Search

IntroductionThe Xinjiang Mongolians, located along the Silk Road, migrated westward from Northeast Asia in the 13th and 14th centuries. Despite its significance, genetic studies on Xinjiang Mongolians have been limited compared to other Mongolian populations.MethodsIn this study, we analyzed the non-recombining region of the Y-chromosome in 165 Xinjiang Mongolian males using 108 biallelic markers and 44 STRs.Results and discussionOur study identified prevalent haplogroups C2a1a3-F1918 (10%), C2a1a2-M48 (8%), N1a1a-M178 (5%), and R1a1a-M17 (10%) in the Xinjiang Mongolians. Additionally, our study suggested a genetic affinity between Xinjiang Mongolians and Inner Mongolia Mongolian populations, as well as other ethnic groups from northwest China, based on the PCA analysis. The Network analysis revealed distinct branching expansion patterns in haplogroups C2a1a3a-F3796, C2a1a2-M48, and N1a1a-M178, with estimated timeframes aligning with Genghis Khan's invasion of Xinjiang in the Yuan Dynasty. Notably, our analysis of the R1a1a-M17 Network highlighted the role of Xinjiang Mongolians in the expansion of Turkic-speaking populations in Xinjiang and surrounding regions. The integration of ancient DNA data suggested that the high frequency haplogroups C2a1a3a-F3796, C2a1a2-M48, and N1a1a-M178 could be traced back to their origin in Northeast Asia. Furthermore, the estimated TMRCA of haplogroup R1a1a-M17 implied cultural and genetic influences from Turkic populations during the Qagatay Khanate period. Overall, our study provided a genetic explanation for the ethnic origin of Xinjiang Mongolians, highlighting their migration from Northeast Asia and subsequent assimilation with the local populations in Xinjiang.

ObjectiveTo assess the effect of B cell depletion therapy (BCDT) on circulating T follicular helper (cTfh) and circulating T helper 17 (cTh17) cells and its relation to clinical improvement in patients with myasthenia gravis (MG).Methods28 anti-AchR positive MG patients treated with ofatumumab and 28 healthy controls (HCs) were included. Frequencies of cTfh and cTh17 cells were monitored by flow cytometry at baseline and 4, and 12 weeks after the initial dose ofatumumab. Serum cytokines associated with cTfh and cTh17, including IL-6, IL-21, and IL-17, were also analyzed.ResultsThe frequency of cTfh and cTh17 significantly increased in MG patients compared with HCs. Additionally, elevated levels of both T-cell subsets correlated with MG severity. During the follow-up, cTfh and cTh17 return to normal after BCDT. Furthermore, the decrease in cTfh and cTh17 was associated with MG scores improvement over time. Notably, cTfh- and cTh17-related cytokines, including IL-6, IL-21, and IL-17, exhibited a marked decrease following ofatumumab therapy.ConclusionsAbnormal expansion of cTfh and cTh17 cells may be key features in the immunopathology of MG. Their levels returned to normal after BCDT, which was closely correlated with clinical amelioration. This result suggests that these two T-cell subsets may be targets for BCDT treatment of MG.

Soy leghemoglobin, when bound to heme, imparts a meat-like color and flavor and can serve as a substitute for animal-derived proteins. Enhancing cellular heme synthesis improves the recombinant expression of leghemoglobin in yeast. To achieve high-level expression of leghemoglobin A (LBA) in Kluyveromyces marxianus, a food-safe yeast, large-scale heme synthesis modules were transferred into K. marxianus using yeast artificial chromosomes (KmYACs). These modules contained up to 8 native and heterologous genes to promote the supply of heme precursors and downstream synthesis. Next, eight genes inhibiting heme or LBA synthesis were individually or combinatorially deleted, with the lsc1Δssn3Δ mutant yielding the best results. Subsequently, heme synthesis modules were combined with the lsc1Δssn3Δ mutant. In the resulting strains, the module genes were all actively expressed. Among these module genes, heterologous S. cerevisiae genes in the downstream heme synthesis pathway significantly enhanced the expression of their counterparts in K. marxianus, resulting in high heme content and LBA yield. After optimizing the medium recipe by adjusting the concentrations of glucose, glycine, and FeSO4·7H2O, a heme content of 66.32 mg/L and an intracellular LBA titer of 7.27 g/L were achieved in the engineered strain in a 5 L fermentor. This represents the highest intracellular expression of leghemoglobin in microorganisms to date. The leghemoglobin produced by K. marxianus can be utilized as a safe ingredient for plant-based protein products.

AbstractThe Kazakhs of Xinjiang province are characterized by their nomadic lifestyle and patrilineal clan system. However, compared to Central Asian Kazakhs, a lack of Y chromosomal high-resolution analysis has hindered our understanding of the paternal history of modern Xinjiang Kazakhs.MethodsIn this study, we present the analysis of 110 Y-SNP data from 209 Altay Kazakhs and 201 Ili Kazakhs in Xinjiang, along with their previously reported 24 Y-STR loci data.Results and discussionWe found that the Y chromosome haplogroups exhibit greater diversity in Altay Kazakhs compared to Kazakhs in Kazakhstan, Russia, and other regions of China. Y-SNP-based PCA plots reveal that both the Altay and Ili Kazakhs are situated between the Turkic, Mongolia, and Tibeto-Burman clusters. The dominant haplogroup C2a1a3-F1918, which originated in northeast Asia during the Neolithic Age, accounts for nearly half of the Altay and Ili Kazakhs. The Y lineage network of C2a1a3-F1918 contained two subclusters. Approximately 60.6% of the Altay Kazakhs belong to the DYS448-23 subcluster, indicating their Kerey-Abakh ancestry. On the other hand, around three-quarters of the Ili Kazakhs belong to the DYS448-22 subcluster, suggesting their Kerey-Ashmaily heritage. Notably, the TMRCA ages of the DYS448-23 subcluster were calculated to be 289.4 ± 202.65 years, which aligns with the historical immigration of the Kerey clan back to the Altay Mountains after the defeat of the Dzungar by the Qing dynasty in the mid-18th century.

IntroductionGenerally, Traditional Chinese Medicine (TCM) courses are now given to modern medicine students without proper course scheduling, resulting in poor teaching results.MethodsTo analyze the main factors affecting TCM learning, we surveyed the medical students and TCM teachers from Xiangya School of Medicine of Central South University via online questionnaires. The questionnaire comprised two parts, the students' part included the basic information, the subjective cognition in TCM, the attitude toward TCM course arrangements, and the attitude toward curriculum content and the design of TCM. The teachers' part included the basic information, the attitudes and opinions on TCM course arrangements, and suggestions and views on TCM teaching reform. The related data were collected from 187 medical students divided into two groups, namely, clinical medical students and non-clinical medical students.ResultsWe found a more positive attitude toward TCM [including “Scientific nature of TCM” (P = 0.03) and “Necessity for modern medicine students to learn TCM” (P = 0.037)] in clinical medical students compared with non-clinical medical students, clinical and non-clinical medical students tended to find TCM courses difficult, and the students prefer clinical training to be better than theoretical teaching, while the teachers believe that lecture-based education should have a more significant proportion.DiscussionHence, to optimize the current TCM teaching, we conducted education reform, including differentiated teaching, hybrid teaching, and selective teaching.

IntroductionWaxy maize, mainly consumed at the immature stage, is a staple and vegetable food in Asia. The pigmentation in the kernel of purple waxy maize enhances its nutritional and market values. Light, a critical environmental factor, affects anthocyanin biosynthesis and results in pigmentation in different parts of plants, including in the kernel. SWL502 is a light-sensitive waxy maize inbred line with purple kernel color, but the regulatory mechanism of pigmentation in the kernel resulting in purple color is still unknown.MethodsIn this study, cyanidin, peonidin, and pelargonidin were identified as the main anthocyanin components in SWL502, evaluated by the ultra-performance liquid chromatography (UPLC) method. Investigation of pigment accumulation in the kernel of SWL502 was performed at 12, 17, and 22 days after pollination (DAP) under both dark and light treatment conditions via transcriptome and metabolome analyses.ResultsDark treatment affected genes and metabolites associated with metabolic pathways of amino acid, carbohydrate, lipid, and galactose, biosynthesis of phenylpropanoid and terpenoid backbone, and ABC transporters. The expression of anthocyanin biosynthesis genes, such as 4CL2, CHS, F3H, and UGT, was reduced under dark treatment. Dynamic changes were identified in genes and metabolites by time-series analysis. The genes and metabolites involved in photosynthesis and purine metabolism were altered in light treatment, and the expression of genes and metabolites associated with carotenoid biosynthesis, sphingolipid metabolism, MAPK signaling pathway, and plant hormone signal transduction pathway were induced by dark treatment. Light treatment increased the expression level of major transcription factors such as LRL1, myc7, bHLH125, PIF1, BH093, PIL5, MYBS1, and BH074 in purple waxy maize kernels, while dark treatment greatly promoted the expression level of transcription factors RVE6, MYB4, MY1R1, and MYB145.DiscussionThis study is the first report to investigate the effects of light on waxy maize kernel pigmentation and the underlying mechanism at both transcriptome and metabolome levels, and the results from this study are valuable for future research to better understand the effects of light on the regulation of plant growth.

IntroductionGastric cancer (GC) remains the major constituent of cancer-related deaths and a global public health challenge with a high incidence rate. Helicobacter pylori (HP) plays an essential role in promoting the occurrence and progression of GC. Cancer-associated fibroblasts (CAFs) are regarded as a significant component in the tumor microenvironment (TME), which is related to the metastasis of GC. However, the regulation mechanisms of CAFs in HP-related GC are not elucidated thoroughly.MethodsHP-related genes (HRGs) were downloaded from the GSE84437 and TCGA-GC databases. The two databases were combined into one cohort for training. Furthermore, the consensus unsupervised clustering analysis was obtained to sort the training cohort into different groups for the identification of differential expression genes (DEGs). Weighted correlation network analysis (WGCNA) was performed to verify the correlation between the DEGs and cancer-associated fibroblasts which were key components in the tumor microenvironment. The least absolute shrinkage and selection operator (LASSO) was executed to find cancer-associated fibroblast-related differential expression genes (CDEGs) for the further establishment of a prognostic model.Results and discussionIn this study, 52 HP-related genes (HRGs) were screened out based on the GSE84437 and TCGA-GC databases. A total of 804 GC samples were analyzed, respectively, and clustered into two HP-related subtypes. The DEGs identified from the two subtypes were proved to have a relationship with TME. After WGCNA and LASSO, the CAFs-related module was identified, from which 21 gene signatures were confirmed. Then, a CDEGs-Score was constructed and its prediction efficiency in GC patients was conducted for validation. Overall, a highly precise nomogram was established for enhancing the adaptability of the CDEGs-Score. Furthermore, our findings revealed the applicability of CDEGs-Score in the sensitivity of chemotherapeutic drugs. In general, our research provided brand-new possibilities for comprehending HP-related GC, evaluating survival, and more efficient therapeutic strategies.

ObjectiveTo determine whether intraoperative transfusion of allogeneic or autologous blood is associated with an increased incidence of postoperative delirium (POD) after total knee arthroplasty (TKA) and total hip arthroplasty (THA).MethodsThe medical records of 1,143 older (≥65 years old) patients who received an intraoperative blood transfusion while undergoing total knee or hip arthroplasty at the First Medical Center of Chinese PLA General Hospital from 2014 to 2019 were reviewed; of these patients, 742 (64.92%) received allogeneic blood, while 401 (35.08%) received autologous blood. Patients who received autologous transfusion were paired with those received allogeneic transfusion using 1:1 propensity score matching method. The primary outcome was POD. The secondary outcomes were postoperative complications, including heart failure, deep vein thrombosis, myocardial infarction, stroke, and lung infection. Multivariable nominal logistic regression was used to identify any independent associations between intraoperative blood transfusions and POD, and secondary postoperative complications, respectively.ResultsPostoperative delirium occurred in 6.6% (49/742) of patients who had received an allogeneic blood transfusion and in 2.0% (8/401) of patients who had received an autologous blood transfusion. It is noteworthy that the multivariable logistic regression demonstrated a significant association between intraoperative allogeneic blood transfusion and POD (odds ratio [OR]: 4.11; 95% confidence interval [CI]: 1.95–9.77; p

Inconsistent training programs for public health emergency (PHE) have been criticized as a contributing factor in PHE's managerial weak points. In response, to analyze the relevant discrepancies among the medical students in the class of 2021 from Xiangya School of Medicine of Central South University, the present study conducted an online questionnaire survey using convenience sampling. The questionnaire comprised four sections, including the basic information, the subjective cognition in PHE, the rescue knowledge and capabilities of PHE, and the mastery of PHE regulations and psychological intervention abilities. To compare the abovementioned aspects, related data were collected from 235 medical students divided into two groups, namely, clinical medical students (Group A) and preventive medical students (Group B). We found a more positive attitude in PHE (P = 0.014) and a better grasp of the PHE classification (P = 0.027) and the reporting system in group B compared with group A. In addition, even if group B showed the same response capability in communicable diseases as group A, the former had less access to clinical practice, resulting in poorer performance in the noncommunicable diseases during a fire, flood, and traffic accidents (P = 0.002, P = 0.018, P = 0.002). The different emphasis of each training program contributed to the uneven distribution of abilities and cognition. Meanwhile, the lack of an integrated PHE curriculum led to unsystematic expertise. Hence, to optimize the PHE management system, equal attention should be paid to medical students with diverse majors along with a complete integrated PHE curriculum.

ObjectiveOveractive bladder (OAB) is a disease that seriously affects patients’ quality of life and mental health. To address this issue, more and more researchers are examining the relationship between OAB treatment and urinary microecology. In this study, we sought to determine whether differences in treatment efficacy were related to microbiome diversity and composition as well as the abundance of specific genera. Machine learning algorithms were used to construct predictive models for urine microbiota-based treatment of OAB.MethodsUrine samples were obtained from 64 adult female OAB patients for 16S rRNA gene sequencing. Patients’ overactive bladder symptom scores (OABSS) were collected before and after mirabegron treatment and patients were divided into effective and ineffective groups. The relationship between the relative abundance of certain genera and OABSS were analyzed. Three machine learning algorithms, including random forest (RF), supporting vector machine (SVM) and eXtreme gradient boosting (XGBoost) were utilized to predict the therapeutic effect of mirabegron based on the relative abundance of certain genera in OAB patients’ urine microbiome.ResultsThe species composition of the two groups differed. For one, the relative abundance of Lactobacillus was significantly higher in the effective group than in the ineffective group. In addition, the relative abundance of Gardnerella and Prevotella in the effective group was significantly lower than in the ineffective group. Alpha-diversity and beta-diversity differed significantly between the two groups. LEfSe analysis revealed that Lactobacillus abundance increased while Prevotella and Gardnerella abundance decreased in the effective group. The Lactobacillus abundance ROC curve had high predictive accuracy. The OABSS after treatment was negatively correlated with the abundance of Lactobacillus, whereas the relationship between OABSS and Prevotella and Gardnerella showed the opposite trend. In addition, RF, SVM and XGBoost models demonstrated high predictive ability to assess the effect of mirabegron in OAB patients in the test cohort.ConclusionsThe results of this study indicate that urinary microbiota might influence the efficacy of mirabegron, and that Lactobacillus might be a potential marker for evaluating the therapeutic efficacy of mirabegron in OAB patients.

K. marxianus is a promising cell factory for producing heterologous proteins. Oxidative stresses were raised during overexpression of heterologous proteins, leading to the shift of the redox state. How to measure the redox state of live K. marxianus cells without perturbing their growth remains a big challenge. Here, a fluorescence lifetime imaging (FLIM)-based method was developed in live K. marxianus cells. During the early exponential growth, K. marxianus cells exhibited an increased mean fluorescence lifetime (τ-mean) of NAD(P)H compared with Saccharomyces cerevisiae cells, which was consistent with the preference for respiration in K. marxianus cells and that for fermentation in S. cerevisiae cells. Upon oxidative stresses induced by high temperature or H2O2, K. marxianus cells exhibited an increased τ-mean in company with decreased intracellular NAD(P)H/NAD(P)+, suggesting a correlation between an increased τ-mean and a more oxidized redox state. The relationship between τ-mean and the expression level of a heterologous protein was investigated. There was no difference between the τ-means of K. marxianus strains which were not producing a heterologous protein. The τ-mean of a strain yielding a high level of a heterologous protein was higher than that of a low-yielding strain. The results suggested the potential application of FLIM in the non-invasive screen of high-yielding cells.

This study intended to explore the current status of psychological problems of preschool teachers in Southwest China 1 year after the COVID-19 pandemic and to assess the association between mental health education and psychological problems and symptoms of psychopathology. A total of 614 preschool teachers from Southwest China were enrolled to complete the questionnaires of the Chinese Symptom Checklist (SCL-90). Notably, 60% of the respondents reported psychological distress with GSI T-scores ≥ 63, especially the high score was reported on obsessive-compulsive disorder, interpersonal sensitivity, and phobic anxiety. Although less than half of the respondents have received mental health education last year, the teachers who received the mental health education reported lower GSI T-scores(β = −1.303, 95% CI: −2.208, −0.397). The results demonstrated the significance of constructing the education of promoting mental health of preschool teachers, and enlightening government or managers of kindergartens to relieve the psychological problems of preschool teachers through mental health education, especially for those with the pressure of overtime. It is recommended that local governments or kindergartens should organize more mental health education for kindergarten teachers to improve their mental health as well as their teaching professionalism.

Han/non-Han interactions were engrained among the border regions of ancient Imperial China. Yet, little is known about either the genetic origins or the lifeways of these border peoples. Our study applies tools from ancient deoxyribonucleic acid (DNA) and stable isotope analysis to the study of a Han dynasty population at the Shichengzi site in modern-day Xinjiang. Isotopic analysis (δ13C and δ15N) of human (n = 8), animal (n = 26), and crop remains (n = 23) from Shichengzi indicated that dietary patterns among site inhabitants could be split among agro-pastoral and agricultural groups based on differences in the collagen 15N ratios. DNA analysis divided the four Shichengzi samples into two groups, with one group primarily harboring the ancient Northeast Asian (ANA) related ancestry, while the other showed a dominant Late Neolithic Yellow River (YR_LN) related ancestry. Both ancient DNA and stable isotope evidence point to the Northeast Asian origins of pastoralists and East Asian origins of Han agriculturalists, who, nonetheless, shared a single burial space at Shichengzi. This study thus provides clear evidence for the multiple origins and identities of populations across the porous border represented by the Han Empire and surrounding regions and proposes a new model for the interpretation of border culture in early Imperial China.

The relationship between archeological culture and ethnicity is invariably complex. This is especially the case for periods of national division and rapid inter-ethnic exchange, such as China’s Sixteen Kingdoms (304–439 CE) and Northern and Southern Dynasties (420–589 CE). Going by tomb shape and grave goods, the Foyemiaowan cemetery at Dunhuang exhibits a typical third–tenth century Han style. Despite this, the ethnic makeup of the Foyemiaowan population has remained unclear. We therefore analyzed 485 Y-chromosomal SNPs and entire mitochondrial genomes of 34 Foyemiaowan samples. Our study yielded the following discoveries: (1) principal component analysis revealed that the Foyemiaowan population was closely clustered with Tibeto-Burman populations on the paternal side and close to Mongolic-speaking populations on the maternal side; (2) lineage comparisons at the individual level showed that the Foyemiaowan population consisted of primarily Tibeto-Burman and Han Chinese related lineages (Oα-M117, 25%;Oβ-F46, 18.75%), partially Altaic speaking North Eurasian lineages (N-F1206, 18.75%) and a slight admixture of southern East Asian lineages (O1b1a2-Page59, 6.25%; O1b1a1-PK4, 3.13%). Similarly, the maternal gene pool of Foyemiaowan contained northern East Asian (A, 4.17%; CZ, 16.67%; D, 20.83%; G, 4.17%; M9, 4.17%), southern East Asian (B, 12.51%; F, 20.83%) and western Eurasian (H, 4.17%; J, 4.17%) related lineages; (3) we discovered a relatively high genetic diversity among the Foyemiaowan population (0.891) in our ancient reference populations, indicating a complex history of population admixture. Archeological findings, stable isotope analysis and historical documents further corroborated our results. Although in this period China’s central government had relinquished control of the Hexi Corridor and regional non-Han regimes became the dominant regional power, Foyemiaowan’s inhabitants remained strongly influenced by Han culture.

Lung adenocarcinoma is increasingly harmful to society and individuals as cancer with an inferior prognosis and insensitive to chemotherapy. Previous studies have demonstrated that oxidative stress and lncRNAs play a vital role in many biological processes. Therefore, we explored the role of lncRNAs associated with oxidative stress in the prognosis and survival of LUAD patients. We examined the expression profiles of lncRNAs and oxidative stress genes in this study. A prognosis prediction model and a nomogram were built based on oxidative stress-related lncRNAs. Functional and drug sensitivity analyses were also performed depending on oxidative stress-related lncRNA signature. Moreover, we investigated the relationship between immune response and immunotherapy. The results showed that a risk scoring model based on 16 critical oxidative stress lncRNAs was able to distinguish the clinical status of LUAD and better predict the prognosis and survival. Additionally, the model demonstrated a close correlation with the tumor immune system, and these key lncRNAs also revealed the relationship between LUAD and chemotherapeutic drug sensitivity. Our work aims to provide new perspectives and new ideas for the treatment and management of LUAD.

ObjectiveWe sought to find a bedside prognosis prediction model based on clinical and image parameters to determine the in-hospital outcomes of acute aortic dissection (AAD) in the emergency department.MethodsPatients who presented with AAD from January 2010 to December 2019 were retrospectively recruited in our derivation cohort. Then we prospectively collected patients with AAD from January 2020 to December 2021 as the validation cohort. We collected the demographics, medical history, treatment options, and in-hospital outcomes. All enrolled patients underwent computed tomography angiography. The image data were systematically reviewed for anatomic criteria in a retrospective fashion by three professional radiologists. A series of radiological parameters, including the extent of dissection, the site of the intimal tear, entry tear diameter, aortic diameter at each level, maximum false lumen diameter, and presence of pericardial effusion were collected.ResultsOf the 449 patients in the derivation cohort, 345 (76.8%) were male, the mean age was 61 years, and 298 (66.4%) had a history of hypertension. Surgical repair was performed in 327 (72.8%) cases in the derivation cohort, and the overall crude in-hospital mortality of AAD was 10.9%. Multivariate logistic regression analysis showed that predictors of in-hospital mortality in AAD included age, Marfan syndrome, type A aortic dissection, surgical repair, and maximum false lumen diameter. A final prognostic model incorporating these five predictors showed good calibration and discrimination in the derivation and validation cohorts. As for type A aortic dissection, 3-level type A aortic dissection clinical prognosis score (3ADPS) including 5 clinical and image variables scored from −2 to 5 was established: (1) moderate risk of death if 3ADPS is

Scaffold protein Ste5 and associated kinases, including Ste11, Ste7, and Fus3, are core components of the mating pheromone pathway, which is required to induce a mating response. Orthologs of these proteins are widely present in fungi, but to which extent one protein can be replaced by its ortholog is less well understood. Here, interspecies complementation was carried out to evaluate the functional homology of Ste5 and associated kinases in Kluyveromyces lactis, K. marxianus, and Saccharomyces cerevisiae. These three species occupy important positions in the evolution of hemiascomycetes. Results indicated that Ste5 and associated kinases in K. lactis and K. marxianus could be functionally replaced by their orthologs to different extents. However, the extent of sequence identity, either between full-length proteins or between domains, did not necessarily indicate the extent of functional replaceability. For example, Ste5, the most unconserved protein in sequence, achieved the highest average functional replaceability. Notably, swapping Ste5 between K. lactis and K. marxianus significantly promoted mating in both species and the weakened interaction between the Ste5 and Ste7 might contribute to this phenotype. Consistently, chimeric Ste5 displaying a higher affinity for Ste7 decreased the mating efficiency, while chimeric Ste5 displaying a lower affinity for Ste7 improved the mating efficiency. Furthermore, the length of a negatively charged segment in the Ste7-binding domain of Ste5 was negatively correlated with the mating efficiency in K. lactis and K. marxianus. Extending the length of the segment in KlSte5 improved its interaction with Ste7 and that might contribute to the reduced mating efficiency. Our study suggested a novel role of Ste5-Ste7 interaction in the negative regulation of the pheromone pathway. Meanwhile, Ste5 mutants displaying improved mating efficiency facilitated the breeding and selection of Kluyveromyces strains for industrial applications.

Rice blast, caused by Magnaporthe oryzae, is one of the most devastating diseases in rice and can affect rice production worldwide. Rice plasma membrane (PM) proteins are crucial for rapidly and precisely establishing a defense response in plant immunity when rice and blast fungi interact. However, the plant-immunity-associated vesicle trafficking network mediated by PM proteins is poorly understood. In this study, to explore changes in PM proteins during M. oryzae infection, the PM proteome was analyzed via iTRAQ in the resistant rice landrace Heikezijing. A total of 831 differentially expressed proteins (DEPs) were identified, including 434 upregulated and 397 downregulated DEPs. In functional analyses, DEPs associated with vesicle trafficking were significantly enriched, including the “transport” term in a Gene Ontology enrichment analysis, the endocytosis and phagosome pathways in a Encyclopedia of Genes and Genomes analysis, and vesicle-associated proteins identified via a protein–protein interaction network analysis. OsNPSN13, a novel plant-specific soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) 13 protein, was identified as an upregulated DEP, and transgenic plants overexpressing this gene showed enhanced blast resistance, while transgenic knockdown plants were more susceptible than wild-type plants. The changes in abundance and putative functions of 20 DEPs revealed a possible vesicle trafficking network in the M. oryzae-rice interaction. A comparative proteomic analysis of plasma membrane proteins in rice leaves revealed a plant-immunity-associated vesicle trafficking network that is provoked by blast fungi; these results provide new insights into rice resistance responses against rice blast fungi.

This study aimed to examine the current suicidal risk and whether the suicidal risk was associated with a wide range of trauma. The self-administered online questionnaire was adopted to collect suicide risk (SR) such as suicidal ideation, self-harm, suicide attempts, and different trauma information of the adolescents by cluster sampling in Chongqing, China. Multivariable linear regression was presented to assess the association between different risks of trauma and SR scores. Approximately 14.7% of adolescents enrolled reported suicide ideation and more than 10% of adolescents have experienced one kind of trauma during the Coronavirus disease 2019 (COVID-19) pandemic period. After adjusting for confounding variables, adolescents who suffered family hurt had a higher risk score of SR (beta coefficients (β) = 0.289, 95% confidence interval (CI) = 0.115–0.463). A positive association was found among participants from junior and senior school (β = 0.415, 95% CI = 0.152, 0.768), and the SR score was positively associated with sexism among participants from the university/college (β = 0.238, 95% CI = 0.042, 0.434). The most potentially obvious trauma that contributed to SR in junior and senior school adolescents might be cyberbullying. Family neglect or abuse might be a detrimental factor in SR for adolescents whether those in junior school or those in university school in China. More interventions, like education related to cyberbullying and family abuse, should be prioritized to reduce the risk of suicide.

The Hexi Corridor was an important arena for culture exchange and human migration between ancient China and Central and Western Asia. During the Han Dynasty (202 BCE–220 CE), subsistence strategy along the corridor shifted from pastoralism to a mixed pastoralist-agriculturalist economy. Yet the drivers of this transition remain poorly understood. In this study, we analyze the Y-chromosome and mtDNA of 31 Han Dynasty individuals from the Heishuiguo site, located in the center of the Hexi Corridor. A high-resolution analysis of 485 Y-SNPs and mitogenomes was performed, with the Heishuiguo population classified into Early Han and Late Han groups. It is revealed that (1) when dissecting genetic lineages, the Yellow River Basin origin haplogroups (i.e., Oα-M117, Oβ-F46, Oγ-IMS-JST002611, and O2-P164+, M134-) reached relatively high frequencies for the paternal gene pools, while haplogroups of north East Asian origin (e.g., D4 and D5) dominated on the maternal side; (2) in interpopulation comparison using PCA and Fst heatmap, the Heishuiguo population shifted from Southern-Northern Han cline to Northern-Northwestern Han/Hui cline with time, indicating genetic admixture between Yellow River immigrants and natives. By comparison, in maternal mtDNA views, the Heishuiguo population was closely clustered with certain Mongolic-speaking and Northwestern Han populations and exhibited genetic continuity through the Han Dynasty, which suggests that Heishuiguo females originated from local or neighboring regions. Therefore, a sex-biased admixture pattern is observed in the Heishuiguo population. Additionally, genetic contour maps also reveal the same male-dominated migration from the East to Hexi Corridor during the Han Dynasty. This is also consistent with historical records, especially excavated bamboo slips. Combining historical records, archeological findings, stable isotope analysis, and paleoenvironmental studies, our uniparental genetic investigation on the Heishuiguo population reveals how male-dominated migration accompanied with lifestyle adjustments brought by these eastern groups may be the main factor affecting the subsistence strategy transition along the Han Dynasty Hexi Corridor.

The spines of cucumber fruit not only have important commercial value but are also a classical tissue to study cell division and differentiation modes of multicellular trichomes. It has been reported that CsTs (C-type Lectin receptor-like kinase) can influence the development of fruit spines. In this study, we took a pair of cucumber materials defined as hard (Ts, wild type) and tender spines (ts, mutant) and defined the developmental process of fruit spines as consisting of four stages (stage I to stage IV) by continuously observing by microscope and SEM. Comparisons of transcriptome profiles at different development stages of wild-type spines showed that 803 and 722 genes were upregulated in the stalk (stage II and stage III) and base (stage IV) development stages of fruit spines, respectively. The function analysis of DEGs showed that genes related to auxin polar transport and HD-ZIP transcription factor are significantly upregulated during the development of the stalk. bHLH transcription factors and cytoskeleton-related genes were significantly upregulated during the development of the base. In addition, stage III is the key point for the difference between wild-type and mutant spines. We detected 628 DEGs between wild type and mutant at stage III. These DEGs are mainly involved in the calcium signaling of the cytoskeleton and auxin polar transport. Coincidentally, we found that CsVTI11, a factor involved in auxin signal transmission, can interact with CsTs in vivo, but this interaction does not occur between CsVTI11 and Csts, further suggesting that CsTs may regulate the development of fruit spines by influencing cell polarity. These results provide useful tools to study the molecular networks associated with cucumber fruit spine development and elucidate the biological pathways that C-type Lectin receptor-like kinase plays in regulating the development of fruit spines.

Kluyveromyces marxianus is the fastest-growing eukaryote and a promising host for producing bioethanol and heterologous proteins. To perform a laboratory evolution of thermal tolerance in K. marxianus, diploid, triploid and tetraploid strains were constructed, respectively. Considering the genetic diversity caused by genetic recombination in meiosis, we established an iterative cycle of “diploid/polyploid - meiosis - selection of spores at high temperature” to screen thermotolerant strains. Results showed that the evolution of thermal tolerance in diploid strain was more efficient than that in triploid and tetraploid strains. The thermal tolerance of the progenies of diploid and triploid strains after a two-round screen was significantly improved than that after a one-round screen, while the thermal tolerance of the progenies after the one-round screen was better than that of the initial strain. After a two-round screen, the maximum tolerable temperature of Dip2-8, a progeny of diploid strain, was 3°C higher than that of the original strain. Whole-genome sequencing revealed nonsense mutations of PSR1 and PDE2 in the thermotolerant progenies. Deletion of either PSR1 or PDE2 in the original strain improved thermotolerance and two deletions displayed additive effects, suggesting PSR1 and PDE2 negatively regulated the thermotolerance of K. marxianus in parallel pathways. Therefore, the iterative cycle of “meiosis - spore screening” developed in this study provides an efficient way to perform the laboratory evolution of heat resistance in yeast.

Objective: Diabetes mellitus (DM) has been critically associated with unfavorable outcomes in the general population. We aimed to investigate the association between type 2 DM and long-term survival outcomes for postoperative ischemic stroke in patients who underwent non-cardiac surgery.Research Design and Methods: This was a retrospective cohort study of patients with non-cardiac surgery who had suffered from postoperative ischemic stroke between January 2008 and August 2019. Diabetic individuals were included in postoperative ischemic stroke patients with the DM group. The outcome of interest was long-term overall survival (OS). We conducted propensity score matching (PSM) and inverse probability treatment weighting (IPTW) to adjust for baseline characteristic differences between groups. Multivariate Cox regression analysis with stepwise selection was used to calculate the adjusted hazard ratio (HR) of OS and type 2 DM.Results: During a median follow-up of 46.2 month [interquartile range (IQR), 21.1, 84.2], 200 of 408 patients (49.0%) died. The OS rates at 3, 5, and 10 years were significantly lower for postoperative ischemic stroke patients with DM than those without DM (3 years OS: 52.2 vs. 69.5%, p < 0.001; 5 years OS: 41.6 vs. 62.4%, p < 0.001; 10 years OS: 37.2 vs. 56.6%, p < 0.001). All covariates were between-group balanced after using PSM or IPTW. The postoperative ischemic stroke patients with type 2 DM had a shortened OS in primary analysis (HR: 1.947; 95% CI: 1.397–2.713; p < 0.001), PSM analysis (HR: 2.190; 95% CI: 1.354–3.540; p = 0.001), and IPTW analysis (HR: 2.551; 95% CI: 1.769–3.679; p < 0.001).Conclusion: Type 2 DM was associated with an unfavorable survival outcome for postoperative ischemic stroke in patients who underwent non-cardiac surgery. When postoperative ischemic stroke co-occurred with type 2 DM, the potential synergies would have multiplicative mortality risk. Further research to assess the adverse effects of type 2 DM on long-term survival may be warranted.

ObjectiveTo evaluate the feasibility and accuracy of mixed reality combined with surgical navigation in oral and maxillofacial tumor surgery.MethodsRetrospective analysis of data of seven patients with oral and maxillofacial tumors who underwent surgery between January 2019 and January 2021 using a combination of mixed reality and surgical navigation. Virtual surgical planning and navigation plan were based on preoperative CT datasets. Through IGT-Link port, mixed reality workstation was synchronized with surgical navigation, and surgical planning data were transferred to the mixed reality workstation. Osteotomy lines were marked with the aid of both surgical navigation and mixed reality images visualized through HoloLens. Frozen section examination was used to ensure negative surgical margins. Postoperative CT datasets were obtained 1 week after the surgery, and chromatographic analysis of virtual osteotomies and actual osteotomies was carried out. Patients received standard oncological postoperative follow-up.ResultsOf the seven patients, four had maxillary tumors and three had mandibular tumors. There were total of 13 osteotomy planes. Mean deviation between the planned osteotomy plane and the actual osteotomy plane was 1.68 ± 0.92 mm; the maximum deviation was 3.46 mm. Chromatographic analysis showed error of ≤3 mm for 80.16% of the points. Mean deviations of maxillary and mandibular osteotomy lines were approximate (1.60 ± 0.93 mm vs. 1.86 ± 0.93 mm). While five patients had benign tumors, two had malignant tumors. Mean deviations of osteotomy lines was comparable between patients with benign and malignant tumors (1.48 ± 0.74 mm vs. 2.18 ± 0.77 mm). Intraoperative frozen pathology confirmed negative resection margins in all cases. No tumor recurrence or complications occurred during mean follow-up of 15.7 months (range, 6-26 months).ConclusionThe combination of mixed reality technology and surgical navigation appears to be feasible, safe, and effective for tumor resection in the oral and maxillofacial region.

Purpose: To detect lung metastases, we conducted a retrospective study to improve patient prognosis.Methods: Hypertension patients with ocular metastases (OM group; n = 58) and without metastases (NM group; n = 1,217) were selected from individuals with lung cancer admitted to our hospital from April 2005 to October 2019. The clinical characteristics were compared by Student's t-test and chi-square test. Independent risk factors were identified by binary logistic regression, and their diagnostic value evaluated by receiver operating characteristic curve analysis.Results: Age and sex did not differ significantly between OM and NM groups; There were significant differences in pathological type and treatment. Adenocarcinoma was the main pathological type in the OM group (67.24%), while squamous cell carcinoma was the largest proportion (46.43%) in the NM group, followed by adenocarcinoma (34.10%). The OM group were treated with chemotherapy (55.17%), while the NM group received both chemotherapy (39.93%) and surgical treatment (37.06%). Significant differences were detected in the concentrations of cancer antigen (CA)−125, CA-199, CA-153, alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), cytokeratin fraction 21-1 (CYFRA21-1), total prostate-specific antigen, alkaline phosphatase, and hemoglobin (Student's t-test). Binary logistic regression analysis indicated that CA-199, CA-153, AFP, CEA, and CYRFA21-1 were independent risk factors for lung cancer metastasis. AFP (98.3%) and CEA (89.3%) exhibited the highest sensitivity and specificity, respectively, while CYRFA21-1 had the highest area under the ROC curve value (0.875), with sensitivity and specificity values of 77.6 and 87.0%, respectively. Hence, CYFRA21-1 had the best diagnostic value.

Background: The American Heart Association (AHA) defined cardiovascular health in terms of four behaviors (smoking, diet, physical activity, body weight) and three factors (plasma glucose, cholesterol, blood pressure). By this definition, the prevalence of ideal cardiovascular health behaviors and factors is negatively correlated with all-cause mortality and risks of cardiovascular and cerebrovascular diseases and malignancy. We analyzed the trends in cardiovascular and cerebrovascular health behaviors and factors in the population of the KaiLuan study for 2006–2011, reported the results, and provided evidence for prevention.Methods and Results: We calculated the prevalence of cardiovascular and cerebrovascular health behaviors and factors from KaiLuan data for 2006–2007, 2008–2009, and 2010–2011. The prevalence of ideal cardiovascular and cerebrovascular health behaviors and factors is low in the KaiLuan population.Conclusions: The prevalence of ideal cardiovascular and cerebrovascular health behaviors and factors is low in the KaiLuan population.Clinical Trial Registration:http://www.chictr.org/cn/proj/show.aspx?proj=1441, unique identifier: ChiCTR-TNC-11001489.

BackgroundClear cell renal cell carcinoma (ccRCC) with venous tumor thrombus (VTT) is associated with a poor clinical outcome. Although several studies have examined the genomic features of ccRCC, the genetic profile of VTT along with its matched primary tumor has not been fully elucidated.Materials and methodsSamples of VTT tissues and matched primary tumor tissues from ccRCC patients (n = 25), as well as primary tumor tissues from patients without VTT (n = 25) were collected and analyzed using whole-exome sequencing. Four additional ccRCC patients who were unfit for surgery were treated with an anti-programmed death receptor-1 (PD-1) monoclonal antibody (Toripalimab, 240 mg, Q3W, IV).ResultsBy comparing the primary kidney tumors from ccRCC patients with or without VTT, a relatively higher prevalence of BAP1 and KDM5C alterations were found in ccRCC patients with VTT, and these alterations were associated with worse overall survival in the kidney renal clear cell carcinoma (KIRC) database. Based on subclone analysis, VTT was predicted to primarily originate directly from the primary renal mass. A significantly higher prevalence of CELSR2 and TET2 alterations were identified in the VTTs compared with the matched primary tumors. An increased prevalence of DNA damage repair genes, especially those involved in homologous recombination repair and non-homologous end joining, was found in ccRCC patients with VTT. Notably, VTT was characterized by the increase incidence of copy number loss in the whole exome (p < 0.05), particularly in the chromosome 9 and 14 regions. Deletion of chromosome 9 and 14 was associated with worse survival, unfavorable clinical features, and the presence of an immunosuppressive microenvironment, which was characterized by higher infiltration of regulatory T cells, follicular helper T cells, and resting mast cells, but lower counts of resting CD4 memory T cells and CD8 positive T cells. A significantly lower count of CD4+ and CD8+ tumor-infiltrated lymphocytes was identified in the VTT samples comparing with matched primary tumor. Of note, three out of the four ccRCC patients with VTT in our cohort who were treated with the anti-PD-1 therapy exhibited remarkable remission in the renal mass but no notable shrinkage in the VTT mass.ConclusionOur study revealed the genetic profile of Chinese ccRCC patients with VTT, and identified multiple features associated with known poor outcomes, including gene alterations and copy number loss. The deletions in chromosomes 9 and 14, and the associated immunosuppressive microenvironment may indicate limited sensitivity to anti-PD-1/PD-L1 monotherapy in VTT.

Kluyveromyces marxianus is a promising host for producing bioethanol and heterologous proteins. It displays many superior traits to a conventional industrial yeast species, Saccharomyces cerevisiae, including fast growth, thermotolerance and the capacity to assimilate a wider variety of sugars. However, little is known about the mechanisms underlying the fast-growing feature of K. marxianus. In this study, we performed a comparative genomic analysis between K. marxianus and other Saccharomycetaceae species. Genes involved in flocculation, iron transport, and biotin biosynthesis have particularly high copies in K. marxianus. In addition, 60 K. marxianus specific genes were identified, 45% of which were upregulated during cultivation in rich medium and these genes may participate in glucose transport and mitochondrion related functions. Furthermore, the transcriptomic analysis revealed that under aerobic condition, normalized levels of genes participating in TCA cycles, respiration chain and ATP biosynthesis in the lag phase were higher in K. marxianus than those in S. cerevisiae. Levels of highly copied genes, genes involved in the respiratory chain and mitochondrion assembly, were upregulated in K. marxianus, but not in S. cerevisiae, in later time points during cultivation compared with those in the lag phase. Notably, during the fast-growing phase, genes involved in the respiratory chain, ATP synthesis and glucose transport were co-upregulated in K. marxianus. A few shared motifs in upstream sequences of relevant genes might result in the co-upregulation. Specific features in the co-regulations of gene expressions might contribute to the fast-growing phenotype of K. marxianus. Our study underscores the importance of genome-wide rewiring of the transcriptional network during evolution.

Selenite and phosphate share similar uptake mechanisms, as a phosphate transporter is involved in the selenite uptake process. However, the mechanism by which selenium (Se) transformation in plants is mediated by phosphorus (P) remains unclear. In this hydroponic study, the absorption, translocation, and biotransformation of Se in selenite-treated rice (Oryza sativa L.) seedlings were investigated under varying P nutrient status. The results showed that P-deficient cultivation increased the Se concentration in roots with Se-only treatment by 2.1 times relative to that of the P-normal condition. However, co-treating roots with additional P caused the Se concentration to decline by 20 and 73% compared to Se treatment alone under P-normal and P-deficient cultivation, respectively. A similar pattern was also observed in Se uptake by rice roots. With an Se-transfer factor elevated by 4.4 times, the shoot Se concentration was increased by 44% with additional P supply compared to the concentration under Se-only treatment of P deficiency; however, no significant differences were observed regarding P-normal cultivation. P deficiency increased the Se percentage by 28% within the cell wall, but reduced it by 60% in the soluble fraction of Se-only treated roots relative to that of the P-normal condition. Contrarily, compared with the Se-only treatment under P deficiency, additional P supply enhanced Se storage in the root soluble fraction by 1.3 times. The opposite tendency was observed for rice shoots. Moreover, P deficiency reduced the proportion of SeMet by 22%, but increased MeSeCys by 1.3 times in Se-only treated roots compared to those under the P-normal condition. Interestingly, MeSeCys was not detected when additional P was added to the two cultivation conditions. Unlike in the roots, only SeMet was generally detected in the rice shoots. The results demonstrate that the P nutrient status strongly affects the Se biofortification efficiency in rice seedlings by altering the Se subcellular distribution and speciation.

Background and Purpose: Hyperhomocysteinemia (Hhcy) is a well-known risk factor for ischemic stroke. However, the role of Hhcy in the clinical outcome of ischemic stroke has not been fully elucidated. In addition, previous studies have found that Hhcy was implicated in the disruption of the blood-brain barrier, which may increase the risk of hemorrhagic transformation (HT) after thrombolysis. Thus, the aim of this study was to investigate the effect of Hhcy on the clinical outcome and HT after thrombolysis in ischemic stroke patients.Methods: Patients who were diagnosed with ischemic stroke and received intravenous thrombolytic therapy between January 2016 and September 2018 were included in this study. Multivariate logistic regression analysis was used to assess the association between Hhcy, clinical outcome, and HT after thrombolysis. Furthermore, the potential interaction between Hhcy and hypertension on the clinical outcome and HT after thrombolysis was also assessed.Results: Of 568 patients, 455 (80.1%) had Hhcy, 66 (11.6%) had HT, and 219 (38.6%) had poor outcome. Patients with Hhcy had a higher incidence of poor outcome than the patients with non-Hhcy (40.9 vs. 29.2%, p = 0.022). However, there was no significant difference in the incidence of HT (11.9 vs. 10.6%, p = 0.711) between patients with Hhcy and non-Hhcy. After adjustment for major covariates, multivariate logistic regression analysis disclosed that Hhcy was independently associated with increased risk of poor outcome (OR = 1.760; 95% CI: 1.069–2.896) but was not associated with the risk of HT (OR = 1.017; 95% CI: 0.495–2.087). In addition, we found no significant interaction between Hhcy and hypertension on the clinical outcome (p = 0.513) or HT (p = 0.170) after thrombolysis.Conclusion: We found that Hhcy was an independent risk factor for poor outcome, but not an independent risk factor for HT after thrombolysis in ischemic stroke patients. In addition, there was no significant interaction of Hhcy and hypertension on the clinical outcome or HT after thrombolysis.

Abnormal corticostriatal resting-state functional connectivity (rsFC) has been implicated in the neuropathology of multiple sclerosis. The striatum, a component of the basal ganglia, is involved in diverse functions including movement, cognition, emotion, and limbic information processing. However, the brain circuits of the striatal subregions contributing to the changes in rsFC in relapsing–remitting multiple sclerosis (RRMS) patients remain unknown. We used six subdivisions of the striatum in each hemisphere as seeds to investigate the rsFC of striatal subregions between RRMS patients and matched healthy controls (HCs). In addition, we also scanned a subcohort of RRMS patients after an average of 7 months to test the reliability of our findings. Compared to HCs, we found significantly increased dorsal caudal putamen (DCP) connectivity with the premotor area, dorsal lateral prefrontal cortex (DLPFC), insula, precuneus, and superior parietal lobule, and significantly increased connectivity between the superior ventral striatum and posterior cingulate cortex (PCC) in RRMS patients following both scans. Furthermore, we found significant associations between the Expanded Disability Status Scale and the rsFC of the left DCP with the DLPFC and parietal areas in RRMS patients. Our results suggest that the DCP may be a critical striatal subregion in the pathophysiology of RRMS.

Introduction: The presence of minimal residual disease (MRD) after curativeintent surgery for early-stage cancers is associated with disease recurrence. Circulating tumour deoxyribonucleic acid (ctDNA) has emerged as a promising biomarker for MRD assessment in patients with colorectal cancer (CRC) who have undergone surgery or completed adjuvant therapy. MRD tests are already available for use in clinics; however, treatment decisions following MRD results obtained in routine practice are infrequently described. Methods: In this observational study, we report on the real-world clinical use of Guardant Reveal, a validated tissue-free MRD assay, in the first 215 consecutive patients (279 samples) with CRC tested in Asia and the Middle East. Results: Overall, 22% of patients had ctDNA detected in their first MRD test, and the frequency of ctDNA positivity increased with increasing tumour stage. 132 samples were tested with an earlier version of Guardant Reveal, one that assessed both genomic and epigenomic features. An updated version of the assay assesses only ctDNA methylation data and was used for the remaining 147 samples. In patients with stage II CRC, 71% of tests were ordered within 12 weeks after tumour resection, while for patients with stage III disease, 69% of tests were ordered after completion of all curative-intent treatment. Discussion: Clinical cases utilizing tissue-free MRD assessment are described. [ABSTRACT FROM AUTHOR]

Background: Anoikis is a form of programmed cell death or programmed cell death(PCD) for short. Studies suggest that anoikis involves in the decisive steps of tumor progression and cancer cellmetastasis and spread, but what part it plays in bladder cancer remains unclear. We sought to screen for anoikis-correlated long non-coding RNA (lncRNA) so that we can build a risk model to understand its ability to predict bladder cancer prognosis and the immune landscape. Methods: We screened seven anoikis-related lncRNAs (arlncRNAs) from The Cancer Genome Atlas (TCGA) and designed a risk model. It was validated through ROC curves and clinicopathological correlation analysis, and demonstrated to be an independent factor of prognosis prediction by uni-and multi-COX regression. In the meantime, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, immune infiltration, and half-maximal inhibitory concentration prediction (IC50) were implemented with the model. Moreover, we divided bladder cancer patients into three subtypes by consensus clustering analysis to further study the differences in prognosis, immune infiltration level, immune checkpoints, and drug susceptibility. Result: We designed a risk model of seven arlncRNAs, and proved its accuracy using ROC curves. COX regression indicated that the model might be an independent prediction factor of bladder cancer prognosis. KEGG enrichment analysis showed it was enriched in tumors and immune-related pathways among the people at high risk. Immune correlation analysis and drug susceptibility results indicated that it had higher immune infiltration and might have a better immunotherapy efficacy for high-risk groups. Of the three subtypes classified by consensus clustering analysis, cluster 3 revealed a positive prognosis, and cluster 2 showed the highest level of immune infiltration and was sensitive to most chemistries. This is helpful for us to discover more precise immunotherapy for bladder cancer patients. [ABSTRACT FROM AUTHOR]

The gallbladder (GB) microbiota plays critical roles in mammalian metabolism and immune homeostasis, and its relationship with human disease has been extensively studied over the past decade. However, very little is known about the interplay between GB microbiota and the immune functions of teleost fish, the earliest bony vertebrate with a GB. Therefore, this study sought to investigate the composition of the teleost GB microbiota and the potential mechanisms through which it affects mucosal immunity. In our results, we found that the GB mucosa (GM) and bile bacterial community shared a similar microbiological composition with that of the gut mucosa in naïve individuals. IHNV infection induced a profound GB inflammation and disrupted their microbial homeostasis followed by a strong anti-bacterial response. Interestingly, beneficial bacteria from the Lactobacillales order showed a significant increase in the abundance of the bile microbial community, whereas the structure of the Mycoplasmatales order in the gut microbial community was markedly changed. All in all, our study characterized the structure of the GB microbial ecosystem in teleost fish, and the fish GB microbiome shared a high similarity with the gut microbiota. More importantly, our findings offer solid evidence that the teleost GB evolved immune functions to preserve its mucosal microbial homeostasis, suggesting that both the microbiota and mucosal immunity of the GB might have coevolved in early vertebrates. [ABSTRACT FROM AUTHOR]

In insects, the shedding of the old exoskeleton is accomplished through ecdysis which is typically followed by the expansion and tanning of the new cuticle. Four neuropeptides, eclosion hormone (EH), ecdysis triggering hormone (ETH), crustacean cardioactive peptide (CCAP) and bursicon (Bur) are known to control ecdysis. However, the regulation of these neuropeptide genes is still poorly understood. Here, we report that in the red flour beetle (RFB) Tribolium castaneumand the fall armyworm (FAW) Spodoptera frugiperda, knockdown or knockout of the SoxC gene caused eclosion defects. The expansion and tanning of wings were not complete. In both RFB and FAW, the knockdown or knockout of SoxC resulted in a decrease in the expression of EH gene. Electrophoretic mobility shift assays revealed that the SfSoxC protein directly binds to a motif present in the promoter of SfEH. The luciferase reporter assays in Sf9 cells confirmed these results. These data suggest that transcription factor SoxC plays a key role in ecdysteroid induction of genes coding for neuropeptides such as EH involved in the regulation of insect eclosion. [ABSTRACT FROM AUTHOR]

Brain disorders, including stroke, Alzheimer's disease, depression, and chronic pain, are difficult to effectively treat. These major brain disorders have high incidence and mortality rates in the general population, and seriously affect not only the patient's quality of life, but also increases the burden of social medical care. Aerobic physical exercise is considered an effective adjuvant therapy for preventing and treating major brain disorders. Although the underlying regulatory mechanisms are still unknown, systemic processes may be involved. Here, this review aimed to reveal that aerobic physical exercise improved depression and several brain functions, including cognitive functions, and provided chronic pain relief. We concluded that aerobic physical exercise helps to maintain the regulatory mechanisms of brain homeostasis through anti-inflammatory mechanisms and enhanced synaptic plasticity and inhibition of hippocampal atrophy and neuronal apoptosis. In addition, we also discussed the cross-system mechanisms of aerobic exercise in regulating imbalances in brain function, such as the "bone-brain axis." Furthermore, our findings provide a scientific basis for the clinical application of aerobic physical exercise in the fight against brain disorders. [ABSTRACT FROM AUTHOR]

In order to enhance the utilization of alkaline carbide slag (CS) and steel slag (SS) in solid waste-based cementitious materials (SWBCM). In this study, slag (GGBS) was utilized as the primary material, phosphogypsum (PG) as the sulfat activator, and carbide slag (CS) and steel slag (SS) as the alkali activators to prepare carbide slag-steel slag-slag-phosphogypsum composite cementitious material (CS-SS-GGBS-PG). The impact of partial SS (mass fraction) substitution by CS on the flowability, mechanical properties, softening coefficient, pore solution pH value, hydration heat, and microstructure of CS-SS-GGBS-PG was studied. The hydration products, microstructure, and pore structure of CS-SS-GGBS-PG were studied via XRD, FTIR, TG-DTG, SEM, and MIP. The results show that CS replacement with SS decreases the flowability of CS-SS-GGBS-PG compared to the specimen without CS doping (A0). The addition of CS provides an abundance of Ca2+ and OH− to facilitate the hydration reaction in the system, prompting CS-SS-GGBS-PG to form more C-(A)-S-H gels and ettringite (AFt) in the early stages. This significantly enhances the 3 and 7 days strength of CS-SS-GGBS-PG. Compared to A0, the sample group with 5% CS substitution for SS showed a respective increase of 400% and 1,150% in flexural strength at 3 and 7 days, and an increase of 800% and 1,633% in compressive strength. However, if CS is substituted for SS in excess, the system’s late hydration process will be inhibited, increasing the volume of harmful pores in the specimen’s microstructure and lowering its degree of compactness. This leads to a decrease of 28 days of strength and a deterioration of the water resistance of CS-SS-GGBS-PG. It is advised that the blending ratio of SS to CS be 3:1 in order to maintain equilibrium between the early strength enhancement of CS-SS-GGBS-PG and the stability of strength and water resistance in the latter stage. This study has a positive impact on improving the utilization of CS and SS in SWBCM, reducing the dependence of SWBCM on traditional high-angstrom chemical alkali activators, and promoting the development of SWBCM.

Background: Lung adenocarcinoma (LUAD) remains a lethal disease worldwide, with numerous studies exploring its potential prognostic markers using traditional RNA sequencing (RNA- seq) data. However, it cannot detect the exact cellular and molecular changes in tumor cells. This study aimed to construct a prognostic model for LUAD using single-cell RNA- seq (scRNA- seq) and traditional RNA- seq data. Methods: Bulk RNA- seq data were downloaded from The Cancer Genome Atlas (TCGA) database. LUAD scRNA- seq data were acquired from Gene Expression Omnibus (GEO) database. The uniform manifold approximation and projection (UMAP) was used for dimensionality reduction and cluster identification. Weighted Gene Correlation Network Analysis (WGCNA) was utilized to identify key modules and differentially expressed genes (DEGs). The non-negative Matrix Factorization (NMF) algorithm was used to identify different subtypes based on DEGs. The Cox regression analysis was used to develop the prognostic model. The characteristics of mutation landscape, immune status, and immune checkpoint inhibitors (ICIs) related genes between different risk groups were also investigated. Results: scRNA- seq data of four samples were integrated to identify 13 clusters and 9cell types. After applying differential analysis, NK cells, bladder epithelial cells, and bronchial epithelial cells were identified as significant cell types. Overall, 329 DEGs were selected for prognostic model construction through differential analysis and WGCNA. Besides, NMF identified two clusters based on DEGs in the TCGA cohort, with distinct prognosis and immune characteristics being observed. We developed a prognostic model based on the expression levels of six DEGs. A higher risk score was significantly correlated with poor survival outcomes but was associated with a more frequent TP53 mutation rate, higher tumor mutation burden (TMB), and up-regulation of PD-L1. Two independent external validation cohorts were also adopted to verify our results, with consistent results observed in them. Conclusion: This study constructed and validated a prognostic model for LUAD by integrating 10× scRNA- seq and bulk RNA- seq data. Besides, we observed two distinct subtypes in this population, with different prognosis and immune characteristics. [ABSTRACT FROM AUTHOR]

The gene kcnma1 encodes the α-subunit of high-conductance calcium- and voltage-dependent K+ (BK) potassium channel. With the development of generation gene sequencing technology, many KCNMA1 mutants have been identified and are more closely related to generalized epilepsy and paroxysmal dyskinesia. Here, we performed a genetic screen of 26 patients with febrile seizures and identified a novel mutation of KCNMA1 (E155Q). Electrophysiological characterization of different KCNMA1 mutants in HEK 293T cells, the previously-reported R458T and E884K variants (not yet determined), as well as the newly-found E155Q variant, revealed that the current density amplitude of all the above variants was significantly smaller than that of the wild-type (WT) channel. All the above variants caused a positive shift of the I-V curve and played a role through the loss-of-function (LOF) mechanism. Moreover, the β4 subunit slowed down the activation of the E155Q mutant. Then, we used kcnma1 knockout (BK KO) mice as the overall animal model of LOF mutants. It was found that BK KO mice had spontaneous epilepsy, motor impairment, autophagic dysfunction, abnormal electroencephalogram (EEG) signals, as well as possible anxiety and cognitive impairment. In addition, we performed transcriptomic analysis on the hippocampus and cortex of BK KO and WT mice. We identified many differentially expressed genes (DEGs). Eight dysregulated genes [i.e., (Gfap and Grm3 associated with astrocyte activation) (Alpl and Nlrp10 associated with neuroinflammation) (Efna5 and Reln associated with epilepsy) (Cdkn1a and Nr4a1 associated with autophagy)] were validated by RT-PCR, which showed a high concordance with transcriptomic analysis. Calcium imaging results suggested that BK might regulate the autophagy pathway from TRPML1. In conclusion, our study indicated that newly-found point E155Q resulted in a novel loss-of-function variant and the dysregulation of gene expression, especially astrocyte activation, neuroinflammation and autophagy, might be the molecular mechanism of BK-LOF meditated epilepsy. [ABSTRACT FROM AUTHOR]

Mycobacterium avium subsp. paratuberculosis (MAP) is the pathogen of Johne's disease (paratuberculosis), which mainly causes chronic infectious granulomatous enteritis in ruminants and has brought huge economic losses to animal husbandry. As a specific intracellular pathogen, when MAP invades the body, it is internalized by macrophages where it is able to replicate by inhibition of the phagosome maturation, escaping the host immune system and surviving, which leads to the spread of the disease. More recent studies have shown that circRNA is involved in many pathological and physiological processes of the body as the molecular sponge of miRNA, the scaffold of RNA binding protein and having the characteristic of being able to translate into protein. In this study, the mRNA and circRNA expression profiles of MAP-infected bovine monocyte-macrophages and uninfected bovine cells were analyzed by high-throughput sequencing. A total of 618 differentially expressed mRNA were screened out, including 322 upregulated mRNA and 296 downregulated mRNA. In addition, the analysis of circRNA differential expression profile showed 39 differentially expressed genes including 12 upregulated and 27 downregulated genes. Moreover, differential genes belonging to cytokine activity, chemokine activity, inflammatory reaction, apoptosis, and other functional groups related to macrophage immune response were significantly enriched in Gene Ontology (GO). Multiple signal pathways including NF-κB, MAPK, Toll-like receptor, IL-17, JAK-STAT, and other signaling pathways related to activating macrophage immune response were significantly enriched in Kyoto Encyclopedia of Genes and Genomes (KEGG). In addition, RT-qPCR technology verified the accuracy of the mRNA sequencing results. In this study, we have obtained the transcriptome information of mRNA and circRNA of bovine monocyte-macrophage infected with MAP. These results will provide data support for the further study of mRNA–miRNA–circRNA network and immune escape mechanism of MAP and will enrich the knowledge of the molecular immune mechanisms of Johne's disease as well. [ABSTRACT FROM AUTHOR]

Therapeutic options for metastatic CRC (mCRC) have changed significantly in recent years, greatly increasing the complexity of therapeutic decision-making. Although oncology guidelines have helped improve the care process, guidelines may also limit the flexibility to individualize in-clinic decision-making. This consensus paper addresses specific gaps in the current international guidelines to assist Taiwanese colon and rectal experts make specific therapeutic choices. Over 3 years and three meetings with selected experts on "real-world" Taiwanese practice patterns for mCRC, consensus was achieved. The experts also discussed specific questions during in-depth one-on-one consultation. Outcomes of the discussion were then correlated with published evidence by an independent medical writer. The final consensus includes clinically implementable recommendations to provide guidance in treating Taiwanese mCRC patients. The consensus includes criteria for defining fit and unfit intensive treatment patients, treatment goals, treatment considerations of molecular profiles, treatment consideration, and optimal treatment choices between different patient archetypes, including optimal treatment options based on RAS , BRAF , and microsatellite instability (MSI) status. This consensus paper is the second in the Taiwan Society of Colon and Rectal Surgeons (TSCRS) Consensus series to address unmet gaps in guideline recommendations in lieu of Taiwanese mCRC management. Meticulous discussions with experts, the multidisciplinary nature of the working group, and the final drafting of the consensus by independent medical professionals have contributed to the strong scientific value of this consensus. [ABSTRACT FROM AUTHOR]

Psychiatry faces fundamental challenges with regard to mechanistically guided differential diagnosis, as well as prediction of clinical trajectories and treatment response of individual patients. This has motivated the genesis of two closely intertwined fields: (i) Translational Neuromodeling (TN), which develops "computational assays" for inferring patient-specific disease processes from neuroimaging, electrophysiological, and behavioral data; and (ii) Computational Psychiatry (CP), with the goal of incorporating computational assays into clinical decision making in everyday practice. In order to serve as objective and reliable tools for clinical routine, computational assays require end-to-end pipelines from raw data (input) to clinically useful information (output). While these are yet to be established in clinical practice, individual components of this general end-to-end pipeline are being developed and made openly available for community use. In this paper, we present the T ranslational A lgorithms for P sychiatry- A dvancing S cience (TAPAS) software package, an open-source collection of building blocks for computational assays in psychiatry. Collectively, the tools in TAPAS presently cover several important aspects of the desired end-to-end pipeline, including: (i) tailored experimental designs and optimization of measurement strategy prior to data acquisition, (ii) quality control during data acquisition, and (iii) artifact correction, statistical inference, and clinical application after data acquisition. Here, we review the different tools within TAPAS and illustrate how these may help provide a deeper understanding of neural and cognitive mechanisms of disease, with the ultimate goal of establishing automatized pipelines for predictions about individual patients. We hope that the openly available tools in TAPAS will contribute to the further development of TN/CP and facilitate the translation of advances in computational neuroscience into clinically relevant computational assays. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the role of contrast-enhanced magnetic resonance imaging (CE-MRI) radiomics for pretherapeutic prediction of the response to transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). Methods: One hundred and twenty-two HCC patients (objective response, n = 63; non-response, n = 59) who received CE-MRI examination before initial TACE were retrospectively recruited and randomly divided into a training cohort (n = 85) and a validation cohort (n = 37). All HCCs were manually segmented on arterial, venous and delayed phases of CE-MRI, and total 2367 radiomics features were extracted. Radiomics models were constructed based on each phase and their combination using logistic regression algorithm. A clinical-radiological model was built based on independent risk factors identified by univariate and multivariate logistic regression analyses. A combined model incorporating the radiomics score and selected clinical-radiological predictors was constructed, and the combined model was presented as a nomogram. Prediction models were evaluated by receiver operating characteristic curves, calibration curves, and decision curve analysis. Results: Among all radiomics models, the three-phase radiomics model exhibited better performance in the training cohort with an area under the curve (AUC) of 0.838 (95% confidence interval (CI), 0.753 - 0.922), which was verified in the validation cohort (AUC, 0.833; 95% CI, 0.691 - 0.975). The combined model that integrated the three-phase radiomics score and clinical-radiological risk factors (total bilirubin, tumor shape, and tumor encapsulation) showed excellent calibration and predictive capability in the training and validation cohorts with AUCs of 0.878 (95% CI, 0.806 - 0.950) and 0.833 (95% CI, 0.687 - 0.979), respectively, and showed better predictive ability (P = 0.003) compared with the clinical-radiological model (AUC, 0.744; 95% CI, 0.642 - 0.846) in the training cohort. A nomogram based on the combined model achieved good clinical utility in predicting the treatment efficacy of TACE. Conclusion: CE-MRI radiomics analysis may serve as a promising and noninvasive tool to predict therapeutic response to TACE in HCC, which will facilitate the individualized follow-up and further therapeutic strategies guidance in HCC patients. [ABSTRACT FROM AUTHOR]

Angiogenesis has been identified as one of the hallmarks of cancer and aggravates cancer development and progression. Accumulating evidence indicated that long noncoding RNAs (lncRNAs) are powerful factors in regulating various cancer behaviors. The aim of this study is to verify the function and potential mechanisms of lncRNA NEAT1 in progression and angiogenesis of esophageal squamous cell carcinoma (ESCC). We found that NEAT1 was overexpressed in ESCC tissues and correlated with clinical characteristics of patients. Silence of NEAT1 inhibited proliferation, migration, invasion and angiogenesis of ESCC cells. High throughput sequencing and western blotting revealed that NEAT1 regulated MDM2/p53 pathway. Rescue of MDM2 restored the effect of NEAT1 on progression and angiogenesis of ESCC cells. Nude mice xenograft models further validated the role of NEAT1 in vivo. Importantly, NEAT1 functioned as a competing endogenous RNA for miR-590-3p to regulate MDM2 expression and miR-590-3p acted as a tumor suppressor in ESCC progression and angiogenesis. These findings suggested that NEAT1/miR-590-3p/MDM2 axis might serve as potential therapeutic targets for ESCC patients. [ABSTRACT FROM AUTHOR]

Background: Bladder cancer (BLCA) is the 11th most common malignancy worldwide. Although significant improvements have been made in screening, diagnosis, and precise management in recent years, the prognosis of BLCA remains bleak. Objectives: This study aimed to investigate the prognostic significance of tumor-infiltrating immune cells and construct ceRNA networks in BLCA patients. Methods: The expression data of BLCA patients were obtained from The Cancer Genome Atlas (TCGA) database. A competing endogenous RNA (ceRNA) network was constructed to identify the hub genes involved in the prognosis of BLCA. The CIBERSORT algorithm was utilized to investigate the infiltration levels of 22 subsets of immune cells. Ultimately, the nomogram was generated to visualize the survival probability of each patient, with the calibration curve being performed to assess its performance. Furthermore, the Pearson correlation test was used to explore the correlation between the identified hub genes in the ceRNA network and the prognostic-related immune cells. Results: A total of eight elements in the ceRNA network were considered as key members and correlated with the prognosis of BLCA, including ELN , SREBF1 , DSC2 , TTLL7 , DIP2C , SATB1 , hsa-miR-20a-5p , and hsa-miR-29c-3p. T cells CD8, T cells follicular helper (Tfh), and neutrophils were identified as independent prognostic factors in BLCA. The co-expression analysis showed that there was a significant correlation between the identified hub genes and immune cells. Conclusion: Our results suggest that the mechanism of hsa-miR-29c-3p regulates the expression of ELN and DSC2 , and the infiltration of Tfh and neutrophils might play pivotal roles in the progression of BLCA. [ABSTRACT FROM AUTHOR]