Napabucasin-loaded PLGA nanoparticles trigger anti-HCC immune responses by metabolic reprogramming of tumor-associated macrophages.

Background: JAK/STAT3 is one of the critical signaling pathways involved in the occurrence and development of hepatocellular carcinoma (HCC). BBI608 (Napabucasin), as a novel small molecule inhibitor of STAT3, has shown previously excellent anti-HCC effects in vitro and in mouse models. However, low bioavailability, high cytotoxicity and other shortcomings limit its clinical application.

TransformerLSR: Attentive joint model of longitudinal data, survival, and recurrent events with concurrent latent structure.

In applications such as biomedical studies, epidemiology, and social sciences, recurrent events often co-occur with longitudinal measurements and a terminal event, such as death. Therefore, jointly modeling longitudinal measurements, recurrent events, and survival data while accounting for their dependencies is critical. While joint models for the three components exist in statistical literature, many of these approaches are limited by heavy parametric assumptions and scalability issues.

Influence of New Internet Usage on Depressive Symptoms Among Older Adults: Does the Effect Vary in People with Different Economic Status?

This study investigated the longitudinal effect of new internet usage on depressive symptoms and whether economic status modified this association. Data were from the China Health and Retirement Longitudinal Study, involving 5,259 participants who were 60 +, did not use the internet in 2015, and were followed up in 2018. Linear regression with standard errors clustered at the city level was employed.

Acid-responsive CST@NPs enhanced diabetic wound healing through rescuing mitochondrial dysfunction.

Diabetic ulcers (DUs) are persistent and challenging complications of diabetes. The consequences of DUs include a decline in functional status, increased risk of infection, hospitalization, and even death. Our study revealed a significant decrease in the levels of cortistatin (CST) in the skin tissue of patients with DUs and diabetic rats.

Eicosapentaenoic acid induces macrophage Mox polarization to prevent diabetic cardiomyopathy.

Diabetic cardiomyopathy (DC) leads to heart failure, with few effective approaches for its intervention. Eicosapentaenoic acid (EPA) is an essential nutrient that benefits the cardiovascular system, but its effect on DC remains unknown. Here, we report that EPA protects against DC in streptozotocin and high-fat diet-induced diabetic mice, with an emphasis on the reduction of cardiac M1-polarized macrophages.

Tumor-Selective Nano-Dispatcher Enforced Cancer Immunotherapeutic Effects via Regulating Lactate Metabolism and Activating Toll-Like Receptors.

The development of tumors relies on lactate metabolic reprogramming to facilitate their unchecked growth and evade immune surveillance. This poses a significant challenge to the efficacy of antitumor immunity. To address this, a tumor-selective nano-dispatcher, PIMDQ/Syro-RNP, to enforce the immunotherapeutic effect through regulation of lactate metabolism and activation of toll-like receptors is developed.

Choroidal Optical Coherence Tomography Angiography: Noninvasive Choroidal Vessel Analysis via Deep Learning.

The choroid is the most vascularized structure in the human eye, associated with numerous retinal and choroidal diseases. However, the vessel distribution of choroidal sublayers has yet to be effectively explored due to the lack of suitable tools for visualization and analysis. In this paper, we present a novel choroidal angiography strategy to more effectively evaluate vessels within choroidal sublayers in the clinic.

Eicosapentaenoic acid activates the P62/KEAP1/NRF2 pathway for the prevention of diabetes-associated cognitive dysfunction.

Diabetes-associated cognitive dysfunction (DCD) is a severe complication of diabetes mellitus (DM), threatening the life quality of the diabetic population. However, there is still a lack of effective approaches for its intervention. Eicosapentaenoic acid (EPA) is an omega-3 polyunsaturated fatty acid that was not previously investigated for its effect on DCD.

Anti-Cracking TEOS-Based Hybrid Materials as Reinforcement Agents for Paper Relics.

Tetraethoxysilane (TEOS) is the most commonly used silicon-based reinforcement agent for conserving art relics due to its cost-effectiveness and commercial maturity. However, the resulting silica gel phase is prone to developing cracks as the gel shrinks during the sol-gel process, potentially causing severe damage to the objects being treated. In this study, dodecyltrimethoxysilane (DTMS) was introduced into TEOS to minimize this shrinkage by adding elastic long chains to weaken the capillary forces.

Function of mast cell and bile-cholangiocarcinoma interplay in cholangiocarcinoma microenvironment.

Objective: The correlation between cholangiocarcinoma (CCA) progression and bile is rarely studied. Here, we aimed to identify differential metabolites in benign and malignant bile ducts and elucidate the generation, function and degradation of bile metabolites.

Design: Differential metabolites in the bile from CCA and benign biliary stenosis were identified by metabonomics.

Continuous-Time Decision Transformer for Healthcare Applications.

Offline reinforcement learning (RL) is a promising approach for training intelligent medical agents to learn treatment policies and assist decision making in many healthcare applications, such as scheduling clinical visits and assigning dosages for patients with chronic conditions. In this paper, we investigate the potential usefulness of Decision Transformer (Chen et al., 2021)-a new offline RL paradigm-in medical domains where decision making in continuous time is desired.

Recent advances of novel targeted drug delivery systems based on natural medicine monomers against hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), the most prevalent type of liver cancer, is often diagnosed at an advanced stage. Surgical interventions are often ineffective, leading HCC patients to rely on systemic chemotherapy. Unfortunately, commonly used chemotherapeutic drugs have limited efficacy and can adversely affect vital organs, causing significant physical and psychological distress for patients.

Effects of dietary Clostridium butyricum and rumen protected fat on meat quality, oxidative stability, and chemical composition of finishing goats.

Background: Clostridium butyricum (CB) is a probiotic that can regulate intestinal microbial composition and improve meat quality. Rumen protected fat (RPF) has been shown to increase the dietary energy density and provide essential fatty acids. However, it is still unknown whether dietary supplementation with CB and RPF exerts beneficial effects on growth performance and nutritional value of goat meat.

Identification of a novel MICB allele, MICB*014:02, by cloning and sequencing.

The novel MICB*014:02 allele differs from MICB*014:01:01 by one nucleotide change in exon 2.

Improved production of recombinant β-mannanase (TaMan5) in and its synergistic degradation of lignocellulosic biomass.

Mannan, a highly abundant and cost-effective natural resource, holds great potential for the generation of high-value compounds such as bioactive polysaccharides and biofuels. In this study, we successfully enhanced the expression of constructed GH5 β-mannanase (TaMan5) from ND-1 by employing propeptide in . By replacing the α-factor with propeptide (MGNRALNSMKFFKSQALALLAATSAVA), TaMan5 activity was significantly increased from 67.

Molecular and clonal evolution reveal a common pathway of distant relapse gliomas.

The evolutionary trajectories of genomic alterations underlying distant recurrence in glioma remain largely unknown. To elucidate glioma evolution, we analyzed the evolutionary trajectories of matched pairs of primary tumors and relapse tumors or tumor fluid (TISF) based on deep whole-genome sequencing data (ctDNA). We found that MMR gene mutations occurred in the late stage in IDH-mutant glioma during gene evolution, which activates multiple signaling pathways and significantly increases distant recurrence potential.

Genomic alterations of oligodendrogliomas at distant recurrence.

Background: Oligodendroglioma is known for its relatively better prognosis and responsiveness to radiotherapy and chemotherapy. However, little is known about the evolution of genetic changes as oligodendroglioma progresses.

Methods: In this study, we evaluated gene evolution invivo during tumor progression based on deep whole-genome sequencing data (ctDNA).

Site-specific nanoswitch circumventing immune resistance via activating TLR and inhibiting PD-L1/PD-1 axis.

Immunotherapy has fundamentally altered cancer treatment; however, its effectiveness is clinically hampered by insufficient intratumoral T lymphocyte infiltration and failed T lymphocyte priming. Additionally, inducing cancer-specific immune responses while sparing normal cells remains challenging. Herein, we developed a redox-activatable polymeric nanoswitch (c-N@IM/JQ) that remained 'off' status in circulation but rapidly switched 'on' after entering the tumor.

Tumor selective self-assembled nanomicelles of carbohydrate-epothilone B conjugate for targeted chemotherapy.

Epothilone B (Epo B) is a potent antitumor natural product with sub-nanomolar anti-proliferation action against several human cancer cells. However, poor selectivity to tumor cells and unacceptable therapeutic windows of Epo B and its analogs are the major obstacles to their development into clinical drugs. Herein, we present self-assembled nanomicelles based on an amphiphilic carbohydrate-Epo B conjugate that is inactive until converted to active Epo B within the tumor.

SAFB associates with nascent RNAs and can promote gene expression in mouse embryonic stem cells.

Scaffold attachment factor B (SAFB) is a conserved RNA-binding protein that is essential for early mammalian development. However, the functions of SAFB in mouse embryonic stem cells (ESCs) have not been characterized. Using RNA immunoprecipitation followed by RNA-seq (RIP-seq), we examined the RNAs associated with SAFB in wild-type and SAFB/SAFB2 double-knockout ESCs.

Cardamonin targets KEAP1/NRF2 signaling for protection against atherosclerosis.

Atherosclerosis (AS)-induced cardiovascular disease is a leading cause of death worldwide. To date, there is still a lack of effective approaches for AS intervention. Cardamonin (CAD) is a bioactive food component, but its effect on AS is unknown.