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Xi Chen,1 Lu Gao,1 Zhen Zhen,1 Ying Wang,1 Jia Na,1 Wen Yu,1 Xinyuan Chu,1 Yue Yuan,1 Suyun Qian2 1Department of Cardiology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, People’s Republic of China; 2Pediatric Intensive Care Unit, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, People’s Republic of ChinaCorrespondence: Yue Yuan, Department of Cardiology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, No. 56, Nanlishilu, District Xicheng, Beijing, 100045, People’s Republic of China, Email yuanyuebjdr@163.com; yuanyuebj22@sina.com Suyun Qian, Pediatric Intensive Care Unit, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, No. 56, Nanlishilu, District Xicheng, Beijing, 100045, People’s Republic of China, Email qiansuyunbj12@163.com; suyunqian1211@163.comPurpose: To explore the risk factors and develop predictive models for intravenous immunoglobulin (IVIG) resistance in children with recurrent Kawasaki disease (KD).Patients and Methods: Patients with recurrent KD were retrospectively reviewed. Clinical and laboratory data at recurrence were collected and compared between patients with and without IVIG resistance. The patients were randomly divided into training and validation cohorts for model development and validation. All variables were subjected to standard Lasso and its variant group Lasso analyses, respectively, to construct predictive models. Model performance was evaluated by receiver operating characteristics (ROC) curves, calibration curves, and Hosmer-Lemeshow tests.Results: A total of 90 children with recurrent KD were included. A total of 16 cases were IVIG resistant. The patients with IVIG resistance had higher age and IVIG resistance probability at the first episode, increased CRP levels, neutrophil count, neutrophil percentage, direct bilirubin level, prothrombin time, and international normalized ratio, and decreased lymphocyte count, lymphocyte percentage, and serum sodium levels. Five variables including age and IVIG resistance at the first episode, lymphocytes count, serum sodium levels, and CRP levels were finally selected by standard Lasso (lLasso model) and four variables including age and IVIG resistance at the first episode, neutrophil percentage, and CRP levels were selected by group Lasso (gLasso). ROC curves suggested lLasso and gLasso models had similar excellent discrimination in both the training cohort (0.895 vs 0.906) and the validation cohort (0.855 vs 0.909). Hosmer-Lemeshow tests suggested the two models exerted a good calibration. Two nomograms were also constructed to facilitate the potential application of the two models.Conclusion: Age and IVIG resistance at the first episode and some laboratory variables may be risk factors for IVIG resistance in recurrent KD. Two predictive models for IVIG resistance with excellent performance were established in recurrent KD. External validation should be performed before clinical use.Keywords: recurrent Kawasaki disease, intravenous immunoglobulin, resistance, risk factor, predictive model

Shuang Li,1,2 Jun Na,1,2 Huijuan Mu,1,2 Yanxia Li,1,2 Li Liu,1,2 Rui Zhang,1,2 Jingyan Sun,1,3 Yuying Li,1,3 Wei Sun,1,3 Guowei Pan,1,3 Lingjun Yan1,3 1Institute of Preventive Medicine, China Medical University, Shenyang, People’s Republic of China; 2Institute of Chronic Diseases, Liaoning Provincial Center for Disease Control and Prevention, Shenyang, People’s Republic of China; 3Research Center for Universal Health, School of Public Health, China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Lingjun YanResearch Center for Universal Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, People’s Republic of ChinaTel + 86 2431939406Email ljyan@cmu.edu.cnPurpose: Few studies have assessed the individual and joint effects of the mother’s, father’s and teacher’s mental health symptoms on schoolchildren’s behavior and emotional well-being simultaneously in the same study.Patients and Methods: A cross-sectional survey was conducted among 8488 Chinese schoolchildren aged 6– 17 years in northeast China. The Strengths and Difficulties Questionnaire (SDQ) and General Health Questionnaire (GHQ) were used to measure the mental health of the students, their parents and the teacher in charge of the class, respectively. A total of 6173 students (72.73%) with full mental health information from all three caretakers were included in the final analysis.Results: We found a significantly elevated risk of mental health symptoms in children when their mothers (odds ratios (OR)=2.30, 95% CI=1.93– 2.73), fathers (OR=2.08, 95% CI=1.73– 2.50) and teachers (OR=1.18, 95% CI=1.01– 1.39) reported poorer mental health, and the risk increased significantly with the number of the caretakers with mental symptoms. A father with poor mental health has both direct and indirect effects on a child’s emotional health, by worsening the influence of a mother’s poor mental health.Conclusion: All three caretakers have a significant negative influence on schoolchildren’s emotional well-being, in the order of mother > father > teacher. It is desirable to assess and manage students’ mental health in the both the family and school contexts.Keywords: combined effects, mental health symptoms, fathers, mothers, teachers, school children

To reconstruct deep fluid chemical composition and increase the confidence in estimated reservoir temperatures, a more integral geothermometry method was compared to other classical geothermometers. Here, we apply the integrated multicomponent geothermometry (IMG) method using the GeoT code to estimate reservoir temperatures at the Tengchong geothermal field in Southwestern China. Results show reservoir temperatures calculated using the quartz geothermometer are closest to those estimated with the IMG method. The concentrations of Al and Mg, as well as selected minerals for geothermometry computations, are key factors for successfully using the IMG. Using the IMG method together with classical geothermometers can significantly increase confidence in reservoir temperature estimations. The methods presented and simulation program used here may be useful for analysis of other geothermal fields under similar conditions.

Abstract To reveal the molecular function of elongation family of very long chain fatty acids(ELO) protein in Cyrtotrachelus buqueti, we have identified 15 ELO proteins from C.buqueti genome. 15 CbuELO proteins were located on four chromosomes. Their isoelectric points ranged from 9.22 to 9.68, and they were alkaline. These CbuELO proteins were stable and hydrophobic. CbuELO proteins had transmembrane movement, and had multiple phosphorylation sites. The secondary structure of CbuELO proteins was mainly α-helix. A total of 10 conserved motifs were identified in CbuELO protein family. Phylogenetic analysis showed that molecular evolutionary relationships of ELO protein family between C. buqueti and Tribolium castaneum was the closest. Developmental transcriptome analysis indicated that CbuELO10, CbuELO13 and CbuELO02 genes were key enzyme genes that determine the synthesis of very long chain fatty acids in pupae and eggs, CbuELO6 and CbuELO7 were that in the male, and CbuELO8 and CbuELO11 were that in the larva. Transcriptome analysis under different temperature conditions indicated that CbuELO1, CbuELO5, CbuELO12 and CbuELO14 participated in regulating temperature stress responses. Transcriptome analysis at different feeding times showed CbuELO12 gene expression level in all feeding time periods was significant downregulation. The qRT-PCR experiment verified expression level changes of CbuELO gene family under different temperature and feeding time conditions. Protein-protein interaction analysis showed that 9 CbuELO proteins were related to each other, CbuELO1, CbuELO4 and CbuELO12 had more than one interaction relationship. These results lay a theoretical foundation for further studying its molecular function during growth and development of C. buqueti.

Abstract DNA binding with one finger(Dof) gene family is a class of transcription factors which play an important role on plant growth and development. Genome-wide identification results indicated that there were 45 Dof genes(ColDof) in C.oleifera genome. All 45 ColDof proteins were non-transmembrane and non-secretory proteins. Phosphorylation site analysis showed that biological function of ColDof proteins were mainly realized by phosphorylation at serine (Ser) site. The secondary structure of 44 ColDof proteins was dominated by random coil, and only one ColDof protein was dominated by α-helix. ColDof genes’ promoter region contained a variety of cis-acting elements, including light responsive regulators, gibberellin responsive regulators, abscisic acid responsive regulators, auxin responsive regulators and drought induction responsive regulators. The SSR sites analysis showed that the proportion of single nucleotide repeats and the frequency of A/T in ColDof genes were the largest. Non-coding RNA analysis showed that 45 ColDof genes contained 232 miRNAs. Transcription factor binding sites of ColDof genes showed that ColDof genes had 5793 ERF binding sites, 4381 Dof binding sites, 2206 MYB binding sites, 3702 BCR-BPC binding sites. ColDof9, ColDof39 and ColDof44 were expected to have the most TFBSs. The collinearity analysis showed that there were 40 colinear locis between ColDof proteins and AtDof proteins. Phylogenetic analysis showed that ColDof gene family was most closely related to that of Camellia sinensis var. sinensis cv.Biyun and Camellia lanceoleosa. Protein-protein interaction analysis showed that ColDof34, ColDof20, ColDof28, ColDof35, ColDof42 and ColDof26 had the most protein interactions. The transcriptome analysis of C. oleifera seeds showed that 21 ColDof genes were involved in the growth and development process of C. oleifera seeds, and were expressed in 221 C. oleifera varieties. The results of qRT-PCR experiments treated with different concentrations NaCl and PEG6000 solutions indicated that ColDof1, ColDof2, ColDof14 and ColDof36 not only had significant molecular mechanisms for salt stress tolerance, but also significant molecular functions for drought stress tolerance in C. oleifera. The results of this study provide a reference for further understanding of the function of ColDof genes in C.oleifera.

Abstract Background Pyrethroid chemicals are one of the main acaricides used against ticks. Resistance to these chemicals has been reported to be associated with mutations in the voltage-gated sodium channel (VGSC) gene of the Rhipicephalus microplus. This study investigates R. microplus resistance to pyrethroids in Guangxi region of China, marking one of the first research efforts in this area. The findings are intended to provide vital baseline for the effective implementation of localized tick control strategies. Methods From March to July 2021, 447 R. microplus tick samples were collected from five prefecture-level cities in Guangxi. Allele-specific polymerase chain reaction (AS-PCR) was used to amplify segments C190A and G215T of the domain II S4-5 linker and T2134A of domain III S6 in the VGSC, to detect nucleotide mutations associated with resistance to pyrethroid acaricides. Subsequent analyses were conducted to ascertain the prevalence, types of mutations, and genotypic distributions within the sampled populations. Results Mutations within VGSC gene were identified across all five studied populations of R. microplus, although the mutation rates remained generally low. Specifically, the most prevalent mutation was C190A, observed in 4.9% of the samples (22/447), followed by G215T at 4.0% (18/447), and T2134A at 1.3% (6/447). The distribution of mutations across three critical sites of the VGSC gene revealed four distinct mutation types: C190A, G215T, C190A + G215T, and T2134A. Notably, the single mutation C190A had the highest mutation frequency, accounting for 4.3%, and the C190A + G215T combination had the lowest, at only 0.7%. The analysis further identified seven genotypic combinations, with the wild-type combination C/C + G/G + T/T predominating at a frequency of 90.4%. Subsequently, the C/A + G/G + T/T combination was observed at a frequency of 4.3%, whereas the C/C + T/T + T/T combination exhibited the lowest frequency (0.2%). Additionally, no instances of simultaneous mutations at all three sites were detected. Geographical differences in mutation types were apparent. Both samples from Hechi to Chongzuo cities exhibited the same three mutation types; however, C190A was the most prevalent in Hechi, while G215T dominated in Chongzuo. In contrast, samples from Beihai to Guilin each exhibited only one mutation type: G215T occurred in 12.5% (4/32) of Beihai samples, and C190A in 7.5% (4/53) of Guilin samples. Conclusions These findings underscore the relatively low frequency of VGSC gene mutations in R. microplus associated with pyrethroid resistance in the Guangxi, China. Moreover, the variation in mutation types and genotypic distributions across different locales highlights the need for regionalized strategies in monitoring and managing pyrethroid resistance in tick populations. This molecular surveillance is crucial for informing targeted control measures and mitigating the risk of widespread resistance emergence. Graphical Abstract

Abstract Dof transcription factor family in Cyperus esculentus genome was identified and analyzed using bioinformatics. The analysis results revealed that C.esculentus genome contains 29 Dof genes (CesDof), all of which are located in the nucleus according to subcellular localization prediction. CesDof proteinrs have a range of 124 to 512 amino acids, with most being basic proteins. Their secondary structure was mainly irregular curl. The promoter sequence of CesDof genes contains cis-acting elements that respond to light, drought, hormones, low temperature, and circadian rhythm. Codon preference analysis showed that CesDof genes' codon preference ends in T/A. Collinearity analysis revealed that C.esculentus had three pairs of collinear CesDof genes. Additionally, there were 15 pairs of collinear genes between C.esculentus and Arabidopsis thaliana. The genetic relationship between C.esculentus and Rhynchospora pubera was found to be the closest. Phylogenetic tree analysis revealed that 29 CesDof genes of C.esculentus can be classified into 4 subgroups. Additionally, 144 miRNAs were predicted to target these CesDof genes. Furthermore, protein interaction analysis indicated that 15 Dof proteins in C.esculentus had interactions. The qRT-PCR verification results of drought stress and salt stress treatment experiments showed that most CesDof genes were involved in drought stress and salt stress responses, and the gene expression trends under drought stress and salt stress conditions were consistent. These results lay a theoretical foundation for further studying the molecular functions of Dof gene family in C.esculentus and its molecular mechanisms in regulating the life activities of C.esculentus.

Ti3AlC2 (TAC) has great potential for use as an ablation material in aerospace applications due to its great oxidation/ablation resistance, but its high-temperature strength and thermal shock resistance still have much room for simultaneous improvement under fast temperature variation conditions. Herein, we used Ti3AlC2 and WC powders as raw materials and successfully fabricated textured (Ti,W)3AlC2 ceramic with small amounts of TiC and Al2O3, and room temperature mechanical properties such as flexural strength (1146±46.9 MPa), fracture toughness (11.78±0.44 MPa·m1/2), and hardness (5.81±0.11 GPa) at 5 wt% WC addition were achieved. The high-temperature strength of the ceramic was significantly improved, and better thermal shock resistance from 298 to 1173 K was simultaneously acquired together with the regulation of the elastic modulus, thermal conductivity, and thermal expansion coefficient, providing (Ti,W)3AlC2 with more possibilities for fast-temperature variation applications. Strengthening and toughening mechanisms were proposed. Scanning transmission electron microscopy high-angle annular dark-field imaging (STEM-HADDF) showed that W randomly replaced the Ti1 and Ti2 sites of Ti3AlC2, providing a good reference for establishing crystal models, and further density functional theory (DFT) calculations based on these models indicated a higher fracture energy of (Ti,W)3AlC2 along different crystal planes, providing superior resistance to transgranular fracture; a lower mismatch degree of (Ti,W)3AlC2/Al2O3 resulted in stronger interface bonding, resulting in greater resistance to intergranular fracture as well as more balanced stress distributions at different interfaces.

Abstract Spotted fever group rickettsiae (SFGR) are obligate intracellular bacteria that cause spotted fever. The limitations of gene manipulation pose great challenges to studying the infection mechanisms of Rickettsia. By combining bioorthogonal metabolism and click chemistry, we developed a method to label R. heilongjiangensis via azide moieties and achieved rapid pathogen localization without complex procedures. Moreover, we constructed a C57BL/6 mice infection model by simulating tick bites and discovered that the stomach is the target organ of R. heilongjiangensis infection through in vivo imaging systems, which explained the occurrence of gastrointestinal symptoms following R. heilongjiangensis infection in some cases. This study offers a unique perspective for subsequent investigations into the pathogenic mechanisms of SFGR and identifies a potential target organ for R. heilongjiangensis.

Abstract Background The persistent infection of high-risk Human papillomavirus(HPV) is considered the main cause of cervical intraepithelial neoplasia and cervical cancer. But various cervical lesions caused by HPV infection can be properly prevented by timely vaccination. However, the distribution of HPV genotypes varies geographically. Methods Retrospective analysis of high-risk HPV prevalence of 16,150 women from 2020 to 2022 in xianning of China. HPV genotyping was performed using a PCR-RDB Kit that can detect 18 high-risk HPV genotypes recommended by China’s National Medical Products Administration. The prevalence of 18 high-risk HPV genotypes and their relationship with cervical lesions as well as vaccine efficacy were analyzed. Results A total of 2431 women were confirmed to have different types of high-risk HPV infections. The overall positive rate reached 15.05%(2431/16,150). The most prevalent high-risk HPV genotypes were HPV52, 16, 58, 53, and 51. The prevalence of high-risk HPV reached peak at age ≤ 20(20.95%) and age ≥ 61(20.56%). The most prevalent high-risk HPV genotypes were HPV16, 58, 18, 33 and 52 in cervical cancer cases, HPV16, 52, 58, 33 and 18 in CIN2/3 cases, and HPV52, 58, 16, 53 and 18 in CIN1 cases, respectively. Conclusion HPV16, 58 and 18 are the most dangerous and carcinogenic genotypes in xianning, China. Conducting epidemiological investigations on high-risk HPV has significant clinical value in guiding HPV vaccination work.

Abstract Ceracris kiangsu Tsai (C. kiangs) is a kind of forest pest, which can harm nearly 100 kinds of weeds and crops. In this study, based on 314 species distribution points of C. kiangsu which were obtained from Chinese herbaria, literatures and investigation, and data of three future climate scenarios presented by CMIP6, two niche models (Garp, Maxent) were used to predict the suitable area of C. kiangsu in China. The result shows that the main environmental factors affecting the distribution of C. kiangsu are precipitation of driest month (bio14) and min temperature of coldest month (bio6). No matter now and future, the potential distribution areas of C. kiangsu in China are mainly in the south of Qinling–Huaihe River. Under current scenarios, the areas of the total, highly, moderately and poorly suitable of C. kiangsu in China are 160.65 × 104 km2, 31.70 × 104 km2, 60.36 × 104 km2 and 68.59 × 104 km2 respectively. The southern Hubei, western Jiangxi and eastern Hunan are highly-suitable areas. Under SSP1-2.6 and SSP2-4.5 scenarios, both the total suitable area and the highly suitable show a decreasing tread in 2050s. Compared to the 2050s, the total suitable area will coninue to decease in 2090s under SSP1-2.6, while it will increase under SSP2-4.5. The highly suitable area will increase in both scenarios, and the increased percentage under SSP2-4.5 is greater than that under SSP1-2.6. Under SSP5-8.5 scenarios, the total suitable area will increase by 1.83% in the 2050s, and decrease by 1.17% in the 2090s. The highly suitable area in the 2050s and 2090s under this scenarios is larger than under current scenarios. No matter what the scenario, the southern part of Yunnan, the southeast of Sichuan and the southwest of Chongqing will become highly-suitable areas as the climate continues to warm and should be monitored more cosely.

Abstract Background Insect Cytochrome P450 monooxygenase (CYPs or P450s) plays an important role in detoxifying insecticides, causing insect populations to develop resistance. However, the molecular functions of P450 gene family in Cyrtotrachelus buqueti genome are still lacking. Results In this study, 71 CbuP450 genes have been identified. The amino acids length of CbuP450 proteins was between 183 aa ~ 1041 aa. They are proteins with transmembrane domains. The main component of their secondary structure is α-helix and random coils. Phylogenetic analysis showed that C. buqueti and Rhynchophorus ferrugineus were the most closely related. This gene family has 29 high-frequency codons, which tend to use A/T bases and A/T ending codons. Gene expression analysis showed that CbuP450_23 in the female adult may play an important role on high temperature resistance, and CbuP450_17 in the larval may play an important role on low temperature tolerance. CbuP450_10, CbuP450_17, CbuP450_23, CbuP450_10, CbuP450_16, CbuP450_20, CbuP450_23 and CbuP450_ 29 may be related to the regulation of bamboo fiber degradation genes in C. buqueti. Protein interaction analysis indicates that most CbuP450 proteins are mainly divided into three aspects: encoding the biosynthesis of ecdysteroids, participating in the decomposition of synthetic insecticides, metabolizing insect hormones, and participating in the detoxification of compounds. Conclusions We systematically analyzed the gene and protein characteristics, gene expression, and protein interactions of CbuP450 gene family, revealing the key genes involved in the stress response of CbuP450 gene family in the resistance of C. buqueti to high or low temperature stress, and identified the key CbuP450 proteins involved in important life activity metabolism. These results provided a reference for further research on the function of P450 gene family in C. buqueti.

Abstract Seven undescribed compounds, including three flavones (1–3), one phenylpropanoid (19), three monoaromatic hydrocarbons (27–29), were isolated from the twigs of Mosla chinensis Maxim together with twenty-eight known compounds. The structures were characterized by HRESIMS, 1D and 2D NMR, and ECD spectroscopic techniques. Compound 20 displayed the most significant activity against A/WSN/33/2009 (H1N1) virus (IC50 = 20.47 μM) compared to the positive control oseltamivir (IC50 = 6.85 µM). Further research on the anti-influenza mechanism showed that compound 20 could bind to H1N1 virus surface antigen HA1 and inhibit the early attachment stage of the virus. Furthermore, compounds 9, 22, 23, and 25 displayed moderate inhibitory effects on the NO expression in LPS inducing Raw 264.7 cells with IC50 values of 22.78, 20.47, 27.66, and 30.14 µM, respectively. Graphical Abstract

With the increasing awareness of healthy diet and environmental protection, plant-based meat products have been rapidly developed at home and abroad. The objective of this study was to examine how the ratio of pea tissue protein to gluten, along with the additions of sweet potato starch, rapeseed oil, and red yeast red, affected the sensory scores and chewiness of plant-based meat. On the basis of single factor experiments, the plant-based formula was optimized using Box Behnken response surface methodology and texture analysis, and the optimal formula was tested for physicochemical indicators and in vitro digestion tests. The results showed that the ratio of pea tissue protein to gluten was 7:3 (g/g), along with 6% sweet potato starch, 10% rapeseed oil, and 0.03% safflower red, resulted in plant-based meat with favorable sensory scores (88.31) and chewability (3.131). The protein content of the plant-based meat obtained from the optimal formula was 15.70%, the fat content was 2.33%, and the moisture content was 57.79%. According to texture analysis, there were significant differences in hardness, adhesiveness, and chewiness between plant meat and pork loin, beef, and chicken, in addition to elasticity. The results of in vitro digestion analysis showed that the protein digestibility of plant meat was 80.83%, while that of beef was 87.50%. The difference between the two was small, indicating that plant meat had good digestion ability. The plant meat made from pea tissue protein provides reference materials for further development, application, and other related industries.

Although aboveground biodiversity has been extensively studied, the impact of nutrient enrichment on soil microbial populations remains unclear. Soil microorganisms serve as important indicators in shaping soil nutrient cycling processes and are typically sensitive to nutrient additions. For this, we employed a factorial combination design to examine the impact of nutrient additions on the composition and function of soil bacteria in a temperate steppe. Nitrogen addition promoted the growth of copiotrophic bacteria (Proteobacteria, Firmicutes, and Bacteroidota) but inhibited the growth of oligotrophic bacteria (Acidobacteria, Chloroflexi, and Verrucomicrobiota). Phosphorus addition alleviated phosphorus deficiency, resulting in a decrease in the abundance of phoD-harboring bacteria (Actinobacteria and Proteobacteria). Significant enhancement of soil bacterial alpha diversity was observed only in treatments with added phosphorus. Changes in NO3−-N, NH4+-N, available phosphorus, and dissolved organic carbon resulting from nutrient addition may have a greater impact on microbial community structure than changes in soil pH caused by nitrogen addition. Moreover, nutrient addition may indirectly impact microbial ecological function by altering nutrient availability in the soil. In conclusion, our study suggests that soil nutrient availability, particularly available phosphorus, affects soil bacterial communities and potentially regulates the biogeochemical cycles of soil ecosystems.

Summary: Biological and artificial neural networks learn by modifying synaptic weights, but it is unclear how these systems retain previous knowledge and also acquire new information. Here, we show that cortical pyramidal neurons can solve this plasticity-versus-stability dilemma by differentially regulating synaptic plasticity at distinct dendritic compartments. Oblique dendrites of adult mouse layer 5 cortical pyramidal neurons selectively receive monosynaptic thalamic input, integrate linearly, and lack burst-timing synaptic potentiation. In contrast, basal dendrites, which do not receive thalamic input, exhibit conventional NMDA receptor (NMDAR)-mediated supralinear integration and synaptic potentiation. Congruently, spiny synapses on oblique branches show decreased structural plasticity in vivo. The selective decline in NMDAR activity and expression at synapses on oblique dendrites is controlled by a critical period of visual experience. Our results demonstrate a biological mechanism for how single neurons can safeguard a set of inputs from ongoing plasticity by altering synaptic properties at distinct dendritic domains.

Glycogen Storage Disease Type VII (GSD VII) is a rare glycogen metabolism disorder resulting from mutations in the PFKM gene, inherited in an autosomal recessive manner. It is characterized by exercise intolerance, muscle cramps, myoglobinuria, compensatory hemolysis, and later onset de novo myasthenia and mild myopathy, contributing to its clinical heterogeneity and diagnostic challenges. Here, we report a rare case of a 17-year-old Chinese woman exhibiting substantial muscle weakness and compensated hemolysis. Muscle biopsies showed glycogen deposition, and blood tests showed hyperuricemia and significantly elevated creatine kinase. Whole genome sequencing (WGS) and whole exome sequencing (WES) identified two compound heterozygous mutations in the PFKM (NM_000289.6) gene: c.626G>A and c.1376G>A in exons 7 and 15, respectively. According to the clinical presentation, diagnostic examination, and WES results, the patient was finally diagnosed with GSDVII. The discovery of these two new PFKM mutations expands the genetic spectrum, and understanding the clinical manifestations of these mutations is critical to preventing diagnostic delays and timely intervention and treatment.

ObjectivesThis study investigated the prevalence of suicidal ideation (SI) among Chinese medical students and its associated risk factors.MethodsA total of 6643 medical students (2383 males/4260 females) were recruited from a medical college in Hebei Province, China. Demographic data were collected via a self-administered questionnaire. The Childhood Trauma Questionnaire Short Form (CTQ-SF) was used to evaluate childhood maltreatment (CM), and the Adolescent Self-Rating Life Events Checklist (ASLEC) was used to evaluate the stressful life events. Suicidal ideation was assessed using the Beck Scale for Suicide Ideation (BSSI). Univariate and multivariate logistic regression models were used to analyze the factors affecting SI.ResultsThe prevalence of SI in medical students was 11.5% (763/6643). Multivariate logistic regression analysis revealed that SI was significantly associated with younger age, a female sex, being lovelorn, being introverted, experiencing CM during childhood, and experiencing stressful life events within the past 12 months. Of the five subtypes of CM, emotional abuse may have the strongest effect on SI (OR=2.76, 95% CI: 1.72–4.42). The joint effects of CM and stressful life events were significantly associated with an increased risk of SI (OR=5.39, 95% CI: 4.15–6.98).ConclusionThe prevalence of SI among medical students is high, and medical students who have experienced CM and stressful life events have a higher tendency towards SI. Screening for both CM and stressful life events may be an effective way of identifying individuals at high risk of SI.

Osteosarcoma is usually resistant to immunotherapy and, thus primarily relies on surgical resection and high-dosage chemotherapy. Unfortunately, less invasive or toxic therapies such as photothermal therapy (PTT) and chemodynamic therapy (CDT) generally failed to show satisfactory outcomes. Adequate multimodal therapies with proper safety profiles may provide better solutions for osteosarcoma. Herein, a simple nanocomposite that synergistically combines CDT, PTT, and chemotherapy for osteosarcoma treatment was fabricated. In this composite, small 2D NiFe-LDH flakes were processed into 3D hollow nanospheres via template methods to encapsulate 5-Fluorouracil (5-FU) with high loading capacity. The nanospheres were then adsorbed onto larger 2D Ti3C2 MXene monolayers and finally shielded by bovine serum albumin (BSA) to form 5-FU@NiFe-LDH/Ti3C2/BSA nanoplatforms (5NiTiB). Both in vitro and in vivo data demonstrated that the 5-FU induced chemotherapy, NiFe-LDH driven chemodynamic effects, and MXene-based photothermal killing collectively exhibited a synergistic “all-in-one” anti-tumor effect. 5NiTiB improved tumor suppression rate from

Abstract Background Sepsis is a life-threatening, systemic inflammatory disease that can lead to a variety of conditions, including septic acute kidney injury (AKI). Recently, multiple circular Rnas (circRNAs) have been implicated in the development of this disease. Methods In this study, we aimed to elucidate the role of circ-Gatad1 in sepsis induced AKI and its potential mechanism of action. High-throughput sequencing was used to investigate abnormal expression of circRNA in AKI and healthy volunteer. Bioinformatics analysis and luciferase reporting analysis were used to clarify the interacted relationship among circRNA, miRNA and mRNA. HK2 cells were treated with lipopolysaccharide (LPS) to establish septic AKI cell model. HK2 cells were employ to analysis the ROS, inflammatory cytokines expression, proliferation and apoptosis under LPS condition. Results The result show that the expression of circ-Gatad1 was increased in septic acute kidney patients. Downregulation circ-Gatad1 suppressed LPS-treated induced HK2 cells injury including apoptosis, proliferation ability, ROS and inflammatory cytokines level. Bioinformatics and luciferase report analysis confirmed that both miR-22-3p and TRPM7 were downstream targets of circ-Gatad1. Overexpression of TRPM7 or downregulation of miR-22-3p reversed the protective effect of si-circ-Gatad1 to HK2 after exposure to LPS (5 µg/ml) microenvironment. Conclusion In conclusion, knockdown of circ-Gatad1 alleviates LPS induced HK2 cell injury via targeting miR-22-3p/TRPM7 axis in septic acute kidney.

Abstract Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening disease caused by a novel bunyavirus (SFTSV), mainly transmitted by ticks. With no effective therapies or vaccines available, understanding the disease’s mechanisms is crucial. Recent studies found increased expression of programmed cell death-1 (PD-1) on dysfunctional T cells in SFTS patients. However, the role of the PD-1/programmed cell death-ligand 1 (PD-L1) pathway in SFTS progression remains unclear. We investigated PD-1 blockade as a potential therapeutic strategy against SFTSV replication. Our study analyzed clinical samples and performed in vitro experiments, revealing elevated PD-1/PD-L1 expression in various immune cells following SFTSV infection. An anti-PD-1 nanobody, NbP45, effectively inhibited SFTSV infection in peripheral blood mononuclear cells (PBMCs), potentially achieved through the mitigation of apoptosis and the augmentation of T lymphocyte proliferation. Intriguingly, subcutaneous administration of NbP45 showed superior efficacy compared to a licensed anti-PD-1 antibody in an SFTSV-infected humanized mouse model. These findings highlight the involvement of the PD-1/PD-L1 pathway during acute SFTSV infection and suggest its potential as a host target for immunotherapy interventions against SFTSV infection.

Abstract We recently detected a HKU4-related coronavirus in subgenus Merbecovirus (named pangolin-CoV-HKU4-P251T) from a Malayan pangolin1. Here we report isolation and characterization of pangolin-CoV-HKU4-P251T, the genome sequence of which is closest to that of a coronavirus from the greater bamboo bat (Tylonycteris robustula) in Yunnan Province, China, with a 94.3% nucleotide identity. Pangolin-CoV-HKU4-P251T is able to infect human cell lines, and replicates more efficiently in cells that express human-dipeptidyl-peptidase-4 (hDPP4)-expressing and pangolin-DPP4-expressing cells than in bat-DPP4-expressing cells. After intranasal inoculation with pangolin-CoV-HKU4-P251, hDPP4-transgenic female mice are likely infected, showing persistent viral RNA copy numbers in the lungs. Progressive interstitial pneumonia developed in the infected mice, characterized by the accumulation of macrophages, and increase of antiviral cytokines, proinflammatory cytokines, and chemokines in lung tissues. These findings suggest that the pangolin-borne HKU4-related coronavirus has a potential for emerging as a human pathogen by using hDPP4.

Abstract Excess body weight (EBW) increases the risk of colorectal cancer (CRC) and is linked to lower colonoscopy compliance. Here, we extensively analyzed 981 metagenome samples from multiple cohorts to pinpoint the specific microbial signatures and their potential capability distinguishing EBW patients with CRC. The gut microbiome displayed considerable variations between EBW and lean CRC. We identify 44 and 37 distinct multi-kingdom microbial species differentiating CRC and controls in EBW and lean populations, respectively. Unique bacterial-fungal associations are also observed between EBW-CRC and lean-CRC. Our analysis revealed specific microbial functions in EBW-CRC, including D-Arginine and D-ornithine metabolism, and lipopolysaccharide biosynthesis. The best-performing classifier for EBW-CRC, comprising 12 bacterial and three fungal species, achieved an AUROC of 0.90, which was robustly validated across three independent cohorts (AUROC = 0.96, 0.94, and 0.80). Pathogenic microbial species, Anaerobutyricum hallii, Clostridioides difficile and Fusobacterium nucleatum, are EBW-CRC specific signatures. This work unearths the specific multi-kingdom microbial signatures for EBW-CRC and lean CRC, which may contribute to precision diagnosis and treatment of CRC.

Abstract Continuously monitoring global population spatial dynamics is crucial for implementing effective policies related to sustainable development, including epidemiology, urban planning, and global inequality. However, existing global gridded population data products lack consistent population estimates, making them unsuitable for time-series analysis. To address this issue, this study designed a data fusion framework based on cluster analysis and statistical learning approaches, which led to the generation of a continuous global gridded population dataset (GlobPOP). The GlobPOP dataset was evaluated through two-tier spatial and temporal validation to demonstrate its accuracy and applicability. The spatial validation results show that the GlobPOP dataset is highly accurate. The temporal validation results also reveal that the GlobPOP dataset performs consistently well across eight representative countries and cities despite their unique population dynamics. With the availability of GlobPOP datasets in both population count and population density formats, researchers and policymakers can leverage the new dataset to conduct time-series analysis of the population and explore the spatial patterns of population development at global, national, and city levels.

Abstract Background Brucellosis is a zoonotic affliction instigated by bacteria belonging to the genus Brucella and is characterized by a diverse range of pervasiveness, multiple transmission routes, and serious hazards. It is imperative to amalgamate the current knowledge and identify gaps pertaining to the role of ticks in brucellosis transmission. Methods We systematically searched China National Knowledge Infrastructure (CNKI), WanFang, Google Scholar, and PubMed on the topic published until April 23, 2022. The procedure was performed in accordance with the Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. The selected articles were categorized across three major topic areas, and the potential data was extracted to describe evidence-practice gaps by two reviewers. Results The search identified 83 eligible studies for the final analyses. The results highlighted the potential capacity of ticks in brucellosis transmission as evidenced by the detection of Brucella in 16 different tick species. The pooled overall prevalence of Brucella in ticks was 33.87% (range: 0.00–87.80%). The review also revealed the capability of Brucella to circulate in parasitic ticks' different developmental stages, thus posing a potential threat to animal and human health. Empirical evidence from in vitro rodent infection experiments has revealed that ticks possess the capability to transmit Brucella to uninfected animals (range: 45.00–80.00%). Moreover, significant epidemiological associations have been found between the occurrence of brucellosis in animals and tick control in rangelands, which further suggests that ticks may serve as potential vectors for brucellosis transmission in ruminants. Notably, a mere three cases of human brucellosis resulting from potential tick bites were identified in search of global clinical case reports from 1963 to 2019. Conclusions It is imperative to improve the techniques used to identify Brucella in ticks, particularly by developing a novel, efficient, precise approach that can be applied in a field setting. Furthermore, due to the lack of adequate evidence of tick-borne brucellosis, it is essential to integrate various disciplines, including experimental animal science, epidemiology, molecular genetics, and others, to better understand the efficacy of tick-borne brucellosis. By amalgamating multiple disciplines, we can enhance our comprehension and proficiency in tackling tick-borne brucellosis.

The continual emergence of tick-borne rickettsioses has garnered widespread global attention. Candidatus Rickettsia barbariae (Candidatus R. barbariae), which emerged in Italy in 2008, has been detected in humans from northwestern China. However, the lack of Candidatus R. barbariae genome and isolated strains limits the understanding of its biological characteristics and genomic features. Here, we isolated the Rickettsia for the first time from eggs of Rhipicephalus turanicus in northwestern China, and assembled its whole genome after next-generation sequencing, so we modified the proposed name to Rickettsia barbariae (R. barbariae) to conform to the International Code of Nomenclature of Prokaryotes. Phylogenetic analysis based on the whole genome revealed that it was most closely related to the pathogenic Rickettsia parkeri and Rickettsia africae. All virulence factors, present in the pathogenic spotted fever group rickettsiae, were identified in the R. barbariae isolate. These findings highlight the pathogenic potential of R. barbariae and the necessity for enhanced surveillance of the emerging Rickettsia in the human population.