Epidemiological trends of subarachnoid hemorrhage at global, regional, and national level: a trend analysis study from 1990 to 2021.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a subtype of hemorrhagic stroke characterized by high mortality and low rates of full recovery. This study aimed to investigate the epidemiological characteristics of SAH between 1990 and 2021. METHODS: Data on SAH incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021 were obtained from the Global Burden of Disease Study (GBD) 2021. Estimated annual percentage changes (EAPCs) were calculated to evaluate changes in the age-standardized rate (ASR) of incidence and mortality, as well as trends in SAH burden. The relationship between disease burden and sociodemographic index (SDI) was also analyzed. RESULTS: In 2021, the incidence of SAH was found to be 37.09% higher than that in 1990; however, the age-standardized incidence rates (ASIRs) showed a decreased [EAPC: -1.52; 95% uncertainty interval (UI) -1.66 to -1.37]. Furthermore, both the number and rates of deaths and DALYs decreased over time. It was observed that females had lower rates compared to males. Among all regions, the high-income Asia Pacific region exhibited the highest ASIR (14.09/100,000; 95% UI 12.30/100,000 - 16.39/100,000) in 2021, with an EPAC for ASIR < 0 indicating decreasing trend over time for SAH ASIR. Oceania recorded the highest age-standardized mortality rates (ASMRs) and age-standardized DALYs rates among all regions in 2021 at values of respectively 8.61 (95% UI 6.03 - 11.95) and 285.62 (95% UI 209.42 - 379.65). The burden associated with SAH primarily affected individuals aged between 50 - 69 years old. Metabolic risks particularly elevated systolic blood pressure were identified as the main risk factors contributing towards increased disease burden associated with SAH when compared against environmental or occupational behavioral risks evaluated within the GBD framework. CONCLUSIONS: The burden of SAH varies by gender, age group, and geographical region. Although the ASRs have shown a decline over time, the burden of SAH remains significant, especially in regions with middle and low-middle SDI levels. High systolic blood pressure stands out as a key risk factor for SAH. More specific supportive measures are necessary to alleviate the global burden of SAH.

Impact of Lymph Node Dissection for Patients With Clinically Node-Negative Intrahepatic Cholangiocarcinoma: A Multicenter Cohort Study.

Background: Lymph node status is a prominent prognostic factor for intrahepatic cholangiocarcinoma (ICC). However, the prognostic value of performing lymph node dissection (LND) in patients with clinical node-negative ICC remains controversial. The aim of this study was to evaluate the clinical value of LND on long-term outcomes in this subgroup of patients. Methods: We retrospectively analyzed patients who underwent radical liver resection for clinically node-negative ICC from three tertiary hepatobiliary centers. The propensity score matching analysis at 1:1 ratio based on clinicopathological data was conducted between patients with and without LND. Recurrence-free survival (RFS) and overall survival (OS) were compared in the matched cohort. Results: Among 303 patients who underwent radical liver resection for ICC, 48 patients with clinically positive nodes were excluded, and a total of 159 clinically node-negative ICC patients were finally eligible for the study, with 102 in the LND group and 57 in the non-LND group. After propensity score matching, two well-balanced groups of 51 patients each were analyzed. No significant difference of median RFS (12.0 vs. 10.0 months, P = 0.37) and median OS (22.0 vs. 26.0 months, P = 0.47) was observed between the LND and non-LND group. Also, LND was not identified as one of the independent risks for survival. Among 51 patients who received LND, 11 patients were with positive lymph nodes (lymph node metastasis (LNM) (+)) and presented significantly worse outcomes than those with LND (-). On the other hand, postoperative adjuvant therapy was the independent risk factor for both RFS (hazard ratio (HR): 0.623, 95% confidence interval (CI): 0.393 - 0.987, P = 0.044) and OS (HR: 0.585, 95% CI: 0.359 - 0.952, P = 0.031). Furthermore, postoperative adjuvant therapy was associated with prolonged survivals of non-LND patients (P = 0.02 for RFS and P = 0.03 for OS). Conclusions: Based on the data, we found that LND did not significantly improve the prognosis of patients with clinically node-negative ICC. Postoperative adjuvant therapy was associated with prolonged survival of ICC patients, especially in non-LND individuals.

Mechanically Interlocked Polyrotaxane Networks with Collective Motions of Multiple Main-Chain Mechanical Bonds.

Type I main-chain polyrotaxanes (PRs) with multiple wheels threaded onto the axle are widely employed to design slide-ring materials. However, Type II main-chain PRs with axles threading into the macrocycles on the polymer backbones have rarely been studied, although they feature special topological structures and dynamic characteristics. Herein, we report the design and preparation of Type II main-chain PR-based mechanically interlocked networks (PRMINs), based on which the relationship between microscopic motion of mechanical bonds on the PRs and macroscopic mechanical performance of materials has been revealed. The representative PRMIN-2 exhibits a robust feature in tensile tests with high stretchability (1680%) and toughness (47.5 MJ/m3). Moreover, it also has good puncture performance with puncture energy of 22.0 mJ. Detailed rheological measurements and coarse-grained molecular dynamics (CGMD) simulation reveal that the embedded multiple [2]rotaxane mechanical bonds on the PR backbones of PRMINs could undergo a synergistic long-range sliding motion under external force, with the introduction of collective dangling chains into the network. As a result, the synchronized motions of coherent PR chains can be readily activated to accommodate network deformation and efficiently dissipate energy, thereby leading to enhanced mechanical performances of PRMINs.

A ratiometric fluorescence sensor for detection of organophosphorus pesticides based on enzyme-regulated multifunctional Fe-based metal-organic framework.

The residues of organophosphorus pesticides (OPs) are increasing environmental pollution and public health concerns. Thus, the development of simple, convenient and sensitive method for detection of OPs is crucial. Herein, a multifunctional Fe-based MOF with fluorescence, catalytic and adsorption, is synthesized by a simple one-pot hydrothermal method. The ratiometric fluorescence sensor for detection of OPs is constructed by using only one multifunctional sensing material. The NH2-MIL-101(Fe) is able catalyze the o-phenylenediamine (OPD) into 2,3-diaminophenazine (DAP) in the presence of H2O2. The generated DAP can significantly quench the intrinsic fluorescence of NH2-MIL-101(Fe) by the fluorescence resonance energy transfer (FRET) and internal filtration effect (IFE), while producing a new measurable fluorescence. Without immobilization or molecular imprinting, pyrophosphate ion (PPi) can inhibit the peroxidase-like activity of the NH2-MIL-101(Fe) by chelating with Fe3+/Fe2+ redox couple. Moreover, PPi can also be hydrolyzed by alkaline phosphatase (ALP), the presence of OPs inhibits the activity of ALP, resulting in the increase of extra PPi preservation and signal changes of ratiometric fluorescence, the interactions of ALP with different OPs are explored by molecular docking, the OPs (e.g., glyphosate) interact with crucial amino acid residues (Asp, Ser, Ala, Lys and Arg) are indicated. The proposed sensor exhibits excellent detection performance for OPs with the detection limit of 18.7 nM, which provides a promising strategy for detection of OPs.

Aneuploidy underlies brefeldin A-induced antifungal drug resistance in Cryptococcus neoformans.

Cryptococcus neoformans is at the top of the list of "most wanted" human pathogens. Only three classes of antifungal drugs are available for the treatment of cryptococcosis. Studies on antifungal resistance mechanisms are limited to the investigation of how a particular antifungal drug induces resistance to a particular drug, and the impact of stresses other than antifungals on the development of antifungal resistance and even cross-resistance is largely unexplored. The endoplasmic reticulum (ER) is a ubiquitous subcellular organelle of eukaryotic cells. Brefeldin A (BFA) is a widely used chemical inducer of ER stress. Here, we found that both weak and strong selection by BFA caused aneuploidy formation in C. neoformans, mainly disomy of chromosome 1, chromosome 3, and chromosome 7. Disomy of chromosome 1 conferred cross-resistance to two classes of antifungal drugs: fluconazole and 5-flucytosine, as well as hypersensitivity to amphotericin B. However, drug resistance was unstable, due to the intrinsic instability of aneuploidy. We found overexpression of AFR1 on Chr1 and GEA2 on Chr3 phenocopied BFA resistance conferred by chromosome disomy. Overexpression of AFR1 also caused resistance to fluconazole and hypersensitivity to amphotericin B. Furthermore, a strain with a deletion of AFR1 failed to form chromosome 1 disomy upon BFA treatment. Transcriptome analysis indicated that chromosome 1 disomy simultaneously upregulated AFR1, ERG11, and other efflux and ERG genes. Thus, we posit that BFA has the potential to drive the rapid development of drug resistance and even cross-resistance in C. neoformans, with genome plasticity as the accomplice.

Stimuli-responsive mechanically interlocked polymer wrinkles.

Artificial wrinkles, especially those with responsive erasure/regeneration behaviors have gained extensive interest due to their potential in smart applications. However, current wrinkle modulation methods primarily rely on network rearrangement, causing bottlenecks in in situ wrinkle regeneration. Herein, we report a dually cross-linked network wherein [2]rotaxane cross-link can dissipate stress within the wrinkles through its sliding motion without disrupting the network, and quadruple H-bonding cross-link comparatively highlight the advantages of [2]rotaxane modulation. Acid stimulation dissociates quadruple H-bonding and destructs network, swiftly eliminating the wrinkles. However, the regeneration process necessitates network rearrangement, making in situ recovery unfeasible. By contrast, alkaline stimulation disrupts host-guest recognition, and subsequent intramolecular motion of [2]rotaxane dissipate energy to eliminate wrinkles gradually. The always intact network allows for the in situ recovery of surface microstructures. The responsive behaviors of quadruple H-bonding and mechanical bond are orthogonal, and their combination leads to wrinkles with multiple but accurate responsiveness.

Spatially Confined Engineering Toward Deep Eutectic Electrolyte in Metal-Organic Framework Enabling Solid-State Zinc-Ion Batteries.

Uncontrollable interfacial side reactions generated from common aqueous electrolytes, just like the hydrogen evolution reaction (HER) and dendrite growth, have severely prevented the practical application of zinc-ion batteries (ZIBs). Solid-state ZIBs are considered to be an efficient strategy by adopting high-quality solid-state electrolytes (SSEs). Here, by confining the deep eutectic electrolyte (DEE) into the nanochannels of the metal-organic framework (MOF)-PCN-222, a stable DEE@PCN-222 SSE with internal Zn2+ transport channels was obtained. A distinctive ion-transport network composed of DEE and PCN-222 in the interior of DEE@PCN-222 realizes the efficient Zn2+ conduction, contributing to a high ionic conductivity of 3.13 × 10-4 S cm-1 at room temperature, a low activation energy of 0.12 eV, and a high Zn2+ transference number of 0.76. Furthermore, experimental and theoretical investigations demonstrate that DEE@PCN-222 with its unique channel structure could homogeneously regulate the Zn2+ distribution and effectively alleviate the side reactions. Highly reversible Zn plating/stripping performance of 2476 h can be realized by the SSE. The solid-state ZIBs show a specific capacity of 306 mAh g-1 and display cycling stability of 517 cycles. This unique design concept provides a new perspective in realizing the high-safety and high-performance ZIBs.

Size Dependence of Ultrafast Electron Transfer from Didodecyl Dimethylammonium Bromide-Modified CsPbBr3 Nanocrystals to Electron Acceptors.

Charge transfer efficiencies in all-inorganic lead halide perovskite nanocrystals (NCs) are crucial for applications in photovoltaics and photocatalysis. Herein, CsPbBr3 NCs with different sizes are synthesized by varying the ligand contents of didodecyl dimethylammonium bromide at room temperature. Adding benzoquinone (BQ) molecules leads to a decrease in the PL intensities and PL decay times in NCs. The electron transfer (ET) efficiency (ηET) increases with NC size in complexes of CsPbBr3 NCs and BQ molecules (NC-BQ complexes), when the same concentration of BQ is maintained, as investigated by transient photobleaching and photoluminescence spectroscopies. Controlling the same number of attached BQ acceptor molecules per NC induces the same ηET in NC-BQ complexes even though with different NC sizes. Our findings provide new insights into ultrafast charge transfer behaviors in perovskite NCs, which is important for designing efficient light energy conversion devices.

Long-Term Detection of Glycemic Glucose/Hypoglycemia by Microfluidic Sweat Monitoring Patch.

A microfluidic sweat monitoring patch that collects human sweat for a long time is designed to achieve the effect of detecting the rise and fall of human sweat glucose over a long period of time by increasing the use time of a single patch. Five collection pools, four serpentine channels, and two different valves are provided. Among them, the three-dimensional valve has a large burst pressure as a balance between the internal and external air pressures of the patch. The bursting pressure of the two-dimensional diverter valve is smaller than that of the three-dimensional gas valve, and its role is to control the flow direction of the liquid. Through plasma hydrophilic treatment of different durations, the optimal hydrophilic duration is obtained. The embedded chromogenic disc detects the sweat glucose value at two adjacent time intervals and compares the information of the human body to increase or reduce glucose. The patch has good flexibility and can fit well with human skin, and because polydimethylsiloxane (PDMS) has good light transmission, it reduces the measurement error caused by the color-taking process and makes the detection results more accurate.

Structural basis of neuropeptide Y signaling through Y1 and Y2 receptors.

Neuropeptide Y (NPY), a 36-amino-acid peptide, functions as a neurotransmitter in both the central and peripheral nervous systems by activating the NPY receptor subfamily. Notably, NPY analogs display varying selectivity and exert diverse physiological effects through their interactions with this receptor family. [Pro34]-NPY and [Leu31, Pro34]-NPY, mainly acting on Y1R, reportedly increases blood pressure and postsynaptically potentiates the effect of other vasoactive substances above all, while N-terminal cleaved NPY variants in human body primary mediates angiogenesis and neurotransmitter release inhibition through Y2R. However, the recognition mechanisms of Y1R and Y2R with specific agonists remain elusive, thereby hindering subtype receptor-selective drug development. In this study, we report three cryo-electron microscopy (cryo-EM) structures of Gi2-coupled Y1R and Y2R in complexes with NPY, as well as Y1R bound to a selective agonist [Leu31, Pro34]-NPY. Combined with cell-based assays, our study not only reveals the conserved peptide-binding mode of NPY receptors but also identifies an additional sub-pocket that confers ligand selectivity. Moreover, our analysis of Y1R evolutionary dynamics suggests that this sub-pocket has undergone functional adaptive evolution across different species. Collectively, our findings shed light on the molecular underpinnings of neuropeptide recognition and receptor activation, and they present a promising avenue for the design of selective drugs targeting the NPY receptor family.

Genomic, transcriptomic, and metabolomic analyses provide insights into the evolution and development of a medicinal plant Saposhnikovia divaricata (Apiaceae).

Saposhnikovia divaricata, 2n = 2x = 16, as a perennial species, is widely distributed in China, Mongolia, Russia, etc. It is a traditional Chinese herb used to treat tetanus, rubella pruritus, rheumatic arthralgia, and other diseases. Here, we assembled a 2.07 Gb and N50 scaffold length of 227.67 Mb high-quality chromosome-level genome of S. divaricata based on the PacBio Sequel II sequencing platform. The total number of genes identified was 42 948, and 42 456 of them were functionally annotated. A total of 85.07% of the genome was composed of repeat sequences, comprised mainly of long terminal repeats (LTRs) which represented 73.7% of the genome sequence. The genome size may have been affected by a recent whole-genome duplication event. Transcriptional and metabolic analyses revealed bolting and non-bolting S. divaricata differed in flavonoids, plant hormones, and some pharmacologically active components. The analysis of its genome, transcriptome, and metabolome helped to provide insights into the evolution of bolting and non-bolting phenotypes in wild and cultivated S. divaricata and lays the basis for genetic improvement of the species.

Determining the Hot Workability and Microstructural Evolution of an Fe-Cr-Mo-Mn Steel Using 3D Processing Maps.

The Laasraoui segmented and Arrhenius flow stress model, dynamic recrystallization (DRX) model, grain size prediction model, and hot processing map (HPM) of Fe-Cr-Mo-Mn steels were established through isothermal compression tests. The models and HPM were proven by experiment to be highly accurate. As the deformation temperature decreased or the strain rate increased, the flow stress increased and the grain size of the Fe-Cr-Mo-Mn steel decreased, while the volume fraction of DRX (Xdrx) decreased. The optimal range of the hot processing was determined to be 1050-1200 °C/0.369-1 s-1. Zigzag-like grain boundaries (GBs) and intergranular cracks were found in the unstable region, in which the disordered martensitic structure was observed. The orderly packet martensite was formed in the general processing region, and the mixed structure with incomplete DRX grains was composed of coarse and fine grains. The microstructure in the optimum processing region was composed of DRX grains and the multistage martensite. The validity of the Laasraoui segmented flow stress model, DRX model, grain size prediction model, and HPM was verified by upsetting tests.

The tumour suppressor Fat1 is dispensable for normal murine hematopoiesis.

Loss and overexpression of FAT1 occurs among different cancers with these divergent states equated with tumor suppressor and oncogene activity, respectively. Regarding the latter, FAT1 is highly expressed in a high proportion of human acute leukemias relative to normal blood cells, with evidence pointing to an oncogenic role. We hypothesized that this occurrence represents legacy expression of FAT1 in undefined hematopoietic precursor subsets that is sustained following transformation, predicating a role for FAT1 during normal hematopoiesis. We explored this concept by using the Vav-iCre strain to construct conditional knockout (cKO) mice where Fat1 expression was deleted at the hematopoietic stem cell stage. Extensive analysis of precursor and mature blood populations using multi-panel flow cytometry revealed no ostensible differences between Fat1 cKO mice and normal littermates. Further functional comparisons involving colony forming unit and competitive bone marrow transplantation assays support the conclusion that Fat1 is dispensable for normal murine hematopoiesis.

The structure and function of FUN14 domain-containing protein 1 and its contribution to cardioprotection by mediating mitophagy.

Cardiovascular disease (CVD) is a serious public health risk, and prevention and treatment efforts are urgently needed. Effective preventive and therapeutic programs for cardiovascular disease are still lacking, as the causes of CVD are varied and may be the result of a multifactorial combination. Mitophagy is a form of cell-selective autophagy, and there is increasing evidence that mitophagy is involved in cardioprotective processes. Recently, many studies have shown that FUN14 domain-containing protein 1 (FUNDC1) levels and phosphorylation status are highly associated with many diseases, including heart disease. Here, we review the structure and functions of FUNDC1 and the path-ways of its mediated mitophagy, and show that mitophagy can be effectively activated by dephosphorylation of Ser13 and Tyr18 sites, phosphorylation of Ser17 site and ubiquitination of Lys119 site in FUNDC1. By effectively activating or inhibiting excessive mitophagy, the quality of mitochondria can be effectively controlled. The main reason is that, on the one hand, improper clearance of mitochondria and accumulation of damaged mitochondria are avoided, and on the other hand, excessive mitophagy causing apoptosis is avoided, both serving to protect the heart. In addition, we explore the possible mechanisms by which FUNDC1-mediated mitophagy is involved in exercise preconditioning (EP) for cardioprotection. Finally, we also point out unresolved issues in FUNDC1 and its mediated mitophagy and give directions where further research may be needed.

A Robust α-l-Fucosidase from Prevotella nigrescens for Glycoengineering Therapeutic Antibodies.

Eliminating the core fucose from the N-glycans of the Fc antibody segment by pathway engineering or enzymatic methods has been shown to enhance the potency of therapeutic antibodies, especially in the context of antibody-dependent cytotoxicity (ADCC). However, there is a significant challenge due to the limited defucosylation efficiency of commercially available α-l-fucosidases. In this study, we report a unique α-l-fucosidase (PnfucA) from the bacterium Prevotella nigrescens that has a low sequence identity compared with all other known α-l-fucosidases and is highly reactive toward a core disaccharide substrate with fucose α(1,3)-, α (1,4)-and α(1,6)-linked to GlcNAc, and is less reactive toward the Fuc-α(1,2)-Gal on the terminal trisaccharide of the oligosaccharide Globo H (Bb3). The kinetic properties of the enzyme, such as its Km and kcat, were determined and the optimized expression of PnfucA gave a yield exceeding 30 mg/L. The recombinant enzyme retained its full activity even after being incubated for 6 h at 37 °C. Moreover, it retained 92 and 87% of its activity after freezing and freeze-drying treatments, respectively, for over 28 days. In a representative glycoengineering of adalimumab (Humira), PnfucA showed remarkable hydrolytic efficiency in cleaving the α(1,6)-linked core fucose from FucGlcNAc on the antibody with a quantitative yield. This enabled the seamless incorporation of biantennary sialylglycans by Endo-S2 D184 M in a one-pot fashion to yield adalimumab in a homogeneous afucosylated glycoform with an improved binding affinity toward Fcγ receptor IIIa.

Cyberbullying victimization and perpetration: The influence on cyberostracism and youth anxiety.

Cyberbullying is considered a major threat to adolescent anxiety. In this study, we aim to explore the simultaneous effects of cyberbullying victimization and perpetration on youth anxiety. Building on the childhood adversity model and the vulnerability-stress model, we test the model wherein cyberbullying exposure is linked with cyberostracism, which in turn is expected to be associated with an increase in anxiety. We collected data from 1115 Chinese youth aged 11-19 years based on the stratified random sampling method. Structure equation modelling was conducted in Amos 26.0 to examine the proposed theoretical model. The findings suggested that compared with cyberbullying perpetration, the experience of cyberbullying victimization led to a significantly higher risk of youth anxiety. Multiple mediation analyses revealed that the three dimensions of cyberostracism, namely cyber direct excluded, cyber indirect excluded and cyber ignored, mediated the association of cyberbullying victimization and perpetration with youth anxiety. These results indicate that cyberostracism could be a risk factor for youth anxiety, thus providing new direction regarding intervention programs to reduce anxiety symptoms in adolescents.

Cost-effective 3D-printed rotatable reflectors for two-dimensional beam steering.

In this paper, we have developed a 2D optical scanning module comprising cascaded 3D-printed one-axis rotating mirrors with large areas (30×30m m 2 for the X-direction scan and 60×25m m 2 for the Y-direction scan). Each mirror device contains a square or rectangular silicon substrate coated with aluminum, serving as the mirror. A 3D-printed structure, including the mirror frame (with four embedded mini permanent magnets on the backside), torsion springs, and base, is combined with the mirror; two electromagnets are situated under the mirror as the actuation mechanism. We apply DC voltage to the electromagnets to create magnetic force. The electromagnets can interact with the permanent magnets to make the mirror rotate. The X scan of the 2D scanning module can achieve a static optical scan angle of ∼11.8deg at the -X corners, and the corresponding Y-scan angle is ∼4.5deg, both with 12 VDC. Moreover, we have observed a fan-shaped distortion, a phenomenon not thoroughly studied previously for combining two single-axis scan mirrors. Therefore, we also perform a simulation to establish and demonstrate a correlation between the simulation prediction and experimental results. The 2D scanning module can be a low-cost alternative to the expensive conventional galvanometer scanners, and it can be used to upgrade a rangefinder to a simplified LiDAR.

Global, regional, and national burden and trends of migraine among women of childbearing age from 1990 to 2021: insights from the Global Burden of Disease Study 2021.

BACKGROUND: Migraine, a neurological disorder with a significant female predilection, is the leading cause of disability-adjusted life years (DALYs) in women of childbearing age (WCBA). There is currently a lack of comprehensive literature analysis on the overall global burden and changing trends of migraines in WCBA. METHODS: This study extracted three main indicators, including prevalence, incidence, and DALYs, related to migraine in WCBA from the Global Burden of Disease(GBD) database from 1990 to 2021. Our study presented point estimates with 95% uncertainty intervals (UIs). It evaluated the changing trends in the burden of migraine in WCBA using the estimated annual percentage change (EAPC) and percentage change. RESULTS: In 2021, the global prevalence, incidence, and DALYs cases of migraine among WCBA were 493.94 million, 33.33 million, and 18.25 million, respectively, with percentage changes of 48%, 43%, and 47% compared to 1990. Over the past 32 years, global prevalence rates and DALYs rates globally have increased, with an EAPC of 0.03 (95% UI: 0.02 to 0.05) and 0.04 (95% UI: 0.03 to 0.05), while incidence rates have decreased with an EAPC of -0.07 (95% UI: -0.08 to -0.05). Among the 5 Socio-Demographic Index (SDI) regions, in 2021, the middle SDI region recorded the highest cases of prevalence, incidence, and DALYs of migraine among WCBA, estimated at 157.1 million, 10.56 million, and 5.81 million, respectively, approximately one-third of the global total. In terms of age, in 2021, the global incidence cases for the age group 15-19 years were 5942.5 thousand, with an incidence rate per 100,000 population of 1957.02, the highest among all age groups. The total number of migraine cases and incidence rate among WCBA show an increasing trend with age, particularly in the 45-49 age group. CONCLUSIONS: Overall, the burden of migraine among WCBA has significantly increased globally over the past 32 years, particularly within the middle SDI and the 45-49 age group. Research findings emphasize the importance of customized interventions aimed at addressing the issue of migraines in WCBA, thus contributing to the attainment of Sustainable Development Goal 3 set by the World Health Organization.

Cytology-histology correlation of atypical glandular cells on cervical Papanicolaou tests: A study of 628 cases.

INTRODUCTION: The finding of atypical glandular cells (AGC) on Papanicolaou test is becoming more important as the incidence of squamous intraepithelial lesions decreases in recent decades. Therefore, the interpretation and follow-up of patients with AGC are particularly important. The aim of our study was to assess the histologic findings and clinical correlations in patients with AGC identified on Papanicolaou test. MATERIALS AND METHODS: A total of 714 patients with AGC identified on cervical Papanicolaou tests were studied for their clinicopathologic features, such as follow-up histology and patient age. We investigated the histologic follow-up results for each individual subcategories of AGC and their correlation with patients' age. RESULTS: Most of the glandular cell abnormalities (80.0%) in the study group were classified as "atypical glandular cells, not otherwise specified (NOS)". About 28.9% of patients' follow-up histology showed malignant or precancerous lesions. The mean age of patients with malignant or precancerous lesions was significantly higher than that of patients with benign or non-precancerous lesions. The malignant histologies included 52 cases of endometrial cancers and 31 cases of cervical carcinomas. The second most common subcategory was "atypical glandular cells, favor neoplastic" (5.0%), while "atypical endocervical cells, favor neoplastic" constituted about 2.7% of cases in our study. The average age of patients with "atypical glandular cells, favor neoplastic" was significantly higher than that of patients with "atypical endocervical cells, favor neoplastic". The follow-up histology of about 82.1% of "atypical glandular cells, favor neoplastic" showed endometrial (73.9%) or cervical malignancies (26.1%). The follow-up histology of about 70.6% of "atypical endocervical cells, favor neoplastic" showed endometrial (50.0%) or cervical cancers (50.0%). Other glandular abnormalities included 25 of 714 cases of "atypical endometrial cells" (3.5%) and 6 of 714 cases of "atypical endocervical cells" (0.8%). CONCLUSION: Based on our data, we have observed significantly more endometrial malignancies in both "atypical glandular cells, NOS" and "atypical glandular cells, favor neoplastic" subcategories and even some in "atypical endocervical cells, favor neoplastic" category. This predominance of endometrial malignancies is also associated with patients' age and tumor types.

Activation of Nrf2 inhibits atherosclerosis in ApoE-/- mice through suppressing endothelial cell inflammation and lipid peroxidation.

BACKGROUND: Nuclear erythroid 2-related factor 2 (Nrf2), a transcription factor, is critically involved in the regulation of oxidative stress and inflammation. However, the role of endothelial Nrf2 in atherogenesis has yet to be defined. In addition, how endothelial Nrf2 is activated and whether Nrf2 can be targeted for the prevention and treatment of atherosclerosis is not explored. METHODS: RNA-sequencing and single-cell RNA sequencing analysis of mouse atherosclerotic aortas were used to identify the differentially expressed genes. In vivo endothelial cell (EC)-specific activation of Nrf2 was achieved by injecting adeno-associated viruses into ApoE-/- mice, while EC-specific knockdown of Nrf2 was generated in Cdh5CreCas9floxed-stopApoE-/- mice. RESULTS: Endothelial inflammation appeared as early as on day 3 after feeding of a high cholesterol diet (HCD) in ApoE-/- mice, as reflected by mRNA levels, immunostaining and global mRNA profiling, while the immunosignal of the end-product of lipid peroxidation (LPO), 4-hydroxynonenal (4-HNE), started to increase on day 10. TNF-α, 4-HNE, and erastin (LPO inducer), activated Nrf2 signaling in human ECs by increasing the mRNA and protein expression of Nrf2 target genes. Knockdown of endothelial Nrf2 resulted in augmented endothelial inflammation and LPO, and accelerated atherosclerosis in Cdh5CreCas9floxed-stopApoE-/- mice. By contrast, both EC-specific and pharmacological activation of Nrf2 inhibited endothelial inflammation, LPO, and atherogenesis. CONCLUSIONS: Upon HCD feeding in ApoE-/- mice, endothelial inflammation is an earliest event, followed by the appearance of LPO. EC-specific activation of Nrf2 inhibits atherosclerosis while EC-specific knockdown of Nrf2 results in the opposite effect. Pharmacological activators of endothelial Nrf2 may represent a novel therapeutic strategy for the treatment of atherosclerosis.