Progress in Lactate Metabolism and Its Regulation via Small Molecule Drugs.

Lactate, once viewed as a byproduct of glycolysis and a metabolic "waste", is now recognized as an energy-providing substrate and a signaling molecule that modulates cellular functions under pathological conditions. The discovery of histone lactylation in 2019 marked a paradigm shift, with subsequent studies revealing that lactate can undergo lactylation with both histone and non-histone proteins, implicating it in the pathogenesis of various diseases, including cancer, liver fibrosis, sepsis, ischemic stroke, and acute kidney injury. Aberrant lactate metabolism is associated with disease onset, and its levels can predict disease outcomes.

Immunomodulatory potential of primary cilia in the skin.

Primary cilia (PC) are essential signaling hubs for proper epithelial formation and the maintenance of skin homeostasis. Found on most cells in the human body, including skin cells, PC facilitate signal transduction that allows ciliated cells to interact with the immune system via multiple pathways, helping to maintain immune system homeostasis. PC can be altered by various microenvironmental stimuli to develop corresponding regulatory functions.

Epstein-Barr virus infection upregulates extracellular OLFM4 to activate YAP signaling during gastric cancer progression.

Extracellular vesicles (EVs) are known to mediate cell communications and shape tumor microenvironment. Compared to the well-studied small EVs, the function of large microvesicles (MVs) during tumorigenesis is poorly understood. Here we show the proteome of MVs in Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC), and identify olfactomedin 4 (OLFM4) is induced by EBV infection and secreted via MVs to promote tumor progression through Hippo signaling.

Brief communication: efficacy and safety of the dolutegravir/lamivudine dual therapy in antiretroviral treatment-experienced Chinese people living with HIV.

This study aimed to evaluate the efficacy and safety of dolutegravir plus lamivudine (DTG/3TC) in antiretroviral treatment (ART)-experienced people living with HIV (PLWH). A total of 303 PLWH in Shanghai, China, who switched from triple ART to DTG/3TC between January 2019 and June 2022, with a minimum ART duration of 6 months, were retrospectively enrolled. More than 95% of PLWH maintained viral suppression with no significant changes in CD4 counts 12 months after switching.

β-cyclodextrin-modified carboxymethyl chitosan/hyaluronic acid-based crosslinked composite nanogels as a dual responsive carrier for targeting anti-tumor therapy.

Advanced nanosized drug delivery systems can significantly improve efficacy and safety of first-line chemotherapeutics by enhancing tumor targeting. Herein, one-pot covalent crosslinking approach was developed to generate biodegradable tumor-targeted composite Nanogels from carboxymethyl chitosan, hyaluronic acid, cystamine and 6-ethylene-diamine-6-deoxy-β-cyclodextrin loaded with doxorubicin (DOX) for controlled intracellular DOX release. The optimized synthetic procedures generated Nanogels of about 190 nm in size and 28.

Event-Triggered Attitude Consensus of Multiple Rigid Body Systems With Prescribed Performance.

The event-triggered almost global attitude consensus problem is considered in this article for multiple rigid body systems with prescribed performance. Two kinds of attitude consensus protocols using axis-angle vectors are proposed at the kinematic level with different prescribed performance constraints. The first protocol aims to achieve the event-triggered attitude consensus almost globally under jointly connected graphs.

In Situ Nanoconfinement Catalysis for Highly Efficient Redox Transformation.

The rapid reduction of Cr(VI) across a wide pH range, from acidic to alkaline pH conditions to stable Cr(III) species for efficient remediation of Cr(VI) pollution, has long been a challenge. Herein, we propose a new concept of nanoconfinement catalysis (NCC) for highly efficient remediation of Cr(VI) by growing nanosheets of layered double hydroxide (LDH) on the surface of Al-Mg-Fe alloy achieving chemical reduction rates of >99% in 1 min from pH 3 to 11 for 100 mg L Cr(VI) with a rate constant of 201 h. In stark contrast, the reduction rate is less than 6% in 12 h with a rate constant of 0.

Effect of Eu Ions Concentration in YO-Based Transparent Ceramics on the Electron Irradiation Induced Luminescence and Damage.

Eu-doped YO-based luminescent materials can be used as a scintillator for electron or high energy β-ray irradiation, which are essential for applications such as electron microscopy and nuclear batteries. Therefore, it is essential to understand their defect mechanisms and to develop materials with excellent properties. In this paper, YO-based transparent ceramics with different Eu doping concentrations were prepared by solid-state reactive vacuum sintering.

Antibiotic resistance and resistome risks of inhalable bioaerosols at aeration tank of a full-scale wastewater treatment plant.

Antibiotic resistome could be aerosolized under wastewater aeration processes, however, their seasonal variation, mobility, hosts, aerosolization behavior, and risk, are largely unknown. Herein, the antibiotic resistant pollution associated with fine particulate matter (PM) from the actual aeration tank (AerT), was analyzed using metagenomic assembly. The antibiotic resistance of AerT-PM was characterized by significant seasonality.

A retrospective comparison of induction chemoimmunotherapy versus chemotherapy followed by concurrent chemoradiotherapy and consolidation immunotherapy in stage III non-small cell lung cancer.

Background: Patients with locally advanced non-small cell lung cancer (LA-NSCLC) usually bear high tumor burden and are not tolerated well to concurrent chemoradiation therapy (CRT) followed by consolidation immunotherapy. We investigated the feasibility of chemoimmunotherapy as induction therapy before CRT for LA-NSCLC.

Methods: We retrospectively analyzed data from 91 patients with unresectable stage III NSCLC treated with either induction chemoimmunotherapy or chemotherapy before CRT.

Energy transfer-mediated multiphoton synergistic excitation for selective C(sp)-H functionalization with coordination polymer.

Activation and selective oxidation of inert C(sp)-H bonds remain one of the most challenging tasks in current synthetic chemistry due to the inherent inertness of C(sp)-H bonds. In this study, inspired by natural monooxygenases, we developed a coordination polymer with naphthalenediimide (NDI)-based ligands and binuclear iron nodes. The mixed-valence FeFe species and chlorine radicals (Cl) are generated via ligand-to-metal charge transfer (LMCT) between Fe and chlorine ions.

Airborne antibiotic resistome from sludge dewatering systems: Mobility, pathogen accessibility, cross-media migration propensity, impacting factors, and risks.

Bioaerosol contamination was considered as a potential health threat in sludge dewatering systems (SDSs), while emission and risk of airborne antibiotic resistome remain largely unclear. Herein, seasonal investigations of fine particulate matter (PM) were conducted using metagenomics-based methods within and around different SDSs, together with an analysis of sewage sludge. Featured with evident seasonality, antibiotic resistance genes (ARGs) in SDS-PM also possessed greater accumulation, transfer, and pathogen accessibility than those in ambient air PM.

A cofactor-induced repressive type of transcription factor condensation can be induced by synthetic peptides to suppress tumorigenesis.

Transcriptional factors (TFs) act as key determinants of cell death and survival by differentially modulating gene expression. Here, we identified many TFs, including TEAD4, that form condensates in stressed cells. In contrast to YAP-induced transcription-activating condensates of TEAD4, we found that co-factors such as VGLL4 and RFXANK alternatively induced repressive TEAD4 condensates to trigger cell death upon glucose starvation.

Leader Selection in Impulsive Multiagent Systems With Switching Topologies.

In leader-follower multiagent systems (MASs), seeking an efficient scheme to select a set of agents as leaders is important for realizing the expected cooperative performance. In this article, the problem of minimal leader selection is investigated for impulsive general linear MASs with switching topologies. This study focuses on selecting a set of agents as leaders that receive information from a reference signal directly, while minimizing the number of leaders, subject to consensus tracking performance.

Indefinite Robust Linear Quadratic Optimal Regulator for Discrete-Time Uncertain Singular Markov Jump Systems.

The robust LQ optimal regulator problem for discrete-time uncertain singular Markov jump systems (SMJSs) is solved by introducing a new quadratic cost function established by the penalty function method, which combines the penalty function and the weighting matrices. First, the indefinite robust optimal regulator problem for uncertain SMJSs is transformed into the robust optimal regulator problem with positive definite weighting matrices for uncertain Markov jump systems (MJSs). The transformed robust LQ problem is settled by the robust least-squares method, and the condition of the existence and analytic form of the robust optimal regulator are proposed.

Minimum-Cost State-Flipped Control for Reachability of Boolean Control Networks Using Reinforcement Learning.

This article proposes model-free reinforcement learning methods for minimum-cost state-flipped control in Boolean control networks (BCNs). We tackle two questions: 1) finding the flipping kernel, namely, the flip set with the smallest cardinality ensuring reachability and 2) deriving optimal policies to minimize the number of flipping actions for reachability based on the obtained flipping kernel. For Question 1), Q-learning's capability in determining reachability is demonstrated.

Anti-PD-L1 antibody ASC22 in combination with a histone deacetylase inhibitor chidamide as a "shock and kill" strategy for ART-free virological control: a phase II single-arm study.

The combination of ASC22, an anti-PD-L1 antibody potentially enhancing HIV-specific immunity and chidamide, a HIV latency reversal agent, may serve as a strategy for antiretroviral therapy-free virological control for HIV. People living with HIV, having achieved virological suppression, were enrolled to receive ASC22 and chidamide treatment in addition to their antiretroviral therapy. Participants were monitored over 24 weeks to measure changes in viral dynamics and the function of HIV-specific CD8 T cells (NCT05129189).

Multimodal magnetic resonance longitudinal study on the deep gray matter in multiple sclerosis patients with teriflunomide.

Disease-modifying therapies (DMTs) are used in an increasing number of patients with multiple sclerosis (MS). However, whether DMTs have intrinsic effects on deep gray matter (DGM) microstructure and atrophy is still poorly understood. In this study, we described the quantitative susceptibility values (QSV) and diffusion kurtosis imaging (DKI) metrics of DGM in relapsing-remitting MS (RRMS) patients and their association with cognitive deficits.

Hybrid Control Policy for Artificial Pancreas Via Ensemble Deep Reinforcement Learning.

Objective: The artificial pancreas (AP) has shown promising potential in achieving closed-loop glucose control for individuals with type 1 diabetes mellitus (T1DM). However, designing an effective control policy for the AP remains challenging due to the complex physiological processes, delayed insulin response, and inaccurate glucose measurements. While model predictive control (MPC) offers safety and stability through the dynamic model and safety constraints, it lacks individualization and is adversely affected by unannounced meals.

Trends in Clinico-Epidemiological Profile and Outcomes of Patients with HIV-Associated Cryptococcal Meningitis in Shanghai, China, 2013-2023.

The study aimed to analyze changes in the clinical and epidemiological aspects of HIV-associated cryptococcal meningitis (CM) patients and to identify factors influencing their prognosis. Clinical data of patients with HIV-associated CM treated in Shanghai, China between 2013 and 2023 were collected. This study included 279 cases, 2.