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Sichuan sun vinegar (SSV) is a traditional Chinese vinegar with a unique flavor and it is fermented with bran as the main raw material. In the present study, we explored the bacterial community succession in fermented grains (Cupei) during SSV production. High-throughput sequencing results showed that bacterial community richness and diversity peaked on day 7 of fermentation. Lactobacillus and Acetobacter were the dominant bacteria throughout the fermentation process. However, Acetobacter, Cupriavidus, Sphingomonas, Pelomonas, and Lactobacillus were the most abundant genera in the late phase of fermentation on day 17. The boundaries of trilateral co-fermentation were determined through cluster analysis. Days 1-3 were considered the early fermentation stage (starch saccharification), days 5-11 were the middle fermentation stage (alcoholic fermentation), and days 13-17 represented the late fermentation stage (acetic acid fermentation). Changes in flavor compounds during Cupei fermentation were subsequently analyzed and a total of 86 volatile compounds, 9 organic acids, and 17 amino acids were detected. Although acetic acid, lactic acid, alcohols, and esters were the main metabolites, butyrate was also detected. Correlation analysis indicated that 20, 21, and 28 microorganisms were positively correlated with the abundance of amino acids, organic acids, and volatile flavor compounds, respectively. We further explored the microbial and metabolic mechanisms associated with the dominant volatile flavor compounds during SSV fermentation. Collectively, the findings of the current study provide detailed insights regarding the fermentation mechanisms of SSV, which may prove relevant for producing high-quality fermented products.

Stagonospora leaf and glume blotch, caused by Parastagonospora nodorum, is a major disease of winter wheat (Triticum aestivum) in the United States capable of significantly reducing grain yield and quality. Pathogens such as P. nodorum that overwinter in crop residue are often an increased concern in cropping systems that utilize no-till farming. In addition, the lack of wheat cultivars with complete resistance to P. nodorum has led to the reliance on foliar fungicides for disease management. Quinone outside inhibitor (QoI) fungicides (Fungicide Resistance Action Committee group 11) are one of the major classes used to manage foliar diseases in wheat. Use of the QoI class of fungicides tends to select isolates of fungal pathogens with resistance due to mutations in the fungal cytochrome b gene. Isolates of P. nodorum were collected from Illinois in 2014 and Kentucky in 2018, 2019, and 2020. Amplification and sequencing of a segment of the cytochrome b gene from these isolates revealed a mutation at codon 143 that confers a change from glycine to alanine in the amino acid sequence (known as the G143A mutation). In vitro plate assays and greenhouse trials were used to confirm and characterize the QoI resistance caused by the G143A mutation. The frequency of the tested isolates with the G143A mutation was 46% (57 of 123 isolates) and 5% (3 of 60 isolates) for Kentucky and Illinois, respectively. This research is the first to identify the G143A mutation in P. nodorum isolates with resistance to QoI fungicides in Illinois and Kentucky.

Neutrophils are the most abundant circulating leukocytes and the first line of defense against invading pathogens. They are key components of the innate immune system. Neutrophils also cause tissue damage in various autoimmune and inflammatory diseases and play an important role in cancer progression. Due to the complex relationship between various diseases and neutrophils, these cells have become potentially important targets for therapeutic interventions. Monitoring neutrophils in the tumor microenvironment is critical for tumor treatment and prognostic analysis but remains challenging. Molecular imaging technology has made great progress as a valuable tool for noninvasively visualizing biological events and establishing effective cancer diagnoses and treatment methods. Molecular probes designed based on the characteristics of neutrophils, such as their flexible morphology, the abundance of surface receptors, and the absence of immunogenicity, have shown great potential. This has created an opportunity for novel ideas and research methods for the diagnosis and targeted therapy of inflammatory diseases and tumors, with the goal of integrated diagnosis and treatment. This review discusses the diverse tumor detection and diagnostic imaging strategies based on neutrophils. It is anticipated that neutrophil-based imaging will soon be gradually integrated into clinical applications.Neutrophils play a role in promoting/inhibiting tumor growth in the tumor microenvironment.To be more conducive to discovering neutrophils in tumors and guiding treatment, medical imaging technology has developed stepwise.In the context of the intersection of imaging technology, great breakthroughs have been made in the individualized research of tumor diagnosis.This article contributes to the promotion of new multimodal molecular imaging technology and the application of rapid diagnosis individualization.

Malignant gliomas occur more often in adults and may affect any part of the central nervous system (CNS). Although their results could be better, surgical excision, postoperative radiation and chemotherapy, and electric field therapy are today’s mainstays of glioma care. However, bacteria can also exert anti-tumor effects via mechanisms such as immune regulation and bacterial toxins to promote apoptosis, inhibit angiogenesis, and rely on their natural characteristics to target the tumor microenvironment of hypoxia, low pH, high permeability, and immunosuppression. Tumor-targeted bacteria expressing anticancer medications will go to the cancer site, colonize the tumor, and then produce the therapeutic chemicals that kill the cancer cells. Targeting bacteria in cancer treatment has promising prospects. Rapid advances have been made in the study of bacterial treatment of tumors, including using bacterial outer membrane vesicles to load chemotherapy drugs or combine with nanomaterials to fight tumors, as well as the emergence of bacteria combined with chemotherapy, radiotherapy, and photothermal/photodynamic therapy. In this study, we look back at the previous years of research on bacteria-mediated glioma treatment and move forward to where we think it is headed.

Chicoric acid (CA) has been used as a nutritional supplement, health food, and medicine because of its antioxidant property. This study aimed to investigate whether CA can improve motor dysfunction in a zebrafish model of Parkinson’s disease (PD). AB-strain zebrafish larvae (24 hours post-fertilization) were incubated with 25 μM 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) with or without CA for 5 days. The levels of malondialdehyde, glutathione, and reactive oxygen species were measured, as were the activities of antioxidant enzymes in brain tissue. Additionally, the expression of molecules from the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway were assayed by western blot. Compared with the control group, zebrafish in the MPTP group had impaired motor function. Treatment with CA improved motor dysfunction and attenuated dopaminergic neuronal injury in the PD zebrafish model. CA treatment also reduced the levels of malondialdehyde and reactive oxygen species and increased the antioxidant enzymes and glutathione level. Furthermore, CA augmented the expression of Nrf2, heme oxygenase, quinone oxidoreductase 1, and glutamate-cysteine ligase in the brain of the PD zebrafish model. CA from health foods also improved motor dysfunction and attenuated dopaminergic neuronal injury in the MPTP-induced PD zebrafish model. Our findings suggest that the mechanism of action of CA is related to its inhibition of oxidative stress via regulation of the Nrf2 pathway.

The world faces the dual pressures of an aging population and the prevalence of metabolic risk factors. The morbidity and mortality of cardiovascular disease (CVD) continue to increase, becoming one of the important causes of death in the population. Chinese herbal medicine can also change abnormal metabolism while lowering blood pressure. It has an extraordinary curative impact and promises to prevent and treat hypertension. Iron-dependent lipid reactive oxygen species buildup and polyunsaturated fatty acid consumption in the plasma membrane, involving three processes—lipid metabolism, amino acid metabolism, and iron metabolism—are always present when ferroptosis occurs. It is crucial for the pathophysiology of CVD. Therefore, finding Chinese herbal medicine to treat ferroptosis, screen out the active ingredients, and explore the therapeutic targets related to ferroptosis in hypertension is an urgent problem. In this study, network pharmacology was used to find that Stigmsterol, sitosterol, kaempferol, beta-sitosterol, and quercetin were the main active constituents of Toosendan Fructus, Jujubae Fructus, Flos Puerariae Lobatae, Peucedani Radix, Crataegi Folium, and Potentiliae. To reach the goal of treating hypertension, these active components target CAV1, IL6, TGFB1, HMOX1, TP53, IL1B, HIF1A, GJA1, EGFR, and NEDD4L to control ferroptosis. The current work provides a more in-depth understanding of Chinese herbal medicine used to treat hypertension through ferroptosis for future drug optimization.

Purpose: To analyze and review the progress of glucose metabolism-based molecular imaging in detecting tumors to guide clinicians for new management strategies.Summary: When metabolic abnormalities occur, termed the Warburg effect, it simultaneously enables excessive cell proliferation and inhibits cell apoptosis. Molecular imaging technology combines molecular biology and cell probe technology to visualize, characterize, and quantify processes at cellular and subcellular levels in vivo. Modern instruments, including molecular biochemistry, data processing, nanotechnology, and image processing, use molecular probes to perform real-time, non-invasive imaging of molecular and cellular events in living organisms.Conclusion: Molecular imaging is a non-invasive method for live detection, dynamic observation, and quantitative assessment of tumor glucose metabolism. It enables in-depth examination of the connection between the tumor microenvironment and tumor growth, providing a reliable assessment technique for scientific and clinical research. This new technique will facilitate the translation of fundamental research into clinical practice.

Glioblastoma (GBM) is the most prevalent form of primary brain cancer. In the therapeutic therapy of GBM, there are still several ambiguities. GBM patients urgently need further research to find significant prognostic markers and more effective treatment choices. However, current stage-based clinical approaches still need to be improved for predicting survival and making decisions. This research intended to develop a new GBM risk assessment model based on glycolysis, immunology, and epithelial-mesenchymal transition (EMT) gene signatures. In this analysis, the cohort was constructed using TCGA-GBM data. Leveraging bioinformatics and machine algorithms, we developed a risk model based on glycolysis, immunological, and EMT gene signatures, which was then employed to classify patients into high and low-risk categories. Subsequently, we evaluated whether the risk score was associated with the immunological microenvironment, immunotherapy response, and numerous anticancer drug sensitivity. The unique risk model based on glycolysis, immunological, and EMT gene signatures could assist in predicting clinical prognosis and directing therapy decisions for GBM patients.

As a new programmed cell death process, ferroptosis has shown great potential and uniqueness in experimental and treatment-resistant cancer models. Currently, the main tools for drug research targeting ferroptosis are tumor cells cultured in vitro and tumor models established in rodents. In contrast, increasing evidence indicates that reactivity may differ from modifications in mice or humans in the process of drug screening. With the blossoming of 3D culture technology, tumor organoid culture technology has gradually been utilized. Compared with traditional 2D culture and tumor tissue xenotransplantation, tumor organoids have a significantly higher success rate. They can be cultured quickly and at a lower cost, which is convenient for gene modification and large-scale drug screening. Thus, combining 3D cell culture technology, drug monitoring, and ferroptosis analysis is necessary to develop the impact of ferroptosis-related agents in tumor treatment.

In the process of continuously promoting safety management, major road accidents have become a key obstacle to improving overall road safety. The analysis of the overall road accidents hides the characteristics and laws of major road accidents. To clarify the causes of major road accidents, an analysis framework of “individual-vehicle-environment-management” is presented based on a literature review. Considering the interaction of the above variables, the fuzz-set qualitative comparative analysis (fsQCA) was used to explore the generating paths of major road accidents based on 42 road accidents. The work shows that: (1) Major road accidents are caused due to the interactive coupling of “individual-vehicle-environment-management” elements. Major road accidents can occur with normal driving behaviors or sufficient response and rescue capabilities. (2) General road accidents and relatively major road accidents are more likely to occur in the presence of driving behavior errors, favorable road facilities, and sufficient response and rescue capabilities. Moreover, major road accidents are more likely to occur due to large vehicles with adverse vehicle performances. (3) There are three path modes and five condition configurations in major road accidents, namely individual-vehicle-management induced, individual-vehicle-environment induced, and vehicle induced mode. This work enriches the accident causation mode from a new configuration perspective and explains which variable combinations lead to the occurrence of major road accidents. Clarification of the differences between general accidents and major accidents will help to accurately predict and restrain the development of major road accidents.

Stagonospora leaf and glume blotch, caused by

Due to the inherent molecular heterogeneity of metastatic tumours and the dynamic evolution ability of tumour genomes, tumour tissues obtained through biopsy and other methods cannot capture all of the features of tumour genomes. A new diagnostic concept called “liquid biopsy” has received widespread attention in recent years. Liquid biopsy has changed the clinical practice of oncology and is widely used to guide targeted drug utilization, monitor disease progression and track drug resistance. The latest research subject in liquid biopsy is platelets. Platelets originate from multifunctional haematopoietic stem cells in the bone marrow haematopoietic system. They are small cells from the cytoplasm of bone marrow megakaryocytes. Their main physiological functions are to participate in the processes of physiological haemostasis and coagulation. Tumour cells transfer biomolecules (such as RNA) to platelets through direct contact and release of exosomes, which changes the platelet precursor RNA. Under the stimulation of tumour cells and the tumour microenvironment, platelet precursor mRNA is spliced into mature RNA and converted into functional protein to respond to external stimuli, forming tumour-educated platelets (TEPs). The detection of TEPs in the peripheral blood of patients is expected to be used in clinical tumour diagnosis. This emerging liquid biopsy method can replace and supplement the current tumour detection methods. Further research on the role of platelets in tumour diagnosis will help provide a novel theoretical basis for clinical tumour diagnosis.

BACKGROUND: Giant cell tumor of bone (GC), osteosarcoma (OS) and Ewing’s sarcoma (ES) are three different types of bone cancer with common and specific pathology features. OBJECTIVE: The purpose of the study was to examine the relationship and differences of the three bone tumors using clinical samples. METHODS: Through screening the profiles of clinical samples from GC, OS and ES patients using a humanoncology array, we found 26, 25 and 15 tumorigenesis factors significantly increased in GS, OS and ES tissues compared to normal individuals. eNOS, endostatin, HIF-1α, IL-6, CCL2/MCP-1, CCL8/MCP-2, CCL7/MCP-3, Tie and VEGF directly or indirectly involve in the metastasis Therefore, expression levels of the 6 factors were further determined by Western blot. RESULTS: The results showed levels of MCP1, MCP2, MCP3 or IL-6 in the GS, OS and ES significantly increased, and the expression levels of angiogenesis and anti-angiogenesis factors containing eNOS, endostatin, HIF-1α, Tie or VEGF were enhanced. CONCLUSIONS: Our results suggest that eNOS, endostatin, HIF-1α, IL-6, CCL2/MCP-1, CCL8/MCP-2, CCL7/MCP-3, Tie and VEGF may play important roles in tumorigenesis, reveal the expression differences of tumor-associated cytokines and angiogenesis related factors, and provide clinical evidence for studying the mechanisms on the metastasis in GC, OS and ES.

The prepared carbon-coated silicon (Si@C) material was blended with graphite powder together to form the specific carbon paste electrode with different mass percent X% of Si@C (CPE-Si@C(X%)). The electrochemical impedance spectroscopy (EIS) was performed on the prepared CPE-Si@C and the pure carbon paste electrode (CPE), and the results show that the CPE-Si@C (X%) electrode has a smaller charge transfer resistance. Pt/CPE and Pt/CPE-Si@C(X%) electrodes were prepared by electrodepositing Pt particles on CPE-Si@C and CPE, and the obtained electrodes were used for electrocatalytic oxidation of methanol in acid media. The results show that the activity of Pt/CPE-Si@C(X%) electrode for electrocatalytic oxidation of methanol was higher than that of Pt/CPE electrode, and the mass peak current density of Pt/CPE-Si@C(10%) electrode for electrocatalytic oxidation of methanol reached 321 mA mg−1, which was 1.8 times higher than that of Pt/CPE electrode. The Pt/CPE-Si@C (10%) electrode and the Pt/CPE electrode were characterized by chronoamperometry. The results show that Pt/CPE-Si@C (10%) has a better stability of activity and stronger tolerance against CO poisoning.

Saccharomyces boulardii (S. boulardii) is a probiotic and is widely used to improve the nutritional and functional value of food. This study aimed to compare the probiotic properties of S. boulardii and Saccharomyces cerevisiae. A series of in vitro probiotic experiments was performed, including simulated gastrointestinal digestion, bile salt tolerance, hydrophobicity, self-aggregation, and antioxidant and antibacterial properties. Self-aggregation and hydrophobic properties of S. boulardii were relatively poor, but they showed high tolerance, antioxidant properties, and broad antibacterial properties. In addition, non-targeted metabolomics was used to comprehensively analyze the active metabolites of S. boulardii and the metabolic differences between S. boulardii and S. cerevisiae were compared. Saccharomyces boulardii produced many bioactive metabolites, which generally showed antioxidant, antibacterial, antitumor, anti-inflammatory, and other properties. In contrast to S. cerevisiae, S. boulardii produced phenyllactic acid and 2-hydroxyisocaproic acid. There were also significant differences in their metabolic pathways. These results may be of great significance in the medical and food industries and provide a basis for understanding the metabolism of S. boulardii. It also shows that metabolomics is an effective and novel method for screening microbial functional metabolites and identifying functional differences between similar microorganisms.

Circulating tumor DNA (ctDNA) correlates with tumor burden and provides early detection of treatment response and tumor genetic alterations in breast cancer. Neoadjuvant chemotherapy (NACT) has become standard therapy for local advanced breast cancer (LABC). The aim of our study was to investigate plasma ctDNA as a prognostic marker for outcome in patients with LABC treated with NACT. A total of 56 patients with LABC were involved in this study. ctDNA mutations were investigated by using a 100 gene panel-target capture next-generation sequencing. The patients then received standard NACT therapy: adriamycin and cyclophosphamide and paclitaxel (AC-T) or AC-TH (AC-T+ Trastuzumab) regimen. The efficacy of NACT was evaluated by Miller-Payne grading system. A predictive and weight model was used to screen ctDNA point mutation biomarkers for NACT. The ctDNA mutational profile of LABC patients was identified. For nonsynonymous mutations, the top 5 mutated genes were MTHFR (51/56, 91.1%), XPC (50/56, 89.3%), ABCB1 (48/51, 94.1%), BRCA2 (38/56, 67.9%), and XRCC1 (38/56, 67.9%). In addition, the mutation frequencies of PIK3CA and TP53 were 32.1% (18/56) and 26.8% (15/56), respectively. The predictive model indicated that XRCC1 44055726 (TG-) mutation (25/56, 44.6%) was significantly associated with Miller-Payne 4-5 and Miller-Payne 3-5 responses. While mTOR 11249132(GC) mutation (23/56, 41.1%) was associated with Miller-Payne 1-4 or Miller-Payne 1-3 responses. Furthermore, XRCC1 44055726 (TG-) accompanied by mTOR wild type predicted a good NACT efficacy in all response classification systems. The ROC curves to discriminate good neoadjuvant chemotherapy efficiency (Miller-Payne 4-5) and poor efficiency (Miller-Payne 1-3) were created, and AUC value was 0.77. Our results suggested that ctDNA mutation of XRCC1 44055726 (TG-) might be a positive biomarker for NACT therapy in LABC, while mTOR 11249132(GC) mutation was potentially associated with NACT resistance.

Selenium (Se) plays an essential role in the growth of fish and performs its physiological functions mainly through incorporation into selenoproteins. Our previous studies suggested that the selenoprotein W gene (selenow) is sensitive to changes in dietary Se in rainbow trout. However, the molecular characterization and tissue expression pattern of selenow are still unknown. Here, we revealed the molecular characterization, the tissue expression pattern of rainbow trout selenow and analyzed its response to dietary Se. The open reading frame (ORF) of the selenow gene was composed of 393 base pairs (bp) and encodes a 130-amino-acid protein. The 3' untranslated region (UTR) was 372 bp with a selenocysteine insertion sequence (SECIS) element. Remarkably, the rainbow trout selenow gene sequence was longer than those reported for mammals and most other fish. A β1-α1-β2-β3-β4-α2 pattern made up the secondary structure of SELENOW. Furthermore, multiple sequence alignment revealed that rainbow trout SELENOW showed a high level of identity with SELENOW from Salmo salar. In addition, the selenow gene was ubiquitously distributed in 13 tissues with various abundances and was predominantly expressed in muscle and brain. Interestingly, dietary Se significantly increased selenow mRNA expression in muscle. Our results highlight the vital role of selenow in rainbow trout muscle response to dietary Se levels and provide a theoretical basis for studies of selenow.

Insulin-like growth factor 1 (IGF-1), a multifunctional peptide that involves in cell proliferation and differentiation, can induce strong osteogenic differentiation in bone marrow mesenchymal stem cells (BMMSCs). However, it remains unknown whether intracellular Ca2+ signal contributes to the IGF-1-induced osteogenic differentiation of BMMSCs. In this study, we attempted to investigate the effect of IGF-1 on the gene expression of intracellular Ca2+-handling proteins and figure out whether the intracellular Ca2+ signal affects IGF-1-induced osteogenic differentiation. We found that IGF-1 treatment significantly increased cell proliferation and induced cell morphological changes with an increase of cell surface area. Quantitative PCR and Western blot analysis showed that osteoblast marker proteins, including alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN) were significantly upregulated by IGF-1 treatment, indicating IGF-1 induced osteogenic differentiation in BMMSCs. Interestingly, the expression levels of the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) 3 and inositol-1,4,5-triphosphate receptor (IP3R) 2 were dramatically elevated during the IGF-1-induced osteogenic differentiation. Consistently, IGF-1-treated cells exhibited greater Ca2+ response to ATP. Importantly, blocking SERCA by thapsigargin markedly impaired IGF-1-induced osteogenic differentiation, indicating that intracellular Ca2+ mediated IGF-1-induced osteogenic differentiation in BMMSCs, probably via Akt signal pathway, which may provide new insight for the treatment of osteoporosis.

The improper usage of antibiotics is known to cause widespread antibiotic resistance. In this study, the antibacterial effects of a polypeptide-enriched extract from the skin of the amphibian Rana chensinensis (RCP) were evaluated against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive bacterium Staphylococcus aureus and the fungus Candida albicans. The mechanisms underlying these effects were also studied, and the minimum inhibitory concentration of RCP was determined for each species. Analyses of the levels of adenosine triphosphates (ATPases), including Na+/K+-ATPase and Ca2+-ATPase, and scanning electron microscopy confirmed that RCP damaged the microbial cell walls and membranes. RCP perturbed microbial metabolism and particularly affected the tricarboxylic acid cycle (TCA), suggesting that this agent downregulated the levels of succinate dehydrogenase, malate dehydrogenase and ATPase activity in cells. Furthermore, RCP caused the leakage of genetic material from all four microbial strains. In conclusion, RCP effectively inhibited the growth of Gram-negative and Gram-positive bacteria and a fungal species by disrupting energy metabolic processes.

Research question Can single-nucleotide polymorphisms (SNP) of genes related to progesterone synthesis predict the risk of premature serum progesterone elevation in women undergoing gonadotrophin-releasing hormone agonist protocols for ovarian stimulation? Design A total of 765 women were divided into high progesterone and normal progesterone groups according to progesterone concentration on the day of human chorionic gonadotrophin (HCG) administration, with the 75th percentile as the threshold between the group. Associations were analysed of genetic information from whole exome sequencing and the clinical characteristics of the two groups to identify the relationship between SNP, haplotypes and serum progesterone elevation. Results Among 40 common SNP of eight genes (FSHR, LHCGR, ESR1, ESR2, PGR, HSD3B1, CYP11A1 and CYP17A1), no statistical significance between the high and normal progesterone groups was identified in the distribution of genotypes and allele frequencies after multiple test correction to adjust the false discovery rate (PFDR > 0.05). When compared with the most common haplotypes of each gene, haplotype GAAG in CYP17A1 was associated with a 1.44-fold increased risk of progesterone elevation (95% confidence interval [CI] 1.22–1.69, PFDR Conclusions Polymorphism in genes involved in enzymes or hormone receptors in the progesterone synthesis pathway may have a role in modifying risk of serum progesterone elevation.

PURPOSE: To evaluate the efficacy of preimplantation genetic testing (PGT) for α- and β-double thalassemia combined with aneuploidy screening using next-generation sequencing (NGS). METHODS: An NGS-based PGT protocol was performed between 2017 and 2018 for twelve couples, each of which carried both α- and β-thalassemia mutations. Trophectoderm biopsy samples underwent whole-genome amplification using multiple displacement amplification (MDA), followed by NGS for thalassemia detection and aneuploidy screening. A selection of several informative single nucleotide polymorphisms (SNPs) established haplotypes. Aneuploidy screening was performed only on unaffected noncarriers and carriers. Unaffected and euploid embryos were transferred into the uterus through frozen-thawed embryo transfer (FET). RESULTS: A total of 280 oocytes were retrieved following 18 ovum pick-up (OPU) cycles, with 182 normally fertilized and 112 cultured to become blastocysts. One hundred and seven (95.5%, 107/112) blastocysts received conclusive PGT results, showing 56 (52.3%, 56/107) were unaffected. Thirty-seven (66.1%, 37/56) of the unaffected were also identified as euploid. One family had no transferable embryos. Unaffected and euploid embryos were then transferred into the uterus of the other 11 couples resulting in 11 healthy live births. The clinical pregnancy rate was 61.1% (11/18) per OPU and 68.8% (11/16) per FET, with no miscarriage reported. Seven families accepted the prenatal diagnosis and received consistent results with the NGS-based PGT. CONCLUSION: This study indicated that NGS could realize the simultaneous PGT of double thalassemia and aneuploidy screening in a reliable and accurate manner. Moreover, it eliminated the need for multiple biopsies, alleviating the potential damages to the pre-implanted blastocysts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10815-020-01732-7) contains supplementary material, which is available to authorized users.

The adverse effects of sleep disorders on male fertility are of increased concern. In this study, a rat model of chronic sleep restriction (CSR) was established using the modified multiplatform method. The effects of CSR on the fertility of male rats were evaluated first based on sexual behavior. Serum hormones, including testosterone (T), prolactin (PRL), luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and sperm parameters (concentration, viability, motility, deformation rate) were measured, and testicular histology was analysed by hematoxylin and eosin staining. The transcriptional differences between CSR rats and control rats were detected by RNA sequencing (RNA-Seq), and DNA methylation was then detected by bisulfite sequencing. After the differentialy expressed genes of CSR rats were sequenced and screened, representative up- and down-regulated genes were randomly sampled to verify the sequencing results by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Finally, functional annotations were completed, including gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomic (KEGG) pathway analyses. The results showed that the sexual behavior of CSR rats did not change when compared with control group rats. The sperm concentration, viability and motility of the CSR rats decreased significantly, while the sperm malformation rate increased significantly. In the KEGG pathway analysis database, some specific differentially expressed genes were screened, which are involved in metabolic pathways, inflammation-related pathways, the renin-angiotensin system, as well as others. However, the aforesaid differentially expressed genes in the testes were not related to their DNA methylation status. CSR could significantly reduce the fertility of male rats, and one of its mechanisms occurs by altering gene expression in the testes, which is not related to their state of DNA methylation. The results of this study suggest that CSR could cause male infertility by significantly altering the testicular transcriptome.

The new coronavirus (2019-nCoV) is an emerging pathogen that can cause severe respiratory infections in humans. It is worth noting that many of the affected COVID-19 patients have malignant tumors. In addition, cancer has been identified as a personal risk factor for COVID-19. Transmembrane proteaseserine-2 (TMPRSS2) is a crucial host protease that mediates S protein activation and initially promotes virus entry into host cells. Moreover, it is abnormally expressed in a variety of tumors. However, the systematic analysis of TMPRSS2 aberrations in human cancer remains to be elucidated. Here, we analyzed the genetic changes, RNA expression, and DNA methylation of TMPRSS2 in more than 30 tumors. It has been reported that TMPRSS2 is overexpressed in tumors such as prostate adenocarcinoma (PRAD), and in contrast, the expression of TMPRSS2 is decreased in tumors such as head and neck cancer (HNSC). In addition, TMPRSS2 low DNA methylation was also found in most of these TMPRSS2 high-expressing tumors in this study. Clinical studies have found that there is a significant correlation between the expression of TMPRSS2 and the prognosis of some tumor patients. The expression of TMPRSS2 is also related to the infiltration of cancer-related fibroblasts, and the potential pathways and functional mechanisms were analyzed through KEGG/GO enrichment. In the end, our study planned the genetic and epigenetic variation of TMPRSS2 in human malignant tumors for the first time and provided a relatively comprehensive understanding of the carcinogenic effects of TMPRSS2.

Accumulating evidence has implicated members of the procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) gene family, PLOD1, PLOD2, and PLOD3, in cancer progression and metastasis. However, their expression, prognostic value, and mechanisms underlying their roles in lung adenocarcinoma (LUAD) have not yet been reported. We downloaded PLOD data for LUAD and normal tissues from The Cancer Genome Atlas (TCGA). PLOD1-3 protein expression was evaluated using the Clinical Proteomics Tumor Analysis Consortium and Human Protein Atlas. Survival analysis was performed using the Kaplan–Meier method. A protein–protein interaction network was constructed using STRING software. The “ClusterProfiler” package was used for functional-enrichment analysis. The relationship between PLOD mRNA expression and immune infiltration was analyzed using the Tumor Immunity Assessment Resource and Tumor Immune System Interaction Database. The expression of PLODs in LUAD tissues was significantly upregulated compared with that in adjacent normal tissues. PLOD mRNA overexpression is associated with lymph node metastasis and high TNM staging. Receiver operating characteristic curve analysis showed that when the cut-off level was 6.073, the accuracy, sensitivity, and specificity of PLOD1 in distinguishing LUAD from adjacent controls were 84.4, 79.7, and 82.6%, respectively. The accuracy, sensitivity, and specificity of PLOD2 in distinguishing LUAD from adjacent controls were 81.0, 98.3, and 68.0%, respectively, at a cut-off value of 4.360. The accuracy, sensitivity, and specificity of PLOD3 in distinguishing LUAD from adjacent controls were 69.0, 86.4, and 52.0%, respectively, with a cut-off value of 5.499. Kaplan–Meier survival analysis demonstrated that LUAD patients with high PLODs had a worse prognosis than those with low PLODs. Correlation analysis showed that PLOD mRNA expression was related to immune infiltration and tumor purity. Upregulation of PLOD expression was significantly associated with poor survival and immune cell infiltration in LUAD. Our research shows that PLOD family members have potential as novel biomarkers for poor prognosis and as potential immunotherapy targets for LUAD.

Radiomics is a novel concept that relies on obtaining image data from examinations such as computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET). With the appropriate algorithm, the extracted results have broad applicability and potential for a massive positive impact in radiology. For example, clinicians can verify treatment efficiency, predict the location of tumor metastasis, correlate results with a histopathological examination, or more accurately define the type of cancer. Combining radiomics with other testing techniques allows every patient to have a personalized treatment plan that is essential for advanced examination and treatment. This article explains the process of radiomics, including data collection mechanisms, combined use with genomics, and artificial intelligence and immunology techniques, which may solve many of the challenges faced by doctors in diagnosing and treating their patients.

The new coronavirus (2019-nCoV) is an emerging pathogen that can cause severe respiratory infections in humans. It is worth noting that many of the affected COVID-19 patients have malignant tumors. In addition, cancer has been identified as a personal risk factor for COVID-19. Transmembrane proteaseserine-2 (TMPRSS2) is a crucial host protease that mediates S protein activation and initially promotes virus entry into host cells. Moreover, it is abnormally expressed in a variety of tumors. However, the systematic analysis of TMPRSS2 aberrations in human cancer remains to be elucidated. Here, we analyzed the genetic changes, RNA expression, and DNA methylation of TMPRSS2 in more than 30 tumors. It has been reported that TMPRSS2 is overexpressed in tumors such as prostate adenocarcinoma (PRAD), and in contrast, the expression of TMPRSS2 is decreased in tumors such as head and neck cancer (HNSC). In addition, TMPRSS2 low DNA methylation was also found in most of these TMPRSS2 high-expressing tumors in this study. Clinical studies have found that there is a significant correlation between the expression of TMPRSS2 and the prognosis of some tumor patients. The expression of TMPRSS2 is also related to the infiltration of cancer-related fibroblasts, and the potential pathways and functional mechanisms were analyzed through KEGG/GO enrichment. In the end, our study planned the genetic and epigenetic variation of TMPRSS2 in human malignant tumors for the first time and provided a relatively comprehensive understanding of the carcinogenic effects of TMPRSS2.

Accumulating evidence has implicated members of the procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) gene family, PLOD1, PLOD2, and PLOD3, in cancer progression and metastasis. However, their expression, prognostic value, and mechanisms underlying their roles in lung adenocarcinoma (LUAD) have not yet been reported. We downloaded PLOD data for LUAD and normal tissues from The Cancer Genome Atlas (TCGA). PLOD1-3 protein expression was evaluated using the Clinical Proteomics Tumor Analysis Consortium and Human Protein Atlas. Survival analysis was performed using the Kaplan-Meier method. A protein-protein interaction network was constructed using STRING software. The "ClusterProfiler" package was used for functional-enrichment analysis. The relationship between PLOD mRNA expression and immune infiltration was analyzed using the Tumor Immunity Assessment Resource and Tumor Immune System Interaction Database. The expression of PLODs in LUAD tissues was significantly upregulated compared with that in adjacent normal tissues. PLOD mRNA overexpression is associated with lymph node metastasis and high TNM staging. Receiver operating characteristic curve analysis showed that when the cut-off level was 6.073, the accuracy, sensitivity, and specificity of PLOD1 in distinguishing LUAD from adjacent controls were 84.4, 79.7, and 82.6%, respectively. The accuracy, sensitivity, and specificity of PLOD2 in distinguishing LUAD from adjacent controls were 81.0, 98.3, and 68.0%, respectively, at a cut-off value of 4.360. The accuracy, sensitivity, and specificity of PLOD3 in distinguishing LUAD from adjacent controls were 69.0, 86.4, and 52.0%, respectively, with a cut-off value of 5.499. Kaplan-Meier survival analysis demonstrated that LUAD patients with high PLODs had a worse prognosis than those with low PLODs. Correlation analysis showed that PLOD mRNA expression was related to immune infiltration and tumor purity. Upregulation of PLOD expression was significantly associated with poor survival and immune cell infiltration in LUAD. Our research shows that PLOD family members have potential as novel biomarkers for poor prognosis and as potential immunotherapy targets for LUAD.

Aim: The primary objective of this study was to evaluate the effects of polypeptide-enriched Gastrodia elata extracts (GE) on vulvovaginal candidiasis (VVC). Materials & methods: A VVC model induced by Candida albicans ( C. albicans) infection was successfully developed in BALB/c mice. After treatment, the colony-forming unit (CFU) of vaginal lavage was measured by plating. The extent of the inflammatory response was assessed by hematoxylin-eosin (H&E) staining and enzyme-linked immunosorbent assay (ELISA). Results: GE had an inhibitory effect on the proliferation of C. albicans and inflammatory reaction. Meanwhile, it had a potentially beneficial effect on the growth of Lactobacillus. Conclusion: These results showed the potential application of GE as an antifungal agent in VVC treatment.

Glioma is the most common malignant tumor of the central nervous system, and it is characterized by high relapse and fatality rates and poor prognosis. Bufalin is one of the main ingredients of Chan-su, a traditional Chinese medicine (TCM) extracted from toad venom. Previous studies revealed that bufalin exerted inhibitory effects on a variety of tumor cells. To demonstrate the inhibitory effect of bufalin on glioma cells and glioma stem-like cells (GSCs) and discuss the underlying mechanism, the proliferation of glioma cells was detected by MTT and colony formation assays following treatment with bufalin. In addition, we investigated whether bufalin inhibits or kills GSCs using flow cytometry, Western blotting, and reverse transcription polymerase chain reaction analysis (RT-PCR). Finally, we investigated whether bufalin could improve the therapeutic effect of temozolomide (TMZ) and discussed the underlying mechanism. Taken together, our data demonstrated that bufalin inhibits glioma cell growth and proliferation, inhibits GSC proliferation, and kills GSCs. Bufalin was found to induce the apoptosis of GSCs by upregulating the expression of the apoptotic proteins cleaved caspase 3 and poly(ADP-ribose) polymerase (PARP) and by downregulating the expression of human telomerase reverse transcriptase, which is a marker of telomerase activity. Bufalin also improved the inhibitory effect of TMZ on GSCs by activating the mitochondrial apoptotic pathway. These results suggest that bufalin damages GSCs, induces apoptosis, and enhances the sensitivity of GSCs to TMZ.

Promoting the antitumor effects of cell-based immunotherapy for clinical application remains a difficult challenge. Nocardia rubra cell-wall skeleton (N-CWS) is an immunotherapeutic agent for cancers that have been proven to possess the ability to activate immune response without showing toxicity. However, its effects on immune cells that are derived from tumor patients and cultured in vitro remain unclear. As expected, N-CWS can enhance the proliferation and viability of cytokine-induced killer (CIK) cells, dendritic cells (DCs), and natural killer (NK) cells. The maturation of DCs and specific cytotoxicity against NK cells and CIK cells were consistently promoted. The TUNEL-staining and the Annexin V/propidium iodide assay revealed that after treatment with N-CWS, the stimulated CIK/NK cells could induce DNA breaks in tumor cells. Furthermore, quantitative real-time polymerase chain reaction and western blot analysis showed upregulation of proapoptotic biomarkers (caspase-3 and caspase-9) and a downregulation of the antiapoptotic biomarker Bcl-2 in the tumor cells of the N-CWS-treated group, indicating that N-CWS could induce hepatocellular carcinoma cell apoptosis via CIK/NK cells. Finally, CIK/NK cells could notably suppress the invasion and migration of tumor cells in the presence of N-CWS. Our study provides evidence that N-CWS could significantly increase the growth of CIK cells, DCs, and NK cells, particularly due to its robust antitumor activities by inducing apoptosis, and attenuate the invasion and migration of tumor cells.

The aim of this study was to provide a practical experimental basis for the development of Neocryptotanshinone (NCTS) as an effective hypoglycemic drug and a theoretical method for the rapid screening of natural compounds with hypoglycemic effects. Molecular docking was used to screen the most suitable ligand. Hematoxylin and eosin, immunohistochemical staining, enzyme-linked immunosorbent assay and Western Blotting approved the hypoglycemic effect of NCTS. According to the free energy of binding, among 180 active compounds from the Traditional Chinese Medicine Integrated Database, NCTS was finally chose for investigation its hypoglycemic effects. In db/db mice, NCTS significantly reduced body weight and plasma glucose, improved glucose tolerance and levels of fasting plasma glucose and glycated hemoglobin A1c, and decreased insulin resistance after six-week administration. NCTS restored the pathological state in the liver of db/db mice and significantly decreased protein tyrosine phosphatase 1B (PTP1B) expression in the liver and muscle of db/db mice, which is related to the regulatory effect of NCTS on insulin receptor substrate 1. In conclusion, we successfully explored the hypoglycemic effect of NCTS in db/db mice via regulating the expression of PTP1B.

Humans are at the core of the social-technical system, and their behavioral errors affect the reliability and safety of the entire system in varying degrees. Occupational accidents and large-scale industrial accidents are often attributed to human errors, accounting for more than 80% of accidents. In view of the complexity of systems and the coupling of elements, a new HFA method is proposed based on a complex network. According to system safety theory, a complex network is regarded as a network composed of humans, matters, environments, and management, and the basic structure of the HFA network is summarized. On this basis, a system safety method of HFA is developed which proposes a universal human error causation model. Moreover, a network analysis method for human errors is also presented, which is a comprehensive analysis of human errors that have occurred. Finally, the above methods are applied to gas explosion accidents that occurred in China. Results show that the two methods proposed are universal to all fields, and their combination improves the effectiveness of human error management and promotes the targeted, proactive, systematic, and dynamic prevention of critical nodes and paths from a holistic perspective.

Bone marrow mesenchymal stem cells (BMMSCs) are characterized by their pluripotent differentiation and self-renewal capability and have been widely applied in regenerative medicine, gene therapy, and tissue repair. However, inflammatory response after BMMSCs transplantation was found to impair the osteogenic differentiation of BMMSCs. Thus, understanding the mechanisms underlying inflammation response will benefit the clinical use of BMMSCs. In this study, using a cell model of TNF-α-induced inflammatory response, we found that TNF-α treatment greatly elevated intracellular oxidative stress and induced endoplasmic reticulum (ER) stress by elevating the expression levels of ER sensors, such as PERK, ATF6 and IRE1A. Oxidative stress and ER stress formed a feedback loop to mediate TNF-α-induced inflammation response in BMMSCs. Moreover, c-Jun N-terminal kinase (JNK) signal pathway that coupled to the ER stress was significantly activated by increasing its phosphorylation upon TNF-α treatment. Importantly, pharmacological inhibition of ER stress effectively eliminated the phosphorylation of JNK and attenuated the TNF-α-induced inflammation response. In conclusion, our results indicated that TNF-α induced oxidative and ER stress, thereby leading to JNK activation, and generating inflammation response in BMMSCs. This pathway underlying TNF-α-induced inflammation response may provide new strategies to improve BMMSCs osteogenesis and other inflammation-associated bone diseases.

Maize is the food crop with the highest total output in the world. However, corn bran is only a by-product with low price. The 5,5'-diferulic acid glucoside esters (DFG) were obtained from corn bran using the enzymatic method. DFG showed obvious antioxidant capacity in cell, Caenorhabditis elegans (C. elegans) and in mouse. DFG decreased ROS and MDA content in 500 μM H2 O2 stimulated ARPE-19 cells to 48.6% and 32.2%, respectively. DFG decreased ROS content in C. elegans to 49.1% and MDA content in acute ethanol (50%, 12 ml/kg) stimulated mouse to 30.4%. DFG also increased SOD protein content significantly in cell, C. elegans and mouse to 175.5%, 120.1%, and 126.2%, respectively. DFG significantly extended the lifespan of C. elegans both under heat stress and natural situation. The median survival time was prolonged to 133.3% and 116.7%, respectively. This capacity relied on the SIR-2.1 activity. SIR-2.1 is an ortholog of human Sirtuin-1 (SIRT-1). DFG also upregulated SIRT-1 and PCG-1α expression level obviously in H2 O2 -stimulated ARPE-19 cells (to 134.4% and 127.1%, respectively) and in acute ethanol stimulated mouse eyes (to 135.1% and 111.5%, respectively) and liver (to 123.3% and 113.6%, respectively). These results indicate that DFG has multiple bioactivities. Our research provides a new application prospect of corn bran. And to our best knowledge, this is the first time, the sirtuins-relied lifespan extension activity of the 5,5'-diferulic acid extracted from corn bran was reported. PRACTICAL APPLICATIONS: The traditional method for extracting diferulic acid from corn bran is to use the strong alkali. Obviously, this is not welcomed by the food industry. We employed the biological enzyme method in a relatively mild pH range during the extraction process. It is more environmentally friendly and more economical. DFG can be added as a raw material for functional foods like yogurt, fruit juice, and cereals. As well, the solid precipitate obtained after extraction can also be used as high-quality dietary fiber to produce functional food. Meanwhile, concerning for the 5,5'-diferulic acid derived from corn bran, the relevant research is still not abundant. And to our best knowledge, we have reported for the first time about the effect of this kinds of diferulic acid on prolonging life span and its SIRT-1-dependent activity. It also provides a new perspective for the study of diferulic acid.

Insulin-like growth factor 1 (IGF-1), a multifunctional peptide that involves in cell proliferation and differentiation, can induce strong osteogenic differentiation in bone marrow mesenchymal stem cells (BMMSCs). However, it remains unknown whether intracellular Ca

Ubiquitin-specific protease 26 (USP26) encodes a predicted protein containing his- and cys- domains that are conserved among deubiquitinating enzymes. USP26 is specifically expressed in testis tissue and is a potential infertility gene. In the present study, we performed genetic testing related to spermatogenesis impairment in a patient with idiopathic severe oligozoospermia to identify the cause. The patient underwent clinical examination and reproductive hormone testing. Genes associated with male infertility, including USP26, were assessed by targeted exome sequencing. A novel frameshift mutation, c.2195delT (p.Phe732Serfs*14), was identified in USP26. This frameshift mutation was located in residue 732 of USP26 gene, leading to loss of the conserved deubiquitinating enzyme His-domain and producing a truncated protein of 744 amino acids. Bioinformatics analysis revealed this mutation to be pathogenic. A novel framshift mutation c.2195delT (p.Phe732Serfs*14) in USP26 gene was reported to be associated with male infertility in a Chinese patient with severe oligozoospermia.

Infantile neuroaxonal dystrophy (INAD) is a rare, lethal, autosomal recessive neurodegenerative disease and leads to progressive impairment of movement and cognition. A couple with a proband child with calcium-independent group VI phospholipase A2 (PLA2G6)-associated INAD and a previous affected pregnancy sought pre-implantation genetic diagnosis (PGD) to bear a healthy child. Intracytoplasmic sperm injection treatment was performed and 15 blastocystic embryos were obtained at days 5 and 6, and these biopsies were amplified. PGD was performed by next-generation sequencing-based linkage analysis in conjunction with aneuploidy screening. Only two embryos were considered for transfer. In the second frozen-thawed embryo transfer cycle, transfer of a mosaic PLA2G6 c.692G>T heterozygous embryo resulted in a singleton ongoing pregnancy. Prenatal diagnosis was performed using amniotic fluid cells, providing results consistent with those of PGD. The aneuploidy screen and karyotype analysis indicated that the chromosomes of the fetus were normal without any mosaicism. The present study reported the first successful PGD for INAD. For parents at risk, this strategy may successfully lead to pregnancies with embryos unlikely to develop INAD, thus providing valuable experience in reproductive management regarding INAD and potentially other single-gene disorders.

Polyaniline (PANI) and poly(o-toluidine) (POT) with various film thickness were electropolymerized using potentiostatic method at the surface of GC electrode. The two conducting polymers were characterized by CV, in situ UV–vis spectroscopy and electrochemical impedance spectroscopy. Two composite catalysts (Pt/PANI/GC and Pt/POT/GC) with various film growth charge have been fabricated by the electro deposition of Pt on the PANI/GC and POT/GC at −0.1 V. then they were used for the electrooxidation of methanol in 0.5 M H2SO4 containing 1.0 M methanol. The properties of both the polymers change with the increase of film growth charge. As-formed composite catalysts were characterized by SEM and the electrochemical methods. The Pt nanoparticles deposited at −0.1 V exhibit thorns morphology and good dispersion on the POT with the film growth charge of 4.5 mC. The electrocatalytic activity for methanol oxidation of Pt/POT/GC is higher than Pt/PANI/GC for all the film charge, and they both exhibit the largest electrocatalytic activity at film charge of 4.5 mC. The present study shows that Pt/POT/GC would be a promising choice for methanol electrooxidation in comparison with Pt/PANI/GC.