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ObjectiveBloodstream infection (BSI) during the peripartum period is a major cause of maternal morbidity and mortality. However, data on maternal BSI during hospitalization for delivery are limited. This study aimed to investigate the incidence, clinical characteristics, risk factors, microbiological features, and antibiotic resistance patterns of maternal peripartum BSI, with a focus on understanding the role of premature rupture of membranes (PROM), fever, and other risk factors in its development.MethodsWe investigated the clinical characteristics associated with maternal BSI during the peripartum period. This study included febrile women with blood cultures obtained during hospitalization for delivery. We analyzed the clinical characteristics, pathogenic microorganisms, antibiotic resistance, and maternal and neonatal outcomes of these patients. Participants were divided into BSI (n = 85) and non-BSI (n = 361) groups.ResultsSpontaneous rupture of membranes, PROM, PROM >24 h before labor, vaginal examinations >5 times, and cesarean sections during labor were more common in the BSI group. Escherichia coli (51.8%; 44/85) was the predominant causative pathogen, followed by Enterococcus faecalis (7.1%, 6/85). Approximately 31.2% of E. coli were resistant to levofloxacin, and 38.6% were extended-spectrum β-lactamase-producing bacteria. The BSI group had higher rates of maternal sepsis and Apgar scores ≤ 7 at 1 min than the non-BSI group. Furthermore, PROM, fever ≥38.9°C (102°F), and fever within 24 h after delivery were risk factors for postpartum BSI in the adjusted analysis.ConclusionMaternal BSI is a potentially life-threatening disease associated with PROM and the timing and severity of fever. Early identification and surveillance of pathogen composition and antimicrobial resistance can help prevent adverse outcomes.

Periodontitis is a condition characterized by dysbiosis of microbiota and compromised host immunological responses, resulting in the degradation of periodontal tissues. The aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, plays a crucial role in the pathogenesis of periodontitis. AHR serves as a pivotal mediator for the adverse impacts of exogenous pollutants on oral health. Research indicates elevated expression of AHR in individuals with periodontitis compared to those without the condition. However, subsequent to the identification of endogenous AHR ligands, researches have elucidated numerous significant advantageous roles associated with AHR activation in bone, immune, and epithelial cells. This review concentrates on the modulation of the AHR pathway and the intricate functions that AHR plays in periodontitis. It discusses the characteristics of AHR ligands, detailing the established physiological functions in maintaining alveolar bone equilibrium, regulating immunity, facilitating interactions between the oral microbiome and host, and providing protection to epithelial tissues, while also exploring its potential roles in systemic disorders related to periodontitis.

PurposeTo highlight the trends and frontiers of RNA methylation in cancer over the past 10 years.MethodsResearch publications on RNA methylation in cancer were retrieved from the Web of Science Core Collection database. VOSviewer, CiteSpace, and Bibliometrix were used to conduct bibliometric and visualization analysis of countries, institutions, authors, journals, and keywords relevant to this field.ResultsFrom 2014 to 2023, research on RNA methylation in cancer has developed rapidly, with an overall increase in the number of publications and citations. China (4320 papers, 115056citations), Sun Yat Sen University (274 papers, 15698 citations), and Zhang, Wei (48 papers, 893 citations) are respectively the countries, institutions, and authors with the highest number of published papers and citations. Frontiers in Oncology (182 papers, 2524 citations) and Molecular Cancer (69 papers, 9224 citations) are the journals with the highest number of published papers and citations in this field, respectively. Co-occurrence analysis of keywords indicates that the research topics can be divided into five clusters: Cluster one: The Role of RNA Methylation in Tumor Heterogeneity, Therapeutic Response, and Prognosis; Cluster two: The Role of Noncoding RNA in RNA Methylation and Tumors; Cluster three: Potential Therapeutic Targets of RNA Methylation in Tumors; Cluster four: The role of RNA methylation in tumor progression and metastasis: A case study of hepatocellular carcinoma and gastric cancer; Cluster five: Regulation mechanisms of m6A methylation in leukemia cell differentiation and tumorigenesis.ConclusionThis is the first comprehensive study using bibliometrics to analyze the trends and frontiers of RNA methylation in cancer over the past 10 years, pointing out promising research directions for the future and providing valuable references for researchers in this field.

A new species of nematode, Molinostrongylus longmenensis n.sp., parasite of the genus Molinostrongylus, is described based on specimens recovered from the small intestine of Scotophilus kuhlii Leach, 1822 (Chiroptera: Vespertilionidae) in Longmen County, Guangdong Province, China. To date, 135 species of bat-parasitic nematodes have been reported worldwide. Overall, 13 species belonging to seven genera in three families have been described in China. The new species is characterized by the presence of three ventral and three dorsal longitudinal cuticular ridges perpendicular to the body surface, which appear posterior to the cephalic vesicle and extend to the caudal bursa in males and the posterior end in females. The female tail has two medium-sized subventral conical processes of equal length, as well as one large dorsal conical process, and one thin spine, lateral alae that extend to the position of the vulva, with a fin-like ending. In addition, the new species was also characterized using molecular approaches, such as sequencing and analyzing the internal transcribed spacer 1 (ITS-1) of the ribosomal DNA.

Avian reoviruses (ARVs) cause viral arthritis or tenosynovitis, resulting in poor weight gain and increased feed conversion ratios in chickens. In this study, we generated three Marek’s disease virus (MDV) recombinants, namely, rMDV-ARV-σB, rMDV-ARV-σC, and rMDV-ARV-σB + C, expressing ARV σB, σC, and both σB and σC, respectively. In rMDV-ARV-σB and rMDV-ARV-σC, the σB or σC gene was inserted into the US2 gene of MDV vaccine strain 814 using a fosmid-based rescue system. In rMDV-ARV-σB + C, the σB and σC genes were cloned into different expression cassettes, which were co-inserted into the US2 gene of the MDV 814 strain. In infected chicken embryo fibroblasts (CEFs), the recombinant virus rMDV-ARV-σB expressed σB, rMDV-ARV-σC expressed σC, and the rMDV-ARV-σB + C virus simultaneously expressed σB and σC. These recombinant viruses exhibited growth kinetics in CEFs similar to those of the parent MDV, and the inserted genes were stably maintained and expressed in the recombinant MDVs after 20 passages in cell cultures. These recombinant MDVs expressing σB and σC will provide potential vaccines against ARV infection in chickens.

Common bunt caused by Tilletia laevis Kühn is one of the most serious fungal diseases of wheat. The root–microbial associations play key roles in protecting plants against biotic and abiotic factors. Managing these associations offers a platform for improving the sustainability and efficiency of agriculture production. Here, by using high throughput sequencing, we aimed to identify the bacterial and fungal associations in wheat, alfalfa, and oat crops cultivated in different years in the Gansu province of China. Soil samples (0–6 cm below the surface) from infected wheat by T. laevis had significantly more bacterial and fungal richness than control samples as per the Chao1 analysis. We found some dominant fungi and bacterial phyla in infected wheat by T. laevis, such as Proteobacteria, Acidobacteria, Actinobacteria, Chloroflexi, Ascomycota, Basidiomycota, and Mortierello mycota. We also analyzed the chemical and enzymatic properties of soil samples after T. laevis inoculation. The total nitrogen, total kalium (TK), ammonium nitrogen, available kalium, organic carbon, invertase, phosphatase, and catalase were more in T. laevis-infected samples as compared to the control samples, while pH, total phosphorus, nitrate nitrogen, available phosphorus, and urease were more in control samples compared to T. laevis-infected samples. The results of this study will contribute to the control of wheat common bunt by candidate antagonistic microorganisms and adverse properties of soil.

IntroductionGalactose-deficient IgA1 (GdIgA1) is critical in the formation of immunodeposits in IgA nephropathy (IgAN), whereas the origin of GdIgA1 is unknown. We focused on the immune response to fecal microbiota in patients with IgAN. MethodsBy running 16S ribosomal RNA gene sequencing, we compared IgAN samples to the control samples from household-matched or non-related individuals. Levels of plasma GdIgA1 and poly-IgA complexes were measured, and candidate microbes that can either incite IgA-directed antibody response or degrade IgA through specific IgA protease activities were identified.ResultsThe IgAN group showed a distinct composition of fecal microbiota as compared to healthy controls. Particularly, high abundance of Escherichia-Shigella was associated with the disease group based on analyses using receiver operating characteristic (area under curve, 0.837; 95% CI, 0.738–0.914), principle coordinates, and the linear discriminant analysis effect size algorithm (linear discriminant analysis score, 4.56; p < 0.001). Accordingly, the bacterial levels directly correlated with high titers of plasma GdIgA1(r = 0.36, p < 0.001), and patients had higher IgA1 against stx2(2.88 ± 0.46 IU/mL vs. 1.34 ± 0.35 IU/mL, p = 0.03), the main antigen of Escherichia-Shigella. Conversely, the healthy controls showed relatively higher abundance of the commensal bacteria that produce IgA-degrading proteases. Particularly, the abundance of some intestinal bacteria expressing IgA proteases showed an inverse correlation with the levels of plasma GdIgA1 in IgAN.ConclusionOur data suggest that mucosal IgA production, including those of GdIgA1, is potentially linked to the humoral response to gut Escherichia-Shigella as one of the sources of plasma GdIgA1. Conversely, the IgA protease-producing microbiota in the gut are suppressed in patients with IgAN.

BackgroundCongenital contractures of the limbs and face, hypotonia, and developmental delay (CLIFAHDD) syndrome (OMIM #616266) is an autosomal dominant hereditary disease that can lead to the congenital contracture of the limbs and face, hypotonia, and developmental delay. In addition, it may result in growth retardation and present various clinical symptoms, such as brain atrophy, a small pituitary gland, musculoskeletal abnormalities, abnormal breathing, abdominal hernia, and abnormal facial features. Herein, we describe a novel de novo missense genetic variant in the sodium leak channel, non-selective (NALCN) gene that is associated with CLIFAHDD syndrome.Case descriptionThis study describes a patient with varus deformities in both feet, deviation of the ulnar side of the fingers, and severe hypotonia. This patient was subsequently confirmed to have CLIFAHDD syndrome through genetic testing, which also revealed a novel missense de novo genetic variant in the NALCN gene (c.3553G > A, p.Ala1185Thr).ConclusionsOur findings further enrich the known variant spectrum of the NALCN gene and may expand the range of clinical options for treating NALCN-related disorders.

As an important carrier of culture, poetry plays a significant role in deepening language learners' understanding of the target language culture as well as enhancing their language skills; however, the effect of the target language culture on language learners' enjoyment of poetry remains unclear. The study served as an attempt to shed light on the point of whether the target language culture has different effects on high- and low-level Chinese Arabic learners' fondness for Arabic poetry with the use of pictures related to Arabic culture and those not related to Arabic culture. In the current study, 40 Arabic learners (20 high-level and 20 low-level) scored the Arabic poem line based on their fondness for it after viewing two kinds of picture with electroencephalogram (EEG) recording. Frontal alpha asymmetry index as a correlate of approach and avoidance related motivation measured by EEG power in the alpha band (8-13 Hz) was calculated for examining whether the behavioral results of Arabic learners' fondness for poetry are in line with the results of changes in the related EEG components. Behavioral results illustrated that low-level subjects showed significantly less liking for Arabic poetry after viewing pictures related to Arabic culture compared to those not related to Arabic culture. The high-level subjects did not show a significant difference in the level of liking for Arabic poetry between the two cases. FAA results demonstrated that low-level subjects presented a significant avoidance-related responses to Arabic poetry after viewing pictures related to Arabic culture in comparison to viewing pictures not related to Arabic culture; while the FAA values did not differ significantly between the two cases in high-level subjects, which is in line with behavioral results. The findings of this research can benefit teachers in motivating students to learn poetry in foreign language curriculum and also contribute to the literature on the effect of target language culture on language learners' enjoyment of poetry.

IntroductionGut microbiota are closely related to the nutrition, immunity, and metabolism of the host and play important roles in maintaining the normal physiological activities of animals. Cranes are important protected avian species in China, and they are sensitive to changes in the ecological environment and are thus good environmental indicators. There have been no reports examining gut fungi or the correlation between bacteria and fungi in wild Demoiselle cranes (Grus virgo) and Common cranes (Grus grus). Related research can provide a foundation for the protection of rare wild animals.Methods16S rRNA and ITS high-throughput sequencing techniques were used to analyze the gut bacterial and fungal diversity of Common and Demoiselle cranes migrating to the Yellow River wetland in Inner Mongolia.ResultsThe results revealed that for gut bacteria α diversity, Chao1 index in Demoiselle cranes was remarkably higher than that in Common cranes (411.07 ± 79.54 vs. 294.92 ± 22.38), while other index had no remarkably differences. There was no remarkable difference in fungal diversity. There were marked differences in the gut microbial composition between the two crane species. At the phylum level, the highest abundance of bacteria in the Common crane and Demoiselle crane samples was Firmicutes, accounting for 87.84% and 74.29%, respectively. The highest abundance of fungi in the guts of the Common and Demoiselle cranes was Ascomycota, accounting for 69.42% and 57.63%, respectively. At the genus level, the most abundant bacterial genus in the Common crane sample was Turicibacter (38.60%), and the most abundant bacterial genus in the Demoiselle crane sample was Catelicoccus (39.18%). The most abundant fungi in the Common crane sample was Penicillium (6.97%), and the most abundant fungi in the Demoiselle crane sample was Saccharomyces (8.59%). Correlation analysis indicated that there was a significant correlation between gut bacteria and fungi.DiscussionThis study provided a research basis for the protection of cranes. Indeed, a better understanding of the gut microbiota is very important for the conservation and management of wild birds, as it not only helps us to understand their life history and related mechanisms, but also can hinder the spread of pathogenic microorganisms.

Objective: This study aimed to investigate the molecular mechanism of triptolide in the treatment of oral squamous cell carcinoma (OSCC) via network pharmacology and experimental validation.Methods: The network pharmacological method was used to predict the key targets, detect the signal pathways for the treatment of OSCC, and screen the critical components and targets for molecular docking. Predicted targets were validated in cellular and xenograft mouse model.Results: In this study, we predicted action on 17 relevant targets of OSCC by network pharmacology. PPI network demonstrated that Jun, MAPK8, TP53, STAT3, VEGFA, IL2, CXCR4, PTGS2, IL4 might be the critical targets of triptolide in the treatment of OSCC. These potential targets are mainly closely related to JAK-STAT and MAPK signaling pathways. The analysis of molecular docking showed that triptolide has high affinity with Jun, MAPK8 and TP53. Triptolide can suppress the growth of OSCC cells and xenograft mice tumor, and downregulate the expression of Jun, MAPK8, TP53, STAT3, VEGFA, IL2, CXCR4, PTGS2 to achieve the therapeutic effect of OSCC.Conclusion: Through network pharmacological methods and experimental studies, we predicted and validated the potential targets and related pathways of triptolide for OSCC treatment. The results suggest that triptolide can inhibit the growth of OSCC via several key targets.

ObjectiveTo investigate the relationship between serum uric acid (SUA) levels and ischemic stroke in young patients in the Ganzi Tibetan plateau area.MethodsA cross-sectional survey was undertaken from January 2020 to June 2023 involving young patients (age: 15–45 years) diagnosed with ischemic stroke. The survey was conducted at the Department of Internal Medicine of the People’s Hospital of Derong County, Ganzi Prefecture. The participants underwent a comprehensive assessment, including questionnaire surveys, physical examinations, laboratory tests, and head computed tomography (CT) examinations. Based on the tertiles of serum uric acid (SUA) levels, the patients were stratified into three groups. Furthermore, stroke severity was classified into mild (1–4 points), moderate (5–15 points), and severe (>15 points) categories using the National Institute of Health Stroke Scale.ResultsThe severe stroke group exhibited higher levels of age, glucose, systolic blood pressure, serum triglyceride, low-density lipoprotein cholesterol, and serum uric acid (SUA) compared to the mild stroke group (P < 0.05). Furthermore, the likelihood of male sex, advanced age, smoking, and a family history of stroke, diabetes mellitus, and heart disease were significantly elevated in the severe stroke group compared to the moderate stroke group (P < 0.05). Multivariate logistic regression analysis conducted on young adults residing in highland areas revealed a significant association between SUA levels and the risk of stroke.ConclusionElevated SUA levels serve as a distinct risk factor for the development of a major stroke in young patients in highland areas. At SUA levels of 320.56 mol/L, the risk of a moderate-to-severe stroke is noticeably elevated.

Background: Epidemiological research has established associations between various inflammatory cytokines and the occurrence of oral cancer and oropharyngeal cancer (OCPC). We performed a Mendelian randomization (MR) analysis to systematically investigate the causal relationship between inflammatory cytokines and OCPC.Methods: We performed a bidirectional two-sample MR analysis using OCPC from 12 studies (6,034 cases and 6,585 controls) and genome-wide association study (GWAS) results for 41 serum cytokines from 8,293 Finns, respectively. Inverse variance weighting was used as the primary MR method and four additional MR methods (MR Egger, Weighted median, Simple mode, Weighted mode) were used to examine genetic associations between inflammatory traits and OCPC, and Cochran’s Q test, MR-Egger intercept, leave-one-out analysis, funnel plot, and multivariate MR (MVMR) analysis were used to assess the MR results.Results: The results suggested a potential association between high gene expression of Macrophage inflammatory protein-1α (MIP1α/CCL3) and an increased risk of OCPC (Odds Ratio (OR): 1.71, 95% Confidence Interval (CI): 1.09–2.68, p = 0.019). Increasing the expression levels of the interleukin-7 (IL-7) gene by 1 standard deviation reduced the risk of OCPC (OR: 0.64, 95%CI: 0.48–0.86, p = 0.003). In addition, multivariate Mendelian randomization analysis also showed the same results (MIP1α/CCL3, OR: 1.002, 95% CI: 0.919–1.092, p = 0.044; IL-7, OR: 0.997, 95% CI: 0.994–0.999, p = 0.011). Conversely, there was a positive correlation between genetic susceptibility to OCPC and an increase in Interleukin-4 (IL-4) (OR: 1.04, 95%CI: 1.00–1.08, p = 0.027).Conclusion: Our study systematically assessed the association between inflammatory cytokines and the risk of OCPC. We identified two upstream regulatory factors (IL-7 and CCL3) and one downstream effector factor (IL-4) that were associated with OCPC, offering potential avenues for the development of novel treatments.

BackgroundCoronavirus disease (COVID-19) has posed a significant threat to the lives and health of people worldwide since its onset in 2019. However, the relationship between the number of vaccination shots and the severity of SARS-CoV-2 infection in Chinese patients remains unclear.MethodsWe retrospectively collected information from 829 patients infected with SARS-CoV-2 in Ningbo Medical Center Lihuili Hospital from December 05, 2022 to March 31, 2023, then divided them into four groups based on the severity of pneumonia. Last, we compared the difference in the number of shots of COVID-19 vaccine between the four groups, considering potential confounding factors using univariate and multivariate logistic regression.ResultsVaccination with two and three doses was positively associated with low prevalence of pneumonia and severe pneumonia both in crude and optimal models, while only three doses of the vaccine was correlated with low prevalence of death in SARS-CoV-2-infected patients. In optimal models, male SARS-CoV-2-infected individuals with advanced age were positively associated with high prevalence of pneumonia, severe pneumonia, and death; comorbidity with hypertension (OR = 2.532, p

BackgroundMethotrexate (MTX), utilized as a graft-versus-host disease (GvHD) prophylactic agent in allogeneic hematopoietic stem cell transplantation (allo-HSCT), has been proven to effectively decrease the occurrence of the peri-engraftment syndrome (Peri-ES) and acute GvHD (aGvHD). Changes in the pharmacodynamics of MTX are closely associated with gene polymorphisms in genes encoding drug-metabolizing enzymes and transporters. Nevertheless, the current studies mainly concentrate on leukemia or autoimmune diseases, and limited studies on allo-HSCT were reported.MethodsHere, we retrospectively assessed the relationship between MTX-related transporter and metabolizing enzyme gene polymorphisms, clinical characteristics, and outcomes in 57 pediatric patients who received haploid HSCT (haplo-HSCT) with malignant tumors at a single center.ResultsWe discovered all gene polymorphisms were in the Hardy–Weinberg equilibrium in our cohort. We discovered a significant correlation between platelet recovery time and ABCB1 (1236C>T) (p = 0.042). Compared with patients with SLCO1B1 (1865+4846T>C) TT, patients with SLCO1B1 (1865+4846T>C) TC/CC had an increased incidence of Peri-ES (p = 0.030). Based on the multivariate Cox analysis, we discovered that SLCO1B1 (1865+4846T>C) TT genotype was an independent protective factor for Peri-ES morbidity (hazard ratio (HR) = 0.464, p = 0.031), and the dose of mononuclear cells reinfused was significantly correlated with II–IV aGvHD (HR = 2.604, p = 0.039).ConclusionIn summary, our findings prove that the host’s genotypes might modify the risk of developing Peri-ES, contribute to a better understanding of the inter-individual difference in efficacy, and facilitate the development of individualized approaches to GvHD prophylaxis.

BackgroundTransbronchial lung biopsy guided by radial probe endobronchial ultrasonography with a guide sheath (EBUS-GS-TBLB) is becoming a significant approach for diagnosing peripheral pulmonary lesions (PPLs). We aimed to explore the clinical value of the resistance of the probe to pass through the lesion in the diagnosis of PPLs when performing EBUS-GS-TBLB, and to determine the optimum number of EBUS-GS-TBLB.MethodsWe performed a prospective, single-center study of 126 consecutive patients who underwent EBUS-GS-TBLB for solid and positive-bronchus-sign PPLs where the probe was located within the lesion from September 2019 to May 2022. The classification of probe resistance for each lesion was carried out by two bronchoscopists independently, and the final result depended on the bronchoscopist responsible for the procedures. The primary endpoint was the diagnostic yield according with the resistance pattern. The secondary endpoints were the optimum number of EBUS-GS-TBLB and factors affecting diagnostic yield. Procedural complications were also recorded.ResultsThe total diagnostic yield of EBUS-GS-TBLB was 77.8%, including 83.8% malignant and 67.4% benign diseases (P=0.033). Probe resistance type II displayed the highest diagnostic yield (87.5%), followed by type III (81.0%) and type I (61.1%). A significant difference between the diagnostic yield of malignant and benign diseases was detected in type II (P = 0.008), whereas others did not. Although most of the malignant PPLs with a definitive diagnosis using EBUS-GS-TBLB in type II or type III could be diagnosed in the first biopsy, the fourth biopsy contributed the most sufficient biopsy samples. In contrast, considerably limited tissue specimens could be obtained for each biopsy in type I. The inter-observer agreement of the two blinded bronchoscopists for the classification of probe resistance was excellent (κ = 0.84).ConclusionThe probe resistance is a useful predictive factor for successful EBUS-GS-TBLB diagnosis of solid and positive-bronchus-sign PPLs where the probe was located within the lesion. Four serial biopsies are appropriate for both probe resistance type II and type III, and additional diagnostic procedures are needed for type I.

The non-invasive and rapid assessment of the developmental potential of embryos is of great clinical importance in assisted reproductive technology (ART). In this retrospective study, we analyzed the metabolomics of 107 samples provided by volunteers and utilized Raman spectroscopy to detect the substance composition in the discarded culture medium of 53 embryos resulting in successful pregnancies and 54 embryos that did not result in pregnancy after implantation. The culture medium from D3 cleavage-stage embryos was collected after transplantation and a total of 535 (107 × 5) original Raman spectra were obtained. By combining several machine learning methods, we predicted the developmental potential of embryos, and the principal component analysis–convolutional neural network (PCA-CNN) model achieved an accuracy rate of 71.5%. Furthermore, the chemometric algorithm was used to analyze seven amino acid metabolites in the culture medium, and the data showed significant differences in tyrosine, tryptophan, and serine between the pregnancy and non-pregnancy groups. The results suggest that Raman spectroscopy, as a non-invasive and rapid molecular fingerprint detection technology, shows potential for clinical application in assisted reproduction.

IntroductionForest spatial structures are the foundations of the structure and function of forest ecosystems. Quantitative descriptions and analyses of forest spatial structure have recently become common tools for digitalized forest management. Therefore, the accuracy and intelligence of acquiring forest spatial structure information are of great significance.MethodsIn this study, we developed a forest measurement system using a mobile phone. Through this system, the following tree measurements can be achieved: (1) point cloud of tree and chest diameter circle to measure tree diameter at breast height (DBH) and position coordinates of tree by using simultaneous localization and mapping (SLAM) technology, (2) virtual boundary creation of the sample plot, and the auxiliary measurement function of tree with the augmented reality (AR) interactive module, and (3) position coordinates and single-tree volume factor to calculate the spatial structural parameters of the forest (e.g., Mingling degree, Dominance index, Uniform angle index, and Crowdedness index).The system was tested in three 32 x 32 martificial forest plots.ResultsThe average DBH estimations showed BIAS of -0.47 to 0.45 cm and RMSEs of 0.57 to 0.95 cm. Its accuracy level met the requirements of forestry sample surveys. The tree position estimates for the three plots had relatively small RMSEs with 0.17 to 0.22 m on the x-axis and 0.16 to 0.26 m on the y-axis. The spatial structural parameters were as follows: the mingling degree of plot 1 was 0.32, and the overall mixing degree of tree species was low. The trees in plots 2 and 3 were all single species, and the mixing degree of both plots was 0. The dominance index of the three plots was 0.56, 0.51, and 0.51, indicating that the competitive advantage of the whole orest species was not obvious. The uniform angle index of the three plots was 0.55, 0.59, and 0.61, indicating that the positions of trees in the three plots were randomly distributed. The crowdedness index of plot 1 was 1.03, indicating that the degree of aggregation of the trees was low and showed a random distribution trend. The crowdedness index of the other plots were 1.36 and 1.40, indicating that the trees in the plots show a trend of uniform distribution, and the uniformity of plot 3 is higher than that of plot 2, but the overall uniformity is relatively weak.DiscussionThe findings of this study provide support for the optimization of forest structures and improve our conceptual understanding of forest community succession and restoration, in addition to the informatization and precision of forest spatial structure surveys.

BackgroundThe development of transoral endoscopic vestibular approach thyroidectomy (TOETVA) has been limited by inherent defects, such as mental nerve injury and carbon dioxide (CO2)-related complications. Herein, we proposed a new technique without CO2 called gasless submental-transoral combined approach endoscopic thyroidectomy (STET) to solve the problems in TOETVA.MethodsWe reviewed 75 patients who successfully underwent gasless STET using novel instruments at our institution from November 2020 to November 2021. A main incision of approximately 2 cm was made in the natural submental crease line and then combined with two vestibule incisions to complete the procedure. Demographic data, surgical technique and perioperative outcomes were retrospectively recorded.ResultsThirteen male and sixty-two female patients with a mean age of 34.0 ± 8.1 years were enrolled in this study. Sixty-eight patients had papillary thyroid carcinomas and seven had benign nodules. We successfully performed all gasless STET without conversion to open surgery. The average postoperative hospital stay was 4.2 ± 1.8 days. One transient recurrent laryngeal nerve injury and two transient hypoparathyroidisms were observed. Three patients complained of slight lower lip numbness on the first postoperative day. One case of lymphatic fistula, subcutaneous effusion, and incision swelling occurred each, all of which were conservatively cured. One patient developed a recurrence six months after surgery.ConclusionsGasless STET using our own designed suspension system is technically safe and feasible with reasonable operative and oncologic results.

Wheat (Triticum aestivum L.) diseases are major factors responsible for substantial yield losses worldwide, which affect global food security. For a long time, plant breeders have been struggling to improve wheat resistance against major diseases by selection and conventional breeding techniques. Therefore, this review was conducted to shed light on various gaps in the available literature and to reveal the most promising criteria for disease resistance in wheat. However, novel techniques for molecular breeding in the past few decades have been very fruitful for developing broad-spectrum disease resistance and other important traits in wheat. Many types of molecular markers such as SCAR, RAPD, SSR, SSLP, RFLP, SNP, and DArT, etc., have been reported for resistance against wheat pathogens. This article summarizes various insightful molecular markers involved in wheat improvement for resistance to major diseases through diverse breeding programs. Moreover, this review highlights the applications of marker assisted selection (MAS), quantitative trait loci (QTL), genome wide association studies (GWAS) and the CRISPR/Cas-9 system for developing disease resistance against most important wheat diseases. We also reviewed all reported mapped QTLs for bunts, rusts, smuts, and nematode diseases of wheat. Furthermore, we have also proposed how the CRISPR/Cas-9 system and GWAS can assist breeders in the future for the genetic improvement of wheat. If these molecular approaches are used successfully in the future, they can be a significant step toward expanding food production in wheat crops.

Ischemic stroke is the most common cerebrovascular disease, and vascular obstruction is an important cause of this disease. As the main method for the management of carotid artery stenosis, carotid endarterectomy (CEA) is an effective and preventive treatment measure in ischemic cerebrovascular disease. This study aims to propose the application of a new enhanced recovery after surgery (ERAS) nutritional support regimen in CEA, which can significantly improve the perioperative nutritional status of patients. A total of 74 patients who underwent CEA were included and randomly divided into two groups: 39 patients received nutritional therapy with the ERAS protocol (ERAS group) and 35 patients received routine perioperative nutritional support (control group). Our results showed that the levels of major clinical and biochemical parameters (albumin, hemoglobin, creatinine, calcium and magnesium levels, etc.) in the ERAS group were significantly higher than those in the control group after surgery (p

Premature ovarian insufficiency (POI) is characterized by early loss of ovarian function before the age of 40 years. It is confirmed to have a strong and indispensable genetic component. Caseinolytic mitochondrial matrix peptidase proteolytic subunit (CLPP) is a key inducer of mitochondrial protein quality control for the clearance of misfolded or damaged proteins, which is necessary to maintain mitochondrial function. Previous findings have shown that the variation in CLPP is closely related to the occurrence of POI, which is consistent with our findings. This study identified a novel CLPP missense variant (c.628G > A) in a woman with POI who presented with secondary amenorrhea, ovarian dysfunction, and primary infertility. The variant was located in exon 5 and resulted in a change from alanine to threonine (p.Ala210Thr). Importantly, Clpp was mainly localized in the cytoplasm of mouse ovarian granulosa cells and oocytes, and was relatively highly expressed in granulosa cells. Moreover, the overexpression of c.628G > A variant in human ovarian granulosa cells decreased the proliferative capacity. Functional experiments revealed that the inhibition of CLPP decreased the content and activity of oxidative respiratory chain complex IV by affecting the degradation of aggregated or misfolded COX5A, leading to the accumulation of reactive oxygen species and reduction of mitochondrial membrane potential, ultimately activating the intrinsic apoptotic pathways. The present study demonstrated that CLPP affected the apoptosis of granulosa cells, which might be one of the mechanisms by which CLPP aberrations led to the development of POI.

ObjectivesThis study aimed to investigate the potential mechanism of hyperoestrogensim elicited by ovulation induction affects endometrial receptivity and leads to embryo implantation abnormality or failure.Study designEstablishment of ovulation induction mouse model. Changes in mouse body weight, ovarian weight, serum E2 level and oestrous cycle were observed. During the peri-implantation period, morphological changes in the mouse uterus and implantation sites and the localization and protein levels of oestrogen receptors ERα and ERβ, the tight junction factors CLDN3 and OCLN, the aquaporins AQP3, AQP4 and AQP8, and the sodium channel proteins SCNN1α, SCNN1β and SCNN1γ were observed. The expression and cellular localization of ERα, CLDN3, AQP8 and SCNN1 β in RL95-2 cell line were also detected by western blotting and immunofluorescence.ResultsOvarian and body weights were significantly higher in the 5 IU and 10 IU groups than in the CON group. The E2 level was significantly higher in the 10 IU group than in the CON group. The mice in the 10 IU group had a disordered oestrous cycle and were in oestrus for a long time. At 5.5 dpc, significantly fewer implantation sites were observed in the 10 IU group than in the CON (p

The purpose of this study was to obtain polysaccharides from Panax ginseng C. A. Meyer stems (PGSPs), agro-byproducts with development potential, and fully explore the potential value in P. ginseng stems. Two novel polysaccharides firstly from P. ginseng stems (PGSP-1 and PGSP-2) were obtained by water extraction and alcohol precipitation method and column chromatography, and then characterized by FT-IR, HPGPC, HPLC, SEM, TGA, GC–MS and NMR. The results demonstrated that PGSP-1 (Mw = 723.83 kDa) and PGSP-2 (Mw = 620.48 kDa) were characterized →4)- β -D-Gal p -(1→, →6)- α -D-Glc p -(1 → and →2)- α -L-Rha p -(1 → as the skeleton, →4,6)- β -D-Gal p -(1 → and →2,6)- α -D-Man p -(1 → as the cross junction, α -L-Araf-(1 → as the terminal unit, and PGSP-1 still contained →4)- β -D-Gal p , while PGSP-2 contained →4)- β -D-Xyl p -(1→, →3)- β -D-Glc p A-(1→, →4)- β -D-Gal p A-(1 →) and α -D-Glc p -(1→, with different microstructures and thermal stability. And the results of hypoglycemic activity revealed that both PGSP-1 and PGSP-2 showed excellent inhibitory activity against α -glucosidase and α -amylase, in which PGSP-2 had the better performance. The inhibition kinetics result showed that PGSPs on α -glucosidase and α -amylase were non-competitive type and mixed type inhibition. This study provided a theoretical basis for making full use of and exploiting the economic value of agro-byproducts such as P. ginseng stems and offered a theoretical reference for the effective utilization of PGSP as a functional component to prevent and reduce T2DM. [ABSTRACT FROM AUTHOR]

Ensemble forecast plays a vital role in numerical weather prediction. Hence, effectively extracting useful information from ensemble members to improve precipitation forecasting skills has always been an important issue. Using the ensemble forecast data on precipitation from the ECMWF-GEPS (Global Ensemble Prediction System), we propose a stepwise correction method, based on segmented hierarchical clustering (SHC), for forecast of daily precipitation. This method employs a segmented correction scheme, thereby generating more probabilistic forecast information and improving forecasts. Validations of the SHC method have been performed by comparison with two other methods, namely the ensemble-mean (EM) method and the direct hierarchical clustering (HC) method. Our results showed that deterministic forecast via SHC improved the ability to forecast heavy precipitation in short- and medium-range forecast timeframes. Therefore, SHC performed better than either EM or HC by effectively extending lead time to impending severe rainfall by 2–3 days relative to the other two methods. SHC also demonstrated better performance than the other methods through continuous forecast verification in summer 2021, and even had better effects in the forecast of multiple heavy-precipitation cases, including the Zhengzhou extreme rainfall on 20 July 2021. Overall, the SHC method has great potential for improving ensemble rainfall forecasts in the current operational system.

Myostatin (MSTN) regulates muscle development and body metabolism through a variety of pathways and is a core target gene for gene editing in livestock. Gut fungi constitute a small part of the gut microbiome and are important to host health and metabolism. The influence of MSTN mutations on bovine gut fungi remains unknown. In this study, Internal Transcribed Spacer (ITS) high-throughput sequencing was conducted to explore the composition of gut fungi in the MSTN mutant (MT) and wild-type (WT) cattle, and 5,861 operational taxonomic units (OTUs) were detected and classified into 16 phyla and 802 genera. The results of the alpha diversity analysis indicated that no notable divergence was displayed between the WT and MT cattle; however, significant differences were noticed in the composition of fungal communities. Eight phyla and 18 genera were detected. According to the prediction of fungal function, saprotroph fungi were significantly more abundant in the MT group. The correlation analysis between gut fungal and bacterial communities revealed that MSTN mutations directly changed the gut fungal composition and, at the same time, influenced some fungi and bacteria by indirectly regulating the interaction between microorganisms, which affected the host metabolism further. This study analyzed the role of MSTN mutations in regulating the host metabolism of intestinal fungi and provided a theoretical basis for the relationship between MSTN and gut fungi.

ObjectivesThis study aimed to identify the key proteins in the bone mass of ovariectomized (OVX) rats after a period of regular moderate-intensity treadmill exercise and to investigate their effects using tag mass spectrometry and quantitative proteomics with a view to improving the understanding and treatment of postmenopausal osteoporosis.MethodsSixty three-month-old female Sprague-Dawley tats of specific-pathogen-free grade were randomly and equally divided into a sham operation group, ovariectomized group (OVX) and ovariectomized combined exercise (OVX + EX) group, and the latter took moderate-intensity treadmill exercise for 17 weeks. After this period of time, body composition and bone density were measured using dual-energy x-ray absorptiometry, and serum bone metabolism indicators were measured using an enzyme immunoassay. In addition, the bone microstructure was examined using micro-computed tomography and scanning of the femur, and femur proteins were subject to proteomic analysis.ResultsCompared with the rats in the OVX group, the bone metabolism indicators in the OVX + EX group decreased significantly, femur bone density increased significantly, the number of the trabeculae increased, and continuity was higher. In the OVX + EX group, 17 proteins were significantly upregulated and 33 significantly downregulated. The main gene ontology and signaling pathways enriched by the proteins were identified as the tumor necrosis factor-mediated signaling pathways. The protein-protein interaction network identified the key proteins, and the correlation analysis of these proteins and the bone parameters found histone deacetylase 8(HDAC8) and leucine-rich transmembrane and O-methyltransferase domain containing (LRTOMT) and trimethylguanosine synthase 1(TGS1) and ankyrin repeat domain 46(ANKRD46) to be the key targets of exercise in relation to postmenopausal osteoporosis.ConclusionModerate-intensity treadmill exercise significantly improved the bone mass of OVX rats, and differentially expressed proteins, such as HDAC8 and LRTOMT and TGS1 and ANKRD46, could be the target of moderate-intensity treadmill exercise.

Background: Calcium signaling is implicated in multiple processes including immune response that important in tumor progression. Kidney renal clear cell carcinoma (KIRC) is the most frequent histological type of renal cell carcinoma with up to a third of cases develop metastases. As a result of a lack of in-depth understanding of the mechanisms underlying KIRC, treatment options have been limited. Here, we aim to comprehensively investigate the landscape of Ca2+ channels, pumps and exchangers in KIRC patients.Methods: The mRNA expression profiles and gene variations of 58 calcium-related genes (CRGs) in KIRC patients and normal control cases were downloaded from TCGA database. CRGs-related risk score was constructed to quantify calcium patterns by using least absolute shrinkage and selection operator (LASSO) regression. The prognostic value, biological functions, immune landscape and therapeutic sensitivities based on CRGs-related risk score were then evaluated using multiple methods. Finally, key gene of CRGs was identified by weighted gene co-expression network analysis (WGCNA). TCGA-CPTAC, GSE53757 datasets, as well as human tissues were used for validation.Results: KIRC patients had significant differences in CRG expression, prognosis, and biological functions between two CRG clusters. CRGs-related risk score was then determined. The prognosis, tumor mutation burden, immune cell infiltration, immune checkpoints, and the response of targeted inhibitors were remarkably different between high and low CRGs-related risk subtypes. CRGs-related high-risk subtype was characterized by immunosuppressive microenvironment with poor prognosis. Meanwhile, several targeted drugs showed distinct sensitivity between CRGs-related risk subtypes. Finally, TRPM3 was identified as a key CRG based on risk score in KIRC patients. TRPM3 mRNA and protein expression were significantly lower in KIRC tumors than in normal controls. Low TRPM3 expression was associated with poor prognosis in KIRC patients.Conclusion: Our study highlighted the promising prognostic value of CRGs in KIRC tumors. The evaluation of CRGs-related risk score will contribute to predicting prognosis and clinical therapy in KIRC patients.

Fueled by the development of neuroscience and artificial intelligence (AI), recent advances in the brain-inspired AI have manifested a tipping-point in the collaboration of the two fields. AI began with the inspiration of neuroscience, but has evolved to achieve a remarkable performance with little dependence upon neuroscience. However, in a recent collaboration, research into neurobiological explainability of AI models found that these highly accurate models may resemble the neurobiological representation of the same computational processes in the brain, although these models have been developed in the absence of such neuroscientific references. In this perspective, we review the cooperation and separation between neuroscience and AI, and emphasize on the current advance, that is, a new cooperation, the neurobiological explainability of AI. Under the intertwined development of the two fields, we propose a practical framework to evaluate the brain-likeness of AI models, paving the way for their further improvements.

This is the first study reporting droplet digital PCR and quantitative real time PCR for detection of Tilletia caries (syn. T. tritici), which causes common bunt of wheat and leads to yield losses of 80% in many wheat growing areas worldwide. To establish an accurate, rapid and quantifiable detection method, we tested 100 inter simple sequence repeats (ISSR) primers and obtained a species-specific fragment (515 bp) generated by ISSR 827. Then, a specific 266 bp band for the sequence characterized amplified region (SCAR) marker was produced from T. caries. The detection limit reached 50 pg/μL. Based on the SCAR marker, we further developed a higher sensitivity of quantitative real time-polymerase chain reaction (qRT-PCR) with a detection limit of 2.4 fg/μL, and droplet digital PCR (ddPCR) with a detection limit of 0.24 fg/μL. Both methods greatly improved the detection sensitivity of T. caries, which will be contribute a lot for quickly and accurately detection of T. caries, which causes wheat common bunt.

BackgroundFor patients with breast cancer, family functioning is an important factor affecting self-transcendence, which is a key source of happiness. However, network analysis studies of family functioning and self-transcendence are lacking, particularly among patients with breast cancer.PurposeThe present study investigated the network structure of family functioning and self-transcendence in patients with breast cancer and aimed to identify bridge items to provide some theoretical support for the improvement and intervention of self-transcendence in patients with breast cancer.MethodsA total of 294 patients with breast cancer were enrolled in our study. Self-transcendence was evaluated with the Self-Transcendence Scale. Family functioning was evaluated with the Family Adaptation, Participation, Growth, Affection, Resolution (APGAR) Scale. Network analyses were used for the statistical analysis.ResultsIn the network of family functioning and self-transcendence in patients with breast cancer, there were 22 edges across communities, of which the 5 strongest edges connected to the 5 dimensions of family functioning are “Adaptation” with “Enjoyment of hobbies”, “Participation” with “Life enjoyment”, “Growth” with “Acceptance of bodily changes”, “Affection” with “Life enjoyment”, “Resolution” with “Help acceptance”. “Adaptation” had the highest bridge expected influence value (0.30) in the family functioning community, while “Life enjoyment” had the highest bridge expected influence value (0.27) in the self-transcendence community.ConclusionComplex patterns of associations existed in the fine-grained relationship between family functioning and self-transcendence in patients with breast cancer. From the perspective of network analysis, the “Adaptation” aspect of family functioning and the “Life enjoyment” aspect of self-transcendence may be the best targets for improving self-transcendence. These results have important implications to clinical practice, which provided potential targets for interventions to improve self-transcendence from the perspective of family functioning.

BackgroundDepression is a serious psychological disorder that causes substantial psychological and physical suffering in adolescents, contributes to over 50% of suicide attempts, and affects the health status and psychosocial functioning of 25% of the adult population. The prevalence of polycystic ovary syndrome (PCOS) in adolescents is 5.6∼11.04%, and the prevalence of depression in adolescents with PCOS is as high as 50–60%. Depression seriously affects the rehabilitation and quality of life of adolescents with PCOS. In this study, we present a protocol for a mixed-method study to develop and evaluate the effectiveness of a psychological adjustment communication system for reducing the prevalence of depression among adolescents with PCOS who are at a high risk of depression in China. This study utilizes social support theory to develop a mobile phone-based intervention for adolescents with PCOS at a high risk of depression.MethodsThis sequential exploratory mixed-method study consists of four consecutive phases. In the first phase, we will review the literature to understand the disease experience and needs of adolescents with PCOS to construct an initial psychological adjustment communication system. In the second phase, researchers will interview patients and their parents using purposeful sampling methods and semi-structured interviews to appropriately modify the psychological adjustment communication system. In the third phase, the Delphi method will be used to improve the psychological adjustment communication system. The fourth phase will employ a quantitative approach using a before-and-after design to measure the effectiveness of the system.DiscussionThe results of this study will indicate the effectiveness of the psychological adjustment communication system in adolescents with PCOS who are at a high risk of depression.Registration numberChiCTR2100050123.

BackgroundThe epigenetic study of childhood trauma has become a valuable field. However, the evolution and emerging trends in epigenetics and childhood trauma have not been studied by bibliometric methods.ObjectiveThis study aims to evaluate status of epigenetic studies in childhood trauma and reveal the research trends based on bibliometrics.MethodsA total of 1,151 publications related to childhood trauma and epigenetics published between 2000 and 2021 were retrieved from the Web of Science Core Collection (WoSCC). CiteSpace (5.8. R 3) was used to implement bibliometric analysis and visualization.ResultsSince 2010, the number of related publications has expanded quickly. The United States and McGill University are the most influential countries and research institutes, respectively. Elisabeth Binder is a leading researcher in childhood trauma and epigenetic-related research. Biological Psychiatry is probably the most popular journal. In addition, comprehensive keyword analysis revealed that “glucocorticoid receptor,” “brain development,” “epigenetic regulation,” “depression,” “posttraumatic stress disorder,” “maternal care,” “histone acetylation,” “telomere length,” “microRNA,” and “anxiety” reflect the latest research trends in the field. A comprehensive reference analysis demonstrated NR3C1 gene methylation, FKBP5 DNA methylation, BDNF DNA methylation, and KITLG methylation have been hot spots in epigenetic studies in the field of childhood trauma in recent years. Notably, the relationship between childhood adversity and NR3C1 gene methylation levels remains unresolved and requires well-designed studies with control for more confounding factors.ConclusionAs the best of our knowledge, this is the first bibliometric analysis of the association between childhood trauma and epigenetics. Our analysis of the literature suggests that childhood trauma may induce depression, anxiety, and post-traumatic stress disorder through epigenetic regulation of glucocorticoid receptor expression and brain development. The hypothalamic-pituitary-adrenal axis is the key points of epigenetic research. The current researches focus on NR3C1 gene methylation, FKBP5 DNA methylation, BDNF DNA methylation, and KITLG methylation. These results provide a guiding perspective for the study of epigenetic effects of childhood trauma, and help researchers choose future research directions based on current keywords.

Hand, foot, and mouth disease (HFMD) is a common childhood infectious disease caused by human enteroviruses (EV). This study aimed to describe the epidemiological features of HFMD and the genetic characteristics of Coxsackievirus A16 (CVA16) in Taiyuan, Shanxi, China, from 2010 to 2021. Descriptive epidemiological methods were used to analyze the time and population distribution of HFMD and the genetic characteristics of CVA16. Except being affected by the COVID-19 epidemic in 2020, HFMD epidemics were sporadic from January to March each year, and began to increase in April, with a major epidemic peak from May to August, which declined in September, followed by a secondary peak from October to December. The prevalence of EV infection was the highest in children aged one to five years (84.42%), whereas its incidence was very low in children under one year of age (5.48%). Enterovirus nucleic acid was detected by real-time reverse transcription polymerase chain reaction in 6641 clinical specimens collected from patients with HFMD from 2010 to 2021, and 4236 EV-positive specimens were detected, including 988 enterovirus A71 (EV-A71), 1488 CVA16, and 1760 other enteroviruses. CVA16 remains prevalent and has co-circulated with other EVs in Taiyuan from 2010 to 2021. A phylogenetic tree constructed based on the VP1 region showed that all CVA16 strains belonged to two different clades of the B1 genotype, B1a and B1b. They showed a nucleotide similarity of 86.5–100%, and an amino acid similarity of 96.9–100%. Overall, these findings add to the global genetic resources of CVA16, demonstrate the epidemiological characteristics of HFMD as well as the genetic features of CVA16 in Taiyuan City during 2010–2021, and provide supporting evidence for the prevention and control of HFMD.

Osteoarthritis (OA) causes intestinal damage. The protective effect of probiotics on the intestine is indeed effective; however, the mechanism of protection against intestinal damage in OA is not clear. In this study, we used meniscal/ligamentous injury (MLI) to mimic OA in rats and explored the colonic protective effects of Bacillus subtilis and Enterococcus faecium on OA. Our study showed that treatment with B. subtilis and E. faecium attenuated colonic injury and reduced inflammatory and oxidative stress factors in the serum of osteoarthritic rats. α- and ß diversity of the fecal flora were not different among groups; no significant differences were observed in the abundances of taxa at the phylum and genus levels. We observed the presence of the depression-related genera Alistipes and Paraprevotella. Analysis of fecal untargeted metabolism revealed that histamine level was significantly reduced in the colon of OA rats, affecting intestinal function. Compared to that in the control group, the enriched metabolic pathways in the OA group were primarily for energy metabolisms, such as pantothenate and CoA biosynthesis, and beta-alanine metabolism. The treatment group had enriched linoleic acid metabolism, fatty acid biosynthesis, and primary bile acid biosynthesis, which were different from those in the control group. The differences in the metabolic pathways between the treatment and OA groups were more evident, primarily in symptom-related metabolic pathways such as Huntington's disease, spinocerebellar ataxia, energy-related central carbon metabolism in cancer, pantothenate and CoA biosynthesis metabolic pathways, as well as some neurotransmission and amino acid transport, and uptake- and synthesis-related metabolic pathways. On further investigation, we found that B. subtilis and E. faecium treatment enhanced the colonic barrier of OA rats, with elevated expressions of tight junction proteins occludin and Zonula occludens 1 and MUC2 mRNA. Intestinal permeability was reduced, and serum LPS levels were downregulated in the treatment group. B. subtilis and E. faecium also regulated the oxidative stress pathway Keap1/Nrf2, promoted the expression of the downstream protective proteins HO-1 and Gpx4, and reduced intestinal apoptosis. Hence, B. subtilis and E. faecium alleviate colonic oxidative stress and inflammation in OA rats by improving fecal metabolism and enhancing the colonic barrier.

Marek’s disease has caused enormous losses in poultry production worldwide. However, the evolutionary process and molecular mechanisms underlying Marek’s disease virus (MDV) remain largely unknown. Using complete genomic sequences spanning an unprecedented diversity of MDVs, we explored the evolutionary history and major patterns in viruses sampled from 1964 to 2018. We found that the evolution of MDV strains had obvious geographical features, with the Eurasian and North American strains having independent evolutionary paths, especially for Asian strains. The evolution of MDVs generally followed a clock-like structure with a relatively high evolutionary rate. Asian strains had evolved at a faster rate than European strains, with most genetic mutations occurring in Asian strains. Our results showed that all recombination events occurred in the UL and US subregions. We found direct evidence of a closer correlation between Eurasian strains, related to a series of reorganization events represented by the European strain ATE2539. We also discovered that the vaccine strains had recombined with the wild virulent strains. Base substitution and recombination were found to be the two main mechanisms of MDV evolution. Our study offers novel insights into the evolution of MDVs that could facilitate predicting the spread of infections, and hence their control.

BackgroundAllergic drug reaction or drug allergy is an immunologically mediated drug hypersensitivity reaction (DHR). G-protein coupled receptors (GPCRs) are common drug targets and communicate extracellular signals that initiate cellular responses. Recent evidence shows that GPCR MRGPRX2 is of major importance in IgE-independent pseudo-allergic DHRs based on the suspected interactions between many FDA-approved peptidergic compounds and MRGPRX2.ObjectiveOur aim was to uncover novel MRGPRX2-selective and -potent agonists as drug candidates responsible for clinical features of pseudo-allergic DHRs.MethodsWe conducted a primary high-throughput screening (HTS), coupled with mutagenesis targeting the MRGPRX2 N62S mutation, on a panel of 3,456 library compounds. We discovered pharmacologically active hit compounds as agonists of the MRGPRX2 protein according to high degrees of potency evaluated by the calcium response and validated by the degranulation assay. Using the molecular tool Forge, we also characterized the structure-activity relationship shared by identified hit compounds.ResultsThe alternative allele of single nucleotide polymorphism rs10833049 (N62S) in MRGPRX2 demonstrated loss-of-function property in response to substance P and antineoplastic agent daunorubicin hydrochloride. We applied a unique assay system targeting the N62S mutation to the HTS and identified 84 MRGPRX2-selective active hit compounds representing diverse classes according to primary drug indications. The top five highly represented groups included fluoroquinolone and non-fluoroquinolone antibiotics; antidepressive/antipsychotic; antihistaminic and antineoplastic agents. We classified hit compounds into 14 clusters representing a variety of chemical and drug classes beyond those reported, such as opioids, neuromuscular blocking agents, and fluoroquinolones. We further demonstrated MRGPRX2-dependent degranulation in the human mast cell line LAD2 cells induced by three novel agonists representing the non-fluoroquinolone antibiotics (bacitracin A), anti-allergic agents (brompheniramine maleate) and tyrosine-kinase inhibitors (imatinib mesylate).ConclusionOur findings could facilitate the development of interventions for personalized prevention and treatment of DHRs, as well as future pharmacogenetic investigations of MRGPRX2 in relevant disease cohorts.

Osteoarthritis (OA) is a common chronic musculoskeletal disease reported in veterinary clinics that severely reduces the quality of life of animals. The natural product, bilobalide, has positive effects on chondroprotection but its exact mechanism of action is unclear. This study aimed to investigate the antioxidant and anti-matrix degradation activities of bilobalide in a rabbit model of OA and its protective effects on joints. We also investigated the possible mechanisms underlying these effects. The rabbit OA model was established by intra-articular injection of 4% papain. Thirty healthy male New Zealand rabbits were randomly divided into control, untreated OA, Cel (100 mg/kg celecoxib intervention as a positive control), BB-L and BB-H (40 mg /kg and 80 mg /kg bilobalide gavage treatment, respectively) groups. Two weeks after surgical induction, bilobalide or celecoxib was administered by gavage daily for 8 weeks. After 8 weeks of bilobalide intervention, cartilage macroscopic observation and histopathological images showed alleviation of cartilage damage after bilobalide treatment, and the Osteoarthritis Research Society International (OARSI) score was significantly lower than that in the OA group. Bilobalide reduced the expression of metalloproteinase 3 (MMP-3) and MMP-13 in cartilage tissue of OA rabbits and reversed the levels of serum C-telopeptides of type II collagen (CTX-II), cartilage oligomeric matrix protein (COMP), interleukin 1(IL-1), and tumor necrosis factor (TNF-α). Bilobalide (80 mg/kg) could improve the biomechanical properties and microstructural changes in subchondral bone in the early stage of OA in rabbits, thereby delaying subchondral bone damage. Mechanistically, bilobalide exerted antioxidant and anti-matrix degradation effects by upregulating the oxidative stress signaling Nrf2/HO-1 pathway and inhibiting cartilage degeneration in rabbit OA. We thus speculate that bilobalide supplements recovery from OA damage.

ObjectivesTraumatic intracerebellar hematoma (TICH) is a very rare entity with a high morbidity and mortality rate, and there is no consensus on its optimal surgical management. In particular, whether and when to place external ventricle drainage in TICH patients without acute hydrocephalus pre-operation is still controversial.MethodsA single-institutional, retrospective analysis of total of 47 TICH patients with craniectomy hematoma evacuation in a tertiary medical center from January 2009 to October 2020 was performed. Primary outcomes were mortality in hospital and neurological function evaluated by GOS at discharge and 6 months after the ictus. Special attention was paid to the significance of external ventricular drainage (EVD) in TICH patients without acute hydrocephalus on admission.ResultsAnalysis of the clinical characteristics of the TICH patients revealed that the odds of use of EVD were seen in patients with IVH, fourth ventricle compression, and acute hydrocephalus. Placement of EVD at the bedside can significantly improve the GCS score before craniotomy, as well as the neurological score at discharge and 6 months. Compared with the only hematoma evacuation (HE) group, there is a trend that EVD can reduce hospital mortality and decrease the occurrence of delayed hydrocephalus, although the difference is not statistically significant. In addition, EVD can reduce the average NICU stay time, but has no effect on the total length of stay. Moreover, our data showed that EVD did not increase the risk of associated bleeding and intracranial infection. Interestingly, in terms of neurological function at discharge and 6 month after the ictus, even though without acute hydrocephalus on admission, the TICH patients can still benefit from EVD insertion.ConclusionFor TICH patients, perioperative EVD is safe and can significantly improve neurological prognosis. Especially for patients whose GCS dropped by more than 2 points before the operation, EVD can significantly improve the patient's GCS score, reduce the risk of herniation, and gain more time for surgical preparation. Even for TICH patients without acute hydrocephalus on admission CT scan, EVD placement still has positive clinical significance.

Osteoarthritis (OA) is driven by chronic low-grade inflammation and subsequent cartilage degradation. OA is the most prevalent degenerative joint disease worldwide, and its treatment remains a challenge. The aim of this study was to explore the potential effects and mechanism underlying the anti-OA properties of ginkgolide C (GC). Protective effects of GC on hydrogen peroxide (H2O2)-treated rat chondrocytes were evaluated using ELISA, qPCR, western blot analysis, flow cytometry, ROS detection and immunofluorescence in vitro. Ameliorating effects of GC on cartilage degeneration in rats were evaluated through behavioral assays, microcomputed tomography, histopathological analysis, western blot analysis and ELISA in vivo. In vitro, GC treatment inhibited the release of pro-apoptotic factors induced by H2O2 and promoted the release of the anti-apoptotic proteins. In addition, GC decreased the expression of matrix metalloproteinase (MMP3 and MMP13), thrombospondin motifs 4 (ADAMTS4), and inflammatory mediators inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and SOX9 thereby inhibiting extracellular matrix (ECM) degradation. Mechanistically, GC exerts its anti-apoptotic and anti-inflammatory effects by upregulating the oxidative stress signaling Nrf2/HO-1 pathway and preventing p65 from binding to DNA. Similarly, In a rat model with post-traumatic OA (PTOA) induced by anterior cruciate ligament transection (ACLT), GC inhibited joint pain, cartilage destruction, and abnormal bone remodeling of subchondral bone. GC inhibited H2O2-induced chondrocyte apoptosis through Nrf2/HO-1 and NF-κB axis, exerted anti-inflammatory effects, and inhibited cartilage degeneration in rat OA. Our findings advanced the concept that GC may contribute to cartilage metabolism through anti-inflammatory and anti-apoptotic effects, and the identified GC is a potential therapeutic agent for the treatment of OA.

Objective: To investigate the efficacy of Integrative medicine (IM), compare with Western medicine (WM), in the treatment of rheumatoid arthritis (RA) in a cohort study.Methods: This is a cohort study with recruitment of RA patients from 10 hospitals in China. The primary outcome was change in disease activity score 28 (DAS28) during 4 follow-up visits. Generalized estimating equation (GEE) models that controlled for variables were used to investigate a time trend and assess group differences in the primary outcome and secondary outcomes after propensity score matching (PSM).Results: A total of 3195 patients with RA received IM (n = 1379, 43.2%) or WM (n = 1816, 56.8%). Following 1:1 propensity score matching, 1,331 eligible patients prescribed IM were compared to 1,331 matched patients prescribed WM. The GEE analysis with PSM showed that the IM was more beneficial to significantly decrease the levels of VAS, PGA and PhGA (VAS: odds ratio (OR), 0.76; 95% CI, 0.63–0.92; p = 0.004; PGA: OR, 0.76; 95% CI, 0.64–0.92; p = 0.007; and PhGA: OR, 0.77; 95% CI, 0.64, 0.93; p = 0.004), and reduce DAS28 (OR, 0.84; 95% CI, 0.73–0.98; p = 0.030) in the per-protocol population.Conclusion: This study suggests that compare to WM, IM has advantages in improving RA-related outcomes. However, the statistical significance might not reveal significant clinical difference. Further studies should be focused on specific treatment strategies and/or disease stages.

PurposeTo investigate the effect of sub-satisfactory stent recanalization on hemodynamic stresses for severe stenoses of the middle cerebral artery (MCA) M 1 segment.Materials and methodsPatients with severe stenoses of the MCA M1 segment treated with endovascular stent angioplasty were retrospectively enrolled. Three-dimensional digital subtraction angiography before and after stenting was performed; the computational fluid dynamics (CFD) analysis of hemodynamic stresses at the stenosis and normal segments proximal and distal to the stenoses was analyzed.ResultsFifty-one patients with severe stenosis at the MCA M1 segment were enrolled, with the stenosis length ranging from 5.1 to 12.8 mm (mean 9 ± 3.3 mm). Stent angioplasty was successful in all (100%) the patients. The angiography immediately after stenting demonstrated a significant (P < 0.05) decrease in MCA stenosis after comparison with before stenting (31.4 ±12.5% vs. 87.5 ± 9.6%), with residual stenosis of 15–30% (mean 22.4 ± 3.5%). Before stenting, the total pressure was significantly higher (P < 0.0001), while the WSS, velocity, and vorticity were all significantly decreased (P < 0.0001) at the normal arterial segment proximal to the stenosis, and the total pressure, WSS, velocity, and vorticity were all significantly decreased (P < 0.0001) at the normal arterial segment distal to the stenosis compared with those at the stenosis. After sub-satisfactory stenting recanalization, all the hemodynamic stresses proximal or distal to the stenosis and at the perforator root were improved compared with those before stenting and were similar to those after virtual stenosis removal.ConclusionSub-satisfactory recanalization of severe MCA stenoses can significantly improve the hemodynamic status for cerebral perfusion at the stenoses.

The proportion of pregnant women giving birth through cesarean section is increasing annually worldwide. However, post-cesarean section scar diverticulum is a common condition that occurs and requires better surgical strategies than the methods currently used. We hypothesized that using biological lubricant topically on the incision area during C-section could be an option to minimize the scar. This water-based polyethylene glycol (PEG)/chitosan (CS) composite lubricant was prepared via ultrasonic blending. The product was characterized using scanning electron microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, and Raman spectroscopy. The thermal stability of the materials and their heat absorption and release during heating were analyzed using thermogravimetric analysis and differential scanning calorimetry. Tribological tests proved that the PEG/CS composite had a better lubrication effect than either the PEG or CS lubricant alone, and the cell viability experiments verified that it had good biocompatibility. Finally, application of the composite lubricant onto the backs of mice modeling full-thickness skin incisions further confirmed that the product improved both the re-epithelialization and the collagen levels of the wounded skin. In conclusion, we expect our newly formulated PEG/CS composite lubricant to be useful not only for managing post-cesarean section scar diverticulum but also for healing skin wounds in general.

Gut microbiota plays a vital role in maintaining the health and immunity of wild birds. However, less is known about the comparison of fecal microbiota between different ecological groups of wild birds, particularly in the Yellow River National Wetland in Baotou, China, an important transit point for birds migrating all over the East Asia-Australian and Central Asian flyways. In this study, we characterized the fecal microbiota and potential microbial function in nine bird species of raptors, waders, and waterfowl using 16S rRNA gene amplicon sequencing to reveal the microbiota differences and interaction patterns. The results indicated that there was no significant difference in α-diversity, but a significant difference in β-diversity between the three groups of birds. The fecal bacterial microbiota was dominated by Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes in all groups of birds. Furthermore, we identified five bacterial genera that were significantly higher in raptors, five genera that were significantly higher in waders, and two genera that were more abundant in waterfowl. The bacterial co-occurrence network results revealed 15 and 26 key genera in raptors and waterfowls, respectively. The microbial network in waterfowl exhibited a stronger correlation pattern than that in raptors. PICRUSt2 predictions indicated that fecal bacterial function was significantly enriched in the antibiotic biosynthesis pathway in all three groups. Metabolic pathways related to cell motility (bacterial chemotaxis and flagellar assembly) were significantly more abundant in raptors than in waders, whereas waders were enriched in lipid metabolism (synthesis and degradation of ketone bodies and fatty acid biosynthesis). The fecal microbiota in waterfowl harbored more abundant vitamin B6 metabolism, RNA polymerase, and tyrosine and tryptophan biosynthesis. This comparative study revealed the microbial community structure, microbial co-occurrence patterns, and potential functions, providing a better understanding of the ecology and conservation of wild birds. Future studies may focus on unraveling metagenomic functions and dynamics along with the migration routine or different seasons by metagenomics or metatranscriptomics.

PurposeTo investigate the effect and safety of flow diverters in the treatment of unruptured dissecting intracranial aneurysms of the vertebral artery in comparison with stent-assisted coiling or stenting alone.Materials and methodsPatients with unruptured dissecting intracranial aneurysms of the vertebral artery treated with the flow diverter, stent-assisted coiling, or stenting alone were retrospectively enrolled. The clinical data were analyzed and compared.ResultsTwenty-five patients were enrolled in the flow diversion group and 42 patients in the stenting group. Twenty-six flow diverters were deployed in the flow diversion group. Immediate angiography revealed contrast agent retention within the aneurysm cavity in all patients. In the stenting group, 48 stents were deployed, and immediate angiographic outcome showed O'Kelly-Marotta (OKM) grade D in 18 (42.9%) aneurysms, grade C in 16 (38.1%), and grade B in 8 (19.0%). Periprocedural ischemic complications of thrombosis occurred in two (4.8%) patients and were treated with thrombolysis. In the flow diversion group, 19 (76%) patients underwent angiographic follow-up 3–46 (median 24) months after the procedure, with the OKM grade D in 11 (57.9%) patients, C in two (10.5%), and B in six (31.6%). The aneurysm recurrence rate was zero, and all diverters remained patent. Asymptomatic instent stenosis occurred in two (10.5%) patients. In seven of the ten patients with mild or moderate parent artery stenosis before the procedure who experienced angiographic follow-up, the stenosis was improved in five (71.4%) patients. In the stenting group, angiographic follow-up was carried out in 33 (78.6%) patients 6–58 months (median 34) after the procedure, with OKM grade D in 22 (66.7%) patients, grade C in five (15.2%), grade B in three (9.1%), and aneurysm recurrence (grade B, with increased contrast agent into the aneurysm cavity) in three (9.1%). Five (16.7%) patients experienced asymptomatic instent stenosis, and six of the 12 patients (50%) with parent artery stenosis were improved.ConclusionFlow diverters with or without selective adjunctive coiling for the treatment of unruptured dissecting intracranial aneurysms of the vertebral artery may be safe and effective with good occlusion effects not inferior to those of stent-assisted coiling and stenting alone even though the long-term effect still warrants confirmation.

BackgroundTumor grade determined by the Ki67 index is the best prognostic factor for pancreatic neuroendocrine tumors (PanNETs). However, we often observe that the grade of metastases differs from that of their primary tumors. This study aimed to investigate the frequency of grade changes between primary tumors and metastases, explore its association with clinical characteristics, and correlate the findings with the prognosis.MethodsSix hundred forty-eight patients with pancreatic neuroendocrine neoplasms treated at Fudan University Shanghai Cancer Center were screened for inclusion, and 103 patients with PanNETs who had paired primary tumors and metastases with an available Ki67 index were included. Re-evaluation of Ki67 was performed on 98 available samples from 69 patients.ResultsFifty cases (48.5%) had a Ki67 index variation, and 18 cases (17.5%) displayed a grade increase. Metachronous metastases showed significantly higher Ki67 index variation than synchronous metastases (P=0.028). Kaplan–Meier analyses showed that high-grade metastases compared to low-grade primary tumors were significantly associated with decreased progression-free survival (PFS, P=0.012) and overall survival (OS, P=0.027). Multivariable Cox regression analyses demonstrated that a low-grade increase to high-grade was an unfavorable and independent prognostic factor for PFS and OS (P=0.010, and P=0.041, respectively).ConclusionsA high-grade increase in metastases was an unfavorable predictor of PanNETs, which emphasized the importance of accurate pathological grading and could provide a reference for clinical decision-making.

Hepatocellular carcinoma (HCC) is a complex issue in cancer treatment in the world at present. Matrine is the main active ingredient isolated from Sophora flavescens air and possesses excellent antitumor effects in HCC. However, the specific underlying mechanisms, especially the possible relationships between the anti-HCC effect of matrine and the related metabolic network of HCC, are not yet clear and need further clarification. In this study, an integrative metabolomic-based bioinformatics algorithm was designed to explore the underlying mechanism of matrine on HCC by regulating the metabolic network. Cell clone formation, invasion, and adhesion assay were utilized in HCC cells to evaluate the anti-HCC effect of matrine. A cell metabolomics approach based on LC-MS was used to obtain the differential metabolites and metabolic pathways regulated by matrine. The maximum activity contribution score model was developed and applied to calculate high contribution target genes of matrine, which could regulate a metabolic network based on the coexpression matrix of matrine-regulated metabolic genes and targets. Matrine significantly repressed the clone formation and invasion, enhanced cell–cell adhesion, and hampered cell matrix adhesion in SMMC-7721 cells. Metabolomics results suggested that matrine markedly regulated the abnormal metabolic network of HCC by regulating the level of choline, creatine, valine, spermidine, 4-oxoproline, D-(+)-maltose, L-(−)-methionine, L-phenylalanine, L-pyroglutamic acid, and pyridoxine, which are involved in D-glutamine and D-glutamate metabolism, glycine, serine and threonine metabolism, arginine and proline metabolism, etc. Our proposed metabolomic-based bioinformatics algorithm showed that the regulating metabolic networks of matrine exhibit anti-HCC effects through acting on MMP7, ABCC1, PTGS1, etc. At last, MMP7 and its related target β-catenin were validated. Together, the metabolomic-based bioinformatics algorithm reveals the effects of the regulating metabolic networks of matrine in treating HCC relying on the unique characteristics of the multitargets and multipathways of traditional Chinese medicine.

Nanoparticles that contact human cells without damaging basic human tissues are becoming more widely used in medicine. Efficient delivery to the intracellular target cell or compartment through the cell membrane must be achieved with minimal cytotoxicity to healthy cells. Fe3O4 nanoparticles have been widely used in biomedical research for their magnetic, non-toxic, and biocompatible properties. However, the effects of Fe3O4 nanoparticles coated with chitosan (CS) on gynecological cells are unclear. In this study, the Fe3O4 nanoparticles were coated with CS to enhance their cytocompatibility and dispersion in water. These CS-Fe3O4 nanoparticles were taken up by gynecological cells and did not affect cell viability in vitro. They have greater cytocompatibility in acidic environments than normal Fe3O4 nanoparticles and have the potential for drug delivery into gynecological cells.