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Predicting traffic speed accurately and in real-time is crucial for the development of smart transportation systems. Given the nonlinear and stochastic nature of vehicle data, integrating diverse spatio-temporal data sources with the Improved Particle Swarm Optimisation (IPSO) offers a promising approach to optimise the Long Short-Term Memory Neural Network (LSTM). Firstly, we enhance the optimisation capabilities of PSO by implementing nonlinear inertial weight and adaptive variation. Secondly, addressing the challenge of selecting the LSTM hyperparameters, the PSO algorithm effectively identifies global optimal solutions for hyperparameter optimisation, ensuring appropriate settings through iterative training. Subsequently, we conduct a case study using multi-source spatio-temporal traffic speed data, comparing our proposed IPSO-LSTM model with traditional neural network prediction models and advanced models. Results from the experiment demonstrate that the IPSO-LSTM model presented in this study addresses issues of parameter selection and inaccurate prediction encountered by traditional LSTM models in traffic state prediction. Moreover, it enhances the model’s ability to capture speed time series dynamics. Notably, in processing complex speed data, our model exhibits superior accuracy and stability in prediction.

Abstract Environmental stimuli not only alter gene expression profiles but also induce structural changes in cells. How distinct nuclear bodies respond to cellular stress is poorly understood. Here, we identify a subnuclear organelle named the nucleolar stress body (NoSB), the formation of which is induced by the inhibition of rRNA transcription or inactivation of rRNA processing and maturation in C. elegans. NoSB does not colocalize with other previously described subnuclear organelles. We conduct forward genetic screening and identify a bZIP transcription factor, named nucleolar stress response-1 (NOSR-1), that is required for NoSB formation. The inhibition of rRNA transcription or inactivation of rRNA processing and maturation increases nosr-1 expression. By using transcriptome analysis of wild-type animals subjected to different nucleolar stress conditions and nosr-1 mutants, we identify that the SR-like protein NUMR-1 (nuclear localized metal responsive) is the target of NOSR-1. Interestingly, NUMR-1 is a component of NoSB and itself per se is required for the formation of NoSB. We conclude that the NOSR-1/NUMR-1 axis likely responds to nucleolar stress and mediates downstream stress-responsive transcription programs and subnuclear morphology alterations in C. elegans.

Abstract Objective To elucidate the impact and predictive value of the Triglyceride Glucose Index (TyG) and the ratio of Triglycerides to High-Density Lipoprotein Cholesterol (TG/HDL-C) in identifying the risk of diabetes progression in Chinese individuals with prediabetes. Methods This longitudinal study enrolled 15,012 prediabetic adults from the Rich Healthcare Group between 2010 and 2016. Diabetes was defined as self-reported diabetes or a fasting glucose level ≥ 7.0 mmol/L. The Cox proportional hazards models was utilized to assess the relationship between the two indices and the risk of developing diabetes. The predictive efficacy of the two markers was gauged by the area under the curve (AUC). Results Over a median follow-up period of 2.87 years, 1,730 (11.5%) prediabetic participants developed diabetes. The adjusted hazard ratios for the top quartile of the TyG index and the TG/HDL-C ratio were 2.03 (95% confidence interval [CI]: 1.71–2.40) and 2.59 (95% CI: 2.20–3.05), respectively, compared to the lowest quartile. A significant trend of increasing diabetes risk with higher quartiles of both indices was observed. The AUC for the adjusted prediction model for prediabetes-to-diabetes transition was 0.726 for the TyG index and 0.710 for the TG/HDL-C ratio. The difference in AUCs was statistically significant (P = 0.03). Conclusions The baseline TyG index or TG/HDL-C ratio was significantly associated with an increased risk of diabetes in prediabetic individuals. The TyG index demonstrated superior predictive accuracy, underscoring its importance in preventing diabetes in prediabetic individuals.

Abstract Improvements in the polarization of environmentally-friendly perovskite ferroelectrics have proved to be a challenging task in order to replace the toxic Pb-based counterparts. In contrast to common methods by complex chemical composition designs, we have formed Mn-inlaid antiphase boundaries in Mn-doped (K,Na)NbO3 thin films using pulsed laser deposition method. Here, we observed that mono- or bi-atomic layer of Mn has been identified to inlay along the antiphase boundaries to balance the charges originated from the deficiency of alkali ions and to induce the strain in the KNN films. Thus, rectangular saturated polarization-electric field hysteresis loops have been achieved, with a significantly improved twice remanent polarization of 114 μC/cm2 with an applied electric field of 606 kV/cm, which can be comparable to that of the typical Pb-based thin films. Moreover, we directly see the Mn occupation at the A-site of KNN perovskite structure using atomic-scale microstructure and composition analysis. The Mn-inlaid antiphase boundary can further enrich the understanding of perovskite crystal structure and give more possibilities for the design and optimization of perovskite materials.

Abstract Introduction Alveolar echinococcosis (AE), caused by the larval forms of Echinococcus multilocularis, is a zoonotic disease affecting the liver, lungs, lymph nodes, kidneys, brain, bones, thyroid, and other organs. Diagnosing AE in a non-endemic area is usually challenging. With the rapid development and increasing application of sequencing techniques in recent years, metagenomic next-generation sequencing (mNGS) has become a powerful tool for diagnosing rare infectious diseases. Case Presentation A 45-year-old woman was admitted to the hospital for the presence of pulmonary shadows for more than 3 months. The lung computed tomography (CT) at a local hospital revealed scattered solid and quasi-circular nodules in the left upper lobe, left lower lobe, right middle lobe, and right lower lobe. The largest nodule was located in the dorsal part of the right lung, measuring 2.0 × 1.7 × 1.5 cm. Moreover, abdominal CT revealed one space-occupying lesion each in the left and right lobes. The pathological analysis of the lung biopsy specimen revealed infiltration of lymphocytes, plasma cells, and eosinophils in the alveolar wall and interstitial area. No pathogenic bacteria were observed in the sputum smear and culture tests. There were no parasite eggs in the stool. The mNGS of the lung puncture tissue revealed 6156 sequence reads matching E. multilocularis; thus, the condition was diagnosed as AE. Albendazole 400 mg was administered twice daily, and the patient was stable during follow-up. Conclusion This case emphasizes the role of mNGS in diagnosing AE. As a novel, sensitive, and accurate diagnostic method, mNGS could be an attractive approach for facilitating early diagnosis and prompt treatment of infectious diseases, especially when the infection was caused by rare pathogens.

Abstract Germ granules are biomolecular condensates present in most animal germ cells. One function of germ granules is to help maintain germ cell totipotency by organizing mRNA regulatory machinery, including small RNA-based gene regulatory pathways. The C. elegans germ granule is compartmentalized into multiple subcompartments whose biological functions are largely unknown. Here, we identify an uncharted subcompartment of the C. elegans germ granule, which we term the E granule. The E granule is nonrandomly positioned within the germ granule. We identify five proteins that localize to the E granule, including the RNA-dependent RNA polymerase (RdRP) EGO-1, the Dicer-related helicase DRH-3, the Tudor domain-containing protein EKL-1, and two intrinsically disordered proteins, EGC-1 and ELLI-1. Localization of EGO-1 to the E granule enables synthesis of a specialized class of 22G RNAs, which derive exclusively from 5’ regions of a subset of germline-expressed mRNAs. Defects in E granule assembly elicit disordered production of endogenous siRNAs, which disturbs fertility and the RNAi response. Our results define a distinct subcompartment of the C. elegans germ granule and suggest that one function of germ granule compartmentalization is to facilitate the localized production of specialized classes of small regulatory RNAs.

Abstract Liquid formulations are ubiquitous yet have lengthy product development cycles owing to the complex physical interactions between ingredients making it difficult to tune formulations to customer-defined property targets. Interpolative ML models can accelerate liquid formulations design but are typically trained on limited sets of ingredients and without any structural information, which limits their out-of-training predictive capacity. To address this challenge, we selected eighteen formulation ingredients covering a diverse chemical space to prepare an open experimental dataset for training ML models for rinse-off formulations development. The resulting design space has an over 50-fold increase in dimensionality compared to our previous work. Here, we present a dataset of 812 formulations, including 294 stable samples, which cover the entire design space, with phase stability, turbidity, and high-fidelity rheology measurements generated on our semi-automated, ML-driven liquid formulations workflow. Our dataset has the unique attribute of sample-specific uncertainty measurements to train predictive surrogate models.

Abstract Base editing (BE) faces protospacer adjacent motif (PAM) constraints and off-target effects in both eukaryotes and prokaryotes. For Streptomyces, renowned as one of the most prolific bacterial producers of antibiotics, the challenges are more pronounced due to its diverse genomic content and high GC content. Here, we develop a base editor named eSCBE3-NG-Hypa, tailored with both high efficiency and -fidelity for Streptomyces. Of note, eSCBE3-NG-Hypa recognizes NG PAM and exhibits high activity at challenging sites with high GC content or GC motifs, while displaying minimal off-target effects. To illustrate its practicability, we employ eSCBE3-NG-Hypa to achieve precise key amino acid conversion of the dehydratase (DH) domains within the modular polyketide synthase (PKS) responsible for the insecticide avermectins biosynthesis, achieving domains inactivation. The resulting DH-inactivated mutants, while ceasing avermectins production, produce a high yield of oligomycin, indicating competitive relationships among multiple biosynthetic gene clusters (BGCs) in Streptomyces avermitilis. Leveraging this insight, we use eSCBE3-NG-Hypa to introduce premature stop codons into competitor gene cluster of ave in an industrial S. avermitilis, with the mutant Δolm exhibiting the highest 4.45-fold increase in avermectin B1a compared to the control. This work provides a potent tool for modifying biosynthetic pathways and advancing metabolic engineering in Streptomyces.

Abstract Background Uveal melanoma (UM) is the most common primary intraocular tumor in adults, and early detection is critical to improve the clinical outcome of this disease. In this study, the diagnostic effectiveness of [18F]AlF-NOTA-PRGD2 (an investigational medicinal product) positron emission tomography (PET) imaging in UM xenografts and UM patients were evaluated. The cell uptake, cell binding ability and in vitro stability of [18F]AlF-NOTA-PRGD2 were evaluated in 92-1 UM cell line. MicroPET imaging and biodistribution study of [18F]AlF-NOTA-PRGD2 were conducted in 92-1 UM xenografts. Then, UM patients were further recruited for evaluating the diagnostic effectiveness of [18F]AlF-NOTA-PRGD2 PET imaging (approval no. NCT02441972 in clinicaltrials.gov). In addition, comparison of [18F]AlF-NOTA-PRGD2 and 18F-labelled fluorodeoxyglucose ([18F]FDG) PET imaging in UM xenografts and UM patients were conducted. Results The in vitro data showed that [18F]AlF-NOTA-PRGD2 had a high cell uptake, cell binding ability and in vitro stability in 92-1 UM cell line. The in vivo data indicated that 92-1 UM tumors were clearly visualized with the [18F]AlF-NOTA-PRGD2 tracer in the subcutaneous and ocular primary UM xenografts model at 60 min post-injection. And the tumor uptake of the tracer was 2.55 ± 0.44%ID/g and 1.73 ± 0.15%ID/g at these two tissue locations respectively, at 7 days after animal model construction. The clinical data showed that tumors in UM patients were clearly visualized with the [18F]AlF-NOTA-PRGD2 tracer at 60 min post-injection. In addition, [18F]AlF-NOTA-PRGD2 tracer showed higher sensitivity and specificity for PET imaging in UM xenografts and UM patients compared to [18F]FDG tracer. Conclusion [18F]AlF-NOTA-PRGD2 PET imaging may be a more preferred approach in the diagnosis of primary UM compared to [18F]FDG PET imaging. Additionally, due to the high tumor-to-background ratio, [18F]AlF-NOTA-PRGD2 PET imaging seems also to be applicable for the diagnosis of UM patients with liver metastasis. Trial registration: ClinicalTrials.gov: NCT02441972, Registered 1 January 2012, https://clinicaltrials.gov/study/NCT02441972 .

Positron Emission Tomography (PET) image reconstruction remains a pivotal area in PET technology, critically influencing clinical diagnostic outcomes. Addressing the need for enhanced image quality, this study introduces a novel algorithm for PET image reconstruction. This algorithm integrates a penalty mechanism, morphological filtering, and the Maximum Likelihood Expectation Maximization (MLEM) algorithm, aiming to improve reconstructed image quality significantly. The operational process of the algorithm within each iteration encompasses two primary phases. Initially, image reconstruction is accomplished via the MLEM algorithm, followed by the application of a morphological filter to attenuate noise in the reconstructed image. Simulation experiments demonstrate that this algorithm effectively mitigates noise while preserving crucial details, such as image edges. Notably, this method presents the dual benefits of straightforward parameter configuration and ease of implementation. The results indicate a substantial enhancement in noise suppression and fine structure preservation in the reconstructed images, marking a significant advancement in PET image reconstruction techniques.

High-field strain and its temperature stability of (1–x) K0.48Na0.52Nb0.96Ta0.04O3-xBaZrO3+8%MnO+3%ZrO2 (in mole, KNNT-xBZ+8Mn) ceramics sintered in reducing atmosphere are improved simultaneously via defect design in A and B site. There is a conducting type transition from n-type to p-type at x = 0.07. The BaZrO3 dopant not only induces the increase of defects (ZrNb′, BaNa·, BaK·) concentration, but also results in the increase of defect (MnNb‴) concentration, because more Mn ions as +2 oxidation state in ceramics is triggered by BaZrO3 doping modification. Defect dipoles (MnNb′′′−Vo··, ZrNb′-Vo··, BaNa·-VNa′, BaK·-VK′) in poled and aged ceramics enhance the reversibility of the non–180° domains switching, which increases the high-field strain of KNNT-xBZ+8Mn ceramics. The reversibility of non–180° domain switching can be preserved to high temperature due to stable defect dipoles (BaNa·-VNa′, BaK·-VK′) in A-site. The KNNT-xBZ+8Mn ceramics at x = 0.07 show the largest high-field strain coefficient (543 pm/V@20 kV/cm) and the highest temperature stability (125 °C). The KNNT-xBZ+8Mn ceramic is a lead-free material with great potential to be applied in the fabrication of multilayer ceramic actuators with Ni inner electrodes in the future.

The rheological behavior of propellant slurries is crucial for ensuring the feasibility of the 3D printing process, controlling print quality, regulating performance, and simulating predictions. However, there have been relatively few prior studies on the rheological properties of composite solid propellant slurries at low temperatures, which hinders the application of 3D printing propellant technology under extreme temperature conditions. In addition, the use of 3D printing technology to manufacture propellants at low temperatures is advantageous for improving safety. This paper investigates the rheological properties of monodisperse systems with aluminum powder as a solid filler and end-hydroxy polybutadiene (HTPB) as the dispersed phase at low temperatures (−15∼10 °C). It explores the effects of solid content, temperature, and particle size on their rheological properties. Results show that the viscosity of the system in the range of −15∼10 °C increases exponentially with the decrease in temperature, and the viscosity at −15 °C increases by 616.90 % compared with that at 10 °C when the volume fraction (φ) of Al-1 is 35.8 %; the larger size of the particles the larger the viscosity is when the temperature and φ are the same, which is interpretes in terms of interfacial properties between the systems. The low-temperature correction factor is introduced into the Einstein-Roscoe equation to obtain the modified viscosity-volume fraction equation, and the correction factor is 0.0173, as evidenced by its excellent agreement with the experimental data.

Abstract Background Glucokinase (GK) plays a key role in glucose metabolism. In the liver, GK is regulated by GK regulatory protein (GKRP) with nuclear sequestration at low plasma glucose level. Some GK activators (GKAs) disrupt GK-GKRP interaction which increases hepatic cytoplasmic GK level. Excess hepatic GK activity may exceed the capacity of glycogen synthesis with excess triglyceride formation. It remains uncertain whether hypertriglyceridemia associated with some GKAs in previous clinical trials was due to direct GK activation or impaired GK-GKRP interaction. Methods Using publicly available genome-wide association study summary statistics, we selected independent genetic variants of GCKR and GCK associated with fasting plasma glucose (FPG) as instrumental variables, to mimic the effects of impaired GK-GKRP interaction and direct GK activation, respectively. We applied two-sample Mendelian Randomization (MR) framework to assess their causal associations with lipid-related traits, risks of metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular diseases. We verified these findings in one-sample MR analysis using individual-level statistics from the Hong Kong Diabetes Register (HKDR). Results Genetically-proxied impaired GK-GKRP interaction increased plasma triglycerides, low-density lipoprotein cholesterol and apolipoprotein B levels with increased odds ratio (OR) of 14.6 (95% CI 4.57–46.4) per 1 mmol/L lower FPG for MASLD and OR of 2.92 (95% CI 1.78–4.81) for coronary artery disease (CAD). Genetically-proxied GK activation was associated with decreased risk of CAD (OR 0.69, 95% CI 0.54–0.88) and not with dyslipidemia. One-sample MR validation in HKDR showed consistent results. Conclusions Impaired GK-GKRP interaction, rather than direct GK activation, may worsen lipid profiles and increase risks of MASLD and CAD. Development of future GKAs should avoid interfering with GK-GKRP interaction.

Abstract Brand design expands the connotation and extension of products, satisfying consumers’ purchase needs to a maximum extent. This study aims to use the S-O-R theory to explore the key factors that stimulate consumers’ behaviors in purchasing bottled water and investigate the influences of design-driven fast-moving consumer goods (FMCG) on purchase intentions of consumers. A questionnaire survey was conducted for data col-lection and the bootstrapping program of PLS-SEM was used in data analysis and significance evaluation of 322 samples finally obtained. The results show that brand image and design-drive attribute can positively affect perceived value, while sensory experience and brand image can positively impact emotional attitude. However, sensory experience does not directly facilitate perceived value and design-driven attribute cannot effectively affect emotional attitude. Both brand image and design-driven attribute can significantly influence purchase intention, while sensory experience does not have such a influence. Emotional attitude has a significant mediating effect on purchase intention, with a partial mediating effect of perceived value on purchase intention. These results have enriched the research on the influence of design-driven attribute on consumer purchase behavior and empirically analyzed the relationships of product knowledge and perceived value of consumers with their purchase intentions, providing new evidence for understanding the relationship between consumer purchase intentions and design-driven brands. The importance of design-driven attribute has been emphasized in this study, which is of important practical significance in exploring the underlying mechanism of consumer purchase intention and promoting the sustainable development of product design.

Abstract To address the challenges posed by imbalanced and limited battlefield data, which typically results in complex models prone to overfitting during training, we introduce a novel diffusion model grounded in Wasserstein distance (WDiffusion) tailored for the multi-categorical and multivariate characteristics inherent to intent recognition data. Subsequently, we propose a streamlined tactical intent recognition framework predicated on gate recurrent unit (GRU), designed to enhance model responsiveness, and train it on an innovative dataset. Comparative experimental analyses corroborate that the synthetic data generated via WDiffusion significantly outperforms other prevalent generation models. Furthermore, the WDiffusion-GRU model achieves a recognition accuracy of 97.09%, surpassing current aerial target intent recognition models by more than 1.07%. This advancement maintains high recognition precision while substantially curtailing model parameters, thereby amplifying the agility and reliability of battlefield commanders’ decision-making processes.

Abstract Drug exposure during pregnancy lacks global fetal safety data. The maternal drug exposure birth cohort (DEBC) study, a prospective longitudinal investigation, aims to explore the correlation of maternal drug exposure during pregnancy with pregnancy outcomes, and establish a human biospecimen biobank. Here we describe the process of establishing DEBC and show that the drug exposure rate in the first trimester of pregnant women in DEBC (n = 112,986) is 30.70%. Among the drugs used, dydrogesterone and progesterone have the highest exposure rates, which are 11.97% and 10.82%, respectively. The overall incidence of adverse pregnancy outcomes is 13.49%. Dydrogesterone exposure during the first trimester is correlated with higher incidences of stillbirth, preterm birth, low birth weight, and birth defects, along with a lower incidence of miscarriage/abortion. Due to the limitations of this cohort study, causative conclusions cannot be drawn. Further follow-up and in-depth data analysis are planned for future studies.

Abstract Chronic obstructive pulmonary disease (COPD) is characterised by persistent airway inflammation even after cigarette smoking cessation. Neutrophil extracellular traps (NETs) have been implicated in COPD severity and acute airway inflammation induced by short-term cigarette smoke (CS). However, whether and how NETs contribute to sustained airway inflammation in COPD remain unclear. This study aimed to elucidate the immunoregulatory mechanism of NETs in COPD, employing human neutrophils, airway epithelial cells (AECs), dendritic cells (DCs), and a long-term CS-induced COPD mouse model, alongside cyclic guanosine monophosphate-adenosine monophosphate synthase and toll-like receptor 9 knockout mice (cGAS -−/− , TLR9 −/− ); Additionally, bronchoalveolar lavage fluid (BALF) of COPD patients was examined. Neutrophils from COPD patients released greater cigarette smoke extract (CSE)-induced NETs (CSE-NETs) due to mitochondrial respiratory chain dysfunction. These CSE-NETs, containing oxidatively-damaged DNA (NETs-DNA), promoted AECs proliferation, nuclear factor kappa B (NF-κB) activation, NF-κB-dependent cytokines and type-I interferons production, and DC maturation, which were ameliorated/reversed by silencing/inhibition of cGAS/TLR9. In the COPD mouse model, blocking NETs-DNA-sensing via cGAS −/− and TLR9 −/− mice, inhibiting NETosis using mitoTEMPO, and degrading NETs-DNA with DNase-I, respectively, reduced NETs infiltrations, airway inflammation, NF-κB activation and NF-κB-dependent cytokines, but not type-I interferons due to IFN-α/β receptor degradation. Elevated NETs components (myeloperoxidase and neutrophil elastase activity) in BALF of COPD smokers correlated with disease severity and NF-κB-dependent cytokine levels, but not type-I interferon levels. In conclusion, NETs-DNA promotes NF-κB-dependent autoimmunity via cGAS/TLR9 in long-term CS exposure-induced COPD. Therefore, targeting NETs-DNA and cGAS/TLR9 emerges as a potential strategy to alleviate persistent airway inflammation in COPD.

Abstract The ability to realize high-fidelity quantum communication is one of the many facets required to build generic quantum computing devices. In addition to quantum processing, sensing, and storage, transferring the resulting quantum states demands a careful design that finds no parallel in classical communication. Existing experimental demonstrations of quantum information transfer in solid-state quantum systems are largely confined to small chains with few qubits, often relying upon non-generic schemes. Here, by using a superconducting quantum circuit featuring thirty-six tunable qubits, accompanied by general optimization procedures deeply rooted in overcoming quantum chaotic behavior, we demonstrate a scalable protocol for transferring few-particle quantum states in a two-dimensional quantum network. These include single-qubit excitation, two-qubit entangled states, and two excitations for which many-body effects are present. Our approach, combined with the quantum circuit’s versatility, paves the way to short-distance quantum communication for connecting distributed quantum processors or registers, even if hampered by inherent imperfections in actual quantum devices.

Abstract Background Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening neurosurgical emergency with a high mortality rate. Delayed cerebral ischemia (DCI) and cerebral vasospasm (CVS) are delayed products of early brain injury (EBI), which may constitute the principal determinant of an unfavorable patient prognosis. Consequently, the mitigation of DCI and CVS assumes paramount significance in the pursuit of enhanced patient outcomes. However, except for oral nimodipine, there is no effective therapy available in the current guideline. Hence, the exigency arises to proffer novel treatment paradigms. The diversity of hydrogen therapeutic targets has been largely reported in basic research, unveiling its latent capacity to ameliorate EBI in aSAH patients. Methods Early Hydrogen–Oxygen Gas Mixture Inhalation in Patients with Aneurysmal Subarachnoid Hemorrhage (HOMA), a single-center, prospective, open-labeled, randomized controlled clinical trial, endeavors to evaluate the efficacy and safety of hydrogen–oxygen gas mixture inhalation therapy in aSAH patients. A cohort of 206 patients will be randomized to either hydrogen–oxygen gas mixture inhalation group (8 h per day, 3 L/min, hydrogen concentration of 67%, oxygen concentration of 33%) or oxygen inhalation group (8 h per day, 3 L/min, oxygen concentration of 33%) within 72 h after aSAH and treated for 7 days in the ICU ward. The primary outcomes are the incidence of DCI and CVS during hospitalization. Discussion The HOMA aims to evaluate the effectiveness of hydrogen–oxygen gas mixture inhalation therapy in preventing DCI or CVS and improving outcomes in aSAH patients. Notably, this is the first large-scale trial of hydrogen therapy in aSAH patients. Given that the Chinese population represents a significant portion of the global population and the increasing incidence of stroke due to aging, optimizing patient care is vital. Given the current challenges in aSAH patient outcomes, initiating more prospective clinical trials is essential. Recent research has shown hydrogen’s therapeutic potential, aligning with EBI in aSAH, driving our exploration of hydrogen therapy’s mechanisms in post-aneurysm rupture damage. Ethics and dissemination The protocol for the HOMA study was approved by the Ethics Committee of Beijing Tiantan Hospital, Capital Medical University (KY 2022–020-02). All results of the present study will be published in peer-reviewed journals and presented at relevant conferences. Trial registration ClinicalTrials.gov NCT05282836. Registered on March 16, 2022.

Abstract During the restoration of iron cultural relics, the removal of rust from these artifacts is necessary. However, this rust removal process may lead to inconsistent local color on the iron relics. To address this, mending materials are applied to treat the surface, ensuring consistent local color. In the surface treatment of iron cultural relics, a significant challenge lies in modulating the color of these mending materials. The corrosion products of Yuquan Iron Pagoda are mainly Fe3O4, γ-FeO(OH), α-FeO(OH) and α-Fe2O3, with contents of 13.1, 16.1, 40.2 and 30.6%, respectively. Due to their structural stability and suitable color characteristics, Fe3O4 and α-Fe2O3 are selected as the primary raw materials for the repair material. This study employs machine learning methods to predict the color of mending materials corresponding to varying contents of α-Fe2O3, Fe3O4, and epoxy resin. The Artificial Neural Network (ANN), eXtreme Gradient Boosting (XGBoost), and Light Gradient Boost Machine (LightGBM) algorithms are utilized to develop the model, and the predictive performance of these three algorithms is compared. XGBoost exhibits the best prediction performance, achieving a square correlation coefficient (R2) of 0.94238 and a mean absolute error (MAE) of 0.68485. Additionally, the SHapley Additive exPlanations (SHAP) method is employed to analyze the most crucial raw material affecting the color of mending materials, which is identified as Fe3O4. The study illustrates the specific process of employing this model by applying it to the surface treatment of the Yuquan Iron Pagoda, demonstrating the practicality of the model. This model can be applied to assist in the surface treatment of other iron cultural relics.

Objective Jining Grey goat is a local Chinese goat breed that is well known for its high fertility and excellent meat quality but shows low meat production performance. Numerous studies have focused on revealing the genetic mechanism of its high fertility, but its highlighting meat quality and muscle growth mechanism still need to be studied. Methods In this research, an integrative analysis of the genomics and transcriptomics of Jining Grey goats compared with Boer goats was performed to identify candidate genes and pathways related to the mechanisms of meat quality and muscle development. Results Our results overlap among five genes (ABHD2, FN1, PGM2L1, PRKAG3, RAVER2) and detected a set of candidate genes associated with fatty acid metabolism (PRKAG3, HADHB, FASN, ACADM), amino acid metabolism (KMT2C, PLOD3, NSD2, SETDB1, STT3B, MAN1A2, BCKDHB, NAT8L, P4HA3) and muscle development (MSTN, PPARGC1A, ANKRD2). Several pathways have also been detected, such as the FoxO signaling pathway and Apelin signaling pathway that play roles in lipid metabolism, lysine degradation, N-glycan biosynthesis, valine, leucine and isoleucine degradation that involving with amino acid metabolism. Conclusion The comparative genomic and transcriptomic analysis of Jining Grey goat and Boer goat revealed the mechanisms underlying the meat quality and meat productive performance of goats. These results provide valuable information for future breeding of goats.

Abstract Chili pepper (Capsicum) is known for its unique fruit pungency due to the presence of capsaicinoids. The evolutionary history of capsaicinoid biosynthesis and the mechanism of their tissue specificity remain obscure due to the lack of high-quality Capsicum genomes. Here, we report two telomere-to-telomere (T2T) gap-free genomes of C. annuum and its wild nonpungent relative C. rhomboideum to investigate the evolution of fruit pungency in chili peppers. We precisely delineate Capsicum centromeres, which lack high-copy tandem repeats but are extensively invaded by CRM retrotransposons. Through phylogenomic analyses, we estimate the evolutionary timing of capsaicinoid biosynthesis. We reveal disrupted coding and regulatory regions of key biosynthesis genes in nonpungent species. We also find conserved placenta-specific accessible chromatin regions, which likely allow for tissue-specific biosynthetic gene coregulation and capsaicinoid accumulation. These T2T genomic resources will accelerate chili pepper genetic improvement and help to understand Capsicum genome evolution.

During the excavation process of deep rock masses, the surrounding rock stress field forms alternating zones of stress increase (loading zones) and stress decrease (unloading zones) near the excavation surface, which can easily trigger instability and failure in high-stress rock masses. Despite numerous studies that have been conducted on rock loading and unloading failures, the understanding of rock failure mechanisms under complex true triaxial stress paths remains insufficient. This study focuses on cubic granite specimens from the Linglong gold mine in Shandong. To comprehensively investigate the strength and failure characteristics of granite samples under complex true triaxial loading and unloading paths, true triaxial loading tests under different lateral stresses were conducted, followed by further true triaxial unloading tests in different unloading directions. The experimental results reveal that with the increase of intermediate principal stress, the failure mode of granite under true triaxial loading condition changes from shear-tensile failure to tensile failure, and the true triaxial loading failure strength increases first and then decreases slowly. Under the same intermediate and minimum principal stress conditions, the true triaxial unloading failure strength of granite is smaller than its loading failure strength, and the Mogi strength formula fits well with the true triaxial unloading strength under the minimum principal stress condition. This study provides an essential theoretical basis and guidance for controlling and designing the stability of deep rock masses in engineering applications.

Abstract Background The prospective phase III multi-centre L-MOCA trial (NCT03534453) has demonstrated the encouraging efficacy and manageable safety profile of olaparib maintenance therapy in the Asian (mainly Chinese) patients with platinum-sensitive relapsed ovarian cancer (PSROC). In this study, we report the preplanned exploratory biomarker analysis of the L-MOCA trial, which investigated the effects of homologous recombination deficiency (HRD) and programmed cell death ligand 1 (PD-L1) expression on olaparib efficacy. Methods HRD status was determined using the ACTHRD assay, an enrichment-based targeted next-generation sequencing assay. PD-L1 expression was assessed by SP263 immunohistochemistry assay. PD-L1 expression positivity was defined by the PD-L1 expression on ≥ 1% of immune cells. Kaplan–Meier method was utilised to analyse progression-free survival (PFS). Results This exploratory biomarker analysis included 225 patients and tested HRD status [N = 190; positive, N = 125 (65.8%)], PD-L1 expression [N = 196; positive, N = 56 (28.6%)], and BRCA1/2 mutation status (N = 219). The HRD-positive patients displayed greater median PFS than the HRD-negative patients [17.9 months (95% CI: 14.5–22.1) versus 9.2 months (95% CI: 7.5–13.8)]. PD-L1 was predominantly expressed on immune cells. Positive PD-L1 expression on immune cells was associated with shortened median PFS in the patients with germline BRCA1/2 mutations [14.5 months (95% CI: 7.4–18.2) versus 22.2 months (95% CI: 18.3–NA)]. Conversely, positive PD-L1 expression on immune cells was associated with prolonged median PFS in the patients with wild-type BRCA1/2 [20.9 months (95% CI: 13.9–NA) versus 8.3 months (95% CI: 6.7–13.8)]. Conclusions HRD remained an effective biomarker for enhanced olaparib efficacy in the Asian patients with PSROC. Positive PD-L1 expression was associated with decreased olaparib efficacy in the patients with germline BRCA1/2 mutations but associated with improved olaparib efficacy in the patients with wild-type BRCA1/2. Trial registration NCT03534453. Registered at May 23, 2018.

Abstract Two-dimensional (2D) materials have garnered significant attention in recent years due to their atomically thin structure and unique electronic and optoelectronic properties. To harness their full potential for applications in next-generation electronics and photonics, precise control over the dielectric environment surrounding the 2D material is critical. The lack of nucleation sites on 2D surfaces to form thin, uniform dielectric layers often leads to interfacial defects that degrade the device performance, posing a major roadblock in the realization of 2D-based devices. Here, we demonstrate a wafer-scale, low-temperature process (

Abstract To explore the influence of the cosmological constant on black hole images, we have developed a comprehensive analytical method for simulating images of Kerr–de Sitter black holes illuminated by equatorial thin accretion disks. Through the application of explicit equations, we simulate images of Kerr–de Sitter black holes illuminated by both prograde and retrograde accretion disks, examining the impact of the cosmological constant on their characteristic curves, relative sizes, and observed intensities. Our findings reveal that, in comparison to Kerr black holes, the cosmological constant not only diminishes the relative size of a black hole but also amplifies its luminosity. Moreover, an observer’s relative position in the universe ( $$r_0/r_C$$ r 0 / r C ) can influence both the relative size and luminosity of a black hole, where $$r_0$$ r 0 is the distance from the observer to the black hole, $$r_C$$ r C is the cosmological horizon determined by the value of the cosmological constant $$\Lambda $$ Λ .

Abstract Background To analyse the causal associations of different physical measures with osteoarthritis knee (KOA). Methods Exposure factors (weight, body mass index (BMI), body fat percentage, waist circumference, hip circumference, waist–hip ratio (WHR), and basal metabolic rate (BMR)), and outcome factor KOA were analyzed by inverse-variance weighted (IVW) method, along with heterogeneity test, sensitivity and pleiotropy analyses. Meta-analysis was used to combine the effect values of IVW methods in different data sources. Results Weight, BMI, body fat percentage, waist circumference, hip circumference and BMR analyses showed causal association with increased KOA risk, while WHR analysis indicated a reduction of the incidence of KOA. P-value for all the results was less than 0.05 and F-value large than 20. All results were negative for heterogeneity tests and sensitivity analyses, and there was pleiotropy in weight and BMR. Meta-analysis results showed that the results of Odds Ratios (95% Confidence Intervals) for Weight (1.43(1.35–1.51)), BMI (1.40(1.10–1.78)), body fat percentage (1.56(1.44–1.68)), waist circumference (1.40(1.10–1.78)), hip circumference (1.37(1.30–1.44)), WHR (0.86(0.71–1.04)) and BMR (1.36(1.27–1.46) were consistent with the ones by Mendelian randomization analyses. Conclusions Body fat percentage may be a better indicator of KOA than BMI. In addition, weight and BMR may have a causal effect in KOA, but WHR does not have a causal relationship. BMI, body fat percentage, waist circumference, and hip circumference has a causal effect on KOA.

Agrobacterium tumefaciens mediated plant transformation is a versatile tool for plant genetic engineering following its discovery nearly half a century ago. Numerous modifications were made in its application to increase efficiency, especially in the recalcitrant major cereals plants. Recent breakthroughs in transformation efficiency continue its role as a mainstream technique in CRISPR/Cas-based genome editing and gene stacking. These modifications led to higher transformation frequency and lower but more stable transgene copies with the capability to revolutionize modern agriculture. In this review, we provide a brief overview of the history of Agrobacterium-mediated plant transformation and focus on the most recent progress to improve the system in both the Agrobacterium and the host recipient. A promising future for transformation in biotechnology and agriculture is predicted.

The conventional building drainage system was constructed based on the theory of two-phase flow involving water and air. However, the drainage system contained a more intricate three-phase flow, encompassing water, air, and solids, which was relatively overlooked in research. This study addressed the impact of solids on pressure fluctuations, air flow rates, and hydraulic jump fullness within the drainage system, considering three factors: the mass factor, cross-section factor, and viscosity. The investigation was conducted within a single-stack system using both experimental methods and CFD simulations. The findings revealed a positive correlation between both positive and negative pressures and above three factors. The mass factor and the cross-section factor had a more significant impact on the negative pressure of the system. The maximum growth rates of negative pressure extremes under different mass and cross-section factors reached 7.72 and 16.52%, respectively. In contrast, the viscosity of fecal sludge had a slightly higher effect on the positive pressure fluctuation of the drainage system, with the maximum growth rate of positive pressure extremes at 3.41%. HIGHLIGHTS Mass factor and cross-section factor are positively correlated with air pressure.; Viscosity has a slightly greater effect on positive pressure.; The negative pressure is proportional to the air flow rate discharging solids.; Hydraulic jump fullness is the main reason for the variation of positive pressure.;

Abstract Electrocardiogram (ECG) signals are very important for heart disease diagnosis. In this paper, a novel early prediction method based on Nested Long Short-Term Memory (Nested LSTM) is developed for sudden cardiac death risk detection. First, wavelet denoising and normalization techniques are utilized for reliable reconstruction of ECG signals from extreme noise conditions. Then, a nested LSTM structure is adopted, which can guide the memory forgetting and memory selection of ECG signals, so as to improve the data processing ability and prediction accuracy of ECG signals. To demonstrate the effectiveness of the proposed method, four different models with different signal prediction techniques are used for comparison. The extensive experimental results show that this method can realize an accurate prediction of the cardiac beat’s starting point and track the trend of ECG signals effectively. This study holds significant value for timely intervention for patients at risk of sudden cardiac death.

White matter, a densely packed collection of myelinated axons, plays an essential part in neural networks. With high spatial resolution and deep penetration, multi-photon microscopy (MPM) is promising for white matter imaging in animal models in vivo. The third harmonic generation (THG) signal can be generated from white matter, but the bottom part of the white matter layer generates weak THG due to its high scattering. Here, we demonstrate an in vivo labeling and imaging technology, capable of visualizing the white matter layer in the mouse brain, combining fluorescence labeling with MitoTracker Red and three-photon fluorescence (3PF) microscopy excited at the 1700 nm window. 3PF signals are several times higher than THG signals, resulting in deeper imaging of the white matter layer with the former. Our results indicate that 3PF microscopy is a promising technology for white matter imaging in the deep brain in vivo.

In barium titanate (BaTiO3) the relative permittivity varies as a function of grain size due to the influence of various sizes and scaling effects. The cold sintering process (CSP) has been applied to sinter nanocrystalline BaTiO3 (

BackgroundPerioperative neurocognitive disorder (PND) is a critical concern for older patients undergoing cardiac surgery, impacting cognitive function and quality of life. Electroacupuncture and transcutaneous electrical acupoint stimulation (TEAS) hold promise for mitigating PND. This protocol outlines a systematic review and meta-analysis to thoroughly assess the efficacy of electroacupuncture and TEAS in older patients undergoing cardiac surgery with PND, providing up-to-date evidence for PND prevention and treatment. ObjectiveThis study aimed to thoroughly assess the efficacy of electroacupuncture and TEAS in older patients undergoing cardiac surgery with PND, providing up-to-date evidence for PND prevention and treatment. MethodsA comprehensive and systematic approach will be used to identify eligible studies from a diverse range of electronic databases, including 9 major sources such as PubMed (NLM) and Cochrane (Wiley), as well as 2 clinical trial registration websites. These studies will focus on investigating the effects of electroacupuncture and TEAS on PND in older patients undergoing cardiac surgery. The study selection will adhere to the criteria outlined in the patient, intervention, comparison, outcome, and studies (PICOS) format. Data extraction will be carried out by 2 independent researchers (YP and LS), using established tools to evaluate the risk of bias. The primary outcome will be PND incidence, with secondary outcomes including Mini Mental State Examination scores, neuron-specific enolase, S100β, interleukin-1β, interleukin-6, tumor necrosis factor-α, time to first flatus, first defecation, bowel sound recovery, and hospitalization duration to be selectively reported. Adverse events linked to acupuncture, such as bleeding, needle site pain, and local reactions, rather than serious adverse events, will also be considered. Meta-analysis will be performed using appropriate statistical methods to assess the overall effect of electroacupuncture and TEAS on PND prevention, treatment, or other relevant outcomes. The Cochrane Collaboration Risk of Bias tool will be used for assessment, and data synthesis will be executed using the RevMan 5.4 software (Cochrane). ResultsWe plan to summarize the eligible studies through the use of a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flowchart. The findings will be showcased in the form of a summary table of evidence. Figures and forest plots will be used to illustrate the outcomes of the meta-analysis. ConclusionsThe impacts of electroacupuncture and TEAS interventions on PND in older patients undergoing cardiac surgery have not yet been established. This protocol addresses a critical gap by thoroughly assessing electroacupuncture and TEAS for PND in older patients undergoing cardiac surgery, enhancing understanding of nonpharmacological interventions, and guiding future research and clinical practices in this field. Its strength lies in rigorous methodology, including comprehensive search strategies, independent review processes, and thorough assessments of the risk of bias. Trial RegistrationPROSPERO CRD42023411927; https://tinyurl.com/39xdz6jb International Registered Report Identifier (IRRID)PRR1-10.2196/55996

Background: Anti-interferon-γ autoantibodies (AIGAs) syndrome is susceptible to disseminated opportunistic infections due to increased AIGAs, but its clinical immunological characteristics remain unrecognized.Methods: We conducted a prospective cohort study between January 2021 and December 2023, recruiting patients with opportunistic infections who were categorized into AIGAs-positive and AIGAs-negative groups. Clinical immunological data and outcomes were documented. A subset of AIGAs-positive patients received glucocorticoid treatment, and its effectiveness was evaluated.Results: A total of 238 patients were enrolled, with 135 AIGAs-positive and 103 AIGAs-negative patients. AIGAs-positive patients showed higher rates of multiple pathogen dissemination, shorter progression-free survival (PFS), and increased exacerbation frequency. They also showed elevated erythrocyte sedimentation rate (ESR), globulin (GLB), immunoglobulin (Ig)G, IgE, and IgG4 levels. Among the 70 AIGAs-positive patients monitored for at least six months, three subtypes were identified: high AIGAs titer with immune damage, high AIGAs titer without immune damage, and low AIGAs titer without immune damage. Of the 55 patients followed for 1 year, decreasing AIGAs titer and immune indices (GLB, IgG, IgE, IgG4) were observed. Among the 31 patients with high AIGAs titer and immune damage treated with low-dose glucocorticoids at the stable phase, reductions were observed in immune indices and AIGAs titer in 67.74% of cases.Conclusions: AIGAs-positive patients exhibit infectious and immunological characteristics. Elevated AIGAs, IgG, IgG4, and IgE indicate abnormal immune damages. AIGAs titer generally decrease over time. Stable-phase AIGAs-positive patients can be categorized into three subtypes, with those having high AIGAs titer and increased immune indices potentially benefitting from glucocorticoid treatment.

IntroductionThere exists a knowledge gap concerning the clinical significance of miRNA-21; therefore, in the present study, we aimed to estimate the diagnostic and prognostic accuracy and sensitivity of miRNA-21 in acute myocardial infarction (AMI) by performing an evidence-based meta-analysis of previous AMI-related clinical studies.MethodsChinese and English literature published before April 2024 were searched, and data were reviewed and extracted. After quality appraisal, the STATA 16.0 software was used for the effect size analysis of the various treatments described in the literature.ResultsA total of 14 valid documents were retrieved from 562 studies. The results of the systematic review revealed that for the patients with AMI vs. those without non-AMI, the aggregated odds ratio reached 5.37 (95% confidence interval 3.70–7.04). The general sensitivity and specificity for the circulating miRNA-21 levels in diagnosing AMI were 0.83 and 0.81, respectively.DiscussionThus, the meta-analysis of 14 AMI-related clinical trials highlighted that miRNA-21 may serve as a promising biomarker for diagnosing AMI.

BackgroundThe human epidermal growth factor receptor 2 gene (HER2) has been identified as a potential therapeutic target in lung adenocarcinoma (LUAD). Non-invasive positron emission tomography (PET) imaging provides a reliable strategy for in vivo determination of HER2 expression through whole-body detection of abnormalities. The PET tracer 68Ga-NOTA-MAL-Cys-MZHER2:342 has shown promising results for HER2-positive breast and gastric cancers. This study aims to evaluate the performance of 68Ga-NOTA-MAL-Cys-MZHER2:342in vitro and in vivo models and in clinical patients with HER2-positive LUAD.MethodsNOTA-MAL-Cys-MZHER2:342 was synthesized and labeled with 68Ga. Cell uptake, cell binding ability, and stability studies of 68Ga-NOTA-MAL-Cys-MZHER2:342 were assessed both in the Calu-3 lung cancer (LC) cell line and normal mice. In vivo assessment in tumor-bearing mice was conducted using microPET imaging and biodistribution experiments. Additionally, preliminary PET/CT imaging analysis was performed on HER2-positive LC patients.Results68Ga-NOTA-MAL-Cys-MZHER2:342 was prepared with a radiochemical purity (RCP) exceeding 95%. The tracer demonstrated high cell uptake in HER2-overexpressing Calu-3 cells, with an IC50 of 158.9, an adequate 1.73 nM. Good stability was exhibited both in vitro and in vivo. MicroPET imaging of Calu-3-bearing mice revealed high tumor uptake and notable tumor-to-background ratios. Positive outcomes were also observed in two HER2-positive LUAD patients.Conclusion68Ga-NOTA-MAL-Cys-MZHER2:342 demonstrated satisfactory stability, sensitivity, and specificity. These findings suggest that 68Ga-NOTA-MAL-Cys-MZHER2:342 PET/CT imaging provides a novel tool for non-invasive visual assessment of HER2 expression in LUAD patients.

Structural lithium batteries integrated with energy storage and mechanical load‐bearing capabilities hold great promise to revolutionize lightweight transport vehicles. However, the current development of structural batteries faces critical challenges in balancing the electrochemical and mechanical properties of the electrolytes. Herein, a super strong quasi‐solid composite polymer electrolyte (QCPE) is successfully fabricated by reinforcing polyelectrolyte with 3D in situ self‐assembled metal–organic framework‐modified glass fiber (MOF@GF) soaking a small amount of liquid electrolyte, which provides continuous ion conductive pathways for fast Li+ transport and contributes to the high ambient ionic conductivity of 1.47 × 10−3 S cm−1. The micropores and abundant polar functional groups selectively restrict the transport of anions to afford a homogeneous Li+ flux and a high Li+ transference number (0.56). Simultaneously, the MOF@GF provides more effective reinforcement and a remarkably high tensile strength of 48.6 MPa, and Young's modulus of 1.66 GPa is achieved. Furthermore, the lithium metal batteries fabricated with this QCPE exhibit a long, stable operation lifespan of 2000 h and excellent cycling performance with LiFePO4 and NCM811 cathodes. This design strategy generally opens a new avenue for structural batteries with high ionic conductivity and outstanding mechanical properties, which holds great promise for industrial translation.

BackgroundIt has been shown that diabetes is associated with insufficient physical activity among middle-aged and older adults, but the association between different physical activity levels (PAL) and diabetes incidence needs to be further explored.ObjectiveThis study aims to explore the correlation and dose–response relationship between different PAL and the diabetes incidence in middle-aged and older adults.MethodsUtilizing data from the 2018 China Health and Retirement Longitudinal Study (CHARLS), this cross-sectional analysis included 17,226 middle-aged and older adults aged 45 and above. Binary logistic regression models and restricted cubic spline (RCS) were used to explore the correlation and dose–response relationship between different PAL and the incidence of diabetes in the total middle-aged and older adults population as well as in subgroups. Sensitivity analyses were also performed to verify the robustness of the findings.ResultsIn the entire study population, compared with the lowest PAL, participants in the third and fourth quartiles PAL saw diabetes incidence significantly reduced by 16% (p = 0.005) and 33% (p

Abstract Immunosuppression is a major hallmark of tumor progression in non‐small cell lung cancer (NSCLC). Cluster of differentiation 147 (CD147), an important pro‐tumorigenic factor, is closely linked to NSCLC immunosuppression. However, the role of CD147 di‐methylation in the immunosuppressive tumor microenvironment (TME) remains unclear. Here, di‐methylation of CD147 at Lys148 (CD147‐K148me2) is identified as a common post‐translational modification (PTM) in NSCLC that is significantly associated with unsatisfying survival outcomes among NSCLC sufferers, especially those in the advanced stages of the disease. The methyltransferase NSD2 catalyzes CD147 to generate CD147‐K148me2. Further analysis demonstrates that CD147‐K148me2 reestablishes the immunosuppressive TME and promotes NSCLC progression. Mechanistically, this modification promotes the interaction between cyclophilin A (CyPA) and CD147, and in turn, increases CCL5 gene transcription by activating p38‐ZBTB32 signaling, leading to increased NSCLC cell‐derived CCL5 secretion. Subsequently, CD147‐K148me2‐mediated CCL5 upregulation facilitates M2‐like tumor‐associated macrophage (TAM) infiltration in NSCLC tissues via CCL5/CCR5 axis‐dependent intercellular crosstalk between tumor cells and macrophages, which is inhibited by blocking CD147‐K148me2 with the targeted antibody 12C8. Overall, this study reveals the role of CD147‐K148me2‐driven intercellular crosstalk in the development of NSCLC immunosuppression, and provides a potential interventional strategy for PTM‐targeted NSCLC therapy.

This study investigated the impact of seasonal environmental factors on microorganisms and flavor compounds during acetic acid fermentation (AAF) of Zhenjiang aromatic vinegar (ZAV). Environmental factors were monitored throughout the fermentation process, which spanned multiple seasons. Methods such as headspace solid phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS), high performance liquid chromatography (HPLC), and high-throughput sequencing were employed to examine how these environmental factors influenced the flavor profile and microbial community of ZAV. The findings suggested that ZAV brewed in autumn had the strongest flavor and sweetness. The key microorganisms responsible for the flavor of ZAV included Lactobacillus acetotolerans, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus fermentum, Acetobacter pasteurianus. Moreover, correlation analysis showed that room temperature had a significant impact on the composition of the microbial community, along with other key seasonal environmental factors like total acid, pH, reducing sugar, and humidity. These results provide a theoretical foundation for regulating core microorganisms and environmental factors during fermentation, enhancing ZAV quality.

Common cancer complications include bone cancer pain (BCP), which was not sufficiently alleviated by traditional analgesics. More safe and effective therapy was urgent needed. Metformin relieved osteoarthritis pain, but the analgesia of Metformin in BCP was not well studied. The study aimed to explore the Metformin-mediated analgesic effect and its molecular mechanisms in BCP rats. We demonstrated that Walker 256 cell transplantation into the medullary cavity of the tibia worsened mechanical allodynia in BCP rats, increased the expression of TGFβ1 in the metastatic bone tissue, and raised the expression of TGFβRI and TRPV1 in the L4-6 dorsal root ganglion (DRG) of BCP rats. While, selectively blockade of TGFβRI by SD208 could obviously elevated the paw withdraw threshold (PWT) of BCP rats, together with decreased TRPV1 expression in L4-6 DRG. Notably, continuous Metformin treatment reduced TGFβ1, TGFβRI and TRPV1 expression, and relieved mechanical allodynia of BCP rats in a long-term effect. In conclusion, these results illustrated that Metformin ameliorated bone cancer pain, and the downregulation of TGFβ1-TGFβRI-TRPV1 might be a potential mechanism of Metformin-mediated analgesia in BCP.

The curved spacetime induced by gravitational waves can give rise to visual effects such as geometric distortions and redshift structures in the observed image. By establishing a mapping from the object's surface coordinates to the observer's screen coordinates, we study these effects in the context of plane gravitational waves. The simulation reveals that the image of an object doesn't merely seem compressed or stretched, but rather appears twisted and wobbled. Furthermore, the redshift structure on the object's surface appears to rotate as a whole. This outcome offers an intuitive depiction of the lensing effect in plane gravitational wave spacetimes.

Background: We assessed the potential role of serial circulating tumor DNA (ctDNA) as a biomarker to monitor treatment response to primary systemic therapy (PST) in breast cancer and evaluated the predictive value of ctDNA to further identify patients with residual disease. Methods: We prospectively enrolled 208 plasma samples collected at three time points (before PST, after 2 cycles of treatment, before surgery) of 72 patients with stage Ⅱ-III breast cancer. Somatic mutations in plasma samples were identified using a customized 128-gene capture panel with next-generation sequencing. The correlation between early change in ctDNA levels and treatment response or long-term clinical outcomes was assessed. Results: 37 of 72 (51.4%) patients harbored detectable ctDNA alterations at baseline. Patients with complete response showed a larger decrease in ctDNA levels during PST. The median relative change of variant allele fraction (VAF) was −97.4%, −46.7%, and +21.1% for patients who subsequently had a complete response (n = 11), partial response (n = 11), and no response (n = 15) (p = 0.0012), respectively. In addition, the relative change of VAF between the pretreatment and first on-treatment blood draw exhibited the optimal predictive value to tumor response after PST (area under the curve, AUC = 0.7448, p = 0.02). More importantly, early change of ctDNA levels during treatment have significant prognostic value for patients with BC, there was a significant correlation between early decrease of VAF and longer recurrence-free survival compared to those with an VAF increase (HR = 12.54; 95% CI, 2.084 to 75.42, p = 0.0063). Conclusion: Early changes of ctDNA are strongly correlated with therapeutic efficacy to PST and clinical outcomes in BC patients. The integration of preoperative ctDNA evaluation could help improving the perioperative management for BC patients receiving PST.

In order to ensure the flight safety of an aircraft and reduce the loss of humidity to the precision instruments and equipment in the aircraft, this study designs a small-size resonator antenna shape based on Radio Frequency Identification (RFID) technology and sensor principles. The resonator antenna makes use of the characteristics of the square ring and bent resonator and, at the same time, adopts the polyvinyl alcohol film with strong hygroscopic performance as the moisture-sensitive material. The equivalent resonant circuit of the sensor is constructed, and the parameters are optimized according to the principle of “coarse tuning of inductance parameters and fine tuning of capacitance parameters” to determine the optimal size. The relationship between the resonance frequency and the resonance response of humidity was investigated by the optimized model of the RFID resonator and polyvinyl alcohol (PVA). The simulation results show that as the relative humidity increases from 29.1 %RH to 90.9 %RH, the dielectric constant of the PVA film increases from 5.3 to 22 and the resonance frequency of the resonator decreases significantly from 4.74 to 4.12 GHz, with a total offset of 620 MHz, and the sensitivity is as high as 10.03 MHz/%RH. The results show that the designed sensor has a high sensitivity to humidity changes and a wide humidity detection range, providing an advanced solution for the detection and control of humidity inside aircraft.

On-Load Tap-Changer (OLTC) is the only core equipment in the ultra-high voltage (UHV) converter transformer that moves frequently, and flexible connection structure (FCS) is the moveable actuating part of the vacuum interrupter drive mechanism of OLTC. Minimizing the transient stress during the movement of FCS is essential for prolonging its fatigue life, thus is pursued by optimizing the shape of the flexible sheet in this paper. Peak transient stress of FCS is defined as the optimization objective, and eight geometrical parameters controlling the shape of flexible sheet are defined as the optimization variables. A progressive three-stage shape optimization strategy is proposed by combing four techniques: Multi-body Dynamic (MBD), Finite Element Analysis (FEA), Correlation Coefficient Analysis (CCA) and Adaptive Single-objective Optimization (ASO). MBD analysis of the vacuum interrupter drive mechanism and FEA of the FCS are utilized for calculating the transient stress distribution. Spearman CCA is performed to quantitively determine the correlation and sensitivity between the optimization variables and the optimization objective. Shape optimization of FCS using ASO is carried out, and results show that the stress concentration is basically eliminated and the peak transient stress decrease by 34.35% after shape optimization. Further analysis of the FCS with multi-layered flexible sheet is conducted, again demonstrating the effectiveness of the shape optimization on minimizing transient stress.

Summary: Background: Whether hepatitis B virus (HBV) infection of women prior to pregnancy can influence risk of congenital malformations in offspring remains controversial. We assessed the association between them by considering congenital malformations in the aggregate as well as risk of organs systems using a large national sample of Chinese women. Methods: We performed a record-linkage cohort study of women who participated in National Free Preconception Health Examination Project, between January 1, 2010, and December 31, 2019 for whom data on congenital malformations in their offspring were available from the National Population-Based Birth Defects Surveillance Network. A total of 498,968 linked records were obtained, of which 127,371 were excluded because HBV status before pregnancy was unknown, the records involved multiple pregnancies, or pre-pregnancy examinations were conducted after conception. Based on pre-pregnancy status, mothers were assigned to two categories of HBsAg− or HBsAg+ and, in certain analyses, to three categories of HBsAg−, HBsAg+/HBeAg− or HBsAg+/HBeAg+. Potential associations of serological status with risk of congenital malformations, considered separately or in aggregate, were explored using multilevel logistic regression. Factors that might influence such associations were also explored. Findings: Among the 371,597 women analyzed, 21,482 (5.78%) were HBsAg+ before pregnancy, and 8333 (2.24%) had a fetus or child diagnosed with congenital malformations, composed of 7744 HBsAg− women and 589 HBsAg+ women. HBsAg+ status was associated with increased risk of congenital malformations in the aggregate (OR 1.14, 95% CI 1.03–1.25) and of cardiovascular malformations specifically (OR 1.18, 95% CI 1.03–1.35). HBsAg+/HBeAg− status was associated with significantly higher risk of cardiovascular malformations (OR 1.19, 95% CI 1.01–1.39) as well as reproductive malformations (OR 1.51, 95% CI 1.02–2.23). Associations between HBsAg+ status before pregnancy and risk of congenital malformations was modified by alanine aminotransferase activity (Pinteraction < 0.05). Interpretation: Prepregnancy HBV infection might be associated with fetal malformations. This association needs further investigation to confirm whether it is a causal association, and assess whether antiviral therapy of women with HBsAg+ planning to conceive might reduce the risk of fetal malformations. Funding: The National Health Commission of the People's Republic of China, China; Science and Technology Department of Sichuan Province, China; and the Ministry of Science and Technology of the People's Republic of China.

Abstract The compound drought‐extreme precipitation event (CDEP) is one of the most impactful successive compound events that shift from drought to extreme precipitation in the same location within a short period. Due to its dual characteristics of drought and flood, CDEP tends to be more destructive than the impact of individual drought or flood. Yet few studies have analyzed the likelihood of CDEP at different time intervals and their potential variations under global warming. In this study, we assessed the coincidence rate between droughts and extreme precipitation events at 1‐month (CDEP‐1), 2‐month (CDEP‐2), and 3‐month (CDEP‐3) intervals, as well as their potential changes in a 1.5 and 2°C warming world (under both SSP2‐4.5 and SSP5‐8.5 scenarios). Our results suggest that global droughts and extreme precipitation events have coincided more frequently at 1‐month interval than at 2‐ and 3‐month intervals during the period 1985–2014. The global average coincidence rates of CDEP‐1, CDEP‐2, and CDEP‐3 are 24%, 10%, and 7%, respectively. Notably, the coincidence rate of CDEP‐1 exceeded 40% in Eastern Asia, north‐eastern North America, and India, indicating that more than 40% of droughts have been followed by extreme precipitation events in the next month after drought termination. Under both SSP2‐4.5 and SSP5‐8.5 scenarios, climate warming will increase the coincidence rate of CDEP‐1, CDEP‐2, and CDEP‐3, especially will lead to higher values in the coincidence rate of CDEP‐1. This study contributes to a better understanding of the patterns of CDEP and helps to develop more targeted risk management strategies.

BackgroundDouzhi, a traditional Chinese fermented beverage, features microbial communities primarily composed of lactic acid bacteria (LAB). As fermented foods continue to gain recognition and popularity, douzhi is attracting growing interest. However, investigation of the critical aspects of douzhi’s fermentation processes, including fermentation characteristics and microbial community dynamics, remains vital for enhancing food safety and quality for douzhi, as well as for similar fermented food products.MethodIn this study, we collected douzhi microbial communities from four chain stores, using them as fermentation starter cultures. The microbial dynamics of the fermentation were analyzed, focusing on the inoculation of LAB strains and the transition from a mung bean-based matrix to skimmed milk. The metabolomic profiles of the fermented mung bean matrices were also studied.ResultsDouzhi samples obtained from representative chain stores were found to be overwhelmingly dominated by LAB. When inoculated along with the douzhi community, both LAB strains exhibited notable and substantial reductions in the pH value of the designated mung bean matrices compared to those inoculated indigenous microbiota. Specifically, Lactiplantibacillus plantarum CGMCC 1.1856 retained its population, whereas Pediococcus pentosaceus CGMCC 1.2695 exhibited a decrease in relative abundance. Using skimmed milk as a fermentation substrate instead of the mung bean matrix resulted in significant shifts in microbial communities, particularly leading to an increase in Escherichia sp. The metagenomic analyses and functional predictions illustrated that various metabolic functions were enhanced during the fermentation process due to LAB inoculation. The liquid chromatography–mass spectrometry based metabolomic analysis revealed that the inoculation of Lactiplantibacillus plantarum and Pediococcus pentosaceus in mung bean matrix did not introduce new metabolites but significantly altered the concentration and profile of existing metabolites, especially increased low molecular carbohydrates, which may enhance the nutritional potential of the fermented product.DiscussionThis study examines the microbial dynamics of douzhi microbiota fermentation, emphasizing the role of lactic acid bacteria in enhancing fermentation activity and metabolite profiles. These insights contribute to improving manufacturing processes and ensuring the safety and quality of douzhi and similar fermented foods.

IntroductionThe Xinjiang Mongolians, located along the Silk Road, migrated westward from Northeast Asia in the 13th and 14th centuries. Despite its significance, genetic studies on Xinjiang Mongolians have been limited compared to other Mongolian populations.MethodsIn this study, we analyzed the non-recombining region of the Y-chromosome in 165 Xinjiang Mongolian males using 108 biallelic markers and 44 STRs.Results and discussionOur study identified prevalent haplogroups C2a1a3-F1918 (10%), C2a1a2-M48 (8%), N1a1a-M178 (5%), and R1a1a-M17 (10%) in the Xinjiang Mongolians. Additionally, our study suggested a genetic affinity between Xinjiang Mongolians and Inner Mongolia Mongolian populations, as well as other ethnic groups from northwest China, based on the PCA analysis. The Network analysis revealed distinct branching expansion patterns in haplogroups C2a1a3a-F3796, C2a1a2-M48, and N1a1a-M178, with estimated timeframes aligning with Genghis Khan's invasion of Xinjiang in the Yuan Dynasty. Notably, our analysis of the R1a1a-M17 Network highlighted the role of Xinjiang Mongolians in the expansion of Turkic-speaking populations in Xinjiang and surrounding regions. The integration of ancient DNA data suggested that the high frequency haplogroups C2a1a3a-F3796, C2a1a2-M48, and N1a1a-M178 could be traced back to their origin in Northeast Asia. Furthermore, the estimated TMRCA of haplogroup R1a1a-M17 implied cultural and genetic influences from Turkic populations during the Qagatay Khanate period. Overall, our study provided a genetic explanation for the ethnic origin of Xinjiang Mongolians, highlighting their migration from Northeast Asia and subsequent assimilation with the local populations in Xinjiang.

Identifying indicators of non-functional overreaching during periods of increased training volume and/or intensity is particularly relevant for understanding the detrimental impacts incurred, as well as how these factors contribute to heightened injury risks among exposed athletes. This study aimed to compare the effects of a congested training period versus a standard training period on the strength levels and landing forces of female young aerobic gymnastics athletes. A prospective cohort study design was implemented, spanning four weeks. Fifty athletes (aged 16.2 ± 1.1 years old) at a trained/developmental level, competing at the regional level, were observed throughout the study. During two of these weeks (specifically weeks 2 and 3), half of the group was subjected to a congested training period consisting of six sessions per week (HTF), while the other half continued with their regular four sessions per week (STF). During each week of observation, participants underwent evaluation using the countermovement jump test (CMJ), squat jump test (SJ), and the leg land and hold test (LHT), with measurements taken on a force platform. The main outcomes repeatedly observed over the four weeks were CMJ peak landing force, CMJ peak power, SJ peak power, SJ maximum negative displacement, LHT time to stabilization, and LHT peak drop landing force. Significant interactions (time*group) were observed in CMJ peak power (p