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Abstract Organic carbon burial (OCB) in lakes, a critical component of the global carbon cycle, surpasses that in oceans, yet its response to global warming and associated feedbacks remains poorly understood. Using a well-dated biomarker sequence from the southern Tibetan Plateau and a comprehensive analysis of Holocene total organic carbon variations in lakes across the region, here we demonstrate that lake OCB significantly declined throughout the Holocene, closely linked to changes in temperature seasonality. Process-based land surface model simulations clarified the key impact of temperature seasonality on OCB in lakes: increased seasonality in the early Holocene saw warmer summers enhancing ecosystem productivity and organic matter deposition, while cooler winters improved organic matter preservation. The Tibetan Plateau’s heightened sensitivity to climate and ecosystem dynamics amplifies these effects. With declining temperature seasonality, we predict a significant slowdown or reduction in OCB across these lake sediments, leading to carbon emissions and amplified global warming.

Abstract Background Carotenoids have been shown to have multiple health benefits, including antioxidant and anti-inflammatory. The data for the effect of dietary specific carotenoids on biological aging is limited. Our study aims to examine the association between dietary carotenoid intake levels and biological aging. Methods This cross-sectional study was performed among 27,338 adults from NHANES 1999–2018. Dietary intake was assessed through two 24-hour dietary recall interviews. Biological aging indices included allostatic load (AL), homeostatic dysregulation (HD), Klemera-Doubal method (KDM), and phenoAge (PA). Multiple linear regression, weighted quantile sum (WQS) regression and quantile g-computation (QG-comp) were used to explore the associations of single carotenoid and mixed carotenoids with biological aging. Results Associations between dietary carotenoid intake levels and biological aging indices were significant among adults across the United States. Multiple linear regression showed that most carotenoids were significantly negatively correlated with AL (β = -0.017 - -0.011), HD (β = -0.045 - -0.032), KDM (β = -0.984 - -0.471), and PA (β = -0.975 - -0.539). Subgroup analysis indicated that male, older individuals, smokers, alcohol drinkers, and less physically active individuals are particularly sensitive populations. Meanwhile, WQS regression and QG-comp analyses consistently indicated a negative association between mixed carotenoids exposure and four biological aging indices, highlighting that lutein/zeaxanthin and β-carotene were responsible for the outcomes. Conclusions Increased dietary intakes of various carotenoids were associated with lower biological aging indices, which was possibly and mainly driven by lutein/zeaxanthin and β-carotene.

Objective The objective of this study was to analyze failed posterior fossa decompression (PFD) in patients with basilar invagination and atlantoaxial dislocation (BI‐AAD). Revision surgery in these patients is challenging and has been rarely reported. In addition, the anatomical variations of the vertebral artery increase the risk of revision surgery. Here, we introduce the implementation of a new type of one‐stage posterior revision surgery, whose difficulties and effects are summarized. Methods A total of 21 patients with BI‐AAD who underwent PFD were retrospectively analyzed in our center from November 2017 to April 2021. The revision surgery in all patients was performed through the posterior approach. The Japanese Orthopaedic Association (JOA) score and the Short Term 12 (SF‐12) score were employed to evaluate the clinical symptoms and health status. The distance from the tip of the odontoid to Chamberlain's line (DCL), the atlantodental interval (ADI), the clivus‐canal angle (CCA), the diameter of the subarachnoid space (DSS), and the craniovertebral junction triangular area (CTA) were assessed radiographically. The pre‐ and postoperative results were compared by paired t test. Results The data of 21 consecutive patients were reviewed, with an average follow‐up period of 28 ± 14 months. Postoperative imaging showed effectively reduced compression of BI‐AAD. No implant failure or neurovascular injury occurred. Eleven patients had vertebral artery abnormalities, but none had vertebral artery injury. All patients had evidence of bone fusion on the CT scan images within a 12‐month follow‐up period. The JOA and SF‐12 scores were significantly improved 1 year postoperatively (p

AIM: To study the causal relationship between obesity-related anthropometric traits and myopia and the mediating role of educational attainment (EA). METHODS: Univariable Mendelian randomization (UVMR) was performed to evaluate the causal association between body mass index (BMI), height, waist-hip ratio (WHR, adjusted for BMI), and mean spherical equivalent (MSE). BMI was divided into fat and fat-free mass and included in multivariable Mendelian randomization (MVMR) to explore the roles of different BMI components in the causal relationship between BMI and MSE. A mediation analysis based on two-step Mendelian randomization (MR) was carried out. Specifically, UVMR was conducted to estimate the causal effect of BMI on EA. The direct effect of EA on MSE was estimated from MVMR. The mediation effect of EA in the BMI-EA-MSE model was calculated by the product of coefficients method. Expression quantitative trait loci (eQTL)-MR, reverse MR, and Linkage Disequilibrium Score Regression (LDSC) were performed to assess the robustness. RESULTS: Genetically predicted higher BMI had a positive total effect on MSE (βIVW=0.26 D, 95%CI=0.14 to 0.37 D, P

Objective The craniovertebral junction (CVJ) presents intricate anatomical challenges. In severe or irreducible malformations, complications such as reduction loss and fixation failure may occur, necessitating revision surgery. The posterior facet joint distraction and fusion (PFDF) technique, offers a solely posterior approach for revisions. Hence, we delineate varied revision scenarios, proposing surgical strategies and technical details to enhance outcomes and mitigate risks, thereby enriching the neurosurgical community's repertoire. Methods This was a retrospective cohort study, analyzed patient data from Xuanwu Hospital, between 2017 to 2023. All patients had a history of surgical treatment for CVJ malformations, and experienced failure or loss of reduction. The distance from the odontoid process tip to the Chamberlain's line (DCL), the atlantodental interval (ADI), clivus‐canal angle, cervicomedullary angle, width of subarachnoid space, CVJ area, and width of syrinx were used for radiographic assessment. Japanese Orthopaedic Association (JOA) scores and SF‐12 scores were used for clinical assessment. Independent sample t‐tests were employed. A significance level of p

Abstract Solid fuel combustion exposure is a leading global health risk factor, yet evidence on its effects, especially on vulnerable children, is sparse. This large-scale, multi-center prospective study aimed to address this gap by involving 9997 schoolchildren across China between 2013 and 2015. Here we show that lung function levels exhibited a marginally significant decline among children exposed to solid fuel usage. Specifically, FVC and FEV1 decreased by 21.2 mL (95% CI: −15.7, 58.1) and 24.1 mL (−8.4, 56.6), respectively. Additionally, PEF, FEF25 and FEF75 decreased by 25.7 mL/s (−46.5, 98.0), 32.7 mL/s (−42.7, 108.2), and 35.4 mL/s (−5.9, 76.7), respectively. Persistent exposure to solid fuel usage in children led to greater lung damage. Children with allergy history were more susceptible to solid fuel exposure. Our study highlights the adverse impact of solid fuel usage on children and the need to promote clean fuel usage for this vulnerable population.

Abstract The recently discovered interaction between presenilin 1 (PS1), a subunit of γ-secretase involved in amyloid-β (Aβ) peptide production, and GLT-1, the major brain glutamate transporter (EAAT2 in the human), may link two pathological aspects of Alzheimer’s disease: abnormal Aβ occurrence and neuronal network hyperactivity. In the current study, we employed a FRET-based fluorescence lifetime imaging microscopy (FLIM) to characterize the PS1/GLT-1 interaction in brain tissue from sporadic AD (sAD) patients. sAD brains showed significantly less PS1/GLT-1 interaction than those with frontotemporal lobar degeneration or non-demented controls. Familial AD (fAD) PS1 mutations, inducing a “closed” PS1 conformation similar to that in sAD brain, and gamma-secretase modulators (GSMs), inducing a “relaxed” conformation, respectively reduced and increased the interaction. Furthermore, PS1 influences GLT-1 cell surface expression and homomultimer formation, acting as a chaperone but not affecting GLT-1 stability. The diminished PS1/GLT-1 interaction suggests that these functions may not work properly in AD.

Abstract Morphine has been suggested to affect cancer cell dynamics and decrease survival rates in lung cancer patients at specific doses, but the precise mechanisms poorly understood. In this study, we aimed to investigate the molecular mechanisms by which morphine modulates the malignant characteristics of non-small cell lung cancer. Cell proliferation was assessed via the Cell Counting Kit-8 assay, and cell migration and invasion were examined via wound healing and Transwell assays. We employed immunofluorescence staining to evaluate E-cadherin expression in A549 and Lewis lung cancer (LLC) cell lines and immunohistochemistry to evaluate E-cadherin expression in nude mice tumours. Additionally, the in vivo effects of morphine on lung cancer progression were explored in a xenograft tumour experiments, in which naloxone was used as a morphine antagonist. Western blot analysis was performed to detect E-cadherin, phosphorylated mTOR (p-mTOR), mTOR, phosphorylated AKT (p-AKT), AKT, phosphorylated PI3K (p-PI3K), and PI3K protein levels in A549 and LLC cells as well as in tumour samples. Morphine (10 µM) significantly increased the proliferation of A549 and LLC cells in vitro (p

[Introduction] China's transportation sector is a significant contributor to carbon emissions. To achieve carbon peaking and neutrality, developing a new transportation-energy integrated system based on energy Internet is a crucial step for the low-carbon transition of this sector. [Method] Focusing on low-carbon transition, this paper provided an overview of the development goals, policy background, innovations, and insights of China's new highway transportation-energy integrated system. [Result] Centered on the multi-objective demand of "energy-saving transportation – economical transportation – low-carbon transportation", various transportation-energy integrated service business models has been developed for China's new highway transportation-energy integrated system, such as battery charging & switching systems, PV-storage-charging integration systems, and oil-gas-hydrogen-electricity-PV charging & storage systems. Corresponding collaborative planning and construction, operation and control, advanced energy storage, multilevel coordination of energy management, and other key technologies are also being gradually developed. However, challenges related to planning, operation and environmental protection remain. To facilitate the rapid advancement of this integrated system, efforts should focus on expanding market awareness, streamlining regulations and strengthening technical collaboration in the next stage. [Conclusion] This paper discussed China's new future-oriented highway transportation-energy integrated system, offering valuable perspectives on enhancing the quality development of China's transportation sector.

Manganese (Mn) is necessary for various biological processes, yet its function in innate immunity has been less studied, especially in fish. Stimulator of interferon (IFN) genes (STING) is an essential factor for IFN induction in virus infection. Our study demonstrated that Mn2+ increases the ability of zebrafish to resist spring viraemia of carp virus (SVCV) infection by enhancing the expression of STING. Further mechanistic studies indicated that Mn2+ promotes the expression of STING by increasing its ubiquitination. Furthermore, Mn2+treatment promoted STING-mediated activation of IFN and reversed the decrease in STING protein induced by SVCV. Collectively, our findings showed the vital involvement and necessity of Mn2+ in protecting fish against SVCV infection.

Chinese Baijiu is among the six major distilled spirits in the world, with a significant output. Consequently, a large quantity of distillers' grains is produced. If these distillers' grains are not promptly treated, they cause a waste of biological resources and environmental problems. Many unused nutrients in distillers' grains can be reused to increase their economic value and minimize the risk of environmental pollution. This review summarizes the efficiency and limitations of the current technical methods of reutilizing distillers' grains concerning fertilizer, feed and energy production, and extraction of functional components. Furthermore, this study discusses the commercial viability, sustainable development goals, and industrial challenges of applying distillers' grains reutilization technology, providing valuable insights into the reutilization strategy of distillers' grains of the Chinese Baijiu. The comprehensive cycle-chain model of distillers' grains is the primary future trend of distillers' grains reuse, which is more conducive to the cleaner production of the Chinese Baijiu.

The genus of Polypedates Tschudi, 1838 currently comprises 25 recognised species with four of these species reported in Yunnan, China. Dubois (1987) speculated the distribution of P. teraiensis in China; however, there was no study carried out to confirm its distribution in the region.We herein describe P. teraiensis as a new national record, based on a specimen collected from Yunnan border region. Phylogenetically, our sequence clustered with the sequences of recognised P. teraiensis specimens from Bangladesh, Myanmar and India. The uncorrected pairwise distances between the specimens from China and other P. teraiensis localities was small, ranging from 0.0-0.7%, based on 16S rRNA gene. Therefore, we report P. teraiensis as a new species record for China.

The Gaoligong Mountains, located in the western part of China’s Yunnan Province adjoining northern Myanmar, harbor a striking diversity of species and endemism. Previous studies have shown that amphibian diversity in this region remains underestimated. A field survey carried out in 2023 oversaw a collection of eight Xenophrys specimens from the Tongbiguan Provincial Nature Reserve, Yunnan Province, China. Subsequent molecular analyses revealed two distinct and previously undescribed lineages. Based on morphological evidence, we formally describe one of the lineages as a new species and tentatively assign the other lineage to X. sp. due to the absence of adult specimens for examination. Our results bring the total number of Xenophrys species to 29 and the number of Xenophrys species known to occur in China to 11. Furthermore, our study reveals that five species and putative species of Xenophrys (X. dehongensis, X. glandulosa, X. periosa, X. yingjiangensis sp. nov., and X. sp.) exhibit sympatric distribution. These findings highlight the need for future research to investigate the mechanisms of sympatric coexistence in Xenophrys. In addition, our study confirms that the amphibian diversity of the Gaoligong Mountains is undoubtedly underestimated. As a result, continued exploration of amphibians in the future is necessary to obtain a clearer understanding of the overall biodiversity in this region.

Abstract Aim Clinical diagnosis and surgical treatment of chondrosarcoma (CS) are continuously improving. The purpose of our study is to evaluate the effectiveness of microwave ablation (MWA) assisted degradation therapy in the surgical treatment of intramedullary chondrosarcoma of the extremities, to provide a new reference and research basis for the surgical treatment of CS. Methods We recruited 36 patients with intramedullary CS who underwent MWA assisted extended curettage. Preoperative patient demographics and clinical data were recorded. Surgery was independently assisted by a medical team. Patients were followed up strictly and evaluated for oncological prognosis, radiological results, limb joint function, pain, and complications. Results We included 15 men and 21 women (mean age: 43.5 ± 10.1). The average length of the lesion was 8.1 ± 2.5 cm. Based on preoperative radiographic, clinical manifestations, and pathological results of puncture biopsy, 28 patients were preliminarily diagnosed with CS-grade I and eight patients with CS-grade II. No recurrence or metastasis occurred in the postoperative follow-up. The average Musculoskeletal Tumor Society score was 28.8 ± 1.0, significantly better than presurgery. Secondary shoulder periarthritis and abduction dysfunction occurred in early postoperative stage CS of the proximal humerus in some, but returned to normal after rehabilitation exercise. Secondary bursitis occurred at the knee joint in some due to the internal fixation device used in treatment; however, secondary osteoarthritis and avascular necrosis of the femoral head were not observed. Overall, oncological and functional prognoses were satisfactory. Conclusions The application of MWA assisted degradation therapy in intramedullary CS can achieve satisfactory oncology and functional prognosis, providing a new option for the limited treatment of CS.

The significant economic losses caused by S. abortus equi in donkey husbandry have increased interest in exploring the potential of phages and their enzymes as control strategies. In this study, a S. abortus equi phage, designated 4FS1, was isolated from sewage at a donkey farm. Transmission electron microscopy (TEM) revealed a typical icosahedral head and a long, non-contractile tail. It exhibited a short latent period of 20 min and a burst size of 160 plaque-forming units (PFU) per cell. It demonstrated a broad host range, infecting 36 out of 60 salmonella strains, with an optimal multiplicity of infection (MOI) of 0.01 for S. abortus equi S1. The phage titer remained stable at 109 PFU/mL between 37°C and 50°C and exceeded 108 PFU/mL at pH from 5.0 to 10.0. After 1 h of UV exposure, the titer remained at 107 PFU/mL and showed no significant variation across NaCl concentrations from 2.5 to 15%. The genome of phage 4FS1 consists of a 42,485 bp linear double-stranded DNA molecule with a G + C content of 49.07%. Of the 56 predicted open reading frames (ORFs), 32 were functional annotated, with no virulence or drug resistance genes identified. ORF36 was predicted to encode a depolymerase responsible for endorhamnosidase activity. Recombinant expression of the Dpo36 protein in prokaryotes significantly reduced biofilm formation and removal. Combined with healthy donkey serum, Dpo36 inhibited bacterial growth in vitro and enhanced the survival rates of mice infected with S. abortus equi. These findings highlight the promising potential of phages and their depolymerases as novel therapeutic agents against S. abortus equi.

ABSTRACT: The differences in lipids in duck eggs between the 2 rearing systems during storage have not been fully studied. Herein, we propose untargeted lipidomics combined with a random forest (RF) algorithm to identify potential marker lipids based on ultra-performance liquid chromatography‒mass spectrometry (UPLPC-MS/MS). A total of 106 and 16 differential lipids (DL) were screened in egg yolk and white, respectively. In yolk, metabolic pathway analysis of DLs revealed that glycerophospholipid metabolism and sphingolipid metabolism were the key metabolic pathways in the traditional free-range system (TFS) during storage, glycosylphosphatidylinositol-anchored biosynthesis and glyceride metabolism were the key pathways in the floor-rearing system (FRS). In egg white, the key pathway in both systems is the biosynthesis of unsaturated fatty acids. Combined with RF algorithm, 12 marker lipids were screened during storage. Therefore, this study elucidates the changes in lipids in duck eggs during storage in 2 rearing systems and provides new ideas for screening marker lipids during storage. This approach is highly important for evaluating the quality of egg and egg products and provides guidance for duck egg production.

Industrial parks are significant consumers of energy, contributing to global carbon emissions and intensifying the need for strategic interventions to meet carbon reduction and energy efficiency goals. In China, the Real Estate Investment Trusts (REITs) model has been adopted to advance the development of Integrated Energy Services (IESs) within these parks. This paper analyzes 23 Chinese government policy documents to explore the key stakeholders in park-based IESs, particularly the central role of energy companies in shaping collective decision-making processes. The study highlights how business models, including financial investment, offline and digital services, and innovative practices, have evolved under the REITs framework to drive the development of IESs and foster collaboration among stakeholders.

Abstract 1D grain boundaries in transition metal dichalcogenides (TMDs) are ideal for investigating the collective electron behavior in confined systems. However, clear identification of atomic structures at the grain boundaries, as well as precise characterization of the electronic ground states, have largely been elusive. Here, direct evidence for the confined electronic states and the charge density modulations at mirror twin boundaries (MTBs) of monolayer NbSe2, a representative charge‐density‐wave (CDW) metal, is provided. The scanning tunneling microscopy (STM) measurements, accompanied by the first‐principles calculations, reveal that there are two types of MTBs in monolayer NbSe2, both of which exhibit band bending effect and 1D boundary states. Moreover, the intrinsic CDW signatures of monolayer NbSe2 are dramatically suppressed as approaching an isolated MTB but can be either enhanced or suppressed in the MTB‐constituted confined wedges. Such a phenomenon can be well explained by the MTB‐CDW interference interactions. The results reveal the underlying physics of the confined electrons at MTBs of CDW metals, paving the way for the grain boundary engineering of the functionality.

We conducted a case-control study to investigate the effects of genetics and gene-environment interactions on major depressive disorders (MDD) in the Chinese population. Using targeted-exome sequencing, we included 984 patients with MDD and 508 healthy controls in our study. A logistic regression model was employed to analyze the association between single nucleotide polymorphisms (SNPs) and MDD. Additionally, a linear regression model was utilized to examine the associations between (1) gene-environment interaction and the 17-item Hamilton Depression Rating Scale, (2) SNPs and the Beck Scale for Suicide Ideation-Chinese version, and gene-environment interaction and the Beck scale for suicide ideation-Chinese version. The association analysis between SNPs and MDD revealed that the following loci reached genome-wide significance: rs2305554 of the cholinergic receptor nicotinic alpha 7 subunit, rs9459173 of synaptojanin 2, rs372369000 of beta-1,4-galactosyltransferase 6, rs866666526 of dopa decarboxylase, rs1254882194 of calcium/calmodulin dependent protein kinase ID, rs199880487 of reelin, rs1167948188 of reelin, rs1390140186 of QKI, KH domain containing RNA binding, and rs1776342 of period circadian regulator 3. The association analysis between SNPs and the Beck Scale for Suicide Ideation-Chinese version indicated that rs264272 and rs1774784888 of piezo type mechanosensitive ion channel component 2 reached genome-wide significance. These findings may enhance our understanding of MDD and contribute to the development of new potential targets for its diagnosis and treatment.

Abstract Background Changes in economy and dietary guidelines brought a great shock to diet quality and meal behaviors, but if these transformations have extended to minerals intake and their sources was still poorly understood. It is essential to evaluate time trends in minerals intake and their sources to inform policy makers. Objective To investigate trends in minerals intake and their sources among U.S. adults. Methods This analysis used dietary data collected by 24-h recalls from U.S. adults (≥ 20 years) in NHANES (1999-March 2020). Minerals intake, age-adjusted percentage of participants meeting recommendations, and minerals sources were calculated among all participants and by population subgroups in each NHANES survey cycle. Weighted linear or logistic regression models were used to examine the statistical significance of time trends. Results A total of 48223 U.S. adults were included in this analysis. From 1999 to March 2020, intake of calcium (from 0.94 to 1.02 g/day), magnesium (from 308.07 to 321.85 mg/day), phosphorus (from 1.24 to 1.30 g/day), and sodium (from 3.24 to 3.26 mg/day) from food and beverages (FB) and dietary supplements (DSs) significantly increased, and intake of iron (from 19.17 to 16.38 mg/day), zinc (from 16.45 to 14.19 mg/day), copper (from 1.79 to 1.38 mg/day), and potassium (from 2.65 to 2.50 g/day) from FB + DSs decreased (all FDR

Abstract Tyrosine kinase inhibitors have been the standard treatment for patients with Philadelphia chromosome-positive (Ph+) leukemia. However, a series of issues, including drug resistance, relapse and intolerance, are still an unmet medical need. Here, we report the targeted siRNA-based lipid nanoparticles in Ph+ leukemic cell lines for gene therapy of Ph+ leukemia, which specifically targets a recently identified NEDD8 E3 ligase RAPSYN in Ph+ leukemic cells to disrupt the neddylation of oncogenic BCR-ABL. To achieve the specificity for Ph+ leukemia therapy, a single-chain fragment variable region (scFv) of anti-CD79B monoclonal antibody was covalently conjugated on the surface of OA2-siRAPSYN lipid nanoparticles to generate the targeted lipid nanoparticles (scFv-OA2-siRAPSYN). Through effectively silencing RAPSYN gene in leukemic cell lines by the nanoparticles, BCR-ABL was remarkably degraded accompanied by the inhibition of proliferation and the promotion of apoptosis. The specific targeting, therapeutic effects and systemic safety were further evaluated and demonstrated in cell line-derived mouse models. The present study has not only addressed the clinical need of Ph+ leukemia, but also enabled gene therapy against a less druggable target. Graphical Abstract

Abstract Iron-based nanotubes are promising candidates for high performance electromagnetic wave absorbing fillers due to their high aspect ratio, light weight, high axial permeability and high saturation magnetization. Furthermore, the introduction of carbon can improve dielectric loss and block the agglomeration of iron nanotubes. Here, Fe@C composite nanotubes were prepared by introducing carbon onto the surface of precursor α-FeOOH’ fibers followed by hydrogen-thermal annealing. We find that Fe@C composite nanotubes retain the one-dimensional nanostructure of the precursor throughout the annealing. The well-developed lattice and nanostructure of Fe@C nanotubes endow high saturation magnetization, high anisotropy, suppressed eddy current effect and cross-particle exchange coupling as well, and thus contribute to an enhanced permeability. Coatings with Fe@C as fillers achieve a reflection loss of up to −69.34 dB at 3.37 GHz at the matching thickness of 3.97 mm. The Fe@C composite nanotubes developed here are a promising candidate for high performance electromagnetic wave absorbing fillers.

Objective Surgical procedures for patients with posttraumatic syringomyelia (PTS) remain controversial. Until now, there have been no effective quantitative evaluation methods to assist in selecting appropriate surgical plans before surgery. Methods We consecutively enrolled PTS patients (arachnoid lysis group, n = 42; shunting group, n = 14) from 2003 to 2023. Additionally, 19 intrathecal anesthesia patients were included in the control group. All patients with PTS underwent physical and neurological examinations and spinal magnetic resonance imaging preoperatively, 3–12 months postoperatively and during the last follow-up. Preoperative lumbar puncture was performed and blood-spinal cord barrier disruption was detected by quotient of albumin (Qalb, cerebrospinal fluid/serum). Results The ages (p = 0.324) and sex (p = 0.065) of the PTS and control groups did not differ significantly. There were also no significant differences in age (p = 0.216), routine blood data and prognosis (p = 0.399) between the arachnoid lysis and shunting groups. But the QAlb level of PTS patients was significantly higher than that of the control group (p < 0.001), and the shunting group had a significantly higher QAlb (p < 0.001) than the arachnoid lysis group. A high preoperative QAlb (odds ratio, 1.091; 95% confidence interval, 1.004–1.187; p = 0.041) was identified as the predictive factor for the shunting procedure, with the receiver operating characteristic curve showing 100% specificity and 80.95% sensitivity for patients with a QAlb > 12.67. Conclusion Preoperative QAlb is a significant predictive factor for the types of surgery. For PTS patients with a QAlb > 12.67, shunting represents the final recourse, necessitating the exploration and development of novel treatments for these patients.

Abstract Background Neurodevelopmental disorders (NDDs), such as Attention-Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), and Tourette Syndrome (TS), have been extensively studied for their multifaceted impacts on social and emotional well-being. Recently, there has been growing interest in their potential relationship with fracture risks in adulthood. This study aims to explore the associations between these disorders and fracture rates, in order to facilitate better prevention and treatment. Methods Employing a novel approach, this study utilized Mendelian randomization (MR) analysis to investigate the complex interplay between ADHD, ASD, TS, and fractures. The MR framework, leveraging extensive genomic datasets, facilitated a systematic examination of potential causal relationships and genetic predispositions. Results The findings unveil intriguing bidirectional causal links between ADHD, ASD, and specific types of fractures. Notably, ADHD is identified as a risk factor for fractures, with pronounced associations in various anatomical regions, including the skull, trunk, and lower limbs. Conversely, individuals with specific fractures, notably those affecting the femur and lumbar spine, exhibit an increased genetic predisposition to ADHD and ASD. In this research, no correlation was found between TS and fractures, or osteoporosis.These results provide a genetic perspective on the complex relationships between NDDs and fractures, emphasizing the importance of early diagnosis, intervention, and a holistic approach to healthcare. Conclusion This research sheds new light on the intricate connections between NDDs and fractures, offering valuable insights into potential risk factors and causal links. The bidirectional causal relationships between ADHD, ASD, and specific fractures highlight the need for comprehensive clinical approaches that consider both NDDs and physical well-being.

[Introduction] The purpose of this paper is to research and analyze the influence of water resources on the development of the green hydrogen industry in China, reveal the contradiction between water resources and the development of green hydrogen industry, analyze the future development trend of the green hydrogen industry and to provide useful reference for the development layout of renewable energy hydrogen production projects in China. [Method] In order to prove that water resources could limit the development of the green hydrogen industry in "Northeast China, North China, Northwest China" and other areas, the analysis and the demonstration were made based on the field investigations and the documentary materials, considering water resources policies, water usage in traditional chemical industries, and hydrogen production technologies. [Result] The analysis results show that under the restriction of China's water resources-related policies, the layout of green hydrogen industry should consider the constraints of water resources, and the large-scale production of green hydrogen and its substitution for fossil energy hydrogen production cannot effectively save water. Instead, it may lead to an increase in water consumption by the chemical industry. Under the constraint of water resources, the development of China's green hydrogen industry must consider the layout from a holistic perspective, fully integrate the development trend of the existing chemical industry, and consider the abundant resources available such as seawater. [Conclusion] The development of the green hydrogen industry in China should not ignore the problems of existing policy framework, technology level, industrial layout and characteristics of existing resources. When arranging the layout of the green hydrogen projects, the current situation and future trends should be fully considered, and the problems posed by water resources on the green hydrogen industry should be solved from the perspective of the overall planning, the coordinated industrial development and the effective utilization of resources.

The performance of a tidal stream turbine array can be affected by numerous factors. Investigating the connection between array power production and these factors will be helpful in improving the development of tidal stream energy. This study investigates the impact of array layout, turbine number, and yaw angles on turbine array performance using an open-source coastal ocean modelling system. The results show that the total power output of the turbine array rises with the number of turbines. Under realistic conditions, there are not many differences in power output between aligned and staggered turbine array configurations. By extending the distance between the turbines, the array power output can be improved in both layouts. It appears that considering each turbine’s yaw angle can improve array power generation, since the downstream turbines will greatly benefit from the steering wake of the upstream turbines. Furthermore, using a gradient-based optimization algorithm to simultaneously adjust the yaw angles and turbine positions will boost the turbine array’s efficiency more than just optimizing the turbine position alone.

Background: Bromodomain and extra-terminal (BET) proteins are critical regulators of gene transcription, as they recognize acetylated lysine residues. The BD1 bromodomain of BRD4, a member of the BET family, has emerged as a promising therapeutic target for various diseases. This study aimed to develop and evaluate a novel C-11 labeled PET radiotracer, [11C]YL10, for imaging the BD1 bromodomain of BRD4 in vivo. Methods: [11C]YL10 was synthesized and evaluated for its ability to bind to the BD1 bromodomain selectively. PET imaging studies were conducted in mice to assess brain penetration, pharmacokinetics, and selectivity. In vitro autoradiography and blocking experiments were performed to confirm the tracer’s specificity for the BD1 domain. Results: [11C]YL10 demonstrated good brain penetration, high selectivity for the BD1 bromodomain, and favorable pharmacokinetics in initial PET imaging studies. In vitro autoradiography and blocking experiments confirmed the specific binding of [11C]YL10 to the BD1 domain of BRD4, further validating its potential as a targeted radiotracer. Conclusions: The development of [11C]YL10 provides a new tool for studying BRD4 bromodomains using PET imaging technology. This radiotracer offers potential advancement in the diagnosis and research of neurodegenerative diseases and related disorders involving BRD4 dysregulation.

Abstract Targeting receptor‐interacting protein kinase 1 (RIPK1) has emerged as a promising therapeutic stratagem for neurodegenerative disorders, particularly Alzheimer's disease (AD). A positron emission tomography (PET) probe enabling brain RIPK1 imaging can provide a powerful tool to unveil the neuropathology associated with RIPK1. Herein, the development of a new PET radioligand, [11C]CNY‐10 is reported, which may enable brain RIPK1 imaging. [11C]CNY‐10 is radiosynthesized with a high radiochemical yield (41.8%) and molar activity (305 GBq/µmol). [11C]CNY‐10 is characterized by PET imaging in rodents and a non‐human primate, demonstrating good brain penetration, binding specificity, and a suitable clearance kinetic profile. It is performed autoradiography of [11C]CNY‐10 in human AD and healthy control postmortem brain tissues, which shows strong radiosignal in AD brains higher than healthy controls. Subsequently, it is conducted further characterization of RIPK1 in AD using [11C]CNY‐10‐based PET studies in combination with immunohistochemistry leveraging the 5xFAD mouse model. It is found that AD mice revealed RIPK1 brain signal significantly higher than WT control mice and that RIPK1 is closely related to amyloid plaques in the brain. The studies enable further translational studies of [11C]CNY‐10 for AD and potentially other RIPK1‐related human studies.

This article presents a study on the distributed optimization operation method for micro-energy grid clusters within an electric, thermal, and hydrogen integrated energy system. The research focuses on precisely modeling the Power-to-Hydrogen (P2H) conversion process in electrolytic cells by considering their startup characteristics. An optimization operation model is established, with each micro-energy grid as the principal entity, to cater to their individual interests and demands. The Alternating Direction Method of Multipliers (ADMM) algorithm is adopted for distributed solution. Case studies demonstrate that the connection topology between micro-energy grids significantly impacts the total operating cost, and the effectiveness of the ADMM algorithm is validated through a comparison with centralized optimization approaches.

Abstract Due to multidimensional complexity of solid tumor, development of rational T‐cell combinations and corresponding formulations is still challenging. Herein, a triple combination of T cells are developed with Indoleamine 2,3‐dioxygenase inhibitors (IDOi) and Cyclin‐dependent kinase 4/6 inhibitors (CDK4/6i). To maximize synergism, a spatiotemporally controlled T‐cell engineering technology to formulate triple drugs into one cell therapeutic, is established. Specifically, a sequentially responsive core‐shell nanoparticle (SRN) encapsulating IDOi and CDK4/6i is anchored onto T cells. The yielded SRN‐T cells migrated into solid tumor, and achieved a 1st release of IDOi in acidic tumor microenvironment (TME). Released IDOi restored tryptophan supply in TME, which activated effector T cells and inhibited Tregs. Meanwhile, 1st released core is internalized by tumor cells and degraded by glutathione (GSH), to realize a 2nd release of CDK4/6i, which induced up‐regulated expression of C‐X‐C motif chemokine ligand 10 (CXCL10) and C‐C motif chemokine ligand 5 (CCL5), and thus significantly increased tumor infiltration of T cells. Together, with an enhanced recruitment and activation, T cells significantly suppressed tumor growth, and prolonged survival of tumor‐bearing mice. This study demonstrated rationality and superiority of a tri‐drug combination mediated by spatiotemporally controlled cell‐engineering technology, which provides a new treatment regimen for solid tumor.

Objective: This study aimed to assess the relationship between implantation and soluble HLA-G (sHLA-G) expression in cleavage embryo culture medium (ECM) in conjunction with early developmental kinetics determined by time-lapse imaging (TLI).Methods: A retrospective, single-center study was conducted involving 238 embryos from 165 patients who underwent Frozen-thawed embryo transfer (FET) using autologous oocytes, with either single or double embryo transfer. TLI morphokinetic parameters (t2, t3, t4, t5, t6, t7, t8, cc2, s2, cc3, s3) of embryos were analyzed, and sHLA-G levels in D3 ECM were measured using an enzyme-linked immunosorbent assay (ELISA). A hierarchical classification model was developed to categorize embryos into five groups (A, B, C, D, E). The correlation between sHLA-G levels, TLI classification of embryos, and embryo implantation was investigated to establish a non-invasive method for evaluating implantation potential. Multivariate logistic regression analysis was performed to identify potential influencing factors, and receiver operating characteristic (ROC) curves were used to evaluate the predictive value for implantation.Results: Multivariate unconditional logistic regression analysis indicated that TLI parameters t5 and s3 and sHLA-G level in ECM were independent risk factors affecting embryo implantation. The implantation rate decreased from TLI classification A to E. The proposed classification model effectively assessed the implantation potential of embryos. The implantation rate was higher in the sHLA-G positive group compared to the sHLA-G negative group (p < 0.001). The expression of sHLA-G in D3 ECM, combined with the TLI classification model, accurately evaluated the implantation potential of embryos with an AUC of 0.876.Conclusion: The integration of cleavage kinetics and embryonic sHLA-G expression could reliably identify embryos with a high likelihood of successful implantation.

BackgroundGlobally, the incidence rates of obesity and its related diseases, such as cardiovascular diseases and type 2 diabetes, are continuously rising, posing a significant public health challenge. Studies have indicated a potential correlation between vitamin D deficiency and obesity. However, a quantitative analysis of the studies related vitamin D and obesity is lacking. This investigation aims to fill this gap by providing a comprehensive bibliometric analysis to uncover the collaborative networks, research hotspots, and evolutionary trends within the field of vitamin D and obesity research.MethodsThis study retrieved literature related to vitamin D and obesity from the Web of Science database spanning from 2000 to 2023. Bibliometric analysis was conducted using tools such as HistCite, VOSviewer, and CiteSpace to excavate multi-dimensional information including countries, institutions, authors, journals, citations, and keywords.ResultsA total of 6,144 records were retrieved, involving 123 countries, 6,726 institutions, and 28,156 authors, published in 1,551 journals. The number of published papers and citations showed a generally increasing trend. The United States led in terms of publication volume and influence, with journals such as Nutrients and Obesity Surgery having the highest publication counts. Nasser M. Al-Daghri was the most prolific and influential author. Keyword clustering revealed that research topics covered metabolic health, nutrition, immunity, and bariatric surgery. Citation burst analysis indicated a shift in research focus from the relationship between dietary calcium and obesity to the preventive effects of vitamin D supplementation on metabolic diseases.ConclusionThe application of bibliometric methods to analyze the research literature in the fields of obesity and vitamin D has provided a comprehensive understanding of the collaborative networks, key research focus, and evolutionary trends in this field, offering insights for guiding future research directions.

Human papillomaviruses (HPVs) account for more than 30% of cancer cases, with definite identification of the oncogenic role of viral E6 and E7 genes. However, the identification of high-risk HPV genotypes has largely relied on lagged biological exploration and clinical observation, with types unclassified and oncogenicity unknown for many HPVs. In the present study, we retrieved and cleaned HPV sequence records with high quality and analyzed their genomic compositional traits of dinucleotide (DNT) and DNT representation (DCR) to overview the distribution difference among various types of HPVs. Then, a deep learning model was built to predict the oncogenic potential of all HPVs based on E6 and E7 genes. Our results showed that the main three groups of Alpha, Beta, and Gamma HPVs were clearly separated between/among types in the DCR trait for either E6 or E7 coding sequence (CDS) and were clustered within the same group. Moreover, the DCR data of either E6 or E7 were learnable with a convolutional neural network (CNN) model. Either CNN classifier predicted accurately the oncogenicity label of high and low oncogenic HPVs. In summary, the compositional traits of HPV oncogenicity-related genes E6 and E7 were much different between the high and low oncogenic HPVs, and the compositional trait of the DCR-based deep learning classifier predicted the oncogenic phenotype accurately of HPVs. The trained predictor in this study will facilitate the identification of HPV oncogenicity, particularly for those HPVs without clear genotype or phenotype.

Constipation symptoms of Parkinson's disease (PD) seriously reduce the quality of life of patients and aggravate the development of the disease, but current treatment options still cannot alleviate the progress of constipation. Electroacupuncture (EA) is a new method for the treatment of constipation, which can effectively treat the symptoms of constipation in PD patients. However, the specific regulatory mechanisms of EA in the treatment of constipation symptoms in PD remain unclear. The aim of this study is to investigate the therapeutic effect of EA on PD constipation rats and its regulatory mechanism. A rotenone (ROT)-induced gastrointestinal motility disorder model was used to simulate the pathological process of constipation in PD. The results showed that EA could effectively promote gastrointestinal peristalsis, reduce α-synuclein accumulation in substantia nigra and colon and colonic injury in rats after ROT administration. Mechanistically, EA activation of the central-cholinergic pathway increases acetylcholine release in the colon. At the same time, EA up-regulated the co-expression of enteric glial cells (EGCs) and α7 nicotinic acetylcholine receptor (α7nAChR). EA increased the expression of choline acetyltransferase (ChAT), neuronal nitric oxide synthase (nNOS), and tyrosine hydroxylase (TH) in the colon of PD rats. Further mechanistic studies showed that EA increased the expression of glial cell-derived neurotrophic factor (GDNF), GFRa1 and p-AKT in colon tissues. The present study confirmed that EA upregulates α7nAChR through a central-cholinergic mechanism to promote GDNF release from EGCs, thereby protecting intestinal neurons and thereby improving gastrointestinal motility.