The genomic basis of childhood T-lineage acute lymphoblastic leukaemia.

T-lineage acute lymphoblastic leukaemia (T-ALL) is a high-risk tumour1 that has eluded comprehensive genomic characterization, which is partly due to the high frequency of noncoding genomic alterations that result in oncogene deregulation2,3. Here we report an integrated analysis of genome and transcriptome sequencing of tumour and remission samples from more than 1,300 uniformly treated children with T-ALL, coupled with epigenomic and single-cell analyses of malignant and normal T cell precursors. This approach identified 15 subtypes with distinct genomic drivers, gene expression patterns, developmental states and outcomes. Analyses of chromatin topology revealed multiple mechanisms of enhancer deregulation that involve enhancers and genes in a subtype-specific manner, thereby demonstrating widespread involvement of the noncoding genome. We show that the immunophenotypically described, high-risk entity of early T cell precursor ALL is superseded by a broader category of 'early T cell precursor-like' leukaemia. This category has a variable immunophenotype and diverse genomic alterations of a core set of genes that encode regulators of hematopoietic stem cell development. Using multivariable outcome models, we show that genetic subtypes, driver and concomitant genetic alterations independently predict treatment failure and survival. These findings provide a roadmap for the classification, risk stratification and mechanistic understanding of this disease.

Blinatumomab for MRD-Negative Acute Lymphoblastic Leukemia in Adults.

BACKGROUND: Many older adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) have a relapse despite having a measurable residual disease (MRD)-negative complete remission with combination chemotherapy. The addition of blinatumomab, a bispecific T-cell engager molecule that is approved for the treatment of relapsed, refractory, and MRD-positive BCP-ALL, may have efficacy in patients with MRD-negative remission. METHODS: In a phase 3 trial, we randomly assigned patients 30 to 70 years of age with BCR::ABL1-negative BCP-ALL (with :: indicating fusion) who had MRD-negative remission (defined as <0.01% leukemic cells in bone marrow as assessed on flow cytometry) after induction and intensification chemotherapy to receive four cycles of blinatumomab in addition to four cycles of consolidation chemotherapy or to receive four cycles of consolidation chemotherapy alone. The primary end point was overall survival, and relapse-free survival was a secondary end point. RESULTS: The data and safety monitoring committee reviewed the results from the third efficacy interim analysis and recommended that they be reported. Complete remission with or without full count recovery was observed in 395 of 488 enrolled patients (81%). Of the 224 patients with MRD-negative status, 112 were assigned to each group. The characteristics of the patients were balanced between the groups. At a median follow-up of 43 months, an advantage was observed in the blinatumomab group as compared with the chemotherapy-only group with regard to overall survival (at 3 years: 85% vs. 68%; hazard ratio for death, 0.41; 95% confidence interval [CI], 0.23 to 0.73; P = 0.002), and the 3-year relapse-free survival was 80% with blinatumomab and 64% with chemotherapy alone (hazard ratio for relapse or death, 0.53; 95% CI, 0.32 to 0.87). A higher incidence of neuropsychiatric events was reported in the blinatumomab group than in the chemotherapy-only group. CONCLUSIONS: The addition of blinatumomab to consolidation chemotherapy in adult patients in MRD-negative remission from BCP-ALL significantly improved overall survival. (Funded by the National Institutes of Health and others; E1910 ClinicalTrials.gov number, NCT02003222.).

Ectoine maintains the flavor and nutritional quality of broccoli during postharvest storage.

The bacterial derived osmolyte ectoine has been shown to stabilize cell structure and function, a property that may help to extend the shelf life of broccoli. The impact of ectoine on broccoli stored for 4 d at 20 °C and 90% relative humidity was investigated. Results indicated that 0.20% ectoine treatment maintained the quality of broccoli, by reducing rate of respiration and ethylene generation, while increasing the levels of total phenolics, flavonoids, TSS, soluble protein, and vitamin C, relative to control. Headspace-gas chromatography-mass spectrometry, transcriptomic and metabolomic analyses revealed that ectoine stabilized aroma components in broccoli by maintaining level of volatile compounds and altered the expression of genes and metabolites associated with sulfur metabolism, as well as fatty acid and amino acid biosynthesis pathways. These findings provide a greater insight into how ectoine preserves the flavor and nutritional quality of broccoli, thus, extending its shelf life.

Bioactive sulforaphane from cruciferous vegetables: advances in biosynthesis, metabolism, bioavailability, delivery, health benefits, and applications.

Chronic inflammation-induced diseases (CID) are the dominant cause of death worldwide, contributing to over half of all global deaths. Sulforaphane (SFN) derived from cruciferous vegetables has been extensively studied for its multiple functional benefits in alleviating CID. This work comprehensively reviewed the biosynthesis, metabolism, bioavailability, delivery, health benefits, and applications of SFN and its potential mechanisms against CID (e.g., cancer, obesity, type 2 diabetes, et al.), and neurological disorders based on a decade of research. SFN exerts its biological functions through the hydrolysis of glucosinolates by gut microbiota, and exhibits rapid metabolism and excretion characteristics via metabolization of mercapturic acid pathway. Microencapsulation is an important way to improve the stability and targeted delivery of SFN. The health benefits of SNF against CID are attributed to the multiple regulatory mechanisms including modulating oxidative stress, inflammation, apoptosis, immune response, and intestinal homeostasis. The clinical applications of SFN and related formulations show promising potential; however, further exploration is required regarding the sources, dosages, toxicity profiles, and stability of SFN. Together, SFN is a natural product with great potential for development and application, which is crucial for the development of functional food and pharmaceutical industries.

Comparison analysis of bioactive metabolites in soybean, pea, mung bean, and common beans: reveal the potential variations of their antioxidant property.

This study showed the significantly differences of basic nutrients and metabolite compounds in nine types of beans involved in soybean, mung bean, pea, and common beans. The metabolomics results showed that serval metabolites such as histidine, proline, 3-alanine, and myricetin which could be used to identify different beans. The random forest model showed that amino acid and fatty acid could be used as special indexes to distinguish different types of beans in practice. The different expressed metabolites among different types of beans were involved in various pathways including alanine, aspartate and glutamate metabolism, arginine and proline metabolism, and purine metabolism. The antioxidant activity was significantly different among different types of beans, and the contents of amino acid, coumarin, and polyphenol contributed the antioxidant activities of beans. Together, these results will provide a comprehensive understanding of metabolites in different types of beans and theoretical guideline for the future application of beans.

Association of leukemic molecular profile with efficacy of inotuzumab ozogamicin in adults with relapsed/refractory ALL.

ABSTRACT: The phase 3 INO-VATE trial demonstrated higher rates of remission, measurable residual disease negativity, and improved overall survival for patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) who received inotuzumab ozogamicin (InO) vs standard-of-care chemotherapy (SC). Here, we examined associations between genomic alterations and the efficacy of InO. Of 326 randomized patients, 91 (InO, n = 43; SC, n = 48) had samples evaluable for genomic analysis. The spectrum of gene fusions and other genomic alterations observed was comparable with prior studies of adult ALL. Responses to InO were observed in all leukemic subtypes, genomic alterations, and risk groups. Significantly higher rates of complete remission (CR)/CR with incomplete count recovery were observed with InO vs SC in patients with BCR::ABL1-like ALL (85.7% [6/7] vs 0% [0/5]; P = .0076), with TP53 alterations (100% [5/5] vs 12.5% [1/8]; P = .0047), and in the high-risk BCR::ABL1- (BCR::ABL1-like, low-hypodiploid, KMT2A-rearranged) group (83.3% [10/12] vs 10.5% [2/19]; P < .0001). This retrospective, exploratory analysis of the INO-VATE trial demonstrated potential for benefit with InO for patients with R/R ALL across leukemic subtypes, including BCR::ABL1-like ALL, and for those bearing diverse genomic alterations. Further confirmation of the efficacy of InO in patients with R/R ALL exhibiting the BCR::ABL1-like subtype or harboring TP53 alterations is warranted. This trial was registered at www.ClinicalTrials.gov as #NCT01564784.

High-efficient separation of deoxyribonucleic acid from pathogenic bacteria by hedgehog-inspired magnetic nanoparticles microextraction.

Efficient separation of deoxyribonucleic acid (DNA) through magnetic nanoparticles (MN) is a widely used biotechnology. Hedgehog-inspired MNs (HMN) possess a high-surface-area due to the distinct burr-like structure of hedgehog, but there is no report about the usage of HMN for DNA extraction. Herein, to improve the selection of MN and illustrate the performance of HMN for DNA separation, HMN and silica-coated Fe3O4 nanoparticles (Fe3O4@SiO2) were fabricated and compared for the high-efficient separation of pathogenic bacteria of DNA. Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) are typical Gram-negative and Gram-positive bacteria and are selected as model pathogenic bacteria. To enhance the extraction efficiency of two kinds of MNs, various parameters, including pretreatment, lysis, binding and elution conditions, have been optimized in detail. In most separation experiments, the DNA yield of HMN was higher than that of Fe3O4@SiO2. Therefore, a HMN-based magnetic solid-phase microextraction (MSPE) and quantitative real-time PCR (qPCR) were integrated and used to detect pathogenic bacteria in real samples. Interestingly, the HMN-based MSPE combined qPCR strategy exhibited high sensitivity with a limit of detection of 2.0 × 101 CFU mL-1 for E. coli and 4.0 × 101 CFU mL-1 for S. aureus in orange juice, and 2.8 × 102 CFU mL-1 for E. coli and 1.1 × 102 CFU mL-1 for S. aureus in milk, respectively. The performance of the proposed strategy was significantly better than that of commercial kit. This work could prove that the novel HMN could be applicable for the efficient separation of DNA from complex biological samples.

Neoadjuvant therapy for non-small cell lung cancer and esophageal cancer.

As the major malignant tumors in the chest, non-small cell lung cancer (NSCLC) and esophageal cancer (EC) bring huge health burden to human beings worldwide. Currently, surgery is still the mainstay for comprehensive treatment for NSCLC and EC, but the prognosis is still poor as the results of cancer recurrence and distant metastasis. Neoadjuvant therapy refers to a single or combined treatment before surgery, aiming to improve the therapeutic effects of the traditional therapies. Unfortunately, the clinical outcomes and effects of neoadjuvant therapy are still controversial due to its apparent advantages and disadvantages, and different patients may respond differentially to the same scheme of neoadjuvant therapy, which makes it urgent and necessary to develop personalized scheme of neoadjuvant therapy for different individuals. Therefore, this review summarizes the novel schemes and strategies of neoadjuvant therapy, which may help to significantly improve of life quality of patients suffering from chest-related malignancies.

Genomic determinants of response and resistance to inotuzumab ozogamicin in B-cell ALL.

ABSTRACT: Inotuzumab ozogamicin (InO) is an antibody-drug conjugate that delivers calicheamicin to CD22-expressing cells. In a retrospective cohort of InO-treated patients with B-cell acute lymphoblastic leukemia, we sought to understand the genomic determinants of the response and resistance to InO. Pre- and post-InO-treated patient samples were analyzed by whole genome, exome, and/or transcriptome sequencing. Acquired CD22 mutations were observed in 11% (3/27) of post-InO-relapsed tumor samples, but not in refractory samples (0/16). There were multiple CD22 mutations per sample and the mechanisms of CD22 escape included epitope loss (protein truncation and destabilization) and epitope alteration. Two CD22 mutant cases were post-InO hyper-mutators resulting from error-prone DNA damage repair (nonhomologous/alternative end-joining repair, or mismatch repair deficiency), suggesting that hypermutation drove escape from CD22-directed therapy. CD22-mutant relapses occurred after InO and subsequent hematopoietic stem cell transplantation (HSCT), suggesting that InO eliminated the predominant clones, leaving subclones with acquired CD22 mutations that conferred resistance to InO and subsequently expanded. Acquired loss-of-function mutations in TP53, ATM, and CDKN2A were observed, consistent with a compromise of the G1/S DNA damage checkpoint as a mechanism for evading InO-induced apoptosis. Genome-wide CRISPR/Cas9 screening of cell lines identified DNTT (terminal deoxynucleotidyl transferase) loss as a marker of InO resistance. In conclusion, genetic alterations modulating CD22 expression and DNA damage response influence InO efficacy. Our findings highlight the importance of defining the basis of CD22 escape and eradication of residual disease before HSCT. The identified mechanisms of escape from CD22-targeted therapy extend beyond antigen loss and provide opportunities to improve therapeutic approaches and overcome resistance. These trials were registered at www.ClinicalTrials.gov as NCT01134575, NCT01371630, and NCT03441061.

Phenotypes of patients with systemic sclerosis in the Chinese Han population: a cluster analysis.

OBJECTIVE: Systemic sclerosis (SSc) is a heterogeneous connective tissue disease that is commonly subdivided into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) based on the extent of skin involvement. This subclassification may not reflect the full range of clinical phenotypic variation. This study aimed to investigate clinical features and aggregation of patients with SSc in Chinese based on SSc manifestations and organ involvements, in order to achieve precise treatment of SSc early prevention of complications. METHODS: In total 287 SSc patients were included in this study. A cluster analysis was applied according to 13 clinical and serologic variables to determine subgroups of patients. Survival rates between obtained clusters and risk factors affecting prognosis were also compared. RESULT: In this study, six clusters were observed: cluster 1 (n = 66) represented the skin type, with all patients showing skin thickening. In cluster 2 (n = 56), most patients had vascular and articular involvement. Cluster 3 (n = 14) individuals mostly had cardiac and pulmonary involvement. In cluster 4 (n = 52), the gastrointestinal type, 50 patients presented with stomach symptoms and 28 patients presented with esophageal symptoms. In cluster 5 (n = 50), patients barely had any major organ involvement. Cluster 6 (n = 49) included 46% of all patients presenting with renal crisis. CONCLUSION: The results of our cluster analysis study implied that limiting SSc patient subgroups to those based only on skin involvement might not capture the full heterogeneity of the disease. Organ damage and antibody profiles should be considered when identifying homogeneous patient groups with a specific prognosis. Key Points • Provides a new method of categorizing SSc patients. • Can better explain disease progression and guide subsequent treatment.

Theoretical study on hydroformylation catalyzed by cationic cobalt(II) complexes.

Hydroformylation is one of the most important homogeneous reactions in industrial production. Herein, a density functional theory (DFT) method was employed to investigate two proposed reaction mechanisms of hydroformylation catalyzed by cationic cobalt(II) complexes, the carbonyl dissociative mechanism and the associative mechanism. The calculated results showed that the heterolytic H2 activation is the rate-determining step for both the dissociative mechanism and the associative mechanism, with energy barriers of 26.8 kcal mol-1 and 40.5 kcal mol-1, respectively. Meanwhile, the regioselectivity, the spin multiplicity of the catalyst and the substituent effects on the reaction were also investigated. The most stable cobalt(II) catalyst has a doublet state and the linear aldehyde is the dominant product. In addition, it was found that the energy barrier of the reaction decreased when the electron density of the Co center of the catalyst was increased by changing the ligand. The catalytic activity of the catalyst was proposed to be the best when the PEt2 group of the ligand is replaced by the P(tBu)2 group. This study might not only provide new insights for hydroformylation catalyzed by cobalt but also facilitate theory-guided design of novel transition metal catalysts for hydroformylation.

Sulfurized polyacrylonitrile as cathodes for advanced lithium-sulfur batteries: advances in modification strategies.

Sulfurized polyacrylonitrile (S@PAN) composites have gathered a lot of interest because of their advantages of high theoretical energy density, excellent cycling stability, and environmental friendliness. Meanwhile, their unique "covalent bonding" mechanism effectively avoids the dissolution and shuttling of polysulfides, and thus they are expected to be the most promising candidate for the cathode material in lithium-sulfur (Li-S) batteries. Over the past five years, S@PAN cathode materials have been widely studied in Li-S batteries, and it is very important to summarize the advances over time for their practical applications. This article reviews the latest progress concerning the modification of S@PAN cathode materials for improving poor electrical conductivity, low sulfur content, and sluggish reaction kinetics, and proposes possible research directions. We hope this review provides valuable insights and references for future research on Li-S batteries.

A comparative metabolomics analysis of phytochemcials and antioxidant activity between broccoli floret and by-products (leaves and stalks).

Leaves and stalks, which account for about 45% and 25% of broccoli biomass, respectively, are usually discarded during broccoli production, leading to the waste of green resources. In this study, the phytochemical composition and antioxidant capacity of broccoli florets and their by-products (leaves and stalks) were comprehensively analyzed. The metabolomics identified several unique metabolites (e.g., scopoletin, Harpagoside, and sinalbin) in the leaves and stalks compared to florets. Notably, the leaves were found to be a rich source of flavonoids and coumarins, with superior antioxidant capacity. The random forest model and correlation analysis indicated that flavonoids, coumarin, and indole compounds were the important factors contributing to the antioxidant activity. Moreover, the stalks contained higher levels of carbohydrates and exhibited better antioxidant enzyme activity. Together, these results provided valuable data to support the comprehensive utilization of broccoli waste, the development of new products, and the expansion of the broccoli industry chain.

Properties of co-gel between Tenebrio Molitor larvae protein and myofibrillar protein induced by transglutaminase.

This study explored the effect of adding transglutaminase (TGase) to a co-gel of Tenebrio Molitor larvae protein (TMLP) and myofibrillar protein (MP). Different concentrations of TGase (0-90 U/g) were added to the co-gel. The results showed that 60 U/g TGase treatment significantly improved the gel strength and water holding capacity (WHC) by 26.51 g and 9.2 %, respectively. TGase promoted the rheological properties and accelerated the three-dimensional network structure of the co-gel. Moreover, TGase significantly increased (P < 0.05) the tyrosine residues, tryptophan residues content and hydrophobic interactions of the aliphatic groups. The chemical forces between the protein molecules changed. TGase promoted the transition of α-helix to ß-sheet and free water to immobilized water, thereby improving the WHC of co-gel. The principal component analysis reflected the links among indicators. This study illustrated that TGase might be an effective strategy to improve the co-gel of TMLP and MP and emulsified meat products with insects.

Molecular pathways in placental-fetal development and disruption.

The first trimester of pregnancy ranks high in priority when minimizing harmful exposures, given the wide-ranging types of organogenesis occurring between 4- and 12-weeks' gestation. One way to quantify potential harm to the fetus in the first trimester is to measure a corollary effect on the placenta. Placental biomarkers are widely present in maternal circulation, cord blood, and placental tissue biopsied at birth or at the time of pregnancy termination. Here we evaluate ten diverse pathways involving molecules expressed in the first trimester human placenta based on their relevance to normal fetal development and to the hypothesis of placental-fetal endocrine disruption (perturbation in development that results in abnormal endocrine function in the offspring), namely: human chorionic gonadotropin (hCG), thyroid hormone regulation, peroxisome proliferator activated receptor protein gamma (PPARγ), leptin, transforming growth factor beta, epiregulin, growth differentiation factor 15, small nucleolar RNAs, serotonin, and vitamin D. Some of these are well-established as biomarkers of placental-fetal endocrine disruption, while others are not well studied and were selected based on discovery analyses of the placental transcriptome. A literature search on these biomarkers summarizes evidence of placenta-specific production and regulation of each biomarker, and their role in fetal reproductive tract, brain, and other specific domains of fetal development. In this review, we extend the theory of fetal programming to placental-fetal programming.

Genomic determinants of response and resistance to inotuzumab ozogamicin in B-cell ALL.

Inotuzumab ozogamicin (InO) is an antibody-drug conjugate that delivers calicheamicin to CD22-expressing cells. In a retrospective cohort of InO treated patients with B-cell acute lymphoblastic leukemia, we sought to understand the genomic determinants of response to InO. Acquired CD22 mutations were observed in 11% (3/27) of post-InO relapsed tumor samples. There were multiple CD22 mutations per sample and the mechanisms of CD22 escape included protein truncation, protein destabilization, and epitope alteration. Hypermutation by error-prone DNA damage repair (alternative end-joining, mismatch repair deficiency) drove CD22 escape. Acquired loss-of-function mutations in TP53 , ATM and CDKN2A were observed, suggesting compromise of the G1/S DNA damage checkpoint as a mechanism of evading InO-induced apoptosis. In conclusion, genetic alterations modulating CD22 expression and DNA damage response influence InO efficacy. The escape strategies within and beyond antigen loss to CD22-targeted therapy elucidated in this study provide insights into improving therapeutic approaches and overcoming resistance. KEY POINTS: We identified multiple mechanisms of CD22 antigen escape from inotuzumab ozogamicin, including protein truncation, protein destabilization, and epitope alteration.Hypermutation caused by error-prone DNA damage repair was a driver of CD22 mutation and escape.

Plant Secondary Compounds Promote White Adipose Tissue Browning via Modulation of the Gut Microbiota in Small Mammals.

The browning of white adipose tissue (WAT) is a promising area of research for treating metabolic disorders and obesity in the future. However, studies on plant secondary compounds promoting WAT browning are limited. Herein, we explored the effects of swainsonine (SW) on gut microbiota and WAT browning in captive pikas. SW inhibited body mass gain, increased brown adipose tissue (BAT) mass, and induced WAT browning in pikas. The 16S rDNA sequencing revealed a significant reduction in the alpha diversity and altered community structure of the gut microbiota in captive pikas. However, the addition of SW to the diet significantly increased the alpha diversity of gut microbiota and the relative abundance of Akkermansia, Prevotella, and unclassified_f__Lachnospiraceae, along with the complexity of the microbial co-occurrence network structure, which decreased in the guts of captive pikas. Functional profiles showed that SW significantly decreased the relative abundances of energy metabolism, lipid metabolism, and glycan biosynthesis and metabolism, which were enriched in captive pikas. Furthermore, SW decreased deterministic processes of gut microbiota assembly in July and increased them in November. Finally, the genera Prevotella and unclassified_f__Prevotellaceae were positively correlated with BAT mass. Our results highlighted that plant secondary compounds promote WAT browning by modulating the gut microbiota in small mammals.

Prediction of Tumor Microenvironment Characteristics and Treatment Response in Lung Squamous Cell Carcinoma by Pseudogene OR7E47P-related Immune Genes.

OBJECTIVE: Pseudogenes are initially regarded as nonfunctional genomic sequences, but some pseudogenes regulate tumor initiation and progression by interacting with other genes to modulate their transcriptional activities. Olfactory receptor family 7 subfamily E member 47 pseudogene (OR7E47P) is expressed broadly in lung tissues and has been identified as a positive regulator in the tumor microenvironment (TME) of lung adenocarcinoma (LUAD). This study aimed to elucidate the correlation between OR7E47P and tumor immunity in lung squamous cell carcinoma (LUSC). METHODS: Clinical and molecular information from The Cancer Genome Atlas (TCGA) LUSC cohort was used to identify OR7E47P-related immune genes (ORIGs) by weighted gene correlation network analysis (WGCNA). Based on the ORIGs, 2 OR7E47P clusters were identified using non-negative matrix factorization (NMF) clustering, and the stability of the clustering was tested by an extreme gradient boosting classifier (XGBoost). LASSO-Cox and stepwise regressions were applied to further select prognostic ORIGs and to construct a predictive model (ORPScore) for immunotherapy. The Botling cohorts and 8 immunotherapy cohorts (the Samstein, Braun, Jung, Gide, IMvigor210, Lauss, Van Allen, and Cho cohorts) were included as independent validation cohorts. RESULTS: OR7E47P expression was positively correlated with immune cell infiltration and enrichment of immune-related pathways in LUSC. A total of 57 ORIGs were identified to classify the patients into 2 OR7E47P clusters (Cluster 1 and Cluster 2) with distinct immune, mutation, and stromal programs. Compared to Cluster 1, Cluster 2 had more infiltration by immune and stromal cells, lower mutation rates of driver genes, and higher expression of immune-related proteins. The clustering performed well in the internal and 5 external validation cohorts. Based on the 7 ORIGs (HOPX, STX2, WFS, DUSP22, SLFN13, GGCT, and CCSER2), the ORPScore was constructed to predict the prognosis and the treatment response. In addition, the ORPScore was a better prognostic factor and correlated positively with the immunotherapeutic response in cancer patients. The area under the curve values ranged from 0.584 to 0.805 in the 6 independent immunotherapy cohorts. CONCLUSION: Our study suggests a significant correlation between OR7E47P and TME modulation in LUSC. ORIGs can be applied to molecularly stratify patients, and the ORPScore may serve as a biomarker for clinical decision-making regarding individualized prognostication and immunotherapy.

Stochastic Processes Derive Gut Fungi Community Assembly of Plateau Pikas (Ochotona curzoniae) along Altitudinal Gradients across Warm and Cold Seasons.

Although fungi occupy only a small proportion of the microbial community in the intestinal tract of mammals, they play important roles in host fat accumulation, nutrition metabolism, metabolic health, and immune development. Here, we investigated the dynamics and assembly of gut fungal communities in plateau pikas inhabiting six altitudinal gradients across warm and cold seasons. We found that the relative abundances of Podospora and Sporormiella significantly decreased with altitudinal gradients in the warm season, whereas the relative abundance of Sarocladium significantly increased. Alpha diversity significantly decreased with increasing altitudinal gradient in the warm and cold seasons. Distance-decay analysis showed that fungal community similarities were significantly and negatively correlated with elevation. The co-occurrence network complexity significantly decreased along the altitudinal gradients as the total number of nodes, number of edges, and degree of nodes significantly decreased. Both the null and neutral model analyses showed that stochastic or neutral processes dominated the gut fungal community assembly in both seasons and that ecological drift was the main ecological process explaining the variation in the gut fungal community across different plateau pikas. Homogeneous selection played a weak role in structuring gut fungal community assembly during the warm season. Collectively, these results expand our understanding of the distribution patterns of gut fungal communities and elucidate the mechanisms that maintain fungal diversity in the gut ecosystems of small mammals.

The theoretical design of manganese catalysts with a Si-N-Si-C-Si-C six-membered ring core-based bowl-shaped quadridentate ligand for the hydrogenation of CO/CN bonds.

Herein, a new series of bowl-shaped quadridentate ligands with a Si-N-Si-C-Si-C six-membered ring core and their manganese catalysts were designed using the density functional theory (DFT) method for the hydrogenation of unsaturated CX (XN, O) bonds. The frameworks of these ligands named by LYG (LYG = P(R1)2CH2Si(CH2)(CH3)NSi(CH3)(CH2Si(CH3)CH2P(R3)2)CH2P(R2)2) have a Si-N-Si-C-Si-C six-membered ring core at the bottom of the bowl structure and each Si atom links with one phosphorus arm (-CH2PR2). The Mn catalyst Mn(CO)-LYG was constructed to catalyze the hydrogenation of CO/CN bonds. The calculated results indicate that due to the bowl-shaped structure of LYG quadridentate ligands, these Mn catalysts could be advantageous not only in the tuneup of catalytic activity and stereoselectivity by modifying three phosphorus arms but also in the homogeneous catalyst immobilization by linking with the Si-N-Si-C-Si-C six-membered ring core using different supports. This work might provide theoretical insights to design new framework transition-metal catalysts for the hydrogenation of CX bonds.