Conversion therapy of tislelizumab plus lenvatinib and GEMOX in unresectable locally advanced biliary tract cancer (ZSAB-TransGOLP): a multicentre, prospective, phase 2 study.

Background: The optimal conversion regimen that allows more patients with unresectable biliary tract cancer to access surgery remains unclear; there is currently no standard conversion therapy for biliary tract cancer in China, with commonly used regimens including immunotherapy-based combinations and local therapy. The ZSAB-TransGOLP study aimed to assess the efficacy and safety of tislelizumab plus lenvatinib and GEMOX (gemcitabine plus oxaliplatin) chemotherapy (GOLP) in patients with this disease.

Methods: This single-arm, phase 2 study was conducted at two centres in China.

Graft PD-L1 as a predictive marker for rejection in PD-1 inhibitor therapy for recurrent liver tumors post-transplant: A prospective pilot trial.

The safety of immunotherapy in transplant patients remains unclear due to rejection risks. This study assessed the safety and efficacy of programmed death-1 (PD-1) inhibitors in post liver-transplantation patients with recurrent tumors, emphasizing the value of using graft programmed death-ligand 1 (PD-L1) expression as a predictor of rejection to guide patient selection. This single-center, open-label, prospective, single-arm study was conducted from July 2019 to May 2024 at Zhongshan Hospital, Fudan University (Shanghai, China).

First-line tislelizumab and ociperlimab combined with gemcitabine and cisplatin in advanced biliary tract cancer (ZSAB-TOP): a multicenter, single-arm, phase 2 study.

Adding a PD-1/PD-L1 inhibitor to gemcitabine plus cisplatin (GemCis) has shown survival benefits in advanced biliary tract cancer (BTC). Dual inhibition of PD-1/PD-L1 and TIGIT may act synergistically, and further enhance antitumor effects. ZSAB-TOP was a single-arm, multicenter, phase 2 study (NCT05023109) evaluating efficacy and safety of first-line tislelizumab (a PD-1 inhibitor) plus ociperlimab (a TIGIT inhibitor) and GemCis in advanced BTC.

A noninvasive and highly efficient epigenetic predictive model for efficacy of the GOLP regimen in patients with intrahepatic cholangiocarcinoma.

The GOLP regimen (Gemcitabine, Oxaliplatin, Lenvatinib and anti-PD1 antibody) has been a promising first-line treatment for advanced intrahepatic cholangiocarcinoma (iCCA). A noninvasive tool to predict the response to GOLP regimen is needed for clinical practice. In this study, 188 cell-free DNA samples were collected before each cycle and after the third cycle (P0 to P3) from 47 iCCA patients receiving GOLP regimen.

Constraint-following control for follow-up support systems under model deviation and time delay.

Follow-up support technology can flexibly and effectively suppress machining chatter in thin-walled components. This paper proposes a servo collaborative constraint handling scheme that focuses on achieving coordinated control for the follow-up support system under multi-source coupled constraints and uncertainties. Firstly, a four-point constraint method is introduced, which simplifies the description of pose coordination through the introduction of auxiliary points, and constructs the coordinated relationship of the dual robots' end-effectors under complex geometric constraints in an intuitive and analytical manner.

A Novel Primary Cell Line Model of Localized Prostate Cancer and Radioresistance-A Role for Nicotinamide N-Methyltransferase.

Prostate cancer cell lines are particularly clinically homogenous, mostly representing metastatic states rather than localized disease. While there has been significant work in the development of additional models, few have been created without oncogenic transformation. We derived a primary prostate cancer cell line from a patient with localized Gleason 7 prostate cancer-designated CaB34-which spontaneously immortalized.

Lysine-specific demethylase 1 deletion reshapes tumour microenvironment to overcome acquired resistance to anti-programmed death 1 therapy in liver cancer.

Background: Immune checkpoint blockade, particularly targeting programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1), shows promise in treating hepatocellular carcinoma (HCC). However, acquired resistance, especially in patients with 'hot tumours', limits sustained benefits. Lysine-specific demethylase 1 (LSD1) plays a role in converting 'cold tumours' to 'hot tumours', but its involvement in PD-1 inhibitor resistance in HCC is unclear.

Unraveling the Lipidomic Determinants of Atrial Fibrillation: An Extensive Mendelian Randomization Study.

Background: Atrial Fibrillation (AF) is the most prevalent form of cardiac arrhythmia, with a complex etiology that implicates lipid metabolism. This study employs Mendelian Randomization (MR) to dissect the causal relationships between lipidomic profiles and AF, utilizing comprehensive genetic data to clarify these associations.

Methods: Summary statistics for 179 lipid species across 13 classes were retrieved from the GWAS Catalog, encompassing 7,174 Finnish individuals from the GeneRISK study.

Inhibition of IGF-1Rα affects the differentiation fate of rat optic cup-derived retinal stem cells to retinal ganglion cells .

Aim: To explore the impact of insulin-like growth factor-1 receptor α (IGF-1Rα) on the differentiation fate of optic-cup-derived retinal stem cells (OC-RSCs) into retinal ganglion cells (RGCs) .

Methods: OC-RSCs were isolated from optic cups of rats on embryonic day 12.5, and high-purity OC-RSCs were obtained by conditioned culture and passage.

FGFR2 fusion/rearrangement analysis in intrahepatic cholangiocarcinoma using DNA/RNA-based NGS and FISH.

Patients with intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 fusion/rearrangement benefit from targeted therapies, highlighting the need for reliable testing strategies to identify FGFR2 alterations. We assessed 226 iCCA cases using RNA-based NGS, DNA-based NGS, and break-apart FISH to evaluate the effectiveness of these methods in detecting FGFR2 fusion/rearrangement. The detection rates for FGFR2 fusion/rearrangement were 9.

The antibacterial efficacy of nitroxoline against multidrug resistant Escherichia coli associated with copper binding.

Nitroxoline (NIT) has been approved for the treatment of uncomplicated urinary tract infections (UTIs) for more than half a century, yet its antimicrobial properties remain incompletely understood. Here, we determined the intricate connections between NIT's metal-chelating capabilities and its antibacterial activity. Metal ion binding characteristics were measured by Ultraviolet-visible (UV-vis) spectroscopy.

Copper(II) enhances the antibacterial activity of nitroxoline against MRSA by promoting aerobic glycolysis.

Nitroxoline (NIT) is an FDA-approved antibiotic with numerous pharmacological properties. However, the intricate connections between its metal-chelating ability and antimicrobial efficacy remain incompletely understood. The specific interactions of NIT with different metal ions were measured via UV-vis absorption spectroscopy.

CaLuScAlSiO:Ce Green Phosphors for High-Quality White LEDs.

Phosphors with broadband green emission are highly desirable for the construction of high-color-rendering warm-white light-emitting diode (LED) devices toward healthy solid-state lighting applications. However, most of the reported green phosphors are subject to an undesirable emission bandwidth and low quantum efficiency. Here, a highly efficient broadband green-emitting garnet phosphor, CaLuScAlSiO:Ce (CLSASO:Ce), is successfully synthesized and investigated in detail.

Accelerated growth and local progression of radiorecurrent prostate cancer in an orthotopic bioluminescent mouse model.

Globally, prostate cancer is the second most common malignancy in males, with over 400 thousand men dying from the disease each year. A common treatment modality for localized prostate cancer is radiotherapy. However, up to half of high-risk patients can relapse with radiorecurrent prostate cancer, the aggressive clinical progression of which remains severely understudied.

Full-Visible-Spectrum White LEDs Enabled by a Blue-Light-Excitable Cyan Phosphor.

Efficient blue-light-excitable broadband cyan-emitting phosphors may yield full-visible-spectrum white light-emitting diodes (WLEDs) with ultrahigh color rendering (Ra > 95). However, this requires closing the "cyan gap" in the 480-520 nm region of the visible spectrum, which is challenging. Herein, a well-performed cyan-emitting garnet phosphor CaLuAlGaSiO:Ce (CLAGSO:Ce) is reported.

Logistic regression model for predicting risk factors and contribution of cerebral microbleeds using renal function indicators.

Background: The brain and kidneys share similar low-resistance microvascular structures, receiving blood at consistently high flow rates and thus, are vulnerable to blood pressure fluctuations. This study investigates the causative factors of cerebral microbleeds (CMBs), aiming to quantify the contribution of each risk factor by constructing a multivariate model via stepwise regression.

Methods: A total of 164 hospitalized patients were enrolled from January 2022 to March 2023 in this study, employing magnetic susceptibility-weighted imaging (SWI) to assess the presence of CMBs.

Potentiating Salvage Radiotherapy in Radiorecurrent Prostate Cancer Through Anti-CTLA4 Therapy: Implications from a Syngeneic Model.

High-risk prostate cancer (PCa) is a leading cause in cancer death and can elicit significant morbidity and mortality. Currently, the salvage of local disease recurrence after radiation therapy (RT) is a major clinical problem. Immune checkpoint inhibitors (ICIs), which enhance immune activation, have demonstrated clinical therapeutic promise in combination with ionizing radiation (IR) in certain advanced cancers.

Targeting PLOD2 suppresses invasion and metastatic potential in radiorecurrent prostate cancer.

Background: Metastatic relapse of prostate cancer after radiotherapy is a significant cause of prostate cancer-related morbidity and mortality. PLOD2 is a mediator of invasion and metastasis that we identified as being upregulated in our highly aggressive radiorecurrent prostate cancer cell line.

Methods: Patient dataset analysis was conducted using a variety of prostate cancer cohorts.

Zn(II) enhances the antimicrobial effect of chloroxine and structural analogues against drug-resistant ESKAPE pathogens in vitro.

The emerging antibiotic-resistant bacteria, especially the "ESKAPE" pathogens, pose a continuous threat to global health. In this study, we explored metalloantibiotics as promising therapeutics and innovative antimicrobial agents. The role of metal in the antimicrobial activity of chloroxine (5,7-dichloro-8-hydroxyquinoline), as a metalloantibiotic, was investigated by minimal inhibit concentration (MIC) assay and a series of assays, including growth curve, time-killing, and UV-visible spectroscopy and PAR (4-(2-pyridylazo)-resorcinol) competition assays.

Prenatal Inflammatory Exposure Predisposes Offspring to Chronic Kidney Diseases Via the Activation of the eIF2α-ATF4 Pathway.

It has recently become more recognized that renal diseases in adults can originate from adverse intrauterine (maternal) environmental exposures. Previously, we found that prenatal lipopolysaccharide (LPS) exposure can result in chronic renal inflammation, which leads to renal damage in older offspring rats. To test whether prenatal inflammatory exposure predisposes offspring to renal damage, a mouse model of oral adenine consumption-induced chronic kidney disease (CKD) was applied to offspring from prenatal LPS-treated mothers (offspring-pLPS) and age-matched control offspring of prenatal saline-treated mothers (offspring-pSaline).

Ce-Activated SrLuAlScSiO Cyan-Green-Emitting Garnet-Structured Inorganic Phosphor Materials toward Application in Blue-Chip-Based Phosphor-Converted Solid-State White Lighting.

Phosphor-converted white-light-emitting diodes (WLEDs) with superhigh color rendering index (CRI) are the ongoing pursuit of next-generation solid-state lighting. One of the most important challenges is the limited improvement in CRI on account of the absence of a cyan component in the typical commercial combination. Here, a bright broad-band cyan-green-emitting phosphor with cubic garnet structure, SrLuAlScSiO:Ce (SLASSO:Ce), was successfully reported, which can compensate for the absence of cyan cavity in the 480-520 nm blue-green emission region.

Targeting S100A9 Prevents β-Adrenergic Activation-Induced Cardiac Injury.

Altered cardiac innate immunity is highly associated with the progression of cardiac disease states and heart failure. S100A8/A9 is an important component of damage-associated molecular patterns (DAMPs) that is critically involved in the pathogenesis of heart failure, thus considered a promising target for pharmacological intervention. In the current study, initially, we validated the role of S100A8/A9 in contributing to cardiac injury and heart failure via the overactivation of the β-adrenergic pathway and tested the potential use of paquinimod as a pharmacological intervention of S100A8/A9 activation in preventing cardiac dysfunction, collagen deposition, inflammation, and immune cell infiltration in β-adrenergic overactivation-mediated heart failure.