Cognitive-behavioral therapy for patients with somatoform disorders: A pilot preliminary randomized controlled trial.

Background and objective: Cognitive-behavioral therapy (CBT) for somatoform disorders (SFDs) is understudied in China. Western findings may not be applicable to Chinese culture. This preliminary study evaluated the efficacy of CBT for patients in China, relative to treatment-as-usual (TAU). Methods: Seventy patients with SFDs randomly received either combined CBT and TAU (CBT + TAU), or TAU alone between January 2018 to May 2019. The CBT + TAU group received 12 weekly individual 50-minute CBT sessions. Participants were blindly assessed at 4 timepoints (baseline, week 6, end of treatment: week 12; 12 weeks post-treatment: week 24) using the following outcome measures: SQSS (Self-screening Questionnaire for Somatic Symptoms); PHQ-15 (Patient-Health-Questionnaire-15) and the WI (Whiteley Index); GAD-7 (General Anxiety Disorder-7); HAMD-17 (Hamilton Depression Rating Scale-17); Family Burden Interview Schedule (FBIS); Sheehan Disability Scale (SDS); and the Short Form of Quality-of-Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF). The primary endpoint was the difference between the SQSS total score at week 24 and the baseline. A mixed model for repeated measures was used to analyze inter- and intra-group changes from the baseline. Results: At week 24, The least-squares mean (LSM) change of the total score on the SQSS was -18.87 points and -9.69 points, respectively in the CBT + TAU group and in the TAU group (LSM difference, -9.18 points; 95% confidence interval, -15.72 to -2.64; P = 0.0068). At week 24, the LSM changes from baseline in the WI, HAMD, PHQ15, FBIS and SDS total scores were significantly different between the two groups, however, there was no significant difference in the Q-LES-Q-SF. The SQSS of group effect sizes were 0.63 at 24 weeks. The dropout rates of the CBT + TAU and TAU groups were comparable (22.9% and 19.3%). Conclusions: These preliminary findings suggest that CBT may be helpful for improving the symptoms of patients with SFDs in China.

Drug-loaded lipid nanoparticles improve the removal rates of the Staphylococcus aureus biofilm.

Biofilms of the foodborne pathogen Staphylococcus aureus show improved resistance to antibiotics and are difficult to eliminate. To enhance antibacteria and biofilm dispersion via extracellular matrix diffusion, a new lipid nanoparticle was prepared, which employed a mixture of phospholipids and a 0.8% surfactin shell. In the lipid nanoparticle, 31.56 µg mL-1 of erythromycin was encapsulated. The lipid nanoparticle size was approximately 52 nm and the zeta-potential was -67 mV, which was measured using a Marvin laser particle size analyzer. In addition, lipid nanoparticles significantly dispersed the biofilms of S. aureus W1, CICC22942, and CICC 10788 on the surface of stainless steel, reducing the total viable count of bacteria in the biofilms by 103 CFU mL-1 . In addition, the lipid nanoparticle can remove polysaccharides and protein components from the biofilm matrix. The results of laser confocal microscopy showed that the lipid nanoparticles effectively killed residual bacteria in the biofilms. Thus, to thoroughly eliminate biofilms on material surfaces in food factories to avoid repeated contamination, drug-lipid nanoparticles present a suitable method to achieve this.

Prevention of high-fat-diet-induced obesity in mice by soluble dietary fiber from fermented and unfermented millet bran.

Obesity-related diabetes, cardiovascular disease, and hypertension pose many risks to human health. Thus, mice on a high-fat diet were gavaged with millet bran (unfermented/fermented) soluble dietary fiber (RSDF/FSDF, 500 mg·kg-1) for 10 weeks in current research, and then evaluated the various biological indicators. These findings revealed that RSDF and FSDF supplements could prevent fat synthesis by inhibiting sterol regulatory element-binding protein-1c gene expression. The RSDF supplements can also accelerate fat catabolism through enhanced the mRNA expression levels of adipose triglyceride lipase and peroxisome proliferator-activated receptor α. FSDF supplements can prevent obesity by decreasing 3-hydroxy-3-methyl-glutaryl-CoA reductase expression and increasing cholesterol 7α-hydroxylase expression. Moreover, FSDF also controls obesity development by lowering total cholesterol and low-density lipoprotein cholesterol levels in the blood, triglyceride, total cholesterol, and bile acid levels in the liver. Notably, FSDF supplements can promote Bacteroides and Prevotella propagation; excretive propionic acid binds to free fatty acid receptor 2/3 and then stimulates intestinal epithelial cells to generate glucagon-like-peptide-1 and peptide YY, which can reduce food and energy intake and ultimately prevent obesity. All evidence suggests that FSDF supplements play a crucial role in preventing obesity.

Self-cascade deoxynivalenol detoxification by an artificial enzyme with bifunctions of dehydrogenase and aldo/keto reductase from genome mining.

Due to the severe health risks for human and animal caused by the intake of toxic deoxynivalenol (DON) derived from Fusarium species, elimination DON in food and feed has been initiated as a critical issue. Enzymatic cascade catalysis by dehydrogenase and aldo-keto reductase represents a fascinating strategy for DON detoxification. Here, one quinone-dpendent alcohol dehydrogenase DADH oxidized DON into less-toxic 3-keto-DON and NADPH-dependent aldo-keto reductase AKR13B3 reduced 3-keto-DON into relatively non-toxic 3-epi-DON were identified from Devosia strain A6-243, indicating that degradation of DON on C3 are two-step sequential cascade processes. To establish the bifunctions, fusion enzyme linking DADH and AKR13B3 was successfully assembled to promote one-step DON degradations with accelerated specific activity and efficiency, resulting 93.29 % of DON removal rate in wheat sample. Three-dimensional simulation analysis revealed that the bifunctional enzyme forms an artificial intramolecular channel to minimize the distance of intermediate from DADH to AKR13B3 for two-step enzymatic reactions, and thereby accelerates this enzymatic process. As the first report of directing single step DON detoxification by an interesting bifunctional artificial enzyme, this work revealed a facile and eco-friendly approach to detoxify DON with application potential and gave valuable insights into execute other mycotoxin detoxification for ensuring food safety.

Greenhouse gas emission in the whole process of forest fire including rescue: a case of forest fire in Beibei District of Chongqing.

In the context of global high temperature, the harm of greenhouse gases (GHG) emissions caused by frequent forest fires to the environment cannot be ignored. Existing research only calculates the GHG generated by the burning of forest vegetation, ignoring the GHG generated by the fire-driven social rescue activities. Taking the forest fire in Beibei District, Chongqing City, China, as an example, this paper studies and establishes the GHG emission accounting method for the whole process of forest fire from ignition to fire extinguishing through three processes: vegetation burning, rescue transportation, and on-site fire extinguishing. It covers three GHG calculation types: biomass burning, traffic activity level comprehensive energy consumption, and machine energy consumption. Among them, the CO2 produced by the burning of coniferous forest, the support transportation of rescue teams in Yunnan province, and the motorcycle transportation at the fire extinguishing site accounted for a relatively high proportion in the corresponding processes, reaching 12,761.445 t, 118.750 t, and 1056.980 t, respectively. Finally, through data analysis, suggestions on GHG emission reduction related to forest tree regulation and optimization of rescue and fire extinguishing management are put forward, which provides a direction for future research on carbon reduction in the whole process of forest fire events.

Establishment of real-time fluorescence and visual LAMP for rapid detection of Escherichia coli O157:H7 and kits construction.

Escherichia coli O157:H7 is a common pathogenic bacterium in food and water that can pose a threat to human health. The aim of this study was to develop loop-mediated isothermal amplification (LAMP) method for the detection of E. coli O157:H7 in food based on the specific gene Ecs_2840 and to construct rapid detection kits based on the established methods. Specifically, we established two methods of real-time fluorescent LAMP (RT-LAMP) and visual LAMP with calcein as an indicator. In pure bacterial culture, the cell sensitivity and genomic sensitivity of the RT-LAMP kit were 8.8 × 100 CFU ml-1 and 4.61 fg µl-1, respectively. The sensitivity of the visual LAMP kit was 2.35 × 100 CFU ml-1 and 4.61 fg µl-1. Both kits had excellent specificity and anti-interference performance. In addition, milk inoculated with 2.26 × 100 CFU ml-1E. coli O157:H7 could be detected within the reaction time after enrichment for 3 h. The results showed that the LAMP kits were rapid, sensitive, and specific for the detection of E. coli O157:H7 in food and had good application prospects in food safety surveillance.

Functional and structural MRI based obsessive-compulsive disorder diagnosis using machine learning methods.

BACKGROUND: The success of neuroimaging in revealing neural correlates of obsessive-compulsive disorder (OCD) has raised hopes of using magnetic resonance imaging (MRI) indices to discriminate patients with OCD and the healthy. The aim of this study was to explore MRI based OCD diagnosis using machine learning methods. METHODS: Fifty patients with OCD and fifty healthy subjects were allocated into training and testing set by eight to two. Functional MRI (fMRI) indices, including amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), degree of centrality (DC), and structural MRI (sMRI) indices, including volume of gray matter, cortical thickness and sulcal depth, were extracted in each brain region as features. The features were reduced using least absolute shrinkage and selection operator regression on training set. Diagnosis models based on single MRI index / combined MRI indices were established on training set using support vector machine (SVM), logistic regression and random forest, and validated on testing set. RESULTS: SVM model based on combined fMRI indices, including ALFF, fALFF, ReHo and DC, achieved the optimal performance, with a cross-validation accuracy of 94%; on testing set, the area under the receiver operating characteristic curve was 0.90 and the validation accuracy was 85%. The selected features were located both within and outside the cortico-striato-thalamo-cortical (CSTC) circuit of OCD. Models based on single MRI index / combined fMRI and sMRI indices underperformed on the classification, with a largest validation accuracy of 75% from SVM model of ALFF on testing set. CONCLUSION: SVM model of combined fMRI indices has the greatest potential to discriminate patients with OCD and the healthy, suggesting a complementary effect of fMRI indices on the classification; the features were located within and outside the CSTC circuit, indicating an importance of including various brain regions in the model.

Excessive bowel volume loss during anus-preserving surgery for rectal cancer affects the bowel function after operation: A prospective observational cohort study (Bas-1611).

Background: Bowel volume loss during anus-preserving surgery (APS) may result in low anterior resection syndrome (LARS). We conducted this prospective observational cohort study to measure the incidence of LARS after surgery and evaluate the relationship between bowel volume loss and bowel function. Methods: Patients with R0 resectable rectal cancer who consented to several bowel function surveys through telephone interviews after the operation were included. Enrolled patients underwent standard APS for rectal cancer, and three length indexes, viz. length of excised bowel, length of the distal margin and length of the proximal margin (LPM) of fresh bowel specimens, were measured in vitro. Results: The three measured variables of the specimens showed a positively skewed distribution. Patient interviews revealed a trend of gradual improvement in bowel function. Univariate analyses revealed that longer LPM was associated with a significantly negative impact on bowel function at all time points. In multivariate analysis, LPM was found to be a significant risk factorstatistically significant, but its impact was not as strong as that of radiotherapy and low-middle tumour. Furthermore, there was no significant difference in the lymph node detection rate between <10-cm and ≥10-cm LPM groups. Conclusion: In APS for rectal cancer, bowel volume loss is an important factor causing postoperative bowel dysfunction. Controlling LPM to <10 cm may help improve postoperative bowel function.

Effects of monolauroyl-galactosylglycerol on membrane fatty acids and properties of Bacillus cereus.

The purpose of this study was to provide new ideas for the antibacterial mechanism of monolauroyl-galactosylglycerol (MLGG) from the perspective of cell membranes. The changes in cell membrane properties of Bacillus cereus (B. cereus) CMCC 66,301 exposed to different concentrations (1 × MIC (minimum inhibitory concentration), 2 × MIC, 1 × MBC (minimum bacterial concentration)) of MLGG were evaluated. It was found that the lag phase of B. cereus cells was prolonged at low concentration MLGG (1 × MIC and 2 × MIC), while about 2 log CFU/mL reduction in B. cereus populations were observed when exposed to high concentration MLGG (1 × MBC). MLGG treated B. cereus displayed obvious membrane depolarization, while membrane permeability had no change using PI (propidium iodide) staining. Significant increase in the membrane fluidity in response to MLGG exposure occurred, which was consistent with the modification of membrane fatty acids compositions, where the relative content of straight-chain fatty acids (SCFAs) and unsaturated fatty acids (UFAs) increased, while branched-chain fatty acids (BCFAs) decreased significantly. The decreased transition Tm value and cell surface hydrophobicity was also observed. Additionally, effect of MLGG on bacterial membrane compositions were explored at the submolecular level by infrared spectroscopy. Resistance tests of B. cereus to MLGG had demonstrated the advantages of MLGG as a bacteriostatic agent. Collectively, these studies indicate that modifying the fatty acid composition and properties of cellular membranes through MLGG exposure is crucial for inhibiting bacteria growth, providing new insights into the antimicrobial mechanisms of MLGG. KEY POINTS: • Monolauroyl-galactosylglycerol inserted into B. cereus lipid bilayer membrane • Monolauroyl-galactosylglycerol treatment caused B. cereus membrane depolarization • Monolauroyl-galactosylglycerol resulted in B. cereus membrane fatty acids alteration.

Effect and regulation of fatty acids on bacillomycin D synthesis.

Bacillomycin D is a cyclic antimicrobial lipopeptide that has excellent antifungal effects, but its application is limited due to its low yield. At present, it is not clear whether fatty acids regulate the synthesis of bacillomycin D. Therefore, the effects of nine fatty acids on the yield of bacillomycin D produced by Bacillus amyloliquefaciens fmbJ were studied. The results showed that sodium propionate, propionic acid, and butyric acid could increase the yield of bacillomycin D by 44, 40, and 10%, respectively. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression levels of bacillomycin D synthesis gene, signaling factors and genes related to fatty acid metabolism, so as to explore the mechanism of sodium propionate regulating bacillomycin D synthesis. In conclusion, sodium propionate could accelerate the tricarboxylic acid cycle and promoted spore formation, cell movement, the secretion of extracellular protease and the transcription of bacillomycin D synthesis gene by upregulating the expression of signal factors degU, degQ, sigH, sigM and spo0A and ultimately promoted the synthesis of bacillomycin D. In this study, the mechanism of sodium propionate increasing bacillomycin D production was explored from multiple perspectives, which provided theoretical support for the large-scale production of bacillomycin D and was expected to promote its wide application in food, agriculture and medicine fields.

Clinical outcomes in dynamic intraligamentary stabilization technique for anterior cruciate ligament tear: A meta-analysis.

BACKGROUND: To compare the clinical outcome between dynamic intraligamentary stabilization (DIS) and anterior cruciate ligament (ACL) reconstruction in ACL tears. METHODS: PubMed, the Cochrane Library, and Embase databases were searched to identify published articles on clinical studies comparing DIS versus ACL reconstruction. The results of the eligible studies were analyzed in terms of anteroposterior knee laxity translation (ΔATT) between the injured and contralateral knees, and subjective International Knee Documentation Committee (IKDC), Lysholm score, Tegner score, and ipsilateral ACL failure, implant removal, and ACL revision. RESULTS: Five clinical studies including 429 patients with ACL tears met the inclusion criteria. DIS showed statistically comparable outcomes of ΔATT (P = .12), IKDC (P = .38), Tegner (P = .82), ACL failure (P = .50), ACL revision (P = .29) with ACL reconstruction. A significantly higher rate of implant removal (odds ratio for DIS vs ACL reconstruction, 7.73; 95% confidence interval [CI], 2.72-22.00; P = .0001) but statistically higher Lysholm score (mean difference between DIS and ACL reconstruction, 1.59; 95% CI, 0.24-2.93; P = .02) were found in DIS group. CONCLUSION: Five clinical studies including 429 patients with ACL tears met the inclusion criteria. DIS showed statistically comparable outcomes of ΔATT (P = .12), IKDC (P = .38), Tegner (P = .82), ACL failure (P = .50), ACL revision (P = .29) with ACL reconstruction. A significantly higher rate of implant removal (odds ratio for DIS vs ACL reconstruction, 7.73; 95% CI, 2.72-22.00; P = .0001) but statistically higher Lysholm score (mean difference between DIS and ACL reconstruction, 1.59; 95% CI, 0.24-2.93; P = .02) were found in DIS group.

Ingestion of Lacticaseibacillus rhamnosus Fmb14 prevents depression-like behavior and brain neural activity via the microbiota-gut-brain axis in colitis mice.

Large preclinical evidence suggested that colitis was one of the risk factors for depression and probiotics were effective therapeutic agents to prevent the disease. The effect of Lacticaseibacillus rhamnosus Fmb14 on colitis-related depression-like behavior and its possible mechanisms were investigated. One week of DSS exposure led to the following changes in male C57BL/6N mice: a reduction in the movement distance from 2218 to 1299 cm, time in central areas from 23.6 s to 11.5 s, and time in the bright box from 217 s to 103 s, which were restored to 1816 cm, 18.4 s, and 181 s, respectively, with preadministration of Fmb14 for 8 weeks. All improvements provided by Fmb14 indicated a remarkable protective effect on depression-like behavior. Fmb14 first worked to repair intestinal barrier damage and the inflammatory response in the colon through ZO1 and Ocln enhancement and IL-1ß, NF-κB and IL-6 reduction, respectively. Second, dysbiosis of the gut microbiota was modulated by Fmb14, including reduction of Akkermansia (18.9% to 5.4%), Mucispirillum (0.6% to 0.1%) and Bifidobacterium (0.32% to 0.03%). Fmb14 supplementation ameliorates the brain inflammatory response via IL-18 and NF-κB reduction and improves the blood-brain barrier via increased levels of ZO1 and Ocln. Moreover, brain activity was facilitated by an increase in BDNF and dopamine and the downregulation of GABA in the Fmb14 group. As a consequence of the modulatory effect on the dysfunction of neurotransmitters and neuroinflammation, Fmb14 prevents neurodegeneration by inhibiting neuronal apoptosis and Nissl edema. In addition, the correlation analysis further demonstrated the preventative effect of Fmb14 on depression-like behavior through the microbiota-gut-brain axis. Together, these findings demonstrated the important role of Fmb14 in biological signal transduction over the microbiota-gut-brain axis to improve mood disorders.

Engineered Cell Membrane Vesicles Expressing CD40 Alleviate System Lupus Nephritis by Intervening B Cell Activation.

Immune intervention of B cell activation to blockade the production of autoantibodies provokes intense interest in the field of systemic lupus erythematosus (SLE) therapy development. Although the survival rate for SLE is improved, many patients die untimely. Engineered cell membrane vesicles manifest remarkable capacity of targeted drug delivery and immunomodulation of immune cells such as B cells. Herein, this work engineered cellular nanovesicles (NVs) presenting CD40 (CD40 NVs) that can blunt B cells and thus alleviate SLE. CD40 NVs disrupt the CD40/CD40 ligand (CD40L) costimulatory signal axis through the blockade of CD40L on CD4+ T cells. Therefore, the CD40 NVs restrain the generation of the germinal center structure and production of antibodies from B cells. Furthermore, immunosuppressive drug mycophenolate mofetil (MMF) is also encapsulated in the vesicles (MMF-CD40 NVs), which is employed to deplete immunocytes including B cells, T cells, and dendritic cells. Together, CD40 NVs are promising formulations for relieving autoimmunity and lupus nephritis in MRL/lpr mice.

Biochemical and molecular regulatory mechanism of the pgpH gene on biofilm formation in Listeria monocytogenes.

AIMS: PgpH gene has an important regulatory role on bacterial physiological activity, but studies on its regulation mechanism on biofilm formation of Listeria monocytogenes are lacking. Our aim was to investigate the effect of pgpH gene deletion on biofilm formation in L. monocytogenes. METHODS AND RESULTS: The ΔpgpH deletion strain of L. monocytogenes LMB 33 426 was constructed by homologous recombination. Deletion of the pgpH gene resulted in a significant reduction in biofilm formation. The swimming ability of the ΔpgpH strain on semisolid plates was unchanged compared to the wild-type strain (WT), and the auto-aggregation capacity of L. monocytogenes was decreased. RNA-seq showed that ΔpgpH resulted in the differential expression of 2357 genes compared to WT. pgpH inactivation resulted in the significant downregulation of the cell wall formation-related genes dltC, dltD, walK, and walR and the flagellar assembly related genes fliG and motB. CONCLUSIONS: This study shows that the deletion of pgpH gene regulates biofilm formation and auto-aggregation ability of L. monocytogenes by affecting the expression of flagellar assembly and cell wall related genes. pgpH has a global regulatory effect on biofilm formation in L. monocytogenes.

Maltose-Enhanced Exopolysaccharide Synthesis of Lactiplantibacillus plantarum through CRP-like Protein.

Carbon sources alter the synthesis of exopolysaccharides (EPS) in Lactiplantibacillus plantarum. Maltose increased the EPS production of L. plantarum 163 6.5-fold. Subsequently, EPS production, transcriptome, and proteome were analyzed using glucose or maltose to further clarify the regulatory mechanism. A cAMP receptor protein (UniProtKB: F9UNI5) has been identified to control EPS synthesis in the presence of cAMP by binding to the EPS synthesis promoter Pcps4A-J. Overexpression of the cAMP synthesis gene cyaA increased cAMP content and EPS production 4.5- and 2.2-fold, respectively. Furthermore, yogurt produced with L. plantarum 163-cyaA had a similar viscosity to that of commercial Greek yogurt; it had 20 and 83.7% greater viscosity than that produced with L. plantarum 163 with maltose and glucose, respectively. These findings indicated that L. plantarum 163-cyaA has potential applications in the production of functional fermented dairy products.

Surfactin Mitigates Dextran Sodium Sulfate-Induced Colitis and Behavioral Disorders in Mice by Mediating Gut-Brain-Axis Balance.

Ulcerative colitis (UC) is associated with brain neurotransmitter disorders and intestinal dysbiosis. Bacillus amyloliquefaciens fmb50 produces the lipopeptide surfactin, which has a wide range of biological activities. However, the effects of surfactin on DSS-induced colitis have not been reported. In the present study, oral surfactin significantly ameliorated colitis in a mouse model and reduced depression-like behavior, such as slowed walking speed, shortened movement distance in the open field test, and weakened exploration ability in the light-dark shuttle test. Surfactin noticeably improved gut microbial dysbiosis, intestinal barrier dysfunction in the colon, and blood-brain barrier dysfunction in the brain. Furthermore, the colon levels of occludin were upregulated by 68.51%, and the brain levels of occludin and ZO-1 were upregulated by 77.81% and 36.42%, respectively. Surfactin supplementation also inhibited inflammatory responses by inactivating the tumor necrosis factor-α (TNF-α), nuclear factor kappa-B (NF-κB), and NLRP3 signaling pathways in the colon and brain. Thus, we believe that surfactin improved the behavioral disorders by upregulating the levels of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine (NE), and brain-derived neurotrophic factor (BDNF), suppressing the inflammatory responses, and improving the blood-brain barrier dysfunction. Surfactin also reduced the abundances of gut microbes that are related to colitis, especially targeting facultative anaerobes of the phylum Proteobacteria, and it increased the abundance of beneficial bacteria such as Lactobacillus and unidentified Prevotella. Combined with its nontoxic nature observed in this long-term study in mice, oral surfactin might be a promising intervention strategy for preventing colitis by acting on the microbiota-gut-brain axis.

Probiotic Yogurt Alleviates High-Fat Diet-Induced Lipid Accumulation and Insulin Resistance in Mice via the Adiponectin Pathway.

A high-fat diet (HFD) easily contributes to the pathogenesis of obesity and insulin resistance. Obesity and insulin resistance have been clinical and public health challenges all over the world. Probiotic-fermented yogurt is one type of popular and functional beverage in people's daily lives. This study mainly explored the lipid- and glucose-lowering effects of Lactobacillus acidophilus NX2-6-fermented yogurt (LA-Y) in HFD-fed mice. The results showed that LA-Y administration improved the lipid profile in the serum and liver, reduced fasting blood glucose levels, and enhanced insulin sensitivity. Protein analysis showed that LA-Y treatment promoted fatty acid oxidation and suppressed de novo lipogenesis in the adipose tissue and liver. LA-Y effectively alleviated glucose metabolism disorders by activating the insulin signaling pathway, suppressing gluconeogenesis in the liver and muscle, reducing the concentration of pro-inflammatory cytokines in the serum, and promoting glycolysis and gluconeogenesis in the small intestine. LA-Y supplementation also promoted fat browning via the adiponectin/AMPKα/PGC-1α/UCP1 pathway and enhanced mitochondrial biogenesis in the liver and muscle by activating the adiponectin/AdipoR1/APPL1/AMPKα/PGC-1α pathway, leading to increased energy expenditure. Therefore, LA-Y may be a functional dairy food for preventing and alleviating diet-induced metabolic disorders.

LsrR-like protein responds to stress tolerance by regulating polysaccharide biosynthesis in Lactiplantibacillus plantarum.

In addition to their biological functions, polysaccharides assist Lactiplantibacillus plantarum in resisting harsh conditions. To enhance the polysaccharide biosynthesis and increase the survival of L. plantarum in gut environment. We analyzed the transcriptional regulators that regulated the polysaccharide biosynthesis. A new transcriptional inhibitor, LsrR (UniProtKB: Q88YH7), had been identified, which repressed polysaccharide synthesis by binding to the polysaccharide synthesis promoter cps4A-J (Pcps4A-J). The EPSs and CPSs production of L. plantarum 163 was reduced by 42 % and 36 % (p < 0.05), respectively, when lsrR was overexpressed. Furthermore, alkaline shock proteins Asp2 and Asp1, heat shock protein Hsp3, and an autoinducer-2 (AI-2) related quorum-sensing regulator Rrp6 recovered the synthesis of polysaccharides to 50, 33, 55, and 60 %, respectively, by inhibiting the LsrR activity. This suggested that LsrR regulates polysaccharide synthesis in response to external stress signals such as pH, temperature, and AI-2 concentration. Finally, we showed that polysaccharides increased the survival rate of L. plantarum (Lp163-ΔlsrR) by 2.1 times during lyophilization and enhanced its tolerance to pH 2.0 and 0.2 % bile salts by 15.3 and 60 times due to increased capsular thickness and enhanced the autoaggregation. We provide critical data regarding Lactobacillus survival during preservative lyophilization and under gastrointestinal conditions.

Prediction of presurgical metabolic syndrome for gastric cancer-specific mortality is more evident in smokers: The FIESTA study.

BACKGROUNDS: We aimed to test whether the prediction of presurgical metabolic syndrome for postsurgical survival outcomes of gastric cancer hinges upon cigarette smoking status. METHODS: This study is a part of the ongoing Fujian prospective investigation of cancer (FIESTA) study. Patients with gastric cancer received radical resection of primary gastric cancer between January 2000 and December 2010, with the latest follow-up ended in December 2015. The 1:1 propensity score matching analysis was adopted to balance confounders between smokers and never-smokers. Effect-size estimates are expressed as hazard ratio (HR) with 95% confidence interval (CI). Model performance was evaluated using the Hosmer and Lemeshow test and 10-fold cross-validated area under the receiver operating characteristic curve (AUROC). Statistical analyses were completed with SAS software (v9.4). RESULTS: Total 2779 patients with gastric cancer were analyzed, including 2223 smokers and 556 never-smokers. Median follow-up time was 45.6 months. Cigarette smoking was not associated with postsurgical survival differences. Presurgical metabolic syndrome complication was significantly associated with increased gastric cancer-specific mortality in smokers (HR [95% CI]: 2.73 [1.53-4.89], p < 0.001), but not in never-smokers. Relative excess risk due to interaction was estimated to be 2.43 (95% CI: 0.40-4.45). After constructing a risk assessment score, one unit increment was associated with 10% reduced risk of gastric cancer-specific mortality (HR [95% CI]: 0.90 [0.88-0.91], p < 0.001), with 10-fold cross-validated AUROC being 0.82 (95% CI: 0.74-0.92). CONCLUSIONS: Our findings showed that the prediction of presurgical metabolic syndrome for gastric cancer-specific mortality was more evident in smokers. Practically, this study provides evidence base for future personalized prediction and helped risk-stratify gastric cancer patients who might experience serious postsurgical consequences.

Biosynthetic neoantigen displayed on bacteria derived vesicles elicit systemic antitumour immunity.

Neoantigens derived from mutant proteins in tumour cells could elicit potent personalized anti-tumour immunity. Nevertheless, the layout of vaccine vehicle and synthesis of neoantigen are pivotal for stimulating robust response. The power of synthetic biology enables genetic programming bacteria to produce therapeutic agents under contol of the gene circuits. Herein, we genetically engineered bacteria to synthesize fusion neoantigens, and prepared bacteria derived vesicles (BDVs) presenting the neoantigens (BDVs-Neo) as personalized therapeutic vaccine to drive systemic antitumour response. BDVs-Neo and granulocyte-macrophage colony-stimulating factor (GM-CSF) were inoculated subcutaneously within hydrogel (Gel), whereas sustaining release of BDVs-Lipopolysaccharide (LPS) and GM-CSF recruited the dendritic cells (DCs). Virtually, Gel-BDVs-Neo combined with the programmed cell death protein 1 (PD-1) antibody intensively enhanced proliferation and activation of tumour-infiltrated T cells, as well as memory T cell clone expansion. Consequently, BDVs-Neo combining with checkpoint blockade therapy effectively prevented tumour relapse and metastasis.