New Atg9 Phosphorylation Sites Regulate Autophagic Trafficking in Glia.

We previously identified a role for dAuxilin (dAux), the fly homolog of Cyclin G-associated kinase, in glial autophagy contributing to Parkinson's disease (PD). To further dissect the mechanism, we present evidence here that lack of glial dAux enhanced the phosphorylation of the autophagy-related protein Atg9 at two newly identified threonine residues, T62 and T69. The enhanced Atg9 phosphorylation in the absence of dAux promotes autophagosome formation and Atg9 trafficking to the autophagosomes in glia.

Understanding phage BX-1 resistance in AP-1 and the role of quorum-sensing regulation.

The marine ecosystem is characterized by a rich diversity of bacterial hosts and their phages. The propagation of phages is primarily limited by their ability to adsorb to host cells and is further challenged by various bacterial defense mechanisms. To fully realize the potential of phage therapy in aquaculture, a comprehensive understanding of phage-host interactions and their regulation is essential.

Mechanically Robust Bismuth-Embedded Carbon Microspheres for Ultrafast Charging and Ultrastable Sodium-Ion Batteries.

Advancements in the development of fast-charging and long-lasting microstructured alloying anodes with high volumetric capacities are essential for enhancing the operational efficiency of sodium-ion batteries (SIBs). These anodes, however, face challenges such as declined cyclability and rate capability, primarily due to mechanical degradation reduced by significant volumetric changes (over 252%) and slow kinetics of sodium-ion storage. Herein, we introduce a novel anode design featuring densely packed bismuth (Bi) embedded within highly conductive carbon microspheres to overcome the aforementioned challenges.

Impact of Frailty on Antihypertensive Treatment in Older Adults.

Background: The association between systolic blood pressure and all-cause mortality differs between frail and nonfrail individuals, highlighting uncertainties about the effectiveness of antihypertensive treatments in frail populations.

Methods: Using data from the SHEP trial (Systolic Hypertension in the Elderly Program), a baseline frailty index (FI), including 55 variables, was constructed. Fine-Gray subdistribution hazard models and Cox proportional hazards regression models were used to explore the association between baseline FI and the risks of stroke, cardiovascular disease, and all-cause death, as well as to examine whether the impact of antihypertensive treatment on these outcomes was modified by baseline FI.

Reversing Cochlear Nucleus Maladaptive Plasticity via Customized Extracochlear Stimulation: A New Approach for Tinnitus Treatment.

Tinnitus, a widespread condition affecting numerous individuals worldwide, remains a significant challenge due to limited effective therapeutic interventions. Intriguingly, patients using cochlear implants (CIs) have reported significant relief from tinnitus symptoms, although the underlying mechanisms remain unclear and intracochlear implantation risks cochlear damage and hearing loss. This study demonstrates that targeted intracochlear electrical stimulation (ES) in guinea pigs with noise-induced hearing loss reversed tinnitus-related maladaptive plasticity in the cochlear nucleus (CN), characterized by reduced auditory innervation, increased somatosensory innervation, and diminished inhibitory neural networks.

Differential expression of osteoblast-like cells on self-organized titanium dioxide nanotubes.

Background/purpose: Titanium dioxide nanotube (TNT) structures have been shown to enhance the early osseointegration of dental implants. Nevertheless, the optimal nanotube diameter for promoting osteogenesis remains unclear due to variations in cell types and manufacture of nanotubes. This study aimed to evaluate the differences in MC3T3-E1 and Saos-2 cells behavior on nanotubes of varying diameters.

Identification of novel ferroptosis-related biomarkers associated with the oxidative stress pathways in ischemic cardiomyopathy.

Background: Ferroptosis is a cell death process that depends on iron and reactive oxygen species. It significantly contributes to cardiovascular diseases. However, its exact role in ischemic cardiomyopathy (ICM) is still unclear.

Spinal astrocyte-derived interleukin-17A promotes pain hypersensitivity in bone cancer mice.

Spinal microglia and astrocytes are both involved in neuropathic and inflammatory pain, which may display sexual dimorphism. Here, we demonstrate that the sustained activation of spinal astrocytes and astrocyte-derived interleukin (IL)-17A promotes the progression of mouse bone cancer pain without sex differences. Chemogenetic or pharmacological inhibition of spinal astrocytes effectively ameliorates bone cancer-induced pain-like behaviors.

Amorphization Stabilizes Te-based Aqueous Batteries via Confining Free Water.

Tellurium (Te), with its rich valence states (-2 to +6), could endow aqueous batteries with potentially high specific capacity. However, achieving complete and stable hypervalent Te0/Te4+ electrochemistry in an aqueous environment poses significant challenges, owing to the sluggish reduction kinetics, the easy dissolution of Te4+ species, and a controversial energy storage mechanism. Herein, for the first time, we demonstrate an amorphous strategy for robust aqueous TeO2/Te electrochemistry.

[Anticoagulation effects of nafamostat mesylate in sustained low-efficiency dialysis and its relevant factors].

To investigate anticoagulation effects of nafamostat mesylate(NM) in sustained low-efficiency dialysis (SLED) and its relevant factors. Critically ill patients with kidney disease who were admitted to Zhongshan Hospital Affiliated to Fudan University and underwent SLED treatment from May to August 2024 were retrospectively included. Baseline clinical data were collected, and the activated partial thromboplastin time (APTT) and activated clotting time (ACT) were measured at the arterial end, before the filter, and at the venous end two hours post-NM anticoagulation treatment.

[Issues and recommendations on antibacterial treatment and post-exposure chemoprophylaxis for pertussis].

Pertussis is an important public health and clinical issue in China currently. Macrolide resistance in is a serious challenge to prevent and manage pertussis in China. Early, timely and effective antimicrobial therapy plays an important role in alleviating disease, reducing complications and severe diseases, eliminating carriers and reducing secondary transmission, and implementing post-exposure chemoprophylaxis in special scenarios is also necessary to protect individuals at high risk of severe diseases.

[Calling for attention to prevention and treatment of infection in children during the fall-winter seasons].

(MP) is a common cause of community-acquired pneumonia in children in China, and it is often prevalent in the autumn and winter seasons. In the autumn and winter of 2023, a large-scale epidemic outbreak of MP pneumonia occurred nationwide in the pediatric population, which brought harm to child health, caused a heavy disease burden, imposed a challenge to the pediatric medical service system, and aroused great attention from medical administration and public health fields. The widespread prevalence of macrolide-resistant MP (MRMP) in China has become a prominent problem in pediatric clinical practice.

Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges.

Targeting deubiquitinase USP7-mediated stabilization of XPO1 contributes to the anti-myeloma effects of selinexor.

Background: Targeting exportin1 (XPO1) with Selinexor (SEL) is a promising therapeutic strategy for patients with multiple myeloma (MM). However, intrinsic and acquired drug resistance constitute great challenges. SEL has been reported to promote the degradation of XPO1 protein in tumor cells.

Specific plasma metabolite profile in intestinal Behçet's syndrome.

Background: Intestinal Behçet's syndrome (IBS) has high morbidity and mortality rates with serious complications. However, there are few specific biomarkers for IBS. The purposes of this study were to investigate the distinctive metabolic changes in plasma samples between IBS patients and healthy people, active IBS and inactive IBS patients, and to identify candidate metabolic biomarkers which would be useful for diagnosing and predicting IBS.

STAT6 deficiency mitigates the severity of pulmonary arterial hypertension caused by chronic intermittent hypoxia by suppressing Th2-inducing cytokines.

Background: Obstructive sleep apnea (OSA) is frequently associated with increased incidence and mortality of pulmonary hypertension (PH). The immune response contributes to pulmonary artery remodeling and OSA-related diseases. The immunologic factors linked to OSA-induced PH are not well understood.

Characterizing tertiary lymphoid structures associated single-cell atlas in breast cancer patients.

The tertiary lymphoid structure (TLS) is recognized as a potential prognosis factor for breast cancer and is strongly associated with response to immunotherapy. Inducing TLS neogenesis can enhance the immunogenicity of tumors and improve the efficacy of immunotherapy. However, our understanding of TLS associated region at the single-cell level remains limited.

Combined exposure to mixed brominated flame retardants on obstructive sleep apnea syndrome in US adults.

Background: Accumulating research highlights that exposure to serum brominated flame retardants (BFRs) may elevate health risks. The effects of serum BFRs, both alone and in combination, on obstructive sleep apnea syndrome (OSAS) have not been thoroughly studied. Our main goal was to examine the association between individual and mixtures of serum BFRs and OSAS risk.

Prevalence and predictors of left atrial thrombus in patients with rheumatic atrial fibrillation undergoing cardiac surgery: a cross-sectional study.

Background: Unlike non-rheumatic atrial fibrillation (AF), where left atrial thrombus (LAT) is predominantly confined to the left atrial appendage (LAA), a significant proportion of LAT in rheumatic AF occurs within the left atrial cavity (LAC). However, LAC thrombosis in rheumatic AF has not been extensively studied. This study aimed to evaluate the prevalence of LAT and its subtypes and identify potential predictors of LAT.

Use of Steered Molecular Dynamics to Explore the Conformational Changes of SNARE Proteins.

Steered Molecular Dynamics (SMD) simulation is a powerful computational simulation technique that enables the controlled manipulation of molecular systems by applying external forces. This method is frequently utilized to investigate the slow processes of biomolecular systems that occur within sub-second to second time scales, achieved through SMD simulations that only span nanoseconds. SMD simulation can be utilized to study the detailed mechanism of protein conformational changes, protein unfolding, and ligand dissociation, etc.

Fruquintinib Plus Sintilimab in Patients with Treatment-Naive and Previously Treated Advanced Renal Cell Carcinoma: Results from a Phase Ib/II Clinical Trial.

Background: Antiangiogenic inhibitors plus immune checkpoint inhibitors have synergistic antitumor activity and have improved treatment outcomes in patients with renal cell carcinoma (RCC).

Objective: We report the RCC cohort from a phase Ib/II study in Chinese patients evaluating the efficacy and safety of fruquintinib plus sintilimab in treating advanced clear cell RCC (ccRCC).

Patients And Methods: Eligible patients had pathologically confirmed advanced ccRCC.

Resolving and routing magnetic polymorphs in a 2D layered antiferromagnet.

Polymorphism, commonly denoting diverse molecular or crystal structures, is crucial in the natural sciences. In van der Waals antiferromagnets, a new type of magnetic polymorphism arises, presenting multiple layer-selective magnetic structures with identical total magnetization. However, resolving and manipulating such magnetic polymorphs remain challenging.

Genome-wide association study unravels mechanisms of brain glymphatic activity.

Brain glymphatic activity, as indicated by diffusion-tensor imaging analysis along the perivascular space (ALPS) index, is involved in developmental neuropsychiatric and neurodegenerative diseases, but its genetic architecture is poorly understood. Here, we identified 17 unique genome-wide significant loci and 161 candidate genes linked to the ALPS-indexes in a discovery sample of 31,021 individuals from the UK Biobank. Seven loci were replicated in two independent datasets.

Nonlinear exposure-response associations of daytime, nighttime, and day-night compound heatwaves with mortality amid climate change.

Heatwaves are commonly simplified as binary variables in epidemiological studies, limiting the understanding of heatwave-mortality associations. Here we conduct a multi-country study across 28 East Asian cities that employed the Cumulative Excess Heatwave Index (CEHWI), which represents excess heat accumulation during heatwaves, to explore the potentially nonlinear associations of daytime-only, nighttime-only, and day-night compound heatwaves with mortality from 1981 to 2010. Populations exhibited high adaptability to daytime-only and nighttime-only heatwaves, with non-accidental mortality risks increasing only at higher CEHWI levels (75th-90th percentiles).

Tailoring Water-in-DMSO Electrolyte for Ultra-stable Rechargeable Zinc Batteries.

Rechargeable zinc batteries (RZBs) are hindered by two primary challenges: instability of Zn anode and deterioration of the cathode structure in traditional aqueous electrolytes, largely attributable to the decomposition of active H2O. Here, we design and synthesize a non-flammable water-in-dimethyl sulfoxide electrolyte to address these issues. X-ray absorption spectroscopy, in situ techniques and computational simulations demonstrate that the activity of H2O in this electrolyte is extremely compressed, which not only suppresses the side reactions and increases the reversibility of Zn anode, but also diminishes the cathode dissolution and proton intercalation.