HMGA1 is a Prognostic Biomarker and Correlated with Glycolysis in Lung Adenocarcinoma.

Purpose: Lung cancer is one of the leading causes with high morbidity and mortality. High mobility group A1 (HMGA1) protein participates in the process of tumorigenesis. This study seeks to explore the specific role of HMGA1 in prognostic value based on The Cancer Genome Atlas (TCGA) database of Lung adenocarcinoma (LUAD) and glycolysis progression in LUAD cells. Patients and Methods: In this research, we compared HMGA1 mRNA expression between tumor tissues and normal samples and evaluated the correlations with clinical characteristics in LUAD patients based on the data of TCGA database. The survival outcome with overall survival (OS), disease-specific survival (DSS) and clinicopathologic characteristics associated were performed using the Kaplan-Meier method and Cox regression. In addition, gene-set enrichment analysis (GSEA) was carried out to explore the biological pathways that related to HMGA1. Cell experiments including cell proliferation assay and glycolysis proteins were performed with A549 and H1299 cells. Results: Our results revealed that HMGA1 mRNA expression was higher in LUAD tissues than in normal tissues. Increased HMGA1 expression in LUAD was associated with Gender (p<0.01), Pathologic stage I&II vs stage III&IV (p<0.001), T1&T2 vs T3&T4 stage (p<0.05), N0 vs N2 stage (p<0.01). Furthermore, multivariate analysis revealed that HMGA1 was an independent risk factor of OS and DSS for LUAD patients (p<0.05). HMGA1 were positively correlated with glycolysis gluconeogenesis pathway and glycolysis markers (HK2, GLUT1, PKM2, LDHA) based on GSEA and Gene Expression Profiling Interactive Analysis (GEPIA) database. At the cellular level, the results of qRT-PCR and western blot assays showed that si-HMGA1 markedly decreased the expression of glycolysis markers. HMGA1 promoted cell glycolysis progression via PI3K/AKT pathway transfected with HMGA1-plasmid and the treatment with 20 µM LY294002. Relevant animal experiments were also synchronously validated and si-HMGA1 groups down-regulated xenograft growth including the weights and size in tumor xenografts. Conclusions: In conclusion, our results suggested that HMGA1 was significantly correlated with poor survival for LUAD tissues and involved in the process of glycolysis in LUAD cells.

Effect of 0.01% atropine combined with orthokeratology lens on axial elongation: a 2-year randomized, double-masked, placebo-controlled, cross-over trial.

Purpose: To evaluate the effect of 0.01% atropine combined with orthokeratology (OK) lens on axial elongation in schoolchildren with myopia. Methods: Sixty children aged 8-12 years with spherical equivalent refraction (SER) from -1.00D to -4.00D in both eyes were enrolled in this randomized, double-masked, placebo-controlled, cross-over trial. Children who had been wearing OK lenses for 2 months were randomly assigned into combination group (combination of OK lens and 0.01% atropine) for 1 year followed by control group (combination of OK lens and placebo) for another 1 year or vice versa. This trial was registered in the Chinese Clinical Trial Registry (Number: ChiCTR2000033904, 16/06/2020). The primary outcome was changes in axial length (AL). Data of right eyes were analyzed. Results: There were statistically significant differences in the changes in AL between combination and control groups after generalized estimating equation model adjusting for age and baseline SER (p = 0.001). The mean axial elongation difference between combination and control groups was 0.10 mm in the first year (0.10 ± 0.13 mm vs. 0.20 ±0.15 mm; p = 0.01), and 0.09 mm in the second year (0.22 ± 0.10 mm vs. 0.13 ± 0.14 mm; p = 0.01), respectively. The mean axial elongation difference of two groups in the first year was similar to that in the second year during the cross-over treatment. Conclusion: In central Mainland China in myopic children, the treatment of combination therapy is more effective than single OK lens in controlling axial elongation.

Effects of Oxygen Therapy on Patients with a Chronic Wound: A Systematic Review and Meta-analysis.

OBJECTIVE: To synthesize the effects of oxygen-based therapy on patients with a chronic wound. DATA SOURCES: The authors searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials for relevant randomized controlled trials from database inception. Investigators measured risk of bias using the Cochrane Collaboration's Risk of Bias tool. STUDY SELECTION: The included randomized controlled trials focused on the effects (short- or long-term wound healing, amputation rate, percentage of reduction in ulcer size, and poststudy transcutaneous oxygen measurement [TcPO2]) of oxygen-based therapy (including hyperbaric oxygen therapy, topical oxygen therapy, and continuous diffusion of oxygen) on patients with a chronic wound. DATA EXTRACTION: Researchers extracted information regarding participant characteristics and primary and secondary outcomes from the included studies. DATA SYNTHESIS: Pooled effects of 31 included studies showed that patients treated with oxygen had better short-term wound healing (risk ratio [RR], 1.544; 95% CI, 1.199 to 1.987), a higher percentage reduction in the ulcer area (standardized mean difference [SMD], 0.999; 95% CI, 0.439 to 1. 599), lower amputation rates (RR, 0.529; 95% CI, 0.325 to 0.862), shorter wound healing time (SMD, -0.705; 95% CI, -0.908 to -0.501), and higher poststudy TcPO2 (SMD, 2.128; 95% CI, 0.978 to 3.278) than those in the control group. For long-term wound healing, there was no statistically significant difference (RR, 1.227; 95% CI, 0.976 to 1.542). CONCLUSIONS: Oxygen-based therapy improves short-term parameters of wound healing in patients with chronic wounds.

Vaginal microbiota molecular profiling and diagnostic performance of artificial intelligence-assisted multiplex PCR testing in women with bacterial vaginosis: a single-center experience.

Background: Bacterial vaginosis (BV) is a most common microbiological syndrome. The use of molecular methods, such as multiplex real-time PCR (mPCR) and next-generation sequencing, has revolutionized our understanding of microbial communities. Here, we aimed to use a novel multiplex PCR test to evaluate the microbial composition and dominant lactobacilli in non-pregnant women with BV, and combined with machine learning algorithms to determine its diagnostic significance. Methods: Residual material of 288 samples of vaginal secretions derived from the vagina from healthy women and BV patients that were sent for routine diagnostics was collected and subjected to the mPCR test. Subsequently, Decision tree (DT), random forest (RF), and support vector machine (SVM) hybrid diagnostic models were constructed and validated in a cohort of 99 women that included 74 BV patients and 25 healthy controls, and a separate cohort of 189 women comprising 75 BV patients, 30 intermediate vaginal microbiota subjects and 84 healthy controls, respectively. Results: The rate or abundance of Lactobacillus crispatus and Lactobacillus jensenii were significantly reduced in BV-affected patients when compared with healthy women, while Lactobacillus iners, Gardnerella vaginalis, Atopobium vaginae, BVAB2, Megasphaera type 2, Prevotella bivia, and Mycoplasma hominis were significantly increased. Then the hybrid diagnostic models were constructed and validated by an independent cohort. The model constructed with support vector machine algorithm achieved excellent prediction performance (Area under curve: 0.969, sensitivity: 90.4%, specificity: 96.1%). Moreover, for subjects with a Nugent score of 4 to 6, the SVM-BV model might be more robust and sensitive than the Nugent scoring method. Conclusion: The application of this mPCR test can be effectively used in key vaginal microbiota evaluation in women with BV, intermediate vaginal microbiota, and healthy women. In addition, this test may be used as an alternative to the clinical examination and Nugent scoring method in diagnosing BV.

Longitudinal association between soft drink consumption and handgrip strength in adults: a prospective analysis from the Tianjin Chronic Low-Grade Systemic Inflammation and Health (TCLSIH) cohort study.

Soft drink consumption has become a highly controversial public health issue. Given the pattern of consumption in China, sugar-sweetened beverage is the main type of soft drink consumed. Due to containing high levels of fructose, a soft drink may have a deleterious effect on handgrip strength (HGS) due to oxidative stress, inflammation and insulin resistance. However, few studies show an association between soft drink consumption and HGS in adults. We aimed to investigate the association between soft drink consumption and longitudinal changes in HGS among a Chinese adult population. A longitudinal population-based cohort study (5-year follow-up, median: 3·66 years) was conducted in Tianjin, China. A total of 11 125 participants (56·7 % men) were enrolled. HGS was measured using a handheld digital dynamometer. Soft drink consumption (mainly sugar-containing carbonated beverages) was measured at baseline using a validated FFQ. ANCOVA was used to evaluate the association between soft drink consumption and annual change in HGS or weight-adjusted HGS. After adjusting for multiple confounding factors, the least square means (95 % CI) of annual change in HGS across soft drink consumption frequencies were -0·70 (-2·49, 1·09) for rarely drinks, -0·82 (-2·62, 0·97) for < 1 cup/week and -0·86 (-2·66, 0·93) for ≥ 1 cup/week (Pfor trend < 0·05). Likewise, a similar association was observed between soft drink consumption and annual change in weight-adjusted HGS. The results indicate that higher soft drink consumption was associated with faster HGS decline in Chinese adults.

Imaging Intratumoral Heterogeneity of Diffuse Pancreatic Neuroendocrine Tumor With Multitracer PET/CT.

ABSTRACT: Diffuse involvement of pancreatic neuroendocrine tumor (PNET) is a rare presentation. Here, we report a case of suspected autoimmune pancreatitis with 18 F-FDG and 18 F-FAPI-42 PET/CT showing increased tracer uptake in the entire pancreas, which was eventually confirmed by biopsy pathologic analysis as diffuse PNET. 18 F-AlF-NOTA-octreotide PET/CT imaging showed heterogeneous tracer uptake in the entire pancreas.

Chimeric mutations in grapevine ENHANCED DISEASE RESISTANCE1 improve resistance to powdery mildew without growth penalty.

Grapevine (Vitis vinifera L.) incurs severequality degradation and yield loss from powdery mildew, a major fungal disease caused by Erysiphe necator. ENHANCED DISEASE RESISTANCE1 (EDR1), a Raf-like mitogen-activated protein kinase kinase kinase (MAPKKK), negatively regulates defense responses against powdery mildew in Arabidopsis (Arabidopsis thaliana). However, little is known about the role of the putatively orthologous EDR1 gene in grapevine. In this study, we obtained grapevine VviEDR1-edited lines using CRISPR/Cas9. Plantlets containing homozygous and bi-allelic indels in VviEDR1 developed leaf lesions shortly after transplanting into the soil and died at the seedling stage. Transgenic plants expressing wild-type VviEDR1 and mutant Vviedr1 alleles as chimera (designated as VviEDR1-chi) developed normally and displayed enhanced resistance to powdery mildew. Interestingly, VviEDR1-chi plants maintained a spatiotemporally distinctive pattern of VviEDR1 mutagenesis: while almost no mutations were detected from terminal buds, ensuring normal function of the apical meristem, mutations occurred in young leaves and increased as leaves matured, resulting in resistance to powdery mildew. Further analysis showed that the resistance observed in VviEDR1-chi plants was associated with callose deposition, increased production of salicylic acid (SA) and ethylene (ET), H2O2 production and accumulation, and host cell death. Surprisingly, no growth penalty was observed with VviEDR1-chi plants. Hence, this study demonstrated a role of VviEDR1 in the negative regulation of resistance to powdery mildew in grapevine and provided an avenue for engineering powdery mildew resistance in grapevine.

Vascular Aging and Atherosclerosis: A Perspective on Aging.

Vascular aging (VA) is recognized as a pivotal factor in the development and progression of atherosclerosis (AS). Although various epidemiological and clinical research has demonstrated an intimate connection between aging and AS, the candidate mechanisms still require thorough examination. This review adopts an aging-centric perspective to deepen the comprehension of the intricate relationship between biological aging, vascular cell senescence, and AS. Various aging-related physiological factors influence the physical system's reactions, including oxygen radicals, inflammation, lipids, angiotensin II, mechanical forces, glucose levels, and insulin resistance. These factors cause endothelial dysfunction, barrier damage, sclerosis, and inflammation for VA and promote AS via distinct or shared pathways. Furthermore, the increase of senescent cells inside the vascular tissues, caused by genetic damage, dysregulation, secretome changes, and epigenetic modifications, might be the primary cause of VA.

Intratumor tertiary lymphatic structure evaluation predicts the prognosis and immunotherapy response of patients with colorectal cancer.

Background: Immune checkpoint therapy, involving the programmed cell death 1 (PD-1) monoclonal antibody, has revolutionized the treatment of cancer. Tertiary lymphatic structure (TLS) serves as an immune indicator to predict the efficacy of PD-1 antibody therapy. However, there is no clear result whether the distribution, quantity, and maturity of TLS can be effective indicators for predicting the clinical efficacy of anti-PD1 immunotherapy in patients with colorectal cancer (CRC). Methods: Fifty-seven patients who underwent surgical resection and thirty-nine patients who received anti-PD-1 immunotherapy were enrolled in this retrospective study. Immunohistochemical staining and multiple fluorescence immunohistochemistry were used to evaluate the mismatch repair (MMR) subtypes and TLS distribution, quantity, and maturity, respectively. Results: A comprehensive patient score system was built based on TLS quantity and maturity. We found that the proportion of patients with score >1 was much higher in the deficient mismatch repair(dMMR) group than in the proficient mismatch repair(pMMR) group, and this difference was mainly due to intratumoral TLS. Patient score, based on the TLS evaluation of whole tumor, peritumor, or intratumor, was used to evaluate the efficacy of anti-PD1 immunotherapy. Based only on the intratumor TLS evaluation, the proportion of patients with a score >1 was higher in the response (PR + CR) group than in the non-response (PD) group. Multivariate analysis revealed that patient scores were positively correlated with the clinical efficacy of immunotherapy. Further analysis of immune-related progression-free survival was performed in patients with CRC who received anti-PD-1 immunotherapy. Patients with score >1 based on the intratumor TLS evaluation had significantly better survival. Conclusions: These results suggest that the patient score based on intratumor TLS evaluation may be a good immune predictive indicator for PD-1 antibody therapy in patients with CRC.

Enhanced polygenic risk score incorporating gene-environment interaction suggests the association of major depressive disorder with cardiac and lung function.

BACKGROUND: Depression has been linked to an increased risk of cardiovascular and respiratory diseases; however, its impact on cardiac and lung function remains unclear, especially when accounting for potential gene-environment interactions. METHODS: We developed a novel polygenic and gene-environment interaction risk score (PGIRS) integrating the major genetic effect and gene-environment interaction effect of depression-associated loci. The single nucleotide polymorphisms (SNPs) demonstrating major genetic effect or environmental interaction effect were obtained from genome-wide SNP association and SNP-environment interaction analyses of depression. We then calculated the depression PGIRS for non-depressed individuals, using smoking and alcohol consumption as environmental factors. Using linear regression analysis, we assessed the associations of PGIRS and conventional polygenic risk score (PRS) with lung function (N = 42 886) and cardiac function (N = 1791) in the subjects with or without exposing to smoking and alcohol drinking. RESULTS: We detected significant associations of depression PGIRS with cardiac and lung function, contrary to conventional depression PRS. Among smokers, forced vital capacity exhibited a negative association with PGIRS (ß = -0.037, FDR = 1.00 × 10-8), contrasting with no significant association with PRS (ß = -0.002, FDR = 0.943). In drinkers, we observed a positive association between cardiac index with PGIRS (ß = 0.088, FDR = 0.010), whereas no such association was found with PRS (ß = 0.040, FDR = 0.265). Notably, in individuals who both smoked and drank, forced expiratory volume in 1-second demonstrated a negative association with PGIRS (ß = -0.042, FDR = 6.30 × 10-9), but not with PRS (ß = -0.003, FDR = 0.857). CONCLUSIONS: Our findings underscore the profound impact of depression on cardiac and lung function, highlighting the enhanced efficacy of considering gene-environment interactions in PRS-based studies.

Effect of tea polyphenols as an antioxidant on pork for frying at different temperatures and times.

The aim of this study was to investigate the effect of frying on the antioxidant properties of tea phenols added to pork. The antioxidant capacity of tea polyphenols with different concentrations was tested using different assays including total antioxidant capacity (T-AOC) (FRAP method), thiobarbituric acid reactive substance, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging, and 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH) radical scavenging. Our results indicated that tea polyphenols have a great antioxidant capacity and that a high frying temperature causes fat oxidation. Our study confirmed that DPPH assay is more suited to lipophilic compounds or compounds with high lipid content. In a frying temperature of 180°C, the DPPH-free radical scavenging ability of pork was not decreased. Further experiments remain necessary to explore specific temperatures with the same results. This study provides new process parameters and new references for processing techniques of healthy and high-quality pork products.

Mendelian randomization study of the relationship between blood and urine biomarkers and schizophrenia in the UK Biobank cohort.

BACKGROUND: The identification of suitable biomarkers is of crucial clinical importance for the early diagnosis of treatment-resistant schizophrenia (TRS). This study aims to comprehensively analyze the association between TRS and blood and urine biomarkers. METHODS: Candidate TRS-related single nucleotide polymorphisms (SNPs) were obtained from a recent genome-wide association study. The UK Biobank cohort, comprising 376,807 subjects with blood and urine biomarker testing data, was used to calculate the polygenic risk score (PRS) for TRS. Pearson correlation analyses were performed to evaluate the correlation between TRS PRS and each of the biomarkers, using calculated TRS PRS as the instrumental variables. Bidirectional two-sample Mendelian randomization (MR) was used to assess potential causal associations between candidate biomarkers with TRS. RESULTS: Here we identify a significant association between TRS PRS and phosphate (r = 0.007, P = 1.96 × 10-4). Sex subgroup analyses identify seven and three candidate biomarkers associated with TRS PRS in male and female participants, respectively. For example, total protein and phosphate for males, creatinine and phosphate for females. Bidirectional two-sample MR analyses indicate that TRS is negatively associated with cholesterol (estimate = -0.363, P = 0.008). Conversely, TRS is positively associated with total protein (estimate = 0.137, P = 0.027), mean corpuscular volume (estimate = 0.032, P = 2.25 × 10-5), and mean corpuscular hemoglobin (estimate = 0.018, P = 0.007). CONCLUSIONS: Our findings provide insights into the roles of blood and urine biomarkers in the early detection and treatment of TRS.

People with schizophrenia experience periods of time during which they misperceive reality. Some people with schizophrenia do not respond well to the usual drugs that are used to relieve their symptoms. This type of schizophrenia is known as treatment-resistant schizophrenia (TRS). We looked at differences in the genes (inherited characteristics), blood and urine of a group of people in the UK with schizophrenia to see if people with TRS have particular characteristics that would enable them to be distinguished from patients with schizophrenia who tend to respond to usual treatment. We found several differences in the blood that could be used to predict which people might get TRS, including some that were specific to men or women. These discoveries are important because they can help doctors identify people who are more likely to develop TRS earlier, enabling them to avoid using treatments that might not work well for them.

Effect of extrusion on the formation, structure and properties of yam starch-gallic acid complexes.

This paper investigated the effects of twin-screw extrusion treatment on the formation, structure and properties of yam starch-gallic acid complexes. Yam starch and gallic acid were extruded. The microstructure, gelatinization characteristics, and rheological properties of the samples were determined. The microstructure of extruded yam starch-gallic acid complexes presented a rough granular morphology, low swelling, and high solubility. The X-ray diffraction analysis showed that the extruded yam starch-gallic acid complexes exhibited A + V-type crystalline structure. Fourier transform infrared spectroscopy results showed that the extrusion treatment could destroy the internal orderly structure of yam starch, and the addition of gallic acid could further reduce its molecular orderliness. Differential scanning calorimetry analysis showed a decrease in the enthalpy of gelatinization of the sample. Dynamic rheological analysis showed that the storage modulus and loss modulus of the extruded yam starch-gallic acid complexes were significantly reduced, exhibiting a weak gel system. The results of viscosity showed that extrusion synergistic gallic acid reduced the peak viscosity and setback value of starch. In addition, extrusion treatment had an inhibitory effect on the digestibility of yam starch, and enhanced the interaction of gallic acid with yam starch or hydrolytic enzymes. Therefore, extrusion synergistic gallic acid has improved the structure and properties of yam starch-related products, which can provide new directions and new ideas for the development of yam starch.

Additional Findings of 18 F-AIF-FAPI-42 PET/CT in a Patient With Mycosis Fungoides-Type Cutaneous T-Cell Lymphoma : Comparisons With 18 F-FDG PET/CT.

ABSTRACT: A 44-year-old woman presented with extensive skin patches and pruritus persisting for 3 years. Histopathological examination of the skin from the right abdomen confirmed mycosis fungoides-type cutaneous T-cell lymphoma. Staging PET with 18 F-FDG PET/CT) showed increased uptake in the skin on the right abdomen and left hip. Subsequently 18 F-FAPI-42 PET/CT revealed additional foci of abnormal uptake on the skin of the chest and back.

Identification of renal ischemia reperfusion injury-characteristic genes, pathways and immunological micro-environment features through bioinformatics approaches.

BACKGROUND: Biomarkers and pathways associated with renal ischemia reperfusion injury (IRI) had not been well unveiled. This study was intended to investigate and summarize the regulatory networks for related hub genes. Besides, the immunological micro-environment features were evaluated and the correlations between immune cells and hub genes were also explored. METHODS: GSE98622 containing mouse samples with multiple IRI stages and controls was collected from the GEO database. Differentially expressed genes (DEGs) were recognized by the R package limma, and the GO and KEGG analyses were conducted by DAVID. Gene set variation analysis (GSVA) and weighted gene coexpression network analysis (WGCNA) had been implemented to uncover changed pathways and gene modules related to IRI. Besides the known pathways such as apoptosis pathway, metabolic pathway, and cell cycle pathways, some novel pathways were also discovered to be critical in IRI. A series of novel genes associated with IRI was also dug out. An IRI mouse model was constructed to validate the results. RESULTS: The well-known IRI marker genes (Kim1 and Lcn2) and novel hub genes (Hbegf, Serpine2, Apbb1ip, Trip13, Atf3, and Ncaph) had been proved by the quantitative real-time polymerase chain reaction (qRT-PCR). Thereafter, miRNAs targeted to the dysregulated genes were predicted and the miRNA-target network was constructed. Furthermore, the immune infiltration for these samples was predicted and the results showed that macrophages infiltrated to the injured kidney to affect the tissue repair or fibrosis. Hub genes were significantly positively or negatively correlated with the macrophage abundance indicating they played a crucial role in macrophage infiltration. CONCLUSIONS: Consequently, the pathways, hub genes, miRNAs, and the immune microenvironment may explain the mechanism of IRI and might be the potential targets for IRI treatments.

Interpretation of vaginal metagenomic characteristics in different types of vaginitis.

Although vaginitis is closely related to vaginal microecology in females, the precise composition and functional potential of different types of vaginitis remain unclear. Here, metagenomic sequencing was applied to analyze the vaginal flora in patients with various forms of vaginitis, including cases with a clue cell proportion ranging from 1% to 20% (Clue1_20), bacterial vaginitis (BV), vulvovaginal candidiasis (VVC), and BV combined with VVC (VVC_BV). Our results identified Prevotella as an important biomarker between BV and Clue1_20. Moreover, a gradual decrease was observed in the relative abundance of shikimic acid metabolism associated with bacteria producing indole as well as a decline in the abundance of Gardnerella vaginalis in patients with BV, Clue1_20, and healthy women. Interestingly, the vaginal flora of patients in the VVC_BV group exhibited structural similarities to that of the VVC group, and its potentially functional characteristics resembled those of the BV and VVC groups. Finally, Lactobacillus crispatus was found in high abundance in healthy samples, greatly contributing to the stability of the vaginal environment. For the further study of L. crispatus, we isolated five strains of L. crispatus from healthy samples and evaluated their capacity to inhibit G. vaginalis biofilms and produce lactic acid in vitro to select the potential probiotic candidate for improving vaginitis in future clinical studies. Overall, we successfully identified bacterial biomarkers of different vaginitis and characterized the dynamic shifts in vaginal flora between patients with BV and healthy females. This research advances our understanding and holds great promise in enhancing clinical approaches for the treatment of vaginitis. IMPORTANCE: Vaginitis is one of the most common gynecological diseases, mostly caused by infections of pathogens such as Candida albicans and Gardnerella vaginalis. In recent years, it has been found that the stability of the vaginal flora plays an important role in vaginitis. Furthermore, the abundant Lactobacillus-producing rich lactic acid in the vagina provides a healthy acidic environment such as Lactobacillus crispatus. The metabolites of Lactobacillus can inhibit the colonization of pathogens. Here, we collected the vaginal samples of patients with bacterial vaginitis (BV), vulvovaginal candidiasis (VVC), and BV combined with VVC to discover the differences and relationships among the different kinds of vaginitis by metagenomic sequencing. Furthermore, because of the importance of L. crispatus in promoting vaginal health, we isolated multiple strains from vaginal samples of healthy females and chose the most promising strain with potential probiotic benefits to provide clinical implications for treatment strategies.

Effects of immunogenic cell death-inducing chemotherapeutics on the immune cell activation and tertiary lymphoid structure formation in melanoma.

Background: The infiltration and activation of immune cells in the tumor microenvironment (TIME) affect the prognosis of patients with cancer. Tertiary lymphoid structure (TLS) formation favors tumour- infiltrating-lymphocyte (TIL) recruitment and is regarded as an important indicator of good prognosis associated with immunotherapy in patients with tumors. Chemotherapy is currently one of the most commonly used clinical treatment methods. However, there have been no clear report to explore the effects of different types of chemotherapy on TLS formation in the TIME. This study examined the effects of immunogenic cell death (ICD)-inducing chemotherapeutics on immune cells, high-endothelial venules (HEV), and TLSs in mouse melanomas. Methods: Doxorubicin (an ICD inducer), gemcitabine (non-ICD inducer), and a combination of the two drugs was delivered intra-peritoneally to B16F1-loaded C57BL/6 mice. The infiltration of immune cells into tumor tissues was evaluated using flow cytometry. HEV and TLS formation was assessed using immunohistochemistry and multiple fluorescent immunohistochemical staining. Results: Doxorubicin alone, gemcitabine alone, and the two-drug combination all slowed tumor growth, with the combined treatment demonstrating a more pronounced effect. Compared with the control group, the doxorubicin group showed a higher infiltration of CD8+ T cells and tissue-resident memory T cells (TRM) and an increase in the secretion of interferon-γ, granzyme B, and perforin in CD8+ T subsets and activation of B cells and dendritic cells. Doxorubicin alone and in combination with gemcitabine decreased regulatory T cells in the TIME. Moreover, doxorubicin treatment promoted the formation of HEV and TLS. Doxorubicin treatment also upregulated the expression of programmed cell death protein (PD)-1 in CD8+ T cells and programmed cell death protein ligand (PD-L)1 in tumor cells. Conclusions: These results indicate that doxorubicin with an ICD reaction promotes TLS formation and increases PD-1/PD-L1 expression in tumor tissues. The results demonstrate the development of a therapeutic avenue using combined immune checkpoint therapy.

Immune checkpoint ligands expressed on mature high endothelial venules predict poor prognosis of NSCLC: have a relationship with CD8+ T lymphocytes infiltration.

Background: An insufficient number of intratumoral CD8+ T lymphocytes is a major barrier to antitumor immunity and immunotherapy. High endothelial venules (HEVs) are the major sites through which lymphocytes enter tumors; however, the molecular mechanism through which HEVs mediate CD8+ T lymphocyte infiltration remains poorly understood. Methods: Forty-two patients with stage IIIA lung adenocarcinoma, who underwent surgery, were recruited. Multiplex immunohistochemical staining was conducted on tumor tissues to detect the immune checkpoint ligands (ICLs) expressed in the HEVs, blood vessels, and lymphatics. A new ICL score model was constructed to evaluate ligand expression. The relationship between ICL score, tumor-infiltrating CD8+ T cell frequency, and survival of patients was investigated. Results: Mature HEVs, but not blood vessels or lymphatics, mediated CD8+ T cell infiltration. However, the ICLs expressed on mature HEVs could negatively regulate CD8+ T cell entry into tertiary lymphoid structures (TLSs). In addition, according to the results obtained using our ICLtotal score model, the expression of ICLs on HEVs was observed to be a predictor of both CD8+ T cell infiltration and survival, in which a high ICLtotal score > 1 represent a weak CD8+ T cell infiltration and a high ICLtotal score > 2 predicts poor survival. Conclusion: Using the ICL score model, we discovered that ICLs expressed on HEVs are indicative of CD8+ T cell subset infiltration in TLSs, as well as of patient survival with lung cancer.

Nomogram for predicting postoperative pulmonary complications in spinal tumor patients.

OBJECTIVES: Although several independent risk factors for postoperative pulmonary complications (PPCs) after spinal tumor surgery have been studied, a simple and valid predictive model for PPC occurrence after spinal tumor surgery has not been developed. PATIENTS AND METHODS: We collected data from patients who underwent elective spine surgery for a spinal tumor between 2013 and 2020 at a tertiary hospital in China. Data on patient characteristics, comorbidities, preoperative examinations, intraoperative variables, and clinical outcomes were collected. We used univariable and multivariable logistic regression models to assess predictors of PPCs and developed and validated a nomogram for PPCs. We evaluated the performance of the nomogram using the area under the receiver operating characteristic curve (ROC), calibration curves, the Brier Score, and the Hosmer-Lemeshow (H-L) goodness-of-fit test. For clinical use, decision curve analysis (DCA) was conducted to identify the model's performance as a tool for supporting decision-making. RESULTS: Among the participants, 61 (12.4%) individuals developed PPCs. Clinically significant variables associated with PPCs after spinal tumor surgery included BMI, tumor location, blood transfusion, and the amount of blood lost. The nomogram incorporating these factors showed a concordance index (C-index) of 0.755 (95% CI: 0.688-0.822). On internal validation, bootstrapping with 1000 resamples yielded a bias-corrected area under the receiver operating characteristic curve of 0.733, indicating the satisfactory performance of the nomogram in predicting PPCs. The calibration curve demonstrated accurate predictions of observed values. The decision curve analysis (DCA) indicated a positive net benefit for the nomogram across most predicted threshold probabilities. CONCLUSIONS: We have developed a new nomogram for predicting PPCs in patients who undergo spinal tumor surgery.

Creation of Interfacial S4 -Sn-N2 Electron Pathways for Efficient Light-Driven Hydrogen Evolution.

Establishing effective charge transfer channels between two semiconductors is key to improving photocatalytic activity. However, controlling hetero-structures in situ and designing binding modes pose significant challenges. Herein, hydrolytic SnCl2 ·2H2 O is selected as the metal source and loaded in situ onto a layered carbon nitriden supramolecular precursor. A composite photocatalyst, S4 -Sn-N2 , with electron pathways of SnS2 and tubular carbon nitriden (TCN) is prepared through pyrolysis and vulcanization processes. The contact interface of SnS2 -TCN is increased significantly, promoting the formation of S4 -Sn-N2 micro-structure in a Z-scheme charge transfer channel. This structure accelerates the separation and transport of photogenerated carriers, maintains the stronger redox ability, and improves the stability of SnS2 in this series of heterojunctions. Therefore, the catalyst demonstrated exceptional photocatalytic hydrogen production efficiency, achieving a reaction rate of 86.4 µmol h-1 , which is 3.15 times greater than that of bare TCN.