Metabolic shifts in tryptophan pathways during acute pancreatitis infections.

Infectious complications (ICs) in acute pancreatitis (AP) are primarily driven by intestinal bacterial translocation, significantly increasing mortality and hospital stays. Despite this, the role of the gut microenvironment, particularly its metabolic aspects, in AP remains poorly understood. In this study, we investigated a cohort of patients with AP, and conducted supplemental murine studies, to explore the relationship between the gut metabolome and the development of ICs.

Risk factors for bloodstream infection among patients admitted to an intensive care unit of a tertiary hospital of Shanghai, China.

Blood flow infections (BSIs) is common occurrences in intensive care units (ICUs) and are associated with poor prognosis. The study aims to identify risk factors and assess mortality among BSI patients admitted to the ICU at Shanghai Ruijin hospital north from January 2022 to June 2023. Additionally, it seeks to present the latest microbiological isolates and their antimicrobial susceptibility.

Bile acid profiling as an effective biomarker for staging in pediatric inflammatory bowel disease.

Rapid and accurate clinical staging of pediatric patients with inflammatory bowel disease (IBD) is crucial to determine the appropriate therapeutic approach. This study aimed to identify effective, convenient biomarkers for staging IBD in pediatric patients. We recruited cohorts of pediatric patients with varying severities of IBD to compare the features of the intestinal microbiota and metabolites between the active and remitting disease stages.

Systematic identification and characterization of five transcription factors mediating the oxidative stress response in Candida albicans.

Candida albicans is an opportunistic human fungal pathogen that causes superficial and systemic infections, particularly in immunocompromised individuals. In response to C. albicans infection, innate immune cells of the host produce and accumulate reactive oxygen species (ROS), which can lead to irreversible damage and apoptosis of fungal cells.

The regulatory subunits of CK2 complex mediate DNA damage response and virulence in Candida Glabrata.

Background: Candida glabrata which belongs to normal microbiota, has caused significant concern worldwide due to its high prevalence and drug resistance in recent years. C. glabrata has developed many strategies to evade the clearance of the host immune system, thereby causing persistent infection.

TCR T cells overexpressing c-Jun have better functionality with improved tumor infiltration and persistence in hepatocellular carcinoma.

Background: The overall 5-year survival rate of hepatocellular carcinoma (HCC), a major form of liver cancer, is merely 20%, underscoring the need for more effective therapies. We recently identified T cell receptors (TCR) specific for the HLA-A2/alpha fetoprotein amino acids 158-166 (AFP) and showed that these TCR engineered T cells could control HCC xenografts in NSG mice. However, their efficacy was limited by poor expansion, loss of function, and short persistence of the TCR T cells.

Altered intestinal microbiome and metabolome correspond to the clinical outcome of sepsis.

Background: The gut microbiome plays a pivotal role in the progression of sepsis. However, the specific mechanism of gut microbiota and its metabolites involved in the process of sepsis remains elusive, which limits its translational application.

Method: In this study, we used a combination of the microbiome and untargeted metabolomics to analyze stool samples from patients with sepsis enrolled at admission, then microbiota, metabolites, and potential signaling pathways that might play important roles in disease outcome were screened out.

aggravates dextran sulfate solution (DSS)-induced colitis by shaping the gut microbiota and promoting neutrophil recruitment.

is a pathogen contributing to increased morbidity and mortality of patients with inflammatory bowel disease (IBD). To determine how affects the severity of colitis, we constructed a dextran sulfate solution-induced colitis model challenged with . Without antibiotic administration, led to transient colonization in mice with colitis, but still significantly enhanced disease severity as assessed by weight loss, histopathological damages, and inflammatory cytokine concentrations.

Diagnostic Efficacy of T-SPOT.TB for Active Tuberculosis in Adult: A Retrospective Study.

Purpose: To explore the diagnostic efficacy and optimal diagnosis threshold of T-SPOT.TB for active tuberculosis in adults and to evaluate the influential factors for T-SPOT.TB results.

A dual action small molecule enhances azoles and overcomes resistance through co-targeting Pdr5 and Vma1.

Fungal infection threatens human health worldwide due to the limited arsenal of antifungals and the rapid emergence of resistance. Epidermal growth factor receptor (EGFR) is demonstrated to mediate epithelial cell endocytosis of the leading human fungal pathogen, Candida albicans. However, whether EGFR inhibitors act on fungal cells remains unknown.

Complete Genome Sequencing and Comparative Phenotypic Analysis Reveal the Discrepancy Between ST81 and ST37 Isolates.

Toxin A-negative, toxin B-positive strains, which primarily include the ST81 and ST37 genotypes, are predominant in infections leading to antibiotic-associated diarrhea in China. Recently, ST81 has been reported as the most prevalent genotype rather than ST37, although the genetic and functional characteristics of the two genotypes remain ambiguous. In this study, we conducted comprehensive comparative analysis of these two genotypes through complete genome sequencing and phenotypic profiling.

Novel low-avidity glypican-3 specific CARTs resist exhaustion and mediate durable antitumor effects against HCC.

Background And Aims: Chimeric antigen receptor engineered T cells (CARTs) for HCC and other solid tumors are not as effective as they are for blood cancers. CARTs may lose function inside tumors due to persistent antigen engagement. The aims of this study are to develop low-affinity monoclonal antibodies (mAbs) and low-avidity CARTs for HCC and to test the hypothesis that low-avidity CARTs can resist exhaustion and maintain functions in solid tumors, generating durable antitumor effects.

Fingolimod Potentiates the Antifungal Activity of Amphotericin B.

() is an opportunistic human fungal pathogen that can cause severe infection in clinic. Its incidence and mortality rate has been increasing rapidly. Amphotericin B (AMB), the clinical golden standard antifungal agent, has severe side effects that limit its clinical application.

High Dose Intravenous Vitamin C for Preventing The Disease Aggravation of Moderate COVID-19 Pneumonia. A Retrospective Propensity Matched Before-After Study.

Coronavirus disease 2019 (COVID-19) pandemic is continuing to impact multiple countries worldwide and effective treatment options are still being developed. In this study, we investigate the potential of high-dose intravenous vitamin C (HDIVC) in the prevention of moderate COVID-19 disease aggravation. In this retrospective before-after case-matched clinical study, we compare the outcome and clinical courses of patients with moderate COVID-19 patients who were treated with an HDIVC protocol (intravenous injection of vitamin C, 100 mg/kg/day, 1 g/h, for 7 days from admission) during a one-month period (between March 18 and april 18, 2020, HDIVC group) with a control group treated without the HDIVC protocol during the preceding two months (January 18 to March 18, 2020).

Repurposing the FDA-approved anticancer agent ponatinib as a fluconazole potentiator by suppression of multidrug efflux and Pma1 expression in a broad spectrum of yeast species.

Fungal infections have emerged as a major global threat to human health because of the increasing incidence and mortality rates every year. The emergence of drug resistance and limited arsenal of antifungal agents further aggravates the current situation resulting in a growing challenge in medical mycology. Here, we identified that ponatinib, an FDA-approved antitumour drug, significantly enhanced the activity of the azole fluconazole, the most widely used antifungal drug.

Optimal Fractional-Order Active Disturbance Rejection Controller Design for PMSM Speed Servo System.

In this paper, a fractional-order active disturbance rejection controller (FOADRC), combining a fractional-order proportional derivative (FOPD) controller and an extended state observer (ESO), is proposed for a permanent magnet synchronous motor (PMSM) speed servo system. The global stable region in the parameter (, )-space corresponding to the observer bandwidth ωo can be obtained by D-decomposition method. To achieve a satisfied tracking and anti-load disturbance performance, an optimal ADRC tuning strategy is proposed.

Optimal robust fractional order PID controller synthesis for first order plus time delay systems.

In this paper, a practical and systematic tuning procedure combining both frequency-domain (FD) and time-domain (TD) specifications is proposed to obtain an optimal robust fractional order (FO) PID (FOPID) controller for the first order plus time delay (FOPTD) processes. The FD specifications (i.e.

Beneficial aspects of high dose intravenous vitamin C on patients with COVID-19 pneumonia in severe condition: a retrospective case series study.

Background: Coronavirus disease 2019 (COVID-19) is a global public health event without specific therapeutic agents till now. We aim to determine if high dose intravenous vitamin C (HDIVC) was effective for COVID-19 patients in severe condition.

Methods: COVID-19 patients admitted in Shanghai Public Health Clinical Center from January 22, 2020 to April 11, 2020 were retrospectively scrolled.

Comprehensive Exome Analysis of Immunocompetent Metastatic Head and Neck Cancer Models Reveals Patient Relevant Landscapes.

Immunocompetent metastatic head and neck cancer (HNC) models, although scarce, can help understanding cancer progression and therapy responses in vivo. Their comprehensive genome characterizations are essential for translational research. We first exome-sequenced the two most widely used spontaneous metastatic immunocompetent models, namely AT-84 and SCC VII, followed by comprehensive genomic analyses with three prior-sequenced models (MOC2, MOC2-10, and 4MOSC2), together with patient tumors for utility assessment.

Synergistic Effect of Pseudolaric Acid B with Fluconazole Against Resistant Isolates and Biofilm of .

Purpose: Candida tropicalis () has emerged as an important fungal pathogen due to its increasing resistance to conventional antifungal agents, especially fluconazole (FLC). Pseudolaric acid B (PAB), a herbal-originated diterpene acid from Pseudolarix kaempferi Gordon, has been reported to possess inhibitory activity against fungus. The present study aims to investigate the antifungal effect of PAB alone and in combination with FLC on planktonic and biofilm cells of .

Risk factors and intestinal microbiota: Clostridioides difficile infection in patients receiving enteral nutrition at Intensive Care Units.

Background: Clostridioides difficile infection (CDI) is a leading cause of nosocomial diarrhea. Patients receiving enteral nutrition (EN) in the intensive care unit (ICU) are potentially at high risk of CDI. In the present study, we assessed the risk factors and intestinal microbiome of patients to better understand the occurrence and development of CDI.

FDA Approved Drug Library Screening Identifies Robenidine as a Repositionable Antifungal.

Due to the increasing prevalence of pathogenic fungal infections, the emergence of antifungal resistant clinical isolates worldwide, and the limited arsenal of available antifungals, developing new antifungal strategies is imperative. In this study, we screened a library of 1068 FDA-approved drugs to identify hits that exhibit broad-spectrum antifungal activity. Robenidine, an anticoccidial agent which has been widely used to treat coccidian infections of poultry and rabbits, was identified in this screen.

Preclinical Studies of the Off-Target Reactivity of AFP-Specific TCR Engineered T Cells.

Autologous T cells engineered with T receptor genes (TCR) are being studied to treat cancers. We have recently identified a panel of mouse TCRs specific for the HLA-A0201/alpha fetoprotein epitope (AFP) complex and have shown that human T cells engineered with these TCR genes (TCR-Ts) can eradicate hepatocellular carcinoma (HCC) xenografts in NSG mice. However, due to TCR's promiscuity, their off-target cross-reactivity must be studied prior to conducting clinical trials.