Alcohol inducing macrophage M2b polarization in colitis by modulating the TRPV1-MAPK/NF-κB pathways.

BACKGROUND: Macrophages exhibit different phenotypes in inflammatory bowel disease (IBD) and promote inflammation or tissue repair depending on their polarization state. Alcohol is a widely used solvent in pharmaceutical formulations, and its consumption is associated with an increased risk of colitis; however, its effects on macrophages in IBD remain poorly understood. PURPOSE: This study aimed to investigate the effect of alcohol on macrophages in dextran sodium sulfate (DSS)-induced colitis and understand the underlying mechanisms. METHODS: DSS-treated C57BL/6 mice were exposed to varying concentrations of alcohol, transient receptor potential vanilloid 1 (TRPV1) antagonist, and 5-aminosalicylic acid. The distal colon was resected, fixed, stained, and histologically analyzed, through hematoxylin and eosin (H&E) staining and immunofluorescence staining. Ratio [Ca2+]i measurements, western blotting, quantitative polymerase chain reaction, cytokine measurements, and RNA sequencing analyses were also performed. Peritoneal macrophages and RAW264.7 cells were used for in vitro experiments, and various assays were performed to evaluate cellular responses, gene expression, and signaling pathways. RESULTS: Alcohol exacerbated DSS-treated mice colitis and promoted the secretion of various inflammatory cytokines from colonic macrophages. Alcohol enhances the calcium ion influx induced by lipopolysaccharide (LPS) in peritoneal macrophages, while the TRPV1 antagonist capsazepine (CPZ) inhibits LPS- and/or alcohol- induced calcium influx in macrophages. Alcohol and LPS activate the MAPK/P38, MAPK/ERK, and NF-κB signaling pathways and induce the macrophage M2b polarization, resulting in the increased expression level of inflammatory cytokines such as Tnf, Il1b, and Il10. Additionally, CPZ can inhibit the facilitatory effects of alcohol or LPS on the abovementioned pathways and inflammatory factors, reversing macrophage M2b polarization and promoting alcohol-induced colitis. The inhibition of nucleotide binding oligomerization domain containing 2 (NOD2) partially suppressed the alcohol and LPS effects on macrophages. CONCLUSION: Alcohol exacerbates experimental colitis and induces M2b polarization of macrophage via TRPV1-MAPK/NF-κB. Our study provides new insights into the potential therapeutic targets for IBD treatment by elucidating the role of TRPV1 in alcohol-exacerbated colitis, using CPZ as a potential therapeutic option. The identification of transient receptor potential ankyrin subtype 1 (TRPA1) as a therapeutic target expands the scope of future research.

Molecular Deformation Is a Key Factor in Screening Aggregation Inhibitor for Intrinsically Disordered Protein Tau.

Direct inhibitor of tau aggregation has been extensively studied as potential therapeutic agents for Alzheimer's disease. However, the natively unfolded structure of tau complicates the structure-based ligand design, and the relatively large surface areas that mediate tau-tau interactions in aggregation limit the potential for identifying high-affinity ligand binding sites. Herein, a group of isatin-pyrrolidinylpyridine derivative isomers (IPP1-IPP4) were designed and synthesized. They are like different forms of molecular "transformers". These isatin isomers exhibit different inhibitory effects on tau self-aggregation or even possess a depolymerizing effect. Our results revealed for the first time that the direct inhibitor of tau protein aggregation is not only determined by the previously reported conjugated structure, substituent, hydrogen bond donor, etc. but also depends more importantly on the molecular shape. In combination with molecular docking and molecular dynamics simulations, a new inhibition mechanism was proposed: like a "molecular clip", IPP1 could noncovalently bind and fix a tau polypeptide chain at a multipoint to prevent the transition from the "natively unfolded conformation" to the "aggregation competent conformation" before nucleation. At the cellular and animal levels, the effectiveness of the inhibitor of the IPP1 has been confirmed, providing an innovative design strategy as well as a lead compound for Alzheimer's disease drug development.

IGF-1-mediated FOXC1 overexpression induces stem-like properties through upregulating CBX7 and IGF-1R in esophageal squamous cell carcinoma.

Substantial evidence attests to the pivotal role of cancer stem cells (CSC) in both tumorigenesis and drug resistance. A member of the forkhead box (FOX) family, FOXC1, assumes significance in embryonic development and organogenesis. Furthermore, FOXC1 functions as an overexpressed transcription factor in various tumors, fostering proliferation, enhancing migratory capabilities, and promoting drug resistance, while maintaining stem-cell-like properties. Despite these implications, scant attention has been devoted to its role in esophageal squamous cell carcinoma. Our investigation revealed a pronounced upregulation of FOXC1 expression in ESCC, correlating with a poor prognosis. The downregulation of FOXC1 demonstrated inhibitory effects on ESCC tumorigenesis, proliferation, and tolerance to chemotherapeutic agents, concurrently reducing the levels of stemness-related markers CD133 and CD44. Further studies validated that FOXC1 induces ESCC stemness by transactivating CBX7 and IGF-1R. Additionally, IGF-1 activated the PI3K/AKT/NF-κB and MEK/ERK/NF-κB pathways through its binding to IGF-1R, thereby augmenting FOXC1 expression. Conversely, suppressing FOXC1 impeded ESCC stemness induced by IGF-1. The presence of a positive feedback loop, denoted by IGF-1-FOXC1-IGF-1R, suggests the potential of FOXC1 as a prognostic biomarker for ESCC. Taken together, targeting the IGF-1-FOXC1-IGF-1R axis emerges as a promising approach for anti-CSC therapy in ESCC.

TRPM8 inhibits substance P release from primary sensory neurons via PKA/GSK-3beta to protect colonic epithelium in colitis.

Transient receptor potential melastatin 8 (TRPM8) is a cold sensory receptor in primary sensory neurons that regulates various neuronal functions. Substance P (SP) is a pro-inflammatory neuropeptide secreted by the neurons, and it aggravates colitis. However, the regulatory role of TRPM8 in SP release is still unclear. Our study aimed to investigate TRPM8's role in SP release from primary sensory neurons during colitis and clarify the effect of SP on colonic epithelium. We analyzed inflammatory bowel disease patients' data from the Gene Expression Omnibus dataset. Dextran sulfate sodium (DSS, 2.5%)-induced colitis in mice, mouse dorsal root ganglion (DRG) neurons, ND7/23 cell line, and mouse or human colonic organoids were used for this experiment. Our study found that TRPM8, TAC1 and WNT3A expression were significantly correlated with the severity of ulcerative colitis in patients and DSS-induced colitis in mice. The TRPM8 agonist (menthol) and the SP receptor antagonist (Aprepitant) can attenuate colitis in mice, but the effects were not additive. Menthol promoted calcium ion influx in mouse DRG neurons and inhibited the combination and phosphorylation of PKAca from the cAMP signaling pathway and GSK-3ß from the Wnt/ß-catenin signaling pathway, thereby inhibiting the effect of Wnt3a-driven ß-catenin on promoting SP release in ND7/23 cells. Long-term stimulation with SP inhibited proliferation and enhanced apoptosis in both mouse and human colonic organoids. Conclusively, TRPM8 inhibits SP release from primary sensory neurons by inhibiting the interaction between PKAca and GSK-3ß, thereby inhibiting the role of SP in promoting colonic epithelial apoptosis and relieving colitis.

Engineering Dual-Responsive Prodrug-MOFs as Immunogenic Cell Death Initiator for Enhancing Cancer Immunotherapy.

In recent years, the anticancer effects of disulfiram, a clinical drug for anti-alcoholism, are confirmed. However, several defects limit the clinical translation of disulfiram obviously, such as Cu(II)-dependent anticancer activity, instability, and non-selectivity for cancer cells. Herein, a phosphate and hydrogen peroxide dual-responsive nanoplatform (PCu-HA-DQ) is reported, which is constructed by encapsulating disulfiram prodrug (DQ) and modifying hyaluronic acid (HA) on copper doping metal-organic frameworks (PCu MOFs). PCu-HA-DQ is expected to accumulate in tumor by targeting CD-44 receptors and enable guidance with magnetic resonance imaging. Inside the tumor, Cu(DTC)2 will be generated in situ based on a dual-responsive reaction. In detail, the high concentration of phosphate can induce the release of DQ, after that, the intracellular hydrogen peroxide will further mediate the generation of Cu(DTC)2 . In vitro and in vivo results indicate PCu-HA-DQ can induce the apoptosis as well as immunogenic cell death (ICD) of tumor cells distinctly, leading to enhanced immune checkpoint inhibitor (ICI) efficacy by combining the anti-programmed death-1 antibody. This work provides a portable strategy to construct a dual-responsive nanoplatform integrating tumor-targeted ability and multi-therapy, and the designed nanoplatform is also an ICD inducer, which presents a prospect for boosting systemic antitumor immunity and ICI efficacy.

Comparative analysis and prediction of avian influenza in Shangrao city, China from 2016 to 2022.

The aim of this study was to investigate the effects of vaccination, COVID-19 pandemic and migration of migratory birds on the avian influenza positivity rate in Shangrao City and to predict the future avian influenza positivity rate. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to detect nucleic acids of avian influenza A viruses. 1795 samples were collected between 2016 and 2022, of which 1086 were positive. In addition, there were seven human cases of avian influenza. The results showed that the positivity rate of H9 subtype in Shangrao City was higher than usual during the COVID-19 pandemic and migratory birds. Predictions suggest that the H9 subtype positivity rate in Shangrao City will be on the rise in the future. In recent years, the H5 positivity rate has gradually increased. Migratory birds and the COVID-19 pandemic have led to an increase in H9 subtype positivity. Therefore, the prevention and control of them should be strengthened.

ELF4 contributes to esophageal squamous cell carcinoma growth and metastasis by augmenting cancer stemness via FUT9.

Esophageal squamous cell carcinoma (ESCC) commonly has aggressive properties and a poor prognosis. Investigating the molecular mechanisms underlying the progression of ESCC is crucial for developing effective therapeutic strategies. Here, by performing transcriptome sequencing in ESCC and adjacent normal tissues, we find that E74-like transcription factor 4 (ELF4) is the main upregulated transcription factor in ESCC. The results of the immunohistochemistry show that ELF4 is overexpressed in ESCC tissues and is significantly correlated with cancer staging and prognosis. Furthermore, we demonstrate that ELF4 could promote cancer cell proliferation, migration, invasion, and stemness by in vivo assays. Through RNA-seq and ChIP assays, we find that the stemness-related gene fucosyltransferase 9 ( FUT9) is transcriptionally activated by ELF4. Meanwhile, ELF4 is verified to affect ESCC cancer stemness by regulating FUT9 expression. Overall, we first discover that the transcription factor ELF4 is overexpressed in ESCC and can promote ESCC progression by transcriptionally upregulating the stemness-related gene FUT9.

Clinical significance of tumor suppressor genes methylation in circulating tumor DNA of patients with pancreatic cancer.

BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a potential diagnostic and prognostic biomarker in various tumors. However, the role of tumor suppressor genes (TSGs) methylation in ctDNA of patients with pancreatic cancer (PC) remains largely unclear. METHODS: Patients with PC (n = 43), pancreatic benign diseases (n = 39), and healthy controls (n = 20) were enrolled in the study. Quantitative analysis of methylation pattern of five candidate TSGs including NPTX2, RASSF1A, EYA2, p16, and ppENK in ctDNA was performed by next generation sequencing (NGS). The diagnostic performances of these 5-TSGs methylation were assessed by the operating characteristic (ROC) curve and clinicopathological features correlation analysis. Meanwhile, the changes in methylation levels of these 5-TSGs on the 7th postoperative day were evaluated in 23 PC patients who underwent radical resection. RESULTS: The methylation levels of RASSF1A, EYA2, ppENK and p16 genes in patients with PC were significantly higher than those in healthy controls. EYA2, p16 and ppENK genes showed significantly hypermethylation in PC than those in pancreatic benign diseases. NPTX2, RASSF1A, EYA2, p16 and ppENK genes showed significantly hypermethylation in pancreatic benign diseases than those in healthy controls (P < 0.05). The methylation levels of these 5 candidate TSGs were not correlated with the tumor size, nerve invasion, lymph node metastasis and TNM stage of PC. The AUC of these biomarkers for diagnosis of PC ranged from 0.65 to 0.96. The AUC values of these methylated genes and CpG sites for differentiating malignant and benign pancreatic diseases were ranging from 0.68 to 0.92. Combined the hypermethylated genes improved the detective ability of PC than single gene. The methylation levels of NPTX2, EYA2 and ppENK genes were significantly decreased after radical resection of PC. CONCLUSION: Quantitative analysis of methylation pattern of NPTX2, RASSF1A, EYA2, p16 and ppENK in ctDNA by NGS could be a valuable non-invasive tool for detection and monitoring of PC.

Immunomodulator-Mediated Suppressive Tumor Immune Microenvironment Remodeling Nanoplatform for Enhanced Immuno/Chemo/Photothermal Combination Therapy of Triple Negative Breast Cancer.

Despite immunotherapy having revolutionized cancer therapy, the efficacy of immunotherapy in triple-negative breast cancer (TNBC) is seriously restricted due to the insufficient infiltration of mature dendritic cells (DCs) and the highly diffusion of immunosuppressive cells in the tumor microenvironment. Herein, an immunomodulatory nanoplatform (HA/Lipo@MTO@IMQ), in which the DCs could be maximally activated, was engineered to remarkably eradicate the tumor via the combination of suppressive tumor immune microenvironment reversal immunotherapy, chemotherapy, and photothermal therapy. It was noticed that the immunotherapy efficacy could be significantly facilitated by this triple-assistance therapy: First, a robust immunogenic cell death (ICD) effect was induced by mitoxantrone hydrochloride (MTO) to boost DCs maturation and cytotoxic T lymphocytes infiltration. Second, the powerful promaturation property of the toll-like receptor 7/8 (TLR7/8) agonist on DCs simultaneously strengthened the ICD effect and restricted antitumor immunity to the tumor bed and lymph nodes. On this basis, tumor-associated macrophages were also dramatically repolarized toward the antitumor M1 phenotype in response to TLR7/8 agonist to intensify the phagocytosis and reverse the immunosuppressive microenvironment. Furthermore, the recruitment of immunocompetent cells and tumor growth inhibition were further promoted by the photothermal characteristic. The nanoplatform with no conspicuous untoward effects exhibited a splendid ability to activate the systemic immune system so as to increase the immunogenicity of the tumor microenvironment, thus enhancing the tumor killing effect. Taken together, HA/Lipo@MTO@IMQ might highlight an efficient combination of therapeutic modality for TNBC.

Dry and wet seasonal variations of the sediment fungal community composition in the semi-arid region of the Dali River, Northwest China.

Microbial communities play an important role in water quality regulation and biogeochemical cycling in freshwater ecosystems. However, there has been a lack of research on the seasonal variation of sediment microorganisms in the sediments of small river basins in typical semi-arid region. In this study, high-throughput DNA sequencing was used to investigate the fungal community and its influencing factors in the sediment of the Dali River in the dry and wet seasons. The results showed that there were obvious seasonal differences in fungal alpha diversity. The diversity and richness of fungi in the dry season were greater than that in the wet season, but the evenness of fungi in the dry season was lower than that in the wet season. In addition, Ascomycota and Basidiomycota were the most important phyla in the Dali River fungal community, but their distributions showed clear seasonal differences. In the dry season, the relative abundance of Ascomycota and Basidiomycota were 12.34-46.42% and 17.59-27.20%, respectively. In the wet season, the relative abundances of these two phyla were 24.33-36.56% and 5.75-12.26%, respectively. PICRUSt2 was used to predict the metabolic function of fungal community in the sediment, and it was found that at the first level, the proportion of biosynthesis in the dry season was higher than that in the wet season. The ecological network structure showed that the fungal community in the wet season was more complex and stable than that in the dry season. The characteristic fungi in the dry season sediment were chytrid fungi in the family Rhizophydiaceae and the order Rhizophydiales, whereas those in the wet season sediment were in the orders Eurotiales and Saccharomycetales. Canonical correspondence analysis (CCA) showed that the physicochemical properties of water and sediment together explained a greater proportion of the dry-season fungal community changes than of the wet-season changes. In the dry season, temperature and ammonia nitrogen in the water were the main factors affecting the change of fungal community, whereas in the wet season, total nitrogen concentration of the water, electrical conductivity, total organic carbon and available phosphorus of the sediment, pH, and temperature were the main factors affecting the changes in fungal community composition. The results of this study enhanced our understanding of microbial communities in semi-arid river ecosystems, and highlight the importance of the management and protection in river ecosystems.

Prediction of reported monthly incidence of hepatitis B in Hainan Province of China based on SARIMA-BPNN model.

In recent years, the incidence of hepatitis B has been serious in Hainan Province of China. To construct a statistical model of the monthly incidence of hepatitis B in Hainan Province of China and predict the monthly incidence of hepatitis B in 2022. Simple central moving average method and seasonal index were used to analyze the trend and seasonal effects of monthly incidence of hepatitis B. Based on the time series of reported monthly incidence of hepatitis B in Hainan Province from 2017 to 2020, a multiplicative seasonal model (SARIMA), multiplicative seasonal model combined with error back propagation neural network model (SARIMA-BPNN), and a gray prediction model were constructed to fit the incidence, and the time series of monthly incidence of hepatitis B in 2021 was used to verify the accuracy of models. The lowest and highest monthly incidence of hepatitis B in Hainan Province were in February and August, respectively, and MAPE of SARIMA, SARIMA-BPNN, and gray prediction models were 0.089, 0.087, and 0.316, respectively. The best fitting model is the SARIMA-BPNN model. The predicted monthly incidence of hepatitis B in 2022 showed a downward trend, with the steepest decline in March, which indicates that the prevention and control of hepatitis B in Hainan Province is effective, and the study can provide scientific and reasonable suggestions for the prevention and control of hepatitis B in Hainan.

TAOK3 Facilitates Esophageal Squamous Cell Carcinoma Progression and Cisplatin Resistance Through Augmenting Autophagy Mediated by IRGM.

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers because of its robust aggressive phenotype and chemoresistance. TAO kinase belongs to mitogen-activated protein kinases, which mediate drug resistance in multiple cancers. However, the role of TAO kinase in ESCC progression and chemoresistance has never been explored. Here, it is reported that TAOK3 augments cell autophagy and further promotes ESCC progression and chemoresistance. Mechanistically, TAOK3 phosphorylates KMT2C at S4588 and strengthens the interaction between KMT2C and ETV5. Consequently, the nuclear translocation of KMT2C is increased, and the transcription of autophagy-relevant gene IRGM is further upregulated. Additionally, the inhibitor SBI-581 can significantly suppress cell autophagy mediated by TAOK3 and synergizes with cisplatin to treat ESCC in vitro and in vivo.

Assessment of transmissibility and measures effectiveness of SARS in 8 regions, China, 2002-2003.

Background: Severe acute respiratory syndrome (SARS) is a form of atypical pneumonia which took hundreds of lives when it swept the world two decades ago. The pathogen of SARS was identified as SARS-coronavirus (SARS-CoV) and it was mainly transmitted in China during the SARS epidemic in 2002-2003. SARS-CoV and SARS-CoV-2 have emerged from the SARS metapopulation of viruses. However, they gave rise to two different disease dynamics, a limited epidemic, and an uncontrolled pandemic, respectively. The characteristics of its spread in China are particularly noteworthy. In this paper, the unique characteristics of time, space, population distribution and transmissibility of SARS for the epidemic were discussed in detail. Methods: We adopted sliding average method to process the number of reported cases per day. An SEIAR transmission dynamics model, which was the first to take asymptomatic group into consideration and applied indicators of R 0, Reff, Rt to evaluate the transmissibility of SARS, and further illustrated the control effectiveness of interventions for SARS in 8 Chinese cities. Results: The R 0 for SARS in descending order was: Tianjin city (R 0 = 8.249), Inner Mongolia Autonomous Region, Shanxi Province, Hebei Province, Beijing City, Guangdong Province, Taiwan Province, and Hong Kong. R 0 of the SARS epidemic was generally higher in Mainland China than in Hong Kong and Taiwan Province (Mainland China: R 0 = 6.058 ± 1.703, Hong Kong: R 0 = 2.159, Taiwan: R 0 = 3.223). All cities included in this study controlled the epidemic successfully (Reff<1) with differences in duration. Rt in all regions showed a downward trend, but there were significant fluctuations in Guangdong Province, Hong Kong and Taiwan Province compared to other areas. Conclusion: The SARS epidemic in China showed a trend of spreading from south to north, i.e., Guangdong Province and Beijing City being the central regions, respectively, and from there to the surrounding areas. In contrast, the SARS epidemic in the central region did not stir a large-scale transmission. There were also significant differences in transmissibility among eight regions, with R0 significantly higher in the northern region than that in the southern region. Different regions were able to control the outbreak successfully in differences time.

Transcription factor 3 promotes migration and invasion potential and maintains cancer stemness by activating ID1 expression in esophageal squamous cell carcinoma.

Transcription factor 3 (TCF3) is a member of the basic Helix - Loop - Helix (bHLH) transcription factor (TF) family and is encoded by the TCF3 gene (also known as E2A). It has been shown that TCF3 functions as a key transcription factor in the pathogenesis of several human cancers and plays an important role in stem cell maintenance and carcinogenesis. However, the effect of TCF3 in the progression of esophageal squamous cell carcinoma (ESCC) is poorly known. In our study, TCF3 was found to express highly and correlated with cancer stage and prognosis. TCF3 was shown to promote ESCC invasion, migration, and drug resistance both from the results of in vivo and in vitro assays. Moreover, further studies suggested that TCF3 played these roles through transcriptionally regulating Inhibitor of DNA binding 1(ID1). Notably, we also found that TCF3 or ID1 was associated with ESCC stemness. Furthermore, TCF3 was correlated with the expression of cancer stemness markers CD44 and CD133. Therefore, maintaining cancer stemness might be the underlying mechanism that TCF3 transcriptionally regulated ID1 and further promoted ESCC progression and drug resistance.

A Dual Stimuli-Responsive Nanoplatform Loaded PtIV -Triptolide Prodrug for Achieving Synergistic Therapy toward Breast Cancer.

To strengthen the antitumor efficacy and avoid toxicity to normal cells of cisplatin and triptolide, herein, an acid and glutathione (GSH) dual-controlled nanoplatform for enhanced cancer treatment through the synergy of both "1+1" apoptosis and "1+1" ferroptosis is designed. Remarkably, ZIF8 in response to tumor microenvironment enhances drug targeting and protects drugs from premature degradation. Meanwhile, the PtIV  center can be easily reduced to cisplatin because of the large amount of GSH, thus liberating the triptolide as the coordinated ligand. The released cisplatin and hemin in turn boost the tumor cell "1+1" apoptosis through chemotherapy and photodynamic therapy, respectively. Furthermore, GSH reduction through PtIV  weakens the activation of glutathione peroxidase 4 (GPX4) effectively. The released triptolide can inhibit the expressions of GSH by regulating nuclear factor E2 related factor 2 (Nrf2), further promoting membrane lipid peroxidation, thus "1+1" ferroptosis can be achieved. Both in vitro and in vivo results demonstrate that the nanosystem can not only perform superior specificity and therapeutic outcomes but also reduce the toxicity to normal cells/tissues of cisplatin and triptolide effectively. Overall, the prodrug-based smart system provides an efficient therapeutic strategy for cancer treatment by virtue of the effect of enhanced "1+1" apoptosis and "1+1" ferroptosis therapies.

The construction of Fe-porphyrin nanozymes with peroxidase-like activity for colorimetric detection of glucose.

As a type of nanomaterials with enzyme-mimetic catalytic properties, nanozymes have attracted wide concern in biological detection. H2O2 was the characteristic product of diverse biological reactions, and the quantitative analysis for H2O2 was an important way to detect disease biomarkers, such as acetylcholine, cholesterol, uric acid and glucose. Therefore, there is of great significance for developing a simple and sensitive nanozyme to detect H2O2 and disease biomarkers by combining with corresponding enzyme. In this work, Fe-TCPP MOFs were successfully prepared by the coordination between iron ions and porphyrin ligands (TCPP). In addition, the peroxidase (POD) activity of Fe-TCPP was proved, in detail, Fe-TCPP could catalyze H2O2 to produce ·OH. Herein, glucose oxidase (GOx) was chosen as the model to build cascade reaction by combining Fe-TCPP to detect glucose. The results indicated glucose could be detected by this cascade system selectively and sensitively, and the limit of detection of glucose was achieved to 0.12 µM. Furthermore, a portable hydrogel (Fe-TCPP@GEL) was further established, which encapsulated Fe-TCPP MOFs, GOx and TMB in one system. This functional hydrogel could be applied for colorimetric detection of glucose by coupling with a smartphone easily.

Trends in disease burden of hepatitis B infection in Jiangsu Province, China, 1990-2021.

Background: The incidence of hepatitis B virus (HBV) has decreased year by year in China after the expansion of vaccination, but there is still a high disease burden in Jiangsu Province of China. Methods: The year-by-year incidence data of HBV in Jiangsu Province from 1990 to 2021 were collected. The incidence rates of males and females age groups were clustered by systematic clustering, and the incidence rates of each age group were analyzed and studied by using Joinpoint regression model and age-period-cohort effect model (APC). Results: Joinpoint regression model and APC model showed a general decrease in HBV prevalence in both males and females. In addition, the results of the APC model showed that the age, period, and cohort effects of patients all affected the incidence of HBV, and the incidence was higher in males than in females. The incidence is highest in the population between the ages of 15 and 30 years (mean: 21.76/100,000), especially in males (mean: 31.53/100,000) than in females (mean:11.67/100,000). Another high-risk group is those over 60 years of age (mean: 21.40/100,000), especially males (mean: 31.17/100,000) than females (mean: 11.63/100,000). The period effect of the APC model suggests that HBV vaccination is effective in reducing the incidence of HBV in the population. Conclusions: The incidence of HBV in Jiangsu Province showed a gradual downward trend, but the disease burden in males was higher than that in females. The incidence is higher and increasing rapidly in the population between the ages of 15 and 30 years and people over 60 years of age. More targeted prevention and control measures should be implemented for males and the elderly.

Solid Pseudopapillary Neoplasm of the Pancreas: A Multi-Institution Study of 118 Cases.

OBJECTIVES: The aim of the study is to summary the clinicopathological characteristics and surgical outcomes of solid pseudopapillary neoplasm (SPN) of the pancreas. METHODS: In this retrospective study, the information of 118 patients with SPN from 3 hospitals were analyzed. RESULTS: A total of 118 patients. The mean age was 30.8 (standard deviation, 14.7) years and the majority were female (n = 95, 80.5%). Sixty-seven patients (56.8%) had clinical symptoms, of which the most common symptom was abdominal pain (49.6%). The mean tumor size was 5.9 (standard deviation, 2.9) cm. Pseudopapillary architecture was the commonest histologic feature, and ß-catenin, CD56, vimentin, neuron-specific enolase, CD10, a1-antitrypsin, cytokeratins showed different degrees of positive expression in immunohistochemical staining. Fourteen patients (11.9%) presented aggressive pathologic behavior, which was correlated to the incomplete tumor capsule. At a median follow-up of 59.2 months, the recurrence rate was 1.8% and the overall 5-year survival rate was 97.7%. CONCLUSIONS: Solid pseudopapillary neoplasm of the pancreas is a potentially low-grade malignant tumor that most frequently found in young females. Its clinical manifestations are nonspecific and the diagnosis mostly depends on pathological examination. Surgical resection is the first choice of treatment for SPN with a good prognosis.

Establishment of a novel signature to predict prognosis and immune characteristics of pancreatic cancer based on necroptosis-related long non-coding RNA.

BACKGROUND: Necroptosis plays an important role in tumorigenesis and tumour progression. Long noncoding RNAs (lncRNAs) have been proven to be regulatory factors of necroptosis in various tumours. However, the real role of necroptosis-related lncRNAs (NRLs) and their potential to predict the prognosis of pancreatic cancer (PC) remain largely unclear. The goal of this study was to identify NRLs and create a predictive risk signature in PC, explore its prognostic predictive performance, and further assess immunotherapy and chemotherapy responses. METHODS: RNA sequencing data, tumour mutation burden (TMB) data, and clinical profiles of 178 PC patients were downloaded from The Cancer Genome Atlas (TCGA) database. NRLs were identified using Pearson correlation analysis. Then, patients were divided into the training set and the validation set at a 1:1 ratio. Subsequently, Cox and LASSO regression analyses were conducted to establish a prognostic NRL signature in the training set and validation set. The predictive efficacy of the 5-NRL signature was assessed by survival analysis, nomogram, Cox regression, clinicopathological feature correlation analysis, and receiver operating characteristic (ROC) curve analysis. Furthermore, correlations between the risk score (RS) and immune cell infiltration, immune checkpoint molecules, somatic gene mutations, and anticancer drug sensitivity were analysed. Finally, we used quantitative reverse transcription polymerase chain reaction (qRT-PCR) to validate the 5-NRLs. RESULTS: A 5-NRL signature was established to predict the prognosis of PC, including LINC00857, AL672291.1, PTPRN2-AS1, AC141930.2, and MEG9. The 5-NRL signature demonstrated a high degree of predictive power according to ROC and Kaplan‒Meier curves and was revealed to be an independent prognostic risk factor via stratified survival analysis. Nomogram and calibration curves indicated the clinical adaptability of the signature. Immune-related pathways were linked to the 5-NRL signature according to enrichment analysis. Additionally, immune cell infiltration, immune checkpoint molecules, somatic gene mutations and the half-maximal inhibitory concentration (IC50) of chemotherapeutic agents were significantly different between the two risk subgroups. These results suggested that our model can be used to evaluate the effectiveness of immunotherapy and chemotherapy, providing a potential new strategy for treating PC. CONCLUSIONS: The novel 5-NRL signature is helpful for assessing the prognosis of PC patients and improving therapy options, so it can be further applied clinically.

Machine learning and single cell RNA sequencing analysis identifies regeneration-related hepatocytes and highlights a Birc5-related model for identifying cell proliferative ability.

BACKGROUND: Partial hepatectomy (PHx) has been shown to induce rapid regeneration of adult liver under emergency conditions. Therefore, an in-depth investigation of the underlying mechanisms that govern liver regeneration following PHx is crucial for a comprehensive understanding of this process. METHOD: We analyzed scRNA-seq data from liver samples of normal and PHx-48-hour mice. Seven machine learning algorithms were utilized to screen and validate a gene signature that accurately identifies and predicts this population. Co-immunostaining of zonal markers with BIRC5 to investigate regional characteristics of hepatocytes post-PHx. RESULTS: Single cell sequencing results revealed a population of regeneration-related hepatocytes. Transcription factor analysis emphasized the importance of Hmgb1 transcription factor in liver regeneration. HdWGCNA and machine learning algorithm screened and obtained the key signature characterizing this population, including a total of 17 genes and the function enrichment analysis indicated their high correlation with cell cycle pathway. It is note-worthy that we inferred that Hmgb1 might be vital in the regeneration-related hepatocytes of PHx_48h group. Parallelly, Birc5 might be closely related to the regulation of liver regeneration, and positively correlated with Hmgb1. CONCLUSIONS: Our study has identified a distinct population of hepatocytes that are closely associated with liver regeneration. Through machine learning algorithms, we have identified a set of 17 genes that are highly indicative of the regenerative capacity of hepatocytes. This gene signature has enabled us to assess the proliferation ability of in vitro cultured hepatocytes using sequencing data alone.