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Zhou (2023) introduced the concept of path-factor critical avoidable graph and determined several parameter bounds for (P≥2,n) or (P≥3,n)-factor critical avoidable graphs. Certain instances are listed in Zhou (2023) to show that these toughness or isolated toughness bounds are sharp. However, the derivation processes are flawed. In this remark, we directly modify the derivation processes and obtain the revised bounds. The counterexamples are updated to satisfy κ(G)=n+2. Finally, richness bounds on binding number for a graph to be path-factor critical avoidable are determined.

The increasing popularity of the Internet of Things and the growing microelectronics market have led to a heightened demand for microscale energy storage devices, such as microbatteries and microsupercapacitors. Although lithium microbatteries have dominated the market, safety concerns arising from incidents like self-ignition and explosions have prompted a shift towards new microscale energy storage devices prioritizing high safety. Zinc-based micro-energy storage devices (ZMSDs), known for their high safety, low cost, and favorable electrochemical performance, are emerging as promising alternatives to lithium microbatteries. However, challenges persist in the fabrication of microelectrodes, electrolyte infusion, device packaging, and integration with microelectronics. Despite these challenges, significant progress has been made over the last decade. This review focuses on the challenges and recent advancements in zinc-based micro-energy storage, offering unique insights into their applications and paving the way for the commercial deployment of high-performance ZMSDs.

The traditional Chinese medicine (TCM) bupleurum-ginger-licorice formula presents significant anti-cancer effects, but its active ingredients and inhibitory mechanism remain unclear. In this work, the core effective ingredient quercetin and its signal transducer and activator of transcription 3 (Stat3) receptor both were identified by network pharmacology. Quercetin is a low-toxicity, non-carcinogenic flavonoid with antioxidant, anti-inflammatory and anticancer activities, which is widely distributed in edible plants. Stat3 can bind to specific DNA response elements and serves as a transcription factor to promote the translation of some invasion/migration-related target genes, considered as a potential anticancer target. Here, molecular docking and molecular dynamics (MD) simulation both were used to explore molecular recognition of quercetin with Stat3. The results show that quercetin impairs DNA transcription efficiency by hindering Stat3 dimerization, partially destroying DNA conformation. Specifically, when the ligand occupies the SH2 cavity of the enzyme, spatial rejection is not conductive to phosphokinase binding. It indirectly prevents the phosphorylation of Y705 and the formation of Stat3 dimer. When the inhibitor binds to the DT1005 position, it obviously shortens the distance between DNA and DBD, enhances their binding capacity, and thereby reduces the degree of freedom required for transcription. This work not only provides the binding modes between Stat3 and quercetin, but also contributes to the optimization and design of such anti-cancer inhibitors.

Background: Even though Thailand has launched multiple migrant health policies, migrants still face various barriers in accessing health care. To some extent, these barriers may be reduced by health microinsurance. The M-FUND is a low-cost, not-for-profit health protection scheme for migrant workers in Thailand, created by Dreamlopments Social Enterprise and Foundation to support sustainable access to quality healthcare services for migrants. We aimed to investigate the impact of the M-FUND on utilization of health services. Methods: Over a period of three months, we conducted quantitative face-to-face interviews with 408 M-FUND members, and 452 age, sex and location matched non-member controls in Tak Province, Thailand. We compared utilization of health services between members and non-members using logistic regression controlling for a number of socio-demographic variables and variables related to migration such as years in Thailand, legal status, etc. Findings: M-FUND members were more likely to have utilized outpatient services (adjusted odds ratio: 1·74, 95 % confidence interval: 1·24–2·44), inpatient services (2·96, 1.11–7·92), and emergency care (1·89, 0·78–4·56), although the latter was not statistically significant. Members were more likely not to have purchased medicines over-the-counter (1·67, 1·22–2·27) than non-members. Members were also more likely to have utilized any additional specific service during a consultation (2·31, 1·49–3·58) including any type of imaging method (2·62, 1·29–5·29) and blood tests (1·64, 0·99–2·71). There were some differences between men and women, but most were not statistically significant. Interpretation: The M-FUND health microinsurance was positively associated with the utilization of all major types of health services among migrant workers and their dependents in Thailand. For migrants, particularly vulnerable migrant workers and their dependents, the M-FUND appears to be a good approach to reducing barriers to health care. This study of the impact of health microinsurance for migrants provides important information for policy and program planners in the field of migrant health. However, more research is needed on health microinsurance schemes for migrants in different settings and for other underserved communities as well as the sex-specific impact on health service utilization.

Abstract Background Cancer‐associated fibroblasts (CAFs), integral to the tumour microenvironment, are pivotal in cancer progression, exhibiting either pro‐tumourigenic or anti‐tumourigenic functions. Their inherent phenotypic and functional diversity allows for the subdivision of CAFs into various subpopulations. While several classification systems have been suggested for different cancer types, a unified molecular classification of CAFs on a single‐cell pan‐cancer scale has yet to be established. Methods We employed a comprehensive single‐cell transcriptomic atlas encompassing 12 solid tumour types. Our objective was to establish a novel molecular classification and to elucidate the evolutionary trajectories of CAFs. We investigated the functional profiles of each CAF subtype using Single‐Cell Regulatory Network Inference and Clustering and single‐cell gene set enrichment analysis. The clinical relevance of these subtypes was assessed through survival curve analysis. Concurrently, we employed multiplex immunofluorescence staining on tumour tissues to determine the dynamic changes of CAF subtypes across different tumour stages. Additionally, we identified the small molecule procyanidin C1 (PCC1) as a target for matrix‐producing CAF (matCAF) using molecular docking techniques and further validated these findings through in vitro and in vivo experiments. Results In our investigation of solid tumours, we identified four molecular clusters of CAFs: progenitor CAF (proCAF), inflammatory CAF (iCAF), myofibroblastic CAF (myCAF) and matCAF, each characterised by distinct molecular traits. This classification was consistently applicable across all nine studied solid tumour types. These CAF subtypes displayed unique evolutionary pathways, functional roles and clinical relevance in various solid tumours. Notably, the matCAF subtype was associated with poorer prognoses in several cancer types. The targeting of matCAF using the identified small molecule, PCC1, demonstrated promising antitumour activity. Conclusions Collectively, the various subtypes of CAFs, particularly matCAF, are crucial in the initiation and progression of cancer. Focusing therapeutic strategies on targeting matCAF in solid tumours holds significant potential for cancer treatment.

This paper investigates the issue of disturbance observer-based fuzzy adaptive optimal finite-time control in light of the backstepping approach for strict-feedback nonlinear systems with bias fault term and full state constraints. Considering that external disturbance and bias fault signal can affect the stability of control and control quality, a disturbance observer is constructed to track the external disturbances and bias fault online. A disturbance observer-based finite-time control strategy is proposed to achieve optimized control by utilizing the fuzzy logic system approximation-based adaptive dynamic programming method under the critic-actor framework. The purpose of the critic is to evaluate control performance and the role of the actor is to execute control behaviour. In addition, it is proved that the proposed fuzzy adaptive optimal finite-time scheme not only realizes all signals in closed-loop system are bounded, but also ensures that system states are restricted within specific sets. Finally, simulation results are shown to demonstrate the effectiveness of the proposed control strategy.

ABSTRACTBackground Multiple myeloma (MM) is a highly heterogeneous disease. Cuproptosis is a novel mode of death that is closely associated with several diseases, such as hepatocellular carcinoma. However, its role in MM is unknown.Methods MM transcriptomic and clinical data were obtained from UCSC Xena and gene expression omnibus (GEO) databases. Following MM samples were divided into different subtypes based on the cuproptosis genes, the differentially expressed genes (DEGs) among different subtypes, namely, candidate cuproptosis related genes were analyzed by univariate Cox and least absolute shrinkage and selection operator (LASSO) regression to construct a cuproptosis-related risk model. After the independent prognostic analysis was performed, a nomogram was constructed. Finally, Functional enrichment analysis and immune infiltration analysis were performed in the high- and low-risk groups, potential therapeutic agents were then predicted.Results The 784 MM samples in UCSC Xena cohorts were divided into three different subtypes, and 4 out of 346 candidate cuproptosis related genes, namely CDKN2A, BCL3, KCNA3 and TTC14 were used to construct a risk model. Risk score was considered a reliable independent prognostic factor for MM patients. It was investigated that the pathway of cell cycle was significantly enriched in the high-risk group. In addition, immune score, ESTIMATE score and cytolytic activity were significantly different between different risk groups, as well as 13 immune cells such as memory B cells. Nine drugs were predicted in our study.Conclusion A cuproptosis-related prognostic model was constructed, which may have a potential guiding role in the treatment of MM.

The toxicity sites and toxicity mechanism of aflatoxin B1（AFB1） were explored in this study, and aiming at the toxicity sites of AFB1, the advantages of microbial degradation of AFB1 were compared. Then the degradation mechanism of AFB1 by detoxifying enzyme method in microbial method was reviewed. Moreover, the composite application of detoxification enzyme method combined with other methods is prospected.

Abstract Background An accurate genotyping analysis is one of the critical prerequisites for patients with colorectal cancer receiving matched therapies. Conventional genotyping analysis is currently used to detect either gene mutations or MSI status, delaying the detection of critical tumor biomarkers and thus the optimal time for treatment. An assay that analyzes both biomarkers in a streamlined process is eagerly needed. Methods We developed an assay combining Multiplex PCR Amplification, Single‐base Extension and capillary electrophoresis (CE) analysis (MASE‐CE) for synchronous detection of KRAS/NRAS/BRAF mutations and MSI status. In a 190 colorectal cancer cohort, we identified seven somatic mutations in KRAS, NRAS and BRAF as well as five MSI loci (D2S123/D5S346/D17S250/BAT‐25/BAT‐26) simultaneously. KRAS/NRAS/BRAF mutations were detected by NGS and MASE‐CE, and MSI status were detected by PCR‐CE and MASE‐CE methods. Results The MASE‐CE method showed high consistency with NGS for mutation detection (Kappa value ≥0.8) and PCR‐CE (Kappa value = 0.79). In addition, the limits of detection (LOD) of MASE‐CE assay for MSI and somatic mutation were 5% and 2%, respectively. Conclusions In somatic mutation detection and MSI detection, the LOD of MASE‐CE assay was superior to that of qPCR and NGS. MASE‐CE assay is a highly sensitive, time‐saving and specimen‐saving method, which can greatly avoid the cumbersome testing process and provide clinical decision for doctors in time.

With the condition of contugous double-thick coal seams downward mining as the background, in view of the adverse effects of upper remaining coal pillars on the stability of mining roadway and stope, the field measurement and theoretical analysis are adopted to study the regional characteristics of the deviatoric stress invariant under section coal pillar, the mechanism of strong strata behaviors during mining cross the upper boundary coal pillar and its scale effect. The research shows that: ① When the position of open-off cuts is not even in the upper seam, a transverse translation layout is adopted for the lower mining roadway, which not only place the roadway in a stable stress environment, but also prevent the collapse disaster by transform the whole mining cross the upper coal pillar into twice small-range processes. ② The stress state of floor rock under section coal pillar is analyzed with the second deviatoric stress invariant (J2) intensity, the third deviatoric stress invariant (J3) intensity, and the second deviatoric stress invariant (J2) horizontal gradient. The floor is partitioned by the three indexes, and the minimum horizontal distance between roadway and section coal pillar is determined to be 24 m. ③ During the mining cross the upper coal pillar, the combined interaction of the first or periodical weighting and the sudden instability of roof and coal pillar system is the basic reasons for the strong strata behaviors. Based on the scale effect of mining cross the upper coal pillar, the maximum horizontal distance between mining roadway and section coal pillar is determined to be 36 m. The feasibility and rationality of the transverse translation layout of 30 m in lower mining roadway was verified by the field measurement of typical coal mine.

As a basic method to quantify the scale effect of porous media materials, representative elementary volume (REV) is an effective means to construct the macro-meso structure of coal. In order to improve the accuracy of REV results of coal meso-structure, a quantitative characterization method of coal meso-structure was proposed based on the study of pore-fracture structure characteristics at meso-scale of coal samples. Based on the binary images of pore-fracture at 423 scales at different positions and different fracture directions of coal samples, the geometric characteristics of coal meso-structure were analyzed from three aspects: pore-fracture distribution density, geometric shape and orientation. Based on the sampling method considering the heterogeneity and anisotropy of coal, the spatial effect and directional effect of REV size are analyzed. Finally, the reasonable microscopic REV size of coal sample is determined by the coefficient of variation method. The results show that: ① A method for accurate identification and quantitative analysis of pore fracture structure is proposed for SEM images of coal samples with uneven gray level, blurred boundary and low contrast. ② A quantitative characterization system of meso-structure reflecting the anisotropy of coal samples was established, including porosity, overall shape factor, fractal dimension and directional distribution coefficient. ③ Compared with the parallel bedding, the micro-fractures in the vertical bedding direction are more developed, the porosity is 2 times that of the parallel bedding, the contribution rate of large aperture pores is 85%, and it has strong spatial filling ability. The overall morphology of pores and fractures is poor, but the edge morphology is smooth and the directional distribution tends to be simpler. ④ Based on the acceptable value of the coefficient of variation of 10%, the size of the coal meso-structure characterization unit is determined to be 200 μm × 200 μm.

A great number of electric vehicle （EV） charging piles can participate in the electricity spot market and auxiliary service market through load aggregation to comprehensively optimize operating costs. The flexible adjustment of charging load， which is more acceptable to charging users， is adopted as a way for EV load aggregators to participate in the frequency modulation auxiliary service market. The scheme research of EV load aggregators’ participation in grid-friendly interaction under the framework of electricity market is carried out from four aspects such as overall technical scheme， market mechanism design， aggregation platform design， and evaluation and verification system design. The scheme proposes a cloud-side-end collaborative architecture of EV charging load aggregation platform under the framework of service frequency modulation auxiliary market to solve the control and communication problems of massive charging piles， which can provide a reference for EV load aggregators to participate in auxiliary service market.

Objective To investigate the selection of treatment strategies and prognostic factors for patients with stage T3 and T4 laryngeal carcinoma. Methods A total of 132 patients with stage T3 and T4 laryngeal cancer admitted to our hospital from March 2010 to March 2019 were retrospectively selected as research objects. According to the different treatment strategies, the patients were divided into simple surgery group (group A, 57 cases), simple chemoradiotherapy group (group B, 32 cases), and surgery combined with chemoradiotherapy group (group C, 43 cases). The general data and clinicopathological features of the three groups were compared, and a survival curve was drawn by the Kaplan–Meier method. The 3-year survival rates of the three groups were compared. Then, the same 132 patients were divided into survival and death groups. The clinical data of the two groups were compared, and the prognostic factors were analyzed by multivariate logistic regression. A back propagation (BP) neural network model was constructed, and its differentiation and accuracy were evaluated. Results The proportions and 3 year survival rates of patients with poor differentiation, lymphatic vascular invasion, and involvement of lymph nodes outside the capsule in group C were significantly higher than those in groups A and B (P < 0.05). The 3 year survival rate of 132 patients was 68.94%(41/132). Poor differentiation, N2-N3 stage, lymphatic vascular invasion, and involvement of lymph nodes outside the capsule were risk factors for death (P < 0.05), whereas surgery combined with radiotherapy and chemotherapy were protective factors (P < 0.05). The BP neural network model exhibited good discrimination and high accuracy. Conclusion Surgery combined with radiotherapy and chemotherapy can significantly improve survival rate in patients with poor differentiation, lymphatic vascular invasion, and involvement of lymph nodes outside the capsule. Close attention should be paid to patients with stage N2-N3 in the formulation of reasonable treatment strategies.

Background: As one of the important components of immunotherapies, mRNA vaccines have displayed promising clinical outcomes in solid tumors. Nonetheless, their efficacy remains unclear in pancreatic adenocarcinoma (PAAD). Given the interaction of pyroptosis with anticancer immunity, our study aims to identify pyroptosis-related antigens for mRNA vaccine development and discern eligible candidates for vaccination. Methods: Utilizing gene expression data from TCGA and ICGC, we integrated RNA-seq data and compared genetic alterations through cBioPortal. Differential gene expressions were integrated using GEPIA. Relationships between immune cell abundance and tumor antigens were analyzed and visualized via TIMER. WGCNA facilitated the clustering of pyroptosis-related genes, identification of hub genes, and pathway enrichment analyses. Pyroptosis landscape was depicted through graph learning-based dimensional reduction. Results: Four overexpressed and mutant pyroptosis-related genes associated with poor prognosis were identified as potential antigens for mRNA vaccines in PAAD, including ANO6, PAK2, CHMP2B, and RAB5A. These genes displayed positive associations with antigen-presenting cells. PAAD patients were stratified into three pyroptosis subtypes. Notably, the PS3 subtype, characterized by a lower mutation count and TMB, exhibited “cold” immunological traits and superior survival compared to other subtypes. The pyroptosis landscape exhibited considerable heterogeneity among individuals. Furthermore, the turquoise module emerged as an independent prognostic indicator and patients with high expressions of hub genes might not be suitable candidates for mRNA vaccination. Conclusions: In PAAD, ANO6, PAK2, CHMP2B, and RAB5A are prospective pyroptosis-related antigens for mRNA vaccine development, which holds potential benefits for patients classified as PS3 and those with diminished hub gene expressions, providing insights into personalized mRNA vaccine strategies.

Neoadjuvant chemoradiotherapy (nCRT) has become the standard treatment for patients with locally advanced rectal cancer (LARC). However, 20–40% of patients with LARC show little to no response to nCRT. Thus, comprehensively understanding the tumor microenvironment (TME), which might influence therapeutic efficacy, and identifying robust predictive biomarkers is urgently needed. Pre-treatment tumor biopsy specimens from patients with LARC were evaluated in detail through digital spatial profiling (DSP), public RNA sequencing datasets, and multiplex immunofluorescence (mIF). DSP analysis revealed distinct characteristics of the tumor stroma compared to the normal stroma and tumor compartments. We identified high levels of human leukocyte antigen-DR/major histocompatibility complex class II (HLA-DR/MHC-II) in the tumor compartment and B cells in the stroma as potential spatial predictors of nCRT efficacy in the Discovery cohort. Public datasets validated their predictive capacity for clinical outcomes. Using mIF in an independent nCRT cohort and/or the total cohort, we validated that a high density of HLA-DR/MHC-II+ cells in the tumor and CD20 + B cells in the stroma was associated with nCRT efficacy (all p ≤ 0.021). Spatial profiling successfully characterized the LARC TME and identified robust biomarkers with the potential to accurately predict nCRT response. These findings have important implications for individualized therapy.

Background: Previous research has highlighted the importance of regularizing daily routines for maintaining mental health. Little is known about whether and how regularity of daily routines is associated with reduced post-traumatic stress disorder (PTSD) symptoms. Objective: We aimed to examine the associations between regularity of daily routines and PTSD symptoms in two studies (N = 796). Method: In Study 1, prospective data were analysed with the latent change score model to investigate the association between sustainment of regular daily routines and change in PTSD symptoms over time amid massive civil unrest in Hong Kong in 2019. Study 2 used vignette as a quasi-experimental method to assess the ability of maintaining regular daily routines in face of a major stressor, and tested its associations with PTSD symptoms. Results: In Study 1, increased regularity of diverse daily routines was inversely associated with increased PTSD symptoms amid the civil unrest in Hong Kong (β = −.427 to −.224, 95% confidence intervals [−.543 to −.359, −.310 to −.090], p values

Vanadium dioxide (VO2) has attracted extensive attention due to the specific metal-insulator phase transition as well as the wide device applications. The practical performance of VO2-based device strongly depends on the quality of VO2, since the higher quality of VO2 film always shows much more pronounced phase transition behavior. Thus, the preparation of high quality VO2 film is essential and highly desirable. In this work, we have prepared high-quality VO2 film on SiC substrate by water vapor oxidation with graphene (G) buffer layer, which showed excellent phase transformation properties. Compared with the VO2/SiC sample without G buffer layer, the VO2/G/SiC films show the resistance changes up to four-orders of magnitude across the phase transition boundary and superior optoelectronic properties, which indicates the significant role of G layer in the film growth process. The current study not only provides an economical and feasible method for VO2/G/SiC thin film preparation with high quality, but also supply some clues for the application of G-based VO2 devices in the future.

Summary: Background: Dengue virus (DENV) infection during pregnancy increases the risk of adverse fetal outcomes, which has become a new clinical challenge. However, the underlying mechanism remains unknown. Methods: The effect of DENV-2 infection on fetuses was investigated using pregnant interferon α/β receptor-deficient (Ifnar1−/−) mice. The histopathological changes in the placentas were analyzed by morphological techniques. A mouse inflammation array was used to detect the cytokine and chemokine profiles in the serum and placenta. The infiltration characteristics of inflammatory cells in the placentas were evaluated by single-cell RNA sequencing. Findings: Fetal growth restriction observed in DENV-2 infection was mainly caused by the destruction of the placental vasculature rather than direct damage from the virus in our mouse model. After infection, neutrophil infiltration into the placenta disrupts the expression profile of matrix metalloproteinases, which leads to placental dysvascularization and insufficiency. Notably, similar histopathological changes were observed in the placentas from DENV-infected puerperae. Interpretation: Neutrophils play key roles in placental histopathological damage during DENV infection, which indicates that interfering with aberrant neutrophil infiltration into the placenta may be an important therapeutic target for adverse pregnancy outcomes in DENV infection. Funding: The National Key Research and Development Plans of China (2021YFC2300200-02 to J.A., 2019YFC0121905 to Q.Z.C.), the National Natural Science Foundation of China (NSFC) (U1902210 and 81972979 to J. A., 81902048 to Z. Y. S., and 82172266 to P.G.W.), and the Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan, China (IDHT20190510 to J. A.).

Manufacturing enterprises will accumulate a large number of manufacturing instances as they run and develop. Being able to excavate and reuse the instance resources reasonably is one of the most effective ways to improve manufacturing and support innovation. To determine the reuse object scientifically and raise the reuse flexibility, a novel system for discovery and reuse of typical process route based on the information entropy and PSO-Kmeans clustering algorithm is proposed in this paper. In this system, a similarity measurement method of machining process routes based on the information entropy of multistage longest common subsequence is developed. Then a discovery method of typical process route based on the spectral clustering idea and PSO-Kmeans clustering algorithm is invented, and the two reuse approaches based on the typical process route are analyzed and discussed. Finally, the three case studies are rendered and the results reveal that the proposed system can provide better support for manufacture instance reuse.

Objective To investigate the effect of the intervention of Hufu Tongbian scraping combined with Traditional Chinese Medicine(TCM) iontophoresis on relieving symptoms of Fontaine's stage II arteriosclerosis obliteration(ASO). Methods Totally 130 cases of hospitalized patients with Fontaine's stage II ASO were randomly divided into 4 groups: group A (control group, n=31) and group B (Hufu Tongbian Scraping group, n=31), group C (TCM Iontophoresis group, n=34), group D (combination group, n=34). Group A was given specialist nursing, group B was given specialist nursing combined with Hufu Tongbian scraping intervention, group C was given specialist nursing combined with TCM iontophoresis intervention, group D was given specialist nursing combined with Hufu Tongbian scraping and TCM iontophoresis intervention. Symptom quantitative score and Visual Analogue Score (VAS)of pain were measured before and 15 days. after intervention. Results After intervention, there were significant differences in each dimension of symptom score and pain score among the four groups (P＜0. 05). the scores of each dimension of symptom score and pain score in groups B, C and D were decreased after intervention compared with those before intervention(P＜0. 05), and the scores in the three groups were lower than those in group A after intervention (P＜0. 05). After intervention, the scores of each dimension of symptom score and pain score in group D were lower than those in groups B and C (P＜0. 05), but there was no significant difference between groups B and C after intervention (P＞0. 05). Conclusion The intervention Hufu Tongbian scraping combined with TCM iontophoresis can significantly reduce the symptom score of ASO patients, relieve the symptoms of acid swelling and numbness, relieve the pain of patients, promote comfort, and provide better nursing for ASO patients. (目的 探讨虎符铜砭刮痧联合中药离子导入干预缓解FontaineⅡ期下肢动脉硬化闭塞症(ASO)患者临床症状的影响。方法 选取河北省中医院周围血管科2020年11月—2021年10月收治的符合诊断的FontaineⅡ期ASO住院患者130例, 随机分为4组: A组(对照组)、B组(虎符铜砭刮痧组)、C组(中药离子导入组)、D组(联合组)。A、B组各31例, C、D组各34例。A组给予专科护理, B组专科护理联合虎符铜砭刮痧干预, C组专科护理联合中药离子导入干预, D组专科护理来讷河虎符铜砭刮痧和中药离子导入干预。共干预15 d, 分别于干预前和干预后测定症状量化评分及疼痛视觉模拟评分。结果 干预后4组症状评分各维度评分和疼痛评分差异有统计学意义(P＜0. 05); 与干预前相比, B、C、D组干预后症状评分各维度评分和疼痛评分均下降(P＜0. 05), 且干预后三组各评分均低于A组(P＜0. 05); 干预后D组症状评分各维度评分和疼痛评分均低于B、C组(P＜0. 05), 但B、C组干预后各评分差异无统计学意义(P＞0. 05)。结论 虎符铜砭刮痧联合中药离子导入干预可更显著地降低ASO患者症状评分, 缓解患者酸胀、麻木等症状, 并可减轻患者疼痛, 促进舒适, 为ASO患者提供更优质护理。)

Abstract Currently little is known about the interrelations between changes in psychiatric symptoms and changes in resources (personal, social, financial) amid large-scale disasters. This study investigated trajectories of psychiatric symptoms and their relationships with different patterns of changes in personal, social, and financial resources between 2020 and 2022 amid the COVID-19 pandemic. A population-representative sample (N = 1333) was recruited to complete self-report instruments at the pandemic’s acute phase (February–July 2020, T1), and again at 1-year (March–August 2021, T2) and 1.5-year (September 2021–February 2022, T3) follow-ups. Respondents reported depressive and anxiety symptoms, self-efficacy, perceived social support, and financial capacity. Growth mixture modeling (GMM) identified four trajectories of depressive and anxiety symptoms: resilience (72.39–74.19%), recovery (8.40–11.93%), delayed distress (7.20–7.35%), and chronic distress (8.33–10.20%). Four patterns were demonstrated in resource changes: persistent high resources (40.89–47.64%), resource gain (12.08–15.60%), resource loss (6.30–10.43%), and persistent low resources (28.73–36.61%). Loss and gain in financial resources characterized chronic distress and resilience, respectively. Loss in personal resources characterized delayed distress, whereas loss or no gain in social resources was related to chronic/delayed distress. Respondents in resilience were also more likely to have persistent high resources while those with delayed/chronic distress were more likely to have persistent low resources. These results provide an initial evidence base for advancing current understanding on trajectories of resilience and psychopathology in the context of resource changes during and after large-scale disasters.

Objective To measure and analyze biological characteristics and aging phenotype of SHJHhr mice and provide basic data for the application of the mouse model in aging mechanisms research and antiaging drug development.MethodsWith ICR mice of the same age as control group, the body mass growth data of SHJHhr mice at the age of 3 to 16 weeks, the reproduction ability of 1 to 4 fetuses and the life cycle of SHJHhr mice were measured. Blood routine (30 items) and serum biochemical indexes (25 items) of 6-week-old SHJHhr mice were measured. The venous blood of 8-week-old SHJHhr mice was collected for flow cytometry analysis to determine the content of immune cells. The aging bone structure of the cancellous bone and bone mineral density of SHJHhr mice aged 4, 8 and 26 weeks were measured by micro-CT. Histopathological changes of bone and joint of 8-week-old mice were observed.ResultsCompared with ICR mice, the female and male body mass of SHJHhr mice were significantly lower at the age of 16 weeks (P < 0.05), and the reproductive performance of female mice was low (P < 0.01) or did not have normal reproductive capacity. The shortest survival time of SHJHhr mice was 57 weeks and the longest was 71 weeks, which was shorter than those of normal ICR mice, showing obvious rapid aging phenomenon. At the same time, some physiological and biochemical indexes of blood and pathological changes of bone and cartilage tissues also showed the accelerated aging and abnormality of animal physiological functions.ConclusionSHJHhr mice have some biological characteristics of rapid aging as well as some physiological and pathological changes caused by aging.

This study used the historical and cultural block of Taiping Street in Changsha as the research object. First the current microclimate environment of the street space was analyzed, then numerical simulations based on ENVI-met software were performed, which compared the microclimate numerical simulation results of three typical greening optimization schemes of the street space in the study area and the benchmark scheme, as well as explained the degree of thermal environment control of the greening optimization scheme. This study is expected to provide a reference for the reconstruction of urban historical blocks as well as optimization and control of the thermal environment. The results showed that: 1) With an hourly change in solar radiation, the thermal environment changed considerably, and the horizontal spatial distribution was characterized by "high temperature and low humidity" and "low temperature and high humidity." Thermal comfort is related to the underlying surface conditions, wind environment, building layout, and other factors. The low temperature and high humidity of the area with relatively concentrated green space along street spaces had a slow-release effect on the thermal environment. The ventilation effect of the area with the dense building layout was poor, and the thermal radiation of the underlying surface was high, affecting the heat dissipation and humidification in the research area. 2) The enclosed space layout of buildings in the study area caused building shadows and poor ventilation to affect the green space, which was not conducive for cooling and humidification. 3) Three types of greening transformation schemes were proposed for the street spaces of three different architectural layouts in the historical block of Taiping Street. The three kinds of street space green space optimization and benchmark schemes (the current street space situation) were simulated using ENVI-met microclimate simulation software. Optimization results showed that the same greening optimization scheme had different regulatory effects on the thermal environment in different building layouts. The three kinds of street spaces significantly reduced the average radiation temperature of the block by increasing the greening area of the block. The optimal regulatory effect of the thermal environment of the tree-shrub+three-dimensional (water) compound green space type was better than that of the tree-shrub and tree-grass scheme in the daytime. Under a certain green space ratio, the area of shade generated by the uniform and decentralized layout of green space in a commercial space covered the largest range of street space. The order of the degree of thermal environment optimization and control was decentralized>parallel>centralized. The residential and square spaces were affected by the architectural layout, and the green space layout should have good ventilation, cooling, and humidification effects; therefore, the maximum degree of thermal environment optimization and control is the centralized layout.

In order to improve the comprehensive properties of Inconel 625 alloy,the alloy was studied using hardness tester,tensile machine,electrochemical workstation,optical microscope and scanning electron microscope based on a change of the solution treatment method,and the effects of five different heat treatment processes on the microstructure evolution law,mechanical properties and corrosion properties of the alloy were discussed.Results showed that the as-cast Inconel 625 alloy was mainly composed of austenite,and the alloy had high hardness but poor corrosion resistance.After a solution treatment at 1090℃and a subsequent water cooling treatment,the precipitated niobium carbide resulting from the heat treatment was retained at the grain boundary,which improved the corrosion resistance of the alloy.Air cooling or furnace cooling caused a reprecipitation of chromium carbide,resulting in a decline in the corrosion performance of the alloy.Special process treatment could effectively improve the corrosion resistance of the alloy and improve the plasticity of the material without reducing the strength.This research achievements could optimize the heat treatment process of Inconel 625 alloy in production and provide effective basis for the improvement of the comprehensive properties of the material.

Objective:. The genomic landscapes of metastatic colorectal cancer (mCRC) have been extensively studied; however, the genetic mechanisms underlying the locoregional recurrence (LR) of CRC remain unclear. The objective of our study was to investigate genomic evolution during LR in CRC using high-throughput sequencing. Methods:. Twenty-three CRC patients with matched primary and LR tissues were recruited from Nanfang Hospital and Zhejiang Cancer Hospital between January 2011 and December 2018. The last date of follow-up was March 2020. Tissue samples were analyzed by whole-exome sequencing and the genomic profiles were depicted by single nucleotide variation, mutational signature, copy number variation, clonal architecture, and other features. The evolutionary process was speculated with comparison of the genetic variations between primary and LR lesions. The disseminating clusters from primary to LR lesions were identified by variant allele frequency dynamics. Furthermore, the early-recurrent biomarker was explored by comparing the indel signature between early- and late-recurrent patients. The study was approved by the Institutional Review Board of Nanfang Hospital of Southern Medical University (approval No. 2020010) on September 11, 2020. Results:. The results highlighted distinct origins of LR between patients with high microsatellite instability and microsatellite stability. LR lesions evolved independently in patients with high microsatellite instability, while LR lesions were highly clonally related to the primary lesions in patients with microsatellite stability. Late-acquired variations in LR lesions encompassed a wide range of driver genes involved in histone methylation, DNA replication, T cell activation, PDCD1 gain, and LMNA loss. Furthermore, clonal analysis of the disseminating cells identified a dominant polyclonal seeding pattern during LR. The indel signature ID4 was associated with significantly shorter disease-free survival in patients with relapsed CRC according to a public dataset. Conclusion:. These findings pose a challenge for the development of new approaches targeting the interactions of multiple clones in the establishment of LR and in terms of optimizing the clinical management of susceptible patients.

Abstract Background Neuroendocrine carcinomas of the gastrointestinal tract (GI‐NECs) remain a disease of grim prognosis with limited therapeutic options. Their molecular characteristics are still undefined. This study aimed to explore the underlying genetic basis and heterogeneity of GI‐NECs. Methods Comprehensive genomic analysis using whole‐exome sequencing was performed on 143 formalin‐fixed, paraffin‐embedded samples of surgically resected GI‐NEC with a thorough histological evaluation. Mutational signatures, somatic mutations, and copy number aberrations were analyzed and compared across anatomic locations and histological subtypes. Survival analysis was conducted to identify the independent factors. Results In total, 143 GI‐NECs were examined: the stomach, 87 cases (60.8%); the esophagus, 29 cases (20.3%); the colorectum, 20 cases (14.0%); and the small intestine, 7 cases (4.9%). Eighty‐three (58.0%) and 60 (42.0%) cases were subclassified into small cell and large cell subtypes, respectively. GI‐NECs showed distinct genetic alterations from their lung counterparts and non‐neuroendocrine carcinomas in the same locations. Obvious heterogeneity of mutational signatures, somatic mutations, and copy number variations was revealed across anatomic locations rather than histological subtypes. Except for tumor protein p53 (TP53) and retinoblastoma 1 (RB1), the most frequently mutated genes in the stomach, esophagus, colorectum, and small intestine were low‐density lipoprotein receptor‐related protein 1B (LRP1B), notch receptor 1 (NOTCH1), adenomatosis polyposis coli (APC), catenin beta 1 (CTNNB1), respectively. Mutations in the WNT‐β‐catenin, NOTCH and erythroblastic leukemia viral oncogene B (ERBB) pathways were prevalently identified in gastric, esophageal, and colorectal NECs, respectively. Importantly, 104 (72.7%) GI‐NECs harbored putative clinically relevant alterations, and non‐gastric location and RB1 bi‐allelic inactivation with copy number alterations were identified as two independent poor prognostic factors. Furthermore, we found that tumor cells in GI‐NECs first gain clonal mutations in TP53, RB1, NOTCH1 and APC, followed by subsequent whole‐genome doubling (WGD) and post‐WGD clonal mutations in LRP1B, CUB and Sushi multiple domains 3 (CSMD3), FAT tumor suppressor homolog 4 (FAT4) and erb‐b2 receptor tyrosine kinase 4 (ERBB4), and finally develop subclonal mutations. Conclusions GI‐NECs harbor distinct genomic landscapes and demonstrate significant genetic heterogeneity across different anatomic locations. Moreover, potentially actionable alterations and prognostic factors were revealed for GI‐NECs.

The hypothalamic-pituitary-adrenal (HPA) axis and hypothalamic-pituitary-gonadal (HPG) axis plays a central role in mediating physiological responses related to the reproductive system under any stressful condition. However, the molecular mechanism underlying the effects of stress on physiology still needs to be elucidated. This study demonstrated that increasing the stocking density from 4 to 8 birds/m2 during the laying period decreased the egg production rate of laying ducks by 13.04 − 63.55% and feed intake by 7.40 − 23.44%. Transcriptome analysis between high- and low-feeding-density laying ducks revealed 469, 509, 428 and 210 differentially expressed genes (DEGs) in the hypothalamus, pituitary, ovary and follicular membrane, respectively. Gene ontology (GO) and KEGG enrichment analysis showed that the DEGs in the hypothalamus and pituitary were primarily enriched in the biostimulation and dopamine secretion pathways. The major enrichment pathways in the ovarian and follicular membranes involved lipid metabolism, negative regulation of inflammatory response, and steroid hormone biosynthesis. Among the DEGs in the HPG system, POMC and GnRH1 were identified, which may be manifesting their crucial roles in regulating the stress response and reproduction. Our data showed that a high stocking density as environmental stress negatively affects the reproductive performance in ducks through transcriptional changes in the HPG axis.Highlights Raising the stocking density from 4 to 8 birds/m2 decreased the egg production rate and feed intake in laying ducks. The transcriptome indicated that stocking density affects the stress response of laying ducks through the hypothalamus-pituitary. The stress signals are subsequently transmitted to affect gene expression related to the reproduction process in laying ducks’ ovarian and follicular tissues. The hypothalamic expression of POMC and GnRH1 may play a central role in integrating stress signals and the reproductive processes of laying ducks.

Eggs are a major animal protein source for humans. Egg formation is a complex process involved in coordinating various tissues and organs, while blood is necessary for gonad differentiation and egg formation. In this study, non-targeted metabolomics technology was employed to determine the serum metabolites at the time point of 70 days (before laying period, T0), 130 days (pre-laying period, T1), 300 days (peak laying period, T2), and 340 days (post laying period, T3) in female ducks, to provide comprehensive metabolic profiling in reflecting the overall temporal changes. The results showed significant differences in the metabolites of different comparison groups (T0 vs. T1, T2 vs. T3, and T0 & T1 vs. T2& T3), supporting the main physiological responses in ducks are differential among laying periods. L-Aspartic Acid, Biotin, and Thyroxine can be considered the potential biomarkers related to sexual maturity. L-Lysine, Lumichrome, Thiamine, Riboflavin, and Pyridoxine may be biomarkers related to egg formation. Sorbitol, Isorhamnetin, Naringenin, and Hydroxykynurenine were the biomarkers associated with the decline of egg production. In addition, the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis showed that sexual maturity was mainly involved in the biosynthesis of secondary plant metabolites, Tricarboxylic Acid Cycle, Mineral absorption, pentose phosphate pathway, and Oxocarboxylic acid metabolism. Egg formation disturbed amino acid metabolism, vitamin metabolism, and carbohydrate metabolism. The neuroactive ligand-receptor interaction pathway may affect egg production. These findings can detect the different physiological statuses in female ducks and provide a theoretical basis for increasing egg production, and ensuring sustainable farming.Highlights The main physiological responses in ducks are differential among laying periods. 3, 6, and 4 biomarkers related to sexual maturity, the formation of the egg, and the decline of egg production, respectively. Sexual maturity was mainly involved in the biosynthesis of secondary plant metabolites, Tricarboxylic Acid Cycle, Mineral absorption, pentose phosphate pathway, and Oxocarboxylic acid metabolism, and egg formation disturbed amino acid metabolism, vitamin metabolism, and carbohydrate metabolism. while the neuroactive ligand-receptor interaction pathway may affect egg production.

Purpose: Oncology studies employing digital dissection methodologies have provided some insight on the biological features of tumor microenvironment of Triple-negative breast cancer (TNBC), but molecular diagnostics rarely have therapeutic impact. We aimed to identify a novel prognostic biomarker to investigate immune characteristics of TNBC using transcriptomic features.Patients and Methods: We extracted whole transcriptome from breast cancer tissue of 30 TNBC patients and then used bioinformatics approaches to characterize the different immune cell contents in tumor tissue and para-cancerous tissue. We extract 2 indicators to describe the major differences in immune infiltration in the microenvironment between tumor tissue and para-cancerous tissue. We then combined the 2 indicators that represent the levels of increased and decreased infiltration in each sample to obtain the Immune Infiltration Score (IIS). Then we compared the tumor-infiltrating immune cell contents and immune infiltrating status in TNBC samples with CIBERSORT and ESTIMATE score to validate the IIS. Finally, 132 TNBC patients from the Cancer Genome Atlas program (TCGA) dataset was used to validate the predictive power of IIS.Results: 4 types of upregulated and 4 types of downregulated immune cells were identified in the tumor tissue samples of the TNBC patients. Then we developed a novel biomarker, IIS. Results showed that IIS score can clearly separate cancer and para-cancerous tissue. Using the same cutoff value of 0 in the TNBC-TCGA cohort, we show that those patients with a higher IIS had significantly higher PD-L1 expression and shorter progression-free survival time than those with a lower IIS value, indicating IIS score can be generalized to other TNBC datasets.Conclusion: we explored the immune infiltration landscape in 30 TNBC patients and provided IIS as a novel and reliable biomarker to evaluate the progression-free survival and prognosis of the TNBC patients.

Abstract Background Orthostatic tremor (OT) is a type of postural tremor of the lower extremities that has not been described in either phenylketonuria (PKU) or hyperphenylalaninemia (HPA). Because little is known about the clinical features and therapeutic responses of OT in mild HPA, we describe a mild HPA patient who presented with OT as an initial symptom. Case presentation A 22-year-old male was admitted for bilateral leg tremor while standing, with symptom onset eight months prior. One month before admission, the tremor disappeared in the left leg but persisted in the right leg. Electromyography recorded from the right gastrocnemius revealed a 6–8 Hz tremor, which appeared when the patient was standing and disappeared when he was resting or walking. Blood screening showed a phenylalanine/tyrosine ratio of 2.06 and a phenylalanine level of 140 μmol/L. Urine metabolic screening was negative. Whole-exome sequencing confirmed the presence of a compound heterozygous mutation, c.158G > A and c.728G > A, in phenylalanine hydroxylase (PAH) gene. After three months of levodopa/benserazide tablets (250 mg, tid) and a low-phenylalanine diet treatment, the tremor disappeared. Conclusions Young-onset mild HPA is a relatively rare autosomal recessive metabolic disease, and slow OT is a rare clinical feature. Metabolic screening and genetic testing are the keys to early diagnosis and treatment. For adolescents and young adults, appropriate medication and long-term dietary therapy remain important treatments. This case expanded the disease spectrum of slow OT.

Penile squamous cell carcinoma (PSCC) is a rare disease. The treatment options for advanced penile cancer are often limited, and the prognosis remains poor. We reported a 52-year-old male recurrent and metastatic PSCC patient with high PD-L1 expression (90%) and TMB (14.4 muts/Mb). He had undergone penectomy, bilateral inguinal lymph node dissection, and excision of the abdominal wall mass. Despite cisplatin-based concurrent chemoradiotherapy and sequential chemotherapy with docetaxel plus cisplatin then being carried out, the carcinoma still progressed. The patient then obtained progression-free survival with continuous sintilimab, although he experienced the new onset of ICI-induced diabetes after 24 cycles of sintilimab and required sustained insulin treatment. He had negative type 1 diabetes-associated autoantibodies and the susceptible HLA genotype DR3-DQ2 haplotype. This is the first patient with radiation and multichemorefractory PSCC who has obtained the remarkable anti-tumor effect of partial regression exceeding 32 months during continuous sintilimab and anlotinib treatment.

Abstract Background Radiotherapy (RT) is one of the major therapeutic approaches to hepatocellular carcinoma (HCC). Ionizing radiation (IR) inducing the generation of reactive oxygen species (ROS) leads to a promising antitumor effect. However, the dysregulation of the redox system often causes radioresistance and impairs the efficacy of RT. Increasing evidence indicates that nuclear protein 1 (NUPR1) plays a critical role in redox reactions. In this study, we aim to explore the role of NUPR1 in maintaining ROS homeostasis and radioresistance in HCC. Methods The radioresistant role of NUPR1 was determined by colony formation assay, comet assay in vitro, and xenograft tumor models in vivo. Probes for ROS, apoptosis assay, and lipid peroxidation assay were used to investigate the functional effect of NUPR1 on ROS homeostasis and oxidative stress. RNA sequencing and co-immunoprecipitation assay were performed to clarify the mechanism of NUPR1 inhibiting the AhR/CYP signal axis. Finally, we analyzed clinical specimens to assess the predictive value of NUPR1 and AhR in the radiotherapeutic efficacy of HCC. Results We demonstrated that NUPR1 was upregulated in HCC tissues and verified that NUPR1 increased the radioresistance of HCC in vitro and in vivo. NUPR1 alleviated the generation of ROS and suppressed oxidative stress, including apoptosis and lipid peroxidation by downregulating cytochrome P450 (CYP) upon IR. ROS scavenger N-acetyl-L-cysteine (NAC) and CYP inhibitor alizarin restored the viability of NUPR1-knockdown cells during IR. Mechanistically, the interaction between NUPR1 and aryl hydrocarbon receptor (AhR) promoted the degradation and decreased nuclear translation of AhR via the autophagy-lysosome pathway, followed by being incapable of CYP’s transcription. Furthermore, genetically and pharmacologically activating AhR abrogated the radioresistant role of NUPR1. Clinical data suggested that NUPR1 and AhR could serve as novel biomarkers for predicting the radiation response of HCC. Conclusions Our findings revealed the role of NUPR1 in regulating ROS homeostasis and oxidative stress via the AhR/CYP signal axis upon IR. Strategies targeting the NUPR1/AhR/CYP pathway may have important clinical applications for improving the radiotherapeutic efficacy of HCC.

At present, there are few studies on the stress corrosion sensitivity of 316L stainless steel in the environment containing Cl- and CH3COOH. In this paper, the effects of Cl- and CH3COOH on the stress corrosion sensitivity of 316L stainless steel were studied by slow strain rate tensile test, scanning electron microscopy (SEM) and X - ray photoelectron spectroscopy (XPS). Results showed that when the concentration of Cl- was higher than 2 000 mg/L, the stress corrosion tendency of 316L stainless steel was obvious, and the stress corrosion sensitivity of 316L stainless steel increased with an increasing rate while the Cl- concentration rised. Under the condition of low concentration of Cl-, CH3COOH could exacerbate stress corrosion. When the concentration of Cl- reached 1 000 mg/L, CH3COOH could inhibit stress corrosion. The XPS results revealed that CH3COOH could change the composition of 316L stainless steel passivation film and then improve its corrosion resistance.

Abstract BRAF V600E-mutant colorectal cancer (CRC) is a rare subtype of colorectal cancer with poor prognosis. Compelling evidence indicates that the heparanase (HPSE) gene has multiple functions in cancer, however, its role in BRAF V600E-mutant CRC remains elusive. Differentially expressed genes between BRAF V600E-mutant and wild-type patients were explored by analyzing public data from The Cancer Genome Atlas and the Gene Expression Omnibus. Clinical samples of 172 patients with BRAF V600E-mutant CRC diagnosed at Zhongshan Hospital Fudan University were collected. Overall survival was analyzed using Kaplan–Meier curves and Cox regression models. Cell models and xenografts were utilized to investigate the effect of HPSE on tumor proliferation. HPSE was significantly highly expressed in the BRAF V600E-mutant group. High HPSE expression level was independently associated with inferior survival in the BRAF V600E-mutant cohort. HPSE knockdown impeded tumor proliferation of BRAF V600E-mutant CRC cells in vitro and in vivo. Mechanistically, HPSE silencing arrested cell cycle in G0/G1 phase by downregulating Cyclin E2 expression via the AKT/p27Kip1 pathway. These findings support a role for HPSE in promoting BRAF V600E-mutant CRC progression, which suggests it holds great promise as a prognostic biomarker and a potential therapeutic target for the aggressive CRC subtype.

PurposeHypertension is an important risk factor for atherosclerotic cerebral small vessel disease (CSVD). Higher blood pressure is associated with a higher CSVD burden and the presence of relevant magnetic resonance imaging (MRI) markers. However, the effect of blood pressure level on CSVD burden and imaging markers including white matter hyperintensity (WHM), lacune, enlarged perivascular spaces (EPVS), and cerebral microbleed (CMB) remains unknown. The purpose of this study was to investigate the correlation between blood pressure level and CSVD burden at different time periods throughout the day.MethodsIn total, 144 in-patients with CSVD (66.4 ± 9.8 years, 50% male) were enrolled and underwent brain MRI, and 24-h ambulatory blood pressure was assessed. Patients were categorized into five groups according to their MRI-evaluated total CSVD burden scores (0–4). Spearman's correlation analysis was performed to examine the correlation between blood pressure levels at different time periods and the total CSVD score or the markers of periventricular WMH, deep WMH, lacune, EPVS, and CMB.ResultsOf the 144 patients, 83.3% (120/144) harbored one or more CSVD markers of interest. The systolic blood pressure (SBP) of 24-h, daytime, nighttime, and morning differed significantly among the five groups. The SBP levels increased significantly with the total CSVD scores during 24 h (P = 0.018), daytime (P = 0.018), and nighttime (P = 0.035). Spearman's correlation analysis demonstrated that the SBP of 24 h, daytime, nighttime, and morning and the diastolic blood pressure (DBP) of 24 h and morning positively and significantly correlated with the total CSVD score (P < 0.05). A logistic regression analysis indicated that both morning SBP and DBP were independent risk factors for total CSVD burden (OR = 1.13, 95% CI: 1.02–1.23, P = 0.015; OR = 1.19, 95% CI: 1.06–1.33, P = 0.005). Spearman's correlation analysis indicated a significant positive correlation between morning SBP and higher deep WMH Fazekas score (r = 0.296, P < 0.001), EPVS grade in the basal ganglia (r = 0.247, P = 0.003), and the presence of lacune (r = 0.173, P = 0.038) and CMB (r = 0.326, P < 0.001). Morning DBP only correlated positively with the presence of CMB (r = 0.292, P < 0.001).ConclusionHigher SBP signficantly correlated with total CSVD burden in patients with atherosclerotic CSVD. Early morning blood pressure level is an important indicator to reflect the severity of CSVD patients.

Vaccines are among the most cost-effective public health measures for controlling infectious diseases. Coxiella burnetii is the etiological agent of Q fever, a disease with a wide clinical spectrum that ranges from mild symptoms, such as fever and fatigue, to more severe disease, such as pneumonia and endocarditis. The formalin-inactivated whole-cell vaccine Q-VAX® contains hundreds of antigens and confers lifelong protection in humans, but prior sensitization from infection or vaccination can result in deleterious reactogenic responses to vaccination. Consequently, there is great interest in developing non-reactogenic alternatives based on adjuvanted recombinant proteins. In this study, we aimed to develop a multivalent vaccine that conferred protection with reduced reactogenicity. We hypothesized that a multivalent vaccine consisting of multiple antigens would be more immunogenic and protective than a monovalent vaccine owing to the large number of potential protective antigens in the C. burnetii proteome. To address this, we identified immunogenic T and B cell antigens, and selected proteins were purified to evaluate with a combination adjuvant (IVAX-1), with or without C. burnetii lipopolysaccharide (LPS) in immunogenicity studies in vivo in mice and in a Hartley guinea pig intratracheal aerosol challenge model using C. burnetii strain NMI RSA 493. The data showed that multivalent vaccines are more immunogenic than monovalent vaccines and more closely emulate the protection achieved by Q-VAX. Although six antigens were the most immunogenic, we also discovered that multiplexing beyond four antigens introduces detectable reactogenicity, indicating that there is an upper limit to the number of antigens that can be safely included in a multivalent Q-fever vaccine. C. burnetii LPS also demonstrates efficacy as a vaccine antigen in conferring protection in an otherwise monovalent vaccine formulation, suggesting that its addition in multivalent vaccines, as demonstrated by a quadrivalent formulation, would improve protective responses.

Colorectal cancer (CRC) remains a challenging and deadly disease with high tumor microenvironment (TME) heterogeneity. Using an integrative multi-omics analysis and artificial intelligence-enabled spatial analysis of whole-slide images, we performed a comprehensive characterization of TME in colorectal cancer (CCCRC). CRC samples were classified into four CCCRC subtypes with distinct TME features, namely, C1 as the proliferative subtype with low immunogenicity; C2 as the immunosuppressed subtype with the terminally exhausted immune characteristics; C3 as the immune-excluded subtype with the distinct upregulation of stromal components and a lack of T cell infiltration in the tumor core; and C4 as the immunomodulatory subtype with the remarkable upregulation of anti-tumor immune components. The four CCCRC subtypes had distinct histopathologic and molecular characteristics, therapeutic efficacy, and prognosis. We found that the C1 subtype may be suitable for chemotherapy and cetuximab, the C2 subtype may benefit from a combination of chemotherapy and bevacizumab, the C3 subtype has increased sensitivity to the WNT pathway inhibitor WIKI4, and the C4 subtype is a potential candidate for immune checkpoint blockade treatment. Importantly, we established a simple gene classifier for accurate identification of each CCCRC subtype. Collectively our integrative analysis ultimately established a holistic framework to thoroughly dissect the TME of CRC, and the CCCRC classification system with high biological interpretability may contribute to biomarker discovery and future clinical trial design.

The terrain of Changbai Mountain has great influence on the distribution of atmospheric flows and the occurrence and development of precipitation. However, quantitative studies on the real terrain characteristics and the terrain effect on precipitation distribution in this region are scant at present. This study quantitatively analyzes the regional characteristic of topographic perturbations and the relationship between terrain, wind, and precipitation in Changbai Mountain region by using a spectral analysis of the two-dimensional discrete cosine transform. Three domains with relatively heavy summer precipitation are selected as the study region. The results indicate that the overall terrain of the Changbai Mountain region exhibits anisotropic characteristics. The terrain spectra of domain B are less than those of domains A and C across the whole wavelength (λ) bands, indicating that the large-scale topographic perturbations of domain B are relatively weak. The largest topographic spectral peak of domain C shows the most pronounced undulation of terrain among the three domains. The dominant wavelengths of terrain height variance for domains A and C, both close to the respective maximum wavelengths, indicate more prominent large-scale topographic perturbations. For domain A, the variation of the precipitation spectra is consistent with that of the wind spectra at the wavelength bands of λ < 390 km, showing a high correlation between wind field and the occurrence of rainfall. The inverse relationship at larger wavelengths indicates that multiple factors contribute to the occurrence of rainfall. For domain B, there is consistency in the fluctuations of terrain spectra, precipitation spectra, and wind spectra at the wavelength bands of λ < 278.3 km, implying that the smaller-scale terrain has an important effect on the occurrence of summer precipitation. For domain C, the variations of terrain spectra, precipitation spectra, and wind spectra are almost consistent across the whole wavelength bands, indicating that the large-scale terrain and minor terrain both play a crucial role in atmospheric uplift and the occurrence and development of summer rainfall.

Climate change mitigation and carbon neutrality are current hot topics. Forests, urban green spaces, and wetland ecosystems are recognized as important carbon sinks. The Yangtze River Delta region in Eastern China, which plays a pivotal role in China’s economic and social development, is rich in such carbon-sink resources. There is, however, a lack of regional carbon data. The investigation of carbon storage and carbon densities of forest, urban green space, and wetland ecosystems is, therefore, of great importance. In this study, the forest resource management map (including wetland) and green space system planning map of Changzhou city, combined with a field investigation and laboratory experimental analysis, were used to estimate the carbon storages and carbon densities of the forest, urban green space, and wetland ecosystems in Changzhou city. The average carbon density and carbon storage in Changzhou were 83.34 ± 4.91 Mg C ha−1 and 11.30 ± 0.67 Tg C, respectively, of which soil accounted for 74%, plants accounted for 25%, and litter accounted for less than 1%. The forest ecosystem contributed the most to the carbon pool (72%), with the green space ecosystem and the wetland ecosystem each accounting for 14% of the carbon pools. Clearly, the forest, green space, and wetland ecosystems in Changzhou city have a large carbon storage capacity. This study is of significance as it provides data on the carbon sink functions of forest, green space, and wetland ecosystems at the provincial and national regional scales.

Different protein sources can impact gut microbiota composition and abundance, and also participate in health regulation. In this study, mice were gavaged with yeast protein (YP), soybean protein isolate (SPI), and whey protein isolate (WPI) for 28 days. Body weights showed similar patterns across different protein administration groups. The ileum in YP-supplemented mice exhibited good morphology, and tight-junction (TJ) proteins were slightly upregulated. Immunoglobulin (Ig)A, IgM, and IgG levels in the ileum of different protein groups were significantly increased (p < 0.05). Interleukin (IL)-10 levels were significantly increased, whereas IL-6 levels were significantly reduced in the YP group when compared with the control (C) (p < 0.05). Glutathione peroxidase (GSH-Px) levels in the ileum were significantly increased in the YP group (p < 0.05). These results indicate that YP potentially improved intestinal immunity and inflammatory profiles. The relative abundances of Parabacteroides, Prevotella, and Pseudobutyrivibrio in the YP group were more enriched when compared with the C and SPI groups, and Parabacteroides was significantly upregulated when compared with the WPI group (p < 0.05). Overall, the results indicate that YP upregulates the beneficial bacteria and improves ileal immunity and anti-inflammatory capabilities.

The Heteracanthocephalidae Petrochenko, 1956 is a rare family of acanthocephalans mainly parasitic in fishes. The pattern of mitogenomic evolution of the Heteracanthocephalidae is still unknown, and the phylogenetic relationships of the Heteracanthocephalidae with the other 14 families within the order Echinorhynchida remain unclear. In the present study, the complete mitochondrial genome of Aspersentis megarhynchus (von Linstow, 1892) Golvan, 1960 was sequenced and annotated for the first time, which represents the first mitogenomic data for the genus Aspersentis and also for the family Heteracanthocephalidae. The mitogenome of A. megarhynchus has 14,661 bp and includes 36 genes, containing 12 protein-coding genes (PCGs) (missing atp8), 22 tRNA genes, and 2 ribosomal RNAs (rrnS and rrnL), plus two non-coding regions. Comparative mitochondrial genomic analysis revealed that the presence of translocations of several tRNA genes (trnV, trnE, and trnT) and the gene arrangement in the mitogenome of A. megarhynchus represents a new type in Acanthocephala. Moreover, the mitogenomic phylogenetic results based on concatenated amino acid sequences of 12 protein-coding genes strongly supported the validity of the Heteracanthocephalidae and suggested close affinity between the Heteracanthocephalidae and Echinorhynchidae in the order Echinorhynchida.

Species of the genus Rhabdias Stiles & Hassall, 1905 are common parasitic nematodes occurring in the lungs of amphibians and reptiles worldwide. In the present study, Rhabdias macrocephalum n. sp. is described using integrated morphological methods (light and scanning electron microscopy) and molecular approaches (sequencing of the nuclear 28S and ITS regions, and mitochondrial cox1, cox2, and 12S genes) based on specimens collected from the green striped tree dragon Diploderma splendidum (Barbour & Dunn) (Reptilia: Agamidae) in China. The complete mitochondrial genome of R. macrocephalum n. sp. was sequenced and annotated: it is 14,819 bp in length, including 12 protein coding genes (missing atp8), 22 tRNA genes, 2 rRNA genes and three non-coding regions. The gene arrangement of R. macrocephalum n. sp. is different from all of the currently available mitogenomes of nematodes and represents a novel type of mitochondrial gene arrangement reported in Nematoda. Molecular phylogenetic results based on the ITS + 28S data support the monophyly of Entomelas, Pneumonema, Serpentirhabdias, and Rhabdias, and showed R. macrocephalum n. sp. forming a most basal lineage in Rhabdias.

Abstract The greatest challenge of electrostatic levitation for containerless material processing is the stable control of charged material during heating. Recently, high-precision self-adaptive control of electrostatic levitation has been achieved in China’s Space Station. Based on the 1D and 3D co-simulation analysis, an optimal scheduling of control strategies of sample release and retrieval in space is developed. Both simulation results and on-orbit experiments demonstrated that the inversion of surface charge is responsible for the heating induced material instability. On-orbit experiments indicated that under laser illuminations, the net surface charge of metal Zr changed from positive to negative at 900 K and from negative to positive at 1300 K. The possible physical mechanism of the charge inversion of heated material is discussed.

Cor triatriatum dexter (CTD) is an extremely rare congenital cardiac malformation in which a membrane divides the right atrium into 2 chambers. Hypertrophic cardiomyopathy (HCM) with restrictive phenotype is also a rare cardiomyopathy. We report a case with an 18-year history of chest discomfort, fatigue and syncope following intense physical activity was finally diagnosed with CTD complicated with HCM, and the HCM is a special type, restrictive phenotype. Multimodal imaging was used to diagnose this complex disease and analyzed the main cause of her heart failure, which provided accurate evidence for clinical treatment and prognosis.

To study the layout of the short-distance thick underlying coal seam stopping roadway in Yanzishan Mine, a mechanical model of the remaining coal pillars in 4216 and 4218 of No. 4 sides of the overlying coal seam through theoretical calculation, and clarified the transfer law of the principal stress difference of the remaining coal pillars in the floor. The author simulated the distribution characteristics of vertical stress, horizontal stress and difference between principal stresses at different depths of floor by using FLAC3D numerical software, and analyzeds the principal stress difference and the stress reducing area roadway within the reasonable factors that influence of the reasonable inner distance. The results show that the roadway layout should avoid the peakand be in the environment of principal stress difference. When the horizontal distance of the lower coal seam is more than 30 m from the edge of the overlying coal pillar, the vertical stress is close to the original rock stress, the average principal stress difference is less than 1.24 MPa, and the principal stress difference change rate is low. Finally, the mining roadway of the working face of the lower coal seam is arranged with an inner stagger distance of 30 m. The field practice shows that the deformation of the surrounding rock is small under the misspacing, which can ensure the safety and efficient production of the mine.

Abstract The effects of adjuvants for increasing the immunogenicity of influenza vaccines are well known. However, the effect of adjuvants on increasing the breadth of cross-reactivity is less well understood. In this study we have performed a systematic screen of different toll-like receptor (TLR) agonists, with and without a squalene-in-water emulsion on the immunogenicity of a recombinant trimerized hemagglutinin (HA) vaccine in mice after single-dose administration. Antibody (Ab) cross-reactivity for other variants within and outside the immunizing subtype (homosubtypic and heterosubtypic cross-reactivity, respectively) was assessed using a protein microarray approach. Most adjuvants induced broad IgG profiles, although the response to a combination of CpG, MPLA and AddaVax (termed ‘IVAX-1’) appeared more quickly and reached a greater magnitude than the other formulations tested. Antigen-specific plasma cell labeling experiments show the components of IVAX-1 are synergistic. This adjuvant preferentially stimulates CD4 T cells to produce Th1>Th2 type (IgG2c>IgG1) antibodies and cytokine responses. Moreover, IVAX-1 induces identical homo- and heterosubtypic IgG and IgA cross-reactivity profiles when administered intranasally. Consistent with these observations, a single-cell transcriptomics analysis demonstrated significant increases in expression of IgG1, IgG2b and IgG2c genes of B cells in H5/IVAX-1 immunized mice relative to naïve mice, as well as significant increases in expression of the IFNγ gene of both CD4 and CD8 T cells. These data support the use of adjuvants for enhancing the breath and durability of antibody responses of influenza virus vaccines.

Most recently, gold nanoparticles due to anticancer properties have been considered in medical science. So the aim of the study was green synthesis of gold nanoparticles using Ocimum basilicum extract and its anticancer activity. The prepared Au nanoparticles were characterized by advanced physicochemical techniques like Fourier Transformed Infrared spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Energy Dispersive X-ray spectroscopy (EDX), X-ray Diffraction (XRD) and UV–vis spectroscopy study. It has been established that Au nanoparticles have a spherical shape with a mean diameter from 19 to 44 nm. In the cellular and molecular part of the recent study, the treated cells with Au nanoparticles were assessed by MTT assay for 48 h about the cytotoxicity and anti-human laryngeal cancer properties on normal (HUVEC) and cancer (HEp-2, TU212, KB, UM-SCC-5, UM-SCC-11A and UM-SCC-11B) cell lines. In the antioxidant test, the IC50 of Au nanoparticles and BHT against DPPH free radicals were 228 and 208 µg/mL, respectively. The IC50 of Au nanoparticles were 174, 231, 179, 143, 230, and 216 µg/mL against HEp-2, TU212, KB, UM-SCC-5, UM-SCC-11A and UM-SCC-11B cell lines, respectively. The viability of malignant cell lines reduced dose-dependently in the presence of Au nanoparticles. It appears that the anti-cancer effect of Au nanoparticles e to their antioxidant effects.

Short-term power load forecasting provides important guidance for the improvement of power marketing and control levels of power enterprises. In this paper, a novel method, named RF-TStacking, is proposed to forecast the short-term load. This study starts from the influence factors of the power load, the random forest is applied to estimate the importance of the influence factors of short-term load. Based on Stacking strategy, the integration of LightGBM and random forest is realized to achieve short-term power load forecasting. To improve the generalization ability of the load model, random put back sampling is used to sample each primary learner, and the average value is taken as the result of each primary learner. The Bayesian optimization is used to adjust the super parameters of the model to improve the accuracy of the selection of influencing factors. The load data of a region in northwest China are used for the testing, and it is found that the model can provide stable prediction results.