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To study the protective effect of Rosa roxburghii Tratt compound plant beverage (RTCPB) against the acute alcoholic liver injury in mice, alcoholic liver injury models were established with 53% alcohol in male ICR mice using oral gavage. The drug was administered continuously for 21 days, the liver index, the content of triglyceride (TG), the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) contents were determined to evaluate the potential protective effect of RTCPB on acute alcohol-induced liver injury in mice. Meanwhile, the pathology analysis was performed on liver tissue to determine pathological changes. The results showed that the liver indices of mice in silymarin control and RTCPB groups were significantly decreased (P

Deep learning methods have recently made substantial advances in polarimetric synthetic aperture radar (PolSAR) image classification. However, supervised training relying on massive labeled samples is one of its major limitations, especially for PolSAR images that are hard to manually annotate. Self-supervised learning (SSL) is an effective solution for insufficient labeled samples by mining supervised information from the data itself. Nevertheless, fully utilizing SSL in PolSAR classification tasks is still a great challenge due to the data complexity. Based on the abovementioned issues, we propose an SSL model with multibranch consistency (SSL-MBC) for few-shot PolSAR image classification. Specifically, the data augmentation technique used in the pretext task involves a combination of various spatial transformations and channel transformations achieved through scattering feature extraction. In addition, the distinct scattering features of PolSAR data are considered as its unique multimodal representations. It is observed that the different modal representations of the same instance exhibit similarity in the encoding space, with the hidden features of more modals being more prominent. Therefore, a multibranch contrastive SSL framework, without negative samples, is employed to efficiently achieve representation learning. The resulting abstract features are then fine-tuned to ensure generalization in downstream tasks, thereby enabling few-shot classification. Experimental results yielded from selected PolSAR datasets convincingly indicate that our method exhibits superior performance compared to other existing methodologies. The exhaustive ablation study shows that the model performance degrades when either the data augmentation or any branch is masked, and the classification result does not rely on the label amount.

Abstract Background The medical community has long been concerned about the cardiovascular disease risk in patients with type 2 diabetes. While liver fibrosis scores were originally designed for application in individuals with liver steatosis, an increasing number of studies have shown that they are also associated with cardiovascular disease risk. However, the association between Fibrosis-4 (Fib-4) in liver fibrosis scores and carotid atherosclerosis (CA) in patients with type 2 diabetes remains unclear. Objective The aim of this study is to investigate the association between the Fib-4 index and CA in patients with Type 2 diabetes. Additionally, it seeks to determine whether this relationship is influenced by factors including gender, age, body mass index (BMI), hypertension, and other variables. Methods Screening based on inclusion and exclusion criteria identified 2658 hospitalized patients with type 2 diabetes. Subsequently, patients were divided into three groups according to Fib-4 values (Fib-4 0.05). The results of the ROC curve analysis indicated that the AUC for Fib-4 predicting CA was 0.602 (P

Abstract Direct resin restoration has been widely used to restore the tooth defect for its convenience and minimal invasion. However, the accuracy of the final contour of class II restoration is often unpredictable and quite technique-sensitive due to the limitation of traditional matrix band system. In this study, the authors developed a novel matrix band system using shape memory polymer (SMP), which possessed two reversible shapes including digitized permanent shape to reproduce anatomical proximal contour and programmable temporary shape for clinical practice and reservation. The permanent shape could be designed and customized in software or retrieved from imaging database collected from large general population. Only warm saline or water was needed to trigger the shape transformation without any auxiliary tools. The results of in vitro class II restoration showed the shape memory matrix bands brought the best proximal profile and contact point, compared to traditional metal matrix and sectional matrix. The novel shape memory matrix system represents the comfortable, precise, and minimally invasive trend of dentistry and has a broad industrialization prospect as a dental instrument.

Abstract One of the key advantages of perovskite light-emitting diodes (PeLEDs) is their potential to achieve high performance at much higher current densities compared to conventional solution-processed emitters. However, state-of-the-art PeLEDs have not yet reached this potential, often suffering from severe current-efficiency roll-off under intensive electrical excitations. Here, we demonstrate bright PeLEDs, with a peak radiance of 2409 W sr−1 m−2 and negligible current-efficiency roll-off, maintaining high external quantum efficiency over 20% even at current densities as high as 2270 mA cm−2. This significant improvement is achieved through the incorporation of electron-withdrawing trifluoroacetate anions into three-dimensional perovskite emitters, resulting in retarded Auger recombination due to a decoupled electron-hole wavefunction. Trifluoroacetate anions can additionally alter the crystallization dynamics and inhibit halide migration, facilitating charge injection balance and improving the tolerance of perovskites under high voltages. Our findings shed light on a promising future for perovskite emitters in high-power light-emitting applications, including laser diodes.

Abstract Aerial manipulators can manipulate objects while flying, allowing them to perform tasks in dangerous or inaccessible areas. Advanced aerial manipulation systems are often based on rigid-link mechanisms, but the balance between dexterity and payload capacity limits their broader application. Combining unmanned aerial vehicles with continuum manipulators emerges as a solution to this trade-off, but these systems face challenges with large actuation systems and unstable control. To address these challenges, we propose Aerial Elephant Trunk, an aerial continuum manipulator inspired by the elephant trunk, featuring a small-scale quadrotor and a dexterous, compliant tendon-driven continuum arm for versatile operation in both indoor and outdoor settings. We develop state estimation for the quadrotor using an Extended Kalman Filter, shape estimation for the continuum arm based on piecewise constant curvature, and whole-body motion planning using minimum jerk principles. Through comprehensive fundamental verifications, we demonstrate that our system can adapt to various constrained environments, such as navigating through narrow holes, tubes, or crevices, and can handle a range of objects, including slender, deformable, irregular, or heavy items. Our system can potentially be deployed in challenging conditions, such as pipeline maintenance or electricity line inspection at high altitudes.

Abstract Background Acute and critical neurological diseases are often accompanied with elevated intracranial pressure (ICP), leading to insufficient cerebral perfusion, which may cause severe secondary lesion. Existing ICP monitoring techniques often fail to effectively meet the demand for real-time noninvasive ICP monitoring and warning. This study aimed to explore the use of electrical impedance tomography (EIT) to provide real-time early warning of elevated ICP by observing cerebral perfusion. Methods An intracranial hypertension model was prepared by injecting autologous un-anticoagulated blood into the brain parenchyma of twelve Landrace swine. Invasive ICP monitoring was used as a control method, and a high-precision EIT system was used to acquire and analyze the changing patterns of cerebral perfusion EIT image parameters with respect to ICP. Four EIT parameters related to cerebral perfusion were extracted from the images, and their potential application in detecting ICP elevation was analyzed. Results When ICP increased, all EIT perfusion parameters decreased significantly (P 22 mmHg), the correlation between EIT perfusion parameters and ICP was more significant (P

Abstract Background The coronavirus disease 2019 (COVID-19) pandemic placed a heavy strain on the United States healthcare system. Common hospital operational performances were impacted to varying degrees by the pandemic. This study examined the healthcare operational measures during COVID-19 pandemic. Methods This cross-sectional study examined the COVID-19 cases and death counts of 56 California counties and hospital-level utilization data of 397 hospitals in California from January 2019 to March 2021. Results A total of 56 California counties were analysed, of which 37 counties were urban and 19 counties were rural. Average patient length of stay was positively associated with the number of intensive care unit visits by COVID-19 patients for all counties, as well as urban and rural counties separately. However, average patient length of stay was negatively associated with the number of inpatient visits by COVID-19 patients for all counties and urban counties. Conclusions The findings suggest that, while the need for additional beds and nursing staff in intensive care units exceeded initial estimates, there were also opportunities to streamline the care process for improved efficiency in regular acute care units. The understanding of factors impacting average patient length of stay would be valuable for hospital administrators in optimizing resource allocation and utilization to balance patient outcomes with financial sustainability during disruptive events.

Abstract Amino acids are important bio-based products with a multi-billion-dollar market. The development of efficient high-throughput screening technologies utilizing biosensors is essential for the rapid identification of high-performance amino acid producers. However, there remains a pressing need for biosensors that specifically target certain critical amino acids, such as l-threonine and l-proline. In this study, a novel transcriptional regulator-based biosensor for l-threonine and l-proline was successfully developed, inspired by our new finding that SerE can export l-proline in addition to the previously known l-threonine and l-serine. Through directed evolution of SerR (the corresponding transcriptional regulator of SerE), the mutant SerRF104I which can recognize both l-threonine and l-proline as effectors and effectively distinguish strains with varying production levels was identified. Subsequently, the SerRF104I-based biosensor was employed for high-throughput screening of the superior enzyme mutants of l-homoserine dehydrogenase and γ-glutamyl kinase, which are critical enzymes in the biosynthesis of l-threonine and l-proline, respectively. A total of 25 and 13 novel mutants that increased the titers of l-threonine and l-proline by over 10% were successfully identified. Notably, six of the newly identified mutants exhibited similarities to the most effective mutants reported to date, indicating the promising application potential of the SerRF104I-based biosensor. This study illustrates an effective strategy for the development of transcriptional regulator-based biosensors for amino acids and other chemical compounds.

Abstract We present a novel approach to realize three-dimensional (3D) matter wave solitons (MWSs) transformation between different optical potential wells by manipulating their depths and centers. The 3D MWSs are obtained by the square operator method, and transformed to other types (elliptical/ring/necklace) by performing time evolution with the split-step Fourier method. The effectiveness and reliability of our approach is demonstrated by comparing the transformed solitons with those obtained iteratively using the square operator method. Redistribution of MWSs are observed due to the modulation of potentials. In certain complex optical potential wells, we demonstrate the generation of exotic MWSs, such as double gyration modes, through this transformation approach. Overall, the controllable soliton transformation provides an excellent opportunity for all-optical switching, optical information processing, and various other applications.

Abstract Separation of multi-component mixtures in an energy-efficient manner has important practical impact in chemical industry but is highly challenging. Especially, targeted simultaneous removal of multiple impurities to purify the desired product in one-step separation process is an extremely difficult task. We introduced a pore integration strategy of modularizing ordered pore structures with specific functions for on-demand assembly to deal with complex multi-component separation systems, which are unattainable by each individual pore. As a proof of concept, two ultramicroporous nanocrystals (one for C2H2-selective and the other for CO2-selective) as the shell pores were respectively grown on a C2H6-selective ordered porous material as the core pore. Both of the respective pore-integrated materials show excellent one-step ethylene production performance in dynamic breakthrough separation experiments of C2H2/C2H4/C2H6 and CO2/C2H4/C2H6 gas mixture, and even better than that from traditional tandem-packing processes originated from the optimized mass/heat transfer. Thermodynamic and dynamic simulation results explained that the pre-designed pore modules can perform specific target functions independently in the pore-integrated materials.

Abstract As batteries drive the transition to electrified transportation and energy systems, ensuring their quality, reliability, lifetime, and safety is crucial. While the solid electrolyte interphase (SEI) is known to govern these performance characteristics, its dynamic nature makes understanding its nucleation, growth, and composition an ambitious, yet elusive aspiration. This work employs chalcogenide fibres embedded in negative electrode materials for operando Infra-red Fibre-optic Evanescent Wave Spectroscopy (IR-FEWS), combined with Multivariate Curve Resolution by Alternating Least Squares (MCR-ALS) algorithms for spectra analysis. By establishing molecular fingerprints that can be used to identify reaction products, IR-FEWS combined with MCR-ALS enables improved understanding of SEI evolution during cell formation with notable differences stemming from electrolyte or anode material. For example, despite operating at an elevated potential, lithium titanate’s SEI has intrinsic instability, evidenced by continued carbonate formation. This approach leads the hunt for the SEI down a new path, giving empirical formulations theoretical roots.

Abstract Financial distress prediction (FDP) is a critical area of study for researchers, industry stakeholders, and regulatory authorities. However, FDP tasks present several challenges, including high-dimensional datasets, class imbalances, and the complexity of parameter optimization. These issues often hinder the predictive model’s ability to accurately identify companies at high risk of financial distress. To mitigate these challenges, we introduce FinMHSPE—a novel multi-heterogeneous self-paced ensemble (MHSPE) FDP learning framework. The proposed model uses pairwise comparisons of data from multiple time frames combined with the maximum relevance and minimum redundancy method to select an optimal subset of features, effectively resolving the high dimensionality issue. Furthermore, the proposed framework incorporates the MHSPE model to iteratively identify the most informative majority class data samples, effectively addressing the class imbalance issue. To optimize the model’s parameters, we leverage the particle swarm optimization algorithm. The robustness of our proposed model is validated through extensive experiments performed on a financial dataset of Chinese listed companies. The empirical results demonstrate that the proposed model outperforms existing competing models in the field of FDP. Specifically, our FinMHSPE framework achieves the highest performance, achieving an area under the curve (AUC) value of 0.9574, considerably surpassing all existing methods. A comparative analysis of AUC values further reveals that FinMHSPE outperforms state-of-the-art approaches that rely on financial features as inputs. Furthermore, our investigation identifies several valuable features for enhancing FDP model performance, notably those associated with a company’s information and growth potential.

Abstract Background Gliomas are the most common malignant primary tumors of the central nervous system. There is an urgent need for new convenient, targeted and specific imaging agents for gliomas. This study aimed to firstly evaluate the feasibility of 68Ga-NOTA-RM26 PET/CT imaging in glioma and analyze the relationship between the imaging characteristics and glioma grade, classification and molecular alterations. Results Twenty-two patients were confirmed as glioma by surgery or biopsy. All patients exhibited 68Ga-NOTA-RM26 uptake. SUVmax was chosen as the imaging marker for analysis. For all glioma patients, there were significant differences between grades (P = 0.047). For primary gliomas, SUVmax had good discrimination for both tumor classifications (P = 0.045) and grades (P = 0.03). There was a positive correlation (P

Abstract Recent studies suggest the role of gut microbes in bile acid metabolism in the development and progression of colorectal cancer. However, the surveys of the association between fecal bile acid concentrations and colorectal cancer (CRC) have been inconsistent. We searched online to identify relevant cross-sectional and case-control studies published online in the major English language databases (Medline, Embase, Web of Science, AMED, and CINAHL) up to January 1, 2024. We selected studies according to inclusion and exclusion criteria and extracted data from them. RevMan 5.3 was used to perform the meta-analyses. In CRC risk meta-analysis, the effect size of CA (cholic acid), CDCA (chenodeoxycholic acid), DCA (deoxycholic acid), and UDCA (ursodeoxycholic acid) were significantly higher (CA: standardized mean difference [SMD] = 0.41, 95% confidence interval [CI]: 0.5–0.76, P = 0.02; CDCA: SMD = 0.35, 95% CI: 0.09–0.62, P = 0.009; DCA: SMD = 0.33,95% CI: 0.03–0.64, P = 0.03; UDCA: SMD = 0.46, 95% CI: 0.14–0.78, P = 0.005), and the combined effect size was significantly higher in the high-risk than the low-risk CRC group (SMD = 0.36, 95% CI: 0.21–0.51, P

Abstract Optical neural networks are considered next-generation physical implementations of artificial neural networks, but their capabilities are limited by on-chip integration scale and requirement for coherent light sources. This study proposes a spectral convolutional neural network (SCNN) with matter meta-imaging. The optical convolutional layer is implemented by integrating very large-scale and pixel-aligned spectral filters on CMOS image sensor. It facilitates highly parallel spectral vector-inner products of incident incoherent natural light i.e., the direct information carrier, which empowers in-sensor optical analog computing at extremely high energy efficiency. To the best of our knowledge, this is the first integrated optical computing utilizing natural light. We employ the same SCNN chip for completely different real-world complex tasks and achieve accuracies of over 96% for pathological diagnosis and almost 100% for face anti-spoofing at video rates. These results indicate a feasible and scalable in-sensor edge computing chip of natural light for various portable terminals.

Abstract The shortwave infrared (SWIR) region is an ideal spectral window for next-generation bioimaging to harness improved penetration and reduced phototoxicity. SWIR spectral activity may also be accessed via supramolecular dye aggregation. Unfortunately, development of dye aggregation remains challenging. We propose a crystal-aided aggregate synthesis (CAASH) approach to introduce a layer of rationality for the development of J-aggregate and the successful development of a water-soluble SWIR JV-aggregate with a bisbenzannulated silicon rhodamine scaffold (ESi5). The resulting SWIR-aggregates exhibit excellent stabilities toward organic solvents, pH, sonication, photobleaching, thiols, and endogenous oxidative species. Notably, the aggregates have a high structure-dependent melting temperature of ca. 330-335 K. In fact, the heating/annealing process can be exploited to reduce aggregation disorder. The aggregates are biocompatible and have broad potential in in vivo fluorescence and photoacoustic imaging and more.

Abstract Low-dimensional lead-free metal halide perovskites are highly attractive for cutting-edge optoelectronic applications. Herein, we report a class of scandium-based double perovskite crystals comprising antimony dopants that can generate multiexcitonic emissions in the ultraviolet, blue, and yellow spectral regions. Owing to the zero-dimensional nature of the crystal lattice that minimizes energy crosstalk, different excitonic states in the crystals can be selectively excited by ultraviolet light, X-ray irradiation, and mechanical action, enabling dynamic control of steady/transient-state spectral features by modulating the excitation modes. Remarkably, the transparent crystal exhibits highly efficient white photoluminescence (quantum yield >97%), X-ray excited blue emission with long afterglow (duration >9 h), and high-brightness self-reproducible violet-blue mechanoluminescence. These findings reveal the exceptional capability of low-dimensional perovskite crystals for integrating various excitonic luminescence, offering exciting opportunities for multi-level data encryption and all-in-one authentication technologies.

Abstract. Background:. Without timely and effective rehabilitation, hearing loss may profoundly affect human life quality. China has a large population of hearing-impaired individuals, which imposes a heavy health burden on society. Moreover, this population is projected to increase rapidly owing to China’s aging society. Methods:. We used data from a population-representative epidemiological investigation of hearing loss and ear diseases in four Chinese provinces. We estimated the national prevalence using multiple linear regression of the age-group proportions and prevalence in 31 provinces with clustering analysis. We used years lived with disability (YLDs) to analyze the disease burden and forecasted the prevalence of hearing loss by 2060 in China. Results:. An estimated 115 million people had moderate-to-complete hearing loss in 2015 across the 31 provinces of China (8.4% of 1.37 billion people). Of these, 85.7% were older than age 50 years (99 million people) and 2.4% were younger than 20 years old (2.8 million people). Of all YLDs attributable to hearing loss, 68.9% were attributable to moderate-to-complete cases. By 2060, a projected 242 million people in China will have moderate-to-complete hearing loss, a 110.0% increase from 2015. Conclusions:. The hearing loss prevalence in China is high. Population aging and socioeconomic factors substantially affect the prevalence and severity of hearing loss and the disease burden. The prevalence and severity of hearing loss are unevenly distributed across different provinces. Future public health policies should take these trends and regional variations into account.

In order to improve the quality characteristics and storage stability of ASO, refining ASO obtained using subcritical extraction to remove phospholipids, peroxides, and free fatty acids. In this paper, the extraction process of subcritical extraction ASO was optimized, and the crude oil was degummed and refined by membrane separation technology. Using membrane flux, degumming rate, iodine value, peroxide value and acid value as indicators, ceramic membranes with different pore sizes and polyethersulfone membranes with different molecular weights were screened. The effects of membrane retention of molecular weight, temperature and pressure on membrane flux were investigated, and the optimal process parameters for refining ASO were determined through response surface methodology. An analysis of the fatty acid composition was conducted using gas chromatography-mass spectrometry both before and after refining. The results showed that, when the particle size was 30 mesh, the extraction temperature was 50 ℃, the solid-liquid ratio was 1:4 g/mL, the molecular weight of the polyethersulfone membrane was 100 kD, the temperature was 44 ℃, the pressure was 1.9 MPa, the average oil yield of ASO was 35.92%, the degumming rate was 86.73%, the flux was 12.51 L/m2·h, the iodine value was 116.93 g/100 g, the peroxide value was 0.06 g/100 g, the acid value was 3.66 g/100 g, and there was no significant loss of fatty acid content compared to crude oil. The results showed that degumming by membrane separation is an effective method to improve the quality of oil, so this study can provide technical support for the production of high-quality Acer truncatum seed oil.

Background/Aims: Growing recognition identifies sessile serrated lesions (SSL) as colorectal cancer (CRC) precursors. However, the SSL detection rate remains debatable and lacks a definitive consensus. Additionally, understanding the influencing factors in SSL development is limited. We aim to retrospectively analyze the true prevalence and risk factors of SSL in China. Materials and Methods: This retrospective study collected medical data from patients who underwent colonoscopy at the Endoscopy Center of Shanghai East Hospital affiliated with Tongji University between March 1, 2019 and February 28, 2022. Data were sourced through the electronic medical record system and included information such as age, sex, lesion location, number, and pathology. This study predominantly focused on the detection rate and the clinical and endoscopic features of SSL. Results: Of 72 287 colonoscopies in 3 years, 3905 cases were histologically confirmed as SSL. Among them, 2290 (58.6%) were male, and 1615 (41.4%) were female. The overall SSL detection rate was 5.40%, slightly surpassing Asian/Chinese averages but lower than Western rates. Males had a higher SSL detection rate (6.1%) than females (4.6%). Univariate analysis revealed a significant association between SSL with dysplasia/adenocarcinoma (SSL-D/AD) and obesity (Body Mass Index, BMI ≥ 24), CRC family history, and hypertension. After multivariable logistic regression, only obesity (BMI ≥ 24) remained a statistically significant independent risk factor for SSL-D/AD. Conclusions: The SSL detection rate at our center is 5.4% and increases with age. Males have a significantly higher detection rate than females. Our findings suggest that endoscopists should consider risk factors for SSL-D/AD, such as obesity, CRC family history, and hypertension.

In semi-supervised object detection (SSOD), the methods based on dense pseudo-labeling bypass complex post-processing while maintaining competitive performance compared to the methods based on sparse pseudo-labeling. However, there are still relatively few researches focused on the dense pseudo-labeling paradigm. In this work, we first experimentally point out the shortcomings of current dense pseudo-labeling methods: 1) Low-quality sampling: the fixed threshold strategies can result in numerous false negatives and false positives. 2) Inconsistency between classification scores and localization quality: classification scores cannot represent localization quality, resulting in poor quality of predicted bounding boxes for sampled positive samples. 3) Suboptimal training approach: current training methods only utilize its knowledge from the perspective of final dense pseudo-labels, failing to fully exploit the teacher model. To address these issues, we propose a method called Dense-Label Refinement and Cross Optimization (DRCO) based on dense pseudo-labels. Specifically, to tackle the issue of low-quality sampling, we introduce the Adaptive Sampling Approach (ASA), which achieves high-quality sampling at the image level and dynamic sampling ratios without introducing any additional hyperparameters. For the inconsistency between classification scores and localization quality, Comprehensive FRS (cFRS) is proposed to jointly optimize the classification and localization branches more efficiently, thereby obtaining a more comprehensive score. Finally, for the suboptimal training approach, we introduce Cross Prediction Optimization (CPO). CPO efficiently leverages the knowledge of the teacher model through a Cross-Head operation, thereby achieving more effective teacher-student interaction. DRCO achieves 27.31% mAP with only 1% COCO labeled data, which is approximately 1.24% mAP higher than the previous state-of-the-art. Based on MS COCO and PASCAL VOC benchmarks, further comprehensive experiments demonstrate that our method alleviates the aforementioned shortcomings and achieves competitive performance.

Abstract Regenerating periodontal bone defect surrounding periodontal tissue is crucial for orthodontic or dental implant treatment. The declined osteogenic ability of periodontal ligament stem cells (PDLSCs) induced by inflammation stimulus contributes to reduced capacity to regenerate periodontal bone, which brings about a huge challenge for treating periodontitis. Here, inspired by the adhesive property of mussels, we have created adhesive and mineralized hydrogel microspheres loaded with traditional compound cordycepin (MMS-CY). MMS-CY could adhere to the surface of alveolar bone, then promote the migration capacity of PDLSCs and thus recruit them to inflammatory periodontal tissues. Furthermore, MMS-CY rescued the impaired osteogenesis and ligament-forming capacity of PDLSCs, which were suppressed by the inflammation stimulus. Moreover, MMS-CY also displayed the excellent inhibitory effect on the osteoclastic activity. Mechanistically, MMS-CY inhibited the premature senescence induced by the inflammation stimulus through the nuclear factor erythroid 2-related factor (NRF2) pathway and reducing the DNA injury. Utilizing in vivo rat periodontitis model, MMS-CY was demonstrated to enhance the periodontal bone regeneration by improving osteogenesis and inhibiting the osteoclastic activity. Altogether, our study indicated that the multi-pronged approach is promising to promote the periodontal bone regeneration in periodontitis condition by reducing the inflammation-induced stem cell senescence and maintaining bone homeostasis.

Abstract Dissection of the physiological interactomes of histone post-translational modifications (hPTMs) is crucial for understanding epigenetic regulatory pathways. Peptide- or protein-based histone photoaffinity tools expanded the ability to probe the epigenetic interactome, but in situ profiling in native cells remains challenging. Here, we develop a nucleus-targeting histone-tail-based photoaffinity probe capable of profiling the hPTM-mediated interactomes in native cells, by integrating cell-permeable and nuclear localization peptide modules into an hPTM peptide equipped with a photoreactive moiety. These types of probes, such as histone H3 lysine 4 trimethylation and histone H3 Lysine 9 crotonylation probes, enable the probing of epigenetic interactomes both in HeLa cell and hard-to-transfect RAW264.7 cells, resulting in the discovery of distinct interactors in different cell lines. The utility of this probe is further exemplified by characterizing interactome of emerging hPTM, such as AF9 was detected as a binder of histone H3 Lysine 9 lactylation, thus expanding the toolbox for profiling of hPTM-mediated PPIs in live cells.

Abstract Background Acute pulmonary embolism represents the third most prevalent cardiovascular pathology, following coronary heart disease and hypertension. Its untreated mortality rate is as high as 20–30%, which represents a significant threat to patient survival. In view of the current lack of real-time monitoring techniques for acute pulmonary embolism, this study primarily investigates the potential of the pulsatility electrical impedance tomography (EIT) technique for the detection and real-time monitoring of acute pulmonary embolism through the collection and imaging of the pulsatile signal of pulmonary blood flow. Methods A before-and-after self-control experiment was conducted on anaesthetised domestic pigs (N = 12, 20.75 ± 2.56 kg). The changes in pulmonary perfusion caused by an acute pulmonary embolism (artificially induced) were monitored in real time using the pulsation method. This enabled the extraction of indicators such as Amplitude, Forward (Negative) Slope, and S ARC , which were used to assess the local pulmonary blood flow perfusion state. Furthermore, the degree of ventilation/perfusion matching in the lungs was evaluated concurrently with the analysis of the pulmonary ventilation area. Subsequently, a control verification was conducted utilising the conventional invasive hypertonic saline (5 ml 10% NaCl) contrast technique. Results The perfusion alterations subsequent to embolism in the pulsatility method are highly concordant with those observed in the hypertonic saline method, as evidenced by the imaging and indicator data. In particular, the perfusion area on the side of the embolism is markedly diminished, and the absolute values of all perfusion indicators are significantly reduced. Among these, Amplitude (P

Abstract Background With the aging of society, cognitive impairment in elderly people is becoming increasingly common and has caused major public health problems. The screening of cognitive impairment in elderly people and its related influencing factors can aid in the development of relevant intervention and improvement strategies. Methods In this study, stratified random cluster sampling was used to conduct a cross-sectional survey of elderly individuals aged 65 years in Chengdu, Sichuan Province, through an electronic questionnaire from November 2022 to November 2023. Descriptive analysis and logistic regression analysis were used to investigate cognitive impairment and its relevant influencing factors. Results Among the 16,609 elderly people, 7524 (45.3%) were males and 9085 (54.7%) were females, with an average age of 73.6 ± 6.5 years (age range 65–101 years). The average years of education was 5.9 ± 6.2 years, and the proportion of individuals with cognitive impairment was 13.1%. With increasing age, the risk of cognitive impairment increased significantly. The risk factors for cognitive impairment in elderly individuals included advanced age, hypertension, heart disease, diabetes, cerebrovascular disease, depressive symptoms, and anxiety symptoms, while the protective factors included higher education level, married status, and greater life satisfaction. Conclusion Cognitive impairment in elderly individuals in Chengdu is serious. We can intervene in and improve cognitive impairment in elderly people by controlling blood pressure and blood sugar, treating depressive and anxiety symptoms and developing community colleges for elderly people and increasing satisfaction with life.

Sustainable Development Science Satellite 1 (SDGSAT-1), an innovative satellite engineered by the Chinese Academy of Sciences, focuses on achieving sustainable development goals (SDGs) by using high-resolution low-light imaging for urban planning and environmental monitoring. Although its potential to provide substantial information relevant to various SDG indicators has been demonstrated across multiple domains, a comprehensive analysis of the potential of SDGSAT-1 glimmer imagery for urban road detection has not yet conducted. To address this gap, we aimed to evaluate the applicability of SDGSAT-1 glimmer imagery in road detection across five cities with well-developed road networks in China, namely Chengdu, Guangzhou, Hangzhou, Shanghai, and Wuhan. Watershed segmentation and optimal thresholding algorithms were applied to extract the road network data of these five cities. We observed that the large connecting roads, including highways (Motorway), urban expressways (Trunk), urban main roads (Primary), urban secondary roads (Secondary), and urban tertiary roads (Tertiary), were visible in the SDGSAT-1 glimmer data. Watershed segmentation and optimal thresholding algorithms demonstrated a remarkable precision of approximately 80% for road extraction across all cities. Approximately, 64% of urban roads were detectable within the SDGSAT-1 glimmer imager data. Our study suggests that the SDGSAT-1 glimmer data have great potential for extracting urban roads.

Digital light processing (DLP)-based bioprinting technology holds immense promise for the advancement of hydrogel constructs in biomedical applications. However, creating high-performance hydrogel constructs with this method is still a challenge, as it requires balancing the physicochemical properties of the matrix while also retaining the cellular activity of the encapsulated cells. Herein, we propose a facile and practical strategy for the 3D bioprinting of high-performance hydrogel constructs through the in-situ birth of stem cell spheroids. The strategy is achieved by loading the cell/dextran microdroplets within gelatin methacryloyl (GelMA) emulsion, where dextran functions as a decoy to capture and aggregate the cells for bioprinting while GelMA enables the mechanical support without losing the structural complexity and fidelity. Post-bioprinting, the leaching of dextran results in a smooth curved surface that promotes in-situ birth of spheroids within hydrogel constructs. This process significant enhances differentiation potential of encapsulated stem cells. As a proof-of-concept, we encapsulate dental pulp stem cells (DPSCs) within hydrogel constructs, showcasing their regenerative capabilities in dentin and neovascular-like structures in vivo. The strategy in our study enables high-performance hydrogel tissue construct fabrication with DLP-based bioprinting, which is anticipated to pave a promising way for diverse biomedical applications.

China has a large number of patients with Alzheimer's disease (AD) and types of other dementia, which places a heavy burden on the public health and medical systems. As global climate change results in more frequent extreme weather events, and there is a current lack of understanding regarding the impact of non-optimal temperatures, especially cold, on AD and other dementia mortality, the study aimed to identify patterns of temperature sensitivity in order to inform targeted public health strategies. The records of 399,214 decedents aged 60 years and older who died due to AD or other dementias from 2013 to 2020 were obtained from the China Cause of Death Reporting System. Using an individual-level time-stratified case-crossover study design, the relationships between ambient temperatures and AD and other dementia mortality were quantified using conditional logistic regression combined with the distributed lag nonlinear model. In addition, the attributable fractions (AFs) of mortality due to non-optimal ambient temperatures were calculated. The study found that both low and high non-optimal temperatures were associated with an increased risk of death from AD and other dementias, with an inverted J-shaped exposure–response curve. Moreover, the AFs of mortality due to full, low and high non-optimal temperatures with lag0–14 were 5.81% (95% empirical confidence interval [eCI]: 4.89%, 6.72%), 5.24% (95% eCI: 4.15%, 6.27%) and 0.58% (95% eCI: 0.27%, 0.90%), respectively. Importantly, AFs varied across administrative regions, influenced by factors such as climate, geography, sociodemographic characteristics and socioeconomic factors. These findings can inform clinical and public health practices to reduce the mortality burden due to non-optimal temperatures on elderly populations with AD and other dementias.

Photosynthetic adaptations to light fluctuations do not occur instantaneously, leading to reduced carbon gain and lower productivity in agricultural crops. Enhancing the rapidity of photosynthetic responses to these fluctuations could potentially increase carbon assimilation by 13–32%, indicating a substantial opportunity for yield improvement of major crops. Most crops can be categorized into C3 or C4 crops by their photosynthetic pathways. This review provides a comparative overview of the photosynthetic responses of both C3 and C4 crops to light fluctuations, highlighting the unique and shared challenges for these two photosynthetic pathways. In C3 crops, fast adjustments in non-photochemical quenching, stomatal and mesophyll conductance, and Rubisco activation are essential for optimizing photosynthesis under variable light conditions. In contrast, C4 crops, including maize, sorghum, and sugarcane, benefit from their carbon concentration mechanism under high light conditions but face challenges in coordinating the C4 and Calvin–Benson–Bassham cycles. Strategies to enhance the activation of pyruvate phosphate dikinase and Rubisco, as well as to improve electron transport capacity and flexibility, could markedly boost the photosynthetic efficiency and productivity. Through a detailed understanding of the distinct mechanisms involved in C3 and C4 photosynthesis, this review underscores the need for tailored strategies to optimize the photosynthetic efficiency specific to each crop type. Exploring and leveraging these differences is crucial for propelling agricultural productivity forward.

Abstract Background While it is well-stablished that scoliosis can lead to neuromuscular control disorders, the specific characteristics of these impairments remain unclear. This study aimed to explore the neuromuscular features of scapula stabilizers in adolescents with idiopathic scoliosis (AIS) through an analysis of anticipatory muscle activations (AMAs). Methods A cross-sectional observational study was conducted with 17 AIS and 19 age-matched healthy subjects. Both the AIS and healthy groups performed right and left upper limb reaching tasks at three different heights while surface electromyography monitored the activity of scapular stabilizers. The muscles examined included the bilateral infraspinatus, upper trapezius, lower trapezius, serratus anterior, latissimus dorsi and the anterior deltoid. The incidence, onset latencies, and amplitude of AMAs were compared between the AIS and healthy groups. Results Among scapular stabilizers, ipsilateral upper trapezius (iUT) and ipsilateral infraspinatus (iIS) exhibited the highest AMAs incidence at 72.59% and 70.06%, respectively. However, AMAs incidence significantly declined on the concave side of the thoracic curve in AIS group, particularly in iUT (55.63 ± 14.74 vs. 45.21 ± 19.92, t = 2.330, P = 0.034) and iIS (59.38 ± 20.16 vs. 48.13 ± 22.11, t = 2.316, P = 0.035). Regarding onset latencies, the AIS group exhibited delayed activation of ipsilateral lower trapezius (F = 3.586, P

Abstract Background To explore the potential impact of lymphovascular invasion (LVI) on overall survival (OS) of pN0 stage gastric cancer (GC) after curative resection. Methods A total of 497 GC patients who underwent curative gastrectomy and postoperative pathology proved negative lymph node metastasis between January 2015 and December 2018 in our center were enrolled in this study. All patients were divided into two groups according to the status of LVI. Their clinical and pathological features were compared and potential prognostic factors were analyzed using the propensity score matching analysis (PSM). Results Ninety-nine (19.9%) patients had LVI. The presence of LVI was associated with significantly worse survival outcomes in both the overall and PSM cohorts (χ2 = 19.635, p

Abstract Ginseng (Panax ginseng C.A. Meyer) is widely used in several functional foods at present. Ginsenosides, is the most crucial bioactive constituents in ginseng whose antitumor activity have been widely reported. In this study, the effect of ginseng glucosyl oleanolate (GGO) produced from ginsenoside Ro through enzymatic transformation, on cervical cancer was evaluated in vitro and in vivo. GGO significantly inhibited the viability and colony forming ability of HeLa cells, and blocked the cell cycle in G0/G1 phase, which showed its ability to inhibit the proliferation of HeLa cells. GGO exhibited anti-angiogenesis effect in HUVECs, chick chorioallantoic membrane (CAM) and Matrigel plugs model. These effects were related to interference with the paracrine axis of VEGF/VEGFR2 and blockage of the downstream PI3K/AKT/HIF-1α signaling pathway of the autocrine axis. The dual inhibitory effects of GGO were also exhibited in immunocompromised mice undergoing heterograft and suppressed tumor growth without any side effects. These findings provide a theoretical basis for further development of GGO as a functional food with anti-tumor properties.

Abstract Macrophages that acquire an immunosuppressive phenotype play a crucial role in establishing the pre-metastatic niche (PMN), which is essential for facilitating breast cancer metastasis to distant organs. Our study showed that increased activity of the aryl hydrocarbon receptor (AHR) in lung macrophages plays a crucial role in establishing the immunosuppressive PMN in breast cancer. Specifically, AHR activation led to high expression of PD-L1 on macrophages by directly binding to the promoter of Pdl1. This upregulation of PD-L1 promoted the differentiation of regulatory T cells (Tregs) within the PMN, further enhancing immunosuppressive conditions. Mice with Ahr conditional deletion in macrophages had reduced lung metastasis of breast cancer. The elevated AHR levels in PMN macrophages were induced by GM-CSF, which was secreted by breast cancer cells. Mechanistically, the activated STAT5 signaling pathway induced by GM-CSF prevented AHR from being ubiquitinated, thereby sustaining its activity in macrophages. In breast cancer patients, the expression of AHR and PD-L1 was correlated with increased Treg cell infiltration, and higher levels of AHR were associated with a poor prognosis. These findings reveal that the crosstalk of breast cancer cells, lung macrophages, and Treg cells via the GM-CSF-STAT5-AHR-PD-L1 cascade modulates the lung pre-metastatic niche during breast cancer progression.

Abstract Poly (ADP-ribose) polymerase 1 (PARP1) catalyzes poly (ADP) ribosylation reaction, one of the essential post-translational modifications of proteins in eukaryotic cells. Given that PARP1 inhibition can lead to synthetic lethality in cells with compromised homologous recombination, this enzyme has been identified as a potent target for anti-cancer therapeutics. However, the clinical application of existing PARP1 inhibitors is restrained by side effects associated with DNA trapping and off-target effects, highlighting the need for improved therapeutic strategies. By integrating protein degradation technology, we synthesized a PROTAC molecule 180055 based on the Rucaparib junction and VHL ligand, which efficiently and selectively degraded PARP1 and inhibited PARP1 enzyme activity without a noticeable DNA trapping effect. Furthermore, 180055 kills tumor cells carrying BRCA mutations with a minor impact on the growth of normal cells both in vitro and in vivo. This suggests that 180055 is a PARP1-degrading compound with excellent pharmacological efficacy and extremely high biological safety that deserves further exploration and validation in clinical trials.

Lead-bismuth coolant in nuclear reactors generates and accumulates 210Po during operation, which has strong toxicity and high volatility. When the coolant leaks or the reactor is opened, some of the 210Po on the surface of the coolant and in the covering gas will diffuse out of the main system if not properly handled and released into the environment, posing a potential serious threat to the ecological environment and human health. The high-temperature distillation capture technology can effectively extract large amounts of 210Po from the lead-bismuth coolant. Since 210Po is an extremely toxic radioactive isotope with no stable isotope, and to facilitate the experimental study of the capture process, this study ultimately chose its isotopic cousin, Te, as a substitute for 210Po for experimental research. Measuring the trace amount of Te in the distillation capture product can provide strong support for the 210Po extraction process. In the experiment, Te was extracted from the distillation capture film using nitric acid, and the 717 strong basic anion resin was used to separate Te from the extraction solution to eliminate the interference of impurity ions. SnCl2 reduced Te4+ to Te in HCl medium, and the absorbance was measured on a spectrophotometer to obtain the content of trace Te in the sample. The influence of interfering ions in the extraction solution on the measurement value of Te was investigated; the effects of the pH of the column liquid, the concentration and amount of the elution agent, and the washing rate on the separation of Te were explored; and a spectrophotometric method for the determination of trace Te in the distillation capture product of lead-bismuth coolant was established. The results show that at room temperature, the HCl concentration of the column liquid is 4 mol/L, the eluent is ultrapure water, the washing rate is 2 mL/min. The 717 strong basic anion resin demonstrates excellent separation performance for Te across a concentration range of 0 to 10 mg/L, where the absorbance shows a strong linear correlation with Te concentration. The correlation coefficient is r2=0.999 9, with a relative standard deviation of measurement ranging from 0.3% to 2.7%(n=6). The recovery rate is between 96.0% and 101.9%. This measurement method satisfies the requirements for researching the 210Po extraction process.

Abstract Walking is fundamental to normal human life. However, many people suffer from walking impairments due to various diseases that may severely affect their daily activities. Early detection of an abnormal gait can aid subsequent treatment and rehabilitation. This paper proposes a novel abnormal gait recognition method based on a perceptual loss convolutional temporal autoencoder (PLCTAE) network. It comprises upstream and downstream tasks, both of which utilise radar micro‐Doppler spectrograms as inputs. The upstream task employs a convolutional autoencoder with the perceptual loss to encode and decode micro‐Doppler spectrograms, achieving unsupervised pretraining and obtaining the initial parameters for the convolutional part of the PLCTAE. The downstream task fine‐tunes the convolutional part of the PLCTAE through supervised training to extract spatial features from the micro‐Doppler spectrograms and incorporates a bidirectional long short‐term memory (BiLSTM) network to further extract temporal features, accomplishing the task of abnormal gait classification. The experimental results demonstrate that the proposed method achieves good classification performance on the self‐established dataset which is collected by Texas Instruments' IWR6843ISK millimetre‐wave radar and contains eight types of abnormal gaits. The generalisation performance is also validated on a public dataset from the University of Glasgow containing six types of human activities.

Abstract A strategy was proposed to predict accurately the dielectric permittivity and dielectric strength based on the Onsager local field theory. The molecular dynamic simulation was utilised to analyse the dipole moment fluctuation in polyimide (PI) to reflect the polarisation response of applied electric field. The simulation results revealed that the optical dielectric permittivity and static dielectric permittivity were 2.62 and 3.34, showing that the electronic displacement polarisation of the PI acted as a major contributor. The deviation between simulated and measured values of the frequency‐dependent relative dielectric permittivity was no more than 5%, which exhibited high accuracy. As the polarisation response of the polar groups in the PI was at infrared frequencies, the conductive loss may be the dominant role in 102–106 Hz at room temperature. Moreover, the effect of Joule heat on the structure, dielectric permittivity and Young modulus was considered to accurately predict the dielectric strength of the PI (359 kV/mm), which was in agreement with experimental values in the literature. These results establish a clear correlation between structural characteristics and dielectric properties of the PI, which would be the theoretical insights into the design and synthesis of the PI with tailored dielectric properties.

Abstract Thyroid nodules are a common endocrine condition with an increasing incidence over the decades. Data-independent acquisition has been widely utilized in discovery proteomics to identify disease biomarkers and therapeutic targets. To analyze the thyroid disease-related proteome in a high-throughput, reproducible and reliable manner, we introduce thyroid-specific peptide spectral libraries. Here, we generated four deep-coverage libraries through four mass spectrometers comprising Q Exactive HF, Orbitrap Exploris 480, ZenoTOF 7600, and timsTOF Pro. These libraries encompass over 215,000 precursors, 172,000 peptides, and 12,000 proteins, derived from 245 tissue samples across nine histological types and 50 cell lines across six histological types. Moreover, the spectral libraries are applied to nine types of thyroid samples to facilitate the exploration of disease-specific proteins. Our spectral libraries serve as a valuable resource for analyzing thyroid protein content, facilitating deeper insights into thyroid disorders.

Abstract Background Lavandula angustifolia Mill., a valuable aromatic plant, often encounters low temperature stress during its growth in Northeast China. Understanding the mechanisms behind its resistance to low temperatures is essential for enhancing this trait. Flavonoids play a vital role as stress-resistant compounds, significantly contributing to plants’ responses to low-temperature stress. However, the molecular mechanism governing flavonoid biosynthesis in L. angustifolia under low-temperature stress is remains inadequately understood. Results In this study, the physiological indexes, metabolome, and transcriptome of L. angustifolia were studied under temperatures of 30 °C, 20 °C, 10 °C, and 0 °C. The activities of peroxidase (POD) and superoxide dismutase (SOD) were notably the highest at 0 ℃, demonstrating optimal scavenging of reactive oxygen species (ROS). Among the 1150 metabolites analyzed, 52 flavonoid differential expression metabolites (DEMs) significantly increased at 10 °C and 0 °C. Furthermore, 55 differential expression genes (DEGs) involved in the flavonoid biosynthesis pathway showed significant up-regulation as the temperature dropped from 30 °C to 0 °C, indicating their role in positively regulating flavonoid biosynthesis under low temperatures. The flavonoid biosynthetic pathway was established based on key DEGs, including LaPAL-5, LaPAL-11, LaC4H-2, LaHCT, LaC3’H-4, LaCHS, LaF3PH-3, LaCCoAOMT-2, LaCCoAOMT-3, and LaDFR. Conserved domains predicted in 10 key proteins were identified as being responsible for catalytic functions that promote flavonoid biosynthesis under low temperatures. The synergistic enhancement between flavonoid DEMs and antioxidant enzymes was found to significantly contribute to the cold resistance of L.angustifolia. Conclusions The findings of this study provide a valuable reference for understanding the molecular regulation of L. angustifolia in response to low temperatures, laying a crucial foundation for future molecular breeding efforts aimed at developing cold-resistant varieties.

Abstract Mechanical ventilation contributes to diaphragm atrophy and muscle weakness, which is referred to as ventilator-induced diaphragmatic dysfunction (VIDD). The pathogenesis of VIDD has not been fully understood until recently. The aim of this study was to investigate the effects of 24 h of mechanical ventilation on fibro-adipogenic progenitor (FAP) proliferation, endothelial-mesenchymal transition (EndMT), and immune cell infiltration driving diaphragm fibrosis in a rabbit model. The rabbits were anaesthetized and randomly divided into two groups (n = 3 each group): a control group and an experimental group. Diaphragm nuclei for sequencing were prepared by dissociating and filtering muscle tissue. 10X Genomics Platform for single-nucleus RNA sequencing (snRNA-seq) was used to profile the cells. Normalization and clustering were performed by Seurat, and clusters were manually annotated as different cell types. In this study, we performed differentially expressed genes (DEGs) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, pseudotime analysis and high dimensional weighted gene coexpression network analysis (hdWGCNA) to identify the key genes and signaling pathways related to the pathogenesis of VIDD. We further performed quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting to verify the results of snRNA-seq. The snRNA-seq results showed that acute postmechanical ventilation diaphragm cell changes included an increase in the proportion of fibroblasts and a decrease in the proportion of myofibres. The DEGs, KEGG, hdWGCNA and pseudotime analyses demonstrated that fibro-adipogenic progenitor (FAP) proliferation, endothelial-mesenchymal transition (EndMT) and immune cell infiltration are the three main processes involved in early stage of fibrosis development, among which Pdgfd, Sema3a, Cxcr2, are the corresponding regulatory genes. Glycolysis and the gene Pfkfb3 are also important metabolic factors for fibrosis formation. Negr1 and Mef2c are involved in phrenic nerve ending loss and diaphragm fibre atrophy. The qRT-PCR data showed that the mRNA levels of the genes Pdgfd, Cxcr2, Pfkfb3 and Negr1 were significantly greater in the experimental group than in the control group (P

Abstract Objective This study aims to introduce a two-stage surgical procedure, namely oblique lateral interbody fusion (OLIF), for spinal disorders treatment. Furthermore, clinical outcomes and imaging results are analyzed between OLIF with posterior fixation and posterior lumbar interbody fusion (PLIF) with fixation for lumbosacral curve-driven degenerative lumbar scoliosis (DLS). Methods 146 patients with type 2 DLS who underwent OLIF or PLIF between January 2019 and November 2023 were included. Spinal and pelvic parameters were measured using X-ray imaging before and after surgery. Clinical symptoms were assessed using Oswestry Disability Index (ODI) and visual analog scale (VAS). Operation time, intraoperative blood loss, surgical fixation segments, drainage tube indwelling time, and drainage volume were recorded. Results 70 patients underwent OLIF and 76 underwent PLIF. Preoperative and postoperative clinical symptoms remain the same (p > 0.05). OLIF group exhibited significantly less intraoperative blood loss, fewer fixation segments, shorter drainage tube retention time, and reduced drainage volume (p

Abstract Comorbidity among atopic diseases (ADs) and gastrointestinal diseases (GIDs) has been repeatedly demonstrated by epidemiological studies, whereas the shared genetic liability remains largely unknown. Here we establish an atlas of the shared genetic architecture between 10 ADs or related traits and 11 GIDs, comprehensively investigating the comorbidity-associated genomic regions, cell types, genes and genetically predicted causality. Although distinct genetic correlations between AD-GID are observed, including 14 genome-wide and 28 regional correlations, genetic factors of Crohn’s disease (CD), ulcerative colitis (UC), celiac disease and asthma subtypes are converged on CD4+ T cells consistently across relevant tissues. Fourteen genes are associated with comorbidities, with three genes are known treatment targets, showing probabilities for drug repurposing. Lower expressions of WDR18 and GPX4 in PBMC CD4+ T cells predict decreased risk of CD and asthma, which could be novel drug targets. MR unveils certain ADs led to higher risk of GIDs or vice versa. Taken together, here we show distinct genetic correlations between AD-GID pairs, but the correlated genomic loci converge on the dysregulation of CD4+ T cells. Inhibiting WDR18 and GPX4 expressions might be candidate therapeutic strategies for CD and asthma. Estimated causality indicates potential guidance for preventing comorbidity.

With the rapid development of nuclear science and technology，medical radioisotopes play an increasingly important role in nuclear medicine，and are widely used in the diagnosis and treatment of cardiovascular and cerebrovascular diseases，tumors and other diseases. Accelerator production of medical radioisotopes has the advantages of flexibility，efficiency，system safety and high nuclide activity，and is one of the important production methods to ensure the safe and stable supply of medical radioisotopes. In 2021，China Atomic Energy Authority together with seven other ministries，jointly released the “Medium - and Long Term Development Plan for Medical Isotopes (2021−2035)”，which clarifies that there are 14 important medical isotopes that China needs to focus on developing before 2035，of which 9 isotopes can be produced by accelerators. This article mainly introduces the production and application overview of accelerators for the 9 important medical isotopes listed in the plan. The 9 important medical isotopes include the imaging nuclides 123I，124I，64Cu，68Ga，89Zr and the therapeutic nuclides 186Re，103Pd，225Ac ,223Ra .Among them,225Ac、68Ge and 223Ra are the focus of isotope production in medium and high energy accelerators，and also are the main development trend of accelerator production radioisotopes. This study provides a comprehensive review of the nuclear properties，applications，reaction cross-sections，yields，and production methods of the diagnostic and therapeutic nuclides mentioned above，providing reference for the production of related nuclides.

68Ge is the parent nuclide of radioactive nuclide 68Ga used in positron emission tomography (PET) diagnostic imaging，which is converted into 68Ga by a 68Ge/68Ga generator for clinical diagnostic imaging applications. Currently，there are 13 kinds of 68Ga labeled radiopharmaceuticals in China that have entered clinical practice and have good application prospects in tumor imaging such as high-grade endocrine tumors and prostate cancer. Therefore，with the approval and widespread use of 68Ga radiopharmaceuticals，68Ge has broad application prospects in both domestic and international markets.In addition,68Ge can also be widely used as a calibration source for PET scanners.China Institute of Atomic Energy (CIAE) plans to build a 75 MeV cyclotron with the maximum beam current of 800 μA and the proton energy range of 75 MeV. It will be used to focus on the production of 68Ge nuclide.This article used the Monte Carlo program FLUKA to simulate in detail the production of 68Ge nuclides yield，reaction products，the variation of impurity nuclide production with cooling time，and long-life nuclides affecting separation processes by irradiating gallium nickel alloy targets and niobium gallium capsule targets in medium to high energy proton cyclotron.The simulation results can provide the useful reference for the production，separation，and purification of 68Ge in medium to high energy cyclotron.

This study focuses on the simulation of target preparation，dissolution，and separation- purification processes for the production of the vital medical radioactive isotope 68Ge using medium-high energy cyclotrons. It encompasses the preparation and quality inspection of gallium-nickel alloy targets，target dissolution，the establishment of analytical detection methods，and the optimization of simulation conditions for the separation and purification of 68Ge. Initially，gallium-nickel alloy targets were prepared on copper backing plates by optimizing the electrodeposition process conditions. Analytical detection methods were then established using inductively coupled plasma mass spectrometry (ICP-MS). Subsequently，the dissolution process of the gallium-nickel alloy targets was studied using an electrochemical anodic oxidation method. Finally，the combined use of Tulsimer CH-90 chelating resin and Sephadex G25 gel resin was employed to optimize the simulation conditions for the separation and purification of 68Ge，completing the process simulation study. The results indicate that the prepared gallium-nickel alloy targets have a smooth and flat surface with a uniform composition distribution，containing 74.7% gallium and 25.3% nickel，and have a thickness of 179 mg/cm2，suitable for medium-high energy proton irradiation above 30 MeV. The established ICP-MS internal standard method enables accurate quantitative detection of germanium and impurity elements. The electrochemical method allows for simple and rapid dissolution of the gallium-nickel alloy layer without heating. The combined use of chelating resin and gel resin for separation and purification yields germanium-containing sample solutions with high recovery rates and purity. Through the aforementioned process simulation studies，a simulated process flow for target preparation，target dissolution，analytical detection，and separation-purification has been established，providing technical support for the production of 68Ge using medium-high energy cyclotrons.

Abstract Purpose To compare five pulmonary surfactant (PS) administration strategies for neonates with respiratory distress syndrome (RDS), including intubation-surfactant-extubation (InSurE), thin catheter administration, laryngeal mask airway (LMA), surfactant nebulization (SN), and usual care, with a particular emphasis on the comparison of the LMA and SN with other strategies. Methods We conducted a systematic search of MEDLINE, EMBASE, PUBMED, and Cochrane CENTRAL databases up to November 2023. Two authors independently conducted data extraction, and assessed bias using the Cochrane Risk of Bias Tool. Frequency-based random-effects network meta-analyses were executed. Results A total of 36 trials and 4035 infants were included in the analysis. LMA (OR: 0.20, 95%CI: 0.09 to 0.42) and Less Invasive Surfactant Administration (LISA) (OR: 0.17, 95%CI: 0.09 to 0.32) significantly reduced intubation rates compared to usual care. SN had a higher intubation rate compared to LISA (OR: 3.36, 95%CI: 1.46 to 7.71) and LMA (OR: 2.92, 95%CI: 1.10 to 7.71). LMA had a higher incidence of BPD compared to LISA (OR: 2.59, 95%CI: 1.21 to 5.54). SN ranked second to LISA in preventing BPD and death, but its efficacy decreased after excluding high-risk studies. SN and LMA had the lowest incidence of adverse events during administration.SN had the highest likelihood of secondary administration. Most results were rated as low or very low quality, with findings related to SN significantly impacted by high-risk trials. Conclusions The thin catheter strategy minimized intubation risk and showed a better composite effect in reducing both mortality and BPD incidence. SN and LMA each showed safety and some clinical benefits in the subpopulations where they were studied, but their efficacy needs further validation through high-quality studies. Registration This study was registered in PROSPERO (CRD42023463756).