PD) and has been linked to a higher risk of cognitive impairment, especially executive dysfunction. The aim of this study was to investigate the brain activation patterns in PD patients with RBD (PD-RBD+) compared to those without RBD (PD-RBD−) and healthy controls (HCs), and to analyze the correlation between changes in cerebral cortex activity and the severity of RBD.MethodsWe recruited 50 PD patients, including 30 PD-RBD+, 20 PD-RBD−, and 20 HCs. We used functional near infrared spectroscopy during a verbal fluency task (VFT-fNIRS) and clinical neuropsychological assessment to explore the correlation between PD-RBD+ and executive function and changes in neural activity.ResultsThe VFT-fNIRS analysis revealed a significant reduction in activation among PD-RBD+ patients across multiple channels when compared to both the PD-RBD− and HC groups. Specifically, PD-RBD+ patients exhibited diminished activation in the bilateral dorsolateral prefrontal cortex (DLPFC) and the right ventrolateral prefrontal cortex (VLPFC) relative to their PD-RBD− counterparts. Furthermore, compared to the HC group, PD-RBD+ patients displayed reduced activation specifically in the right DLPFC. Significantly, a noteworthy negative correlation was identified between the average change in oxygenated hemoglobin concentration (ΔHbO2) in the right DLPFC of PD-RBD+ patients and the severity of their RBD.ConclusionOur study offers compelling evidence that RBD exacerbates cognitive impairment in PD, manifested as executive dysfunction, primarily attributed to reduced prefrontal activation. These aberrations in brain activation may potentially correlate with the severity of RBD.

A significant amount of natural gas resources has been discovered in the Ordovician reservoirs under a thick layer of gypsum-salt strata as a result of ongoing research into deep natural gas in China’s Ordos Basin, however, the genetic type and source of the Ordovician sub-salt natural gas remain contentious. These limits understanding how the geochemical properties of the natural gas in Ordos Basin have evolved and how to best guide future exploration and development. Based on the components, carbon and hydrogen isotopic ratios of natural gas from the latest exploration wells, combined with the geological background, this study systematically analyzed the genetic types and sources of sub-salt natural gas of the central and eastern Ordos Basin. The results show that the Ordovician natural gas is mainly composed of hydrocarbon gases with low content of heavy hydrocarbons and dryness (CCH4/CCH4+) above 0.95, belonging to typical dry gas. Non-hydrocarbon gases mainly include N2 and CO2, and some natural gas samples contained H2S. The Ordovician sub-salt natural gas is primarily a self-generating and self-preserving oil-cracking gas with relatively high maturity (Ro ranging from 1.5% to 2.1%) mixed with coal-derived gas generated from upper-Paleozoic coal with relatively low maturity (Ro ranging from 1.1% to 1.5%). Due to the dual-source hydrocarbon supply, the Ordovician sub-salt reservoirs provide favorable gas accumulation conditions and development prospects. This study offers a reasonable explanation for the anomalous geochemical characteristics of the Ordovician sub-salt reservoirs in the Ordos Basin, and also may serve as a guide for future exploration of natural gas in the carbonate gypsum-salt sedimentary system in other basins.

Trophoblast cell surface antigen 2 (Trop2) exhibits limited expression in normal tissues but is over-expressed across various solid tumors. The effectiveness of anti-Trop2 antibody-drug conjugate (ADC) in managing breast cancer validates Trop2 as a promising therapeutic target for cancer treatment. However, excessive toxicity and a low response rate of ADCs pose ongoing challenges. Safer and more effective strategies should be developed for Trop2-positive cancers. The dynamic structural attributes and the oligomeric assembly of Trop2 present formidable obstacles to the progression of innovative targeted therapeutics. In this review, we summarize recent advancements in understanding Trop2’s structure and provide an overview of the epitope characteristics of Trop2-targeted agents. Furthermore, we discuss the correlation between anti-Trop2 agents’ epitopes and their respective functions, particularly emphasizing their efficacy and specificity in targeted therapies.

Cross-presentation (XPT) is an adaptation of the cellular process in which dendritic cells (DCs) present exogenous antigens on major histocompatibility complex (MHC) class I molecules for recognition of the cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, resulting in immunity or tolerance. Recent advances in DCs have broadened our understanding of the underlying mechanisms of XPT and strengthened their application in tumor immunotherapy. In this review, we summarized the known mechanisms of XPT, including the receptor-mediated internalization of exogenous antigens, endosome escape, engagement of the other XPT-related proteins, and adjuvants, which significantly enhance the XPT capacity of DCs. Consequently, various strategies to enhance XPT can be adopted and optimized to improve outcomes of DC-based therapy.

AbstractObjective This study compared the feasibility and efficacy of transabdominal ultrasound (TAU) and combined transabdominal and transvaginal ultrasound (TA/TV US)-guided percutaneous microwave ablation (PMWA) for uterine myoma (UM).Method This study enrolled 73 patients with UM who underwent PMWA via the transabdominal ultrasound-guided (TA group) or the combined transabdominal and transvaginal ultrasound-guided (TA/TV group) approaches. The intraoperative supplementary ablation rates, postoperative immediate ablation rates, lesion reduction rates and other indicators three months postoperatively were compared between the groups. The display of the needle tip, endometrium, uterine serosa, rectum and myoma feeding vessels under the guidance of TAU, transvaginal ultrasound (TVU) and TA/TV US were evaluated in the TA/TV group.Results In the TA/TV group, the real-time position of the needle tip and the endometrium complete display rate of the same lesions with TVU guidance were significantly higher than those using TAU. TA/TV US guidance significantly improved the complete display rate of each indicator. The intraoperative supplementary ablation rate in the TA/TV group was lower than that in the TA group. Similarly, the postoperative immediate ablation and volume reduction rates of the lesions three months postoperatively were higher than those in the TA group, especially for lesions with a maximum diameter ≥6 cm.Conclusion TA/TV US is an effective monitoring method that can be used to improve imaging display. Its use is recommended in patients with obesity, poor transabdominal ultrasound image quality and large myoma volumes.

Volunteer service activities of college students are crucial for universities to educate students on civic engagement. Education laws and scientific methods must be employed to enhance college students' willingness to volunteer and actively participate in volunteer service activities. Based on literature collection and collation, this study takes the theory of planned behaviour as the basic framework, includes the dimension of ''cognition,'' designs the questionnaire, and discusses the relationship among the relevant factors that affect the volunteer service behaviour of college students. Cognition, defined as understanding volunteerism's personal and social benefits, positively predicted attitudes, norms, and control, but not directly behaviour. A sample survey of Chinese college students and a correlation analysis of effective questionnaires demonstrate that college students' volunteer service attitudes, subjective norms, and perceived behaviour control positively impact volunteer service behaviour intention, which can predict volunteer service behaviour. College students' cognition of volunteer service significantly and positively impacts their attitude toward it, subjective norms, and perceived behavioural control but does not directly impact their volunteer service behaviour. Thus, the following aspects must be improved: guiding attitude, creating atmosphere, improving mechanisms, innovating projects, strengthening cognition, and implementing practical education. The findings of this study can help colleges and universities to clarify the impact mechanism of college students' volunteer service cognition on their volunteer service behaviour. It contributes new evidence on optimising the student environment to engage youth in building community well.

Abstract Objective Cystic echinococcosis (CE), a zoonotic parasitic disease caused by Echinococcus granulosus, remains a public health and socioeconomic issue worldwide, making its prevention and treatment of vital importance. The aim of this study was to investigate changes in the intestinal microbiota of mice immunized with three peptide vaccines based on the recombinant antigen of E. granulosus, P29 (rEg.P29), with the hope of providing more valuable information for the development of vaccines against CE. Methods Three peptide vaccines, rEg.P29T, rEg.P29B, and rEg.P29T + B, were prepared based on rEg.P29, and a subcutaneous immunization model was established. The intestinal floras of mice in the different immunization groups were analyzed by 16 S rRNA gene sequencing. Results The intestinal microbiota analysis at both immunization time points revealed that Firmicutes, Bacteroidota, and Verrucomicrobiota were the predominant flora at the phylum level, while at the genus level, Akkermansia, unclassified_Muribaculaceae, Lachnospiraceae_NK4A136_group, and uncultured_rumen bacterium were the dominant genera. Some probiotics in the intestines of mice were significantly increased after immunization with the peptide vaccines, such as Lactobacillus_taiwanensis, Lactobacillus_reuteri, Lachnospiraceae_NK4A136_group, Bacteroides_acidifaciens, and so forth. Meanwhile, some harmful or conditionally pathogenic bacteria were decreased, such as Turicibacter sanguinis, Desulfovibrio_fairfieldensis, Clostridium_sp, and so forth, most of which are associated with inflammatory or infectious diseases. Kyoto Encyclopaedia of Genes and Genomes enrichment analysis revealed that the differential flora were enriched in multiple metabolic pathways, primarily biological systems, human diseases, metabolism, cellular processes, and environmental information processing. Conclusion In this study, we comprehensively analyzed and compared changes in the intestinal microbiota of mice immunized with three peptide vaccines as well as their related metabolic pathways, providing a theoretical background for the development of novel vaccines against E. granulosus.

IntroductionThe use of the fungus Cordyceps sinensis (CS), which has a long history of use in China for its tonic properties, has sparked controversy based on the risk from high arsenic levels in CS.MethodsThis study collected all 24 online dispute cases related to CS from the China Legal Documents Network. Excel software was applied to fit the distribution of the sample data and analyze the trend of trial results of CS disputes and the tendency of professional claims trials. The analysis covers the trend of trial results of contract dispute cases involving CS products (CDCCS), and the tendency of the results of CDCCS, using correlation to analyze the factors influencing the results. We analyzed trial tendencies in CDCCS by the methods of complex network analysis (Gephi software) to explore each factor’s effect on the trial outcome of in these claims cases and to predict the trial outcomes of new cases. Simultaneously use KNN to train and predict CS cases.ResultsThe peak number of trial cases was in 2018, and there has been a gradual increase in the rate of losing claims on the claimant. Correlation analysis was used to obtain that the likelihood of the defendant winning a claim is positively correlated with DR, FSS, IDP, and KSP, and negatively correlated with the adoption of JIFDD (3), JIFDD (15), and APL. Gephi software was used to conduct a complex network analysis of the factors influencing the tendency of trial results in CS disputes, showing that noncompliance with FSS, existence of KSP, and submission of IDP evidence by the buyer are the direct factors influencing the seller’s defeat. The seller’s “failure to perform DR” is the key factor in the seller’s defeat in cases. On this basis a probability function is developed to predict a trial win rate of 0.7803 for freshman cases, classifier to predict the remaining four samples and new cases, and get the prediction accuracy is 0.8, 95% CI: (0.2836, 0.9949), and the latter was higher than the former.DiscussionIt is concluded that the attribute of CS products is a scientific issue, the jurisdiction of CS disputes is confusing and needs to be clarified, and the application of the provisions in judicial trials is cannot adapt to the current environment and needs to be resolved. This study advocates that the government design policy from the top and establish a study on the boundary between administrative and judicial functions to provide a theoretical guarantee to circumvent lazy administration and unscientific law enforcement. The government can provide a legal and regulatory system to improve food quality and regulate management.

Background Dose reduction of direct oral anticoagulant (DOAC) medications is inconsistently applied to older adults with multiple morbidities, potentially due to perceived harms and unknown benefits of standard dosing. Methods and Results Using 2013 to 2017 US Medicare claims linked to Minimum Data Set records, we conducted a retrospective cohort study. We identified DOAC initiators (apixaban, dabigatran, rivaroxaban) aged ≥65 years with nonvalvular atrial fibrillation residing in a nursing home. We estimated inverse‐probability of treatment weights for DOAC dose using propensity scores. We examined safety (hospitalization for major bleeding) and effectiveness outcomes (all‐cause mortality, thrombosis [myocardial infarction, stroke, systemic embolism, venous thromboembolism]). We estimated hazard ratios (HRs) and 95% CIs using cause‐specific hazard‐regression models. Of 21 878 DOAC initiators, 48% received reduced dosing. The mean age of residents was 82.0 years, 66% were female, and 31% had moderate/severe cognitive impairment. After estimating inverse‐probability of treatment weights, standard dosing was associated with a higher rate of bleeding (HR, 1.18 [95% CI, 1.03–1.37]; 9.4 versus 8.0 events per 100 person‐years). Standard‐dose therapy was associated with the highest rates of bleeding among those aged >80 years (9.1 versus 6.7 events per 100 person‐years) and with a body mass index

Ag nanoparticles (AgNPs) are toxic and can accumulate in the human body or the environment, resulting in biotoxic effects. Ti3C2Tx, a new class of graphene-like 2D nanomaterials, is used in numerous applications due to its special physicochemical properties. There is great concern about the potential damage that this material may cause to the environment and human health. In this study, the interaction mechanisms of Ti3C2Tx, AgNPs and Ti3C2Tx/AgNPs materials with human serum albumin (HSA) were characterized using multispectral analysis and zeta potential measurements, respectively. The results showed that the effects of the three materials on the conformational changes of HSA were AgNPs > Ti3C2Tx/AgNPs > Ti3C2Tx in order. Hydrogen bonding and electrostatic interaction forces played an important role in the binding process of Ti3C2Tx and its complexes with HSA. Ag nanoparticles have a comparatively high level of biotoxicity and have a more significant effect on the conformational changes of proteins. Ti3C2Tx itself has biocompatibility and a large specific surface area. The biotoxicity of Ti3C2Tx/AgNPs complex is lower than that of AgNPs, indicating that the addition of Ti3C2Tx can reduce the biotoxicity of Ag nanoparticles, and Ti3C2Tx may be used as a carrier substance for Ag nanoparticles, which can reduce the toxicity of AgNPs while giving it unique properties similar to those of Ti3C2Tx, thus improve the biosafety of Ag nanoparticles in the application process.

Background: Acute pancreatitis (AP) is a potentially lethal disease related to prominent microcirculation dysfunction. Pancreatic microvascular endothelial dysfunction enhances oxidative stress with tissue damage. Increased superoxide production disrupts endothelial junction integrity and increases endothelial permeability. Endothelial mitochondrial ROS (mtROS) represent a major intracellular source of superoxide anions. The non-canonical function of telomerase reverse transcriptase (TERT) involves the maintenance of cellular redox homeostasis in somatic tissues. Methods: We investigated whether TERT restores microcirculation dysfunction and attenuates the endothelium injury by inhibiting superoxide production during AP progression. We established TERT transgenic and TERT knock-down mice and used cerulein (CER) and lipopolysaccharide (LPS) injections to induce AP models. In addition, we exposed HUVECs to LPS following TERT overexpression or silencing to explore the role of TERT in endothelial dysfunction. We also performed flow cytometry and confocal microscopy assays by using HUVECs. And a mtROS inhibitor, MitoTempo, was used to scavenge mitochondria superoxide and alkyl. Results: TERT transgenic mice were found to have restored pancreatic microcirculation profiles and microvascular endothelial morphology compared with wild-type mice under cerulein injection. In contrast, TERT silencing displayed the opposite effect in response to cerulein. Subsequently, we showed that TERT overexpression attenuates mtROS production and mitochondrial dysfunction during LPS-stimulated endothelial dysfunction. Furthermore, we found that TERT overexpression maintains the balance between mitochondrial contents and ATP level during endothelial dysfunction. In addition, the protective trend of MitoTempo is impeded after TERT silencing. Conclusion: TERT restores pancreatic microcirculation dysfunction and attenuates microvascular endothelium lesions by inhibiting the increase of superoxide production and mitochondrial dysfunction.

Pulmonary fibrosis (PF) is the pathological structure of incurable fibroproliferative lung diseases that are attributed to the repeated lung injury-caused failure of lung alveolar regeneration (LAR). Here, we report that repetitive lung damage results in a progressive accumulation of the transcriptional repressor SLUG in alveolar epithelial type II cells (AEC2s). The abnormal increased SLUG inhibits AEC2s from self-renewal and differentiation into alveolar epithelial type I cells (AEC1s). We found that the elevated SLUG represses the expression of the phosphate transporter SLC34A2 in AEC2s, which reduces intracellular phosphate and represses the phosphorylation of JNK and P38 MAPK, two critical kinases supporting LAR, leading to LAR failure. TRIB3, a stress sensor, interacts with the E3 ligase MDM2 to suppress SLUG degradation in AEC2s by impeding MDM2-catalyzed SLUG ubiquitination. Targeting SLUG degradation by disturbing the TRIB3/MDM2 interaction using a new synthetic staple peptide restores LAR capacity and exhibits potent therapeutic efficacy against experimental PF. Our study reveals a mechanism of the TRIB3–MDM2–SLUG–SLC34A2 axis causing the LAR failure in PF, which confers a potential strategy for treating patients with fibroproliferative lung diseases.

Abstract Antigen self-assembly nanovaccines advance the minimalist design of therapeutic cancer vaccines, but the issue of inefficient cross-presentation has not yet been fully addressed. Herein, we report a unique approach by combining the concepts of “antigen multi-copy display” and “calcium carbonate (CaCO3) biomineralization” to increase cross-presentation. Based on this strategy, we successfully construct sub-100 nm biomineralized antigen nanosponges (BANSs) with high CaCO3 loading (38.13 wt%) and antigen density (61.87%). BANSs can be effectively uptaken by immature antigen-presenting cells (APCs) in the lymph node upon subcutaneous injection. Achieving efficient spatiotemporal coordination of antigen cross-presentation and immune effects, BANSs induce the production of CD4+ T helper cells and cytotoxic T lymphocytes, resulting in effective tumor growth inhibition. BANSs combined with anti-PD-1 antibodies synergistically enhance anti-tumor immunity and reverse the tumor immunosuppressive microenvironment. Overall, this CaCO3 powder-mediated biomineralization of antigen nanosponges offer a robust and safe strategy for cancer immunotherapy.

Abstract A double‐stranded RNA (dsRNA) phage phiYY is able to kill a pyomelanin‐producing Pseudomonas aeruginosa strain, which was isolated from a 40‐year‐old man with interstitial lung disease (ILD) and chronic lung infection. Phage therapy was used as a last resort for this patient. The three‐course nebulized phiYY treatment was used to reduce the bacterial burden and clinical symptoms of the patient. Recurrences of P. aeruginosa infections were observed 1–3 days post phage therapy. The recurrent isolates exhibited distinct antibiotic‐susceptibility profiles compared with the original strain yet were still susceptible to phiYY. This assay represents the application of dsRNA phage in the treatment of chronic lung infection, albeit the safety and efficacy of the dsRNA phage require further assessment.

Predicting the post-blast re-entry time precisely can improve productivity and reduce accidents significantly. The empirical formulas for the time prediction are practical to implement, but lack accuracy. In this study, a novel method based on the back-propagation neural network (BPNN) was proposed to tackle the drawbacks. A numerical model was constructed and 300 points of sample data were recorded, with consideration to fresh air volume, occupational exposure limit, toxic gas volume per kg of explosives and roadway length. The BPNN model with six neurons in a hidden layer was then developed and prediction performance was discussed in terms of four indicators, namely, the root mean square error (RMSE), the coefficient of determination (R2), the mean absolute error (MAE) and the sum of squares error (SSE). Furthermore, one representative empirical formula was introduced and calibrated for the comparison. The obtained results showed that the BPNN model had a more remarkable performance, with RMSE of 21.45 (R2: 0.99, MAE: 10.78 and SSE: 40934), compared to the empirical formula, with RMSE of 76.89 (R2: 0.90, MAE: 42.06 and SSE: 526147). Hence, the BPNN model is a superior method for predicting the post-blast re-entry time. For better practical application, it was then embedded into the software.

This study aims to examine the effects of various maternity leave support on the quiet quitting behaviors and mental health conditions of working mothers across industries during the post-pandemic period. Through an empirical survey method of 310 valid responses from a panel data, the study results indicated that working mothers who took maternity leave were less likely to adopt quiet quitting behaviors when they returned to work after childbirth and showed better mental health at work compared to their peers who did not take maternity leave because of childbirth and/or childcare. Additionally, paid maternity leave was not found to have a significant effect on quiet quitting behaviors and mental health of working mothers across industries, but the duration of maternity leave was found as a significant factor in impacting working mothers’ quiet quitting behaviors and their mental health conditions. Moreover, peer workers’ quiet quitting behaviors and supervisors’ support for childcare (e.g., flexible work schedule) were found significantly to improve working mothers’ quiet quitting tendencies at work. Lastly, there exist significant differences in age and race in the working mothers’ quiet quitting behaviors at work.

Abstract Background and aims Chimeric antigen receptor (CAR)-T cell therapy is a novel type of immunotherapy. However, the use of CAR-T cells to treat acute myeloid leukaemia (AML) has limitations. B7-H3 is expressed in several malignancies, including some types of AML cells. However, its expression in normal tissues is low. Therefore, B7-H3 is ideal for targeted AML therapy. Materials and methods First, we constructed B7-H3 CAR that can target B7-H3, and then constructed B7-H3-CAR-T cells in vitro, which were co-incubated with six AML cell lines expressing different levels of B7-H3, respectively. The toxicity and cytokines were detected by flow cytometry. In vivo, AML model was established in B-NSG mice to study the toxicity of B7-H3-CAR T on AML cells. Results In vitro functional tests showed that B7-H3-CAR-T cells were cytotoxic to B7-H3-positive AML tumor cells and had good scavenging effect on B7-H3-expressing AML cell lines, and the cytokine results were consistent. In vivo, B7-H3-CAR-T cells significantly inhibited tumor cell growth in a mouse model of AML, prolonging mouse survival compared with controls. Conclusion B7-H3-CAR-T cells may serve as a novel therapeutic method for the targeted treatment of AML.