Analysis of stage parameters of low-temperature oxidation of water-soaked coal based on kinetic principles.

Mine fires caused by spontaneous coal combustion are major disasters in coal mines. The staged oxidation kinetic parameters of various coal samples at oxygen concentrations of 21 %, 15 %, 10 %, 5 %, and 3 % were analyzed using a programmed temperature testing system. Herein, the temperature increase rate of coal, the temperature difference between the furnace and coal, and the oxygen consumption characteristics were obtained. Based on the amount of CO produced and the temperature sensitivity coefficient, three characteristic temperatures and four stages of low-temperature oxidation (LTO) were identified. The results showed that at a critical temperature (TC), the amount of CO gas released from the coal samples increased with increasing oxygen concentration, and the difference in the oxygen consumption rate increased. After the limit temperature (Tu), the amount of CO gas increased steadily, and the increase in the oxygen consumption rate stagnated. CO production, the maximum heating rate, and the maximum heat release rate were positively correlated with the oxygen concentration. As the oxygen concentration increased, the activation energy during the oxygen absorption stage gradually decreased. The average reaction enthalpy (ΔH) of pre-oxidized water-immersed coal was 19.37 kJ/kg greater than that of raw coal. The equation for the conservation of energy of the coal oxidation warming process was normalized. The theoretical values of the awakening stage and the stable stage were τν and τν (1-B), respectively. When B was >1, pre-oxidized water-immersed coal at a low oxygen concentration was prone to crossover points during the oxygen absorption stage, which increased the risk of coal spontaneous combustion (CSC). The research results could provide a theoretical basis for the staged control of the spontaneous combustion of water-immersed coal in goaf areas.

Pitfalls in Developing Machine Learning Models for Predicting Cardiovascular Diseases: Challenge and Solutions.

UNSTRUCTURED: In recent years, there has been an explosive development of artificial intelligence (AI), which has been widely applied in the healthcare field. As a typical AI technology, machine learning (ML) models have emerged as great potential in predicting cardiovascular diseases (CVDs) by leveraging large amounts of medical data for training and optimization, which are expected to play a crucial role in reducing the incidence and mortality rates of CVDs. Although the field has become a research hotspot, there are still many pitfalls that researchers need to pay close attention to. These pitfalls may affect the predictive performance, credibility, reliability, reproducibility of the studied models, ultimately reducing the value of the research and affecting the prospects for clinical application. Therefore, identifying and avoiding these pitfalls is a crucial task before implementing the research. However, there is currently a lack of comprehensive summary on this topic. This viewpoint aims to analyze the existing problems in terms of data quality, dataset characteristics, model design and statistical methods as well as clinic implication, and provide possible solutions to these problems, like gathering objective data, improving training, repeating measurements, increasing sample size, preventing overfitting using statistical methods, utilizing specific AI algorithms to address targeted issues, standardizing outcomes and evaluation criteria, as well as enhancing fairness and replicability, with the goal of offering reference and assistance to researchers, algorithm developers, policy makers, and clinical practitioners.

Artificial intelligence in the risk prediction models of cardiovascular disease and development of an independent validation screening tool: a systematic review.

BACKGROUND: A comprehensive overview of artificial intelligence (AI) for cardiovascular disease (CVD) prediction and a screening tool of AI models (AI-Ms) for independent external validation are lacking. This systematic review aims to identify, describe, and appraise AI-Ms of CVD prediction in the general and special populations and develop a new independent validation score (IVS) for AI-Ms replicability evaluation. METHODS: PubMed, Web of Science, Embase, and IEEE library were searched up to July 2021. Data extraction and analysis were performed for the populations, distribution, predictors, algorithms, etc. The risk of bias was evaluated with the prediction risk of bias assessment tool (PROBAST). Subsequently, we designed IVS for model replicability evaluation with five steps in five items, including transparency of algorithms, performance of models, feasibility of reproduction, risk of reproduction, and clinical implication, respectively. The review is registered in PROSPERO (No. CRD42021271789). RESULTS: In 20,887 screened references, 79 articles (82.5% in 2017-2021) were included, which contained 114 datasets (67 in Europe and North America, but 0 in Africa). We identified 486 AI-Ms, of which the majority were in development (n = 380), but none of them had undergone independent external validation. A total of 66 idiographic algorithms were found; however, 36.4% were used only once and only 39.4% over three times. A large number of different predictors (range 5-52,000, median 21) and large-span sample size (range 80-3,660,000, median 4466) were observed. All models were at high risk of bias according to PROBAST, primarily due to the incorrect use of statistical methods. IVS analysis confirmed only 10 models as "recommended"; however, 281 and 187 were "not recommended" and "warning," respectively. CONCLUSION: AI has led the digital revolution in the field of CVD prediction, but is still in the early stage of development as the defects of research design, report, and evaluation systems. The IVS we developed may contribute to independent external validation and the development of this field.

The "Trinity" smart hospital construction policy promotes the development of hospitals and health management in China.

Recently, in order to comprehensively promote the development of medical institutions and solve the nationwide problems in the healthcare fields, the government of China developed an innovative national policy of "Trinity" smart hospital construction, which includes "smart medicine," "smart services," and "smart management". The prototype of the evaluation system has been established, and a large number of construction achievements have emerged in many hospitals. In this article, the summary of this field was performed to provide a reference for medical workers, managers of hospitals, and policymakers.

ELABELA-APJ-Akt/YAP Signaling Axis: A Novel Mechanism of Aerobic Exercise in Cardioprotection of Myocardial Infarction Rats.

PURPOSE: The aim of this study was to investigate the function and mechanisms of ELABELA (ELA) in the aerobic exercise-induced antiapoptosis and angiogenesis of ischemic heart. METHODS: The myocardial infarction (MI) model of Sprague-Dawley rat was established by the ligation of the left anterior descending coronary artery. MI rats underwent 5 wk of Fc-ELA-21 subcutaneous injection and aerobic exercise training using a motorized rodent treadmill. Heart function was evaluated by hemodynamic measures. Cardiac pathological remodeling was evaluated by Masson's staining and the calculation of left ventricular weight index. Cell proliferation, angiogenesis, and Yes-associated protein (YAP) translocation were observed by immunofluorescence staining. Cell apoptosis was analyzed by TUNEL. Cell culture and treatment were used to elucidate the molecular mechanism of ELA. Protein expression was detected by Western blotting. Angiogenesis was observed by tubule formation test. One-way or two-way ANOVA and Student's t -test were used for statistical analysis. RESULTS: Aerobic exercise stimulated the endogenous ELA expression. Exercise and Fc-ELA-21 intervention significantly activated APJ-Akt-mTOR-P70S6K signaling pathway, kept more cardiomyocytes alive, and increased angiogenesis, so as to inhibit the cardiac pathological remodeling and improved the heart function of MI rats. Fc-ELA-32 also had the cellular and functional cardioprotective activities in vivo . In vitro , ELA-14 peptide regulated the phosphorylation and nucleoplasmic translocation of YAP and activated the APJ-Akt signaling pathway so as to increase the proliferation of H9C2 cells. Moreover, the antiapoptosis and the tubule formation of HUVECs were also enhanced by ELA-14, whereas the inhibition of Akt activity weakened such effects. CONCLUSIONS: ELA is a potential therapeutic member that plays a key role through APJ-Akt/YAP signaling axis in aerobic exercise-induced cardioprotection of MI rats.

Engineered Phomopsis liquidambaris with Fhb1 and Fhb7 Enhances Resistance to Fusarium graminearum in Wheat.

Fusarium head blight is one of the most serious diseases caused by Fusarium graminearum in wheat. Here, we developed a new way to prevent and control Fusarium head blight by introducing the resistance genes Fhb1 and Fhb7 into the endophytic fungus Phomopsis liquidambaris, named PL-Fhb1 and PL-Fhb7, respectively, which could colonize wheat. The wheat seedlings were preinoculated with PL-Fhb1 and PL-Fhb7 to enhance the resistance against deoxynivalenol (DON) and PL-Fhb1 and PL-Fhb7 inhibited the growth of F. graminearum by 73% and 49%, respectively. The incidence rate of diseased spikes decreased to 35.2% and 45.4%, and the corresponding DON levels for wheat grains decreased from 13.2 to 1.79 µg/g and from 13.2 µg/g to 0.39 µg/g when the leaves were preinoculated with PL-Fhb1 and PL-Fhb7 after overwintering, respectively. The incidence rates of diseased spikes decreased to 25.7% and 34.7%, and the DON levels for wheat grains decreased from 17.48 µg/g to 1.23 µg/g and from 17.48 µg/g to 0 µg/g when the wheat flowers were inoculated with PL-Fhb1 and PL-Fhb7, and the wheat flowers were subsequently infected with F. graminearum, respectively. It was confirmed that DON was transformed into DON-glutathione (GSH) by PL-Fhb7 using high-performance liquid chromatography-mass spectrometry (HPLC-MS). However, PL-Fhb1 may have increased plant immunity and enhanced the resistance to F. graminearum. This study indicates that engineered endophytes can improve the resistance to Fusarium head blight and presents a new method for the biological control of Fusarium head blight.

Comparative Study of Elabela and Apelin on Apelin Receptor Activation Through ß-Arrestin Recruitment.

Apelin receptor (APJ) ligands elabela (ELA) and apelin have divergent distributions and function differently in vitro and in vivo. Whether differences exist in their capacity of recruitment of ß-arrestins (ARRBs) to APJ remains unknown. The aim of the current study was to investigate the different effects of ELA and apelin on the interaction between APJ and ARRBs in live cells by NanoBiT®. NanoBiT® system is a new technology for studying protein-protein interaction in real-time in live cells, based on the emission of luminescence when two split components of NanoLuc luciferase, large Bit (LgBit) and small Bit (SmBit), complement each other to form an enzymatically active entity. We tagged the APJ and ARRBs with LgBit or SmBit and then evaluated their interactions in transiently transfected HEK293T cells, and determined the signal strength yielded as a result of the interaction. We also investigated the concentration-dependent response of the APJ-ARRB interaction in response to ELA and apelin. Finally, we assessed the effect of F13A, an APJ antagonist which is structurally very similar to apelin-13, on ELA- and apelin-mediated APJ-ARRB interactions. The NanoLuc® luciferase signal was highest in the pair of APJ-LgBit with SmBit-ARRB1 or SmBit-ARRB2. NanoLuc® luciferase signal increased in a concentration-dependent manner from 0.1 nM to 10 µM in response to ELA or apelin. Interestingly, ELA elicited weaker APJ-ARRB interaction signals than apelin. Pre-treatment with F13A potently reduced the APJ-ARRB interaction in response to both ELA and apelin. Our results demonstrated that both ELA and apelin promoted the interaction of APJ and ARRBs in a concentration-dependent manner, and ELA is less efficacious than apelin in inducing the recruitment of ARRBs to APJ, providing a biased functional aspect of ELA vs. apelin at the receptor signaling level. Additionally, ELA and apelin may share the same binding site(s) or pocket(s) at the APJ level.

[Effects of Microplastic Exposure on Crucian Growth, Liver Damage, and Gut Microbiome Composition].

Microplastics (MPs), which are widely present in the natural environment, may be harmful to the growth and health of aquatic organisms, though studies in this area are lacking. In this study, the crucian carp (Carassius carassius), a type of omnivorous freshwater fish, was chosen as the target, which was fed with fish food containing different concentrations of MPs for a 30-day food exposure experiment to study the effects of MPs on crucian growth, liver damage, and gut microbiome composition. Compared with that in the control group, the body length of the crucians in the environmental groups did not change significantly. The weight of the crucians in the low PE-MPs group increased significantly, but the weight of crucians in the medium and high PE-MPs groups decreased markedly. The liver tissues of the low PE-MPs group of crucians were basically normal, whereas crucians in the medium and high PE-MPs groups had varying degrees of liver damage, and crucians in the high PE-MPs group had the most serious liver damage. At the phylum level, Proteobacteria, Fusobacteria, Firmicutes, and Bacteroides were the dominant species in the gut of the crucians. Pathogens such as Staphylococcus and Ralstonia were present in the crucian gut of environmental groups. Alpha diversity results showed that the gut microbiome of crucians in the high PE-MPs group was the most abundant. PCoA results indicated that the gut microbiome of crucians in the control and environmental groups had obvious clustering characteristics.

Effects of heavy ions (12C6+) on malignant melanoma B16F10 cells.

Background: This study aimed to investigate the effects of heavy ion (12C6+) irradiation on the proliferation, apoptosis, cell cycle, migration, and epithelial-mesenchymal transition (EMT) of B16F10 cells. Methods: The B16F10 cells, which is a malignant melanoma cell line widely used in research, irradiated by 12C6+ and X-ray were detected by Hoechst 33342/propidium iodide double staining, Western blot, flow cytometry, and cell scratch tests to evaluate cell proliferation, expression of apoptosis-related proteins, G2/M phase arrest, cell migration, cell invasion and EMT. Results: Compared with the same physical X-ray dose, 12C6+ could effectively inhibit the proliferation of B16F10 cells, inhibit the expression of B-cell lymphoma-2 (Bcl-2) and cellular-myelocytomatosis viral oncogene (c-Myc), and induce the expression of Bax to promote the apoptosis of B16F10 cells. After 12C6+ irradiation, the B16F10 cells exhibited G2/M phase arrest. B16F10 cells were highly sensitive to 12C6+ irradiation. Moreover, compared with X-ray, the 12C6+ irradiation significantly inhibited the migration of B16F10 cells and inhibited extracellular matrix cleavage, induced E-cadherin expression, enhanced cell adhesion, and further inhibited cell invasion, migration, and EMT. Conclusions: The B16F10 cells were highly radiosensitive to 12C6+. Compared with X-ray, B16F10 cells irradiated by 12C6+ significantly reduced the expressions of matrix metalloproteinases to inhibit extracellular matrix cleavage and, thus, effectively inhibit cell invasion and metastasis. However, although the issue of the different therapeutic effects of heavy ion and X-ray radiotherapy on malignant melanoma was investigated and preliminary research results were obtained, several problems must be further studied.

Effect of Fc-Elabela-21 on renal ischemia/reperfusion injury in mice: Mediation of anti-apoptotic effect via Akt phosphorylation.

INTRODUCTION: Renal ischemia/reperfusion injury (IRI) is the most common cause of acute kidney injury (AKI), and patients with AKI have a high rate of mortality. Apelin is a therapeutic candidate for treatment of IRI and Elabela (ELA) is a recently discovered hormone that also activates the apelin receptor (APJ). We examined the use of ELA as a preventive treatment for IRI using in vitro and in vivo models. METHODS: Male mice were subjected to renal IRI, with or without administration of a stabilized form of ELA (Fc-ELA-21) for 4 days. Renal tubular lesions were measured using H&E staining, reactive oxygen species (ROS) were measured using a dihydroethidium stain assay, and renal cell apoptosis was measured using the TUNEL assay and flow cytometry. Immortalized human proximal tubular epithelial (HK-2) cells were pretreated with or without LY294002 and/or ELA-32, maintained at normoxic or hypoxic conditions, and then returned to normal culture conditions to mimic IRI. Cell apoptosis was determined using the TUNEL assay and cell proliferation was determined using the MTT assay. The levels of Akt, p-Akt, ERK1/2, p- ERK1/2, Bcl-2, Bax, caspase-3 and cleaved caspase-3 were measured using western blotting. RESULTS: Fc-ELA-21 administration reduced renal tissue damage, ROS production, and apoptosis in mice that had renal IRI. ELA-32 reduced HK-2 cell apoptosis and restored the proliferation of cells subjected to IRI. Akt phosphorylation had a role in the anti-apoptotic effect of ELA. CONCLUSION: This study of in vitro and in vivo models of IRI indicated that the preventive and anti-apoptotic effects of ELA were mediated via the PI3K/Akt signaling pathway.

STK38 is a PPARγ-interacting protein promoting adipogenesis.

Peroxisome proliferator-activated receptor-γ (PPARγ) is the master regulator of adipogenesis, but knowledge about how PPARγ is regulated at the protein level is very limited. We aimed to identify PPARγ-interacting proteins which modulate PPARγ's protein levels and transactivating activities in human adipocytes. We expressed Flag-tagged PPARγ in human preadipocytes as bait to capture PPARγ-associated proteins, followed by mass spectroscopy and proteomics analysis, which identified serine/threonine kinase 38 (STK38) as a major PPARγ-associated protein. Protein pulldown studies confirmed this protein-protein interaction in transfected cells, and reporter assays demonstrated that STK38 enhanced PPARγ's transactivating activities without requiring STK38's kinase activity. In cell-based assays, STK38 increased PPARγ protein stability, extending PPARγ's half-life from ~1.08 to 1.95 h. Notably, in human preadipocytes, the overexpression of STK38 enhanced adipogenesis, whereas knockdown impaired the process in a PPARγ-dependent manner. Thus, we discovered that STK38 is a novel PPARγ-cofactor promoting adipogenesis, likely through stabilization of PPARγ.

Mechanical Properties of Porcine and Fish Skin-Based Collagen and Conjugated Collagen Fibers.

Collagen is a protein that is a major component of animal skins and tendons. It is used in various medical, cosmetic, and food products through extraction and purification. The fibrous products of purified collagen fibers extracted from raw mammal materials have relatively excellent mechanical properties and are used for high-end medical products. In this study, we examined collagen materials produced from porcine and fish skins, which are major sources of collagen raw materials. We examined a method for spinning collagen fibers from fish skin-based collagen and analyzed the physical properties of those collagen fibers. In addition, we examined the characteristics and advantages of conjugated fibers according to their porcine- and/or fish skin-based compositions. The spinnability and mechanical properties of these conjugated fibers were analyzed according to their compositions. The mechanical properties of collagen structure are determined by hydroxyproline content and can be manipulated by the composition of collagen in the conjugated fibers.

Activation of Naringenin and Kaempferol through Pathway Refactoring in the Endophyte Phomopsis Liquidambaris.

Abundant gene clusters of natural products are observed in the endophytic fungus Phomopsis liquidambaris; however, most of them are silent. Herein, a plug-and-play DNA assembly tool has been applied for flavonoid synthesis in P. liquidambaris. A shuttle plasmid was constructed based on S. cerevisiae, E. coli, and P. liquidambaris with screening markers URA, Amp, and hygR, respectively. Each fragment or cassette was successively assembled by overlap extension PCR with at least 40-50 bp homologous arms in S. cerevisiae for generating a new vector. Seven native promoters were screened by the DNA assembly based on the fluorescence intensity of the mCherry reporter gene in P. liquidambaris, and two of them were new promoters. The key enzyme chalcone synthase was the limiting step of the pathway. The naringenin and kaempferol pathways were refactored and activated with the titers of naringenin and kaempferol of 121.53 mg/L and 75.38 mg/L in P. liquidambaris using fed-batch fermentation, respectively. This study will be efficient and helpful for the biosynthesis of secondary metabolites.

A decellularized porcine pulmonary valved conduit embedded with gelatin.

To prepare a tissue-engineered pulmonary valved conduit (PVC) with good tensile strength and biocompatibility. Sixty adult porcine PVCs were used to determine the optimal decellularization time. Five juvenile porcine decellularized PVCs and five juvenile porcine crosslinked PVCs were subsequently prepared according to the optimized decellularization and crosslinking methods. All PVCs were implanted into juvenile sheep for 8 months and then were harvested for staining. With a low concentration of detergent (0.25% Triton X-100+0.25% sodium deoxycholate), the decellularization effect on porcine PVCs was complete by 24 hours, and there was minimal damage to the matrix. Gelatin embedding and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) crosslinking improved the biomechanical properties of decellularized PVCs and reduced their immunogenicity. After implantation, the diameter and thickness of the PVCs in the decellularized and crosslinked groups increased significantly. In both groups, the conduits were unobstructed, with soft and smooth inner walls and without thrombosis, ulceration or neoplasia. The valves slightly degenerated with mild to moderate regurgitation. CD31-positive endothelial cells were visible on the inner surface of the conduits and valves. Scattered smooth muscle actin-positive cells were found in the middle layer of the conduit. The percentage of CD4- and CD68-positive cells and the calcium content were highest in decellularized porcine PVCs and lowest in ovine PVCs. The percentage of the matrix that was laminin-positive in decellularized and crosslinked porcine PVCs was lower than it was in ovine PVCs. Gelatin-embedded and EDC-crosslinked porcine PVCs can be "hosted" in sheep, with good biocompatibility, growth potential, and reduced calcification.

Dynamic resistance exercise increases skeletal muscle-derived FSTL1 inducing cardiac angiogenesis via DIP2A-Smad2/3 in rats following myocardial infarction.

PURPOSE: The aim of this study was to investigate the potential of dynamic resistance exercise to generate skeletal muscle-derived follistatin like-1 (FSTL1), which may induce cardioprotection in rats following myocardial infarction (MI) by inducing angiogenesis. METHODS: Male, adult Sprague-Dawley rats were randomly divided into 5 groups (n = 12 in each group): sham group (S), sedentary MI group (MI), MI + resistance exercise group (MR), MI + adeno-associated virus (AAV)-FSTL1 injection group (MA), and MI + AAV-FSTL1 injection + resistance exercise group (MAR). The AAV-FSTL1 vector was prepared by molecular biology methods and injected into the anterior tibialis muscle. The MI model was established by ligation of the left anterior descending coronary artery. Rats in the MR and MAR groups underwent 4 weeks of dynamic resistance exercise training using a weighted climbing-up ladder. Heart function was evaluated by hemodynamic measures. Collagen volume fraction of myocardium was observed and analyzed by Masson's staining. Human umbilical vein vessel endothelial cells culture and recombinant human FSTL1 protein or transforming growth factor-ß receptor 1 (TGFßR1) inhibitor treatment were used to elucidate the molecular signaling mechanism of FSTL1. Angiogenesis, cell proliferation, and disco interacting protein 2 homolog A (DIP2A) location were observed by immunofluorescence staining. The expression of FSTL1, DIP2A, and the activation of signaling pathways were detected by Western blotting. Angiogenesis of endothelial cells was observed by tubule experiment. One-way analysis of variance and Student's t test were used for statistical analysis. RESULTS: Resistance exercise stimulated the secretion of skeletal muscle FSTL1, which promoted myocardial angiogenesis, inhibited pathological remodeling, and protected cardiac function in MI rats. Exercise facilitated skeletal muscle FSTL1 to play a role in protecting the heart. Exogenous FSTL1 promoted the human umbilical vein vessel endothelial cells proliferation and up-regulated the expression of DIP2A, while TGFßR1 inhibitor intervention down-regulated the phosphorylation level of Smad2/3 and the expression of vascular endothelial growth factor-A, which was not conducive to angiogenesis. FSTL1 bound to the receptor, DIP2A, to regulate angiogenesis mainly through the Smad2/3 signaling pathway. FSTL1-DIP2A directly activated Smad2/3 and was not affected by TGFßR1. CONCLUSION: Dynamic resistance exercise stimulates the expression of skeletal muscle-derived FSTL1, which could supplement the insufficiency of cardiac FSTL1 and promote cardiac rehabilitation through the DIP2A-Smad2/3 signaling pathway in MI rats.

Fc-Elabela fusion protein attenuates lipopolysaccharide-induced kidney injury in mice.

Endotoxemia-induced acute kidney injury (AKI) is a common clinical condition that lacks effective treatments. Elabela (ELA) is a recently discovered kidney peptide hormone, encoded by the gene apela, and has been reported to improve cardio-renal outcomes in sepsis. However, ELA is a small peptide and is largely unsuitable for clinical use because of its short in vivo half-life. In the present study, we evaluated the potential renoprotective effects of a long-acting constant fragment (Fc)-ELA fusion protein in liposaccharide (LPS)-induced AKI in mice. LPS administration in mice for 5 days greatly lowered the gene expression of apela and impaired kidney function, as evidenced by elevated serum creatinine and the ratio of urine protein to creatinine. In addition, renal inflammation and macrophage infiltration were apparent in LPS-challenged mice. Treatment with the Fc-ELA fusion protein partially restored apela expression and attenuated the kidney inflammation. Moreover, LPS treatment induced reactive oxygen species (ROS) production and apoptosis in kidney HK-2 cells as well as in the mouse kidney, which were mitigated by ELA or Fc-ELA treatment. Finally, we found that ELA promoted the survival of HK-2 cells treated with LPS, and this action was abolished by LY204002, a PI3K/Akt inhibitor. Collectively, we have demonstrated that the Fc-ELA fusion protein has significant renoprotective activities against LPS-induced AKI in mice.

Novel Bacillus strains from the human gut exert anticancer effects on a broad range of malignancy types.

Cancer is one of the leading causes of death worldwide, but effective therapies remain the topic of many research activities. Many recent studies have thus focused on particular gut microbiota due to their important roles in treating cancers, but very few microbes of therapeutic value have been reported. In this study, we isolated four bacterial strains, BY38, BY40, BY43 and BY45, from the fecal specimens of healthy individuals and cancer patients. The treatment of cancer cells with the products of these cultured bacteria induced significant inhibitory effects on the proliferation of ovarian cancer cells and colorectal cancer cells in a dose-dependent manner. A phylogenetic analysis showed that the four anticancer strains belong to the genus Bacillus, and flow cytometry assays indicated that the inhibitory effects might be achieved through the induction of cell apoptosis. These results suggest that these bacteria could be novel and promising anticancer agents against cancers.

E. coli diversity: low in colorectal cancer.

BACKGROUND: Escherichia coli are mostly commensals but also contain pathogenic lineages. It is largely unclear whether the commensal E. coli as the potential origins of pathogenic lineages may consist of monophyletic or polyphyletic populations, elucidation of which is expected to lead to novel insights into the associations of E. coli diversity with human health and diseases. METHODS: Using genomic sequencing and pulsed field gel electrophoresis (PFGE) techniques, we analyzed E. coli from the intestinal microbiota of three groups of healthy individuals, including preschool children, university students, and seniors of a longevity village, as well as colorectal cancer (CRC) patients, to probe the commensal E. coli populations for their diversity. RESULTS: We delineated the 2280 fresh E. coli isolates from 185 subjects into distinct genome types (genotypes) by PFGE. The genomic diversity of the sampled E. coli populations was so high that a given subject may have multiple genotypes of E. coli, with the general diversity within a host going up from preschool children through university students to seniors. Compared to the healthy subjects, the CRC patients had the lowest diversity level among their E. coli isolates. Notably, E. coli isolates from CRC patients could suppress the growth of E. coli bacteria isolated from healthy controls under nutrient-limited culture conditions. CONCLUSIONS: The coexistence of multiple E. coli lineages in a host may help create and maintain a microbial environment that is beneficial to the host. As such, the low diversity of E. coli bacteria may be associated with unhealthy microenvironment in the intestine and hence facilitate the pathogenesis of diseases such as CRC.

A potent risk model for predicting new-onset acute coronary syndrome in patients with type 2 diabetes mellitus in Northwest China.

AIMS: Type 2 diabetes mellitus (T2DM) is now very prevalent in China. Due to the lower rate of controlled diabetes in China compared to that in developed countries, there is a higher incidence of serious cardiovascular complications, especially acute coronary syndrome (ACS). The aim of this study was to establish a potent risk predictive model in the economically disadvantaged northwest region of China, which could predict the probability of new-onset ACS in patients with T2DM. METHODS: Of 456 patients with T2DM admitted to the First Affiliated Hospital of Xi'an Jiaotong University from January 2018 to January 2019 and included in this study, 270 had no ACS, while 186 had newly diagnosed ACS. Overall, 32 demographic characteristics and serum biomarkers of the study patients were analysed. The least absolute shrinkage and selection operator regression was used to select variables, while the multivariate logistic regression was used to establish the predictive model that was presented using a nomogram. The area under the receiver operating characteristics curve (AUC) was used to evaluate the discriminatory capacity of the model. A calibration plot and Hosmer-Lemeshow test were used for the calibration of the predictive model, while the decision curve analysis (DCA) was used to evaluate its clinical validity. RESULTS: After random sampling, 319 and 137 T2DM patients were included in the training and validation sets, respectively. The predictive model included age, body mass index, diabetes duration, systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein cholesterol, serum uric acid, lipoprotein(a), hypertension history and alcohol drinking status as predictors. The AUC of the predictive model and that of the internal validation set was 0.830 [95% confidence interval (CI) 0.786-0.874] and 0.827 (95% CI 0.756-0.899), respectively. The predictive model showed very good fitting degree, and DCA demonstrated a clinically effective predictive model. CONCLUSIONS: A potent risk predictive model was established, which is of great value for the secondary prevention of diabetes. Weight loss, lowering of SBP and blood uric acid levels and appropriate control for DBP may significantly reduce the risk of new-onset ACS in T2DM patients in Northwest China.