The prognostic value of anti-gp210 and anti-centromere antibodies in patients with primary biliary cholangitis: Enhancing the prognostic utility on the GLOBE scoring system.

Background: Positivity for anti-gp210 and anti-centromeric antibodies (ACA) in patients with primary biliary cholangitis (PBC) have been associated with the progression of liver failure and portal hypertension (PH), respectively. The value of combining risk autoantibody assessments with prognostic scoring systems in improving risk assessment in patients with PBC remains unclear.

Aims: To investigate the prognostic significance of various combinations of anti-gp210 and ACA statuses and their enhancing the prognostic utility on the GLOBE scoring system.

Core-shell vector-mediated co-delivery of CRISPR/Cas9 system and hydrophobic drugs against triple-negative breast cancer stem cells.

Cancer stem cells (CSCs) play an important role in the development of triple-negative breast cancer (TNBC), including metastasis, invasion, tumorigenicity, and drug resistance. Moreover, non-CSCs can spontaneously transform into CSCs in special tumor microenvironments, thereby leading to poor prognosis or even failed treatments. Therefore, reversing CSCs into normal tumor cells in a sustained-acting manner is a promising strategy.

Does amide proton transfer-weighted MRI have diagnostic and differential value in ovarian cystic and predominantly cystic lesion?

Objectives: This study aims to evaluate the diagnostic value of amide proton transfer-weighted (APTw) imaging in distinguishing cystic or predominantly cystic ovarian lesions.

Materials And Methods: 49 patients underwent APTw imaging at 3T-MR before surgery, with 20 volunteers serving as the control group. Participants were divided into the following groups: solid components of normal ovaries (Group A, n = 29), solid components of malignant lesions (Group B, n = 7), cystic fluid of follicles (Group C, n = 31), cystic fluid of benign lesions (Group D, n = 46), functional cysts (Group d1, n = 8), endometriomas (Group d2, n = 28), cystadenomas (Group d3, n = 10), and cystic fluid of malignant lesions (Group E, n = 12).

Simulation and Prediction of Springback in Sheet Metal Bending Process Based on Embedded Control System.

Amidst the accelerating pace of automation in sheet metal bending, the need for small-batch, multi-varietal, efficient, and adaptable production modalities has become increasingly pronounced. To address this need and to enhance the efficacy of the bending process, this study presents the design and development of an embedded soft PLC (Programmable Logic Controller) rooted in the Codesys development platform and leveraging the ARM Cortex-A55 architecture. This controller employs the EtherCAT communication protocol to facilitate seamless and efficient interactions with fully electric servo-driven CNC (Computerized Numerical Control) bending machinery.

Low-risk individuals with primary biliary cholangitis and significant liver stiffness: prognosis and treatment.

Background: Some patients treated with ursodeoxycholic acid (UDCA) or combined fenofibrate had well-controlled biochemical parameters but high liver stiffness, and the prognosis as well as therapeutic options for these patients may be an area worthy of further exploration.

Aims: To explore the prognosis and treatment of patients with low-risk and high liver stiffness.

Methods: A retrospective study included 424 cases of UDCA monotherapy and 102 cases of combined fenofibrate treatment.

Surveillance and management of hepatocellular carcinoma after treatment of hepatitis C with direct-acting antiviral drugs.

Hepatitis C virus (HCV) belongs to the Flaviviridae family, and is a single-stranded RNA virus with positive polarity. It is the primary cause of hepatocellular carcinoma (HCC) worldwide. The treatment of HCV has entered a new era with the advent of direct-acting antiviral drugs (DAAs) and is associated with cure rates of more than 95 %, making HCV the only curable viral disease.

Prescribed Fixed-Time Control for Constrained Uncertain Nonlinear Cyber-Physical Systems Against Deception Attacks.

In this note, a novel prescribed fixed-time adaptive tracking control scheme is developed to cope with the fixed-time tracking control issue for a category of constrained MIMO nonlinear cyber-physical systems (CPSs) with exogenous perturbations, which suffer from deception attacks started in controller-actuator (C-A) channel. Distinguished from the conservative dynamic surface control (DSC) schemes with a linear filter, a novel nonlinear filter is designed in our strategy, which can tackle the intrinsic issue of explosion of computational complexity and promote the system performance. Besides, a new barrier Lyapunov function (BLF) is designed to ulteriorly enhance the tracking performance on the basis of the prescribed performance function (PPF) approach.

Error-controlled adaptive machining of aeronautical cabin structures by laser triangulation on-machine measurement.

Laser Triangulation On-Machine Measurement (LTOMM) is being implemented increasingly to inspect aeronautical components accurately and efficiently, with its enhanced application in adaptive machining. This work proposes an error compensation and controlling method for measuring the typical features of steps, holes, and freeform surfaces to improve accuracy. Then, the global path to inspect the cabin's structures is planned by introducing optimization algorithms, thus providing an appropriate sequence to shorten the traveling length.

Glucocorticoid efficacy and treatment strategies for drug-induced liver injury: a literature review.

Drug-induced liver injury (DILI) is an adverse reaction to drugs and their metabolites. The activation of adaptive immune and inflammatory responses plays an important role in the pathogenesis of DILI. Glucocorticoids (GCs) have powerful anti-inflammatory and immunosuppressive effects and have been used to treat a variety of immune-mediated liver diseases.

A knowledge-enhanced interpretable network for early recurrence prediction of hepatocellular carcinoma via multi-phase CT imaging.

Background: Predicting early recurrence (ER) of hepatocellular carcinoma (HCC) accurately can guide treatment decisions and further enhance survival. Computed tomography (CT) imaging, analyzed by deep learning (DL) models combining domain knowledge, has been employed for the prediction. However, these DL models utilized late fusion, restricting the interaction between domain knowledge and images during feature extraction, thereby limiting the prediction performance and compromising decision-making interpretability.

Pharmacokinetics, mass balance, and metabolism of [C]envonalkib (TQ-B3139), a novel ALK tyrosine kinase inhibitor, in healthy Chinese subjects.

Purpose: Envonalkib (TQ-B3139) is a novel, potent anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor used to treat ALK-positive non-small cell lung cancer. This phase I mass balance study investigated the pharmacokinetics, metabolism, and excretion of C-radiolabeled envonalkib in healthy Chinese male subjects.

Methods: A single oral dose of 600 mg (150 µCi) [C]envonalkib was administered to healthy male subjects under fasted state.

Enhancing photodynamic immunotherapy by reprograming the immunosuppressive tumor microenvironment with hypoxia relief.

Tumor hypoxia impairs the generation of reactive oxygen species and the induction of immunogenic cell death (ICD) for photodynamic therapy (PDT), thus impeding its efficacy and the subsequent immunotherapy. In addition, hypoxia plays a critical role in forming immunosuppressive tumor microenvironments (TME) by regulating the infiltration of immunosuppressive tumor-associated macrophages (TAMs) and the expression of programmed death ligand 1 (PD-L1). To simultaneously tackle these issues, a MnO-containing albumin nanoplatform co-delivering IR780, NLG919, and a paclitaxel (PTX) dimer is designed to boost photodynamic immunotherapy.

Observation of an isothermal glass transition in metallic glasses.

Glass transition, commonly manifested upon cooling a liquid, is continuous and cooling rate dependent. For decades, the thermodynamic basis in liquid-glass transition has been at the center of debate. Here, long-time isothermal annealing was conducted via molecular dynamics simulations for metallic glasses to explore the connection of physical aging in supercooled liquid and glassy states.

Recent Advances of Tumor Microenvironment-Responsive Nanomedicines-Energized Combined Phototherapy of Cancers.

Photodynamic therapy (PDT) has emerged as a powerful tumor treatment tool due to its advantages including minimal invasiveness, high selectivity and thus dampened side effects. On the other side, the efficacy of PDT is severely frustrated by the limited oxygen level in tumors, thus promoting its combination with other therapies, particularly photothermal therapy (PTT) for bolstered tumor treatment outcomes. Meanwhile, nanomedicines that could respond to various stimuli in the tumor microenvironment (TME) provide tremendous benefits for combined phototherapy with efficient hypoxia relief, tailorable drug release and activation, improved cellular uptake and intratumoral penetration of nanocarriers, etc.

Prognostic significance of liver stiffness in patients with primary biliary cholangitis: validation of Baveno VII criteria.

Background: The role of liver stiffness measurements (LSM) in patients with primary biliary cholangitis (PBC) remains to be further elucidated.

Aims: To clarify the prognostic role of LSM and to validate the "novel concepts" proposed by the Baveno VII Working Group.

Methods: An analysis of the prognostic significance of LSM was performed involving 672 patients.

Steerable Microneedles Enabling Deep Delivery of Photosensitizers and CRISPR/Cas9 Systems for Effective Combination Cancer Therapy.

Although gene therapy has shown prospects in treating triple-negative breast cancer, it is insufficient to treat such a malignant tumor. Herein, nanoparticles (NPs)-embedded dissolving microneedles (IR780-PL/pFBXO44@MNs) with steerable and flectional property were developed to achieve the codelivery of FBXO44-targeted CRISPR/Cas9 plasmids (pFBXO44) and hydrophobic photosensitizers. For improved NP penetration in tumor tissue, collagenase@MNs were preapplied to degrade the tumor matrix.

Controllable hypoxia-activated chemotherapy as a dual enhancer for synergistic cancer photodynamic immunotherapy.

The efficacy of photodynamic therapy (PDT) is severely limited by the hypoxic tumor microenvironment (TME), while the performance of PDT-aroused antitumor immunity is frustrated by the immunosuppressive TME and deficient immunogenic cell death (ICD) induction. To simultaneously tackle these pivotal problems, we herein create an albumin-based nanoplatform co-delivering IR780, NLG919 dimer and a hypoxia-activated prodrug tirapazamine (TPZ) as the dual enhancer for synergistic cancer therapy. Under NIR irradiation, IR780 generates O for PDT, which simultaneously cleaves the ROS-sensitive linker for triggered TPZ release, and activates its chemotherapy via exacerbated tumor hypoxia.

Iron deposition in ovarian endometriosis evaluated by magnetic resonance imaging R2* correlates with ovarian function.

Research Question: Does iron overload in patients with endometriosis affect ovarian function? Can a method be developed to visually reflect this?

Design: Magnetic resonance imaging (MRI) R2* was used to evaluate the correlation between iron deposition of ovarian and anti-Müllerian hormone (AMH) in patients with endometriosis. All patients underwent T2* MRI scanning. Serum AMH levels were measured preoperatively.

Reactive oxygen species-powered cancer immunotherapy: Current status and challenges.

Reactive oxygen species (ROS) are crucial signaling molecules that can arouse immune system. In recent decades, ROS has emerged as a unique therapeutic strategy for malignant tumors as (i) it can not only directly reduce tumor burden but also trigger immune responses by inducing immunogenic cell death (ICD); and (ii) it can be facilely generated and modulated by radiotherapy, photodynamic therapy, sonodynamic therapy and chemodynamic therapy. The anti-tumor immune responses are, however, mostly downplayed by the immunosuppressive signals and dysfunction of effector immune cells within the tumor microenvironment (TME).

Quantum Instruction Set Design for Performance.

A quantum instruction set is where quantum hardware and software meet. We develop characterization and compilation techniques for non-Clifford gates to accurately evaluate its designs. Applying these techniques to our fluxonium processor, we show that replacing the iSWAP gate by its square root SQiSW leads to a significant performance boost at almost no cost.

Distinct relaxation mechanism at room temperature in metallic glass.

How glasses relax at room temperature is still a great challenge for both experimental and simulation studies due to the extremely long relaxation time-scale. Here, by employing a modified molecular dynamics simulation technique, we extend the quantitative measurement of relaxation process of metallic glasses to room temperature. Both energy relaxation and dynamics, at low temperatures, follow a stretched exponential decay with a characteristic stretching exponent β = 3/7, which is distinct from that of supercooled liquid.

Fenofibrate normalizes alkaline phosphatase and improves long-term outcomes in patients with advanced primary biliary cholangitis refractory to ursodeoxycholic acid.

Background: Although patients with advanced liver disease have been included in studies evaluating fibrates for the treatment of primary biliary cholangitis (PBC), the frequency of biochemical responses and adverse effects for this group of patients was not reported separately and comprehensively.

Aims: to evaluate the efficacy and safety of additional fenofibrate therapy in patients with advanced and ursodeoxycholic acid (UDCA)-refractory PBC.

Methods: Patients were analyzed retrospectively to determine the clinical therapeutic effects of UDCA with additional fenofibrate therapy versus continued UDCA monotherapy.

A multi-scale, multi-region and attention mechanism-based deep learning framework for prediction of grading in hepatocellular carcinoma.

Background: Histopathological grading is a significant risk factor for postsurgical recurrence in hepatocellular carcinoma (HCC). Preoperative knowledge of histopathological grading could provide instructive guidance for individualized treatment decision-making in HCC management.

Purpose: This study aims to develop and validate a newly proposed deep learning model to predict histopathological grading in HCC with improved accuracy.

Photoclick and Release: Co-activation of Carbon Monoxide and a Fluorescent Self-reporter, COS or Sulfonamide with Fast Kinetics.

Bioorthogonal prodrugs with both fast reaction kinetics and multiple outputs are highly desirable but are only found sporadically. Herein, we report a novel photoclick-and-release strategy for the co-activation of carbon monoxide and a self-reporter, carbonyl sulfide, or sulfonamide with fast reaction kinetics (k: 1.4-22.