The IRE1 endoplasmic reticulum stress sensor activates natural killer cell immunity in part by regulating c-Myc.

Natural killer (NK) cells are critical mediators of host immunity to pathogens. Here, we demonstrate that the endoplasmic reticulum stress sensor inositol-requiring enzyme 1 (IRE1α) and its substrate transcription factor X-box-binding protein 1 (XBP1) drive NK cell responses against viral infection and tumors in vivo. IRE1α-XBP1 were essential for expansion of activated mouse and human NK cells and are situated downstream of the mammalian target of rapamycin signaling pathway. Transcriptome and chromatin immunoprecipitation analysis revealed c-Myc as a new and direct downstream target of XBP1 for regulation of NK cell proliferation. Genetic ablation or pharmaceutical blockade of IRE1α downregulated c-Myc, and NK cells with c-Myc haploinsufficency phenocopied IRE1α-XBP1 deficiency. c-Myc overexpression largely rescued the proliferation defect in IRE1α-/- NK cells. Like c-Myc, IRE1α-XBP1 also promotes oxidative phosphorylation in NK cells. Overall, our study identifies a IRE1α-XBP1-cMyc axis in NK cell immunity, providing insight into host protection against infection and cancer.

Evidence for the association of triatomic molecules in ultracold 23Na40K + 40K mixtures.

Ultracold assembly of diatomic molecules has enabled great advances in controlled chemistry, ultracold chemical physics and quantum simulation with molecules1-3. Extending the ultracold association to triatomic molecules will offer many new research opportunities and challenges in these fields. A possible approach is to form triatomic molecules in a mixture of ultracold atoms and diatomic molecules by using a Feshbach resonance between them4,5. Although ultracold atom-diatomic-molecule Feshbach resonances have been observed recently6,7, using these resonances to form triatomic molecules remains challenging. Here we report on evidence of the association of triatomic molecules near the Feshbach resonance between 23Na40K molecules in the rovibrational ground state and 40K atoms. We apply a radio-frequency pulse to drive the free-bound transition in ultracold mixtures of 23Na40K and 40K and monitor the loss of 23Na40K molecules. The association of triatomic molecules manifests itself as an additional loss feature in the radio-frequency spectra, which can be distinguished from the atomic loss feature. The observation that the distance between the association feature and the atomic transition changes with the magnetic field provides strong evidence for the formation of triatomic molecules. The binding energy of the triatomic molecules is estimated from the measurements. Our work contributes to the understanding of the complex ultracold atom-molecule Feshbach resonances and may open up an avenue towards the preparation and control of ultracold triatomic molecules.

Heterodimensional superlattice with in-plane anomalous Hall effect.

Superlattices-a periodic stacking of two-dimensional layers of two or more materials-provide a versatile scheme for engineering materials with tailored properties1,2. Here we report an intrinsic heterodimensional superlattice consisting of alternating layers of two-dimensional vanadium disulfide (VS2) and a one-dimensional vanadium sulfide (VS) chain array, deposited directly by chemical vapour deposition. This unique superlattice features an unconventional 1T stacking with a monoclinic unit cell of VS2/VS layers identified by scanning transmission electron microscopy. An unexpected Hall effect, persisting up to 380 kelvin, is observed when the magnetic field is in-plane, a condition under which the Hall effect usually vanishes. The observation of this effect is supported by theoretical calculations, and can be attributed to an unconventional anomalous Hall effect owing to an out-of-plane Berry curvature induced by an in-plane magnetic field, which is related to the one-dimensional VS chain. Our work expands the conventional understanding of superlattices and will stimulate the synthesis of more extraordinary superstructures.

HERC3 promotes YAP/TAZ stability and tumorigenesis independently of its ubiquitin ligase activity.

YAP/TAZ transcriptional co-activators play pivotal roles in tumorigenesis. In the Hippo pathway, diverse signals activate the MST-LATS kinase cascade that leads to YAP/TAZ phosphorylation, and subsequent ubiquitination and proteasomal degradation by SCFß-TrCP . When the MST-LATS kinase cascade is inactive, unphosphorylated or dephosphorylated YAP/TAZ translocate into the nucleus to mediate TEAD-dependent gene transcription. Hippo signaling-independent YAP/TAZ activation in human malignancies has also been observed, yet the mechanism remains largely elusive. Here, we report that the ubiquitin E3 ligase HERC3 can promote YAP/TAZ activation independently of its enzymatic activity. HERC3 directly binds to ß-TrCP, blocks its interaction with YAP/TAZ, and thus prevents YAP/TAZ ubiquitination and degradation. Expression levels of HERC3 correlate with YAP/TAZ protein levels and expression of YAP/TAZ target genes in breast tumor cells and tissues. Accordingly, knockdown of HERC3 expression ameliorates tumorigenesis of breast cancer cells. Our results establish HERC3 as a critical regulator of the YAP/TAZ stability and a potential therapeutic target for breast cancer.

Pre-Corrosion of Zinc Metal Anodes for Enhanced Stability and Kinetics.

Non-uniform zinc plating/stripping in aqueous zinc-ion batteries (ZIBs) often leads to dendrites formation and low Coulombic efficiency (CE), limiting their large-scale application. In this study, a pre-corroded Zn (PC-Zn) anode with 3D ridge-like structure is constructed by a facile solution etching in sodium hypophosphite (NaH2PO2) solution. The surface preparation process can significantly remove impurities from the passivation layer of bare Zn anode, thus exposing a great quantity of active sites for easy plating/stripping. Moreover, the pre-corroded structure enables a uniform-distributed electric field to promote the 3D Zn2+ diffusion process and accelerate the transfer kinetics, thereby suppressing the zinc dendrites and interfacial side reactions. Consequently, symmetric cells with PC-Zn electrodes demonstrate remarkable stability, maintaining cycles for over 3200 h under 1 mA cm-2. The PC-Zn/VO2 full cell maintains a specific capacity of 361 mAh g-1 at 0.1 A g-1, and a capacity retention rate of ≈80% over 1000 cycles at 4 A g-1. Notably, no obvious dendrites and side reactions are detected after extended cycling. Leveraging the cost-effectiveness, environmentally friendly nature, and easy fabrication of the PC-Zn electrode, this Zn protection strategy holds promise for advancing the industrial application of ZIBs.

Industrial Waste Derived Separators for Zn-Ion Batteries Achieve Homogeneous Zn(002) Deposition Through Low Chemical Affinity Effects.

Designing a cost-effective and multifunctional separator that ensures dendrite-free and stable Zn metal anode remains a significant challenge. Herein, a multifunctional cellulose-based separator is presented consisting of industrial waste-fly ash particles and cellulose nanofiber using a facile solution-coating method. The resulting fly ash-cellulose (FACNF) separators enable a high ion conductivity (5.76 mS cm-1) and low desolvation energy barrier of hydrated Zn2+. These features facilitate fast ion transfer kinetics and inhibit water-induced side reactions. Furthermore, experimental results and theoretical simulations confirm that the presence of fly ash particles in FACNF separators effectively accommodate the preferential deposition of Zn(002) planes, due to the weak chemical affinity between Zn(002) plane and fly ash, to mitigate dendrite formation and growth. Consequently, the utilization of FACNF separators causes an impressive cycling performance in both Zn||Zn symmetric cells (1600 h at 2 mA cm-2/1 mAh cm-2) and Zn||(NH4)2V10O25 (NVO) full cells (4000 cycles with the capacity retention of 92.1% at 5 A g-1). Furthermore, the assembled pouch cells can steadily support digital thermometer over two months without generating gas and volume expansion. This work provides new insights for achieving crystallographic uniformity in Zn anodes and realizing cost-effective and long-lasting aqueous zinc-ion batteries (AZIBs).

Proteomic analysis of mitochondria associated membranes in renal ischemic reperfusion injury.

BACKGROUND: The mitochondria and endoplasmic reticulum (ER) communicate via contact sites known as mitochondria associated membranes (MAMs). Many important cellular functions such as bioenergetics, mitophagy, apoptosis, and calcium signaling are regulated by MAMs, which are thought to be closely related to ischemic reperfusion injury (IRI). However, there exists a gap in systematic proteomic research addressing the relationship between these cellular processes. METHODS: A 4D label free mass spectrometry-based proteomic analysis of mitochondria associated membranes (MAMs) from the human renal proximal tubular epithelial cell line (HK-2 cells) was conducted under both normal (N) and hypoxia/reperfusion (HR) conditions. Subsequent differential proteins analysis aimed to characterize disease-relevant signaling molecules. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was applied to total proteins and differentially expressed proteins, encompassing Biological Process (BP), Cell Component (CC), Molecular Function (MF), and KEGG pathways. Further, Protein-Protein Interaction Network (PPI) exploration was carried out, leading to the identification of hub genes from differentially expressed proteins. Notably, Mitofusion 2 (MFN2) and BCL2/Adenovirus E1B 19-kDa interacting protein 3(BNIP3) were identified and subsequently validated both in vitro and in vivo. Finally, the impact of MFN2 on MAMs during hypoxia/reoxygenation was explored through regulation of gene expression. Subsequently, a comparative proteomics analysis was conducted between OE-MFN2 and normal HK-2 cells, providing further insights into the underlying mechanisms. RESULTS: A total of 4489 proteins were identified, with 3531 successfully quantified. GO/KEGG analysis revealed that MAM proteins were primarily associated with mitochondrial function and energy metabolism. Differential analysis between the two groups showed that 688 proteins in HR HK-2 cells exhibited significant changes in expression level with P-value < 0.05 and HR/N > 1.5 or HR/N < 0.66 set as the threshold criteria. Enrichment analysis of differentially expressed proteins unveiled biological processes such as mRNA splicing, apoptosis regulation, and cell division, while molecular functions were predominantly associated with energy metabolic activity. These proteins play key roles in the cellular responses during HR, offering insights into the IRI mechanisms and potential therapeutic targets. The validation of hub genes MFN2 and BNIP3 both in vitro and vivo was consistent with the proteomic findings. MFN2 demonstrated a protective role in maintaining the integrity of mitochondria associated membranes (MAMs) and mitigating mitochondrial damage following hypoxia/reoxygenation injury, this protective effect may be associated with the activation of the PI3K/AKT pathway. CONCLUSIONS: The proteins located in mitochondria associated membranes (MAMs) are implicated in crucial roles during renal ischemic reperfusion injury (IRI), with MFN2 playing a pivotal regulatory role in this context.

Observation of Photoassociation Resonances in Ultracold Atom-Molecule Collisions.

We report on the observation of photoassociation resonances in ultracold collisions between ^{23}Na^{40}K molecules and ^{40}K atoms. We perform photoassociation in a long-wavelength optical dipole trap to form deeply bound triatomic molecules in electronically excited states. The atom-molecule Feshbach resonance is used to enhance the free-bound Franck-Condon overlap. The photoassociation into well-defined quantum states of excited triatomic molecules is identified by observing resonantly enhanced loss features. These loss features depend on the polarization of the photoassociation lasers, allowing us to assign rotational quantum numbers. The observation of ultracold atom-molecule photoassociation resonances paves the way toward preparing ground-state triatomic molecules, provides a new high-resolution spectroscopy technique for polyatomic molecules, and is also important to atom-molecule Feshbach resonances.

Cross-country inequalities in disease burden and care quality of chronic kidney disease due to type 2 diabetes mellitus, 1990-2021: Findings from the global burden of disease study 2021.

AIM: To explore the trend of burden and care quality of chronic kidney disease due to type 2 diabetes mellitus (CKD-T2DM) and their cross-country inequalities from 1990 to 2021. MATERIALS AND METHODS: Data were from the Global Burden of Disease 2021 study. Disease burden and care quality were quantified using the disability-adjusted life years rate and the quality-of-care index (QCI). Trend analyses of the age-standardized disability-adjusted life years rate (ASDR) and age-standardized QCI from 1990 to 2021 were conducted using the estimated annual percentage change. The associations of disease burden and care quality with the socio-demographic index (SDI) were explored. Cross-country inequalities in disease burden and care quality were assessed using the slope index of inequality (SII) and concentration index. RESULTS: From 1990 to 2021, the global ASDR for CKD-T2DM increased, while the age-standardized QCI slightly decreased, with an estimated annual percentage change of 0.81 [95% confidence interval (CI): 0.75, 0.87] and -0.08 (95% CI: -0.09, -0.07). The ASDR escalated with increasing SDI, reaching a peak at mid-level SDI, followed by a decrease. The age-standardized QCI was higher with increasing SDI. Globally, ASDR concentrated on countries/territories with a lower SDI. The SII of ASDR was -96.64 (95% CI: -136.94, -56.35) in 1990 and -118.15 (95% CI: -166.36, -69.94) in 2021,  with a concentration index of -0.1298 (95% CI: -0.1904, -0.0692) in 1990 and -0.1104 (95% CI: -0.1819, -0.0389) in 2021. In 1990 and 2021, countries/territories at higher SDI levels exhibited increased age-standardized QCI, indicated by an SII of 15.09 (95% CI: 10.74, 19.45) and 15.75 (95% CI: 10.92, 20.59), and a concentration index of 0.0393 (95% CI: 0.0283, 0.0503) and 0.0400 (95% CI: 0.0264, 0.0536). CONCLUSIONS: Our study highlights considerable disparities in the burden and care quality of CKD-T2DM. Regions experiencing an increasing burden and a declining care quality simultaneously underscore the need for further research and tailored health interventions.

Eco-friendly one-step egg white gel preparation for sensitive detection of 13 trichothecenes in oats using UHPLC-MS/MS.

Oat products have gained widespread recognition as a health food due to their rich and balanced nutritional profile and convenience. However, the unique matrix composition of oats, which differs significantly from other cereals, presents specific challenges for mycotoxin analysis. This study presents an ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method enhanced with an innovative egg white gel pretreatment for the simultaneous analysis of 13 regulated and unregulated trichothecenes in oats. The method demonstrated excellent performance with high accuracy (> 87.5%), repeatability (< 5.7%), and reproducibility (< 8.1%). Analysis of 100 commercial oat products revealed a concerning detection rate (78%) for at least one of the 11 trichothecenes investigated. Notably, deoxynivalenol, exceeding the standard limit in 2% of samples, exhibited the highest detection rate (62%). Additionally, concerning co-occurrence patterns and positive correlations were observed, highlighting potential synergistic effects. The first-time detection of unregulated mycotoxins (T-2 triol, 4,15-diacetoxyscirpenol, 15-acetoxyscirpenol, and neosolaniol) underscores the need for comprehensive monitoring. This method, while developed for oats, shows potential for broader application to other cereals, though further investigation and confirmation are necessary. These findings suggest a potentially underestimated risk of trichothecenes in oats, necessitating continuous monitoring to ensure consumer safety.

Cavomycins A-C, Linear Oligomer Depsipeptides from an Annelid-Associated Streptomyces cavourensis.

Three unique linear oligomeric depsipeptides, designated as cavomycins A-C (1-3), were identified from Streptomyces cavourensis, a gut bacterium associated with the annelid Paraleonnates uschakovi. The structures of these depsipeptides were determined through a combination of spectroscopic methods and chemical derivatization techniques, including methanolysis, the modified Mosher's method, advanced Marfey's methods, and phenylglycine methyl ester derivatization. The unique dipeptidyl residue arrangements in compounds 1-3 indicate that they are not degradation products of valinomycin. Compound 2 and its methylation derivative 2a exhibited antiproliferative activity against PANC-1 pancreatic cancer cells with IC50 values of 1.2 and 1.7 µM, respectively.

The altered hippocampal functional connectivity and serum brain-derived neurotrophic factor level predict cognitive decline in patients with knee osteoarthritis.

Patients with knee osteoarthritis (KOA) often suffer from cognitive decline and increased dementia risk, but the neurobiological mechanisms remain unclear. In this study, we evaluated cognitive performance and collected brain magnetic resonance imaging (MRI) data and blood samples from cognitively normal KOA patients at baseline sessions and reevaluated their cognition after 5 years. We also collected MRI data from matched healthy controls. Results showed that KOA patients exhibited dysregulated functional connectivities between the hippocampus and thalamus/superior frontal gyrus compared with healthy controls. The altered hippocampal functional connectivities were associated with serum brain-derived neurotrophic factor (BDNF) levels and spatial expression of genes enriched in synaptic plasticity. The hippocampus-thalamus functional connectivity was significantly correlated with patients' memory scores. Moreover, the baseline hippocampus-thalamus functional connectivity and BDNF levels significantly predicted the development of cognitive decline in KOA patients in the follow-up session. Our findings provide insight into the neurobiological underpinnings of KOA and cognitive decline.

Associations of serum uric acid with hypertension status, stages, phenotypes and progressions among Chinese middle-aged and elderly.

BACKGROUND AND AIMS: No consensus has been reached on the association between serum uric acid (SUA) and hypertension. This study aimed to investigate the associations between SUA and hypertension, including its status, stages, phenotypes and progressions, among middle-aged and older Chinese. METHODS AND RESULTS: Data were obtained from the China Health and Retirement Longitudinal Study 2011-2015. Binary logistic regression was used to evaluate the association between SUA and hypertension status. Multinomial logistic regression was used to explore the associations of SUA with hypertension stages, phenotypes and hypertension status progressions. Models were adjusted for potential confounders and stratified by sex. A total of 7931 individuals aged ≥45 years were included, with 39.16 % of hypertension. Significant associations were found of SUA with stage2 and above hypertension (quartile 4 [Q4] vs quartile 1 [Q1]: odds ratio 1.78, 95 % confidence interval 1.31-2.42, P < 0.001), and systolic diastolic hypertension (SDH) (Q4 vs Q1: 1.53, 1.14-2.06, P = 0.005). In sex stratification, significant associations were found between SUA and stage2 and above hypertension and SDH only for men. Moreover, higher quartiles of baseline SUA showed increased risks of maintained hypertension from 2011 to 2015 (Q3 vs Q1: 1.23, 1.03-1.48, P = 0.024; Q4 vs Q1: 1.73, 1.43-2.10, P < 0.001). CONCLUSION: Higher SUA was associated with hypertension and maintained hypertension among Chinese middle-aged and elderly. Sex-specific associations of SUA with hypertension stages and phenotypes were observed. Regular measurement of SUA in clinical practice may indicate hypertension and its progression, particularly among men.

Propagation properties of a partially coherent electromagnetic hyperbolic-sine-Gaussian vortex beam through anisotropic atmospheric turbulence.

Using the extended Huygens-Fresnel principle and the Rytov approximation, the analytical formula for the propagation of a partially coherent electromagnetic hyperbolic-sine-Gaussian vortex beam (PCEShVB) in anisotropic atmospheric turbulence has been theoretically derived. Detailed studies have been conducted on the evolution characteristics of the average intensity, the degree of coherence (DOC), and the degree of polarization (DOP) of the beam in turbulence. The results show that during propagation, the intensity distribution of the beam will exhibit a spiral structure, and the overall distribution of the light spots will rotate in a direction related to the sign of the topological charge. The DOC distribution of PCEShVB will display a pattern reminiscent of beam interference fringes with an increase in propagation distance, with the number of "interference fringes" greatly impacted by the hyperbolic sine parameter. Furthermore, PCEShVB with a large initial coherent length and hyperbolic sine parameter will increase the degree of separation of the spots and yield a large DOP. Finally, for the validation of the theoretical findings, the random phase screen method was employed to simulate the propagation of PCEShVB through anisotropic atmospheric turbulence. The studies revealed a consistent alignment between the simulation results and the theoretical predictions.

Preparation and Application of Volatilized Wormwood Essence Derived Naturally into Green Insecticide.

Naturally occurring substances and their derivatives function as vital resources for pesticides that can be used in fields, such as insecticide production and fungicide development. As a botanical entity displaying multifaceted biological functions, wormwood has received thorough scrutiny across multiple sectors. The insect repellency potency combined with antibacterial and antifungal activities of wormwood position it as a potential candidate for prospective development into eco-friendly chemical pesticides. In this research, Wormwood essential oil was procured via ethanol water under ultrasonic scenarios and subsequently diluted with PEG 400 to formulate green chemical pesticides. The defensive efficacy of this green pesticide on plants was validated through 2 weeks of clustered plant growth experiments. Active constituents that exerted their effects were scrutinized by GC-MS. Furthermore, this green pesticide also displays efficacious effects on the prevention and management of aphids, exhibiting a dose-dependent relationship. 4-terpenol, eucalyptol, carvacrol, and L-borneol were identified by GC-MS as the predominant active constituents in this green chemical pesticide. Wormwood can be leveraged to develop green chemical pesticides, which can protect plants without contaminating the environment.

UPLC-MS/MS-Based Target Screening of 90 Phosphodiesterase Type 5 Inhibitors in 5 Dietary Supplements.

The aim of individuals consuming health supplements is to attain a robust state through nutritional regulation. However, some unscrupulous manufacturers, motivated by profit, fraudulently incorporate drugs or unauthorized components with therapeutic effects into the product for instant product performance enhancement. The long-term use of these products may inadvertently inflict harm on human health and fail to promote nutritive healthcare. The illegal inclusion of these substances is prevalent in kidney-tonifying and sexuality-enhancing products. Developing effective analytical methods to identify these products and screen for illegal added ingredients can effectively prevent such products from reaching and remaining on the market. A target screening method for the detection and quantification of 90 phosphodiesterase type 5 inhibitors (PDE-5is) in 5 kinds of health products was developed and validated. The type of dietary supplements varied from tablets, capsules, and protein powder to wine and beverages. Sample preparation was completed with a one-step liquid phase extraction. The screening process of 90 PDE-5is was done efficiently within 25 min by ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) using the dynamic multiple reaction monitoring (dMRM) technique. The LODs of 90 PDE-5is were detected at levels ranging from 25 to 85 ng/g or ng/mL. This novel targeting methodology was effective and can be applied to routine market supervision. Among 286 batches of samples, 8 batches were found to be positive. Three kinds of PDE-5is were first detected in healthy products. The screening method demonstrated herein will be a promising and powerful tool for rapid screening of PDE-5is.

Genetic evidence for the causal relationships between migraine, dementia, and longitudinal brain atrophy.

BACKGROUND: Migraine is a neurological disease with a significant genetic component and is characterized by recurrent and prolonged episodes of headache. Previous epidemiological studies have reported a higher risk of dementia in migraine patients. Neuroimaging studies have also shown structural brain atrophy in regions that are common to migraine and dementia. However, these studies are observational and cannot establish causality. The present study aims to explore the genetic causal relationship between migraine and dementia, as well as the mediation roles of brain structural changes in this association using Mendelian randomization (MR). METHODS: We collected the genome-wide association study (GWAS) summary statistics of migraine and its two subtypes, as well as four common types of dementia, including Alzheimer's disease (AD), vascular dementia, frontotemporal dementia, and Lewy body dementia. In addition, we collected the GWAS summary statistics of seven longitudinal brain measures that characterize brain structural alterations with age. Using these GWAS, we performed Two-sample MR analyses to investigate the causal effects of migraine and its two subtypes on dementia and brain structural changes. To explore the possible mediation of brain structural changes between migraine and dementia, we conducted a two-step MR mediation analysis. RESULTS: The MR analysis demonstrated a significant association between genetically predicted migraine and an increased risk of AD (OR = 1.097, 95% CI = [1.040, 1.158], p = 7.03 × 10- 4). Moreover, migraine significantly accelerated annual atrophy of the total cortical surface area (-65.588 cm2 per year, 95% CI = [-103.112, -28.064], p = 6.13 × 10- 4) and thalamic volume (-9.507 cm3 per year, 95% CI = [-15.512, -3.502], p = 1.91 × 10- 3). The migraine without aura (MO) subtype increased the risk of AD (OR = 1.091, 95% CI = [1.059, 1.123], p = 6.95 × 10- 9) and accelerated annual atrophy of the total cortical surface area (-31.401 cm2 per year, 95% CI = [-43.990, -18.811], p = 1.02 × 10- 6). The two-step MR mediation analysis revealed that thalamic atrophy partly mediated the causal effect of migraine on AD, accounting for 28.2% of the total effect. DISCUSSION: This comprehensive MR study provided genetic evidence for the causal effect of migraine on AD and identified longitudinal thalamic atrophy as a potential mediator in this association. These findings may inform brain intervention targets to prevent AD risk in migraine patients.

Proteome-wide Mendelian randomization identified potential drug targets for migraine.

BACKGROUND: Migraine is a highly prevalent and complex neurovascular disease. However, the currently available therapeutic drugs often fall to adequately meet clinical needs due to limited effectiveness and numerous undesirable side effects. This study aims to identify putative novel targets for migraine treatment through proteome-wide Mendelian randomization (MR). METHODS: We utilized MR to estimate the causal effects of plasma proteins on migraine and its two subtypes, migraine with aura (MA) and without aura (MO). This analysis integrated plasma protein quantitative trait loci (pQTL) data with genome-wide association studies (GWAS) findings for these migraine phenotypes. Moreover, we conducted a phenome-wide MR assessment, enrichment analysis, protein-protein interaction networks construction, and mediation MR analysis to further validate the pharmaceutical potential of the identified protein targets. RESULTS: We identified 35 protein targets for migraine and its subtypes (p < 8.04 × 10-6), with prioritized targets showing minimal side effects. Phenome-wide MR identified novel protein targets-FCAR, UBE2L6, LATS1, PDCD1LG2, and MMP3-that have no major disease side effects and interacted with current acute migraine medication targets. Additionally, MMP3, PDCD1LG2, and HBQ1 interacted with current preventive migraine medication targets. The causal effects of plasma protein on migraine were partly mediated by plasma metabolites (proportion of mediation from 3.8% to 21.0%). CONCLUSIONS: A set of potential protein targets for migraine and its subtypes were identified. These proteins showed rare side effects and were responsible for biological mechanisms involved in migraine pathogenesis, indicating priority for the development of migraine treatments.

In-Situ Ultrafast Construction of Zinc Tungstate Interface Layer for Highly Reversible Zinc Anodes.

Constructing artificial solid electrolyte interface on the Zn anode surface is recognized as an appealing method to inhibit zinc dendrites and side reactions, whereas the current techniques are complex and time-consuming. Here, a robust and zincophilic zinc tungstate (ZnWO4) layer has been in situ constructed on the Zn anode surface (denoted as ZWO@Zn) by an ultrafast chemical solution reaction. Comprehensive characterizations and theoretical calculations demonstrate that the ZWO layer can effectively modulate the interfacial electric field distribution and promote the Zn2+ uniform diffusion, thus facilitating the uniform Zn2+ nucleation and suppressing zinc dendrites. Besides, ZWO layer can prevent direct contact between the Zn/water and increase the hydrogen evolution reaction overpotential to eliminate side reactions. Consequently, the in situ constructed ZWO layer facilitates remarkable reversibility in the ZWO@Zn||Ti battery, achieving an impressive Coulombic efficiency of 99.36 % under 1.0 mA cm-2, unprecedented cycling lifespan exceeding 1800 h under 1.0 mA cm-2 in ZWO@Zn||ZWO@Zn battery, and a steady and reliable operation of the overall ZWO@Zn||VS2 battery. The work provides a simple, low cost, and ultrafast pathway to crafting protective layers for driving advancements in aqueous zinc-metal batteries.

[Temporal trend of the global prevalence rate of tension-type headache in children and adolescents in 1990-2021]. / 1990­2021å¹´å ¨çƒå„¿ç«¥é’å°‘å¹´ç´§å¼ æ€§å¤´ç—›æ‚£ç— çŽ‡æ—¶é—´å˜åŒ–è¶‹åŠ¿ç ”ç©¶.

OBJECTIVES: To investigate the prevalence of tension-type headache (TTH) in children and adolescents aged 0-19 years globally in 1990-2021, and to provide a basis for the prevention and treatment of TTH. METHODS: Based on the Global Burden of Disease Study data, the age-standardized prevalence distribution of TTH and its changing trend were analyzed among the children and adolescents aged 0-19 years, with different sexes, age groups, sociodemographic index (SDI) regions and countries/territories. RESULTS: The age-standardized prevalence rate (ASPR) of TTH in children and adolescents aged 0-19 globally in 2021 was 17 339.89/100 000, which was increased by 1.73% since 1990. The ASPR in females was slightly higher than that in males (1990: 17 707.65/100 000 vs 16 403.78/100 000; 2021: 17 946.29/100 000 vs 16 763.09/100 000). The ASPR in adolescence was significantly higher than that in school-aged and preschool periods (1990: 27 672.04/100 000 vs 10 134.16/100 000; 2021: 28 239.04/100 000 vs 10 059.39/100 000). Regions with high SDI exhibited a higher ASPR than the other regions, with significant differences in prevalence rates across different countries. From 1990 to 2021, there was a slight increase in global ASPR, with an average annual percentage change (AAPC) of 0.06%. Females experienced a smaller increase than males based on AAPC (0.04% vs 0.07%). There was reduction in ASPR in preschool and school-aged groups, with an AAPC of -0.02%, while there was a significant increase in ASPR in adolescence, with an AAPC of 0.07%. ASPR decreased in regions with low-middle and low levels of SDI, with an AAPC of -0.02% and -0.04%, respectively, while it increased in regions with middle SDI, with an AAPC of 0.24%. CONCLUSIONS: There is a consistent increase in the ASPR of TTH in children and adolescents aged 0-19 years globally, with significant differences across sexes, age groups, SDI regions and countries/territories.