CAR T Cells Engineered to Secrete IFNκ Induce Tumor Ferroptosis via an IFNAR/STAT1/ACSL4 Axis.

Ferroptosis is an iron-dependent form of cell death that influences cancer immunity. Therapeutic modulation of ferroptosis is considered a potential strategy to enhance the efficacy of other cancer therapies, including immunotherapies such as chimeric antigen receptor (CAR) T-cell therapy. In this study, we demonstrated that IFNκ influenced the induction of ferroptosis.

Family Function and Problematic Social Media Use Among Adolescents in Vocational Schools: A Moderated Mediation Model.

With the outburst of social medias in current life, problematic use is prevalent in adolescents and has become a contemporary concern. Although family environment has been identified as a risk factor, little is known how family environment is associated with problematic social media use (PSMU). Drawing on Snyder's hope theory and Davis's cognitive-behavioral model, this study examines how family function is linked with PSMU hope.

Fluorescence quenching of deprotonated phenylurea through twisting motion induced by an electron-donating substituent group.

The excited-state proton transfer (ESPT) reaction between anthracen-2-yl-3-phenylurea (PUA) derivatives and tetrabutylammonium acetate (TBAAc) in dimethyl sulfoxide (DMSO) solvent was theoretically investigated using time-dependent density functional theory. The electron-donating methoxy group (OMe) and electron-withdrawing trifluoromethyl group (CF) were bonded to 2PUA to form OMe-2PUA and CF-2PUA, respectively. Two hydrogen bonds formed in the 1 : 1 hydrogen-bonded complexes between the 2PUA derivative and acetate ion (AcO), namely N1-H1⋯O1 and N2-H2⋯O2.

Spatial selectivity of ATase inhibition in mouse models of Charcot-Marie-Tooth disease.

The endoplasmic reticulum acetylation machinery has emerged as a new branch of the larger endoplasmic reticulum quality control system. It regulates the selection of correctly folded polypeptides as well as reticulophagy-mediated removal of toxic protein aggregates with the former being a particularly important aspect of the proteostatic functions of endoplasmic reticulum acetylation. Essential to this function is the Nε-lysine acetyltransferase activity of acetyltransferase 1 and acetyltransferase 2, which regulates the induction of endoplasmic reticulum-specific autophagy through the acetylation of the autophagy-related protein 9A.

Comprehension of the Synergistic Effect between m&t-BiVO/TiO-NTAs Nano-Heterostructures and Oxygen Vacancy for Elevated Charge Transfer and Enhanced Photoelectrochemical Performances.

Through the utilization of a facile procedure combined with anodization and hydrothermal synthesis, highly ordered alignment TiO nanotube arrays (TiO-NTAs) were decorated with BiVO with distinctive crystallization phases of monoclinic scheelite (m-BiVO) and tetragonal zircon (t-BiVO), favorably constructing different molar ratios and concentrations of oxygen vacancies (V) for m&t-BiVO/TiO-NTAs heterostructured nanohybrids. Simultaneously, the m&t-BiVO/TiO-NTAs nanocomposites significantly promoted photoelectrochemical (PEC) activity, tested under UV-visible light irradiation, through photocurrent density testing and electrochemical impedance spectra, which were derived from the positive synergistic effect between nanohetero-interfaces and V defects induced energetic charge transfer (CT). In addition, a proposed self-consistent interfacial CT mechanism and a convincing quantitative dynamic process (i.

Excited-state intramolecular proton transfer with and without the assistance of vibronic-transition-induced skeletal deformation in phenol-quinoline.

The excited-state intramolecular proton transfer (ESIPT) reaction of two phenol-quinoline molecules (namely PQ-1 and PQ-2) were investigated using time-dependent density functional theory. The five-(six-) membered-ring carbocycle between the phenol and quinolone moieties in PQ-1 (PQ-2) actually causes a relatively loose (tight) hydrogen bond, which results in a small-barrier (barrier-less) on an excited-state potential energy surface with a slow (fast) ESIPT process with (without) involving the skeletal deformation motion up to the electronic excitation. The skeletal deformation motion that is induced from the largest vibronic excitation with low frequency can assist in decreasing the donor-acceptor distance and lowering the reaction barrier in the excited-state potential energy surface, and thus effectively enhance the ESIPT reaction for PQ-1.

ATase inhibition rescues age-associated proteotoxicity of the secretory pathway.

Malfunction of autophagy contributes to the progression of many chronic age-associated diseases. As such, improving normal proteostatic mechanisms is an active target for biomedical research and a key focal area for aging research. Endoplasmic reticulum (ER)-based acetylation has emerged as a mechanism that ensures proteostasis within the ER by regulating the induction of ER specific autophagy.

Menopause-specific quality of life during ovarian aging among Chinese women: A prospective cohort study.

Objective: To describe the menopause-specific quality of life of Chinese urban women at midlife.

Study Design: Prospective cohort study.

Main Outcome Measures: This study included 920 natural menopausal midlife Chinese women who were followed up for 10 years.

ATG9A regulates proteostasis through reticulophagy receptors FAM134B and SEC62 and folding chaperones CALR and HSPB1.

The acetylation of ATG9A within the endoplasmic reticulum (ER) lumen regulates the induction of reticulophagy. ER acetylation is ensured by AT-1/SLC33A1, a membrane transporter that maintains the cytosol-to-ER flux of acetyl-CoA. Defective AT-1 activity, as caused by heterozygous/homozygous mutations and gene duplication events, results in severe disease phenotypes.

Deficient Endoplasmic Reticulum Acetyl-CoA Import in Pancreatic Acinar Cells Leads to Chronic Pancreatitis.

Background & Aims: Maintaining endoplasmic reticulum (ER) proteostasis is essential for pancreatic acinar cell function. Under conditions of severe ER stress, activation of pathogenic unfolded protein response pathways plays a central role in the development and progression of pancreatitis. Less is known, however, of the consequence of perturbing ER-associated post-translational protein modifications on pancreatic outcomes.

Insomnia symptoms in relation to menopause among middle-aged Chinese women: Findings from a longitudinal cohort study.

Objective: Our study aims to investigate the differences in insomnia between Chinese and Western women during menopause to fill the gaps in the research on menopause in Chinese women, and to examine the premenopausal factors predictive of moderate to severe insomnia during menopause.

Study Design: This is a longitudinal cohort study conducted in an urban Chinese community with a total of 458 participants.

Main Outcome Measures: Presence of insomnia symptoms (trouble falling asleep, waking up early); vasomotor symptoms; anxiety and depression assessed by the Hospital Anxiety and Depression Scale; and menopausal stages.

Relationships Between Vasomotor Symptoms and Mood in Midlife Urban Chinese Women: Observations in a Prospective Study.

Context: During the menopausal transition, there is a greater likelihood of the prevalence of various bothersome symptoms, including vasomotor symptoms (VMS) and mood symptoms.

Objective: To investigate the association among bothersome VMS and symptoms of anxiety and depression in Chinese women during perimenopause and early in menopause.

Design, Patients, Setting, And Interventions: This study included 430 midlife Chinese women who had experienced natural menopause and were followed up for 10 years.

The absorption and fluorescence spectra of 4-(3-methoxybenzylidene)-2-methyl-oxazalone interpreted by Franck-Condon simulation in various pH solvent environments.

The absorption and fluorescence spectra of 4-(3-methoxybenzylidene)-2-methyl-oxazalone (m-MeOBDI) dissolved in neutral, acidic, and basic solvent environments have been investigated and assigned by using Franck-Condon (FC) simulations at the quantum TDDFT level. Four different structures of m-MeOBDI in the ground and excited states are optimized and are found to be responsible for the observed absorption and fluorescence spectra. The (absorption) fluorescence of m-MeOBDI in pure methanol and neutral/basic methanol/water (1/9 vol) mixed solvent is found to arise from the (ground neutral N-I) excited neutral N-I* and cationic C-III* species, respectively.

Nectin-like molecule 2, a necessary sexual maturation regulator, participates in congenital hypogonadotropic hypogonadism.

Background: Congenital hypogonadotropic hypogonadism (CHH) is a rare genetically heterogeneous disorder. We aimed to determine the prevalence and pathogenesis of NECL2 (Nectin-like molecule 2) variants in a cohort of female patients with CHH.

Methods: We sequenced and determined the prevalence of NECL2 variants in 68 female patients with CHH and 243 healthy controls collected from an academic medical center.

Changes in ultrasound uterine morphology and endometrial thickness during ovarian aging and possible associated factors: findings from a prospective study.

Objective: The aim of the study was to provide reference values for sonographic measurements of uterine morphology, quantify changes in uterine morphology across the menopausal transition, and identify possible factors associated with sonographic findings in uterine morphology.

Methods: This is a longitudinal cohort study conducted in middle-aged Chinese women. Using transvaginal ultrasound, we measured morphologic parameters of the uterus (volume and endometrial thickness) under standardized conditions every year for over a decade.

Symptoms of anxiety and depression among Chinese women transitioning through menopause: findings from a prospective community-based cohort study.

Objective: To determine the prevalence of symptoms of anxiety and depression in Chinese women during and after menopause, and the associated risk factors.

Design: Prospective community-based cohort study.

Setting: An urban community in Beijing, People's Republic of China.

Mass Spectrometry Imaging of N-Glycans from Formalin-Fixed Paraffin-Embedded Tissue Sections Using a Novel Subatmospheric Pressure Ionization Source.

N-linked glycosylation, featuring various glycoforms, is one of the most common and complex protein post-translational modifications (PTMs) controlling protein structures and biological functions. It has been revealed that abnormal changes of protein N-glycosylation patterns are associated with many diseases. Hence, unraveling the disease-related alteration of glycosylation, especially the glycoforms, is crucial and beneficial to improving our understanding about the pathogenic mechanisms of various diseases.

Acetyl-CoA flux regulates the proteome and acetyl-proteome to maintain intracellular metabolic crosstalk.

AT-1/SLC33A1 is a key member of the endoplasmic reticulum (ER) acetylation machinery, transporting acetyl-CoA from the cytosol into the ER lumen where acetyl-CoA serves as the acetyl-group donor for Nε-lysine acetylation. Dysfunctional ER acetylation, as caused by heterozygous or homozygous mutations as well as gene duplication events of AT-1/SLC33A1, has been linked to both developmental and degenerative diseases. Here, we investigate two models of AT-1 dysregulation and altered acetyl-CoA flux: AT-1 mice, a model of AT-1 haploinsufficiency, and AT-1 sTg mice, a model of AT-1 overexpression.

Hypothalamic mTORC2 is essential for metabolic health and longevity.

The mechanistic target of rapamycin (mTOR) is an evolutionarily conserved protein kinase that regulates growth and metabolism. mTOR is found in two protein complexes, mTORC1 and mTORC2, that have distinct components and substrates and are both inhibited by rapamycin, a macrolide drug that robustly extends lifespan in multiple species including worms and mice. Although the beneficial effect of rapamycin on longevity is generally attributed to reduced mTORC1 signaling, disruption of mTORC2 signaling can also influence the longevity of worms, either positively or negatively depending on the temperature and food source.

Golgi-resident TRIO regulates membrane trafficking during neurite outgrowth.

Neurite outgrowth requires coordinated cytoskeletal rearrangements in the growth cone and directional membrane delivery from the neuronal soma. As an essential Rho guanine nucleotide exchange factor (GEF), TRIO is necessary for cytoskeletal dynamics during neurite outgrowth, but its participation in the membrane delivery is unclear. Using co-localization studies, live-cell imaging, and fluorescence recovery after photobleaching analysis, along with neurite outgrowth assay and various biochemical approaches, we here report that in mouse cerebellar granule neurons, TRIO protein pools at the Golgi and regulates membrane trafficking by controlling the directional maintenance of both RAB8 (member RAS oncogene family 8)- and RAB10-positive membrane vesicles.

Distinct functions of Trio GEF domains in axon outgrowth of cerebellar granule neurons.

As a critical guanine nucleotide exchange factor (GEF) regulating neurite outgrowth, Trio coordinates multiple processes of cytoskeletal dynamics through activating Rac1, Cdc42 and RhoA small GTPases by two GEF domains, but the in vivo roles of these GEF domains and corresponding downstream effectors have not been determined yet. We established multiple lines of knockout mice and assessed the respective roles of Trio GEF domains and Rac1 in axon outgrowth. Knockout of total Trio in cerebellar granule neurons (CGNs) led to an impaired F-actin rearrangement of growth cone and hence a retarded neurite outgrowth.

Predicting the Initial Thermal Decomposition Path of Nitrobenzene Caused by Mode Vibration at Moderate-Low Temperatures: Temperature-Dependent Anti-Stokes Raman Spectra Experiments and First-Principals Calculations.

The lack of understanding of the initial decomposition micromechanism of energetic materials subjected to external stimulation has hindered its safe storage, usage, and development. The initial thermal decomposition path of nitrobenzene triggered by molecular thermal motion is investigated using temperature-dependent anti-Stokes Raman spectra experiments and first-principles calculations to clarify the initial thermal decomposition micromechanism. The experiment shows that the symmetric nitro stretching, antisymmetric nitro stretching, and phenyl ring stretching vibration modes are active as increasing temperature below 500 K.

Increased transport of acetyl-CoA into the endoplasmic reticulum causes a progeria-like phenotype.

The membrane transporter AT-1/SLC33A1 translocates cytosolic acetyl-CoA into the lumen of the endoplasmic reticulum (ER), participating in quality control mechanisms within the secretory pathway. Mutations and duplication events in AT-1/SLC33A1 are highly pleiotropic and have been linked to diseases such as spastic paraplegia, developmental delay, autism spectrum disorder, intellectual disability, propensity to seizures, and dysmorphism. Despite these known associations, the biology of this key transporter is only beginning to be uncovered.

A survey of the pyrabactin resistance-like abscisic acid receptor gene family in poplar.

The conserved PYR/PYL/RCAR family acts as abscisic acid (ABA) receptors for land plants to adapt to terrestrial environments. Our recent study reported that the exogenous overexpression of poplar PtPYRL1 and PtPYRL5, the PYR/PYL/RCAR orthologs, promoted the sensitivity of transgenic Arabidopsis to ABA responses. Here, we surveyed the PtPYRL family in poplar, and revealed that although the sequence and structure are relatively conserved among these receptors, PtPYRL members have differential expression patterns and the sensitivity to ABA or drought treatment, suggesting that PtPYRLs might be good candidates to a future biotechnological use to enhance poplar resistance to water-stress environments.

Mechanism of Excited-State Intramolecular Proton Transfer for 1,2-Dihydroxyanthraquinone: Effect of Water on the ESIPT.

Mechanisms of excited-state intramolecular proton transfer (ESIPT) of 1,2-dihydroxyanthraquinone (ALR) in ethanol solvent and binary solvent of water and ethanol are investigated using the density functional theory and time-dependent density functional theory. The intramolecular hydrogen bond is found to be reinforced in the excited state based on the bond lengths, bond angles, and infrared vibrational spectra of relevant group. The reinforcement of intramolecular hydrogen bond is attributed to the charge transfer in the excited state, which leads the ESIPT to form a keto isomer.