Recent advances in IgG4-related autoimmune pancreatitis.

The incidence of IgG4-related autoimmune pancreatitis (IgG4-AIP) is high in Asia and other countries, and unnecessary treatment is often undertaken due to both missed diagnosis and misdiagnosis in clinical practice. Although IgG4-AIP has attracted increasing attention, the details of IgG4-AIP pathogenesis and systemic immune response, including its relationship to tumor pathogenesis, are still unclear. In recent years, research on serum immunological detection, pathological features, clinical manifestations, diagnosis and treatment measures for IgG4-AIP has gradually increased. It is of great importance to summarize and discuss the latest progress regarding IgG4-AIP disease.

Glucose metabolism-based signature predicts prognosis and immunotherapy strategies for colon adenocarcinoma.

BACKGROUND: The global prevalence and metastasis rates of colon adenocarcinoma (COAD) are high, and therapeutic success is limited. Although previous research has primarily explored changes in gene phenotypes, the incidence rate of COAD remains unchanged. Metabolic reprogramming is a crucial aspect of cancer research and therapy. The present study aims to develop cluster and polygenic risk prediction models for COAD based on glucose metabolism pathways to assess the survival status of patients and potentially identify novel immunotherapy strategies and related therapeutic targets. METHODS: COAD-specific data (including clinicopathological information and gene expression profiles) were sourced from The Cancer Genome Atlas (TCGA) and two Gene Expression Omnibus (GEO) datasets (GSE33113 and GSE39582). Gene sets related to glucose metabolism were obtained from the MSigDB database. The Gene Set Variation Analysis (GSVA) method was utilized to calculate pathway scores for glucose metabolism. The hclust function in R, part of the Pheatmap package, was used to establish a clustering system. The mutation characteristics of identified clusters were assessed via MOVICS software, and differentially expressed genes (DEGs) were filtered using limma software. Signature analysis was performed using the least absolute shrinkage and selection operator (LASSO) method. Survival curves, survival receiver operating characteristic (ROC) curves and multivariate Cox regression were analyzed to assess the efficacy and accuracy of the signature for prognostic prediction. The pRRophetic program was employed to predict drug sensitivity, with data sourced from the Genomics of Drug Sensitivity in Cancer (GDSC) database. RESULTS: Four COAD subgroups (i.e., C1, C2, C3 and C4) were identified based on glucose metabolism, with the C4 group having higher survival rates. These four clusters were bifurcated into a new Clust2 system (C1 + C2 + C3 and C4). In total, 2175 DEGs were obtained (C1 + C2 + C3 vs. C4), from which 139 prognosis-related genes were identified. ROC curves predicting 1-, 3- and 5-year survival based on a signature containing nine genes showed an area under the curve greater than 0.7. Meanwhile, the study also found this feature to be an important predictor of prognosis in COAD and accordingly assessed the risk score, with higher risk scores being associated with a worse prognosis. The high-risk and low-risk groups responded differently to immunotherapy and chemotherapeutic agents, and there were differences in functional enrichment pathways. CONCLUSIONS: This unique signature based on glucose metabolism may potentially provide a basis for predicting patient prognosis, biological characteristics and more effective immunotherapy strategies for COAD.

Prediction and therapeutic targeting of the tumor microenvironment-associated gene CTSK in gastric cancer.

BACKGROUND: Cathepsin-K (CTSK) is overexpressed in Gastric cancer (GC) and the mechanism of its overexpression in GC is still unclear. The present work found CTSK as a potential predictive biomarker and immunotherapeutic target for GC based on the tumor microenvironment (TME). METHODS: From public databases, gene expression profiles and clinical data of GC were downloaded to analyze the distribution of stromal and immune cells and tumor abundance in TME. Differentially expressed genes (DEGs) associated with TME were obtained by differential analysis, followed by cross-screening to obtain CTSK as a gene associated with TME. Next, a series of methods and tools were employed to explore the relationships between clinicopathological features of GC and CTSK expression as well as prognosis, tumor immune microenvironment, immune checkpoints and drug sensitivity. And GSEA was used to investigate the potential role of CTSK in the tumor microenvironment of GC. RESULTS: From the dataset, we obtained a total of 656 DEGs associated with TME and the stromal component of TME was found to be closely involved in GC prognosis. CTSK was cross-screened as the key gene associated with TME by the PPI network and univariate Cox regression analysis. Pan-cancer analysis revealed significant high expression of CTSK in a variety of cancers. Subsequently, we hypothesized that high-expressed CTSK was closely correlated with poor prognosis and lymph node metastasis of tumors, and that CTSK, a GC TME-related gene, was largely involved in a range of biological behaviors of tumors, with a significant correlation between several immune cells. CONCLUSION: CTSK was validated as a potential prognostic biomarker related to TME of GC and could be a promising next-generation immunotherapeutic target for GC.

Efficacy and safety of piperacillin-tazobactam compared with meropenem in treating complicated urinary tract infections including acute pyelonephritis due to extended-spectrum ß-lactamase-producing Enterobacteriaceae.

Introduction: Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae pose a huge threat to human health, especially in the context of complicated urinary tract infections (cUTIs). Carbapenems and piperacillin-tazobactam (PTZ) are two antimicrobial agents commonly used to treat cUTIs. Methods: A monocentric retrospective cohort study focused on the treatment of cUTIs in adults was conducted from January 2019 to November 2021. Patients with a positive urine culture strain yielding ≥ 103 colony-forming units per milliliter (CFU/mL), and sensitive to PTZ and carbapenems, were included. The primary endpoint was clinical success after antibiotic therapy. The secondary endpoint included rehospitalization and 90-day recurrence of cUTIs caused by ESBL-producing Enterobacteriaceae. Results: Of the 195 patients included in this study, 110 were treated with PTZ while 85 were administered meropenem. The rate of clinical cure was similar between the PTZ and meropenem groups (80% vs. 78.8%, p = 0.84). However, the PTZ group had a lower duration of total antibiotic use (6 vs. 9; p < 0.01), lower duration of effective antibiotic therapy (6 vs. 8; p < 0.01), and lower duration of hospitalization (16 vs. 22; p < 0.01). Discussion: In terms of adverse events, the safety of PTZ was higher than that of meropenem in the treatment of cUTIs.

SIM imaging resolves endocytosis of SARS-CoV-2 spike RBD in living cells.

It is urgent to understand the infection mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for the prevention and treatment of COVID-19. The infection of SARS-CoV-2 starts when the receptor-binding domain (RBD) of viral spike protein binds to angiotensin-converting enzyme 2 (ACE2) of the host cell, but the endocytosis details after this binding are not clear. Here, RBD and ACE2 were genetically coded and labeled with organic dyes to track RBD endocytosis in living cells. The photostable dyes enable long-term structured illumination microscopy (SIM) imaging and to quantify RBD-ACE2 binding (RAB) by the intensity ratio of RBD/ACE2 fluorescence. We resolved RAB endocytosis in living cells, including RBD-ACE2 recognition, cofactor-regulated membrane internalization, RAB-bearing vesicle formation and transport, RAB degradation, and downregulation of ACE2. The RAB was found to activate the RBD internalization. After vesicles were transported and matured within cells, RAB was finally degraded after being taken up by lysosomes. This strategy is a promising tool to understand the infection mechanism of SARS-CoV-2.

Different 18F-FDG imaging: A rare case of liver multiple carcinomas.

A 49-year-old man was referred to the hospital with the complaints of haematochezia and weight loss. Colonoscopy and pathological needle biopsy suggested moderately to highly differentiated adenocarcinoma. The patient underwent abdominal CT examination, which demonstrated two augmented and irregular masses in the liver. However, the glucose metabolism of 18F-FDG in these two lesions was completely different. Considering the different glucose metabolism, a needle biopsy of the liver mass was performed, and the diagnosis was rectal cancer with liver metastasis and primary hepatocellular carcinoma.

A Cell Membrane Fluorogenic Probe for Gram-Positive Bacteria Imaging and Real-Time Tracking of Bacterial Viability.

Bacterial infections are a global healthcare problem, resulting in serious clinical morbidities and mortality. Real-time monitoring of live bacteria by fluorescent imaging technology has potential in diagnosis of bacterial infections, elucidating antimicrobial agents' mode of action, assessing drug toxicity, and examining bacterial antimicrobial resistance. In this work, a naphthalimide-derived fluorescent probe ZTRS-BP was developed for wash-free Gram-positive bacteria imaging. The probe aggregated in aqueous solutions and exhibited aggregation-caused fluorescence quenching (ACQ). The interaction with Gram-positive bacteria cell walls would selectively disaggregate the probe and the liberated probes were dispersed on the outside of the bacteria cell walls to achieve surface fluorescence imaging. There were no such interactions with Gram-negative bacteria, which indicates that selective binding and imaging of Gram-positive bacteria was achieved. The binding of zinc ions by ZTRS-BP can enhance the fluorescent signals on the bacterial surface by inhibiting the process of photoinduced electron transfer. ZTRS-BP-Zn(II) complex was an excellent dye to discriminate mixed Gram-positive and Gram-negative bacteria. Also, live and dead bacteria can be differentially imaged by ZTRS-BP-Zn(II). Furthermore, ZTRS-BP-Zn(II) was used for real-time monitoring bacteria viability such as B. cereus treated with antibiotic vancomycin.

A UPLC-MS/MS method for determination of endogenous l-carnitine and acetyl-l-carnitine in serum of patients with depression.

A simple, rapid, and selective ultra-performance liquid chromatography-tandem mass spectrometry method for determination of l-carnitine (LC) and acetyl-l-carnitine (ALC) in human serum was developed. Acetyl-l-carnitine-d3 (ALC-d3 ) was selected as internal standard (IS). After protein precipitation with acetonitrile-water (1 mL, 2:1, v/v), the analytes and IS were separated on a 2.5-µm XSelect HSS T3 C18 column by gradient elution with methanol-water (containing 0.01% ammonia water) as the mobile phase at a flow rate of 0.2 mL/min. Analytes were detected with multiple reaction monitoring using a positive scan mode with electrospray ionization. Good linearity (R2 > 0.999) was observed in the concentration range for LC and ALC. The inter- and intra-day values of relative error were -10.4% to 10.0% with CVs less than 9.84%. The average recoveries of the two analytes were 91.29%-98.23%. Blood samples containing LC and ALC were stable under various storage conditions. Normal, haemolytic, and hyperlipidaemic serum had no significant effect on the quantification of LC and ALC. This method was successfully applied to study the concentrations of endogenous LC and ALC in the serum of patients with first-episode depression.

Integrated silica membrane-based nucleic acid purification, amplification, and visualization platform for low-cost, rapid detection of foodborne pathogens.

Real-time fluorescence detection of nucleic acid exhibit excellent performance in analytical and diagnostic applications. However, the requirement of laboratory-based instrument and complex nucleic acid extraction greatly limits their application in point-of-care testing (POCT). Herein, a novel integrated silica membrane-based platform incorporating nucleic acid purification, amplification, and detection steps was developed. A universal and portable visualization platform was fabricated by incorporating denaturation bubble-mediated strand exchange amplification (SEA) reaction with silica membrane. The fluorescence signal of SYBR Green I with amplification products was visualized by the naked eye using a simple ultraviolet light on the silica membrane, and significant discrimination between the positive and negative samples could be easily and visually obtained. Besides, chitooligosaccharide-modified silica membrane allows the purification of nucleic acid in a totally aqueous system and enables in situ SEA. With the proposed integrated platform, 102-108 cfu/mL Vibrio parahaemolyticus could be successfully detected and excellent performance was also revealed for gram-positive pathogens. The detection limit of the method for artificially spiked oysters was 103 cfu/g and reached 100 cfu/g after 12 h enrichment. This proof-of-concept method could also be applied to a variety of nucleic acid amplification methods. We believe that the proposed silica membrane-based platform has great potential for the rapid and low-cost detection of nucleic acids especially in low-resource settings. Graphical abstract.

Evidence of a Relationship Between Plasma Leptin, Not Nesfatin-1, and Craving in Male Alcohol-Dependent Patients After Abstinence.

The goal of this study was to determine whether the plasma leptin, nesfatin-1, cortisol, brain-derived neurotrophic factor (BDNF), and inflammatory cytokines could be used as potential biomarkers for the degree of craving in the alcohol-dependent patients after 1 month of abstinence. A total of 83 patients with alcohol use disorder (AUD) and 61 healthy subjects were assessed. Patients with AUD were selected from Department of Material Dependence, Anhui Mental Health Center, and subjects in the control group were selected from healthy volunteers. The Alcohol Urge questionnaire Scale (AUQ) was used to evaluate the extent of craving for alcohol, and the Michigan Alcoholism Screening Test (MAST), the Fagerstrom Test for Nicotine Dependence (FTND), the Self-Rating Anxiety Scale (SAS), and the Self-Rating Depression Scale (SDS) were also assessed in patients with AUD. Enzyme-Linked Immunosorbent Assay (ELISA) was used for the measurement of plasma leptin, nesfatin-1, cortisol, BDNF, Interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) levels. Compare with healthy controls, the average leptin, leptin/BMI, IL-6, CRP, and TNF-α levels in patients with AUD were significantly increased, while the BDNF levels were significantly decreased. Moreover, the partial correlational analysis showed that the AUQ scores of the alcohol-dependent patients were positively correlated with the plasma leptin levels (r = 0.613, P < 0.001), rather than nesfatin-1 (r = 0.066, P = 0.569) after controlling for age as covariate. Furthermore, plasma nesfatin-1 levels were found to be correlated with the SDS scores (r = 0.366, P = 0.001) in the AUD group. In addition, plasma leptin levels were positively associated with the plasma IL-6 (r = 0.257, P = 0.033), CRP (r = 0.305, P = 0.011), and TNF-α (r = 0.311, P = 0.009) levels, and negatively associated with the BDNF levels (r = -0.245, P = 0.042) in patients with AUD. These results suggest that plasma leptin, but not nesfatin-1, might be a potential biomarker for the degree of craving in alcohol-dependent patients after 1 month of abstinence, the mechanism of which might be related to the dysfunction of the inflammatory cytokines and BDNF levels.

Development of a direct and visual isothermal method for meat adulteration detection in low resource settings.

Simple, fast and efficient method for on-site detection of meat adulteration is of increasing demand in low-resource regions. Here, a direct and visual denaturation bubble-mediated strand exchange amplification method (SEA) was developed to detect meat adulteration by targeting the mitochondrial sequence from duck, which required only a heating block. The method allowed detecting as low as 10 pg/µL duck DNA and 0.1% duck meat in binary mixtures, sufficiently meeting the demand of meat adulteration detection. Notably, the method realized instrument-free readout by significant color discrimination of positive and negative results. By coupling with fast DNA release, a direct SEA method was developed and reduced the whole detection time to 1 h, eliminating complex DNA extraction process. The developed method provided a promising strategy with integration of fast sample lysis, miniaturized reaction platform and visual readout for meat adulteration, especially suitable for low resource point-of-care settings.

Factors related to lithium blood concentrations in Chinese Han patients with bipolar disorder.

Background: The goal of this study was to identify the physiological factors related to the blood concentration of lithium in Chinese Han patients with bipolar disorder (BD). Materials and methods: A total of 186 Chinese Han patients with BD were assessed. Patients were recruited from the Anhui Mental Health Center. The concentrations of serum lithium were measured by a Dimension RxL Max biochemistry analyzer. Physiological factors, including body weight, body mass index (BMI), and routine laboratory parameters, were collected. Relationships between the serum lithium concentration and relevant clinical data were analyzed by Pearson correlation tests, and the independent relationships were determined by multivariate linear regression analysis. Results: Pearson correlation analysis showed that serum lithium concentrations were positively correlated with creatinine concentrations (r=0.147, P=0.046), Mg2+ concentrations (r=0.151, P=0.04), and the percentage of neutrophils (r=0.178, P=0.015) and negatively correlated with high-density lipoprotein (HDL) concentrations (r=-0.142, P=0.05), apolipoprotein A1 concentrations (r=-0.169, P=0.02), and Na+ concentrations (r=-0.148, P=0.046) in 186 patients with BD. Furthermore, multivariate linear regression analysis showed that serum lithium concentrations were negatively associated with Na+ concentrations and positively associated with the percentage of neutrophils. Conclusion: These results suggest that physiological factors, including creatinine, HDL, apolipoprotein A1, Na+, and Mg2+ concentrations and percentage of neutrophils, might be related to serum lithium concentrations and provide a basis for parameter selection of lithium population pharmacokinetics in Chinese Han patients with BD.

Up-regulation of miR-155 contributes to TNF-mediated hepatocyte apoptosis in acute liver failure.

BACKGROUND/AIMS: Acute liver failure (ALF) is due to severe immune response, resulting in massive apoptosis/necrosis of hepatocytes. The precise mechanism has not been explored yet. MATERIALS AND METHODS: The mouse with ALF model was induced by D-GalN/LPS; the hepatic miRNAs expression profile was evaluated by miRNA microarray and verified by RT-PCR. During the ALF in mice, the miR-155 expression was detected in the liver as well as in spleen. Then the correlation between miR-155 and inflammatory cytokines was evaluated. Furthermore, the miR-155 expression in activated Raw264.7 cells and apoptotic hepatocytes was also studied. Finally, the regulatory roles of miR-155 in TNF expression of apoptotic hepatocytes were shown. RESULTS: It was shown that miRNAs changed in the mice with ALF relating to hepatocytes apoptosis/necrosis; the selected miRNAs were confirmed with RT-PCR. miR-155 was up-regulated, but miR-698, -720, and -329 were down-regulated. Moreover, hepatic miR-155 was up-regulated at all-time points in the liver, but only at 7 h in spleen of mice with ALF. A significant correlation was observed between hepatic miR-155 and TNF/IL-6 in mice with ALF, which was supported by the findings in vitro showing up-regulated miR-155 in Raw264.7 cells and Hepa1-6 cells under LPS or D-GalN+TNF induction, respectively. Moreover, a correlation was observed between miR155 and TNF levels in vivo and in vitro. CONCLUSION: These data demonstrate that miR-155 regulates TNF-mediated hepatocyte apoptosis in ALF, which provides some useful information in both basic and clinical researches.

A novel LRR and Ig domain-containing protein could function as an immune effector in Crassostrea gigas.

A variety of combinations of leucine-rich repeat (LRR) and immunoglobulin-like (Ig) domains have been found and discovered in invertebrates and vertebrates, but the functions remain largely unexplored. In the present study, a novel LRR and Ig domain-containing protein (LRRIG), CgLRRIG-3, was identified and characterized from oyster Crassostrea gigas. It contained two typical LRR motifs, a LRRNT motif and an Ig domain and PSI-BALST and phylogeny analysis revealed that the sequence of CgLRRIG-3 was most related with leucine-rich repeat neuronal 1 proteins from vertebrate. Its mRNA transcripts were constitutively expressed in muscle, gill, hepatopancreas, mantle, gonad and hemocytes with the highest level in hepatopancreas. The mRNA expression level of CgLRRIG-3 in hemocytes could respond to the stimulations of variety PAMPs including lipopolysaccharide (LPS), peptidoglycan (PGN), glucan (GLU) and polyinosinic-polycytidylic acid (poly I:C). The recombinant proteins exhibited a wide PAMP binding repertoire to four typical PAMPs and could significantly induce the expression of CgTNF-1 and CgIL17-5 as well as increase phagocytosis in primary cultured oyster hemocytes. In hepatopancreas, CgLRRIG-3 was mainly distributed in the basolateral membrane of digestive tubule and the hemocoel sinusoid between the digestive tubules. And in hemocytes, the positive signal was mainly distributed in a special group of granulocytes. These results collectively indicated that CgLRRIG-3 could not only function as an immune effector.

On-site Method for Beef Detection Based on Strand Exchange Amplification.

Meat screening plays a significant role in human health and religion. But the identification methods for beef were little reported. In this work, a simple colorimetric method based on denaturation bubble-mediated strand exchange amplification (SEA) was developed for the rapid and sensitive identification of beef. The whole strategy was performed on a portable metal bath and the distinguishable color between positive and negative controls was observed directly by the naked eyes. The feasibility using crude extraction samples by a heating treatment in PBS for 2 min was evaluated in duck spiked by beef. The result demonstrated that the developed method could identify as low as 1% (w/w) beef/duck within 50 min. Meanwhile, the results showed the method had a good repeatability and specificity. Therefore, this assay allows for the rapid, sensitive, specific detection of beef, and can be recommended as an effective, promising strategy for on-site meat identification.

Nesfatin-1 and cortisol: potential novel diagnostic biomarkers in moderate and severe depressive disorder.

BACKGROUND: This study aimed to determine whether plasma nesfatin-1, cortisol, and inflammatory cytokines could be used as novel noninvasive biomarkers for the diagnosis of moderate and severe depressive disorder (MSDD). MATERIALS AND METHODS: A total of 70 patients with MSDD and 70 healthy subjects were assessed. Patients with MSDD were selected from Hefei Fourth People's Hospital, Anhui Mental Health Center, and subjects in the control group were selected from healthy volunteers. Hamilton Depression Rating Scale-17 (HAMD-17) was used to evaluate the two groups. ELISA was used for the measurement of plasma nesfatin-1, cortisol, IL-6, C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) levels. The diagnostic value of plasma nesfatin-1, cortisol, IL-6, CRP, and TNF-α for MSDD was assessed. RESULTS: Compared to healthy controls, the HAMD-17 scores and average nesfatin-1, cortisol, IL-6, and CRP levels in patients with MSDD were significantly increased. Moreover, multivariate linear regression analysis showed that HAMD-17 score was positively associated with plasma nesfatin-1 and cortisol. Furthermore, the results of the receiver operating characteristic (ROC) curve analysis revealed an area under curve (AUC) of 0.985 with 94.3% sensitivity and 97.1% specificity of nesfatin-1, and an AUC of 0.957 with 91.4% sensitivity and 85.7% specificity of cortisol in discriminating patients with MSDD from healthy volunteers. A combined ROC analysis using nesfatin-1 and cortisol revealed an AUC of 0.993 with a sensitivity of 97.1% and a specificity of 98.6% in separating patients with MSDD from healthy volunteers. CONCLUSION: These results suggest that plasma nesfatin-1 and cortisol might be potential novel biomarkers for the diagnosis of MSDD.

Draft genome sequence of cyanobacteria Arthrospira sp. TJSD091 isolated from seaside wetland.

The cyanobacteria TJSD091 strain, a member of the genus Arthrospira was isolated from seaside wetland in China, Bohai. The draft genome sequence of Arthrospira sp. TJSD091 with a genome size of approximately 6.3 Mbp and a G+C content of 44.75% is reported.