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BackgroundBenign prostatic hyperplasia (BPH) is a common disease occurring in elderly and middle-aged men, and cardiovascular diseases (CVDs) are one of the major causes of death worldwide. Many observational studies examined have found a strong association between BPH and CVDs, but the causal relationship between them is unclear. The aim of this study was to determine the causal relationship between BPH and CVDs, specifically five diseases: stroke, coronary heart disease (CHD), heart failure, myocardial infarction (MI), and atrial fibrillation (AF).MethodsIn this study, we obtained single nucleotide polymorphisms (SNPs) of patients with BPH from the UK Biobank database and patients with CVDs from the UK Biobank, the HERMES Consortium, and the FinnGen Genome Database, each used as a genetic tool for a Mendelian randomization (MR) study. We used conventional MR analysis to assess potential causal direction between BPH and CVDs, as well as MR-Egger, MR-PRESSO, model-based estimation (MBE) and weighted median methods for sensitivity analysis.ResultsUsing a bidirectional two-sample MR study, we found that BPH patients had an increased risk of developing CHD (ConMix OR = 1.152, 95% CI: 1.011–1.235, p = 0.035) and MI (ConMix OR = 1.107.95% CI: 1.022–1.164, p = 0.013), but a decreased risk of stroke (ConMix OR = 0.872, 95% CI: 0.797–0.926, p = 0.002). The reverse study was not statistically significant and further research may be needed.ConclusionOur study suggests a potential causal relationship between BPH and CVDs. BPH appears to be a risk factor for CHD and MI, but it may be protective against stroke. There was no evidence of a causal association in the reverse study, and a larger sample size was needed in follow-up to further explore the potential association.

BackgroundResistance training is often a part of the routine training regimen for competitive swimmers. However, due to the variety of resistance training methodology, the results can be inconsistent and sometimes unsatisfactory. Clear recommendations are still lacking at present.Aims1) Quantify the impact of resistance training on swimmers’ upper limb maximum strength, front crawl performance and key technical parameters; 2) Find out the key technical parameters for improving front crawl performance—stroke rate or length; 3) Through subgroup analysis determine the best methodology of resistance training to enhance the front crawl.MethodsSystematic search in the PubMed, Embase, and Web of Science databases. Meta-analyses using the inverse-variance are performed to compare swimmers’ upper limb maximum strength, front crawl performance and key technical parameters in resistance training and habitual aquatic training. A subgroup analysis was performed to examine whether the results were affected by the methodology of resistance training.ResultsThirteen studies (267 competitive swimmers) met the inclusion criteria. The results of meta-analysis showed that resistance training significantly improved upper limbs maximum muscle strength, and 25, 50, 100, and 200 m front crawl performance in competitive swimmers. And improvements in swimming performance may simply resulted from resistance training increasing stroke rate rather than stroke length. In addition, the results of subgroup analysis showed that only concurrent resistance training (CRT) and power training (PT) ultimately improved swimming performance by increasing the maximum muscle strength of the upper limbs.ConclusionResistance training significantly enhances competitive swimmers’ upper limb strength and front crawl performance across various distances. The improvement in performance is likely attributed to an increased stroke rate rather than stroke length. In addition, CRT and PT are particularly effective, indicating the importance of selecting the appropriate methodology of resistance training for optimal swimming performance enhancement.Systematic review registrationhttps://doi.org/10.17605/OSF.IO/3JEGW.

Notch signaling pathway is activated abnormally in solid and hematological tumors, which perform essential functions in cell differentiation, survival, proliferation, and angiogenesis. The activation of Notch signaling and communication among Notch and other oncogenic pathways heighten malignancy aggressiveness. Thus, targeting Notch signaling offers opportunities for improved survival and reduced disease incidence. Already, most attention has been given to its role in the cancer cells. Recent research shows that natural bioactive compounds can change signaling molecules that are linked to or interact with the Notch pathways. This suggests that there may be a link between Notch activation and the growth of tumors. Here, we sum up the natural bioactive compounds that possess inhibitory effects on human cancers by impeding the Notch pathway and preventing Notch crosstalk with other oncogenic pathways, which provoke further study of these natural products to derive rational therapeutic regimens for the treatment of cancer and develop novel anticancer drugs. This review revealed Notch as a highly challenging but promising target in oncology.

Objective To study the mechanism by which conditioned medium of bone marrow mesenchymal stem cells (BMSCs-CM) facilitates the transition of pro-inflammatory polarized microglia to an anti-inflammatory phenotype. Methods BV2 cells, a mouse microglia cell line, were transformed into a pro-inflammatory phenotype using lipopolysaccharide. The expression of phenotypic genes in BV2 cells was detected using real-time quantitative PCR (RT-qPCR). Enzyme-linked immunosorbent assay was used to measure inflammatory cytokine levels in BV2 cells co-cultured with BMSCs-CM. The expressions of mitophagy-associated proteins were determined using western blot. The mitochondrial membrane potential and ATP levels in BV2 cells were measured using JC-1 staining and an ATP assay kit, respectively. Additionally, we examined the proliferation, apoptosis, and migration of C8-D1A cells, a mouse astrocyte cell line, co-cultured with BV2 cells. Results After co- culture with BMSCs -CM, the mRNA expression of tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase significantly decreased in pro-inflammatory BV2 cells, whereas the expression of CD206 and arginase-1 significantly increased. Moreover, TNF-α and interleukin-6 levels significantly decreased, whereas transforming growth factor-β and interleukin-10 levels significantly increased. Furthermore, co-culture with BMSCs-CM increased mitophagy-associated protein expression, ATP levels, mitochondrial and lysosomal co-localization in these cells and decreased reactive oxygen species levels. Importantly, BMSCs-CM reversed the decrease in the proliferation and migration of C8-D1A cells co-cultured with pro-inflammatory BV2 cells and inhibited the apoptosis of C8-D1A cells. Conclusion BMSCs-CM may promote the transition of polarized microglia from a pro-inflammatory to an anti-inflammatory phenotype by regulating mitophagy and influences the functional state of astrocytes.

ObjectivesThis study aimed to gain insights into pediatric clinical trials conducted in children's hospitals in China and provide valuable references for the development of children's hospitals and the research and development of pediatric drugs.MethodsA comprehensive search was performed on the Chinese Clinical Trial Registry (Chi CTR) and ChinaDrugTrials.org.cn to collect information on all clinical trials involving subjects under 18 years, including those conducted in children's hospitals. The retrieval period was extended until 31 December 2022.ResultsA total of 459 pediatric clinical trials were collected, comprising 299 from Chi CTR and 160 from the Drug Clinical Trial Registration and Information Publicity Platform (Information Platform). Post-marketing drug studies and phase III clinical trials accounted for the majority of research stages. These trials covered a wide range of diseases/systems, with a particular focus on respiratory system disorders, tumors, endocrine disorders, and nutritional or metabolic diseases. Chemical drugs constituted the most extensively studied category, while traditional Chinese medicine/natural drugs received comparatively less attention. Clinical trial activities were primarily geographically focused on the eastern coastal regions of China, with multicenter trials being the most predominant. Ethics committee approval was obtained for 427 studies.ConclusionThe pediatric clinical trials conducted by children's hospitals in China have shown an overall upward trend; however, there is limited research focusing on traditional Chinese medicine, along with significant regional and institutional imbalances. Furthermore, there is still room for improvement regarding ethical review processes. It is recommended that children's hospitals enhance their scientific research capabilities while optimizing resource allocation to meet medical service demands effectively. Additionally, fostering more research-focused children's hospitals will contribute to the high-quality development of children's health in China.

Temperature stability is a critical factor affecting the performance of the most subsystems in the lithography system, due to the high precision and sensitivity of system components to temperature variations. The temperature control system of the lithography machine is characterized by its large inertial constant, time delay characteristics, as well as susceptibility to multiple disturbances. The temperature control system of the lithography machine chiefly requires response speed, high accuracy, and stable and constant temperature control. The contribution of this study is not only avoiding complex precision modeling processes based on real-time parameter estimation and neural network self-tuning but also improving the performance of temperature control in real time under external disturbances. A novel adaptive algorithm with a cascade structure based on generalized predictive control (GPC) and backpropagation (BP) neural network proportional-integral (PI) control is successfully proposed for high accuracy temperature control of lithography machine with a large inertial constant, time delay, and multiple disturbances. In this study, firstly, the liquid circulating temperature control system is developed based on heat exchanger and heater. Secondly, an adaptive controller composed of GPC and BP neural network PI control is successfully proposed. A BP neural network is employed to enable the parameters of the PI controller to adjust in real time, and the mathematical model parameters of the control system are identified in real time by the least square method. Also, the performance of the proposed controller is evaluated comparing with conventional PI controller and GPC controller in terms of robustness and quantitative study of error analysis. Finally, the temperature stability and robustness of the temperature control system controlled with the proposed adaptive GPC-PI algorithm has been investigated by the simulation results carried out in different working scenarios. The simulation results show that the steady-state error from the proposed algorithm is less than 0.01°C under the action of disturbance input. It can effectively counteract the influence of environmental interference and time-varying system parameters. The results of the simulation experiment indicate that the proposed adaptive GPC and PI control algorithm exhibits significant advantages in terms of control accuracy, anti-interference ability, and robustness compared to the conventional control method.

Geo-solar systems, comprising ground-source heat pumps (GSHP) and solar thermal collectors, offer promising solutions for sustainable space heating and hot water provision in residential buildings. However, optimizing these systems for maximum energy efficiency and cost-effectiveness remains a challenge. In this context, this study presents a comprehensive approach to enhancing the performance and cost-effectiveness of geo-solar systems. The proposed methodology integrates artificial neural network (ANN) techniques and multi-aspect optimization to optimize system parameters. The detailed of building mathematical model incorporating energy and exergy equations, thermodynamic, and economic relations for all system components. The neural network model inputs to the include five neurons represents Geothermal temperature, Solar radiation levels, System pressure levels, Ambient temperature, and Operational time, and the model outputs represent Energy efficiency and Exergy destruction rate. Through the training of ANN using simulation data and the application of a multi-objective genetic algorithm, the system is optimized for energy efficiency, cost, and environmental impact simultaneously. The results of analysis show that the exergy efficiency of system is 22.02 % and turbine generates 1963 kW. Changes in P10, ranging from 2000 to 3400 kPa leads to the exergy destruction reduction from 8350 kW to 8000 kW, while the other parameters exhibit an increasing trend.

Soil-rock mixtures (SRM) are abundant worldwide and often used as foundations. However, their heterogeneity, inherent weakness, and collapsibility present significant challenges in stabilization. This study introduces a novel approach to foundation treatment, combining ''shallow drainage'' and ''deep sealing'' techniques. Comprehensive on-site vibratory reinforcement trials were conducted using a gas-vibration coupling method called jet-vibratory probe compaction (JVPC). The method successfully created an oriented particle distribution and a dual-layer system within the depth. The effectiveness of this reinforcement and its mechanisms were thoroughly assessed through various in-situ tests, including triaxial vibration testing (TVT), multi-channel analysis of surface waves (MASW), dynamic penetration test (DPT), sand cone method (SCM), and plate doad test (PLT). The findings reveal that JVPC eliminated the collapsibility of the SRM and significantly enhanced the bearing capacity of foundations. A notable outcome was the formation of a distinct stratification within the foundation, characterized by a coarser upper section, a finer lower section, and a watertight boundary at the base. This innovative approach demonstrates a promising advancement in foundation engineering, particularly for challenging SRM-based constructions.

Special planar structure endows two-dimensional (2D) materials with unique physical and chemical properties and the application of 2D materials to cement-based materials ensures the mechanical properties of buildings and infrastructures. Herein, a novel 2D nanoplate is synthesized through hydrothermal method with controlled sizes and morphologies. TEM and SEM measurements are used to characterize the nanostructures, confirming the morphologies, the distribution of elements among the structures and the crystal structure. The as-prepared nanoplates are able to enhance the mechanical strength of the cement mortar by its specific morphology and pozzolanic activity. The flexural strength was improved by 45.73 % after 1 d curing due to the acceleration of cement hydration. From the analysis of XRD and TG-DTG patterns, the nanoplates have strong interaction with the cement paste and the amount of the hydration products varied by the addition of the nanoplates. This approach helps promote the development of cement-based materials with high performance.

Background: Approximately 10%–30% of patients with Hodgkin's lymphoma (HL) experience relapse or refractory (R/R) disease after first-line standard therapy. Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) have important roles in the salvage treatment of R/R HL. However, subsequent treatment for HL refractory to BV and/or ICI treatment is challenging. Methods: We retrospectively analyzed patients in two institutions who had R/R HL, experienced BV or ICI treatment failure, and received radiotherapy (RT) thereafter. The overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were analyzed. Results: Overall, 19 patients were enrolled. First-line systemic therapy comprised doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD, 84.2%); AVD plus ICIs (10.5%); and bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP, 5.3%). After first-line therapy, 15 (78.9%) and four patients (21.1%) had refractory disease and relapsed, respectively. After R/R HL diagnosis, six (31.6%), two (10.5%), and 11 (57.9%) patients received BV and ICIs concurrently, BV monotherapy, and ICI monotherapy, respectively. All patients received intensity-modulated RT (n = 12, 63.2%) or volumetric modulated arc therapy (VMAT; n = 7, 36.8%). The ORR as well as the complete response (CR) rate was 100%; the median DOR to RT was 17.2 months (range, 7.9–46.7 months). Two patients showed progression outside the radiation field; one patient had extensive in-field, out-of-field, nodal, and extranodal relapse. With a median follow-up time of 16.2 months (range, 9.2–23.2 months), the 1-year PFS and OS were 84.4% and 100%, respectively. PFS was associated with extranodal involvement (P = 0.019) and gross tumor volume (P = 0.044). All patients tolerated RT well without adverse events of grade ≥ 3. Conclusion: RT is effective and safe for treating HL refractory to BV or ICIs and has the potential to be part of a comprehensive strategy for HL.

Abstract The effects of technology-supported behavior change interventions for reducing sodium intake on health outcomes in adults are inconclusive. Effective intervention characteristics associated with sodium reduction have yet to be identified. A systematic review and meta-analysis were conducted, searching randomized controlled trials (RCTs) published between January 2000 and April 2023 across 5 databases (PROSPERO: CRD42022357905). Meta-analyses using random-effects models were performed on 24-h urinary sodium (24HUNa), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Subgroup analysis and meta-regression of 24HUNa were performed to identify effective intervention characteristics. Eighteen RCTs involving 3505 participants (51.5% female, mean age 51.6 years) were included. Technology-supported behavior change interventions for reducing sodium intake significantly reduced 24HUNa (mean difference [MD] −0.39 gm/24 h, 95% confidence interval [CI] −0.50 to −0.27; I 2 = 24%), SBP (MD −2.67 mmHg, 95% CI −4.06 to −1.29; I 2 = 40%), and DBP (MD −1.39 mmHg, 95% CI −2.31 to −0.48; I 2 = 31%), compared to control conditions. Interventions delivered more frequently (≤weekly) were associated with a significantly larger effect size in 24HUNa reduction compared to less frequent interventions (>weekly). Other intervention characteristics, such as intervention delivery via instant messaging and participant-family dyad involvement, were associated with larger, albeit non-significant, effect sizes in 24HUNa reduction when compared to other subgroups. Technology-supported behavior change interventions aimed at reducing sodium intake were effective in reducing 24HUNa, SBP, and DBP at post-intervention. Effective intervention characteristics identified in this review should be considered to develop sodium intake reduction interventions and tested in future trials, particularly for its long-term effects.

Abstract Background Fecal impaction is a digestive system disease, that is most common in the elderly population and becomes more prevalent with increasing age. Manual removal can successfully remove the impaction in 80% of fecal impaction cases. In severe cases, endoscopy and surgery may be necessary. Case presentation A 78-year-old Han Chinese man living in a nursing home was diagnosed with fecal impaction; his initial symptom was overflow diarrhea, which is a rare occurrence with regard to fecal impaction. Nevertheless, we were able to effectively treat this situation by employing a new medical device that presents a novel method for addressing fecal impaction. Conclusion Early identification of fecal impaction with atypical symptoms is crucial to provide proper emergency management. A safe and noninvasive treatment method, especially for elderly patients with fecal impaction, should be chosen.

Abstract Background The relaxation of the “zero-COVID” policy on Dec. 7, 2022, in China posed a major public health threat recently. Complete blood count test was discovered to have complicated relationships with COVID-19 after the infection, while very few studies could track long-term monitoring of the health status and identify the characterization of hematological parameters prior to COVID-19. Methods Based on a 13-year longitudinal prospective health checkup cohort of ~ 480,000 participants in West China Hospital, the largest medical center in western China, we documented 998 participants with a laboratory-confirmed diagnosis of COVID-19 during the 1 month after the policy. We performed a time-to-event analysis to explore the associations of severe COVID-19 patients diagnosed, with 34 different hematological parameters at the baseline level prior to COVID-19, including the whole and the subtypes of white and red blood cells. Results A total of 998 participants with a positive SARS-CoV-2 test were documented in the cohort, 42 of which were severe cases. For white blood cell-related parameters, a higher level of basophil percentage (HR = 6.164, 95% CI = 2.066–18.393, P = 0.001) and monocyte percentage (HR = 1.283, 95% CI = 1.046–1.573, P = 0.017) were found associated with the severe COVID-19. For lymphocyte-related parameters, a lower level of lymphocyte count (HR = 0.571, 95% CI = 0.341–0.955, P = 0.033), and a higher CD4/CD8 ratio (HR = 2.473, 95% CI = 1.009–6.059, P = 0.048) were found related to the risk of severe COVID-19. We also observed that abnormality of red cell distribution width (RDW), mean corpuscular hemoglobin concentration (MCHC), and hemoglobin might also be involved in the development of severe COVID-19. The different trajectory patterns of RDW-SD and white blood cell count, including lymphocyte and neutrophil, prior to the infection were also discovered to have significant associations with the risk of severe COVID-19 (all P

Fermented meat products is the meat products with special flavor, color, texture and longer shelf life formed by a series of changes under natural or artificially controlled conditions by the action of microorganisms or enzymes. Fermented meat products is popular with consumers, but they are rich in protein and have a great potential for high levels of biogenic amines. Among them, histamine and tyramine are the most toxic. Consumption of tyramine-rich foods might cause headache, hypertension and other adverse reactions. Therefore, it is extremely necessary to control the tyramine content in fermented meat products. In this paper, the formation pathways, control methods and effects of tyramine in fermented meat products are reviewed. Among them, the main formation pathway is the decarboxylation of tyrosine by the action of decarboxylase, in addition to the existence of chemical pathways related to lipid oxidation products, while the more effective control methods are the addition of auxiliaries and the inoculation of fermentation agents. This paper aims to provid a theoretical support for reducing the tyramine content in fermented meat products and improving the safety of fermented meat products.

Abstract Background Hydrogen sulfide (H2S) is a novel signaling molecule involved in the growth and development of plants and their response to stress. However, the involvement of H2S in promoting the growth and development of tobacco plants is still unclear. Results In this study, we explored the effect of pre-soaking or irrigating the roots of tobacco plants with 0.0, 2.0, 4.0, 6.0, and 8.0 mM of sodium hydrosulfide (NaHS) on endogenous H2S production, antioxidant enzymatic and cysteine desulfhydrase activities, seed germination, agronomic traits, photosynthetic pigments contents, and root vigor. The results revealed that exogenous NaHS treatment could significantly promote endogenous H2S production by inducing gene expression of D/L-CD and the activities of D/L-CD enzymes. Additionally, a significant increase in the agronomic traits and the contents of photosynthetic pigments, and no significant difference in carotenoid content among tobacco plants treated with 0.0 to 8.0 mM of NaHS was observed. Additionally, a significant increase in the germination speed, dry weight, and vigor of tobacco seeds, whereas no significant effect on the percentage of seed germination was observed on NaHS treatment. Furthermore, NaHS treatment could significantly increase the activity of superoxide dismutase (SOD) and peroxidase (POD) enzymes, which reduces damage due to oxidative stress by maintaining reactive oxygen species homeostasis. Conclusions These results would aid in enhancing our understanding of the involvement of H2S, a novel signaling molecule to promote the growth and development of tobacco plants.

Abstract Backgroud We aimed to develop a novel preoperative nomogram to predict lymph node metastasis (LNM) in perihilar cholangiocarcinoma (pCCA) patients. Methods 160 pCCA patients were enrolled at Lihuili Hospital from July 2006 to May 2022. A novel nomogram model was established to predict LNM in pCCA patients based on the independent predictive factors selected by the multivariate logistic regression model. The precision of the nomogram model was evaluated through internal and external validation with calibration curve statistics and the concordance index (C-index). Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate and determine the clinical utility of the nomogram. Results Multivariate logistic regression demonstrated that age (OR = 0.963, 95% CI: 0.930–0.996, P = 0.030), CA19-9 level (> 559.8 U/mL vs. ≤559.8 U/mL: OR = 3.162, 95% CI: 1.519–6.582, P = 0.002) and tumour diameter (OR = 1.388, 95% CI: 1.083–1.778, P = 0.010) were independent predictive factors of LNM in pCCA patients. The C-index was 0.763 (95% CI: 0.667–0.860) and 0.677 (95% CI: 0.580–0.773) in training cohort and validation cohort, respectively. ROC curve analysis indicated the comparative stability and adequate discriminative ability of nomogram. The sensitivity and specificity were 0.820 and 0.652 in training cohort and 0.704 and 0.649 in validation cohort, respectively. DCA revealed that the nomogram model could augment net benefits in the prediction of LNM in pCCA patients. Conclusions The novel prediction model is useful for predicting LNM in pCCA patients and showed adequate discriminative ability and high predictive accuracy.

Abstract Gasdermin E (GSDME) has recently been identified as a critical executioner to mediate pyroptosis. While epidermal keratinocytes can initiate GSDME-mediated pyroptosis, the role of keratinocyte GSDME in psoriatic dermatitis remains poorly characterized. Through analysis of GEO datasets, we found elevated GSDME levels in psoriatic lesional skin. Additionally, GSDME levels correlated with both psoriasis severity and response to biologics treatments. Single-cell RNA sequencing (scRNA-seq) from a GEO dataset revealed GSDME upregulation in keratinocytes of psoriasis patients. In the imiquimod (IMQ)-induced psoriasis-like dermatitis mouse model, both full-length and cleaved forms of caspase-3 and GSDME were elevated in the epidermis. Abnormal proliferation and differentiation of keratinocytes and dermatitis were attenuated in Gsdme -/- mice and keratinocyte-specific Gsdme conditional knockout mice after IMQ stimulation. Exposure of keratinocytes to mixed cytokines (M5), mimicking psoriatic conditions, led to GSDME cleavage. Moreover, the interaction between GSDME-FL and p65 or c-jun was significantly increased after M5 stimulation. GSDME knockdown inhibited nuclear translocation of p65 and c-jun and decreased upregulation of psoriatic inflammatory mediators such as IL1β, CCL20, CXCL1, CXCL8, S100A8, and S100A9 in M5-challenged keratinocytes. In conclusion, GSDME in keratinocytes contributes to the pathogenesis and progression of psoriasis, potentially in a pyroptosis-independent manner by interacting and promoting translocation of p65 and c-jun. These findings suggest that keratinocyte GSDME could serve as a potential therapeutic target for psoriasis treatment.

Abstract Here we report on the development and comprehensive evaluations of an mRNA vaccine for chronic hepatitis B (CHB) treatment. In two different HBV carrier mouse models generated by viral vector-mediated HBV transfection (pAAV-HBV1.2 and rAAV8-HBV1.3), this vaccine demonstrates sufficient and persistent virological suppression, and robust immunogenicity in terms of induction of strong innate immune activation, high-level virus-specific antibodies, memory B cells and T cells. mRNA platform therefore holds prospects for therapeutic vaccine development to combat CHB.

Abstract Persimmon anthracnose, a severe disease caused by the hemibiotrophic fungus Colletotrichum horii, poses a substantial threat to China’s persimmon industry. Previous research showed that ‘Kangbing Jianshi’ cultivar exhibits strong resistance to anthracnose. Notably, ‘Kangbing Jianshi’ branches exhibit greater lignification compared with the susceptible ‘Fuping Jianshi’ cultivar. In this study, higher lignin content was observed in ‘Kangbing Jianshi’ compared with ‘Fuping Jianshi’, and this difference was associated with disease resistance. Transcriptome and metabolome analyses revealed that the majority of differentially expressed genes and differentially accumulated metabolites were primarily enriched in the phenylpropanoid biosynthesis and lignin synthesis pathways. Furthermore, significant upregulation of DkCAD1, a pivotal gene involved in lignin metabolism, was observed in the resistant cultivar when inoculated with C. horii. Transient overexpression of DkCAD1 substantially increased lignin content and improved resistance to C. horii in a susceptible cultivar. Furthermore, through yeast one-hybrid (Y1H) assays, we identified two WRKY transcription factors, DkWRKY8 and DkWRKY10, which interacts with the DkCAD1 promoter and induces its activity. Overexpression of DkWRKY8 and DkWRKY10 not only increased leaf lignin content but also enhanced persimmon tolerance to C. horii. Moreover, the expression levels of DkCAD1, DkWRKY8, and DkWRKY10 were significantly increased in response to salicylic acid and jasmonic acid in the resistant cultivar. These findings enhance our understanding of the molecular functions of DkWRKY8, DkWRKY10, and DkCAD1 in persimmons, as well as their involvement in molecular breeding processes in persimmons.

Abstract Background Calmodulins (CaMs)/CaM-like proteins (CMLs) are crucial Ca2+-binding sensors that can decode and transduce Ca2+ signals during plant development and in response to various stimuli. The CaM/CML gene family has been characterized in many plant species, but this family has not yet been characterized and analyzed in peanut, especially for its functions in response to Ralstonia solanacearum. In this study, we performed a genome-wide analysis to analyze the CaM/CML genes and their functions in resistance to R. solanacearum. Results Here, 67, 72, and 214 CaM/CML genes were identified from Arachis duranensis, Arachis ipaensis, and Arachis hypogaea, respectively. The genes were divided into nine subgroups (Groups I-IX) with relatively conserved exon‒intron structures and motif compositions. Gene duplication, which included whole-genome duplication, tandem repeats, scattered repeats, and unconnected repeats, produced approximately 81 pairs of homologous genes in the AhCaM/CML gene family. Allopolyploidization was the main reason for the greater number of AhCaM/CML members. The nonsynonymous (Ka) versus synonymous (Ks) substitution rates (less than 1.0) suggested that all homologous pairs underwent intensive purifying selection pressure during evolution. AhCML69 was constitutively expressed in different tissues of peanut plants and was involved in the response to R. solanacearum infection. The AhCML69 protein was localized in the cytoplasm and nucleus. Transient overexpression of AhCML69 in tobacco leaves increased resistance to R. solanacearum infection and induced the expression of defense-related genes, suggesting that AhCML69 is a positive regulator of disease resistance. Conclusions This study provides the first comprehensive analysis of the AhCaM/CML gene family and potential genetic resources for the molecular design and breeding of peanut bacterial wilt resistance.

Abstract Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by inflammation of the synovial tissue and joint bone destruction, often leading to significant disability. The main pathological manifestation of joint deformity in RA patients is bone destruction, which occurs due to the differentiation and proliferation of osteoclasts. The transcription factor nuclear factor-activated T cell 1 (NFATc1) plays a crucial role in this process. The regulation of NFATc1 in osteoclast differentiation is influenced by three main factors. Firstly, NFATc1 is activated through the upstream nuclear factor kappa-B ligand (RANKL)/RANK signaling pathway. Secondly, the Ca2+-related co-stimulatory signaling pathway amplifies NFATc1 activity. Finally, negative regulation of NFATc1 occurs through the action of cytokines such as B-cell Lymphoma 6 (Bcl-6), interferon regulatory factor 8 (IRF8), MAF basic leucine zipper transcription factor B (MafB), and LIM homeobox 2 (Lhx2). These three phases collectively govern NFATc1 transcription and subsequently affect the expression of downstream target genes including TRAF6 and NF-κB. Ultimately, this intricate regulatory network mediates osteoclast differentiation, fusion, and the degradation of both organic and inorganic components of the bone matrix. This review provides a comprehensive summary of recent advances in understanding the mechanism of NFATc1 in the context of RA-related bone destruction and discusses potential therapeutic agents that target NFATc1, with the aim of offering valuable insights for future research in the field of RA. To assess their potential as therapeutic agents for RA, we conducted a drug-like analysis of potential drugs with precise structures.

Abstract The well-known strength-toughness trade-off has long been an obstacle in the pursuit of advanced structural alloys. Here, we develop a eutectic high entropy alloy that effectively overcomes this limitation. Our alloy is composed of face-centered cubic and body-centered cubic crystalline phases, and demonstrates attractive mechanical properties by harnessing microstructural hybridization and a strain-induced phase transition between phases. Unlike conventional eutectic alloys, the compositionally complexity of our alloy allows control of its microstructural and chemical heterogeneities across multiple length scales, ranging from atomic- and nano-scales to meso-scales. Optimizing these microstructural and chemical heterogeneities within our alloy enables high strength and ductility because of enhanced fracture resistance, outperforming alternative high and medium entropy alloys with similar compositions and microstructures.

Highlights A percolating network of distorted 2D Pt nanomembranes was synthesized by polymer surface buckling-enabled exfoliation for hydrogen evolution reaction. The 2D Pt nanomembrane enabled important technological applications for its high efficiency, low costs, and good stability, making it potential alternative to commercial Pt/C. Our 2D Pt nanomembranes offer insights into a new mechanism for efficient catalyst design strategy: lattice distortion-induced heterogeneous strain.

Pansharpening is a process that fuses a multispectral (MS) image with a panchromatic (PAN) image to generate a high-resolution multispectral (HRMS) image. Current methods often overlook scale inconsistency and the correlation within and between a window domain, resulting in suboptimal outcomes. In addition, the use of deep convolutional neural network or transformer often leads to high computational expenses. To address these challenges, we present a lightweight pansharpening network that leverages cross-scale interaction and spatial-spectral enhanced window attention. We first design a spatial-spectral enhanced window transformer (SEWformer) to effectively capture crucial attention within and between interleaved windows. To improve scale consistency, we develop a cross-scale interactive encoder that interacts with different scale attentions derived from the SEWformer. Furthermore, a multiscale residual network with channel attention is constructed as a decoder, which, in conjunction with the encoder, ensures precise detail extraction. The final HRMS image is obtained by combining the extracted details with the UPMS image. Extensive experimental validation on diverse datasets showcases the superiority of our approach over state-of-the-art pansharpening techniques in terms of both performance and efficiency. Compared to the second-best comparison approach, our method achieves significant improvements in the ERGAS metric: 29.6$\%$ on IKONOS, 43.8$\%$ on Pléiades, and 27.6$\%$ on WorldView-3 datasets.

Abstract Background Prognosis is critically important in stroke cases, with angiogenesis playing a key role in determining outcomes. This study aimed to investigate the potential protective effects of Atractylenolide I (Atr I), Atractylenolide III (Atr III), and Paeoniflorin (Pae) in promoting angiogenesis following cerebral ischemia. Methods The bEnd.3 cell line was used to evaluate the effects of these three compounds on vascular endothelial cell proliferation, migration, and tube formation. Male C57BL/6 mice underwent transient middle cerebral artery occlusion (MCAO), followed by daily intragastric administration of the Chinese medicine compounds to assess their impact on brain protection and angiogenesis. In vivo experiments included measuring infarct size and assessing neurological function. Immunofluorescence staining and an angiogenesis antibody array were used to evaluate angiogenesis in ischemic brain tissue. Functional enrichment analysis was performed to further investigate the pathways involved in the protective effects of the compounds. Molecular docking analysis explored the potential binding affinity of the compounds to insulin-like growth factor 2 (IGF-2), and Western blotting was used to measure levels of angiogenesis-related proteins. Results In vitro, the combination of Atr I, Atr III, and Pae enhanced cell proliferation, promoted migration, and stimulated tube formation. In vivo, the combined treatment significantly facilitated neurological function recovery and angiogenesis by day 14. The treatment also increased levels of angiogenesis-related proteins, including IGF-2. Pearson correlation analysis revealed a strong positive association between IGF-2 levels in ischemic brain tissue and angiogenesis, suggesting a good affinity of the compounds for the IGF-2 binding site, as supported by molecular docking analysis. Conclusion The administration of Atr I, Atr III, and Pae has shown significant enhancements in long-term stroke recovery in mice, likely due to the promotion of angiogenesis via increased activation of the IGF-2 pathway in ischemic brain tissue. Graphical Abstract

Abstract Background CC chemokine receptors are responsible for regulating the tumor microenvironment (TME) and participating in carcinogenesis and tumor advancement. However, no functional study has investigated CC chemokine receptors in gastric cancer (GC) prognosis, risk, immunotherapy, or other treatments. Methods We conducted a bioinformatics analysis on GC data using online databases, including the Human Protein Atlas (HPA), Kaplan-Meier (KM) plotter, GeneMANIA, MethSurv, the University of ALabama at Birmingham CANcer (UALCAN) Data Analysis Portal, Gene Set Cancer Analysis (GSCA), cBioportal, and Tumor IMmune Estimation Resource (TIMER). Results We noted that CC chemokine receptor expression correlated with survival in GC. CC chemokine receptor expression was also strongly linked to different tumor-infiltrating immune cells. Additionally, CC chemokine receptors were found to be broadly drug-resistant in GC. Conclusion Our study identifed CC chemokine receptor expression helped in predicting the prognosis of patients diagnosed with GC. The expression level of the CC chemokine receptors was also positively related to multiple tumor-infiltrating lymphocytes (TILs). These findings provide evidence to monitor patients with GC using CC chemokine receptors, which can be used as an effective biomarker for predicting the disease prognosis and be regarded as a therapeutic target for modulating the tumor immune microenvironment.

Wireless charging has become increasingly popular in low and medium-power applications, such as motor-driven carriers, unmanned aerial vehicles, electric bicycles, and inspection robots. Nevertheless, pad misalignment can significantly affect the system performance, leading to higher losses and a reduction in the power output. Particularly in the all directions of anti-misalignment strategies, a greater number of inverters and compensations are necessitated, leading to increased system dimensions and heightened complexity. This article proposes a new hybrid coupler that only uses a bipolar pad as the secondary pad and a solenoid (S coil) with an added quadrature coil (Q coil) as the primary pad. We develop and test a 50W prototype in the laboratory. The size of the coupler is 355 mm $ \times 290$ mm. The experimental and simulation results demonstrate that when the distance between the transmitter and receiver is 60 mm, the transmission efficiency remains within a range of 72% to 90% for all directions of anti-misalignment, while the output voltage exhibits fluctuations within a margin of 10%. The results indicate that the coupler has a great potential for use in low and medium power applications, and can even be used in high-power equipment.

Ischemic stroke is a major global health crisis, characterized by high morbidity and mortality rates. Although there have been significant advancements in treating the acute phase of this condition, there remains a pressing need for effective treatments that can facilitate the recovery of neurological functions. Danggui-Shaoyao-San (DSS), also known as the Decoction of Chinese Angelica and Peony, is a traditional Chinese herbal formula. It has demonstrated promising results in the regulation of microglial polarization and modulation of neurosteroid receptor expression, which may make it a potent strategy for promoting the recovery of neurological functions. Microglia, which plays a crucial role in neuroplasticity and functional reconstruction poststroke, is regulated by neurosteroids. This review posits that DSS could facilitate the recovery of neuronal function poststroke by influencing microglial polarization through the neurosteroid receptor pathway. We will further discuss the potential mechanisms by which DSS could enhance neural function in stroke, including the regulation of microglial activation, neurosteroid regulation, and other potential mechanisms.

By inserting a modulator in the imaging system and scanning in different positions, ptychographic modulation imaging can achieve higher quality reconstruction for smooth or weakly scattered objects compared to conventional ptychography imaging. However, its imaging resolution is still limited by the pixel size of the detector. In this paper, divergent illumination is introduced to enhance imaging resolution. Compared with the original planar illumination scheme, our proposed method can achieve two-fold resolution improvement with only the use of thirty diffraction patterns for ten iterations. The quantitative phase imaging capability of the proposed method is also demonstrated by testing the binary phase sample. In the reconstruction, the divergent illumination geometry is converted to planar illumination model. The equivalent sampling intervals and diffraction distances of the modulator, object, and detector planes are analyzed in detail. In addition, a new high-accuracy distance calibration method for point light sources is proposed and verified in experiments.

Abstract Background Cadmium (Cd) exposure has been found to have detrimental effects on the development of the central nervous system and cognitive ability in children. However, there is ongoing debate regarding the impact of maternal Cd exposure on the cognitive ability of offspring. In this study, we aimed to investigate the mechanisms underlying the influence of maternal Cd exposure on the cognitive ability of offspring rats. Methods Here, we constructed a model of cadmium poisoning in first-generation rats through gavage. The cognitive and memory abilities of its offspring were evaluated by water maze experiment. Then, we used the gene chip to find out the key genes, and we performed qRT-PCR detection of these genes. Subsequently, enrichment analysis was employed to identify pathways. Finally, we constructed a co-expression network consisting of LncRNAs and mRNAs to elucidate the biological functions and regulatory mechanisms of LncRNAs. Results The results of the water maze trial demonstrated that the offspring of rats exposed to cadmium in the first generation had reduced cognitive and memory abilities. Through an analysis of gene expression in the hippocampus of the cadmium-treated rats' offspring and the control group, we identified a correlation between the islet secretion pathway and the cognitive impairment observed in the offspring. Utilizing various algorithms, we identified Cpa1 and Prss1 as potential key genes associated with the cognitive impairment caused by cadmium. The results of qRT-PCR demonstrated a decrease in the expression levels of these genes in the hippocampus of the cadmium-treated rats’ offspring. In addition, in the co-expression network, we observed that Cpa1 was co-expressed with 11 LncRNAs, while Prss1 was associated with 4 unexplored LncRNAs. Furthermore, we conducted an analysis to examine the relationship between Cpa1, Prss1-related transcription factors, and LncRNAs. Conclusion Overall, this study provides novel insights into the molecular effects of first generation Cd exposure on the cognitive ability of offspring. The target genes and signaling pathways investigated in this study could serve as potential targets for improving neurodevelopment and cognitive ability in children.

In this paper, a high-sensitivity cross-axial extrinsic Fabry-Perot interferometric (EFPI) acoustic sensor is proposed and experimentally demonstrated. The cross-axial EFPI is constructed by optical fiber and cantilever's inner surface, assisted with an adjustable 45° mirror. Herein, the 45° mirror is utilized to achieve beam total reflection and flexibly adjust the parallelism of the two reflectors. A quarter-pitch graded index fiber (GIF) is introduced as an in-fiber collimator to reduce beam propagation loss and thus enhance coupling efficiency. Experimental results show that the proposed sensor achieves a high fringe visibility of up to 41 dB, greatly enhancing acoustic sensing performance. Furthermore, the sensitivity and the minimum detectable pressure (MDP) measured at resonance frequency (@2.05 kHz) are significantly improved to be 70.67 mV/Pa that is corresponding to mechanical sensitivity of ∼2490 nm/Pa, and 13.4 μPa/Hz1/2, respectively. The proposed sensor demonstrates the potential for low-frequency vibration monitoring with the advantages of easy fabrication, high-sensitivity and flexible manipulability.

Building a human-like dialogue system is a challenging task that requires effective use of context, common sense and personal information. In a conversation, the responder usually analyzes the emotion, intention, and common sense involved in the speaker’s sentence. Based on this analysis, the responder considers both the above-mentioned content and their personal information to formulate a response. Previous work in this area has only focused on one or some aspects, such as emotion, intention, common sense or persona, rather than considering all of them together. To address this issue, we propose a response generation framework called EFCP, which is based on empathy factors, common sense, and persona. This framework simulates a rich dialogue generation process that is rarely seen in previous work. In predicting the type of empathy factors a responder should adopt, we consider both the responder’s personal information and the conversation history. Our experiments show that this method effectively improves the accuracy of prediction. EFCP outperforms the baseline on a variety of automatic metrics and manual metrics, showing its potential for building more effective and human-like dialogue systems.

Multispectral (MS) image pansharpening is a significant technology for remote sensing image analysis, aiming to restore a high-resolution MS image by merging a high-resolution panchromatic image with a low-resolution MS image. While the convolutional neural networks (CNNs) have garnered considerable attention for their exceptional fusion capabilities in recent years, the existing CNN-based methods cannot effectively integrate spectral–spatial information. In this article, we introduce a novel MS pansharpening framework that integrates spectral and spatial networks in a bilateral pyramid form, allowing for the extraction of hierarchical spectral–spatial information. The proposed reduced residual dense (RRD) module serves as the fundamental building block of the spatial network. The RRD module gradually reduces the dimension of feature maps and employs the concatenation of RRD with global residual learning for comprehensive feature representation. In the spectral network, we present a cooperative attention fusion module to further enhance the correlation between spectral and spatial features. Through extensive experiments conducted on benchmarking simulated and real datasets, our proposed framework consistently outperforms state-of-the-art methods, demonstrating its effectiveness in MS image pansharpening applications.

The potato cyst nematode (Globodera rostochiensis) is an obligate root pathogen of potatoes. G. rostochiensis encodes several highly expanded effector gene families, including the Gr4D06 family; however, little is known about the function of this effector family. We cloned four 29D09 genes from G. rostochiensis (named Gr29D09v1/v2/v3/v4) that share high sequence similarity and are homologous to the Hg29D09 and Hg4D06 effector genes from the soybean cyst nematode (Heterodera glycines). Phylogenetic analysis revealed that Gr29D09 genes belong to a subgroup of the Gr4D06 family. We showed that Gr29D09 genes are expressed exclusively within the nematode's dorsal gland cell and are dramatically upregulated in parasitic stages, indicating involvement of Gr29D09 effectors in nematode parasitism. Transgenic potato lines overexpressing Gr29D09 variants showed increased susceptibility to G. rostochiensis. Transient expression assays in Nicotiana benthamiana demonstrated that Gr29D09v3 could suppress reactive oxygen species (ROS) production and defense gene expression induced by flg22 and cell death mediated by immune receptors. These results suggest a critical role of Gr29D09 effectors in defense suppression. The use of affinity purification coupled with nanoliquid chromatography–tandem mass spectrometry identified potato hexokinase 1 (StHXK1) as a candidate target of Gr29D09. The Gr29D09–StHXK1 interaction was further confirmed using in planta protein–protein interaction assays. Plant HXKs have been implicated in defense regulation against pathogen infection. Interestingly, we found that StHXK1 could enhance flg22-induced ROS production, consistent with a positive role of plant HXKs in defense. Altogether, our results suggest that targeting StHXK1 by Gr29D09 effectors may impair the positive function of StHXK1 in plant immunity, thereby aiding nematode parasitism. [Graphic: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Abstract Information regarding regional arterial stiffness assessment in osteoarthritis (OA) was scarce and sometimes contradictory. We aimed to investigate the aortic, lower limb peripheral arterial stiffness and their associations with knee OA. Patients with primary knee OA and matched non-OA controls were prospectively enrolled from two medical centers in China. The carotid-femoral pulse wave velocity (cfPWV) and femoral-ankle pulse wave velocity (faPWV) were measured using a novel ultrasound technique. A total of 238 participants (including 128 patients with knee OA and 110 controls) were included. In OA patients, cfPWV was significantly higher than that of non-OA controls (9.40 ± 1.92 vs 8.25 ± 1.26 m/s, P

Vegetable fields are often contaminated by heavy metals, and Spodoptera exigua is a major vegetable pest which is stressed by heavy metals mainly by feeding. In this study, cadmium accumulation in the tissues of S. exigua exposed to cadmium and its effects on the growth and development of the parents and the offspring were investigated. Under the stress of different concentrations of cadmium (0.2, 3.2, and 51.2 mg kg–1), the cadmium content in each tissue of S. exigua increased in a dose-dependent manner. At the larval stage, the highest cadmium accumulation was found in midgut in all three cadmium treatments, but at the adult stage, the highest cadmium content was found in fat body. In addition, the cadmium content in ovaries was much higher than in testes. When F1 S. exigua was stressed by cadmium and the F2 generation was not fed a cadmium-containing diet, the larval survival, pupation rate, emergence rate and fecundity of the F2 generation were significantly reduced in the 51.2 mg kg–1 treatment compared to the corresponding F1 generation. Even in the F2 generation of the 3.2 mg kg–1 treatment, the fecundity was significantly lower than in the parental generation. The fecundity of the only-female stressed treatment was significantly lower than that of the only-male stressed treatment at the 3.2 and 51.2 mg kg–1 cadmium exposure levels. When only mothers were stressed at the larval stage, the fecundity of the F2 generation was significantly lower than that of the F1 generation in the 51.2 mg kg–1 treatment, and it was also significantly lower than in the 3.2 and 0.2 mg kg–1 treatments. The results of our study can provide useful information for forecasting the population increase trends under different heavy metal stress conditions and for the reliable environmental risk assessment of heavy metal pollution.

Abstract Background Radiotherapy (RT) is an effective and available local treatment for patients with refractory or relapsed (R/R) aggressive B-cell lymphomas. However, the value of hypofractionated RT in this setting has not been confirmed. Methods We retrospectively analyzed patients with R/R aggressive B-cell lymphoma who received hypofractionated RT between January 2020 and August 2022 at a single institution. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and acute side effects were analyzed. Results A total of 30 patients were included. The median dose for residual disease was 36 Gy, at a dose per fraction of 2.3–5 Gy. After RT, the ORR and complete response (CR) rates were 90% and 80%, respectively. With a median follow-up of 10 months (range, 2–27 months), 10 patients (33.3%) experienced disease progression and three died. The 1-year OS and PFS rates for all patients were 81.8% and 66.3%, respectively. The majority (8/10) of post-RT progressions involved out-of-field relapses. Patients with relapsed diseases, no response to systemic therapy, multiple lesions at the time of RT, and no response to RT were associated with out-of-field relapses. PFS was associated with response to RT (P = 0.001) and numbers of residual sites (P

The effect of target tracking is not ideal when facing various complex tracking scenarios such as non-rigid deformation of target, frequent occlusion, clutter of target background and interference of similar objects. In this paper, the feature based on deep convolutional neural network is used for target tracking in moving scenes, and a sliding window target segmentation method is proposed to study the impact of data normalization and data set expansion on the final result. In order to select more distinguishing features, principal component analysis is used to process the features of Deep Convolution Neural Network (DCNN), and the features of different network layers of DCNN are compared. The feature coding algorithm is studied, and the extracted DCNN features are encoded by Fisher Vectors algorithm, and compared with the locality-constrained linear encoding technique. Experiments show that the feature based on deep convolutional neural network in this paper can obtain higher accuracy than the traditional feature fusion method. According to the result analysis, the tracking accuracy of deep convolutional neural network algorithm is improved under the condition of illumination variation. In the case of local occlusion, the tracking accuracy is also improved.

mRNA platform holds promise for next-generation Varicella-zoster Virus (VZV) vaccine development due to its high potency at inducing strong T-cell response. Built upon the design of our 1st-generation VZV mRNA vaccine that encodes for full-length gE antigen, in this study we reported on a novel combinatorial strategy to further optimize the gE-encoding mRNA sequence through signal peptide replacement, C-terminal modification, and insertion of mRNA-stabilizing motif, which collectively contributed to significantly improved vaccine immunogenicity. In adult mice, aged mice, and immunocompromised mice, this optimized VZV mRNA vaccine showed strong superiority in multiple aspects including the induction of gE-specific antibodies, specific memory B-cell response, as well as Th1-type T-cell response.

AbstractPain management remains among the most common and largely unmet clinical problems today. Local anesthetics play an indispensable role in pain management. The main limitation of traditional local anesthetics is the limited duration of a single injection. To address this problem, catheters are often placed or combined with other drugs in clinical practice to increase the time that local anesthetics act. However, this method does not meet the needs of clinical analgesics. Therefore, many researchers have worked to develop local anesthetic extended-release types that can be administered in a single dose. In recent years, drug extended-release systems have emerged dramatically due to their long duration and efficacy, providing more possibilities for the application of local anesthetics. This paper summarizes the types of local anesthetic drug delivery systems and their clinical applications, discusses them in the context of relevant studies on local anesthetics, and provides a summary and outlook on the development of local anesthetic extended-release agents.

AbstractIt is difficult to accurately predict and assess the instability of the stope. This article uses the improved Mathews stability graph method to scientifically analyse and evaluate the quality and stability of the surrounding rock. It utilizes the failure factor (FF) to express the degree of rock failure under different stress states based on the Mohr–Coulomb criterion and to determine the new rock stress factor. This new method is successfully applied in a case study at a lead–zinc mine in Hongling and makes a comparative analysis with the actual situation of the site.

ABSTRACTThe COVID-19 pandemic presents a major threat to global public health. Several lines of evidence have shown that the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), along with two other highly pathogenic coronaviruses, SARS-CoV and Middle East Respiratory Syndrome (MERS-CoV) originated from bats. To prevent and control future coronavirus outbreaks, it is necessary to investigate the interspecies infection and pathogenicity risks of animal-related coronaviruses. Currently used infection models, including in vitro cell lines and in vivo animal models, fail to fully mimic the primary infection in human tissues. Here, we employed organoid technology as a promising new model for studying emerging pathogens and their pathogenic mechanisms. We investigated the key host-virus interaction patterns of five human coronaviruses (SARS-CoV-2 original strain, Omicron BA.1, MERS-CoV, HCoV-229E, and HCoV-OC43) in different human respiratory organoids. Five indicators, including cell tropism, invasion preference, replication activity, host response and virus-induced cell death, were developed to establish a comprehensive evaluation system to predict coronavirus interspecies infection and pathogenicity risks. Using this system, we further examined the pathogenicity and interspecies infection risks of three SARS-related coronaviruses (SARSr-CoV), including WIV1 and rRsSHC014S from bats, and MpCoV-GX from pangolins. Moreover, we found that cannabidiol, a non-psychoactive plant extract, exhibits significant inhibitory effects on various coronaviruses in human lung organoid. Cannabidiol significantly enhanced interferon-stimulated gene expression but reduced levels of inflammatory cytokines. In summary, our study established a reliable comprehensive evaluation system to analyse infection and pathogenicity patterns of zoonotic coronaviruses, which could aid in prevention and control of potentially emerging coronavirus diseases.

ABSTRACTHerpes zoster remains an important global health issue and mainly occurs in aged and immunocompromised individuals with an early exposure history to Varicella Zoster Virus (VZV). Although the licensed vaccine Shingrix has remarkably high efficacy, undesired reactogenicity and increasing global demand causing vaccine shortage urged the development of improved or novel VZV vaccines. In this study, we developed a novel VZV mRNA vaccine candidate (named as ZOSAL) containing sequence-optimized mRNAs encoding full-length glycoprotein E encapsulated in an ionizable lipid nanoparticle. In mice and rhesus macaques, ZOSAL demonstrated superior immunogenicity and safety in multiple aspects over Shingrix, especially in the induction of strong T-cell immunity. Transcriptomic analysis revealed that both ZOSAL and Shingrix could robustly activate innate immune compartments, especially Type-I IFN signalling and antigen processing/presentation. Multivariate correlation analysis further identified several early factors of innate compartments that can predict the magnitude of T-cell responses, which further increased our understanding of the mode of action of two different VZV vaccine modalities. Collectively, our data demonstrated the superiority of VZV mRNA vaccine over licensed subunit vaccine. The mRNA platform therefore holds prospects for further investigations in next-generation VZV vaccine development.

The soaking process of glutinous rice allows the growth and reproduction of microorganisms, which can easily cause food safety problems. In this work, the effects of different ultrasonic powers (150 W, 300 W, 450 W, and 600 W) on the bactericidal effect of glutinous rice, the physicochemical properties of starch and the quality characteristics of sweet dumplings were studied. Compared with soaking for 0 and 2 h, sonication of glutinous rice after soaking for 4 h was more effective at reducing the number of microorganisms in soaked glutinous rice, and the bactericidal effect increased with increasing ultrasound intensity. After 30 min, the total number of bacteria decreased by 2.04 log CFU/g. Moreover, ultrasonic treatment destroys the grain structure of glutinous rice starch, resulting in the formation of dents and cracks on the starch surface, increasing the amylose content, improving its expansion, reducing its short-range order and relative crystallinity, and altering its gelatinization characteristics. In addition, ultrasonic treatment increased the soup transparency of sweet dumplings from 51.8 % to 63.95 %, reducing their hardness, chewiness and adhesiveness. In summary, ultrasonic treatment can not only effectively kill microorganisms in soaked glutinous rice but also improve the quality of glutinous rice dumplings by changing the physicochemical properties of glutinous rice starch. The results of this study provide theoretical support for the application of ultrasonic technology in glutinous rice food production.

Coal worker's pneumoconiosis (CWP), a pulmonary condition resulting from prolonged exposure to coal mining environments, not only leads to a high prevalence of morbidity and mortality among miners but also incurs substantial economic burdens and diminishes the labor force within society. In light of evolving trends in the global coal industry, the ramifications of CWP are anticipated to manifest in new patterns and variations. This study seeks to comprehensively assess the present landscape, trend dynamics, and future projections of the global CWP burden from 1990 to 2019. The objective is to provide a scientific framework for nations to develop and enhance pertinent policies and preventative strategies, thereby promoting the health and occupational safety of coal miners.

Objective: To observe the clinical efficacy of Chinese herbal medicine combined with Liuzijue exercise on the physiological symptoms and quality of life (QoL) in postoperative patients with early-stage lung cancer. Methods: One hundred and eighty-three lung cancer patients who underwent video-assisted thoracoscopic surgery (VATS) were categorize into either a traditional Chinese medicine treatment group (CM) or a control group (non-traditional Chinese medicine treatment, NC), among whom 73 underwent Chinese herbal medicine and Liuzijue therapy, while 110 underwent no comprehensive treatment with traditional Chinese medicine. The propensity score matching (PSM) method with a 1:2 ratio was used to balance the baseline characteristics and evaluate the efficacy of CM in improving postoperative symptoms and QoL. Results: Cough, dyspnea, chest pain, and fatigue were the most common clinical symptoms after VATS. Except for chest pain, they were all correlated with the scope of operation ( P .05). In the domain of global health status, the improvement in QoL in CM was greater than that in NC (6.06 ± 15.83 vs −1.06 ± 14.68, P = .005). In terms of symptoms, improvements in cough (1.69 ± 3.15 vs 0.38 ± 2.63, P = .006), dyspnea during climbing stairs (−10.30 ± 16.82 vs −1.82 ± 17.97, P = .004), and pain (−0.76 ± 1.32 vs −0.08 ± 1.31, P = .002) in CM were better than in NC. Conclusion: Comprehensive treatment with traditional Chinese medicine (TCM) can provide therapeutic benefits in physiological rehabilitation after VATS for cancer.

ObjectiveTo examine the dose–response relationship between specific types of exercise for alleviating Timed up and Go (TUG) in Parkinson’s disease PD.DesignSystematic review and Bayesian network meta-analysis.Data sourcesPubMed, Medline, Embase, PsycINFO, Cochrane Library, and Web of Science were searched from inception until February 5th, 2024.Study analysisData analysis was conducted using R software with the MBNMA package. Effect sizes of outcome indicators were expressed as mean deviation (MD) and 95% confidence intervals (95% CrI). The risk of bias in the network was evaluated independently by two reviewers using ROB2.ResultsA total of 73 studies involving 3,354 PD patients. The text discusses dose–response relationships in improving TUG performance among PD patients across various exercise types. Notably, Aquatic (AQE), Mix Exercise (Mul_C), Sensory Exercise (SE), and Resistance Training (RT) demonstrate effective dose ranges, with AQE optimal at 1500 METs-min/week (MD: −8.359, 95% CI: −1.398 to −2.648), Mul_C at 1000 METs-min/week (MD: −4.551, 95% CI: −8.083 to −0.946), SE at 1200 METs-min/week (MD: −5.145, 95% CI: −9.643 to −0.472), and RT at 610 METs-min/week (MD: −2.187, 95% CI: −3.161 to −1.278), respectively. However, no effective doses are found for Aerobic Exercise (AE), Balance Gait Training (BGT), Dance, and Treadmill Training (TT). Mind–body exercise (MBE) shows promise with an effective range of 130 to 750 METs-min/week and an optimal dose of 750 METs-min/week (MD: −2.822, 95% CI: −4.604 to −0.996). According to the GRADE system, the included studies’ overall quality of the evidence was identified moderate level.ConclusionThis study identifies specific exercise modalities and dosages that significantly enhance TUG performance in PD patients. AQE emerges as the most effective modality, with an optimal dosage of 1,500 METs-min/week. MBE shows significant benefits at lower dosages, catering to patients with varying exercise capacities. RT exhibits a nuanced “U-shaped” dose–response relationship, suggesting an optimal range balancing efficacy and the risk of overtraining. These findings advocate for tailored exercise programs in PD management, emphasizing personalized prescriptions to maximize outcomes.Systematic Review Registration: International Prospective Register of Systematic Reviews (PROSPERO) (CRD42024506968).