Effect of different isolation sources of Lactococcus lactis subsp. lactis on volatile metabolites in fermented milk.

Lactococcus lactis subsp. lactis (L. lactis subsp. lactis) is a commonly used starter cultures in fermented dairy products, contributing distinct flavor and texture characteristics with high application value. However, the strains from different isolates have different contributions to milk fermentation. Therefore, this study aimed to investigate the influence of L. lactis subsp. lactis isolated from various sources on the volatile metabolites present in fermented milk. In this study, L. lactis subsp. lactis from different isolation sources (yogurt, koumiss and goat yogurt) was utilized as a starter culture for fermentation. The volatile metabolites of fermented milk were subsequently analyzed by headspace solid phase microextraction gas chromatography-mass spectrography (HS-SPME-GC-MS). The results indicated significant differences in the structure and abundance of volatile metabolites in fermented milk produced with different isolates (R2Y = 0.96, Q2 = 0.88). Notably, the strains isolated from goat yogurt appeared to enhance the accumulation of ketones (goat yogurt vs yogurt milk: 50 %; goat yogur vs koumiss: 27.3 %)and aldehydes (goat yogurt vs yogurt milk: 21.4 %; goat yogurt vs koumiss: 54.5 %) in fermented milk than strains isolated from koumiss and yogurt milk. It significantly promoted the production of 8 flavor substances (1 substance with OAV ≥ 1 and 6 substances with OAV > 0.1) and enhanced the biosynthesis of valine, leucine, and isoleucine. This study provides valuable insights for the application of Lactococcus lactis subsp. lactis isolated from different sources in fermented dairy production and screening of potential starter cultures.

Genome-wide molecular evolution analysis of the GRF and GIF gene families in Plantae (Archaeplastida).

BACKGROUND: Plant growth-regulating factors (GRFs) and GRF-interacting factors (GIFs) interact with each other and collectively have important regulatory roles in plant growth, development, and stress responses. Therefore, it is of great significance to explore the systematic evolution of GRF and GIF gene families. However, our knowledge and understanding of the role of GRF and GIF genes during plant evolution has been fragmentary. RESULTS: In this study, a large number of genomic and transcriptomic datasets of algae, mosses, ferns, gymnosperms and angiosperms were used to systematically analyze the evolution of GRF and GIF genes during the evolution of plants. The results showed that GRF gene first appeared in the charophyte Klebsormidium nitens, whereas the GIF genes originated relatively early, and these two gene families were mainly expanded by segmental duplication events after plant terrestrialization. During the process of evolution, the protein sequences and functions of GRF and GIF family genes are relatively conservative. As cooperative partner, GRF and GIF genes contain the similar types of cis-acting elements in their promoter regions, which enables them to have similar transcriptional response patterns, and both show higher levels of expression in reproductive organs and tissues and organs with strong capacity for cell division. Based on protein-protein interaction analysis and verification, we found that the GRF-GIF protein partnership began to be established in pteridophytes and is highly conserved across different terrestrial plants. CONCLUSIONS: These results provide a foundation for further exploration of the molecular evolution and biological functions of GRF and GIF genes.

Genome-wide identification and expression analysis of PtJAZ gene family in poplar (Populus trichocarpa).

BACKGROUND: The jasmonate ZIM domain (JAZ) protein is a key repressor of the jasmonate signal transduction pathway, which plays an important role in plant growth and development and defense responses. In this study, based on the published whole-genome data, we identified members of the JAZ gene family in Populus trichocarpa. Through a series of bioinformatic approaches, their expression patterns under various stress conditions have been analyzed to explore and excavate the endogenous resistance genes of poplar and provide a theoretical basis for breeding new varieties of poplar resistance. RESULTS: A total of 13 PtJAZ genes have been identified in P. trichocarpa and designated as PtJAZ1-PtJAZ13. Those 13 PtJAZ genes were unevenly distributed on nine chromosomes, and they could be divided into four subfamilies. The gene structures and motif composition of the members derived from the same subfamily were similar. Collinearity analysis demonstrated that, compared with Arabidopsis thaliana and Oryza sativa, the most collinear pairs (13) were found in P. trichocarpa and Eucalyptus robusta. Cis-acting element analysis suggested that the promoter regions of PtJAZs contained a large number of hormones and stress response elements, of which abscisic acid (ABA) and methyl jasmonate (MeJA) hormone response elements were the most abundant. The PtJAZ genes not only had diverse expression patterns in different tissues, but they also responded to various abiotic and biotic stress conditions. The co-expression network and GO and KEGG analyses showed that JAZ genes were closely related to insect resistance. CONCLUSIONS: In this study, applying bioinformatic methods, 13 PtJAZ gene family members from P. trichocarpa were identified and comprehensively analyzed. By further studying the function of the poplar JAZ gene family, the aim is to select genes with better insect resistance and stress resistance so as to lay a solid foundation for the subsequent breeding of new poplar varieties.

Identification of Differentially Expressed lncRNAs in Response to Blue Light and Expression Pattern Analysis of Populus tomentosa Hybrid Poplar 741.

Poplar is an important shelterbelt, timber stand, and city tree species that has been the focus of forestry research. The regulatory role of the long non-coding RNA molecule (lncRNA; length > 200 nt) has been a research hotspot in plants. In this study, seedlings of 741 poplar were irradiated with LED blue and white light, and the Illumina HiSeq 2000 sequencing platform was used to identify lncRNAs. |logFC| > 1 and p < 0.05 were considered to indicate differentially expressed lncRNAs, and nine differentially expressed lncRNAs were screened, the target genes of which were predicted, and three functionally annotated target genes were obtained. The differentially expressed lncRNAs were identified as miRNA targets. Six lncRNAs were determined to be target sites for twelve mRNAs in six miRNA families. LncRNAs and their target genes, including lncRNA MSTRG.20413.1-ptc-miR396e-5p-GRF9, were verified using quantitative real-time polymerase chain reaction analysis, and the expression patterns were analyzed. The analysis showed that the ptc-miR396e-5p expression was downregulated, while lncRNA MSTRG.20413.1 and GRF9 expression was upregulated, after blue light exposure. These results indicate that lncRNAs interact with miRNAs to regulate gene expression and affect plant growth and development.

Analysis of the RNA Editing Sites and Orthologous Gene Function of Transcriptome and Chloroplast Genomes in the Evolution of Five Deutzia Species.

In this study, the chloroplast genomes and transcriptomes of five Deutzia genus species were sequenced, characterized, combined, and analyzed. A phylogenetic tree was constructed, including 32 other chloroplast genome sequences of Hydrangeoideae species. The results showed that the five Deutzia chloroplast genomes were typical circular genomes 156,860-157,025 bp in length, with 37.58-37.6% GC content. Repeat analysis showed that the Deutzia species had 41-45 scattered repeats and 199-201 simple sequence repeats. Comparative genomic and pi analyses indicated that the genomes are conservative and that the gene structures are stable. According to the phylogenetic tree, Deutzia species appear to be closely related to Kirengeshoma palmata and Philadelphus. By combining chloroplast genomic and transcriptomic analyses, 29-31 RNA editing events and 163-194 orthologous genes were identified. The ndh, rpo, rps, and atp genes had the most editing sites, and all RNA editing events were of the C-to-U type. Most of the orthologous genes were annotated to the chloroplast, mitochondria, and nucleus, with functions including energy production and conversion, translation, and protein transport. Genes related to the biosynthesis of monoterpenoids and flavonoids were also identified from the transcriptome of Deutzia spp. Our results will contribute to further studies of the genomic information and potential uses of the Deutzia spp.

Incorporating global change reveals extinction risk beyond the current Red List.

Global changes over the past few decades have caused species distribution shifts and triggered population declines and local extinctions of many species. The International Union for Conservation of Nature (IUCN) Red List of Threatened Species (Red List) is regarded as the most comprehensive tool for assessing species extinction risk and has been used at regional, national, and global scales. However, most Red Lists rely on the past and current status of species populations and distributions but do not adequately reflect the risks induced by future global changes. Using distribution maps of >4,000 endemic woody species in China, combined with ensembled species distribution models, we assessed the species threat levels under future climate and land-cover changes using the projected changes in species' suitable habitats and compared our updated Red List with China's existing Red List. We discover an increased number of threatened species in the updated Red List and increased threat levels of >50% of the existing threatened species compared with the existing one. Over 50% of the newly identified threatened species are not adequately covered by protected areas. The Yunnan-Guizhou Plateau, rather than the Hengduan Mountains, is the distribution center of threatened species on the updated Red Lists, as opposed to the threatened species on the existing Red List. Our findings suggest that using Red Lists without considering the impacts of future global changes will underestimate the extinction risks and lead to a biased estimate of conservation priorities, potentially limiting the ability to meet the Kunming-Montreal global conservation targets.

A lightweight neural network for lung nodule detection based on improved ghost module.

Background: Computer tomography images are the preferred method of preoperative evaluation for lung disease. However, it remains difficult to detect and recognize nodules accurately and efficiently due to poor data imaging quality, heavy reliance on physician experience and the need for more human-computer interaction for diagnosis. Currently, image nodule detection based on deep convolutional neural networks has gained much momentum. Methods: To alleviate doctors' tremendous labor in the diagnosis procedure, and improve the accuracy of intelligent detection of lung nodules, we improved GhostNet and proposed a lightweight neural network for object detection for lung nodule image detection. Firstly, the bneck structure in the backbone feature extraction network is adopted and improved from the structure of MobileNetV3. The weights are adjusted by changing the initial channel attention mechanism and introducing a spatial-temporal attention mechanism. Then, in the enhanced feature extraction part, we mainly use depth-separable convolution blocks to replace the 3×3 convolution of the original network for the purpose of reducing the model parameters, and make more improvements based on the network structure to enhance the applicability of the network. Diagnostic precision, recall, F1-score, mAP and parameter count were calculated. Results: According to our lightweight neural network, F1-score, precision, and recall were 0.87, 86.34%, and 86.69%, respectively. Based on our dataset, the Yolov4-GNet network proposed in this research outperforms the current neural networks on both precision and recall as well as F1. Conclusions: The lung nodule detection method proposed in this research not only simplifies the processing of images, but also outperforms comparable methods in nodule detection rate and positioning accuracy, providing a new way for lung nodule detection.

Progress in the understanding of WRKY transcription factors in woody plants.

The WRKY transcription factor (TF) family, named for its iconic WRKY domain, is among the largest and most functionally diverse TF families in higher plants. WRKY TFs typically interact with the W-box of the target gene promoter to activate or inhibit the expression of downstream genes; these TFs are involved in the regulation of various physiological responses. Analyses of WRKY TFs in numerous woody plant species have revealed that WRKY family members are broadly involved in plant growth and development, as well as responses to biotic and abiotic stresses. Here, we review the origin, distribution, structure, and classification of WRKY TFs, along with their mechanisms of action, the regulatory networks in which they are involved, and their biological functions in woody plants. We consider methods currently used to investigate WRKY TFs in woody plants, discuss outstanding problems, and propose several new research directions. Our objective is to understand the current progress in this field and provide new perspectives to accelerate the pace of research that enable greater exploration of the biological functions of WRKY TFs.

Short-term effect of polyethylene glycol loxenatide on weight loss in overweight or obese patients with type 2 diabetes: An open-label, parallel-arm, randomized, metformin-controlled trial.

Objective: Polyethylene glycol loxenatide (PEG-Loxe) is a novel, once-weekly glucagon-like peptide 1 receptor agonist that is approved in doses of 0.1 mg and 0.2 mg for the treatment of type 2 diabetes mellitus (T2DM). However, no clinical trials have been designed to determine the effect of 0.3 mg PEG-Loxe on weight loss in overweight or obese patients with T2DM. This trial aimed to evaluate the short-term effect of 0.3 mg PEG-Loxe, injected subcutaneously once weekly, for weight management in overweight or obese patients with T2DM. Methods: This 16-week, open-label, parallel-arm, randomized, metformin-controlled trial was conducted at Shandong Provincial Hospital in Shandong, China. Patients with T2DM, who were overweight or obese (body mass index ≥ 25.0 kg/m2) and had been treated with lifestyle interventions or a combination with oral antidiabetic drug monotherapy were randomized (2:1) to receive 0.3 mg PEG-Loxe or 1500 mg metformin. The primary endpoint was a change in body weight from baseline to week 16. Results: Overall, 156 patients were randomized and exposed to treatment. Weight loss was 7.52 kg (8.37%) with PEG-Loxe and 2.96 kg (3.00%) with metformin, with a between-group difference of 4.55 kg (95% CI, 3.43 to 5.67) (P < 0.001). A significantly higher proportion of patients lost ≥5% (61.5% vs. 25.0%) or 10% (26.9% vs. 5.8%) body weight in the PEG-Loxe group than in the metformin group (P < 0.01). Additionally, PEG-Loxe resulted in marked improvements in several cardiovascular risk factors compared to metformin, including body mass index, waist circumference, visceral fat area, blood pressure, and lipid profile. PEG-Loxe and metformin displayed almost equal potency for glycemic control. The incidence of adverse events was 46.2% (48/104) and 44.2% (23/52) in the PEG-Loxe and metformin groups, respectively. Conclusion: In overweight or obese patients with T2DM, a once-weekly subcutaneous administration of PEG-Loxe for 16 weeks, in addition to lifestyle interventions or oral antidiabetic drug therapy, resulted in significantly greater weight loss compared to metformin. Additional trials are necessary to establish whether these effects can be maintained in the long term. Clinical trial registration: www.chictr.org.cn, identifier ChiCTR2200057800.

Efficacy of statin therapy in chronic obstructive pulmonary disease: a systematic review and meta-analysis from 2008-2019.

INTRODUCTION: Statins produce significant hypolipidemic effects and reduce C-reactive protein (CRP) in patients with chronic obstructive pulmonary disease (COPD). It has been reported that statins did not prevent the acute exacerbation of COPD or improve clinical outcomes. Therefore, we analyzed the actual therapeutic effects of statins on COPD therapy during long-term clinical trials. EVIDENCE ACQUISITION: Relevant studies were retrieved from various databases from 2008 to 2019. For each study, Odds Ratios (ORs), mean difference (MD) and 95% confidence interval (95% CI) were assessed. EVIDENCE SYNTHESIS: Thirty-two studies were retrieved with 3137 patients receiving statin therapy and 3140 controls. Satins significantly increased exercise capacity (47.21, 95% CI: 20.79-73.63), lung FEV1 (4.02, 95% CI: 2.28-5.75), forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) (3.56, 95% CI: 2.01-5.10) and high-density lipoproteins (HDL) (5.573, 95% CI: 1.74-9.41). In addition, statins downregulated CRP function (W=-1.60, 95% CI: -2.45-0.76), IL-6 (-3.35, 95% CI: -4.94 to -1.76), St George's breath questionnaire (SGRQ) scores (-9.96, 95% CI: -12.83 to -7.10), COPD assessment test (CAT) (-3.49, 95% CI: -4.70 to 2.29) and systolic blood pressure (-4.992, 95% CI: -5.17 to -4.818). Total cholesterol (TC) (-37.84, 95% CI: -46.10 to 29.58) low-density lipoproteins (LDL) (-26.601, 95% CI: -26.688 to 26.514) and triglycerides (TG) (-42.914, 95% CI: -61.809 to 24.02) were also decreased. CONCLUSIONS: Clinical trials conducted over a 10-year period revealed beneficial advantages of statin therapy in COPD patients, permitting increased exercise capacity, FEV1/FVC and HDL. In addition, CRP, IL-6, systolic blood pressure, SGRQ scores and CAT were significantly decreased as well as lipid levels.

Composition and factors influencing community structure of lactic acid bacterial in dairy products from Nyingchi Prefecture of Tibet.

This study investigated the community composition of lactic acid bacteria (LAB) from yaks' milk (YM) Tibetan yellow cattle milk (TM) and their fermented products from different counties in the Nyingchi Prefecture, Tibet using Pacific Biosciences (PacBio) single-molecule real-time (SMRT) sequencing. Sequencing revealed 26 genera and 94 species from 71 dairy samples; amongst these Lactobacillus delbrueckii (36.17%), Streptococcus thermophilus (19.46%) and Lactococcus lactis (18.33%) were the predominant species. This study also identified the main factors influencing LAB community composition by comparing amongst samples from different locations, from different milk types, and from different altitudes. The LAB communities in YM and TM were more diverse than in fermented yaks' milk (FYM) and fermented Tibetan yellow cattle milk (FTM) samples. Similarly, whether milk was fermented or not accounted for differences in LAB species composition while altitude of the dairy products had very little effect. Milk source and production process were the most likely causes of drastic shifts in microbial community composition. In addition, fermented dairy products were enriched in genes responsible for secondary metabolic pathways that were potentially beneficial for health. Comprehensive descriptions of the microbiota in different dairy products from the Nyingchi Prefecture, Tibet might help elucidate evolutionary and functional relationships amongst bacterial communities in these products.

Metabolomics analysis reveals differences in milk metabolism and fermentation rate between individual Lactococcus lactis subsp. lactis strains.

The bacterial starter has a crucial role in fermentation of dairy products; however, knowledge about metabolic differences in Lactococcus (L.) lactis subsp. lactis strains with different fermentation rates is limited. We analyzed the fermentation capacity and metabolic profiles of 17 L. lactis subsp. lactis strains through ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry Elevated Energy. Metabolomics results revealed significant differences in metabolites between the fast group (fermentation time < 16 h) and slow group (fermentation time ≥ 16 h). In the fast group, 98 and 55 metabolites were increased and decreased, respectively. The fast group was enriched with peptides and lipids, and we found that peptides, esters, and tributyrin can be used as biomarkers to distinguish between groups. Our results implicated that tributyrin plays a role in regulating strain growth. This study provides a novel insight into the metabolic cause of different acid production rates between individuals L. lactis subsp. lactis strains.

Cold Resistance of Euonymus japonicus Beihaidao Leaves and Its Chloroplast Genome Structure and Comparison with Celastraceae Species.

Euonymus japonicus Beihaidao is one of the most economically important ornamental species of the Euonymus genus. There are approximately 97 genera and 1194 species of plants worldwide in this family (Celastraceae). Using E. japonicus Beihaidao, we conducted a preliminary study of the cold resistance of this species, evaluated its performance during winter, assembled and annotated its chloroplast genome, and performed a series of analyses to investigate its gene structure GC content, sequence alignment, and nucleic acid diversity. Our objectives were to understand the evolutionary relationships of the genus and to identify positive selection genes that may be related to adaptations to environmental change. The results indicated that E. japonicus Beihaidao leaves have certain cold resistance and can maintain their viability during wintering. Moreover, the chloroplast genome of E. japonicus Beihaidao is a typical double-linked ring tetrad structure, which is similar to that of the other four Euonymus species, E. hamiltonianus, E. phellomanus, E. schensianus, and E. szechuanensis, in terms of gene structure, gene species, gene number, and GC content. Compared to other Celastraceae species, the variation in the chloroplast genome sequence was lower, and the gene structure was more stable. The phylogenetic relationships of 37 species inferred that members of the Euonymus genus do not form a clade and that E. japonicus Beihaidao is closely related to E. japonicus and E. fortunei. A total of 11 functional positive selected genes were identified, which may have played an important role in the process of Celastraceae species adapting to environmental changes. Our study provides important genetic information to support further investigations into the phylogenetic development and adaptive evolution of Celastraceae species.

Monitoring early dynamic changes of plasma cell-free DNA and pretreatment pre-albumin to predict chemotherapy effectiveness and survival outcomes in advanced non-small cell lung cancer.

Background: This study aimed to determine whether plasma cell-free DNA (cfDNA) and pretreatment parameters provide useful therapeutic response and prognostic information for advanced non-small cell lung cancer (NSCLC) patients. Methods: A total of 114 patients with advanced NSCLC who underwent systemic chemotherapy were included in this study. Detection of plasma cfDNA concentration and blood parameters before and at the sixth week after treatment was performed. The prognostic value of cfDNA dynamic changes and laboratory parameters was determined via a receiver operating characteristic (ROC) curve, and then analyzed by comparing with the therapeutic efficacy and progression-free survival (PFS). Based on the ROC curve, it revealed a pretreatment pre-albumin (PA) concentration of 21.7 mg/dL was the cut-off value. The Cox proportional hazards regression model was used to evaluate the predictive factors for treatment response and PFS via univariate and multivariate analyses. Results: Patients with cfDNA reduction ≥20% at the sixth week after treatment reported a significantly better disease control rate (DCR) and prolonged PFS (median PFS: 10.0 vs. 4.0 months, P<0.001). The median PFS of low PA group (PA <21.7 mg/dL) was 6.0 months, while the median PFS of high PA group (PA ≥21.7 mg/dL) was 8.0 months. The combined assessment of cfDNA and pretreatment pre-albumin was associated with significantly better survival outcomes compared with the remaining population (P<0.001). Multivariate analysis for DCR indicated that cfDNA reduction ≥20% was an independent factor (OR =0.419, P=0.001). In addition, multivariate analysis identified 6 significant factors associated with PFS: cfDNA reduction of ≥20%, age <65 years, Eastern Cooperative Oncology Group (ECOG) score ≥2, driver gene mutation, chemotherapy combined regimen, and treatment response of complete response (CR) and partial response (PR). The nomogram could predict the 2-year PFS probability of advanced NSCLC patients after treatment, and the C-index was 0.817. Conclusions: Monitoring cfDNA changes and pretreatment pre-albumin level in advanced NSCLC patients receiving treatment is an accurate predictor of tumor response and PFS. Combined assessment of cfDNA and pretreatment pre-albumin is helpful for predicting survival outcomes. These findings may assist in identifying high-risk patients and guiding treatment strategies.

ZNF488 Promotes the Invasion and Migration of Pancreatic Carcinoma Cells through the Akt/mTOR Pathway.

OBJECTIVE: Studies have demonstrated that zinc finger protein 488 (ZNF488) is highly expressed in pancreatic carcinoma (PC), but its effect on PC and its molecular mechanism remains unclear. METHODS: Real-time fluorescent quantitative PCR (RT-qPCR) was employed to detect the ZNF488 expression in PC patients' cancer tissues and cell lines. After interfering with or overexpressing ZNF488 in PANC-1 and AsPC-1 cells, respectively, the CCK-8, cell cloning, Transwell, and scratch assays were performed to detect cell proliferation, cell viability, invasion ability, and migration ability. In addition, Western blot was applied to assess the protein expression of Akt, p-Akt, mTOR, and p-mTOR in the Akt-mTOR pathway. RESULTS: The ZNF488 expression was evidently raised in PC tissues and cell lines, and the starBase V3.0 database indicated that the higher the ZNF488 expression, the lower the survival rate of PC patients. Furthermore, we discovered that overexpressing ZNF488 can markedly promote the proliferation, invasion, and migration of PC cells. At the same time, highly expressed ZNF488 distinctly increased the p-Akt and p-mTOR expressions and the p-Akt/Akt and p-mTOR/mTOR ratios. However, after knocking down the ZNF488 expression, it had the opposite results. In addition, the Akt agonist SC79 can alleviate the effect of ZNF488 knockdown on Akt/mTOR pathway-related proteins, while Akt inhibitor AZD5363 had the opposite effect. CONCLUSION: ZNF488 could promote the proliferation, invasion, and migration of PC cells, and its mechanism may be related to the activation of the Akt/mTOR pathway. This study demonstrated that ZNF488 could be used as a molecular target for diagnosing and treating PC.

Xuanfei Pingchuan Capsules Ameliorate Autophagy in Human Bronchial Epithelial Cells by Inhibiting p38 Phosphorylation.

Background: This study aimed to investigate the protective effect of Xuanfei Pingchuan Capsules (XFPC) on autophagy and p38 phosphorylation in human bronchial epithelial (HBE) cells induced by cigarette smoke extract (CSE). Methods: HBE cells were divided into five groups: blank, CSE, low XFPC dose (XFPC-L), medium XFPC dose (XFPC-M), and high XFPC dose (XFPC-H). HBE cells were induced by CSE to establish a cell model for chronic obstructive pulmonary disease, and different doses of XFPC medicated serum were used to treat the cells. The Cell Counting Kit-8 was used to detect cell viability. Flow cytometry was used to detect cell apoptosis. Fluorescence microscopy and the expression level of microtubule-associated protein light chain 3 (LC3)-II in immunohistochemical method were used to observe autophagy in cells. Western blot was used to detect the protein expression level of p38, phospho-p38 (p-p38), LC3-I, LC3-II and Beclin 1. Real-time polymerase chain reaction was used to detect the expression of LC3-I, LC3-II and Beclin 1 on mRNA level. Results: Compared with the blank group, the cell viability of the CSE group was significantly decreased, and apoptosis and the level of autophagy in cells were significantly increased. The mRNA and protein expression of LC3-I, LC3-II, Beclin 1 and the protein level of p-p38 were significantly increased in the CSE-HBE cells. Compared to the CSE group, the different doses of XFPC medicated serum increased cell viability, decreased cell apoptosis, and inhibited mRNA and protein expression of LC3-I, LC3-II, Beclin 1 and protein level of p-p38. These results were especially observed in the group XFPC-H. After adding a p38 agonist, the therapeutic effect of XFPC on cell viability and autophagy was suppressed. Conclusion: XFPC significantly increased cell viability in a CSE-induced HBE cell model for chronic obstructive pulmonary disease through inhibiting the level of autophagy mediated by phosphorylation of p38.

Multi-classification of arrhythmias using a HCRNet on imbalanced ECG datasets.

BACKGROUND AND OBJECTIVE: Cardiac arrhythmia, which is an abnormal heart rhythm, is a common clinical problem in cardiology. Arrhythmias can be divided into many Categories, and accurate detection of arrhythmias can effectively prevent heart disease and reduce mortality. However, existing screening methods require long time monitoring and are low cost and low yield. Our goal is to develop a mixed depth model for processing time series to predict multi-classification electrocardiograph (ECG). METHODS: In this study, we developed a new, more robust network model named Hybrid Convolutional Recurrent Neural Network (HCRNet) for the time-series signal of ECG. This model utilized a nine-class ECG dataset containing tens of thousands of data to automatically detect cardiac arrhythmias. At the same time, a large imbalance arose because some of the cases in our selected MIT-BIH atrial fibrillation database had less than 100 records, but some had more than 10,000 records. Therefore, during data preprocessing, we adopted a scientific and efficient method to solve the ECG data imbalance problem. In the experimental studies, 10-fold cross validation technique is employed to evaluate performance of the model. RESULTS: In order to fully validate our proposed model, we conducted a comprehensive experiment to investigate the performance of the proposed method. Our proposed HCRNet achieved the average accuracy of 99.01% performance and the average sensitivity of 99.58% performance on this dataset. Results suggest that the proposed model outperformed some state-of-the-art studies in ECG classification with a high overall performance value. CONCLUSION: The HCRNet model can effectively classify arrhythmia signals in nine categories and obtain high efficiency, accuracy and F1 values. These improvements in efficiency and accuracy explain the rationality and science of setting up the modules in the HCRNet. By using this model, it can help cardiologists to correctly identify heartbeat types and perform arrhythmia diagnosis quickly.

Comparative genomics of in vitro and in vivo evolution of probiotics reveals energy restriction not the main evolution driving force in short term.

Probiotics have attracted much attention because of their health-promoting effects, but little is known about the in vivo evolution of probiotics. This study analyzed the genome adaptation of the probiotic Lactiplantibacillus plantarum P-8 strain cultivated in ordinary and glucose restrictive growth media. Then, this study re-analyzed genomes of P-8 isolates recovered from the gut contents of subjects in two feeding trials (in rat and human). The sampling time points were similar to that of the in vitro evolution experiment, which might give parallel comparison of the in vitro and in vivo evolution processes. Our results showed that intra-individual specific microbial genomic variants of the original strain were detected in all human and some rat subjects. The divergent patterns of evolution within the host gastrointestinal tract suggested intra-individual-specific environmental adaptation. Based on comprehensive analysis of adapted-isolates recovered from these experiments, our results showed that the energy restriction was not the main driving force for evolution of probiotics. The individual-specific adaptation of probiotics might partially explain the varying extent of health effects seen between different individuals after probiotic consumption. In addition, the results suggest that probiotics should not only adapt to the environment of the birth canal, but also adapt to other species in the gut, revealing the Red Queen hypothesis in the process of intestinal flora.

SARS-CoV-2 Gastrointestinal Infection Prolongs the Time to Recover From COVID-19.

Objectives: We previously reported that SARS-CoV-2 infects the gastrointestinal (GI) epithelium. In this study, we aimed to explore the impact of SARS-CoV-2 GI infection on clinical outcomes of COVID-19. Materials and Methods: For this retrospective cohort study, 104 patients with COVID-19 were classified into a SARS-CoV-2 GI infection group and a non-infection group. The primary endpoint was the time of negative conversion of SARS-CoV-2 RNA in respiratory tract samples. The secondary outcome was the time of hospitalization for COVID-19. Results: Patients with SARS-CoV-2 GI infection had a longer duration of positive SARS-CoV-2 RNA in respiratory tract samples (median 12.0 days [95% CI: 10.0-13.2] vs. 9.0 days [95% CI: 7.5-10.5]; HR 0.575 [95% CI: 0.386-0.857]; P = 0.003) and hospitalization (median 28.0 days [95% CI: 23.2-32.8] vs. 15.0 days [95% CI: 13.6-16.4]; HR 0.149 [95% CI: 0.087-0.252]; P < 0.001) than patients without SARS-CoV-2 GI infection. Subgroup analyses for sex, age, epidemiological history, clinical classification and antiviral treatment showed consistent results. Conclusion: Our study indicates that SARS-CoV-2 GI infection prolongs the duration of SARS-CoV-2 shedding and hospitalization in the patients with COVID-19. More attention should be paid to SARS-CoV-2 GI infection of COVID-19 and fecal SARS-CoV-2 RNA test should be completed in time.

Effects of Climate, Plant Height, and Evolutionary Age on Geographical Patterns of Fruit Type.

Fruit type is a key reproductive trait associated with plant evolution and adaptation. However, large-scale geographical patterns in fruit type composition and the mechanisms driving these patterns remain to be established. Contemporary environment, plant functional traits and evolutionary age may all influence fruit type composition, while their relative importance remains unclear. Here, using data on fruit types, plant height and distributions of 28,222 (∼ 90.1%) angiosperm species in China, we analyzed the geographical patterns in the proportion of fleshy-fruited species for all angiosperms, trees, shrubs, and herbaceous species separately, and compared the relative effects of contemporary climate, ecosystem primary productivity, plant height, and evolutionary age on these patterns. We found that the proportion of fleshy-fruited species per grid cell for all species and different growth forms all showed significant latitudinal patterns, being the highest in southeastern China. Mean plant height per grid cell and actual evapotranspiration (AET) representing ecosystem primary productivity were the strongest drivers of geographical variations in the proportion of fleshy-fruited species, but their relative importance varied between growth forms. From herbaceous species to shrubs and trees, the relative effects of mean plant height decreased. Mean genus age had significant yet consistently weaker effects on proportion of fleshy-fruited species than mean plant height and AET, and environmental temperature and precipitation contributed to those of only trees and shrubs. These results suggest that biotic and environmental factors and evolutionary age of floras jointly shape the pattern in proportion of fleshy-fruited species, and improve our understanding of the mechanisms underlying geographical variations in fruit type composition. Our study also demonstrates the need of integrating multiple biotic and abiotic factors to fully understand the drivers of large-scale patterns of plant reproductive traits.