Aluminum Carboxylate Modification Enabled Efficient and Stable Perovskite-Polystyrene Thin Films for Light-Emitting Applications.

Lead halide perovskite nanocrystals (PNCs) have demonstrated great potential in emerging display technologies. However, the practical application of PNCs is hindered by the inherent instability of their ionic surface. Here, we proposed a surface modification approach to enhance the stability of CsPbBr3 PNCs by postsynthetic treatment with aluminum phenylbutyrate (Al(PA)3). Our study reveals that Al(PA)3 displaces ammonium ligands and binds tightly on surface halide, providing excellent air and moisture resistance while preserving a high quantum efficiency of 81.6%. The modified PNCs maintain a constant photoluminescence intensity under continuous UV light illumination for 500 h. Additionally, the Al(PA)3 ligand is compatible with styrene, enabling homogeneous dispersion of PNCs in polystyrene matrices to form bright and uniform PNC-PS thin films. We demonstrated the application of the composite films for display backlighting, which exhibits a wide color gamut of 125% NTSC. The result highlights the potential of AlPA-modified PNCs in light-emitting and other optoelectronic devices.

Water-Oil Interfacial Synthesis of Two-Dimensional Colloidal Lead-Iodide Perovskites with Enhanced Efficiency and Stability.

Two-dimensional Ruddlesden-Popper perovskites L2PbI4 (L = alkylammonium cation) (RPPs) have attracted significant attention due to their unique excitonic characteristics. However, their ultrafast reaction dynamics exacerbates the structural distortion of the inorganic framework, leading to severe deterioration in photoluminescence. Here, we propose a water-oil interfacial synthesis approach to achieve controlled growth of the RPPs nanosheets. By segregating Pb and I precursors in two immiscible solvents, the nucleation and growth of RPPs are prolonged to the minute level. L2PbI4 nanosheets terminated with various alkylammonium are synthesized, and the factors influencing the growth kinetics of RPPs nanosheets are investigated. The resulting (PEA)2PbI4 nanosheets exhibit a 3.6-time enhancement in quantum efficiency and 3.2-time improvement photostability compared to those synthesized using the classical recrystallization method. A white light-emitting diode based on (HDA)2PbI4 nanosheets is fabricated, achieving a color gamut of 119.7% of the NTSC display standards. This innovative approach offers a new method for the controlled growth of 2D RPPs with improved optical quality and stability.

Somatostatin alleviates diversion colitis after fecal-stream bypass colostomy surgeries in rats.

BACKGROUND: Diversion colitis (DC) is a prevalent complication of colostomy characterized by intestinal inflammation. This study aimed to investigate the therapeutic potential of somatostatin (SST) in managing DC. METHODS: After establishing a rat DC model, SST was administered via Mini Osmotic Pumps 2001W at a pumping rate of 1.0 µL/h. Various techniques, including hematoxylin and eosin staining, periodic acid-Schiff staining, immunofluorescence staining, and electron microscopy were employed to assess the effects of SST. Intestinal barrier functions were evaluated using Evans blue, enzyme-linked immunosorbent assay, and MacConkey agar. RESULTS: After SST treatment, the significant weight loss and associated high mortality in the DC group were successfully mitigated. Upregulation of claudin-3 and claudin-4 restored mechanical barriers in colon epithelial tissue, whereas protection of goblet cells and stimulation of mucus secretion enhanced mucus barriers. SST effectively reduced leaky gut and alleviated systemic inflammation. CONCLUSION: This study provides initial evidence supporting the efficacy of SST in the treatment of DC. It offers insights into the role of SST in DC by elucidating its ability to restore damaged intestinal barriers.

High lymphocyte signature genes expression in parathyroid endocrine cells and its downregulation linked to tumorigenesis.

BACKGROUND: To date, because of the difficulty in obtaining normal parathyroid gland samples in human or in animal models, our understanding of this last-discovered organ remains limited. METHODS: In the present study, we performed a single-cell transcriptome analysis of six normal parathyroid and eight parathyroid adenoma samples using 10 × Genomics platform. FINDINGS: We have provided a detailed expression atlas of parathyroid endocrine cells. Interestingly, we found an exceptional high expression levels of CD4 and CD226 in parathyroid endocrine cells, which were even higher than those in lymphocytes. This unusual expression of lymphocyte markers in parathyroid endocrine cells was associated with the depletion of CD4 T cells in normal parathyroid glands. Moreover, CD4 and CD226 expression in endocrine cells was significantly decreased in parathyroid adenomas, which was associated with a significant increase in Treg counts. Finally, along the developmental trajectory, we discovered the loss of POMC, ART5, and CES1 expression as the earliest signature of parathyroid hyperplasia. INTERPRETATION: We propose that the loss of CD4 and CD226 expression in parathyroid endocrine cells, coupled with an elevated number of Treg cells, could be linked to the pathogenesis of parathyroid adenoma. Our data also offer valuable information for understanding the noncanonical function of CD4 molecule. FUNDING: This work was supported by the National Key R&D Program of China (2022YFA0806100), National Natural Science Foundation of China (82130025, 82270922, 31970636, 32211530422), Shandong Provincial Natural Science Foundation of China (ZR2020ZD14), Innovation Team of Jinan (2021GXRC048) and the Outstanding University Driven by Talents Program and Academic Promotion Program of Shandong First Medical University (2019LJ007).

Achieving Clearance of Drug-Resistant Bacterial Infection and Rapid Cutaneous Wound Regeneration Using an ROS-Balancing-Engineered Heterojunction.

Intractable infected microenvironments caused by drug-resistant bacteria stalls the normal course of wound healing. Sono-piezodynamic therapy (SPT) is harnessed to combat pathogenic bacteria, but the superabundant reactive oxygen species (ROS) generated during SPT inevitably provoke severe inflammatory response, hindering tissue regeneration. Consequently, an intelligent nanocatalytic membrane composed of poly(lactic-co-glycolic acid) (PLGA) and black phosphorus /V2C MXene bio-heterojunctions (2D2-bioHJs) is devised. Under ultrasonication, 2D2-bioHJs effectively eliminate drug-resistant bacteria by disrupting metabolism and electron transport chain (ETC). When ultrasonication ceases, they enable the elimination of SPT-generated ROS. The 2D2-bioHJs act as a "lever" that effectively achieves a balance between ROS generation and annihilation, delivering both antibacterial and anti-inflammatory properties to the engineered membrane. More importantly, in vivo assays corroborate that the nanocatalytic membranes transform the stalled chronic wound environment into a regenerative one by eradicating the bacterial population, dampening the NF-κB inflammatory pathway and promoting angiogenesis. As envisaged, this work demonstrates a novel tactic to arm membranes with programmed antibacterial and anti-inflammatory effects to remedy refractory infected wounds from drug-fast bacteria.

Postoperative recurrence of diffuse sclerosing thyroid cancer in an adolescent patient: A case report.

BACKGROUND: Papillary thyroid cancer is an inert malignant tumor with a good response to surgical treatment, low recurrence and metastasis rate, and good prognosis. Diffuse sclerosing thyroid cancer is an invasive subtype that is more common in young people, with a higher rate of lymph node metastasis and recurrence, and a relatively poor prognosis. PATIENT CONCERNS: A 13-year-old girl underwent radical surgery for diffuse sclerosing thyroid cancer. Eight years later, due to a large number of lymph node metastases, she underwent another radical surgery on her neck lymph nodes. METHODS: The patient thyroid ultrasound and neck enhanced CT indicated that the patient had multiple enlarged lymph nodes in the neck with irregular morphology and structure, and the possibility of metastatic lymph nodes was high. Subsequently, the patient underwent thyroid fine-needle aspiration and the results showed that cancer cells were detected in both cervical lymph nodes. DIAGNOSIS: The patient was diagnosed with bilateral cervical lymph node metastases after thyroid surgery. RESULTS: After the second surgery, the patient recovered well, and no residual or focal iodine uptake tissue was found on the enhanced CT examination. CONCLUSION: As diffuse sclerosing thyroid cancer is prone to lymph node and recurrent metastases, once it is diagnosed, radical treatment should be actively performed. Postoperative adjuvant radiation therapy should be administered according to the patient condition and regular follow-ups should be conducted to monitor neck lymph node metastasis.

Compromised NHE8 Expression Is Responsible for Vitamin D-Deficiency Induced Intestinal Barrier Dysfunction.

Objectives: Vitamin D (VitD) and Vitamin D receptor (VDR) are suggested to play protective roles in the intestinal barrier in ulcerative colitis (UC). However, the underlying mechanisms remain elusive. Evidence demonstrates that Na+/H+ exchanger isoform 8 (NHE8, SLC9A8) is essential in maintaining intestinal homeostasis, regarded as a promising target for UC therapy. Thus, this study aims to investigate the effects of VitD/VDR on NHE8 in intestinal protection. Methods: VitD-deficient mice, VDR-/- mice and NHE8-/- mice were employed in this study. Colitis mice were established by supplementing DSS-containing water. Caco-2 cells and 3D-enteroids were used for in vitro studies. VDR siRNA (siVDR), VDR over-expression plasmid (pVDR), TNF-α and NF-κb p65 inhibitor QNZ were used for mechanical studies. The expression of interested proteins was detected by multiple techniques. Results: In colitis mice, paricalcitol upregulated NHE8 expression was accompanied by restoring colonic mucosal injury. In VitD-deficient and VDR-/- colitis mice, NHE8 expression was compromised with more serious mucosal damage. Noteworthily, paricalcitol could not prevent intestinal barrier dysfunction and histological destruction in NHE8-/- mice. In Caco-2 cells and enteroids, siVDR downregulated NHE8 expression, further promoted TNF-α-induced NHE8 downregulation and stimulated TNF-α-induced NF-κb p65 phosphorylation. Conversely, QNZ blocked TNF-α-induced NHE8 downregulation in the absence or presence of siVDR. Conclusions: Our study indicates depressed NHE8 expression is responsible for VitD-deficient-induced colitis aggravation. These findings provide novel insights into the molecular mechanisms of VitD/VDR in intestine protection in UC.

Recent Advances and Perspectives of Metal Halide Perovskite Heteronanocrystals.

Heteronanocrystals that combine multiple semiconductors into a nanoscale heterostructure possess excellent optical performance and flexibility in property engineering compared with their single-component counterparts. The successes in fabricating lead halide perovskite-based heteronanocrystals (PHNCs) have drastically improved the stability and tunability of the optical and electrical properties. However, the epitaxial growth of semiconductor materials on perovskite nanocrystals remains a fundamental challenge because of the mismatch in their surface structure and crystal growth kinetics. Here, we review recent progress in the development of PHNCs with emphasis on their synthesis methods and surface chemistry that led to new insights and reaction protocols for the design and fabrication of PHNCs. In addition, the optical features of different types of PHNCs and nanocomposites and their application perspectives are summarized. Finally, we conclude with a discussion of the remaining issues, challenges, and opportunities in epitaxial growth of Janus and core-shell structure PHNCs.

Norfloxacin versus alternative antibiotics for prophylaxis of spontaneous bacteria peritonitis in cirrhosis: a systematic review and meta-analysis.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a life-threatening complication in patients with advanced cirrhosis. Prophylactic Norfloxacin used to be considered effective in SBP prevention, but in recent years its efficacy has been partially compromised by increasing quinolone-resistant bacteria. However, whether the effects of alternative prophylactic regimens are superior to norfloxacin remains controversial. The goal of this study is to compare the effects of norfloxacin with other antibiotics in SBP prophylaxis for cirrhotic patients. METHODS: We systematically searched Pubmed, Embase, and Cochrane Library Databases. Two reviewers independently identified relevant random control trials (RCTs) comparing the role of norfloxacin and other antibiotics in SBP prevention. RESULTS: Eight studies comprising 1043 cirrhotic patients were included in this study. Norfloxacin and alternative antibiotics displayed comparable effects in SBP prophylaxis, survival benefit, overall infection prevention, and safety. Subgroup analyses revealed that rifaximin prophylaxis could reduce the recurrence of SBP with fewer adverse events but failed to improve overall survival compared with norfloxacin. CONCLUSIONS: Other antibiotics are a reasonable alternative to norfloxacin in the prophylaxis of SBP. Rifaximin prophylaxis could be an alternative choose of antibiotic for SBP prevention because of its better protective effect and safety.

Uncovering key molecules and immune landscape in cholestatic liver injury: implications for pathogenesis and drug therapy.

Background: Cholestasis is a common pathological process in a variety of liver diseases that may lead to liver fibrosis, cirrhosis, and even liver failure. Cholestasis relief has been regarded as a principal target in the management of multiple chronic cholestasis liver diseases like primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) at present. However, complicated pathogenesis and limited acknowledgments fettered therapeutic development. Therefore, this study aimed to systematically analyze miRNA-mRNA regulatory networks in cholestatic liver injury in order to provide new treatment strategies. Methods: Gene Expression Omnibus (GEO) database (GSE159676) was used to screen differentially expressed hepatic miRNAs and mRNAs in the PSC vs. control comparison and the PBC vs. control comparison, respectively. MiRWalk 2.0 tool was used to predict miRNA-mRNA pairs. Subsequently, functional analysis and immune cell infiltration analysis were performed to explore the pivotal functions of the target genes. RT-PCR was used to verify the result. Results: In total, a miRNA-mRNA network including 6 miRNAs (miR-122, miR-30e, let-7c, miR-107, miR-503, and miR-192) and 8 hub genes (PTPRC, TYROBP, LCP2, RAC2, SYK, TLR2, CD53, and LAPTM5) was constructed in cholestasis. Functional analysis revealed that these genes were mainly involved in the regulation of the immune system. Further analysis revealed that resting memory CD4 T cells and monocytes could potentially participate in cholestatic liver injury. The expressions of DEMis and eight hub genes were verified in ANIT-induced and BDL-induced cholestatic mouse models. Furthermore, SYK was found to have an impact on the response to UDCA, and its mechanism was possibly associated with complement activation and monocyte reduction. Conclusion: In the present study, a miRNA-mRNA regulatory network was constructed in cholestatic liver injury, which mostly mediated immune-related pathways. Moreover, the targeted gene SYK and monocytes were found to be related to UDCA response in PBC.

Controlled growth of lead-free cesium zirconium halide double perovskite nanocrystals through a microfluidic reactor.

Vacancy-ordered Cs2ZrX6 (X = Cl, Br) double perovskite nanocrystals (NCs) have recently attracted increasing attention in optoelectronic applications due to their promising photoluminescence property, high photostability, and low toxicity. However, their ultra-fast reaction limits the growth control and kinetics study of these Cs2ZrX6 NCs. Here we report the synthesis of Cs2ZrX6 NCs through a microfluidic reactor and achievement of tunable emission wavelengths by controlling the NC size and hybrid halogen ions. Reaction kinetics study reveals that the amine ligand and reaction temperature play dominate roles in the growth and optical performance of the Cs2ZrX6 NCs. The effects of flow rate, precursors, and ligand ratio on the morphology and optical property of the NCs were also investigated. This study provides an insight into the growth kinetics of the Cs2ZrX6 perovskite NCs and their continuous production through a microfluidic reactor that could facilitate the development and optical application of lead-free vacancy-ordered double perovskite NCs.

Preoperative ultrasound identification and localization of the inferior parathyroid glands in thyroid surgery.

Introduction: The parathyroid glands are important endocrine glands for maintaining calcium and phosphorus metabolism, and they are vulnerable to accidental injuries during thyroid cancer surgery. The aim of this retrospective study was to investigate the application of high-frequency ultrasound imaging for preoperative anatomical localization of the parathyroid glands in patients with thyroid cancer and to analyze the protective effect of this technique on the parathyroid glands and its effect on reducing postoperative complications. Materials and methods: A total of 165 patients who were operated for thyroid cancer in our hospital were included. The patients were assigned into two groups according to the time period of surgery: Control group, May 2018 to February 2021 (before the application of ultrasound localization of parathyroid in our hospital); PUS group, March 2021 to May 2022. In PUS group, preoperative ultrasound was used to determine the size and location of bilateral inferior parathyroid glands to help surgeons identify and protect the parathyroid glands during operation. We compared the preoperative ultrasound results with the intraoperative observations. Preoperative and first day postoperative serum calcium and PTH were measured in both groups. Results: Our preoperative parathyroid ultrasound identification technique has more than 90% accuracy (true positive rate) to confirm the location of parathyroid gland compared to intraoperative observations. Postoperative biochemical results showed a better Ca2+ [2.12(0.17) vs. 2.05(0.31), P=0.03] and PTH [27.48(14.88) vs. 23.27(16.58), P=0.005] levels at first day post-operation in PUS group compared to control group. We also found a reduced risk of at least one type of hypoparathyroidism after surgery in control group:26 cases (31.0%) vs. 41 cases (50.6%), p=0.016. Conclusion: Ultrasound localization of the parathyroid glands can help in the localization, identification and in situ preservation of the parathyroid glands during thyroidectomy. It can effectively reduce the risk of hypoparathyroidism after thyroid surgery.

Downregulation of SLC9A8 Promotes Epithelial-Mesenchymal Transition and Metastasis in Colorectal Cancer Cells via the IL6-JAK1/STAT3 Signaling Pathway.

BACKGROUND: SLC9A8 has been shown to be involved in mucus layer formation, intestinal mucosal integrity, and hyperproliferation of colitis-associated tumor development. However, its effects on the epithelial-mesenchymal transition (EMT) and the metastasis of colorectal cancer (CRC) remain unknown. AIMS: To explore whether SLC9A8 participates in EMT and the metastasis of CRC. METHODS: Western blotting and immunohistochemistry were performed to evaluate the expression of SLC9A8 in CRC patients. At the cellular level, the effect of SLC9A8 on proliferation, migration, and invasion was measured using cell viability analysis, flow cytometry analysis, and Transwell assays. Mouse tumor xenograft and metastasis models were established to analyze whether knockdown of SLC9A8 increased tumor volume, tumor weight, and metastasis. Moreover, whether downregulated expression of SLC9A8 promotes EMT via activation of the IL6-JAK1-STAT3 signaling pathway was investigated. RESULTS: SLC9A8 protein was downregulated in CRC tissues, and this downregulation was significantly associated with tumor size, lymph node status, pTNM stage, and poor prognosis. SLC9A8 overexpression markedly suppressed cell proliferation, migration, and invasion. Downregulation of SLC9A8 promoted CRC cell proliferation, migration, and invasion. Moreover, knockdown of SLC9A8 also increased tumor volume, tumor weight, and metastasis in vivo. Meanwhile, downregulation of SLC9A8 significantly promoted the in vitro migration of CRC cells via EMT by activating the IL6-JAK1/STAT3 signaling pathway. CONCLUSIONS: Downregulation of SLC9A8 plays an important role in EMT and metastasis of CRC progression and may become a new potential therapeutic target for the treatment of CRC.

Vitamin D receptor involves in the protection of intestinal epithelial barrier function via up-regulating SLC26A3.

BACKGROUND: Vitamin D receptor (VDR) and SLC26A3 (DRA) have been identified as pivotal protective factors in maintaining gut homeostasis in IBD patients. However, the specific mechanism underlying the increased intestinal susceptibility to inflammation induced by the loss of VDR and whether DRA participates in the role of VDR regulating intestinal epithelial barrier function are undefined. AIM: The current study is undertaken to elucidate the regulatory effects of VDR on DRA and VDR prevents intestinal epithelial barrier dysfunction via up-regulating the expression of DRA. METHODS: WT and VDR-/- mice are used as models for intestinal epithelial response. Paracellular permeability is measured by TEER and FD-4 assays. Immunohistochemistry, immunofluorescence, qPCR and immunoblotting are performed to determine the effects of VDR and DRA on gut epithelial barrier function. RESULTS: VDR-/- mice exhibits significant hyperpermeability of intestine with greatly decreased levels of ZO-1 and Claudin1 proteins. DRA is located on the intestinal epithelial apical membrane and is tightly modulated by VDR in vivo and in vitro via activating ERK1/2 MAPK signaling pathway. Notably, the current study for the first time demonstrates that VDR maintains intestinal epithelial barrier integrity via up-regulating DRA expression and the lack of DRA induced by VDR knockdown leads to a more susceptive condition for intestine to DSS-induced colitis. CONCLUSION: Our study provides evidence and deep comprehension regarding the role of VDR in modulating DRA expression in gut homeostasis and makes novel contributions to better generally understanding the links between VDR, DRA and intestinal epithelial barrier function.

Effects and mechanisms of GSG2 in esophageal cancer progression.

BACKGROUND: Esophageal cancer was recognized as one of the malignant tumors with poor prognosis. Germ cell associated 2 (GSG2) has been reported to be of great significance in cell growth and tumor formation. This study aimed to investigate the biological function and molecular mechanism of GSG2 in esophageal cancer. METHODS: First, relationship between GSG2 expression and tumor characteristics in esophageal cancer patients was analyzed through immunohistochemical (IHC) staining. MTT assay, flow cytometry, cloning formation assay, wound-healing assay and Transwell assay were used to determine proliferation, apoptosis and migration of esophageal cancer cell with GSG2 knockdown in vitro. Expression of apoptosis related proteins and downstream pathway proteins after GSG2 knockdown were detected through Human Apoptosis Antibody Array and western blot analysis. The GSG2 knockdown function in vivo was explored through a xenograft tumor model. RESULTS: GSG2 was highly expressed in tumor tissues, which has clinical significance in predicting the malignant degree of patients with esophageal cancer. In addition, GSG2 knockdown significantly inhibited a variety of malignant biological behaviors of esophageal cancer cells, such as inhibiting proliferation, reducing colony formation, promoting apoptosis, hindering migration. The decrease of GSG2 expression in esophageal cancer cells can inhibit the xenograft tumor growth. CONCLUSIONS: In conclusion, GSG2 was involved in esophageal cancer progression and development, which may provide an effective molecular target for the treatment of esophageal cancer in the future.

Preventive Effects of Long-Term Intake of Plant Oils With Different Linoleic Acid/Alpha-Linolenic Acid Ratios on Acute Colitis Mouse Model.

Objective: To investigate the preventive effects of plant oils with different linoleic acid/alpha-linolenic acid (LA/ALA) ratios against colitis symptoms, and dysbiosis of gut microbiota in acute colitis mouse model. Methods: Sixty male C57BL/6 mice were assigned into six groups (n = 10): three groups were fed low-fat diets with low, medium, and high LA/ALA ratios; and three groups were fed with high-fat diets with low, medium, and high LA/ALA ratios. After 3 months of diet, the mice were exposed to dextran sodium sulfate solution to induce acute colitis. The severity of colitis was estimated by disease activity index (DAI) and histopathological examination. 16S rRNA gene sequencing was used for the analysis of gut microbiota. Results: Plant oils with a lower LA/ALA ratio showed higher alleviating effects on the symptoms of colitis, which were accompanied by the better prebiotic characteristics manifested as effectively inhibiting the abnormal expansion of phylum Proteobacteria and genus Escherichia-Shigella in the gut microbiota of colitis mouse models. Conclusion: A potential IBD prevention strategy of reducing the LA/ALA ratio in the daily consumed plant oils was proposed in this study. Furthermore, based on the optimized LA/ALA ratio, this preventive effect might not be weakened by the high intake of plant oils.

Metabolic profile differences in ACTH-dependent and ACTH-independent Cushing syndrome.

Background: The most common etiologies of Cushing's syndrome (CS) are adrenocorticotropic hormone (ACTH)-producing pituitary adenoma (pitCS) and primary adrenal gland disease (adrCS), both of which burden patients with metabolic disturbance. The aim of this study was to compare the metabolic features of pitCS and adrCS patients. Methods: A retrospective review including 114 patients (64 adrCS and 50 pitCS) diagnosed with CS in 2009-2019 was performed. Metabolic factors were then compared between pitCS and adrCS groups. Results: Regarding sex, females suffered both adrCs (92.2%) and pitCS (88.0%) more frequently than males. Regarding age, patients with pitCS were diagnosed at a younger age (35.40 ± 11.94 vs. 39.65 ± 11.37 years, p = 0.056) than those with adrCS, although the difference was not statistically significant. Moreover, pitCS patients had much higher ACTH levels and more serious occurrences of hypercortisolemia at all time points (8 AM, 4 PM, 12 AM) than that in adrCS patients. Conversely, indexes, including body weight, BMI, blood pressure, serum total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides, fasting plasma glucose, and uric acid, showed no differences between adrCS and pitCS patients. Furthermore, diabetes prevalence was higher in pitCS patients than in adrCS patients; however, there were no significant differences in hypertension or dyslipidemia prevalence between the two. Conclusions: Although adrCS and pitCS had different pathogenetic mechanisms, different severities of hypercortisolemia, and different diabetes prevalences, both etiologies had similar metabolic characteristics.

Roles of gastrointestinal polypeptides in intestinal barrier regulation.

The intestinal barrier is a dynamic entity that is organized as a multilayer system and includes various intracellular and extracellular elements. The gut barrier functions in a coordinated manner to impede the passage of antigens, toxins, and microbiome components and simultaneously preserves the balanced development of the epithelial barrier and the immune system and the acquisition of tolerance to dietary antigens and intestinal pathogens.Numerous scientific studies have shown a significant association between gut barrier damage and gastrointestinal and extraintestinal diseases such as inflammatory bowel disease, celiac disease and hepatic fibrosis. Various internal and external factors regulate the intestinal barrier. Gastrointestinal peptides originate from enteroendocrine cells in the luminal digestive tract and are critical gut barrier regulators. Recent studies have demonstrated that gastrointestinal peptides have a therapeutic effect on digestive tract diseases, enhancing epithelial barrier activity and restoring the gut barrier. This review demonstrates the roles and mechanisms of gastrointestinal polypeptides, especially somatostatin (SST) and vasoactive intestinal peptide (VIP), in intestinal barrier regulation.

Screening and identifying a novel M-MDSCs-related gene signature for predicting prognostic risk and immunotherapeutic responses in patients with lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) shows intratumoral heterogeneity, a highly complex phenomenon that known to be a challenge during cancer therapy. Considering the key role of monocytic myeloid-derived suppressor cells (M-MDSCs) in the tumor microenvironment (TME), we aimed to build a prognostic risk model using M-MDSCs-related genes. Methods: M-MDSCs-related genes were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Utilized univariate survival analysis and random forest algorithm to screen candidate genes. A least absolute shrinkage and selection operator (LASSO) Cox regression analysis was selected to build the risk model. Patients were scored and classified into high- and low-risk groups based on the median risk scores. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis along with R packages "estimate" and "ssGSEA" were performed to reveal the mechanism of risk difference. Prognostic biomarkers and tumor mutation burden (TMB) were combined to predict the prognosis. Nomogram was carried out to predict the survival probability of patients in 1, 3, and 5 years. Results: 8 genes (VPREB3, TPBG, LRFN4, CD83, GIMAP6, PRMT8, WASF1, and F12) were identified as prognostic biomarkers. The GEO validation dataset demonstrated the risk model had good generalization effect. Significantly enrichment level of cell cycle-related pathway and lower content of CD8+ T cells infiltration in the high-risk group when compared to low-risk group. Morever, the patients were from the intersection of high-TMB and low-risk groups showed the best prognosis. The nomogram demonstrated good consistency with practical outcomes in predicting the survival rate over 1, 3, and 5 years. Conclusion: The risk model demonstrate good prognostic predictive ability. The patients from the intersection of low-risk and high-TMB groups are not only more sensitive response to but also more likely to benefit from immune-checkpoint-inhibitors (ICIs) treatment.