The efficacy of hyperthermia-based multimodal therapy is dependent on gatekeeper protein, BID.

Objectives: The combination of ferroptotic agent artesunate (ART) and apoptotic agent rhTRAIL (recombinant human tumor necrosis factor-related apoptosis-inducing ligand) has been shown to synergistically enhance apoptosis in various cancer cell lines via crosstalk between the endoplasmic reticulum (ER) stress response, the rhTRAIL-induced extrinsic cell death receptor pathway, and the intrinsic BID-Bax-mitochondrial-dependent-apoptosis pathway. This synergistic interaction has been demonstrated to be effective in multiple types of cancer cell lines, making artesunate combined with rhTRAIL a promising second-line therapy for colon cancer patients after cytoreductive surgery and chemotherapeutic treatments. To further enhance the second-line therapy's tumoricidal effect, a multimodal therapy was developed by combining artesunate, rhTRAIL, and hyperthermic conditions where samples were treated at 42 °C for 1 h.

Tumoricidal Efficacy of Artesunate-Eluting Microsphere: Differential Role of Bax/Bak in Orchestration of Cell Death Pathways.

Artesunate (ART), an antimalarial drug, has been identified as a ferroptotic agent, inducing the generation of reactive oxygen species (ROS) and lipid peroxidation, which, in turn, activate endoplasmic reticulum (ER) stress responses and promote mitochondrial-dependent apoptosis. In our previous studies, we demonstrated that ART enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through crosstalk between the ER stress-mediated signal pathway and the Bid-Bax mitochondrial apoptotic cascade. To further explore the mechanisms underlying ferroptotic-apoptotic crosstalk and evaluate the potential of intra-arterial drug-eluting microspheres for targeted tumor therapy, we developed artesunate-eluting microspheres (ART-EMs) and investigated the tumoricidal efficacy of ART-EMs combined with TRAIL.

The impact of high-frequency rTMS treatment on brain activity in PSCI patients: a TMS-EEG study.

Objectives: This study employed Transcranial Magnetic Stimulation combined with Electroencephalography (TMS-EEG) to examine the impacts of high-frequency repetitive transcranial magnetic stimulation (rTMS) on brain activity and cognitive function in patients with post-stroke cognitive impairment (PSCI), focusing on changes in connectivity of the left dorsolateral prefrontal cortex (DLPFC) across different frequency bands.

Methods: Twenty subacute PSCI patients were recruited for a 20-day rTMS treatment, consisting of 10 days of sham stimulation followed by 10 days of actual stimulation. Clinical function scale data and TMS-EEG data were collected before treatment (Pre), after sham stimulation (Sham), and after rTMS treatment (TMS) to analyze transcranial magnetic stimulation evoked potentials (TEP), time-frequency, and functional connectivity.

Cytosolic cytochrome c represses ferroptosis.

The release of cytochrome c, somatic (CYCS) from mitochondria to the cytosol is an established trigger of caspase-dependent apoptosis. Here, we unveil an unexpected role for cytosolic CYCS in inhibiting ferroptosis-a form of oxidative cell death driven by uncontrolled lipid peroxidation. Mass spectrometry and site-directed mutagenesis revealed the existence of a cytosolic complex composed of inositol polyphosphate-4-phosphatase type I A (INPP4A) and CYCS.

Tailoring TSH suppression in differentiated thyroid carcinoma: evidence, controversies, and future directions.

Purpose: This review focus on the controversial benefits of thyroid hormone suppression therapy (THST) in differentiated thyroid carcinoma (DTC) and its associated risks, highlighting the need for individualized strategies to optimize therapeutic outcomes and guide future research.

Methods: A systematic literature search on TSH suppression in DTC over the past 10 years was conducted, prioritizing RCTs, large cohort studies, and non-inferiority trials, with additional references identified from retrieved articles.

Results: Tailored postoperative TSH strategies should consider factors such as risk stratification, treatment modality, histologic subtype, and adverse effect risks.

Benchmarking Corrosion with Anionic Polarity Index for Stable and Fast Aqueous Batteries Even in Low-Concentration Electrolyte.

Despite aqueous electrolyte endowing batteries with the merits of safe operation, low-cost fabrication, and high ionic conductivity, water-induced corrosion, including spontaneous chemical and electrochemical hydrogen evolution corrosion, adversely affects lifespan and rate capability. There is still a lack of selection criteria for benchmarking corrosion behavior qualitatively. Through theoretical simulation, an anionic polarity index (API) tactic is proposed to resist corrosion by manipulating interfacial and solvated water concomitantly, thus realizing stable and fast Zn aqueous batteries (ZABs).

Yeast TIA1 coordinates with Npl3 to promote ATG1 translation during starvation.

Macroautophagy/autophagy is crucial for cell survival during nutrient starvation. Autophagy requires the coordinated function of several Atg proteins, including the Atg1 kinase, for efficient induction and execution. Recently, several RNA-binding proteins (RBPs) have been shown to post-transcriptionally regulate ATG1.

Mcl-1 is a Gatekeeper Molecule to Regulate the Crosstalk Between Ferroptotic Agent-Induced ER Stress and TRAIL-Induced Apoptosis.

We previously reported that ferroptosis interplays with apoptosis through the integration of two independent pathways: the endoplasmic reticulum (ER) stress signaling pathway and the mitochondria-dependent apoptotic signaling pathway. In this study, we investigated a potential gatekeeper molecule, Mcl-1, between the two signal transduction pathways. Morphology studies and cell death analyses confirmed that a combination treatment of ferroptotic agent erastin (ERA) and apoptotic agent TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) synergistically enhances TRAIL-induced apoptosis in human pancreatic adenocarcinoma BxPC3 and human colorectal carcinoma HCT116 cells.

SRC kinase drives multidrug resistance induced by KRAS-G12C inhibition.

Direct targeting of the -mutant protein using covalent inhibitors (G12Ci) acts on human non-small cell lung cancer (NSCLC). However, drug resistance is an emerging concern in this approach. Here, we show that MRTX849, a covalent inhibitor targeting the mutation, leads to the reactivation of the mitogen-activated protein kinase signaling pathway in MRTX849-resistant NSCLC and pancreatic ductal adenocarcinoma.

Theoretical and Experimental Raman Investigation of Mechanical Strain and Electric Field Effects on Conductive Polymers.

Mechanical strain and electric field affect the performance of conductive polymer devices, for which the underlying mechanism should be investigated at the molecular level. This study combines theoretical and experimental Raman approaches to explore the changes in the molecular structure of poly(3-hexylthiophene) (P3HT) and poly(3,4-ethylenedioxythiophene) (PEDOT) under the influence of mechanical strain and external electric fields. Theoretical calculations reveal the pronounced shifts in the main Raman peak if the conjugating length is changed by the mechanical strain, while in experiments, the peak position is unaffected under tensile and bending strain.

Big1 is a newly identified autophagy regulator that is critical for a fully functional V-ATPase.

The vacuolar-type H-translocating ATPase (V-ATPase) is the major proton pump for intraorganellar acidification. Therefore, the integrity of the V-ATPase is closely associated with cellular homeostasis, and mutations in genes encoding V-ATPase components and assembly factors have been reported in certain types of diseases. For instance, the recurrent mutations of , a gene encoding a V-ATPase accessory protein, have been associated with cancers and immunodeficiency.

Tuning Immune-Cold Tumor by Suppressing USP10/B7-H4 Proteolytic Axis Reinvigorates Therapeutic Efficacy of ADCs.

Tuning immune-cold tumor hot has largely attracted attention to improve cancer treatment, including immunotherapy and antibody-drug conjugates (ADCs). Utilizing multiomic analyses and experimental validation, this work identifies a pivotal role for the USP10/B7-H4 proteolytic axis in mediating the interplay between tumor immune responses and ADC efficacy, particularly for sacituzumab govitecan (SG) in treating triple negative breast cancers (TNBCs). Mechanistically, the inhibition of autocrine motility factor receptor (AMFR)-mediated ubiquitylation of B7-H4 by the deubiquitinase USP10 leads to the stabilization of B7-H4, which suppresses tumor immune activity and reduces SG treatment effectiveness.

Reactive oxygen species responsive chitooligosaccharides based nanoplatform for sonodynamic therapy in mammary cancer.

Sonodynamic therapy (SDT) has been extensively studied as a new type of non-invasive treatment for mammary cancer. However, the poor water solubility and defective biocompatibility of sonosensitizers during SDT hinder the sonodynamic efficacy. Herein, a nanoplatform has been developed to achieve high efficient SDT against mammary cancer through the host-guest interaction of β-cyclodextrin/5-(4-hydroxyphenyl)-10,15,20-triphenylporphyrin (β-CD-TPP) and ferrocenecarboxylic acid/chitooligosaccharides (FC-COS).

NF-κB1 deficiency promotes macrophage-derived adrenal tumors but decreases neurofibromas in HTLV-I LTR-Tax transgenic mice.

Human T-cell leukemia virus type I (HTLV-I) is an oncogenic virus whose infection can cause diverse diseases, most notably adult T-cell leukemia/lymphoma (ATL or ATLL), an aggressive and fatal malignancy of CD4 T cells. The oncogenic ability of HTLV-I is mostly attributed to the viral transcriptional transactivator Tax. Tax alone is sufficient to induce specific tumors in mice depending on the promotor used to drive Tax expression, thereby being used to understand HTLV-I tumorigenesis and model the tumor types developed in Tax transgenic mice.

The proliferation of antibiotic resistance genes (ARGs) and microbial communities in industrial wastewater treatment plant treating N,N-dimethylformamide (DMF) by AAO process.

The excessive use of antibiotics has resulted in the contamination of the environment with antibiotic resistance genes (ARGs), posing a significant threat to public health. Wastewater treatment plants (WWTPs) are known to be reservoirs of ARGs and considered to be hotspots for horizontal gene transfer (HGT) between bacterial communities. However, most studies focused on the distribution and dissemination of ARGs in hospital and urban WWTPs, and little is known about their fate in industrial WWTPs.

Diverse functions of cytochrome c in cell death and disease.

The redox-active protein cytochrome c is a highly positively charged hemoglobin that regulates cell fate decisions of life and death. Under normal physiological conditions, cytochrome c is localized in the mitochondrial intermembrane space, and its distribution can extend to the cytosol, nucleus, and extracellular space under specific pathological or stress-induced conditions. In the mitochondria, cytochrome c acts as an electron carrier in the electron transport chain, facilitating adenosine triphosphate synthesis, regulating cardiolipin peroxidation, and influencing reactive oxygen species dynamics.

Chlorogenic Acid from Burdock Roots Ameliorates Oleic Acid-Induced Steatosis in HepG2 Cells through AMPK/ACC/CPT-1 Pathway.

Hepatic steatosis can cause liver dysfunction and cell injury, on which natural functional factors are expected to be an effective approach for long-term intervention. However, the cellular molecular mechanisms are unclear. Chlorogenic acid is a phenolic compound, which can regulate lipid metabolism and is abundant in burdock root.

Synergistic Cooperation of Zn(002) Texture and Amorphous Zinc Phosphate for Dendrite-Free Zn Anodes.

Zn anodes of aqueous Zn metal batteries face challenges from dendrite growth and side reactions. Building Zn(002) texture mitigates the issues but does not eradicate them. Zn(002) still faces severe challenges from corrosive electrolytes and dendrite growth, especially after hundreds of cycles.

Dynamic Zn/Electrolyte Interphase and Enhanced Cation Transfer of Sol Electrolyte for All-Climate Aqueous Zinc Metal Batteries.

Zn metal as one of the promising anodes of aqueous batteries possesses notable advantages, but it faces severe challenges from severe side reactions and notorious dendrite growth. Here, ultrathin nanosheets of α-zirconium phosphate (ZrP) are explored as an electrolyte additive. The nanosheets not only create a dynamic and reversible interphase on Zn but also promote the Zn transportation in the electrolyte, especially in the outer Helmholtz plane near ZrP.

Tunable resonance Raman scattering of quantum dots in a nonlinear excitation regime.

Controllable tuning of electron-phonon coupling strength and excited state dynamics is important for the understanding of resonance Raman scattering in low-dimensional semiconductors. Here, we report a significant and reversible field-induced modulation in absolute resonance Raman intensity of quantum dots using ionic liquid gating. Meanwhile, a potential-dependent nonlinear relationship is present between Raman intensity and excitation power density.

1-Methylcyclopropene and UV-C Treatment Effect on Storage Quality and Antioxidant Activity of 'Xiaobai' Apricot Fruit.

The 'Xiaobai' apricot fruit is rich in nutrients and is harvested in summer, but the high temperature limits its storage period. To promote commercial quality and extend shelf life, we investigated the effectiveness of Ultraviolet C (UV-C) combined with 1-methylcyclopropene (1-MCP) treatment on 'Xiaobai' apricot fruit stored at 4 ± 0.5 °C for 35 days.

β-Glucan attenuates cognitive impairment of APP/PS1 mice via regulating intestinal flora and its metabolites.

Background: The intestinal flora has been shown to be involved in the progression of Alzheimer's disease (AD) and can be improved by β-glucan, a polysaccharide derived from Saccharomyces cerevisiae, which affects cognitive function through the intestinal flora. However, it is not known if this effect of β-glucan is involved in AD.

Method: This study used behavioral testing to measure cognitive function.

Mutations and clinical characteristics of dRTA caused by mutations: Analysis based on published patients.

Background And Aims: The genetic and clinical characteristics of patients with distal renal tubular acidosis (dRTA) caused by mutations have not been systematically recorded before. Here, we summarized the mutations and clinical characteristics associated with dRTA.

Methods: Database was searched, and the mutations and clinical manifestations of patients were summarized from the relevant articles.