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Abstract Background Yes-associated protein (YAP) is a crucial mechanosensor involved in mechanotransduction, but its role in regulating mechanical force-induced bone remodeling during orthodontic tooth movement (OTM) is unclear. This study aims to elucidate the relationship between mechanotransduction and mechanical force-induced alveolar bone remodeling during OTM. Results Our study confirms an asynchronous (temporal and spatial sequence) remodeling pattern of the alveolar bone under mechanical force during OTM. Both compression and tension activate osteoclasts recruiting to the alveolar bone, whereas no significant presence of osteoblasts in the alveolar bone at the early stages of bone remodeling. Specifically, applying different force magnitudes (10, 25, 50, 100 g) to rats’ 1st molars affected OTM distance. Force-induced alveolar bone remodeling was characterized by osteoclastogenesis and YAP activation at compressive/tensile sites on day 1 of OTM. Notably, 25 g force triggered peak YAP expression and osteoclastic activity early on. Time-course analysis revealed two YAP activity peaks on day1 and 14, contrasting with one peak of type I collagen expression on day14. In addition, RNA-sequencing highlighted increased nuclear factor kappa B (NF-κB) signaling, mineral absorption, and osteoclast differentiation at day-1 and 3. Moreover, gene expression analysis showed similar trends for NF-κB p65, YAP1, and TEA domain 1 (TEAD1) during this time. Furthermore, experiments on osteoclast cultures indicated YAP activation via large tumor suppressor (LATS) and TEAD under mechanical stimuli (compression/tension), promoting osteoclastogenesis by regulating NF-κB p65 and receptor activator of NF-κB (RANK). Inhibiting YAP with verteporfin delayed OTM by impairing force-induced osteoclastic activities in vivo and ex-vivo. Conclusions We propose that YAP mediates alveolar bone remodeling through NF-κB p65-induced osteoclastogenesis in an asynchronous remodeling pattern during OTM. Both compression and tension activate osteoclasts recruiting to the alveolar bone at early stages of bone remodeling, offering evidence for orthodontists as a reference.

Abstract Fish diversity, an important indicator of aquatic ecosystem health, is declining due to water pollution, overfishing, climate change, and invasive species. Effective surveying and monitoring are required to protect fish diversity. Here, a high-sensitivity environmental DNA (eDNA) metabarcoding technique was used to investigate fish diversity in the Danjiang River, Shaanxi Province, China. In total, 59 species were identified in eight orders, 19 families, and 40 genera. Cypriniformes and Perciformes were the main groups in the survey area, while Cyprinidae accounted for 50.85% of the total fish species. Rhinogobius similis (19%), Hemibarbus umbrifer (11%), Gnathopogon herzensteini (10%), Triplophysa stewarti (8%), and Zacco platypus (7%) were the dominant species. Eight rare and two exotic fish species were identified. Combined with analysis of historical data, the richness of fish identified using eDNA metabarcoding was significantly higher than that of fish captured in ground cages. Temperature, pH, and oxidation-reduction potential are the main environmental factors that affect the spatial distribution of fish communities. These results suggest that eDNA metabarcoding could be a new tool with broad application prospects; however, local databases must be improved. This study provides theoretical data and a methodological reference for protecting and managing fish diversity in the Qinling Mountains.

Supercritical lens (SCL) can break the diffraction limit in the far field and has been demonstrated for high-resolution scanning confocal imaging. Its capability in sharper focusing and needle-like long focal depth should allow high-resolution lithography at violet or ultraviolet (UV) wavelength, however, this has never been experimentally demonstrated. As a proof of concept, in this paper SCLs operating at 405 nm (h-line) wavelength with smaller full-width-at-half-maximum focal spot and longer depth of focus than conventional Fresnel zone lens while maintaining controlled side lobes are designed for direct laser writing (DLW) lithography. Aluminum nitride (AlN) with a high refractive index and low loss in UV-visible range is used to fabricate nanopillar-based metasurfaces structure for the metalens. Grating arrays with improved pitch resolution are fabricated using the SCLs with sub-diffraction-limit focusing capability. The AlN-based metasurface for SCLs at short wavelength for DLW could extend further to UV or deep UV lithography and might be of great interest to both the research and industry applications.

Abstract Advances in symmetry-breaking engineering of heterointerfaces for optoelectronic devices have garnered significant attention due to their immense potential in tunable moiré quantum geometry and enabling polarization light detection. Despite several proposed approaches to breaking the symmetry of low-dimensional materials, there remains a lack of universal methods to create materials with prominent polarization detection capabilities. Here, we introduce a reliable strategy for manipulating the symmetry of low-dimensional materials through a programmable ferroelectric-doping patterns technique. This method introduces a spontaneous photocurrent and enables the detection of linearly polarization light in isotropic 2H-MoTe2. The 2H-MoTe2 photodetector exhibits a significant short-circuit photocurrent intensity (J sc = 29.9 A/cm2) and open-circuit voltage V oc of 0.12 V ( ~ 3 × 105 V/cm). Under a specific bias, the polarization ratio transitions from 1 to ∞/−∞, shifting from a positive state (unipolar regime) to a negative state (bipolar regime). These findings underscore the potential of ferroelectric-doping patterns as a promising approach to creating composite materials with artificial bulk photovoltaic effect and achieving high-performance polarization light detection.

Abstract Background Gram-negative bacteria are the main bacterial pathogens infecting Chinese giant salamanders (Andrias davidianus; CGS) in captivity and the wild, causing substantial economic losses in the CGS industry. However, the molecular mechanisms underlying pathogenesis following infection remain unclear. Results Spleen-derived macrophages from healthy CGS were isolated, cultured, and identified using density gradient centrifugation and immunofluorescence. A macrophage transcriptome database was established 0, 6, and 12 h post lipopolysaccharide stimulation using RNA-sequencing. In the final database 76,743 unigenes and 4,698 differentially expressed genes (DEGs) were functionally annotated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results showed that DEGs were concentrated in toll-like receptor–nuclear factor kappa B-related immune pathways. Ten DEGs were validated 12 h after lipopolysaccharide (LPS) stimulation. Although the common LPS recognition receptor toll-like receptor 4 was not activated and the key adaptor protein MyD88 showed no significant response, we observed significant up-regulation of the following adaptors: toll/interleukin-1 receptor domain-containing adaptor inducing interferon-β, tumour necrosis factor receptor-associated factor 6, and transforming growth factor-β activated kinase 1, which are located downstream of the non-classical MyD88 pathway. Conclusions In contrast to that in other species, macrophage activation in CGS could depend on the non-classical MyD88 pathway in response to bacterial infection. Our study provides insights into the molecular mechanisms regulating CGS antibacterial responses, with implications for disease prevention and understanding immune evolution in amphibians.

Abstract The middle and lower reaches of the Yangtze River are frequently affected by the Western Pacific Subtropical High (WPSH) in summer. This leads to phenomena including air subsidence, high temperatures, low rainfall, and weak winds, all of which affect the urban heat island (UHI) effect. Currently, there are few studies on the influence of WPSH on the UHI effect. In this study, we analysed the temporal and spatial distributions of the influence of WPSH on the UHI effect by establishing two scenarios: with and without WPSH. We calculated the UHI intensity and the urban heat island proportion index (UHPI) to analyse the temporal and spatial distributions of the UHI effect. The geographical detector method was then used to analyse the factors influencing UHI. The results indicate the strong heat island effect during the day in provincial capitals and some developed cities. The area of high UHI intensity was larger under the influence of WPSH than in the years without WPSH. WPSH affected UHPI at both day and night, although the effect was more pronounced at night. The factors affecting daytime UHI intensity are mainly POP and NTL, O3 plays a large role in the years with WPSH control. The main factors affecting the UHI intensity at night are AOD, POP and NTL were mainly factors in the years without WPSH control, POP and WPSH were mainly factors in the years with WPSH control. The interactions of the factors are mainly POP and multi-factors during the daytime, and DEM and multi-factors during the nighttime. It was found that the UHI intensity was enhanced under the control of the WPSH, and the influencing factors of the diurnal UHI differed with and without the WPSH control, which ultimately provides realistic suggestions for mitigating the intensity of the UHI in areas affected by the WPSH.

Abstract Background Coal-burning fluorosis is a chronic poisoning resulting from the prolonged use of locally available high-fluoride coal for heating and cooking. Prolonged fluoride exposure has been demonstrated to decrease PPARGC1A levels. Therefore, this case-control aims to evaluate the genetic association of PPARGC1A gene polymorphisms and methylation of the mitochondrial D-loop region with coal-burning fluorosis. Result The results showed that the TT genotype at rs13131226 and the AA genotype at rs1873532 increased the risk of coal-burning fluorosis (OR = 1.84, P = 0.004; OR = 1.97, P = 0.007), the CT and CC genotypes at rs7665116 decreased the risk of coal-burning fluorosis (OR = 0.54, P = 0.003). The TT genotype at the rs2970847 site and the AA genotype at the rs2970870 site increase the risk of developing skeletal fluorosis (OR = 4.12, P = 0.003; OR = 2.22, P = 0.011). Haplotype AG constructed by rs3736265-rs1873532 increased the risk of the prevalence of coal-burning fluorosis (OR = 1.465, P = 0.005); CG decreased the risk of the prevalence of coal-burning fluorosis (OR = 0.726, P = 0.020). Haplotype CGGT constructed by rs6821591-rs768695-rs3736265-rs2970847 increased the risk of the prevalence of skeletal fluorosis (OR = 1.558, P = 0.027). A 1% increase in CpG_4 methylation levels in the mtDNA D-loop region is associated with a 2.3% increase in the risk of coal-burning fluorosis. Additionally. There was a significant interaction between rs13131226 and rs1873532; CpG_4 and CpG_8.9; rs13131224,rs6821591 and rs7665116 were observed in the occurrence of fluorosis in the Guizhou population (χ 2 = 16.917, P

Lilium are highly economically valuable ornamental plants that are susceptible to Fusarium wilt caused by Fusarium oxysporum. Lilium regale Wilson, a wild lily native to China, is highly resistant to F. oxysporum. In this study, a WRKY transcription factor, WRKY11, was isolated from L. regale, and its function during the interaction between L. regale and F. oxysporum was characterized. The ectopic expression of LrWRKY11 in tobacco increased the resistance to F. oxysporum, moreover, the transcriptome sequencing and UHPLC-MS/MS analysis indicated that the methyl salicylate and methyl jasmonate levels rose in LrWRKY11 transgenic tobacco, meanwhile, the expression of lignin/lignans biosynthesis-related genes including a dirigent (DIR) was up-regulated. The lignin/lignans contents in LrWRKY11-transgenic tobacco also significantly increased compared with the wild-type tobacco. In addition, the resistance of L. regale scales in which LrWRKY11 expression was silenced by RNAi evidently decreased, and additionally, the expression of lignin/lignans biosynthesis-related genes including LrDIR1 was significantly suppressed. Therefore, LrDIR1 and its promoter (PLrDIR1) sequence containing the W-box element were isolated from L. regale. The interaction assay indicated that LrWRKY11 specifically bound to the W-box element in PLrDIR1 and activated LrDIR1 expression. Additionally, β-glucuronidase activity in the transgenic tobacco co-expressing LrWRKY11/PLrDIR1-β-glucuronidase was higher than that in transgenic tobacco expressing PLrDIR1-β-glucuronidase alone. Furthermore, the ectopic expression of LrDIR1 in tobacco enhanced the resistance to F. oxysporum and increased the lignin/lignans accumulation. In brief, this study revealed that LrWRKY11 positively regulated L. regale resistance to F. oxysporum through interaction with salicylic acid/jasmonic acid signaling pathways and modulating LrDIR1 expression to accumulate lignin/lignans.

Abstract Background The chronic digestive condition gallstones is quite common around the world, the development of which is closely related to oxidative stress, inflammatory response and abnormalities of lipid metabolism. In the last few years, as a novel biomarker of lipid metabolism, the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) has garnered significant interest. However, its relationship with gallstones has not been studied yet. Methods 3,772 people, all under 50, were included in this study, and their full data came from the National Health and Nutrition Examination Survey (NHANES) database for the years 2017–2020. Information on gallstones was obtained through self-reported questionnaires. Smoothed curve fitting multifactorial logistic regression was utilized to evaluate the connection of NHHR with gallstone formation incidence. Subsequently, subgroup analysis and interaction tests were applied. Finally, to create a prediction model, logistic regression and feature screening by last absolute shrinkage and selection operator (LASSO) were used. The resulting model was displayed using a nomogram. Results In multivariate logistic regression that accounted for all factors, there was a 77% increase in the likelihood of gallstones for every unit rise in lnNHHR (OR 1.77 [CI 1.11–2.83]). Following NHHR stratification, the Q4 NHHR level was substantially more linked to the risk of gallstones than the Q1 level (OR 1.86 [CI 1.04–3.32]). This correlation was stronger in women, people under 35, smokers, abstainers from alcohol, non-Hispanic White people, those with excessively high cholesterol, people with COPD, and people without diabetes. After feature screening, a predictive model and visualized nomogram for gallstones were constructed with an AUC of 0.785 (CI 0.745–0.819), which was assessed by DCA to be clinically important. Conclusion In the group of people ≤ 50 years of age, elevated NHHR levels were substantially linked to a higher incidence of gallstones. This correlation was stronger in several specific groups such as females, under 35 years of age, smokers, and so on. Predictive models constructed using the NHHR have potential clinical value in assessing gallstone formation.

We report a case of a Chinese girl who presented with multiple seizure types of epilepsy, followed by motor and intellectual regression, vision impairment, and cerebral and cerebellar atrophy. She carries an unreported compound heterozygous variant of the ASAH1 gene and is diagnosed with spinal muscular atrophy associated with progressive myoclonic epilepsy (SMA-PME), a disorder in which ceramide accumulation in lysosomes due to a decrease in acid ceramidase activity. This case suggests attention to this rare class of deceases involving both the central and peripheral nervous systems.

ObjectivesBesides physical health risks, large public health events also exert negative impacts on people's mental health. We aimed to explore the prevalence and correlates of mental distress and its association with psychological resilience among countries amid the Omicron wave.MethodsWe conducted cross-sectional surveys simultaneously in China and South Korea from March 15 to 30, 2023. Brief Resilience Scale (BRS), Generalized Anxiety Disorder 7-item (GAD-7) scale, and Patient Health Questionnaire-9 (PHQ-9) scale were used to measured psychological resilience and mental distress.ResultsSelf-reported rates of anxiety and depressive symptoms in 3,000 Chinese participants were 24.5% and 30.5%, while the above-mentioned rates were 17.2%and 34.4% in 1,000 Korean participants. Chinese participants had a marginally higher BRS score. Psychological resilience was inversely associated with the prevalence of anxiety symptoms and depressive symptoms. Similar results can be observed in Korea. Results remained robust in all models.ConclusionChinese and Korean populations reported a high prevalence of mental distress with variations in different characteristics, indicating practical implications for developing tailored mental health policies and services in the context of large public health events.

This study investigates the perceived English proficiency and teaching practices of non-native and native English-speaking teachers (NNESTs and NESTs) in Chinese universities, utilizing a multi-method approach including surveys, classroom observations, interviews, and focus groups. Data were collected from 118 students, four NNESTs, four NESTs, and two administrators to assess proficiency in English for general purposes (EGP) and English for teaching purposes (ETP). Qualitative and quantitative analyses indicate that NNESTs rate their ETP proficiency higher than their EGP, while NESTs perceive their EGP and ETP proficiencies to be superior to those of NNESTs. Administrators affirm NNESTs' ETP proficiency but raise concerns about NESTs' writing skills for ETP. Although a majority of students (n=65) showed no preference, focus groups suggest their preferences are context-dependent. The findings contribute to the understanding of ETP versus EGP proficiency and highlight the need for professional development in teaching competencies for both NESTs and NNESTs.

Snow cover significantly influences the Earth’s climate system and global hydrological cycle through its thermal insulation properties and high albedo, and is an important component of the cryosphere. Currently, the most efficient means of quantifying snow depth at both global and regional scales is through passive microwave remote sensing. However, the accuracy of passive microwave remote sensing inversion of snow depth in forested areas is affected by the forest canopy. In this study, a normalized maximum stem volume (NMSV) index was constructed by combining canopy height and tree cover data obtained through remote sensing techniques. The NMSV index was then incorporated into development of snow depth retrieval algorithm to improve accuracy of passive microwave snow depth estimation in forested areas. Compared to the Chang algorithm and the AMSR-E snow depth product, this study demonstrated higher accuracy in the mid- to high-latitude forested areas of Eurasia, with an R value approximately twice as high and a reduction in the overall root mean square error (RMSE) by 2.3 cm and 7.2 cm, respectively. The relative mean bias of this study in the Western Russia, the Eastern Siberian Mountains and the Northeast China is significantly reduced than that of the existing remote sensing algorithms. Against the ERA5 and GlobSnow datasets, with the exception of the Western Russia, the performance of this study in the mid- to high-latitude forested areas of Eurasia is comparable to the ERA5 dataset and superior to the other datasets. Based on the performance of the algorithms in different NMSV values, we observe a decline in the accuracy of this algorithm when the value exceeds 0.8, which was caused by small size of high NMSV values among the ground observation sites involved in the development of snow depth retrieval algorithm. Overall, the NMSV index proposed in this study, which integrates information from both the horizontal and vertical structures of forest, can better characterize the microwave radiation properties of sparse and moderately dense forests, facilitating improvements in the accuracy of passive microwave snow depth retrieval in global forested areas.

Zanthoxylum rust (ZR) poses a significant threat to Zanthoxylum bungeanum Maxim.(ZBM) production, impacting both the yield and quality. The lack of current research on ZR using unmanned aerial vehicle (UAV) remote sensing poses a challenge to achieving precise management of individual ZBM plant. This study acquired six UAV hyperspectral images to create a ZR inversion dataset . This dataset, to our knowledge, is the first dataset for remote sensing deep learning (DL) of ZR using UAV. To facilitate automated extraction of individual ZBM plant and the quantitative inversion of ZR disease index (DI), we introduced the object-based quantitative inversion framework (OQIF). OQIF achieved high accuracy in recognizing ZBM (average precision at an intersection over union threshold of 0.5 was 90.0 %). Remarkably, OQIF demonstrates outstanding quantitative inversion results for ZR DI (R2 = 0.90, RMSE = 3.97, n = 8166). For DI < 10, the RMSE was 2.48, showcasing early detection capability. Our research has significant implications for ZBM cultivation and precision management, pioneering object-based quantitative inversion for tree diseases and yield estimation, with potential for early ZR detection.

Summary: Background: Dengue remains a global threat to public health, however, its disease burden among children and adolescents has always been poorly quantified. Therefore, we aimed to systematically estimate the global, regional, and national burden and temporal trends of dengue infection in children and adolescents from 1990 to 2021. Methods: Data on the number and rate of incidence and disability-adjusted life-years (DALYs) of dengue infection among children and adolescents under 20 years were obtained from the Global Burden of Disease Study (GBD) 2021. Estimated annual percentage changes (EAPCs) of the age-standardised incidence rate (ASIR) and age-standardised DALYs rate (ASDR), by age, sex, and different countries and regions, were calculated to quantify the temporal trends of dengue burden. The association between development levels (measured using the socio-demographic index [SDI]) and dengue burden was also determined. Findings: From 1990 to 2021, the global burden of dengue incidence and its associated DALYs was consistently higher in children and adolescents than in the entire population. Globally, among children and adolescents, there were 21,641,016 incident cases in 2021, an increase of 64.43% compared to 13,241,719 in 1990. The ASIR per 100,000 population increased from 587.81 in 1990 to 812.16 in 2021, with an EAPC of 1.39% (95% confidence interval [CI], 1.13%–1.65%). Besides, the number of dengue-associated DALYs among children and adolescents increased by 16.36%, from 910,458.60 in 1990 to 1,059,428.31 in 2021. The increase in DALYs was less pronounced than incidence, with the ASDR per 100,000 population increasing from 40.17 in 1990 to 41.50 in 2021, and the EAPC was only 0.67% (95% CI, 0.40%–0.95%). The incidence and DALYs burden of dengue in children and adolescents was highest in middle SDI regions, followed by low-middle SDI regions, with the lowest burden in high SDI regions. Furthermore, Tropical Latin America had an extremely high ASIR (6040.29 per 100,000 population in 2021), and Southeast Asia had an extremely high ASDR (298.20 per 100,000 population in 2021), much higher than other regions around the world. Interpretation: The global dengue burden in children and adolescents is high and has been increasing from 1990 to 2021, even though the distribution patterns vary across different countries and territories. This study first reported the global disease burden and temporal trends of children and adolescents, which has significant implications for policymakers and public health officials, as it underscores the need for age- and region-specific strategies to mitigate the growing global burden of dengue. Funding: National Natural Science Foundation of China.

Objectives: Four and a half LIM domain 2 protein (FHL2) was reported to regulate the progression of various cancers and this study aimed to clarify the intrinsic mechanism of FHL2 facilitating the progression of lung adenocarcinoma. Methods: In this study, bioinformatic analysis and immunohistochemistry staining were used to confirm the FHL2 levels in patients with lung adenocarcinoma. The potential influence of FHL2 on the biological function of lung adenocarcinoma cells was verified in vitro and in vivo. To uncover the potential mechanism contributing to the advance of lung adenocarcinoma, liquid chromatography‒mass spectrometry and immunoprecipitation assays were performed to detect the partners of FHL2. Results: FHL2 levels were upregulated in lung adenocarcinoma and contributed to a dismal prognosis. Moreover, in vitro and in vivo assays suggested that genetic inhibition of FHL2 undermined the viability, migration and invasion of lung adenocarcinoma cells, while forced expression of FHL2 showed the opposite trend. Mechanistically, liquid chromatography‒mass spectrometry and coimmunoprecipitation assays revealed that FHL2 could function as a scaffold to enhance TRIM63-mediated ubiquitination of APC. The degradation of APC further stabilized β-catenin and activated Wnt signaling pathway. Conclusion: Collectively, this study uncovered the underlying mechanism by which FHL2 regulates the biological characteristics of tumors and provided a novel target for lung adenocarcinoma treatment.

Abstract Background and Aims This study aimed to evaluate the hemodynamic alterations and right heart remodeling dynamics in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) undergoing treatment with balloon pulmonary angioplasty (BPA). Methods This retrospective cohort study involved a cohort of 31 patients with a confirmed diagnosis of CTEPH. Comprehensive clinical evaluations were systematically performed before BPA, and at 3 and 6 months following the procedure. Results Significant clinical progress was evidenced by the uplift in the percentage of patients achieving WHO‐FC II, escalating from 19.35% at baseline to 51.61% at 6 months after BPA (p = 0.003). NT‐proBNP levels significantly dropped from a median of 614.6 to 69.9 pg/mL (p

Top-down projections transmit a series of signals encoding pain sensation to the ventrolateral periaqueductal gray (vlPAG), where they converge with various incoming projections to regulate pain. Clarifying the upstream regulatory hierarchy of vlPAG can enhance our understanding of the neural circuitry involved in pain modulation. Here, we show that a in a mouse model of spared nerve injury (SNI), activation of a circuit arising from posterior paraventricular thalamic nucleus CaMKIIα-positive neurons (PVPCaMKIIα) projects to gamma-aminobutyric acid neurons in the rostral zona incerta (ZIrGABA) to facilitate the development of pain hypersensitivity behaviors. In turn, these ZIrGABA neurons project to CaMKIIα-positive neurons in the vlPAG (vlPAGCaMKIIα), a well-known neuronal population involved in pain descending modulation. In vivo calcium signal recording and whole-cell electrophysiological recordings reveal that the PVPCaMKIIα→ZIrGABA→vlPAGCaMKIIα circuit is activated in SNI models of persistent pain. Inhibition of this circuit using chemogenetics or optogenetics can alleviate the mechanical pain behaviors. Our study indicates that the PVPCaMKIIα→ZIrGABA→vlPAGCaMKIIα circuit is involved in the facilitation of neuropathic pain. This previously unrecognized circuit could be explored as a potential target for neuropathic pain treatment.

Microorganisms on amphibian skin reduce disease susceptibility and play an important role in pathogen defense. We hypothesized that anuran skin bacterial communities would change in response to seasonal variation and host species. To test this hypothesis, we used 16S rRNA amplicon sequencing to identify cutaneous bacterial communities of two frogs from the Qinling Mountains of China, Pelophylax nigromaculatus and Nanorana quadranus. We matched the amplicon sequence variants (ASVs) of microbes exhibiting protective effects against the pathogen Batrachochytrium dendrobatidis (Bd), using a database containing over 1900 16S rRNA gene sequences from amphibian skin bacteria. The results showed that seasonal variation had a stronger effect than host species on the structure (alpha-diversity, beta-diversity, species composition and abundance, and biomarkers) and anti-Bd function of cutaneous bacterial communities. These communities were highly dynamic but varied similarly between hosts. Their structural similarities were more consistent at the phylum level, but markedly less so at finer taxonomic levels. The highest relative abundance of anti-Bd reads was observed in P. nigromaculatus during summer, but anti-Bd reads were present in both frog species during different seasons. Therefore, the protective function of cutaneous microbial communities appears to be continuous despite between-species differences in anti-Bd ASV abundance. This observation does not directly explain why Bd infections have not been recorded in the region, butprovides important insight on anuran pathogen defense mechanisms. Our findings also suggest that specific seasons can be periods of high infection risk, with major implications for research on amphibian ecology and conservation.

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is a novel MRI technology to image certain compounds at extremely low concentrations. Long acquisition time to measure signals at a set of offset frequencies of the Z-spectra and to repeat measurements to reduce noise pose significant challenges to its applications. This study explores correlations of CEST MR images along the spatial and Z-spectral dimensions to improve MR image quality and robustness of magnetization transfer ratio (MTR) asymmetry estimation via a joint k-ω reconstruction model. The model was formulated as an optimization problem with respect to MR images at all frequencies ω, while incorporating regularizations along the spatial and spectral dimensions. The solution was subject to a self-consistency condition that the Z-spectrum of each pixel follows a multi-peak data fitting model corresponding to different CEST pools. The optimization problem was solved using the alternating direction method of multipliers. The proposed joint reconstruction method was evaluated on a simulated CEST MRI phantom and semi-experimentally on choline and iopamidol phantoms with added Gaussian noise of various levels. Results demonstrated that the joint reconstruction method was more tolerable to noise and reduction in number of offset frequencies by improving signal-to-noise ratio (SNR) of the reconstructed images and reducing uncertainty in MTR asymmetry estimation. In the choline and iopamidol phantom cases with 10.5% noise in the measurement data, our method achieved an averaged SNR of 31.0 dB and 32.2 dB compared to the SNR of 24.7 dB and 24.4 dB in the conventional reconstruction approach. It reduced uncertainty of the MTR asymmetry estimation over all regions of interest by 54.4% and 43.7%, from 1.71 and 2.38 to 0.78 and 1.71, respectively.

Abstract Background Environmental factors greatly impact infectious disease-related mortality, yet there's a lack of comprehensive global studies on the contemporary burden and trends. This study aims to evaluate the global burden and trends of infectious disease mortality caused by air pollution, unsafe water, poor sanitation, and non-optimal temperature across Socio-Demographic Index (SDI) regions from 1990 to 2019. Methods This observational study utilized data from the Global Burden of Diseases Study to examine mortality rates from infectious diseases attributed to environmental risk factors between 1990 and 2019, including air pollution, unsafe water, sanitation, handwashing facilities (UWSH), and non-optimal temperatures. Age-standardized mortality rates (ASMRs) and estimated annual percentage change (EAPC) were utilized to present infectious disease mortality, and its trajectory influenced by environmental risk factors over the years. Nonlinear regression was conducted to explore the association between the SDI and ASMRs across regions from 1990 to 2019. Results In 2019, global infectious disease deaths linked to air pollution, UWSH, and non-optimal temperature reached a startling 2,556,992. Disease mortality varied widely across SDI regions, with the highest number of deaths due to air pollution and UWSH in Low SDI regions, and deaths from non-optimal temperature primarily in High SDI regions. Age disparities emerged, with children under five and the elderly most affected. However, an increasing mortality trend was observed among seniors (65–69, 75–79, and over 80) in High SDI regions due to enteric infections linked to UWSH. Globally, a consistent decrease in ASMR was seen from 1990 to 2019 for all diseases connected to these factors, except for respiratory infections linked to non-optimal temperature. Conclusions Our study underscores the significant impact of air pollution, UWSH, and non-optimal temperatures on global infectious disease mortality, particularly among vulnerable groups such as children and the elderly. It's important to tackle these challenges with targeted interventions aiming to enhance environmental quality, improve water and sanitation systems, and control extreme temperatures. In addition, international cooperation is essential for bridging regional disparities and driving global public health initiatives forward, thereby helping achieve Sustainable Development Goals more effectively.

Abstract Intimal hyperplasia (IH) is a negative vascular remodeling after arterial injury. IH occasionally occurs in elastase‐induced abdominal aortic aneurysm (AAA) mouse models. This study aims to clarify the incidence and histological characteristics of IH in aneurysmal mice. A retrospective study was conducted by including 42 male elastase‐induced mouse AAA models. The IH incidence, aortic diameters with or without IH, and hyperplasia lesional features of mice were analyzed. Among 42 elastase‐induced AAA mouse models, 10 mice developed mild IH (24%) and severe IH was found in only 2 mice (5%). The outer diameters of the AAA segments in mice with and without IH did not show significant difference. Both mild and severe IH lesions show strong smooth muscle cell positive staining, but endothelial cells were occasionally observed in severe IH lesions. There was obvious macrophage infiltration in the IH lesions of the AAA mouse models, especially in mice with severe IH. However, only a lower numbers of T cells and B cells were found in the IH lesion. Local cell‐secreted matrix metalloproteinases (MMP) 2 was highly expressed in all IH lesions, but MMP9 was only overexpressed in severe lesions. In conclusion, this study is the first to demonstrate the occurrence of aneurysmal IH and its histological characteristics in an elastase‐induced mouse AAA model. This will help researchers better understand this model, and optimize it for use in AAA‐related research.

Abstract Biomolecular coacervates are emerging models to understand biological systems and important building blocks for designer applications. DNA can be used to build up programmable coacervates, but often the processes and building blocks to make those are only available to specialists. Here, we report a simple approach for the formation of dynamic, multivalency-driven coacervates using long single-stranded DNA homopolymer in combination with a series of palindromic binders to serve as a synthetic coacervate droplet. We reveal details on how the length and sequence of the multivalent binders influence coacervate formation, how to introduce switching and autonomous behavior in reaction circuits, as well as how to engineer wetting, engulfment and fusion in multi-coacervate system. Our simple-to-use model DNA coacervates enhance the understanding of coacervate dynamics, fusion, phase transition mechanisms, and wetting behavior between coacervates, forming a solid foundation for the development of innovative synthetic and programmable coacervates for fundamental studies and applications.

Precise and timely mapping of winter wheat is essential for food security. Current methods are limited by insufficient training data and a lack of long-term early mapping verification. This research proposes a framework that uses a cascade index to generate high-quality training samples for winter wheat mapping automatically. By considering the phenological characteristics of winter wheat and similar crops, the cascade index method screens and acquires these samples. Combined with a random forest model, mapping was conducted in Henan Province and the Agricultural Statistics District (ASD) 2020 area in the U.S. In Henan, early mapping from 2018 to 2022 assessed differences between model transfer and current-year samples. Results showed that using October-April imagery based on model migration achieved an overall accuracy (OA) of over 90%, while October-February imagery based on current-year samples also exceeded 90%. In some years, early mapping using only October-December data also achieved over 90% OA. These findings demonstrate the proposed model's viability for large-scale early winter wheat mapping using satellite imagery. Furthermore, this method demonstrates adaptability, mapping results achieving over 93.69% OA when transferred to the United States.

Summary: Background: Vaccination hesitancy poses a serious threat to mpox vaccination programs. Historically, vaccine uptake in the African region has been low, and this trend may impact future vaccination efforts. Our aim was to investigate the relationships between mpox vaccination hesitancy, immunisation coverage for other vaccines, and vaccination readiness among African adults. Methods: A multinational commercial web panel survey was conducted among 1832 African adults across six countries (Uganda, Nigeria, Morocco, Egypt, Kenya, and South Africa) from October 1 to October 10, 2024. Mpox vaccination hesitancy for themselves and children was defined as the reluctance to receive vaccines against mpox (if vaccines were available) for themselves and for children (if they had children). Vaccination readiness was assessed via the 7Cs model, which includes confidence, complacency, constraints, calculation, collective responsibility, compliance, and conspiracy. Weighted logistic regression models with the set of calibration sampling weights were used to estimate odds ratios (ORs) with 95% confidence intervals (95% CIs). The analysis explored the effects of immunisation coverage for other vaccines and vaccination readiness on hesitancy toward mpox vaccination, including mediation and joint relationships. DerSimonian-Laird random-effects meta-analyses were utilised to pool the results from six countries. Findings: The pooled weighted rate of mpox vaccination hesitancy among participants was 32.7% (95% CI: 25.4–40.0, I2 = 91.5%, p

Abstract Modular reconfigurable robots exhibit prominent advantages in the reconnaissance and exploration tasks within unstructured environments for their characteristics of high adaptability and high robustness. However, due to the limitations in locomotion mechanism and integration requirements, the modular design of miniature robots in the aquatic environment encounters significant challenges. Here, a modular strategy based on the synthetic jet principle is proposed, and a modular reconfigurable robot system is developed. Specialized bottom and side jet actuators are designed with vibration motors as excitation sources, and a motion module is developed incorporating the jet actuators to realize three‐dimensional agile motion. Its linear, rotational, and ascending motion speeds reach 70.7 mm s−1, 3.3 rad s−1, and 28.7 mm s−1, respectively. The module integrates the power supply, communication, and control system with a small size of 48 mm × 38 mm × 38 mm, which ensures a wireless controllable motion. Then, various configurations of the multi‐module robot system are established with corresponding motion schemes, and the experiments with replaceable intermediate modules are further conducted to verify the transportation and image‐capturing functions. This work demonstrates the effectiveness of synthetic jet propulsion for aquatic modular reconfigurable robot systems, and it exhibits profound potential in future underwater applications.

ObjectiveHec1 is a component of the Ndc80 kinetochore complex and is frequently upregulated in various cancers. However, the clinical significance of Hec1 in cervical cancer remains largely unknown. This study aimed to investigate the expression patterns of Hec1 in cervical cancer and its relationship with the clinicopathological characteristics of patients diagnosed with the disease.MethodsImmunohistochemistry was used to assess the expression of Hec1 in 136 cervical cancer tissue samples and 82 normal cervical tissue samples. The relationship between Hec1 protein expression and the clinicopathological characteristics of cervical cancer patients was analyzed using the Chi-square test. Additionally, the association between Hec1 protein expression and patient survival was examined using Kaplan-Meier survival curves. Independent risk factors affecting the prognosis of cervical cancer patients were analyzed using the Cox proportional hazards regression model.ResultsThe positive expression rate of Hec1 protein in cervical cancer tissues was 83.82%, significantly higher than the 7.31% in normal cervical tissues. Compared to patients with negative Hec1 expression, those with positive expression exhibited significantly higher FIGO staging, increased lymph node metastasis, greater depth of tumor stromal infiltration, and larger tumor diameter. Multivariable analysis using the Cox proportional hazards regression model indicated that Hec1 positive expression was an independent risk factor for both overall survival (HR = 2.79, 95% CI: 1.65–4.05, p = 0.012) and progression-free survival (HR = 1.81, 95% CI: 1.22-3.18, p = 0.002) in cervical cancer patients. Kaplan-Meier survival curve analysis showed that patients with positive Hec1 expression experienced a lower overall survival (HR: 2.72, 95% CI: 1.15–4.52, p = 0.004) and progression-free survival (HR: 3.12, 95% CI: 1.62–5.03, p = 0.002) when compared to those with negative Hec1 expression.ConclusionHec1 is significantly upregulated in cervical cancer tissues and associated with poor prognosis in cervical cancer patients. Therefore, Hec1 could be a novel biomarker, not only for the diagnosis and treatment evaluation of cervical cancer but also as an indicator for predicting the prognosis of cervical cancer patients.

IntroductionIt is well known that there are significant differences in the prevalence of chronic pain between males and females. Human and animal imaging studies have shown that chronic pain profoundly alters the structure and function of brain regions. However, there is limited research on the sex-specific mechanisms underlying the brain plasticity and adaptive changes associated with chronic pain. In this article, we conducted a multimodal study to evaluate how nerve injury-induced chronic pain affects the brain.MethodsMale and female Sprague-Dawley (SD) rats with spared nerve injury (SNI) model underwent resting-state functional magnetic resonance imaging (rs-fMRI) (male sham group: n = 18; male SNI group: n = 18; female sham group: n = 20; female SNI group: n = 18) and magnetic resonance diffusion tensor imaging (DTI) (male sham group: n = 23; male SNI group: n = 21; female sham group: n = 20; female SNI group: n = 21) scanning. ICA method, Fractional amplitude of low-frequency fluctuations (fALFF), immunofluorescence staining, and graph theory analysis was utilized to extract the rs-fMRI changes of brain regions of each group.ResultsUsing SNI model, which promotes long-lasting mechanical allodynia, we found that neuropathic pain deeply modified the intrinsic organization of the brain functional network in male and female rats (main effect of operation: F = 298.449, P < 0.001). 64 independent components (ICs) in the brain were divided and assigned to 16 systems. In male rats, we observed significant alterations in the microstructure of the hippocampal cornu ammonis 1 and cornu ammonis 2 (CA1/CA2) region, as indicated by increased mean diffusivity (MD) (CA1_L: P = 0.02; CA1_R: P = 0.031; CA2_L: P = 0.035; CA2_R: P = 0.015) and radial diffusivity (RD) (CA1_L: P = 0.028; CA1_R: P = 0.033; CA2_L: P = 0.037; CA2_R: P = 0.038) values, along with enhanced activating transcription factor 3 (ATF3) expression. Conversely, in female rats, we found significant increases in the fractional amplitude of low frequency fluctuations (fALFF) value within the hippocampal dentate gyrus (DG) (F = 5.419, P = 0.023), accompanied by elevated c-Fos signal (F = 6.269, P = 0.031). Furthermore, graph theory analysis revealed notable differences in the small-world network of the hippocampal system in female rats, characterized by reduced small-world attributes and increased inter-nodal transmission efficiency.DiscussionOur study indicates sex differences in structural and functional alterations in the hippocampal system in rats under chronic pain conditions. The results suggest that the hippocampus system plays an important role in the different mechanisms of chronic pain in different sexes. These findings provide reliable insights to explore the complex mechanisms underlying sex differences in chronic pain.

Monkeypox, a communicable disease instigated by the monkeypox virus, transmits through direct contact with infectious skin lesions or mucosal blisters, posing severe complications such as pneumonia, encephalitis, and even fatality. Traditional clinical diagnostics, heavily reliant on the discerning judgment of clinical experts, are both time-consuming and labor-intensive, with inherent infection risks, underscoring the critical need for automated, efficient auxiliary diagnostic models. In response, we have developed a deep learning classification model augmented by self-attention mechanisms and feature pyramid integration, employing attentional strategies to amalgamate image features across varying scales and assimilating a priori knowledge from the VGG model to selectively capture salient features. Aiming to enhance task performance and model generalizability, we incorporated different components into the baseline model in a series of ablation studies, revealing the contribution of each component to overall model efficacy. In comparison with state-of-the-art deep learning models, our proposed model achieved the highest accuracy and precision, marking a 6% improvement over the second-best model. The results from ablation experiments corroborate the effectiveness of individual module components in enhancing model performance. Our method for diagnosing monkeypox demonstrates improved diagnostic precision and extends the reach of medical services in resource-constrained settings.

BackgroundThe disorder of uric acid metabolism is closely associated with gut microbiota and short-chain fatty acids (SCFAs) dysregulation, but the biological mechanism is unclear, limiting the development of uric acid-lowering active polysaccharides. Konjac glucomannan (KGM) could attenuate metabolic disturbance of uric acid and modulate the gut microbiota. However, the relationship between uric acid metabolism and gut microbiota is still unknown.MethodsIn this study, The fecal samples were provided by healthy volunteers and hyperuricemia (HUA) patients. Fecal samples from healthy volunteers was regarded as the NOR group. Similarly, 10% HUA fecal suspension was named as the HUA group. Then, fecal supernatant was inoculated into a growth basal medium containing glucose or KGM, and healthy fecal samples were designated as the NOR-GLU and NOR-KGM groups, while HUA fecal samples were designated as the HUA-GLU and HUA-KGM groups. All samples were cultured in an anaerobic bag system. After fermentation for 24 h, the samples were collected for further analysis of composition of intestinal microbiota, SCFAs concentration and XOD enzyme activity.ResultsThe results showed that KGM could be utilized and degraded by the gut microbiota from HUA subjects, and it could modulate the composition and structure of their HUA gut microbiota to more closely resemble that of a healthy group. In addition, KGM showed a superior modulated effect on HUA gut microbiota by increasing Megasphaera, Faecalibacterium, Lachnoclostridium, Lachnospiraceae, Anaerostipes, and Ruminococcus levels and decreasing Butyricicoccus, Eisenbergiella, and Enterococcus levels. Furthermore, the fermentation solution of KGM showed an inhibitory effect on xanthine oxidase (XOD) enzyme activity, which might be due to metabolites such as SCFAs.ConclusionIn conclusion, the effect of KGM on hyperuricemia subjects was investigated based on the gut microbiota in vitro. In the present study. It was found that KGM could be metabolized into SCFAs by HUA gut microbiota. Furthermore, KGM could modulate the structure of HUA gut microbiota. At the genus level, KGM could decrease the relative abundances of Butyricicoccus, Eisenbergiella, and Enterococcus, while Lachnoclostridium and Lachnospiraceae in HUA gut microbiota were significantly increased by the addition of KGM. The metabolites of gut microbiota, such as SCFAs, might be responsible for the inhibition of XOD activity. Thus, KGM exhibited a superior probiotic function on the HUA gut microbiota, which is expected as a promising candidate for remodeling the HUA gut microbiota.

Abstract Clinically, chronic pain and depression often coexist in multiple diseases and reciprocally reinforce each other, which greatly escalates the difficulty of treatment. The neural circuit mechanism underlying the chronic pain/depression comorbidity remains unclear. The present study reports that two distinct subregions in the paraventricular thalamus (PVT) play different roles in this pathological process. In the first subregion PVT posterior (PVP), glutamatergic neurons (PVPGlu) send signals to GABAergic neurons (VLPAGGABA) in the ventrolateral periaqueductal gray (VLPAG), which mediates painful behavior in comorbidity. Meanwhile, in another subregion PVT anterior (PVA), glutamatergic neurons (PVAGlu) send signals to the nucleus accumbens D1‐positive neurons and D2‐positive neurons (NAcD1→D2), which is involved in depression‐like behavior in comorbidity. This study demonstrates that the distinct thalamo‐subcortical circuits PVPGlu→VLPAGGABA and PVAGlu→NAcD1→D2 mediated painful behavior and depression‐like behavior following spared nerve injury (SNI), respectively, which provides the circuit‐based potential targets for preventing and treating comorbidity.

Objectives To estimate the interaction between economic status (ES) and healthy lifestyle in long COVID among Chinese older people infected with SARS-CoV-2.Design A cross-sectional study based on the Peking University Health Cohort in Anning, Yunnan.Setting All primary health institutions in Anning, Yunnan Province, China, from April to May 2023.Participants A total of 4804 people aged 60 and older infected with SARS-CoV-2 were included in this study.Primary and secondary outcome measures Long COVID was measured by participants’ self-reported symptoms using structured questionnaires. ES was measured by last-month personal income, and participants’ ES was defined as low if their income was below the per capita monthly income of local residents. Lifestyle score was equal to the number of healthy behaviours (including smoking, drinking, weight, exercise and diet) and grouped using the median score as the cut-off point. Univariate and multivariate logistic models were employed to estimate the association of ES with long COVID. Interaction between ES and lifestyle in long COVID was assessed by multiplicative interaction term.Results We enrolled a total of 4804 participants infected with SARS-CoV-2, of whom 57.3% (2754 of 4804) had at least one long COVID symptom. Fatigue (1546, 56.1%), cough (1263, 45.9%) and muscle pain (880, 32.0%) were the top three common symptoms. Patients with low ES had a 48% (adjusted OR: 1.48; 95% CI 1.22, 1.82) increased risk of long COVID. A significant interaction was observed between ES and lifestyle (p value for interaction

An increase in acute myocardial infarction (AMI)-related deaths has been reported during the COVID-19 pandemic. Despite evidence suggesting the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and AMI, the underlying mechanisms remain unclear. Here, we integrated mRNA and microRNA expression profiles related to SARS-CoV-2 infection and AMI from public databases. We then performed transcriptomic analysis using bioinformatics and systems biology approaches to explore the potential molecular mechanisms of SARS-CoV-2 infection affects AMI. First, twenty-one common differentially expressed genes (DEGs) were identified from SARS-CoV-2 infection and AMI patients in endothelial cells datasets and then we performed functional analysis to predict the roles of these DEGs. The functional analysis emphasized that the endothelial cell response to cytokine stimulus due to excessive inflammation was essential in these two diseases. Importantly, the tumor necrosis factor and interleukin-17 signaling pathways appeared to be integral factors in this mechanism. Interestingly, most of these common genes were also upregulated in transcriptomic datasets of SARS-CoV-2-infected cardiomyocytes, suggesting that these genes may be shared in cardiac- and vascular-related injuries. We subsequently built a protein-protein interaction network and extracted hub genes and essential modules from this network. At the transcriptional and post-transcriptional levels, regulatory networks with common DEGs were also constructed, and some key regulator signatures were further identified and validated. In summary, our research revealed that a highly activated inflammatory response in patients with COVID-19 might be a crucial factor for susceptibility to AMI and we identified some candidate genes and regulators that could be used as biomarkers or potential therapeutic targets.

ABSTRACT Stripe rust of wheat is caused by the fungal pathogen Puccinia striiformis f. sp. tritici (Pst). Breeding durably resistant wheat varieties by disrupting the susceptibility (S) gene has an important impact on the control of wheat stripe rust. Mingxian169 (MX169) showed strong stripe rust susceptibility to all the races of Pst. However, molecular mechanisms and responsive genes underlying susceptibility of the wheat variety MX169 to Pst have not been elucidated. Here, we utilized next-generation sequencing technology to analyze transcriptomics data of “MX169” and high-resistance wheat “Zhong4” at 24, 48, and 120 h post-inoculation (hpi) with Pst. Comparative transcriptome analysis revealed 3,494, 2,831, and 2,700 differentially expressed genes (DEGs) at different time points. We observed an upregulation of DEGs involved in photosynthesis, flavonoid biosynthesis, pyruvate metabolism, thiamine metabolism, and other biological processes, suggesting their involvement in MX169’s response to Pst. DEGs encoding transcription factors were also identified. Our study suggested the potential susceptibility gene resources in MX169 related to stripe rust response could be valuable for understanding the mechanisms involved in stripe rust susceptibility and for improving wheat resistance to Pst.IMPORTANCEOur study suggests the potential susceptibility gene resources in MX169 related to stripe rust response could be valuable for understanding the mechanisms involved in stripe rust susceptibility and for improving wheat resistance to Pst.

Abstract Miniature resonant piezoelectric robots have the advantages of compact structure, fast response, high speed, and easy control, which have attracted the interest of many scholars in recent years. However, piezoelectric robots usually suffer from the problem of poor adaptability due to the micron‐level amplitude at the feet. Inspired by the fact that earthworms have actuation trajectories all around their bodies to move flexibly under the ground, a miniature piezoelectric robot with circumferentially arranged driving feet to improve adaptability is proposed. Notably, a longitudinal‐vibration‐compound actuation principle with multilegged collaboration is designed to achieve the actuation trajectories around the robot, similar to the earthworms. The structure and operating principle are simulated by the finite element method, and the prototype is fabricated. The robot weighs 22.7 g and has dimensions of 35.5 × 36.5 × 47 mm3. The robot is tethered to an ultrasonic power supply, and the experimental results show that the speed reaches 179.35 mm s−1 under an exciting signal with a frequency of 58.5 kHz and a voltage of 200 Vp‐p. High adaptability is achieved by the proposed robot, it can move on flat, fold, concave, and convex surfaces, and even in an inclined or rotating tube.

Abstract The precipitation of magnesium oxide (MgO) from the Earth's core has been proposed as a potential energy source to power the geodynamo prior to the inner core solidification. Yet, the stable phase and exact amount of MgO exsolution remain elusive. Here we utilize an iterative learning scheme to develop a unified deep learning interatomic potential for the Mg‐Fe‐O system valid over a wide pressure‐temperature range. This potential enables direct, large‐scale simulations of MgO exsolution processes at the Earth's core‐mantle boundary. Our results suggest that Mg exsolve in the form of crystalline Fe‐poor ferropericlase as opposed to a liquid MgO component presumed previously. The solubility of Mg in the core is limited, and the present‐day core is nearly Mg‐free. The resulting exsolution rate is small yet nonnegligible, suggesting that MgO exsolution may provide a potentially important energy source, although it alone may be difficult to drive an early geodynamo.

The recent advances in aqueous magnesium-ion hybrid supercapacitor (MHSC) have attracted great attention as it brings together the benefits of high energy density, high power density, and synchronously addresses cost and safety issues. However, the freeze of aqueous electrolytes discourages aqueous MHSC from operating at low-temperature conditions. Here, a low-concentration aqueous solution of 4 mol L−1 Mg(ClO4)2 is devised for its low freezing point (−67 °C) and ultra-high ionic conductivity (3.37 mS cm−1 at −50 °C). Both physical characterizations and computational simulations revealed that the Mg(ClO4)2 can effectively disrupt the original hydrogen bond network among water molecules via transmuting the electrolyte structure, thus yielding a low freezing point. Thus, the Mg(ClO4)2 electrolytes endue aqueous MHSC with a wider temperature operation range (−50 °C–25 °C) and a higher energy density of 103.9 Wh kg−1 at 3.68 kW kg−1 over commonly used magnesium salts (i.e., MgSO4 and Mg(NO3)2) electrolytes. Furthermore, a quasi-solid-state MHSC based on polyacrylamide-based hydrogel electrolyte holds superior low-temperature performance, excellent flexibility, and high safety. This work pioneers a convenient, cheap, and eco-friendly tactic to procure low-temperature aqueous magnesium-ion energy storage device.

Abstract Objective To investigate the effectiveness and tolerability of ketogenic diet therapy (KDT) in patients with developmental and epileptic encephalopathy (DEE) associated with genetic etiology which onset within the first 6 months of life, and to explore the association between response to KDT and genotype/clinical parameters. Methods We retrospectively reviewed data from patients with genetic DEE who started KDT at Beijing Children's Hospital between January 1, 2016, and December 31, 2021. Results A total of 32 patients were included, involving 14 pathogenic or likely pathogenic single genes, and 16 (50.0%) patients had sodium/potassium channel gene variants. The median age at onset of epilepsy was 1.0 (IQR: 0.1, 3.0) months. The median age at initiation of KDT was 10.0 (IQR: 5.3, 13.8) months and the median duration of maintenance was 14.0 (IQR: 7.0, 26.5) months, with a mean blood β‐hydroxybutyrate of 2.49 ± 0.62 mmol/L. During the maintenance period of KDT, 26 (81.3%) patients had a ≥50% reduction of seizure frequency, of which 12 (37.5%) patients achieved seizure freedom. Better responses were observed in patients with STXBP1 variants, with four out of five patients achieving seizure freedom. There were no statistically differences in the age of onset, duration of epilepsy before KDT, blood ketone values, or the presence of ion channel gene variants between the seizure‐free patients and the others. The most common adverse effects were gastrointestinal side effects, which occurred in 21 patients (65.6%), but all were mild and easily corrected. Only one patient discontinued KDT due to nephrolithiasis. Significance KDT is effective in treating early onset genetic DEE, and no statistically significant relationship has been found between genotype and effectiveness in this study. KDT is well tolerated in most young patients, with mild and reversible gastrointestinal side effects being the most common, but usually not the reason to discontinue KDT. Plain Language Summary This study evaluated the response and side effects of ketogenic diet therapy (KDT) in patients who had seizures within the first 6 months of life, and were diagnosed with genetic developmental and epileptic encephalopathy (DEE), a type of severe epilepsy with developmental delay caused by gene variants. Thirty‐two patients involving 14 gene variants who started KDT at Beijing Children's Hospital between were included. KDT was effective in treating early onset genetic DEE in this cohort, and patients with STXBP1 variants responded better; however, no statistically significant relationship was found between gene variant and response. Most young patients tolerated KDT well, with mild and reversible gastrointestinal side effects being the most common.

Abstract To determine the association between complement C1q and vulnerable plaque morphology among coronary artery disease (CAD) patients. We conducted a retrospective observational study of 221 CAD patients admitted to The Second Affiliated Hospital of Xi’an Jiaotong University. Intravascular optical coherence tomography was utilized to describe the culprit plaques’ morphology. Using logistic regression analysis to explore the correlation between C1q and vulnerable plaques, and receiver operator characteristic (ROC) analysis assess the predictive accuracy. As reported, the complement C1q level was lower in ACS patients than CCS patients (18.25 ± 3.88 vs. 19.18 ± 4.25, P = 0.045). The low complement-C1q-level group was more prone to develop vulnerable plaques. In lipid-rich plaques, the complement C1q level was positively correlated with the thickness of fibrous cap (r = 0.480, P = 0.041). Univariate and multivariate logistic regression analyses suggested that complement C1q could be an independent contributor to plaques’ vulnerability. For plaque rupture, erosion, thrombus, and cholesterol crystals, the areas under the ROC curve of complement C1q level were 0.873, 0.816, 0.785, and 0.837, respectively (P

Abstract Background COVID-19 vaccines are authorized for use in children in the United States; real-world assessment of vaccine effectiveness in children is needed. This study’s objective was to estimate the effectiveness of receiving a complete primary series of monovalent BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine in US children. Methods This cohort study identified children aged 5–17 years vaccinated with BNT162b2 matched with unvaccinated children. Participants and BNT162b2 vaccinations were identified in Optum and CVS Health insurance administrative claims databases linked with Immunization Information System (IIS) COVID-19 vaccination records from 16 US jurisdictions between December 11, 2020, and May 31, 2022 (end date varied by database and IIS). Vaccinated children were followed from their first BNT162b2 dose and matched to unvaccinated children on calendar date, US county of residence, and demographic and clinical factors. Censoring occurred if vaccinated children failed to receive a timely dose 2 or if unvaccinated children received any dose. Two COVID-19 outcome definitions were evaluated: COVID-19 diagnosis in any medical setting and COVID-19 diagnosis in hospitals/emergency departments (EDs). Propensity score-weighted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with Cox proportional hazards models, and vaccine effectiveness (VE) was estimated as 1 minus HR. VE was estimated overall, within age subgroups, and within variant-specific eras. Sensitivity, negative control, and quantitative bias analyses evaluated various potential biases. Results There were 453,655 eligible vaccinated children one-to-one matched to unvaccinated comparators (mean age 12 years; 50% female). COVID-19 hospitalizations/ED visits were rare in children, regardless of vaccination status (Optum, 41.2 per 10,000 person-years; CVS Health, 44.1 per 10,000 person-years). Overall, vaccination was associated with reduced incidence of any medically diagnosed COVID-19 (meta-analyzed VE = 38% [95% CI, 36–40%]) and hospital/ED–diagnosed COVID-19 (meta-analyzed VE = 61% [95% CI, 56–65%]). VE estimates were lowest among children 5–11 years and during the Omicron-variant era. Conclusions Receipt of a complete BNT162b2 vaccine primary series was associated with overall reduced medically diagnosed COVID-19 and hospital/ED–diagnosed COVID-19 in children; observed VE estimates differed by age group and variant era. Registration The study protocol was publicly posted on the BEST Initiative website ( https://bestinitiative.org/wp-content/uploads/2022/03/C19-VX-Effectiveness-Protocol_2022_508.pdf ).

A high-quality snow depth product is very import for cryospheric science and its related disciplines. Current long time-series snow depth products covering the Northern Hemisphere can be divided into two categories: remote sensing snow depth products and reanalysis snow depth products. However, existing gridded snow depth products have some shortcomings. Remote sensing-derived snow depth products are temporally and spatially discontinuous and tend to underestimate snow depth, while reanalysis snow depth products have coarse spatial resolutions and great uncertainties. To overcome these problems, in our previous work we proposed a novel data fusion framework based on Random Forest Regression of snow products from Advanced Microwave Scanning Radiometer for the Earth Observing System (AMSR-E), Advanced Microwave Scanning Radiometer-2 (AMSR2), Global Snow Monitoring for Climate Research (GlobSnow), the Northern Hemisphere Snow Depth (NHSD), ERA-Interim, and Modern-Era Retrospective Analysis for Research and Applications, version 2 (MERRA-2), incorporating geolocation (latitude and longitude), and topographic data (elevation), which were used as input independent variables. More than 30,000 ground observation sites were used as the dependent variable to train and validate the model in different time periods. This fusion framework resulted in a long time series of continuous daily snow depth product over the Northern Hemisphere with a spatial resolution of 0.25°. Here, we compared the fused snow depth and the original gridded snow depth products with 13,272 observation sites, showing an improved precision of our product. The evaluation indices of the fused (best original) dataset yielded a coefficient of determination R2 of 0.81 (0.23), Root Mean Squared Error (RMSE) of 7.69 (15.86) cm, and Mean Absolute Error (MAE) of 2.74 (6.14) cm. Most of the bias (88.31%) between the fused snow depth and in situ observations was in the range of −5 cm to 5 cm. The accuracy assessment of independent snow observation sites – Sodankylä (SOD), Old Aspen (OAS), Old Black Spruce (OBS), and Old Jack Pine (OJP) – showed that the fused snow depth dataset had high precision for snow depths of less than 100 cm with a relatively homogeneous surrounding environment. The results of random point selection and independent in situ site validation show that the accuracy of the fused snow depth product is not significantly improved in deep snow areas and areas with complex terrain. In the altitude range of 100 m to 2000 m, the fused snow depth had a higher precision, with R2 varying from 0.73 to 0.86. The fused snow depth had a decreasing trend based on the spatiotemporal analysis and Mann-Kendall trend test method. This fused snow depth product provides the basis for understanding the temporal and spatial characteristics of snow cover and their relation to climate change, hydrological and water cycle, water resource management, ecological environment, snow disaster and hazard prevention.

Abstract Background Familial hypercholesterolemia (FH) is an autosomal semi-dominant disease, characterized by markedly elevated levels of low-density lipoprotein cholesterol (LDL-c) from conception and accelerated atherosclerotic cardiovascular disease, often resulting in early death. The aim of this study was to evaluate the prevalence of clinically defined FH in Chinese Han patients with acute coronary syndrome (ACS) and compare the long-term prognosis of ACS patients with and without FH receiving lipid-lowering therapy containing statins after a coronary event. Methods All ACS patients were screened at the Second Affiliated Hospital of Xi’an Jiaotong University between Jan 2019 and Sep 2020, and 531 participants were enrolled. All were examined for FH under the Dutch Lipid Clinical Network (DLCN) criteria, and those patients were divided into definite/probable FH, possible FH and unlikely FH. The severity of coronary artery disease was evaluated by the Gensini scoring system. Plasma levels of total cholesterol (TC), triacylglycerol (TG), HDL-cholesterol (HDL-c), LDL-cholesterol (LDL-c), very low-density lipoproteins-cholesterol (VLDL-c), apolipoprotein A1 (apoA1), apolipoprotein B (apoB) and lipoprotein (a) (Lp(a)) were determined centrally at baseline and the last follow-up visit in the fasting state. The non-high-density lipoprotein cholesterol (non-HDL-c) concentration, the TC/HDL-c and apoB/apoA1 ratios were calculated. After FH patients received lipid-lowering treatment containing statin, the target LDL-c levels recommended by the guidelines (LDL-c 50% from baseline) were evaluated, and the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) during the 12-month follow-up was recorded. Results The prevalence of clinically definite or probable FH was 4.3%, and the prevalence of possible FH was 10.6%. Compared with the unlikely FH patients with ACS, the FH patients had higher levels of TC, LDL-c, apoB, Lp(a), non-HDL-c, TC/HDL-c and apoB/apoA1 ratio, more severe coronary artery diseases and greater prevalence of left main and triple or multiple vessel lesions. After lipid-lowering therapy containing statins, a minority of FH patients reached the target LDL-c levels defined by the guidelines (χ2 = 33.527, P 0.05). Conclusions FH was an independent risk factor for MACCE in adult patients after a coronary event during long-term follow-up. However, there was inadequate high-intensity statins prescriptions for high-risk patients in this current study. It is important for FH patients to optimize lipid-lowering treatment strategies to reach the target LDL-c level to improve the long-term prognosis of clinical outcomes.

Objective Defining the distribution of sweet spots in tight reservoirs is the focus of tight oil and gas exploration. Methods Using core observation, thin section identification, X-ray diffraction, homogenization temperature measurements of inclusions, and conventional physical property analysis, the sedimentary characteristics, reservoir characteristics, and diagenesis of Upper Palaeozoic tight sandstones in the Binchang area, southern Ordos Basin were studied in detail.The main controlling factors of reservoir formation were identified and the development model of high-quality reservoirs was established. Results The results show that sedimentary facies are the basis of reservoir formation, and the core beach microfacies of the braided river delta plain have coarse grain sizes, small pore-medium-fine throat pore structures, and relatively good reservoir physical properties. The underwater distributary channel and estuary bar in front of the meandering river delta have fine grain sizes and pore throat structures of micropore-microat throat pore structure, and the reservoir's physical properties are relatively poor. Diagenesis plays an important role in controlling the development and distribution of high-quality reservoirs. Intermittent volcanic tuff is transformed into kaolinite in acidic strata and altered into chlorite sheaths in alkaline strata, which inhibits quartz overgrowth and calcite cementation and protects the reservoir space. The secondary enlargement of quartz is mainly caused by the leaching of SiO2 from mudstone to sandstone.The main reasons for the cementation of calcite roof and floor are the filling of feldspar and the dissolution of cuttings in the middle and late stages of calcite. The microfractures formed by late tectonic transformation have no calcite cementation, which improves the physical properties of the reservoir and plays an adjusting role in the gas reservoir. There are two solution pore development zones near burial depths of 3 750 m and 3 900 m in the Binchang area. The optimal reservoir is the medium-coarse-grained sandstone rich in chlorite mantle formed by the transformation of volcanic tuffaceous matter in the dissolution pore development zone. The sub-optimal reservoir is mainly distributed in the middle and lower parts of the sand body with a greater single-body thickness, cyclicity and no mudstone interval in the dissolution pore development zone.This zone is composed mainly of medium-coarse-grained sandstone lacking chlorite film, calcite cementation and secondary enlargement of quartz are the lowest. Conclusion These research results further increase the understanding of the genesis of the development of high-quality tight sandstone reservoirs in the Upper Palaeozoic, providing important guidance for natural gas exploration and development in this area.

Abstract In recent decades, more than 100,000 scientific articles have been devoted to the development of electrode materials for supercapacitors and batteries. However, there is still intense debate surrounding the criteria for determining the electrochemical behavior involved in Faradaic reactions, as the issue is often complicated by the electrochemical signals produced by various electrode materials and their different physicochemical properties. The difficulty lies in the inability to determine which electrode type (battery vs. pseudocapacitor) these materials belong to via simple binary classification. To overcome this difficulty, we apply supervised machine learning for image classification to electrochemical shape analysis (over 5500 Cyclic Voltammetry curves and 2900 Galvanostatic Charge-Discharge curves), with the predicted confidence percentage reflecting the shape trend of the curve and thus defined as a manufacturer. It’s called “capacitive tendency”. This predictor not only transcends the limitations of human-based classification but also provides statistical trends regarding electrochemical behavior. Of note, and of particular importance to the electrochemical energy storage community, which publishes over a hundred articles per week, we have created an online tool to easily categorize their data.

A hail process in Xunyi hail suppression experimental area of Shaanxi Province at 13:00 （Beijing Time） on 28 July 1997 was simulated by using a three-dimensional strong storm dynamic electric coupling numerical model.This paper analyzes the influence of artificial hail suppression on the concentration and temporal and spatial variation of ice particles in clouds， as well as its influence on electrification and discharge.The results show that， overall， the concentration and specific water content of ice crystals， snowflakes and graupel particles increase in the range of -40~0 ℃.AgI seeding reduces the average scale of graupel and greatly reduces the conversion ratio to hail， resulting in the reduction of specific water content and number concentration of hail.With the increase of AgI seeding dose， hail suppression effect will be better， but the rainfall will first increase and then decrease.Therefore， the seeding dose should take an appropriate value between balanced hail suppression and precipitation enhancement.AgI seeding will lead to the positive lower non-induced electrification zone appears earlier， the center is enhanced and the upper boundary is raised in the early stage， while in the late stage， the center of the negative upper non-induced electrification zone is enhanced.Therefore， the bottom sub-positive charge area was enhanced in the early stage after seeding， and the upper main positive charge area and the middle negative charge area were enhanced in the late stage.With the increase of catalytic dose， these changes became more obvious.AgI seeding has a certain inhibitory effect on ground lightning， but the cloud flash and total flash increase a little after seeding， the peak time of the first discharge and cloud flash is earlier， the discharge duration is stronger， and the lightning frequency is slightly reduced in the lightning frequent period.

Background: Although the changes of mitogen-activated protein kinase (MAPK) pathway in the central nervous system (CNS) induced by excessive fluoride has been confirmed by our previous findings, the underlying mechanism(s) of the action remains unclear. Here, we investigate the possibility that microRNAs (miRNAs) are involved in the aspect. Methods: As a model of chronic fluorosis, SD rats received different concentrations of fluoride in their drinking water for 3 or 6 months and SH-SY5Y cells were exposed to fluoride. Literature reviews and bioinformatics analyses were used to predict and real-time PCR to measure the expression of 12 miRNAs; an algorithm-based approach was applied to identify multiply potential target-genes and pathways; the dual-luciferase reporter system to detect the association of miR-132–3p with MAPK1; and fluorescence in situ hybridization to detect miR-132–3p localization. The miR-132–3p inhibitor or mimics or MAPK1 silencing RNA were transfected into cultured cells. Expression of protein components of the MAPK pathway was assessed by immunofluorescence or Western blotting. Results: In the rat hippocampus exposed with high fluoride, ten miRNAs were down-regulated and two up-regulated. Among these, miR-132–3p expression was down-regulated to the greatest extent and MAPK1 level (selected from the 220 genes predicted) was corelated with the alteration of miR-132–3p. Furthermore, miR-132–3p level was declined, whereas the protein levels MAPK pathway components were increased in the rat brains and SH-SY5Y cells exposed to high fluoride. MiR-132–3p up-regulated MAPK1 by binding directly to its 3′-untranslated region. Obviously, miR-132–3p mimics or MAPK1 silencing RNA attenuated the elevated expressions of the proteins components of the MAPK pathway induced by fluorosis in SH-SY5Y cells, whereas an inhibitor of miR-132–3p just played the opposite effect. Conclusion: MiR-132–3p appears to modulate the changes of MAPK signaling pathway in the CNS associated with chronic fluorosis.

Chest wall pain syndromes can emerge following local therapies for lung cancer and can adversely affect patients’ quality-of-life. This can occur after lung surgery, radiation therapy, or percutaneous image-guided thermal ablation. This review describes the multifactorial pathophysiology of chest wall pain syndromes that develop following surgical and non-surgical local therapies for lung cancer and summarizes evidence-based management strategies for inflammatory, neuropathic, myofascial, and osseous pain. It discusses a step-wise approach to treating chest wall pain that begins with non-opioid oral analgesics and includes additional pharmacologic treatments as clinically indicated, such as anticonvulsants, serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, and various topical treatments. For myofascial pain, physical medicine techniques, such as acupuncture, trigger point injections, deep tissue massage, and intercostal myofascial release can also offer pain relief. For severe or refractory cases, opioid analgesics, intercostal nerve blocks, or intercostal nerve ablations may be indicated. Fortunately, palliation of treatment-related chest wall pain syndromes can be managed by most clinical providers, regardless of the type of local therapy utilized for a patient’s lung cancer treatment. In cases where a patient’s pain fails to respond to initial medical management, clinicians can consider referring to a pain specialist who can tailor a more specific pharmacologic approach or perform a procedural intervention to relieve pain.

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.

Piezoelectric actuation technology has been widely used in various precise‐oriented fields. Its notable advantages include high resolution, rapid response speed, output force with high density, and immunity to electromagnetic interference. Characteristics of cross‐scale and multiple‐degree‐of‐freedom (multi‐DOF) output motions are of utmost importance in the context of micro‐/nanopositioning technology. For decades, researchers have been working to develop various piezoelectric devices that exploit these important properties. In this review, a comprehensive review of recent research efforts in the field of cross‐scale multi‐DOF piezoelectric drive technology is provided. To commence, it provides an in‐depth exploration of the unique advantages associated with piezoelectric actuation, demonstrating them through comparative analyses with alternative actuation methods. Subsequently, the complexity of piezoelectric cross‐scale motion is introduced, and the multi‐DOF piezoelectric motion is classified in detail. Furthermore, the practical applications of multi‐DOF cross‐scale piezoelectric actuation technology are systematically elucidated, highlighting its versatility and suitability in real‐world environments. Finally, an in‐depth discussion that addresses the challenges encountered in the field is provided, and the prospective directions for further developments in piezoelectric actuation technology are outlined. This scholarly contribution plays an important role in guiding future research and innovative initiatives.