Proteasomes suppress anticancer drug-induced cytotoxicity by inhibiting mitochondrial protein import and promoting ROS-BNIP3-mediated mitophagy.

Multidrug resistance (MDR) is associated with increased proteasome activity, which facilitates the clearance of damaged proteins and reduced mitochondrial activity, which contributes to quiescence. However, the mechanistic link between protein damage, mitochondrial dysfunction, and proteasome activity remains elusive. Here, we demonstrate that chemical drugs bind to newly synthesized mitochondrial proteins, which are largely unfolded and are coimported into the mitochondrion before appearing in the lysosome and/or nucleus.

Integrative machine learning approach for forecasting lung cancer chemosensitivity: From algorithm to cell line validation.

Background: Chemotherapy remains the primary treatment modality for patients with lung cancer; however, substantial inter-patient variability exists in responses to chemotherapeutic agents. Therefore, predicting individual responses is critical for optimizing treatment outcomes and improving patient prognosis.

Methods: This study developed a model to predict chemotherapy response in lung cancer patients by integrating multi-omics and clinical data from the Genomics of Drug Sensitivity in Cancer database, employing 45 machine learning algorithms.

AKT inhibitors in gynecologic oncology: past, present and future.

The PI3K/AKT/mTOR pathway serves as a critical signaling nexus in cancer, with AKT acting as a central regulator of tumor cell proliferation, survival, metabolism, and therapy resistance. AKT inhibitors show promising but variable anti-tumor activity in preclinical and clinical studies. Currently, multiple classes of AKT inhibitors-PH domain competitors (perifosine), allosteric inhibitors (MK-2206), and ATP-competitive agents (AZD5363, GSK2110183, GSK2141795, and GDC-0068) are under development, with several agents in phase II/III trials.

Parvalbumin Interneuron-Dependent Hippocampal Neurogenesis Evoked by Prolonged Rhythmic Light Flicker.

Rhythmic light flicker alleviates cognitive impairments in various animal models of neurological diseases. However, its long-term effects and underlying mechanisms remain unclear. Here, a cohort of adult mice is subjected to long-term exposure to 40 Hz light flicker (1 hour daily for 30 days) and observed significant enhancements in hippocampal neurogenesis and spatial learning without any adverse behavioral effects.

Immunotherapy-induced cholestasis in cancer: insights from the two real-world pharmacovigilance databases of FAERS and VigiBase.

Background: The US Food and Drug Administration (FDA) recently issued a safety alert regarding cholestasis as a potential adverse reaction to immune checkpoint inhibitor (ICI) therapy. However, the underlying mechanisms of ICI-induced cholestasis remain poorly elucidated.

Methods: This study analyzed adverse event reports of cancer patients treated with ICIs, extracted from the FAERS (2013-2023) and VigiBase (1968-2023) databases.

Low Expression of Selenoprotein S Promotes Osteogenic Differentiation in Bone Marrow Mesenchymal Stromal Cells.

Selenium performs biological functions in the human body primarily through selenoproteins, which are known to play critical roles in bone metabolism. Normal osteogenic function is maintained by steady bone metabolism in the mandible. The role of selenoprotein S (SelS), one of the 25 identified selenoproteins, in osteogenic differentiation remains unclear.

CLDN18.2-targeting STAR-T cell therapy for pancreatic cancer: a strategy to minimize gastric off-tumor toxicity compared to CLDN18.2 CAR-T.

Claudin18 isoform 2 (CLDN18.2), primarily expressed in gastric tissue and upregulated in pancreatic cancer (PC), is a key target for innovative treatments like chimeric antigen receptor T (CAR-T) cell therapy. However, CAR-T's effectiveness comes with a significant risk of on-target, off-tumor (OTOT) toxicity due to CLDN18.

The "don't eat me" signal CD47 is associated with microglial phagocytosis defects and autism-like behaviors in 16p11.2 deletion mice.

Various pathological characteristics of autism spectrum disorder (ASD) stem from abnormalities in brain resident immune cells, specifically microglia, to prune unnecessary synapses or neural connections during early development. Animal models of ASD exhibit an abundance of synapses in different brain regions, which is strongly linked to the appearance of ASD behaviors. Overexpression of CD47 on neurons acts as a "don't eat me" signal, safeguarding synapses from inappropriate pruning by microglia.

Integration of machine learning and experimental validation reveals new lipid-lowering drug candidates.

Hyperlipidemia, a major risk factor for cardiovascular diseases, is associated with limitations in clinical lipid-lowering medications. Drug repurposing strategies expedite the research process and mitigate development costs, offering an innovative approach to drug discovery. This study employed systematic literature and guidelines review to compile a training set comprising 176 lipid-lowering drugs and 3254 non-lipid-lowering drugs.

MLKL triggers NLRP3 activation in sodium arsenite-induced myocardial necroinflammation.

Prolonged exposure to arsenic elevates the risk of developing a range of cardiovascular disorders. However, the mechanisms underlying myocardial damage from arsenic exposure remain elusive. Our earlier research suggest that drinking arsenic-contaminated water can lead to substantial inflammatory and necrotic injury in the myocardium of rats.

Targeting MLKL ameliorates T-2 toxin-induced cartilage damage by inhibiting chondrocyte death and matrix degradation in mice.

T-2 toxin is the most toxic mycotoxin found in contaminated food and animal feed that threatens health. Exposure to T-2 toxin causes cartilage damage and leads to joint disorders, but the mechanisms underlying T-2 toxin-induced cartilage damage remain unclear. The results showed that T-2 toxin-induced chondrocyte death in articular cartilage from rats fed T-2 toxin (200 ng/g b.

Computational frameworks transform antagonism to synergy in optimizing combination therapies.

While drug combinations are increasingly important in disease treatment, predicting their therapeutic interactions remains challenging. This review systematically analyzes computational methods for predicting drug combination effects through multi-omics data integration. We comprehensively assess key algorithms including DrugComboRanker and AuDNNsynergy, and evaluate integration approaches encompassing kernel regression and graph networks.

Downregulation of HSP47 triggers ER stress-mediated apoptosis of hypertrophic chondrocytes contributing to T-2 toxin-induced cartilage damage.

T-2 toxin contamination in food and feed is a growing global concern, with its toxic effects on developing cartilage remaining poorly understood. In this study, we constructed an animal model using 4-week-old male Sprague-Dawley rats, which were administered T-2 toxin (200 ng/g body weight per day) by gavage for one month. Histological analysis showed a significant reduction in hypertrophic chondrocytes and increased caspase-3 expression and TUNEL staining in the deep cartilage zone of T-2 toxin-treated rats.

Susceptibility of Mitophagy-Deficient Tumors to Ferroptosis Induction by Relieving the Suppression of Lipid Peroxidation.

The identification of ferroptosis-sensitive cancers is critical for the application of ferroptosis-inducing therapies in cancer therapy. Here, patient-derived organoid screening models of colorectal cancer are established to identify tumors that are sensitive to ferroptosis-inducing therapy. This study discovers that patient-derived tumors characterized by mitophagy deficiency are hypersensitive to ferroptosis-inducing therapies.

Clinical and pathological characteristics of cervical clear cell carcinoma in patients not exposed to diethylstilbestrol: a comprehensive analysis of 49 cases.

Purpose: This study aimed to investigate the clinical and pathological characteristics, treatment strategies, and prognosis of cervical clear cell carcinoma (CCCC) in patients not exposed to diethylstilbestrol .

Methods: The patients diagnosed with CCCC at West China Second University Hospital of Sichuan University between January 2011 and Jun 2023 were enrolled for this retrospective study. The clinical characteristics and information on treatment and follow-up were collected.

Maternal linoleic acid-rich diet ameliorates bilirubin neurotoxicity in offspring mice.

Hyperbilirubinaemia is a prevalent condition during the neonatal period, and if not promptly and effectively managed, it can lead to severe bilirubin-induced neurotoxicity. Sunflower seeds are a nutrient-rich food source, particularly abundant in linoleic acid. Here, we provide compelling evidence that lactating maternal mice fed a sunflower seed diet experience enhanced neurological outcomes and increased survival rates in hyperbilirubinemic offspring.

Low expression of selenoprotein S induces oxidative damage in cartilages.

Low levels of the indispensable trace element selenium (Se) can cause oxidative stress and disrupt environmental homeostasis in humans and animals. Selenoprotein S (Selenos), of which Se is a key component, is a member of the selenoprotein family involved in various biological processes. This study aimed to investigate whether low-level SELENOS gene expression can induce oxidative stress and decrease the antioxidative capacity of chondrocytes.

CDK4/6 inhibition augments anti-tumor efficacy of XPO1 inhibitor selinexor in natural killer/T-cell lymphoma.

XPO1 is an attractive and promising therapeutic target frequently overexpressed in multiple hematological malignancies. The clinical use of XPO1 inhibitors in natural killer/T-cell lymphoma (NKTL) is not well documented. Here, we demonstrated that XPO1 overexpression is an indicator of poor prognosis in patients with NKTL.

Durable, multifunctional cotton fabrics with in situ deposited micro/nanomaterials for effective self-cleaning, oil-water separation and antibacterial activity.

The facile modification of cotton fabrics for excellent self-cleaning, oil-water separation, and antibacterial activity is of great interest for multifunctional requirements. Herein, a durable, robust, fluorine-free multifunctional cotton fabric was fabricated via in-situ growing zeolitic imidazolate framework-67 (ZIF-67) on the cotton surface, followed by depositing hydrophobic SiO (H-SiO) nanoparticles synthesized via an improved Stöber reaction. Meanwhile, the abundant hydroxyls of the cotton fabrics provided the necessary ion interaction sites for the uniform deposition of micro/nanomaterials, confirmed by the visualized Raman imaging technology.

BET inhibition induces synthetic lethality in PTEN deficient colorectal cancers via dual action on p21.

Loss of PTEN tumor suppressor is an important event during colorectal cancer (CRC) development and is a target for therapeutic exploitation. This study reports that bromodomain and extra-terminal motif (BET) is a synthetic lethal partner of PTEN in CRC. BET inhibition (BETi) selectively induced G1 cell cycle arrest and apoptosis in CRC.

Conformal Engineering of Both Electrodes Toward High-Performance Flexible Quasi-Solid-State Zn-Ion Micro-Supercapacitors.

The severe Zn-dendrite growth and insufficient carbon-based cathode performance are two critical issues that hinder the practical applications of flexible Zn-ion micro-ssupercapacitors (FZCs). Herein, a self-adaptive electrode design concept of the synchronous improvement on both the cathode and anode is proposed to enhance the overall performance of FZCs. Polypyrrole doped with anti-expansion graphene oxide and acrylamide (PPy/GO-AM) on the cathode side can exhibit remarkable electrochemical performance, including decent capacitance and cycling stability, as well as exceptional mechanical properties.

Potential Function of 3,5-Dihydroxy-4-Methoxybenzyl Alcohol from Pacific Oyster (Crassostrea gigas) in Brain of Old Mice.

Scope: 3,5-Dihydroxy-4-methoxybenzyl alcohol (DHMBA) is found in oyster extracts in recent years and is reported to have antioxidant activity. Although it has been reported to be protective in various models of oxidative stress, the therapeutic effect of DHMBA on neurological damage caused by aging remains to be demonstrated.

Methods And Results: The present study investigates the potential functions of DHMBA in brain of old C57BL/6J mice and aging cell model.

Characteristics of germline DNA damage response gene mutations in ovarian cancer in Southwest China.

DNA damage response (DDR) pathways are responsible for repairing endogenous or exogenous DNA damage to maintain the stability of the cellular genome, including homologous recombination repair (HRR) pathway, mismatch repair (MMR) pathway, etc. In ovarian cancer, current studies are focused on HRR genes, especially BRCA1/2, and the results show regional and population differences. To characterize germline mutations in DDR genes in ovarian cancer in Southwest China, 432 unselected ovarian cancer patients underwent multi-gene panel testing from October 2016 to October 2020.