The Oncogenic Role of TNFRSF12A in Colorectal Cancer and Pan-Cancer Bioinformatics Analysis.

Purpose: Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms. Materials and Methods: Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A. Results: TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased NF-κB signaling and significant upregulation of BIRC3, a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer. Conclusion: TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.

Reduced Risk of Cardiovascular Diseases after Bariatric Surgery Based on the New PREVENT Equations.

Background: We applied the novel Predicting Risk of Cardiovascular Disease EVENTs (PREVENT) equations to evaluate cardiovascular-kidney-metabolic (CKM) health and estimated CVD risk, including heart failure (HF), after bariatric surgery. Methods: Among 7804 patients (20-79 years) undergoing bariatric surgery at Vanderbilt University Medical Center during 1999-2022, CVD risk factors at pre-surgery, 1-year, and 2-year post-surgery were extracted from electronic health records. The 10- and 30-year risks of total CVD, atherosclerotic CVD (ASCVD), coronary heart disease (CHD), stroke, and HF were estimated for patients without a history of CVD or its subtypes at each time point, using the social deprivation index-enhanced PREVENT equations. Paired t-tests or McNemar tests were used to compare pre- with post-surgery CKM health and CVD risk. Two-sample t-tests were used to compare CVD risk reduction between patient subgroups defined by age, sex, race, operation type, weight loss, and history of diabetes, hypertension, and dyslipidemia. Results: CKM health was significantly improved after surgery with lower systolic blood pressure, non-high-density-lipoprotein cholesterol (non-HDL), and diabetes prevalence, but higher HDL and estimated glomerular filtration rate (eGFR). The 10-year total CVD risk decreased from 6.51% at pre-surgery to 4.81% and 5.08% at 1- and 2-year post-surgery (relative reduction: 25.9% and 16.8%), respectively. Significant risk reductions were seen for all CVD subtypes (i.e., ASCVD, CHD, stroke, and HF), with the largest reduction for HF (relative reduction: 55.7% and 44.8% at 1- and 2-year post-surgery, respectively). Younger age, White race, >30% weight loss, diabetes history, and no dyslipidemia history were associated with greater HF risk reductions. Similar results were found for the 30-year risk estimates. Conclusions: Bariatric surgery significantly improves CKM health and reduces estimated CVD risk, particularly HF, by 45-56% within 1-2 years post-surgery. HF risk reduction may vary by patient's demographics, weight loss, and disease history, which warrants further research.

Radiomics analysis based on CT for predicting lymph node metastasis and prognosis in duodenal papillary carcinoma.

OBJECTIVES: Radiomics has been demonstrated to be strongly associated with TNM stage and patient prognosis. We aimed to develop a model for predicting lymph node metastasis (LNM) and survival. METHODS: For radiomics texture selection, 3D Slicer 5.0.3 software and the least absolute shrinkage and selection operator (LASSO) algorithm were used. Subsequently, the radiomics model, computed tomography (CT) image, and clinical risk model were compared. The performance of the three models was evaluated using receiver operating characteristic (ROC) curves, decision curve analysis (DCA), calibration plots, and clinical impact curves (CICs). RESULTS: For the LNM prediction model, 224 patients with LNM information were used to construct a model that was applied to predict LNM. According to the CT data and clinical characteristics, we constructed a radiomics model, CT imaging model and clinical model. The radiomics model for evaluating LNM status showed excellent calibration and discrimination in the training cohort (AUC = 0.926, 95% CI = 0.869-0.982) and the validation cohort (AUC = 0.872, 95% CI = 0.802-0.941). DeLong's test demonstrated that the difference among the three models was significant. Similarly, DCA and CIC showed that the radiomics model has better clinical utility than the CT imaging model and clinical model. Our model also exhibited good performance in predicting survival-in line with the findings of the model built with clinical risk factors. CONCLUSIONS: CT radiomics models exhibited better predictive performance for LNM than models built based on clinical risk characteristics and CT imaging and had comparative clinical utility for predicting patient prognosis. CRITICAL RELEVANCE STATEMENT: The radiomics model showed excellent performance and discrimination for predicting LNM and survival of duodenal papillary carcinoma (DPC). KEY POINTS: LNM status determines the most appropriate treatment for DPC. Our radiomics model for evaluating the LNM status of DPC performed excellently. The radiomics model had high sensitivity and specificity for predicting survival, exhibiting great clinical value.

3D bioprinting platform development for high-throughput cancer organoid models construction and drug evaluation.

The evaluation of anti-tumor drugs is critical for their development and clinical guidance. Tumor organoid models are gaining increased attention due to their ability to better mimic real tumor tissues, as well as lower time and economic costs, which makes up for the shortcomings of cell lines and xenograft models. However, current tumor organoid cultures based on the Matrigel have limitations in matching with high-throughput engineering methods due to slow gelation and low mechanical strength. Here, we present a novel composite bioink for culturing colorectal cancer organoids that provides an environment close to real tissue growth conditions and exhibits excellent photocrosslinking properties for rapid gel formation. Most importantly, the tumor organoids viability in the composite bioink after printing was as high as 97%, which also kept multicellular polar structures consistent with traditional culture methods in the Matrigel. Using 3D bioprinting with this composite bioink loaded with organoids, we demonstrated the feasibility of this drug evaluation model by validating it with clinically used colorectal cancer treatment drugs. Our results suggested that the composite bioink could effectively cultivate tumor organoids using 3D bioprinting, which had the potential to replace less reliable manual operations in promoting the application of tumor organoids in drug development and clinical guidance.

Cigarette smoke-induced dysbiosis: comparative analysis of lung and intestinal microbiomes in COPD mice and patients.

BACKGROUND: The impact of cigarette smoke (CS) on lung diseases and the role of microbiome dysbiosis in chronic obstructive pulmonary disease (COPD) have been previously reported; however, the relationships remain unclear. METHODS: Our research examined the effects of 20-week cigarette smoke (CS) exposure on the lung and intestinal microbiomes in C57BL/6JNarl mice, alongside a comparison with COPD patients' intestinal microbiome data from a public dataset. RESULTS: The study found that CS exposure significantly decreased forced vital capacity (FVC), thickened airway walls, and induced emphysema. Increased lung damage was observed along with higher lung keratinocyte chemoattractant (KC) levels by CS exposure. Lung microbiome analysis revealed a rise in Actinobacteriota, while intestinal microbiome showed significant diversity changes, indicating dysbiosis. Principal coordinate analysis highlighted distinct intestinal microbiome compositions between control and CS-exposed groups. In the intestinal microbiome, notable decreases in Patescibacteria, Campilobacterota, Defferibacterota, Actinobacteriota, and Desulfobacterota were observed. We also identified correlations between lung function and dysbiosis in both lung and intestinal microbiomes. Lung interleukins, interferon-É£, KC, and 8-isoprostane levels were linked to lung microbiome dysbiosis. Notably, dysbiosis patterns in CS-exposed mice were similar to those in COPD patients, particularly of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 4 patients. This suggests a systemic impact of CS exposure. CONCLUSION: In summary, CS exposure induces significant dysbiosis in lung and intestinal microbiomes, correlating with lung function decline and injury. These results align with changes in COPD patients, underscoring the important role of microbiome in smoke-related lung diseases.

Biosynthetic potential of uncultured anammox community bacteria revealed through multi-omics analysis.

Microbial secondary metabolites (SMs) and their derivatives have been widely used in medicine, agriculture, and energy. Growing needs for renewable energy and the challenges posed by antibiotic resistance, cancer, and pesticides emphasize the crucial hunt for new SMs. Anaerobic ammonium-oxidation (anammox) systems harbor many uncultured or underexplored bacteria, representing potential resources for discovering novel SMs. Leveraging HiFi long-read metagenomic sequencing, 1,040 biosynthetic gene clusters (BGCs) were unearthed from the anammox microbiome with 58% being complete and showcasing rich diversity. Most of them showed distant relations to known BGCs, implying novelty. Members of the underexplored lineages (Chloroflexota and Planctomycetota) and Proteobacteria contained lots of BGCs, showcasing substantial biosynthetic potential. Metaproteomic results indicated that Planctomycetota members harbored the most active BGCs, particularly those involved in producing potential biofuel-ladderane. Overall, these findings underscore that anammox microbiomes could serve as valuable resources for mining novel BGCs and discovering new SMs for practical application.

DNA Damage-Induced Apoptosis Suppressor Triggers Progression and Stemness of Glioma by Enhancing Lymphoid Enhancer-Binding Factor 1 Expression.

Background: DNA damage-induced apoptosis suppressor (DDIAS) has recently been discovered to induce cancer progression, but its functions and mechanisms in glioma have not been well studied. Methods: DDIAS expression in glioma tissues was analyzed by the Gene Expression Profiling Interactive Analysis server (GEPIA) and the Gene Expression database of Normal and Tumor tissue 2 (GENT2) databases. The role of DDIAS in glioma progression was studied by short hairpin RNA (shRNA) targeting DDIAS. The effects of DDIAS on glioma cell viability, cell proliferation, invasion, migration, and tumor sphere formation were determined by cell counting kit-8 (CCK-8), EdU, Transwell, tumor spheroid formation, extreme limiting dilution analysis assays in vitro and xenograft model construction in vivo. In addition, RNA sequencing and further functional experiments were used to analyze the DDIAS regulatory mechanism in glioma. Results: We found that DDIAS was highly expressed in glioma and that upregulated DDIAS indicated poor prognosis. Functionally, DDIAS knockdown inhibited glioma cell viability, cell proliferation, invasion and migration in vitro and tumor growth in vivo. In addition, lymphoid enhancer-binding factor 1 (LEF1) was identified as the downstream effector of DDIAS by RNA sequencing. DDIAS downregulation inhibited LEF1 mRNA and protein expression. The expression of DDIAS and LEF1 was positively correlated, and LEF1 overexpression rescued the inhibitory phenotype induced by DDIAS downregulation. We further showed that DDIAS downregulation inhibited cyclin A1, vimentin and the stemness-related factor CD133 and decreased the sphere formation capability, but these features were rescued by upregulation of LEF1. Conclusion: Taken together, these findings suggest that DDIAS promotes glioma progression and stemness by inducing LEF1 expression, proving that DDIAS may be a potential target for the treatment of glioma.

Comparison of three-dimensional heads-up system versus traditional microscopic system in medical education for vitreoretinal surgeries: a prospective study.

BACKGROUND: To compare the value and efficiency of the three-dimensional (3D) heads-up surgical system and traditional microscopic (TM) system in teaching and learning vitreoretinal surgeries. METHODS: Twenty ophthalmologists and scrub nurses were recruited as teachers, and 45 junior ophthalmology residents and trainee doctors, trainee nurses, and medical students were recruited as observers. Each teacher and observer were assigned to both a 3D-assisted and TM-assisted vitreoretinal surgery and then asked to complete satisfaction questionnaires for both surgical systems at the end of each surgery. RESULTS: The 3D heads-up surgical system was rated significantly higher in most of the subscales and overall satisfaction score by both teachers and observers (P < 0.05). However, ratings for instrument adjustment were significantly higher in the TM group compared to the 3D group for junior ophthalmology residents and trainee doctors (6.1 ± 1.7 vs. 8.8 ± 1.1, P < 0.001). CONCLUSIONS: The 3D heads-up surgical system has great didactical value in the medical education of vitreoretinal surgeries, but it is important to consider the specific needs of different learners when choosing between the two systems. TRIAL REGISTRATION: Not applicable.

Cardiometabolic Improvements After Metabolic Surgery and Related Presurgery Factors.

Context: Metabolic surgery remains the most effective and durable treatment for severe obesity and related metabolic diseases. Objective: We examined cardiometabolic improvements after metabolic surgery and associated presurgery demographic and clinical factors in a large multiracial cohort. Methods: Included were 7804 patients (20-79 years) undergoing first-time metabolic surgery at Vanderbilt University Medical Center from 1999 to 2022. Pre- and 1-year postsurgery cardiometabolic profiles were extracted from medical records, including body mass index (BMI), blood pressure, blood lipids, glucose, and hemoglobin A1c. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk was estimated per American College of Cardiology/American Heart Association equations. Pre- to postsurgery cardiometabolic profiles were compared by paired t-test, and associated factors were identified by multivariable linear and logistic regression. Results: Among 7804 patients, most were women and White, while 1618 were men and 1271 were Black; median age and BMI were 45 years [interquartile range (IQR): 37-53] and 46.4 kg/m2 (IQR: 42.1-52.4). At 1-year postsurgery, patients showed significant decreases in systolic blood pressure (10.5 [95% confidence interval: 10.1, 10.9] mmHg), total cholesterol (13.5 [10.3, 16.7] mg/dL), glucose (13.6 [12.9, 14.4] mg/dL), hemoglobin A1c (1.13% [1.06, 1.20]), and 10-year ASCVD risk (absolute reduction: 1.58% [1.22, 1.94]; relative reduction: 34.4% [29.4, 39.3]); all P < .0001. Older, male, or Black patients showed less reduction in 10-year ASCVD risk and lower odds of diabetes/hypertension/dyslipidemia remission than younger, female, or White patients. Patients with a history of diabetes, hypertension, dyslipidemia, or cardiovascular disease showed less cardiometabolic improvements than those without. Results were similar with or without further adjusting for weight loss and largely sustained at 2-year postsurgery. Conclusion: Metabolic surgery results in significant cardiometabolic improvements, particularly among younger, female, or White patients and those without comorbidities.

Sex- and operation-dependent effects on 5-year weight loss results of bariatric surgery.

BACKGROUND: Weight loss response after bariatric surgery is highly variable, and several demographic factors are associated with differential responses to surgery. Preclinical studies demonstrate numerous sex-specific responses to bariatric surgery, but whether these responses are also operation dependent is unknown. OBJECTIVE: To examine sex-specific weight loss outcomes up to 5 years after laparoscopic Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). SETTING: Single center, university, United States. METHODS: Retrospective, observational cohort study including RYGB (n = 5057) and vertical SG (n = 2041) patients from a single, academic health center. Percentage total weight loss (TWL) over time was examined with generalized linear mixed models to determine the main and interaction effects of surgery type on weight loss by sex. RESULTS: TWL demonstrated a strong sex-by-procedure interaction, with women having a significant advantage with RYGB compared with SG (adjusted difference at 5 yr: 8.0% [95% CI: 7.5-8.5]; P < .001). Men also experienced greater TWL over time with RYGB or SG, but the difference was less and clinically insignificant (adjusted difference at 5 yr: 2.9% [2.0-3.8]; P < .001; P interaction between sex and procedure type = .0001). Overall, women had greater TWL than men, and RYGB patients had greater TWL than SG patients (adjusted difference at 5 yr: 3.1% [2.4-3.2] and 6.9% [6.5-7.3], respectively; both P < .0001). Patients with diabetes lost less weight compared with those without (adjusted difference at 5 yr: 3.0% [2.7-3.2]; P < .0001). CONCLUSIONS: Weight loss after bariatric surgery is sex- and procedure-dependent. There is an association suggesting a clinically insignificant difference in weight loss between RYGB and SG among male patients at both the 2- and 5-year postsurgery time points.

Injectable Hydrogel Delivery System with High Drug Loading for Prolonging Local Anesthesia.

Peripheral nerve block is performed for precise pain control and lesser side effects after surgery by reducing opioid consumption. Injectable hydrogel delivery systems with high biosafety and moisture content have good clinical application prospects for local anesthetic delivery. However, how to achieve high drug loading and long-term controlled release of water-soluble narcotic drugs remains a big challenge. In this study, heterogeneous microspheres and an injectable gel-matrix composite drug delivery system are designed in two steps. First, heterogeneous hydrogel microspheres loaded with ropivacaine (HMS-ROP) are prepared using a microfluidic chip and in situ alkalization. An injectable self-healing hydrogel matrix (Gel) is then prepared from modified carboxymethylcellulose (CMC-ADH) and oxidized hyaluronic acid (OHA). A local anesthetic delivery system, Gel/HMS-ROP/dexmedetomidine (DEX), with long-term retention and drug release in vivo is prepared by combining HMS-ROP and Gel/DEX. The drug loading of HMS-ROP reached 41.1%, with a drug release time of over 160 h in vitro, and sensory and motor blockade times in vivo of 48 and 36 h, respectively. In summary, the sequential release and synergistic analgesic effects of the two anesthetics are realized using core-shell microspheres, DEX, and an injectable gel, providing a promising strategy for long-acting postoperative pain management.

Single-cell RNA sequencing reveals immune cell dysfunction in the peripheral blood of patients with highly aggressive gastric cancer.

Highly aggressive gastric cancer (HAGC) is a gastric cancer characterized by bone marrow metastasis and disseminated intravascular coagulation (DIC). Information about the disease is limited. Here we employed single-cell RNA sequencing to investigate peripheral blood mononuclear cells (PBMCs), aiming to unravel the immune response of patients toward HAGC. PBMCs from seven HAGC patients, six normal advanced gastric cancer (NAGC) patients, and five healthy individuals were analysed by single-cell RNA sequencing. The expression of genes of interest was validated by bulk RNA-sequencing and ELISA. We found a massive expansion of neutrophils in PBMCs of HAGC. These neutrophils are activated, but immature. Besides, mononuclear phagocytes exhibited an M2-like signature and T cells were suppressed and reduced in number. Analysis of cell-cell crosstalk revealed that several signalling pathways involved in neutrophil to T-cell suppression including APP-CD74, MIF-(CD74+CXCR2), and MIF-(CD74+CD44) pathways were increased in HAGC. NETosis-associated genes S100A8 and S100A9 as well as VEGF, PDGF, FGF, and NOTCH signalling that contribute to DIC development were upregulated in HAGC too. This study reveals significant changes in the distribution and interactions of the PBMC subsets and provides valuable insight into the immune response in patients with HAGC. S100A8 and S100A9 are highly expressed in HAGC neutrophils, suggesting their potential to be used as novel diagnostic and therapeutic targets for HAGC.

Are Radiomic Spleen Features Useful for Assessing the Response to Infliximab in Patients With Crohn's Disease? A Multicenter Study.

INTRODUCTION: To develop and validate a radiomics nomogram for assessing the response of patients with Crohn's disease (CD) to infliximab. METHODS: Radiomics features of the spleen were extracted from computed tomography enterography images of each patient's arterial phase. The feature selection process was performed using the least absolute shrinkage and selection operator algorithm, and a radiomics score was calculated based on the radiomics signature formula. Subsequently, the radiomic model and the clinical risk factor model were separately established based on the radiomics score and clinically significant features, respectively. The performance of both models was evaluated using receiver operating characteristic curves, decision curve analysis curves, and clinical impact curves. RESULTS: Among the 175 patients with CD, 105 exhibited a clinical response, and 60 exhibited clinical remission after receiving infliximab treatment. Our radiomic model, comprising 20 relevant features, demonstrated excellent predictive performance. The radiomic nomogram for predicting clinical response showed good calibration and discrimination in the training cohort (area under the curve [AUC] 0.909, 95% confidence interval [CI] 0.840-0.978), the validation cohort (AUC 0.954, 95% CI 0.889-1), and the external cohort (AUC = 0.902, 95% CI 0.83-0.974). Accordingly, the nomogram was also suitable for predicting clinical remission. Decision curve analysis and clinical impact curves highlighted the clinical utility of our nomogram. DISCUSSION: Our radiomics nomogram is a noninvasive predictive tool constructed from radiomic features of the spleen. It also demonstrated good predictive accuracy in evaluating CD patients' response to infliximab treatment. Multicenter validation provided high-level evidence for its clinical application.

Hydrogen sulfide responsive nanoplatforms: Novel gas responsive drug delivery carriers for biomedical applications.

Hydrogen sulfide (H2S) is a toxic, essential gas used in various biological and physical processes and has been the subject of many targeted studies on its role as a new gas transmitter. These studies have mainly focused on the production and pharmacological side effects caused by H2S. Therefore, effective strategies to remove H2S has become a key research topic. Furthermore, the development of novel nanoplatforms has provided new tools for the targeted removal of H2S. This paper was performed to review the association between H2S and disease, related H2S inhibitory drugs, as well as H2S responsive nanoplatforms (HRNs). This review first analyzed the role of H2S in multiple tissues and conditions. Second, common drugs used to eliminate H2S, as well as their potential for combination with anticancer agents, were summarized. Not only the existing studies on HRNs, but also the inhibition H2S combined with different therapeutic methods were both sorted out in this review. Furthermore, this review provided in-depth analysis of the potential of HRNs about treatment or detection in detail. Finally, potential challenges of HRNs were proposed. This study demonstrates the excellent potential of HRNs for biomedical applications.

Measuring Associations Between Community-Level Social Determinants of Health and Bariatric Surgery Weight Loss Outcomes.

Bariatric surgery is a crucial intervention in managing obesity and related conditions. However, weight loss outcomes can vary significantly, and social determinants of health (SDoH) at the community level may play a role. Our objective is to identify community-level SDoH factors associated with reduced weight loss after bariatric surgery. We conducted an analysis of electronic health records and the social vulnerability index (SVI) of 3,800 patients who underwent bariatric surgery at Vanderbilt University Medical Center. We measured the associations between SVI social factors and the percent change in body mass index three months after surgery using linear regression. The SVI factors with a false discovery rate-adjusted p-value < 0.05 were deemed significant. Statistical results show that patients who reside in communities with racial minority groups or lower insurance rates had reduced weight loss three months after surgery.

Enhanced Patient Portal Engagement Associated with Improved Weight Loss Outcomes in Post-Bariatric Surgery Patients.

Background: Bariatric surgery is an effective intervention for obesity, but it requires comprehensive postoperative self-management to achieve optimal outcomes. While patient portals are generally seen as beneficial in engaging patients in health management, the link between their use and post-bariatric surgery weight loss remains unclear. Objective: This study investigated the association between patient portal engagement and postoperative body mass index (BMI) reduction among bariatric surgery patients. Methods: This retrospective longitudinal study included patients who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) at Vanderbilt University Medical Center (VUMC) between January 2018 and March 2021. Using generalized estimating equations, we estimated the association between active days of postoperative patient portal use and the reduction of BMI percentage (%BMI) at 3, 6, and 12 months post-surgery. Covariates included duration since surgery, the patient's age at the time of surgery, gender, race and ethnicity, type of bariatric surgery, severity of comorbid conditions, and socioeconomic disadvantage. Results: The study included 1,415 patients, mostly female (80.9%), with diverse racial and ethnic backgrounds. 805 (56.9%) patients underwent RYGB and 610 (43.1%) underwent SG. By one-year post-surgery, the mean (SD) %BMI reduction was 31.1% (8.3%), and the mean (SD) number of patient portal active days was 61.0 (41.2). A significantly positive association was observed between patient portal engagement and %BMI reduction, with variations revealed over time. Each 10-day increment of active portal use was associated with a 0.57% ([95% CI: 0.42- 0.72], P < .001) and 0.35% ([95% CI: 0.22- 0.49], P < .001) %BMI reduction at 3 and 6 months postoperatively. The association was not statistically significant at 12 months postoperatively (ß=-0.07, [95% CI: -0.24- 0.09], P = .54). Various portal functions, including messaging, visits, my record, medical tools, billing, resources, and others, were positively associated with %BMI reduction at 3- and 6-months follow-ups. Conclusions: Greater patient portal engagement, which may represent stronger adherence to postoperative instructions, better self-management of health, and enhanced communication with care teams, was associated with improved postoperative weight loss. Future investigations are needed to identify important portal features that contribute to the long-term success of weight loss management.

Motility behavior and physiological response mechanisms of aerobic denitrifier, Enterobacter cloacae strain HNR under high salt stress: Insights from individual cells to populations.

The motility behaviors at the individual-cell level and the collective physiological responsive behaviors of aerobic denitrifier, Enterobacter cloacae strain HNR under high salt stress were investigated. The results revealed that as salinity increased, electron transport activity and adenosine triphosphate content decreased from 15.75 µg O2/g/min and 593.51 mM/L to 3.27 µg O2/g/min and 5.34 mM/L, respectively, at 40 g/L, leading to a reduction in the rotation velocity and vibration amplitude of strain HNR. High salinity stress (40 g/L) down-regulated genes involved in ABC transporters (amino acids, sugars, metal ions, and inorganic ions) and activated the biofilm-related motility regulation mechanism in strain HNR, resulting in a further decrease in flagellar motility capacity and an increase in extracellular polymeric substances secretion (4.08 mg/g cell of PS and 40.03 mg/g cell of PN at 40 g/L). These responses facilitated biofilm formation and proved effective in countering elevated salt stress in strain HNR. Moreover, the genetic diversity associated with biofilm-related motility regulation in strain HNR enhanced the adaptability and stability of the strain HNR populations to salinity stress. This study enables a deeper understanding of the response mechanism of aerobic denitrifiers to high salt stress.

Amelioration of the brain structural connectivity is accompanied with changes of gut microbiota in a tuberous sclerosis complex mouse model.

Tuberous sclerosis complex (TSC) is a genetic disease that causes benign tumors and dysfunctions in many organs, including the brain. Aside from the brain malformations, many individuals with TSC exhibit neuropsychiatric symptoms. Among these symptoms, autism spectrum disorder (ASD) is one of the most common co-morbidities, affecting up to 60% of the population. Past neuroimaging studies strongly suggested that the impairments in brain connectivity contribute to ASD, whether or not TSC-related. Specifically, the tract-based diffusion tensor imaging (DTI) analysis provides information on the fiber integrity and has been used to study the neuropathological changes in the white matter of TSC patients with ASD symptoms. In our previous study, curcumin, a diet-derived mTOR inhibitor has been shown to effectively mitigate learning and memory deficits and anxiety-like behavior in Tsc2+/- mice via inhibiting astroglial proliferation. Recently, gut microbiota, which is greatly influenced by the diet, has been considered to play an important role in regulating several components of the central nervous system, including glial functions. In this study, we showed that the abnormal social behavior in the Tsc2+/- mice can be ameliorated by the dietary curcumin treatment. Second, using tract-based DTI analysis, we found that the Tsc2+/- mice exhibited altered fractional anisotropy, axial and radial diffusivities of axonal bundles connecting the prefrontal cortex, nucleus accumbens, hypothalamus, and amygdala, indicating a decreased brain network. Third, the dietary curcumin treatment improved the DTI metrics, in accordance with changes in the gut microbiota composition. At the bacterial phylum level, we showed that the abundances of Actinobacteria, Verrucomicrobia, and Tenericutes were significantly correlated with the DTI metrics FA, AD, and RD, respectively. Finally, we revealed that the expression of myelin-associated proteins, myelin bassic protein (MBP) and proteolipid protein (PLP) was increased after the treatment. Overall, we showed a strong correlation between structural connectivity alterations and social behavioral deficits, as well as the diet-dependent changes in gut microbiota composition.

Pien Tze Huang Inhibits Proliferation of Colorectal Cancer Cells through Suppressing PNO1 Expression and Activating p53/p21 Signaling Pathway.

OBJECTIVE: To explore the regulatory effect of Pien Tze Huang (PZH) on targeting partner of NOB1 (PNO1) and it's down-stream mediators in colorectal cancer (CRC) cells. METHODS: Quantitative polymerase chain reaction was performed to determine mRNA levels of PNO1, TP53, and CDKN1A. Western blotting was performed to determine protein levels of PNO1, p53, and p21. HCT-8 cells were transduced with a lentivirus over-expressing PNO1. Colony formation assay was used to detect cell survival in PNO1 overexpression of HCT-8 cells after PZH treatment. Cell-cycle distribution, cell viability and cell apoptosis were performed to identify the effect of PNO1 overexpression on cell proliferation and apoptosis of HCT-8 cells after PZH treatment. Xenograft BALB/c nude mice bearing HCT116 cells transduced with sh-PNO1 or sh-Ctrl lentivirus were evaluated. Western blot assay was performed to detect PNO1, p53, p21 and PCNA expression in tumor sections. Terminal deoxynucleotidyl transferase dUTP nick end labling (TUNEL) assay was used to determine the apoptotic cells in tissues. RESULTS: PZH treatment decreased cell viability, down-regulated PNO1 expression, and up-regulated p53 and p21 expressions in HCT-8 cells (P<0.05). PNO1 overexpression attenuated the effects of PZH treatment, including the expression of p53 and p21, cell growth, cell viability, cell cycle arrest and cell apoptosis in vitro (P<0.05). PNO1 knockdown eliminated the effects of PZH treatment on tumor growth, inhibiting cell proliferation inhibition and apoptosis induction in vivo (P<0.05). Similarly, PNO1 knockdown attenuated the effects of PZH treatment on the down-regulation of PNO1 and up-regulation of p53 and p21 in vivo (P<0.05). CONCLUSION: The mechanism by which PZH induces its CRC anti-proliferative effect is at least in part by regulating the expression of PNO1 and its downstream targets p53 and p21.

Cerebrospinal Fluid Interleukin-10 Biomarker for Vitreoretinal Lymphoma.

PURPOSE: To analyze the correlation between cerebrospinal fluid (CSF) interleukin-10 (IL-10) levels and the clinical characteristics in patients with vitreoretinal lymphoma (VRL). DESIGN: Retrospective observational case series. METHODS: Forty-one patients were diagnosed as VRL and underwent lumbar puncture for CSF examination. Aqueous humor cytokine detection, vitreous cytopathologic analysis, monoclonal gene rearrangement, and flow cytometry were performed. The CSF was assessed through biochemical and cytologic examination, flow cytometry, and cytokine detection. RESULTS: The median levels of aqueous humor IL-10 and IL-6 were 415.0 and 40.7 pg/mL. The median CSF levels of IL-10 and IL-6 were 35.7 and 3.5 pg/mL, respectively. IL-10 levels in CSF were higher than normal in 37 patients (90.2%) and higher in patients with intracranial lesions. The level of CSF IL-10 decreased after systemic treatment, and it rose before intracranial lesion onset or recurrence. The level of IL-10 in CSF was related to the duration of ocular symptoms, but was not related to the level of IL-10 in aqueous humor. There was no significant difference in CSF IL-10 levels between patients with and without anterior chamber inflammation or retinal lesions. In eyes with recurrent vitreoretinal lymphoma, the level of IL-10 in aqueous humor increased significantly, but there was no corresponding increase in the level of IL-10 in CSF. CONCLUSION: CSF IL-10 is a potentially important biomarker in VRL, especially in the monitoring of intracranial lesions.