Metabolic and Bioprocess Engineering of Clostridium tyrobutyricum for Butyl Butyrate Production on Xylose and Shrimp Shell Waste.

Microbial conversion of agri-food waste to valuable compounds offers a sustainable route to develop the bioeconomy and contribute to sustainable biorefinery. Clostridium tyrobutyricum displays a series of native traits suitable for high productivity conversion of agri-food waste, which make it a promising host for the production of various compounds, such as the short-chain fatty acids and their derivative esters products. In this study, a butanol synthetic pathway was constructed in C. tyrobutyricum, and then efficient butyl butyrate production through in situ esterification was achieved by the supplementation of lipase into the fermentation. The butyryl-CoA/acyl-CoA transferase (cat1) was overexpressed to balance the ratio between precursors butyrate and butanol. Then, a suitable fermentation medium for butyl butyrate production was obtained with xylose as the sole carbon source and shrimp shell waste as the sole nitrogen source. Ultimately, 5.9 g/L of butyl butyrate with a selectivity of 100%, and a productivity of 0.03 g/L·h was achieved under xylose and shrimp shell waste with batch fermentation in a 5 L bioreactor. Transcriptome analyses exhibited an increase in the expression of genes related to the xylose metabolism, nitrogen metabolism, and amino acid metabolism and transport, which reveal the mechanism for the synergistic utilization of xylose and shrimp shell waste. This study presents a novel approach for utilizing xylose and shrimp shell waste to produce butyl butyrate by using an anaerobic fermentative platform based on C. tyrobutyricum. This innovative fermentation medium could save the cost of nitrogen sources (~97%) and open up possibilities for converting agri-food waste into other high-value products.

PANoptosis subtypes predict prognosis and immune efficacy in gastric cancer.

PANoptosis is a form of inflammatory programmed cell death that is regulated by the PANoptosome. This PANoptosis possesses key characteristics of pyroptosis, apoptosis, and necroptosis, yet cannot be fully explained by any of these cell death modes. The unique nature of this cell death mechanism has garnered significant interest. However, the specific role of PANoptosis-associated features in gastric cancer (GC) is still uncertain. Patients were categorized into different PAN subtypes based on the expression of genes related to the PANoptosome. We conducted a systematic analysis to investigate the variations in prognosis and tumor microenvironment (TME) among these subtypes. Furthermore, we developed a risk score, called PANoptosis-related risk score (PANS), which is constructed from genes associated with the PANoptosis. We comprehensively analyzed the correlation between PANS and GC prognosis, TME, immunotherapy efficacy and chemotherapeutic drug sensitivity. Additionally, we performed in vitro experiments to validate the impact of Keratin 7 (KRT7) on GC. We identified two PAN subtypes (PANcluster A and B). PANoptosome genes were highly expressed in PANcluster A. PANcluster A has the characteristics of favorable prognosis, abundant infiltration of anti-tumor lymphocytes, and sensitivity to immunotherapy, thus it was categorized as an immune-inflammatory type. Meanwhile, our constructed PANS can effectively predict the prognosis and immune efficacy of GC. Patients with low PANS have a good prognosis, and have the characteristics of high tumor mutation load (TMB), high microsatellite instability (MSI), low tumor purity and sensitivity to immunotherapy. In addition, PANS can also identify suitable populations for different chemotherapy drugs. Finally, we confirmed that KRT7 is highly expressed in GC. Knocking down the expression of KRT7 significantly weakens the proliferation and migration abilities of GC cells. The models based on PANoptosis signature help to identify the TME features of GC and can effectively predict the prognosis and immune efficacy of GC. Furthermore, the experimental verification results of KRT7 provide theoretical support for anti-tumor treatment.

Programming therapeutic probiotics by self-tunable sense-and-respond genetic circuits.

Probiotics can be programmed to sense and respond to intracellular disease signals to deliver the desired therapeutic effectors. The sense-and-respond genetic circuits, especially self-tunable ones, hold promise in improving the precision, effectiveness, and intelligence of therapeutic activities. Here, we present notable advances in the creation of engineered probiotics that harbour sense-and-respond genetic circuits.

An immunogenic cell death-related signature predicts prognosis and immunotherapy response in stomach adenocarcinoma.

The immunogenic cell death (ICD) is a specific type of regulatory cell death (RCD), which induces adaptive immunity against antigens of dead cells. ICDs have received increasing attention for their potential role in tumor microenvironment reprogramming and immunotherapy. However, the relationship between ICD-related features and stomach adenocarcinoma (STAD) prognosis, immune cell infiltration and immunotherapy remains unclear. Patients were divided into different ICD-related subtypes by consensus clustering. The differences in prognosis, Tumor microenvironment (TME), and immune checkpoint expression between different ICD-related subtypes were systematically assessed. Additionally, we constructed an ICD-related gene risk score (ICDRS). We systematically analyzed the correlation between ICDRS and prognosis, TME, immunotherapy response and drug sensitivity of gastric cancer. In addition, we explored the role of TGM2 in promoting gastric cancer progression through in vitro experiments. We identified three ICD-associated subtypes by consensus clustering. The ICD gene was highly expressed in Cluster B. Compared with the other two subtypes, Cluster B had better prognosis, higher immune response signaling activity, massive immune cell infiltration and lower tumor purity. Immune checkpoint (ICP) and human leukocyte antigen (HLA) related genes were also highly expressed in Cluster B. In addition, we found that ICDRS is an effective indicator for predicting the prognosis and immune efficacy of STAD. The low ICDRS group has the characteristics of good prognosis, high tumor mutation burden (TMB), high microsatellite instability (MSI), and sensitivity to immunotherapy, while the high ICDRS group is prone to immune escape and immunotherapy resistance. In addition, we found that down-regulating TGM2 gene can inhibit the proliferation and migration of gastric cancer cells through in vitro experiments. Our study found that the model based on ICD features is helpful to clarify the TME characteristics of STAD, and has important clinical significance for evaluating the prognosis and immunotherapy response of STAD patients. TGM2 plays an important role in the progression of STAD, suggesting that TGM2 can be used as a new target for the treatment of STAD.

Endogenous CRISPR-Cas mediated in situ genome editing: State-of-the-art and the road ahead for engineering prokaryotes.

The CRISPR-Cas systems have shown tremendous promise as heterologous tools for genome editing in various prokaryotes. However, the perturbation of DNA homeostasis and the inherent toxicity of Cas9/12a proteins could easily lead to cell death, which led to the development of endogenous CRISPR-Cas systems. Programming the widespread endogenous CRISPR-Cas systems for in situ genome editing represents a promising tool in prokaryotes, especially in genetically intractable species. Here, this review briefly summarizes the advances of endogenous CRISPR-Cas-mediated genome editing, covering aspects of establishing and optimizing the genetic tools. In particular, this review presents the application of different types of endogenous CRISPR-Cas tools for strain engineering, including genome editing and genetic regulation. Notably, this review also provides a detailed discussion of the transposon-associated CRISPR-Cas systems, and the programmable RNA-guided transposition using endogenous CRISPR-Cas systems to enable editing of microbial communities for understanding and control. Therefore, they will be a powerful tool for targeted genetic manipulation. Overall, this review will not only facilitate the development of standard genetic manipulation tools for non-model prokaryotes but will also enable more non-model prokaryotes to be genetically tractable.

Application of Circulating Tumor Cells and Interleukin-6 in Preoperative Prediction of Peritoneal Metastasis of Advanced Gastric Cancer.

Background: The purpose of this study was to explore the clinical significance of circulating tumor cells (CTCs) and cytokines in peripheral blood in preoperative prediction of peritoneal metastasis (PM) in advanced gastric cancer (AGC). Methods: The clinicopathological characteristics of 282 patients with AGC were retrospectively analyzed. The patients were divided into training and validation groups according to the time of receiving treatment. We used univariate analysis and multivariate logistic regression analysis to screen out the independent risk factors of PM in AGC. Then, we incorporated independent risk factors into the nomogram, and evaluated the discriminative ability. Results: The levels of CTCs and interleukin-6 (IL-6) of AGC patients with PM were higher than those without PM (P<0.05). Moreover, the levels of CTCs and IL-6 in the occult peritoneal metastasis (OPM) group and the CT-positive PM group were higher than those in the negative PM (P<0.05). Multivariate logistic regression analysis showed that IL-6 > 12.22 pg/mL, CTCs > 4/5mL, CA724 > 6 IU/mL, CA125 > 35 U/mL and tumor size > 5 cm were independent risk factors for PM of AGC. The area under the ROC curve of the nomogram were 0.898 and 0.926 in the training and validation sets, respectively. The clinical decision curve showed that the nomogram had good clinical utility. Conclusion: CTCs and IL-6 in peripheral blood are promising biomarkers for predicting the risk of PM in AGC. The nomogram constructed from five risk factors can effectively assess the risk of PM in AGC patients individually.

The Upregulation of GSTO2 is Associated with Colon Cancer Progression and a Poor Prognosis.

Colorectal cancer is the second-leading cause of cancer-related mortality in the United States. Glutathione S-transferase can affect the development of cancer. Glutathione S-transferase omega 2, a member of the GST family, plays an important role in many tumors. However, the role of Glutathione S-transferase omega 2 in the development of colon cancer remains unclear. Herein, our study aimed to investigate the exact role of Glutathione S-transferase omega 2 in colon cancer. We used RNA sequencing data from The Cancer Genome Atlas and the Genotype-Tissue Expression database to analyze Glutathione S-transferase omega 2 expressions. Then, we explore the protein information of Glutathione S-transferase omega 2 in the Human Protein Atlas, GeneCards, and String database. In addition, western blot and immunohistochemistry were performed to evaluate the protein levels of Glutathione S-transferase omega 2 in colon cancer tissues. We acquire data from the Gene Expression Omnibus and The Cancer Genome Atlas databases. Also, we performed relevant prognostic analyses of these data. In addition, we performed a statistical analysis of the clinical data from The Cancer Genome Atlas database and the expression level of Glutathione S-transferase omega 2. Then, we performed Cox regression analysis and found independent risk factors for prognosis in patients with colon cancer. The Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses were used to explore the potential biological functions of Glutathione S-transferase omega 2. The infiltration of colon cancer-immune cells was evaluated by the CIBERSORT method. RNA silencing was performed using siRNA constructs in HCT-116 and HT-29 cell lines. Cell Counting Kit-8 and EdU assays were performed to determine cell proliferation. Transwell experiments and scratch tests were used to determine cell migration. As for the mRNA and protein expression levels of cells, we used quantitative real-time PCR and western blot to detect them. Our research shows that Glutathione S-transferase omega 2 is overexpressed in colon cancer patients, and this overexpression is associated with a poor prognosis. The high expression of Glutathione S-transferase omega 2 is significantly correlated stage with stage, M, and N classification progression in colon cancer by statistical analysis. Univariate and multivariate Cox regression analyses showed that Glutathione S-transferase omega 2 was an independent risk factor for poor prognosis in colon cancer. In addition, we also found that Glutathione S-transferase omega 2 expression levels can affect the immune microenvironment of colon cancer cells. Gene silencing of Glutathione S-transferase omega 2 in HT-29 and HCT-116 cells significantly inhibited tumor growth and migration. In summary, we found that Glutathione S-transferase omega 2 can be used as a molecular indicator of colon cancer prognosis. In vitro, gene silencing of Glutathione S-transferase omega 2 inhibited colon cancer cells' growth and migration.

Impact of primary tumor resection on the survival of patients with unresectable colon cancer liver metastasis at different colonic subsites: a propensity score matching analysis.

OBJECTIVE: To investigate the effect of primary tumor resection (PTR) on the prognosis of patients with unresectable colon cancer liver metastasis (UCCLM) at seven colonic subsites using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Propensity score matching (PSM) was performed to balance selection bias using all available variables that could be of potential relevance. After matching, the groups were redefined in a 1:1 ratio using the nearest method. Cancer-specific survival (CSS) was compared among the patients of PTR and non-PTR groups. Cox regression models were used to identify the prognostic factors for CSS. RESULTS: CSS was significantly different between all groups. Cox regression analysis showed that PTR was an independent prognostic factor for all groups. After PSM, PTR significantly prolonged CSS for all groups. Subgroup analysis showed that PTR did not improve the prognosis of N2 stage patients in the cecum, ascending colon, and descending colon groups; T1 + T2 stage patients in the hepatic flexure group; and patients with a tumor size ≤5 cm in the splenic flexure group. Segmental colectomy could prolong CSS of patients in the cecum, ascending colon, transverse colon, splenic flexure, and sigmoid colon groups, while extended colectomy could prolong CSS of patients in the hepatic flexure and descending colon groups. CONCLUSION: At different colonic subsites, UCCLM patients had different CSS. PTR could improve their prognosis, however, N stage, T stage, and tumor size are important reference indicators. In addition to patients in the hepatic flexure and descending colon groups, we suggested that patients in other groups should choose segmental colectomy.

Uncovering the information immunology journals transmitted for COVID-19: A bibliometric and visualization analysis.

Background: Since the global epidemic of the coronavirus disease 2019 (COVID-19), a large number of immunological studies related to COVID-19 have been published in various immunology journals. However, the results from these studies were discrete, and no study summarized the important immunological information about COVID-19 released by these immunology journals. This study aimed to comprehensively summarize the knowledge structure and research hotspots of COVID-19 published in major immunology journals through bibliometrics. Methods: Publications on COVID-19 in major immunology journals were obtained from the Web of Science Core Collection. CiteSpace, VOSviewer, and R-bibliometrix were comprehensively used for bibliometric and visual analysis. Results: 1,331 and 5,000 publications of 10 journals with high impact factors and 10 journals with the most papers were included, respectively. The USA, China, England, and Italy made the most significant contributions to these papers. University College London, National Institute of Allergy and Infectious Diseases, Harvard Medical School, University California San Diego, and University of Pennsylvania played a central role in international cooperation in the immunology research field of COVID-19. Yuen Kwok Yung was the most important author in terms of the number of publications and citations, and the H-index. CLINICAL INFECTIOUS DISEASES and FRONTIERS IN IMMUNOLOGY were the most essential immunology journals. These immunology journals mostly focused on the following topics: "Delta/Omicron variants", "cytokine storm", "neutralization/neutralizing antibody", "T cell", "BNT162b2", "mRNA vaccine", "vaccine effectiveness/safety", and "long COVID". Conclusion: This study systematically uncovered a holistic picture of the current research on COVID-19 published in major immunology journals from the perspective of bibliometrics, which will provide a reference for future research in this field.

Revealing novel synergistic defense and acid tolerant performance of Escherichia coli in response to organic acid stimulation.

Escherichia coli is an important producer of mono- and di-acids, such as D-lactic acid, itaconic acid, and succinic acid. However, E. coli has limited acid tolerance and requires neutralizers in large-scale fermentation, which leads to increased production costs. Mutagenesis breeding has been shown to be inefficient in improving the acid tolerance of strains. Therefore, it is crucial to analyze the acid resistance mechanism of E. coli. To this end, important regulatory genes and metabolic pathways in the highly evolved acid-resistant E. coli were identified based on transcriptome sequencing. By analyzing the overlap of the genes with significantly different expression levels in the four groups, a synergistic membrane-centric defense mechanism for E. coli against organic acid stress was identified. The mechanism includes four modules: signal perception, energy countermeasures, input conditioning, and envelope reinforcement. In addition, genes related to the ABC transporter pathway, polyketide metabolism, pyrimidine metabolism, and dual-arginine translocation system pathways were found for the first time to be potentially resistant to organic acid stress after overexpression. A new antacid ingredient, RffG, increases the survival rate of E. coli by 4509.6 times. This study provides new clues for improving the performance of acid-tolerant cells and reducing the production cost of industrial organic acid fermentation. KEY POINTS: • Systematic analysis of the mechanism of membrane protein partitioning in E. coli to resist organic acids • TAT system transports correctly folded hydrogenase accessory proteins to resist D-lactic acid stress • Enhanced PG synthesis and weakened hydrolysis to reduce acid penetration into cells • Overexpression of RffG in the polyketide synthesis pathway enhances acid tolerance.

Nano-drug delivery system for pancreatic cancer: A visualization and bibliometric analysis.

Background: Nano drug delivery system (NDDS) can significantly improve the delivery and efficacy of drugs against pancreatic cancer (PC) in many ways. The purpose of this study is to explore the related research fields of NDDS for PC from the perspective of bibliometrics. Methods: Articles and reviews on NDDS for PC published between 2003 and 2022 were obtained from the Web of Science Core Collection. CiteSpace, VOSviewer, R-bibliometrix, and Microsoft Excel were comprehensively used for bibliometric and visual analysis. Results: A total of 1329 papers on NDDS for PC were included. The number of papers showed an upward trend over the past 20 years. The United States contributed the most papers, followed by China, and India. Also, the United States had the highest number of total citations and H-index. The institution with the most papers was Chinese Acad Sci, which was also the most important in international institutional cooperation. Professors Couvreur P and Kazuoka K made great achievements in this field. JOURNAL OF CONTROLLED RELEASE published the most papers and was cited the most. The topics related to the tumor microenvironment such as "tumor microenvironment", "tumor penetration", "hypoxia", "exosome", and "autophagy", PC treatment-related topics such as "immunotherapy", "combination therapy", "alternating magnetic field/magnetic hyperthermia", and "ultrasound", and gene therapy dominated by "siRNA" and "miRNA" were the research hotspots in the field of NDDS for PC. Conclusion: This study systematically uncovered a holistic picture of the performance of NDDS for PC-related literature over the past 20 years. We provided scholars to understand key information in this field with the perspective of bibliometrics, which we believe may greatly facilitate future research in this field.

Prognostic significance of the preoperative hemoglobin to albumin ratio for the short-term survival of gastric cancer patients.

BACKGROUND: Hemoglobin and albumin are associated with the prognosis of gastric cancer (GC) patients. However, the prognostic value of the hemoglobin to albumin ratio (HAR) for the short-term survival of GC patients with D2 radical resection has not been studied. AIM: To investigate the significance of the HAR in evaluating the short-term survival of GC patients after D2 radical resection and to construct a nomogram to predict the prognosis in GC patients after surgery, thus providing a reference for the development of postoperative individualized treatment and follow-up plans. METHODS: Cox regression and Kaplan-Meier analysis was used for prognostic analysis. Logistic regression was used to analyze the relationships between HAR and the clinicopathological characteristics of the GC patients. A prognostic nomogram model for the short-term survival of GC patients was constructed by R software. RESULTS: HAR was an independent risk factor for the short-term survival of GC patients. GC patients with a low HAR had a poor prognosis (P < 0.001). Low HAR was markedly related to high stage [odds ratio (OR) = 0.45 for II vs I; OR = 0.48 for III vs I], T classification (OR = 0.52 for T4 vs T1) and large tumor size (OR = 0.51 for ≥ 4 cm vs < 4 cm) (all P < 0.05). The nomogram model was based on HAR, age, CA19-9, CA125 and stage, and the C-index was 0.820. CONCLUSION: Preoperative low HAR was associated with short-term survival in GC patients. The prognostic nomogram model can accurately predict the short-term survival of GC patients with D2 radical resection.

Complete Genome Sequencing Analysis of Deinococcus wulumuqiensis R12, an Extremely Radiation-Resistant Strain.

Genome sequencing was performed by the PacBio RS II platform and Illumina HiSeq 4000 platform to discover the metabolic profile of the Deinococcus wulumuqiensis R12, which was isolated from radiation-contaminated soils in Xinjiang Uygur Autonomous Region of northwest China. The genome of 3.5 Mbp comprises one circular chromosome and four circular plasmids with 3679 genes and a GC content of 66.97%. A total of 41 new transcriptional factors were identified using the DeepTFactor tool. Genomic analysis revealed the presence of genes for homologous recombination repair, which suggested high recombination efficiency in R12. Three Type I and one Type II RM systems, two CRISPR arrays, and one Cas-Type IC protein were found, allowing the development of endogenous CRISPR-Cas gene-editing tools. Additionally, we found that R12 has a broad spectrum of substrate utilization, which was validated by physiological experiments. Genes involved in the carotenoid biosynthesis pathway and the antioxidative system were also identified. Overall, the comprehensive description of the genome of R12 will facilitate the additional exploitation of this strain as a versatile cell factory for biotechnological applications.

Comparative transcriptome analysis reveals the contribution of membrane transporters to acid tolerance in Lactococcus lactis.

Acid stress caused by the accumulation of acidic metabolites severely affects the fermentation performance of lactic acid bacteria. In this study, to overcome the impact of acid stress during growth, nine membrane transporters were introduced in Lactococcus lactis NZ9000 to study their effects on acid tolerance. The engineered strains that overexpressed the metal ATP-binding cassette (ABC) transporters zitP (metal ABC transporter permease) and zitQ (metal ABC transporter ATP-binding protein) exhibited 14.5 and 9.5-fold higher survival rates, respectively, at pH 4.0 for 4 h than the control strain. During acid stress, the two recombinant strains maintained relatively higher ATP concentrations, i.e., 7.7- and 11.7-fold higher, respectively, than the control strain at pH 4.0 for 3 h. Subsequently, transcriptome analysis revealed that genes associated with ABC transporters, metal ion transport, transcriptional regulation, and stress response exhibited differentially expressed. The transcriptional level of ecfA2 gene (energy-coupling factor transporter ATPase) was substantially higher in L. lactis (ZitQ) during acid stress, and the ecfA2 gene was overexpressed in L. lactis. This recombinant strain L. lactis (EcfA2) exhibited a 598.7-fold higher survival rate than the control strain at pH 4.0 for 4 h. This study showed that the membrane transporters ZitP and ZitQ could increase acid tolerance and provided a strategy for constructing robust strains that can be used in food industry.

Clostridium as microbial cell factory to enable the sustainable utilization of three generations of feedstocks.

The sustainable production of chemicals and biofuels from non-fossil carbon sources is considered key to reducing greenhouse gas (GHG) emissions. Clostridium sp. can convert various substrates, including the 1st-generation (biomass crops), the 2nd-generation (lignocellulosic biomass), and the 3rd-generation (C1 gases) feedstocks, into high-value products, which makes Clostridia attractive for biorefinery applications. However, the complexity of lignocellulosic catabolism and C1 gas utilization make it difficult to construct efficient production routes. Accordingly, this review highlights the advances in the development of three generations of feedstocks with Clostridia as cell factories. At the same time, more attention was given to using agro-industrial wastes (lignocelluloses and C1 gases) as the feedstocks, for which metabolic and process engineering efforts were comprehensively analyzed. In addition, the challenges of using agro-industrial wastes are also discussed. Lastly, several new synthetic biology tools and regulatory strategies are emphasized as promising technologies to be developed to address the aforementioned challenges in Clostridia and realize the efficient utilization of agro-industrial wastes.

Role of CNSs Conserved Distal Cis-Regulatory Elements in CD4 + T Cell Development and Differentiation.

Naïve CD4+ T cells differentiate into diverse subsets of effector cells and perform various homeostatic and immune functions. The differentiation and maintenance of these different subsets are controlled through the upregulation and silencing of master genes. Mechanistic studies of the regulation of these master genes identified conserved and distal intronic regulatory elements, which are accessible subsets of conserved non-coding sequences (CNSs), acting as cis-regulatory elements in a lineage-specific manner that controls the function of CD4+ T cells. Abnormal CNS activity is associated with incorrect expression of master genes and development of autoimmune diseases or immune suppression. Here, we describe the function of several conserved, distal cis-regulatory elements at the Foxp3, Rorc, Il-4, Il-10 and Il-17 gene locus were shown to play important roles in CD4+ T cells differentiation. Together, this review briefly outlines currently known CNSs, with a focus on their regulations and functions in complexes modulating the differentiation and maintenance of various CD4+ T cells subsets, in health and disease contexts, as well as during the conversion of T regulatory cells to T helper 17 cells. This article will provide a comprehensive view of CNSs conserved distal cis-regulatory elements at a few loci that control aspects of CD4+ T cells function.

Functional Characterization of Clostridium tyrobutyricum L319: A Promising Next-Generation Probiotic for Short-Chain Fatty Acid Production.

Probiotics contribute a lot to human health and the occurrence of diseases. Correspondingly, probiotics' safety evaluation and probiotic properties have received increasing attention in the food industry and disease treatment. Clostridium tyrobutyricum L319 is a short-chain fatty acid (SCFA)-producing strain isolated from Grana Padano cheese with a blowing defect. Our previous study has shown its safety at the genomic level. This study focused more on the safety evaluation and probiotic properties in vitro. According to the results, this strain has no potential virulence factors or the possibility of antibiotic resistance genes propagation. It also fulfilled several criteria to be used as a probiotic, including significant hydrophobicity under an acidic condition (pH 5.0) and resistance to simulate gastric juice and intestinal juice. Additionally, this strain was found to be tolerant to the harsh conditions of the external environment, including resistance to low (20°C) and high (50°C) temperatures, high salts (3% NaCl), and low pH (pH 5.0). Finally, we found that this strain could ferment prebiotics, such as chito-oligosaccharides, to produce SCFAs. It exhibited excellent growth performance whether using chito-oligosaccharide as a sole carbon source or combining glucose as the mixed carbon source. Furthermore, chito-oligosaccharide and glucose (1:1) mixed carbon sources were the optimal strategy for the production of SCFAs. Our findings demonstrated that this strain might be considered a promising candidate for future use as a probiotic to promote health benefits.

FAT10 promotes chemotherapeutic resistance in pancreatic cancer by inducing epithelial-mesenchymal transition via stabilization of FOXM1 expression.

Pancreatic cancer (PC) is one of the deadliest malignant tumors, and its resistance to gemcitabine chemotherapy is the primary reason for poor prognosis in patients. Ubiquitin-like protein FAT10 has recently been reported to promote tumor chemotherapy resistance. In this study, the expression of FAT10 in PC was significantly higher than that in adjacent noncancerous tissues. Increased expression of FAT10 in PC was related to a late TNM stage and decreased overall survival. Functional experiments revealed that downregulating the expression of FAT10 inhibits the proliferation and epithelial-mesenchymal transition (EMT) of PC cells, promotes the apoptosis of PC cells, and enhances sensitivity to gemcitabine chemotherapy. In addition, upregulation of FAT10 increased the expression of FOXM1 protein. The effect of downregulating FAT10 was reversed by FOXM1 overexpression, and FOXM1 knockdown inhibited EMT driven by FAT10 overexpression. Mechanistically, FAT10 stabilized the expression of FOXM1 by competing with ubiquitin to bind FOXM1 and inhibiting the ubiquitination-mediated degradation of FOXM1. In conclusion, the FAT10-FOXM1 axis is a pivotal driver of PC proliferation and gemcitabine resistance, and the results provide novel insights into chemotherapy resistance in PC.

Establishment of a Dynamic Nomogram for Predicting the Risk of Lymph Node Metastasis in T1 Stage Colorectal Cancer.

Background: Accurate prediction of the risk of lymph node metastasis in patients with stage T1 colorectal cancer is crucial for the formulation of treatment plans for additional surgery and lymph node dissection after endoscopic resection. The purpose of this study was to establish a predictive model for evaluating the risk of LNM in patients with stage T1 colorectal cancer. Methods: The clinicopathological and imaging data of 179 patients with T1 stage colorectal cancer who underwent radical resection of colorectal cancer were collected. LASSO regression and a random forest algorithm were used to screen the important risk factors for LNM, and a multivariate logistic regression equation and dynamic nomogram were constructed. The C index, Calibration curve, and area under the ROC curve were used to evaluate the discriminant and prediction ability of the nomogram. The net reclassification index (NRI), comprehensive discriminant improvement index (IDI), and clinical decision curve (DCA) were compared with traditional ESMO criteria to evaluate the accuracy, net benefit, and clinical practicability of the model. Results: The probability of lymph node metastasis in patients with T1 colorectal cancer was 11.17% (20/179). Multivariate analysis showed that the independent risk factors for LNM in T1 colorectal cancer were submucosal invasion depth, histological grade, CEA, lymphovascular invasion, and imaging results. The dynamic nomogram model constructed with independent risk factors has good discrimination and prediction capabilities. The C index was 0.914, the corrected C index was 0.890, the area under the ROC curve was 0.914, and the accuracy, sensitivity, and specificity were 93.3, 80.0, and 91.8%, respectively. The NRI, IDI, and DCA show that this model is superior to the ESMO standard. Conclusion: This study establishes a dynamic nomogram that can effectively predict the risk of lymph node metastasis in patients with stage T1 colorectal cancer, which will provide certain help for the formulation of subsequent treatment plans for patients with stage T1 CRC after endoscopic resection.

Dynamic regulation of gut Clostridium-derived short-chain fatty acids.

Short-chain fatty acids (SCFAs) are major products of intestinal microbial fermentation with beneficial effects for human health. The dynamic balance and real-time monitoring of endogenous SCFA biosynthesis are important for understanding their physiological functions. We discuss the promising future of applying CRISPRi genetic systems and biosensors for targeted SCFA improvement.