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Mesenchymal stem cells (MSCs) have demonstrated significant therapeutic potential in heart failure (HF) treatment. However, their clinical application is impeded by low retention rate and low cellular activity of MSCs caused by high inflammatory and reactive oxygen species (ROS) microenvironment. In this study, monascus pigment (MP) nanoparticle (PPM) was proposed for improving adverse microenvironment and assisting in transplantation of bone marrow-derived MSCs (BMSCs). Meanwhile, in order to load PPM and reduce the mechanical damage of BMSCs, injectable hydrogels based on Schiff base cross-linking were prepared. The PPM displays ROS-scavenging and macrophage phenotype-regulating capabilities, significantly enhancing BMSCs survival and activity in HF microenvironment. This hydrogel demonstrates superior biocompatibility, injectability, and tissue adhesion. With the synergistic effects of injectable, adhesive hydrogel and the microenvironment-modulating properties of MP, cardiac function was effectively improved in the pericardial sac of rats. Our results offer insights into advancing BMSCs-based HF therapies and their clinical applications.

Abstract Wearable optical sensors have emerged as a promising technology, opening up a new way to monitor human sweat. With the advancement of integrated optical devices, optical materials, and structure design, the current optical skin interfaces primarily employ four analytical methods to transmit sweat chemical information into optical signals: colorimetry, surface-enhanced Raman spectroscopy, fluorescence, and electrochemiluminescence. To improve portability, many external laser source devices and imaging modules are upgraded based on different optical methods. Here, we summarize recent progress in optical sweat sensors, focusing on their principles, development, advantages, and limitations. Finally, current challenges and future prospects of wearable optical sensors in materials, sweat collection, data analysis, and external integrated electronics are discussed.

Abstract Entanglement serves as the resource to empower quantum computing. Recent progress has highlighted its positive impact on learning quantum dynamics, wherein the integration of entanglement into quantum operations or measurements of quantum machine learning (QML) models leads to substantial reductions in training data size, surpassing a specified prediction error threshold. However, an analytical understanding of how the entanglement degree in data affects model performance remains elusive. In this study, we address this knowledge gap by establishing a quantum no-free-lunch (NFL) theorem for learning quantum dynamics using entangled data. Contrary to previous findings, we prove that the impact of entangled data on prediction error exhibits a dual effect, depending on the number of permitted measurements. With a sufficient number of measurements, increasing the entanglement of training data consistently reduces the prediction error or decreases the required size of the training data to achieve the same prediction error. Conversely, when few measurements are allowed, employing highly entangled data could lead to an increased prediction error. The achieved results provide critical guidance for designing advanced QML protocols, especially for those tailored for execution on early-stage quantum computers with limited access to quantum resources.

Nowadays, the rapid development of the social economy inevitably leads to global energy and environmental crisis. For this reason, more and more scholars focus on the development of photocatalysis and/or electrocatalysis technology for the advantage in the sustainable production of high-value-added products, and the high efficiency in pollutants remediation. Although there is plenty of outstanding research has been put forward continuously, most of them focuses on catalysis performance and reaction mechanisms in laboratory conditions. Realizing industrial application of photo/electrocatalytic processes is still a challenge that needs to be overcome by social demand. In this regard, this review comprehensively summarized several explorations in the field of photo/electrocatalytic reduction towards potential industrial applications in recent years. Special attention is paid to the successful attempts and the current status of photo/electrocatalytic water splitting, carbon dioxide conversion, resource utilization from waste, etc., by using advanced reactors. The key problems and challenges of photo/electrocatalysis in future industrial practice are also discussed, and the possible development directions are also pointed out from the industry view.

Abstract Background Gastric emptying (GE), with wide inter-individual but lesser intra-individual variations, is a major determinant of postprandial glycaemia in health and type 2 diabetes (T2D). However, it is uncertain whether GE of a carbohydrate-containing liquid meal is predictive of the glycaemic response to physiological meals, and whether antecedent hyperglycaemia influences GE in T2D. We evaluated the relationships of (i) the glycaemic response to both a glucose drink and mixed meals with GE of a 75 g glucose drink, and (ii) GE of a glucose drink with antecedent glycaemic control, in T2D. Methods Fifty-five treatment-naive Chinese adults with newly diagnosed T2D consumed standardised meals at breakfast, lunch and dinner with continuous interstitial glucose monitoring. On the subsequent day, a 75 g glucose drink containing 150 mg 13C-acetate was ingested to assess GE (breath test) and plasma glucose response. Serum fructosamine and HbA1c were also measured. Results Plasma glucose incremental area under the curve (iAUC) within 2 hours after oral glucose was related inversely to the gastric half-emptying time (T50) (r = −0.34, P = 0.012). The iAUCs for interstitial glucose within 2 hours after breakfast (r = −0.34, P = 0.012) and dinner (r = −0.28, P = 0.040) were also related inversely to the T50 of oral glucose. The latter, however, was unrelated to antecedent fasting plasma glucose, 24-hour mean interstitial glucose, serum fructosamine, or HbA1c. Conclusions In newly diagnosed, treatment-naive, Chinese with T2D, GE of a 75 g glucose drink predicts the glycaemic response to both a glucose drink and mixed meals, but is not influenced by spontaneous short-, medium- or longer-term elevation in glycaemia.

Neuropathic pain (NP) is a common, intractable chronic pain caused by nerve dysfunction and primary lesion of the nervous system. The etiology and pathogenesis of NP have not yet been clarified, so there is a lack of precise and effective clinical treatments. In recent years, traditional Chinese medicine (TCM) has shown increasing advantages in alleviating NP. Our review aimed to define the therapeutic effect of TCM (including TCM prescriptions, TCM extracts and natural products from TCM) on NP and reveal the underlying mechanisms. Literature from 2018 to 2024 was collected from databases including Web of Science, PubMed, ScienceDirect, Google academic and CNKI databases. Herbal medicine, Traditional Chinese medicines (TCM), neuropathic pain, neuralgia and peripheral neuropathy were used as the search terms. The anti-NP activity of TCM is clarified to propose strategies for discovering active compounds against NP, and provide reference to screen anti-NP drugs from TCM. We concluded that TCM has the characteristics of multi-level, multi-component, multi-target and multi-pathway, which can alleviate NP through various pathways such as anti-inflammation, anti-oxidant, anti-apoptotic pathway, regulating autophagy, regulating intestinal flora, and influencing ion channels. Based on the experimental study and anti-NP mechanism of TCM, this paper can offer analytical evidence to support the effectiveness in treating NP. These references will be helpful to the research and development of innovative TCM with multiple levels and multiple targets. TCM can be an effective treatment for NP and can serve as a treasure house for new drug development.

The Western Sichuan Plateau stands as a vital ecological barrier in China. In recent years, rapid urbanization and infrastructure development have led to increased ecosystem fragmentation in the region, compression of species habitats, and significant challenges to ecosystem service functions and biodiversity conservation. Constructing ecological corridors can help maintain landscape connectivity and preserve biodiversity by providing habitats for various species. Additionally, they can enhance population viability and species richness at both local and regional scales. Current research focuses on the construction of ecological networks and the potential impacts of corridors. Few studies consider corridor width as an object of study. This study addresses the width of corridor construction, aiming to support the practical implementation of corridor projects and explore the coordination between corridor costs and functionality at different widths. Based on an evaluation of ecosystem service functions and in conjunction with natural reserves, this study identified significant ecological source. Four primary resistance factors—land use type, elevation, slope, and Degree of relief—were selected to construct resistance surfaces. The MAXENT model is introduced to identify potential landslide-prone areas, and the resistance surfaces are accordingly adjusted. Potential corridors are identified utilising circuit theory. Subsequently, by employing the IEW-TOPSIS model, different ecological corridor widths are evaluated in terms of “cost-function-ecological benefits” to determine suitable corridor widths for the Western Sichuan Plateau. Results reveal significant variations in ecological corridor widths across different regions of the plateau. Taking topographical factors into account, 1400 m emerges as the most optimal width twice, while 800 m, 1700 m, and 2000 m each appear once. The corridor width evaluation system can provide decision support for ecological corridor construction in the Western Sichuan Plateau, contributing to the preservation of ecological security in the Qinghai-Tibet Plateau in China.

In this paper, a dual deep Q-network (DDQN) energy management model based on long-short memory neural network (LSTM) speed prediction is proposed under the model predictive control (MPC) framework. The initial learning rate and neuron dropout probability of the LSTM speed prediction model are optimized by the genetic algorithm (GA). The prediction results show that the root-mean-square error of the GA-LSTM speed prediction method is smaller than the SVR method in different speed prediction horizons. The predicted demand power, the state of charge (SOC), and the demand power at the current moment are used as the state input of the agent, and the real-time control of the control strategy is realized by the MPC method. The simulation results show that the proposed control strategy reduces the equivalent fuel consumption by 0.0354 kg compared with DDQN, 0.8439 kg compared with ECMS, and 0.742 kg compared with the power-following control strategy. The difference between the proposed control strategy and the dynamic planning control strategy is only 0.0048 kg, 0.193%, while the SOC of the power battery remains stable. Finally, the hardware-in-the-loop simulation verifies that the proposed control strategy has good real-time performance.

The AMP-activated protein kinase α (AMPKα) subunit is the catalytic subunit in the AMPK complex, playing a crucial role in AMPK activation. It has two isoforms: AMPKα1 and AMPKα2. Emerging evidence suggests that the AMPKα subunit exhibits subtype-specific effects in Alzheimer's disease (AD). This review discusses the role of the AMPKα subunit in the pathogenesis of AD, including its impact on β-amyloid (Aβ) pathology, Tau pathology, metabolic disorders, inflammation, mitochondrial dysfunction, inflammasome and pyroptosis. Additionally, it reviews the distinct roles of its isoforms, AMPKα1 and AMPKα2, in AD, which may provide more precise targets for future drug development in AD.

Controlling the creep instability of the surrounding rock of the deep soft rock roadway is a necessary prerequisite to achieve safe mining operations. This paper takes Guqiao Coal Mine as the engineering background, uses experimental testing, theoretical analysis, industrial experiments, on-site monitoring and other methods to conduct in-depth research. The study results show that the strength of the surrounding rock of the deep roadway in Guqiao Coal Mine is weak, and it is easy to cause a significant decline in long-term strength, elastic modulus, cohesion and internal friction angle after immersion, rock softening, continuous expansion of floor loose zone and reduction of overall stability of surrounding rock; the special shape of internal and external bearing structure of surrounding rock is defined: approximate vertical ellipse, based on improving the stability of the bearing structure, the deep hole grouting technology of the bottom plate is proposed. The deep hole grouting of the bottom plate can quickly change the shape of the bearing structure and change the unstable approximate vertical ellipse shape into the approximate circular shape with high stability.

Abstract Background Docetaxel resistance represents a significant obstacle in the treatment of prostate cancer. The intricate interplay between cytokine signalling pathways and transcriptional control mechanisms in cancer cells contributes to chemotherapeutic resistance, yet the underlying molecular determinants remain only partially understood. This study elucidated a novel resistance mechanism mediated by the autocrine interaction of interleukin-11 (IL-11) and its receptor interleukin-11 receptor subunit alpha(IL-11RA), culminating in activation of the JAK1/STAT4 signalling axis and subsequent transcriptional upregulation of the oncogene c-MYC. Methods Single-cell secretion profiling of prostate cancer organoid was analyzed to determine cytokine production profiles associated with docetaxel resistance.Analysis of the expression pattern of downstream receptor IL-11RA and enrichment of signal pathway to clarify the potential autocrine mechanism of IL-11.Next, chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) was performed to detect the nuclear localization and DNA-binding patterns of phosphorylated STAT4 (pSTAT4). Coimmunoprecipitation and reporter assays were utilized to assess interaction between pSTAT4 and the cotranscription factor CREB-binding protein (CBP) as well as their role in c-MYC transcriptional activity. Results Autocrine secretion of IL-11 was markedly increased in docetaxel-resistant prostate cancer cells. IL-11 stimulation resulted in robust activation of JAK1/STAT4 signalling. Upon activation, pSTAT4 translocated to the nucleus and associated with CBP at the c-MYC promoter region, amplifying its transcriptional activity. Inhibition of the IL-11/IL-11RA interaction or disruption of the JAK1/STAT4 pathway significantly reduced pSTAT4 nuclear entry and its binding to CBP, leading to downregulation of c-MYC expression and restoration of docetaxel sensitivity. Conclusion Our findings identify an autocrine loop of IL-11/IL-11RA that confers docetaxel resistance through the JAK1/STAT4 pathway. The pSTAT4-CBP interaction serves as a critical enhancer of c-MYC transcriptional activity in prostate cancer cells. Targeting this signalling axis presents a potential therapeutic strategy to overcome docetaxel resistance in advanced prostate cancer. Graphical Abstract

Abstract The Coronavirus Disease 2019 (COVID‐19) epidemic has constituted a Public Health Emergency of International Concern. Chest computed tomography (CT) can help early reveal abnormalities indicative of lung disease. Thus, accurate and automatic localisation of lung lesions is particularly important to assist physicians in rapid diagnosis of COVID‐19 patients. The authors propose a classifier‐augmented generative adversarial network framework for weakly supervised COVID‐19 lung lesion localisation. It consists of an abnormality map generator, discriminator and classifier. The generator aims to produce the abnormality feature map M to locate lesion regions and then constructs images of the pseudo‐healthy subjects by adding M to the input patient images. Besides constraining the generated images of healthy subjects with real distribution by the discriminator, a pre‐trained classifier is introduced to enhance the generated images of healthy subjects to possess similar feature representations with real healthy people in terms of high‐level semantic features. Moreover, an attention gate is employed in the generator to reduce the noise effect in the irrelevant regions of M. Experimental results on the COVID‐19 CT dataset show that the method is effective in capturing more lesion areas and generating less noise in unrelated areas, and it has significant advantages in terms of quantitative and qualitative results over existing methods.

Objective Currently, there is no simple and valid method to predict the length and size of the native anterior cruciate ligament (ACL) in each adult patient who will undergo ACL reconstruction. This study aimed to develop an imaging prediction method that can predict the length and size of ACL grafts using the intact posterior cruciate ligament (PCL), in order to enhance the graft preparation individualized sizing. Methods Three hundred and nineteen patients aged 18 years or older who underwent magnetic resonance imaging (MRI) of the knee at an orthopaedic clinic between September 9, 2021, and February 5, 2023, were included. The length, sagittal diameter, and coronal diameter of the ACL and PCL were measured in all patients, and F‐test were performed to explore linear relationship between ligament measurements. Results Equations were established to predict a variable of the native ACL for the corresponding variable of the intact PCL (i.e., sagittal diameter of the ACL = 4.32 + 1.08 × sagittal diameter of the PCL, and coronal diameter of the ACL = 2.45 + 0.59 × coronal diameter of the PCL, length of the male ACL = 10.92 + 0.64 × length of the male PCL, length of the female ACL = 11.76 + 0.58 × length of the female PCL) (R2 = 0.532; R2 = 0.417; R2 = 0.488; R2 = 0.509; respectively). Conclusions The length and size of the intact PCL in cases without PCL buckling are predictors of the length and size of the native ACL in adults, respectively. The use of this information to optimize graft diameter may lower the rates of ACL graft failure in the future.

Abstract To investigate the influence of thermal treatment on the rockburst in granite caverns, true-triaxial compression tests were conducted on pre-heated granite cubic samples containing a circular through-hole using a true-triaxial test system, and the micro camera was used to monitor and record the rockburst process in realtime. Test results show that the uniaxial compressive strength and elastic modulus first increase and then decrease as the temperature increases, which reach the maximums at 200 °C and sharply decrease at temperatures from 400 to 600 °C. The density and P-wave velocity decrease and the peak strain increases with increasing temperature. The main failure mode is X-shaped shear-tension failure at 25 and 200 °C, and single-slope shear failure at 400 and 600 °C. Thermal treatment exhibits slight effect on the rockburst incubation process in granite caverns. The stress required for rockburst decreases when the temperature increases or decreases from 200 °C. The higher the temperature, the lower the required stress. At 25 and 200 °C, rockburst is violent, and fine particles and large slabs are mainly produced; at 400 and 600 °C, the intensity of rockburst is relatively weak, and fine particles are mainly generated. Thermal treatment exhibits double effects on rockburst. The mechanism of thermal treatment on granite rockburst is the strengthening effect caused by water loss and the weakening effect caused by thermal expansion cracking. This study can provide theoretical guidance for the stability analysis and rockburst prevention of temperature-affected granite caverns.

Efficient decision-making in earthquake emergencies plays a crucial role in ensuring individual safety, protecting personal property, and maintaining societal stability. However, traditional approaches to earthquake emergency decision-making rely on manual analysis or rule-based methods, which often struggle to fully leverage the wealth of information and uncover hidden data connections. Consequently, the efficiency of earthquake emergency decision-making is compromised. To address this issue, this study proposes a method for constructing an earthquake event knowledge graph and utilizing it for decision-making in earthquake emergencies. Firstly, specialized earthquake event knowledge ontology is developed, tailored to the unique characteristics of earthquake event data. Secondly, structured instances of earthquake event knowledge are extracted from text using transfer learning techniques, enabling the construction of the earthquake event knowledge graph. Thirdly, the earthquake event knowledge is represented as multidimensional vectors using knowledge graph representation learning technology. This facilitates the identification of similar earthquake events through inference based on vector similarity computation. In conclusion, the results of a case-based study demonstrate the effectiveness of the proposed method in providing accurate outcomes, facilitating earthquake event matching, enabling the retrieval and reuse of historical earthquake event knowledge, and serving as a valuable reference for earthquake emergency decision-making.

ABSTRACTGlobally, hepatitis E virus (HEV) infections are prevalent. The finding of high viral loads and persistent viral shedding in ejaculate suggests that HEV replicates within the human male genital tract, but its target organ is unknown and appropriate models are lacking. We aimed to determine the HEV tropism in the human testis and its potential influence on male reproductive health. We conducted an ex vivo culture of human testis explants and in vitro culture of primary human Sertoli cells. Clinically derived HEV genotype 1 (HEV1) and HEV3 virions, as well as rat-derived HEV-C1, were used for inoculation. Transcriptomic analysis was performed on testis tissues collected from tacrolimus-treated rabbits with chronic HEV3 infection. Our findings reveal that HEV3, but not HEV1 or HEV-C1, can replicate in human testis explants and primary human Sertoli cells. Tacrolimus treatment significantly enhanced the replication efficiency of HEV3 in testis explants and enabled successful HEV1 infection in Sertoli cells. HEV3 infection disrupted the secretion of several soluble factors and altered the cytokine microenvironment within primary human Sertoli cells. Finally, intratesticular transcriptomic analysis of immunocompromised rabbits with chronic HEV infection indicated downregulation of genes associated with spermatogenesis. HEV can infect the human testicular tissues and Sertoli cells, with increased replication efficiency when exposed to tacrolimus treatment. These findings shed light on how HEV may persist in the ejaculate of patients with chronic hepatitis E and provide valuable ex vivo tools for studying countermeasures.

Coral reefs are severely threatened by global and local disturbances that can shift reefs from coral to algal dominance. Coral-macroalgae competition is expected to exacerbate coral decline as the interactions increase in frequency. Whereas numerous studies over the last decade have aimed to characterize the interactions and impacts on coral growth and physiology, the underlying mechanisms remain controversial. This study tested the impact of different macroalgal species, densities, and contact status with corals on the physiological response of corals in Sanya Reefs. The results revealed that direct contact with increasing densities of fleshy macroalgae had a negative impact on the photosynthesis, growth rate, and tissue biomass of the two common corals. However, calcified macroalgae did not significantly affect the corals, regardless of whether there was direct contact or not. Under the same conditions, Acropora intermedia appeared to be more susceptible to fleshy macroalgae compared to Porites lutea. This suggested that different corals varied in their susceptibility to various macroalgae. Additionally, the results of the generalized linear mixed model revealed that macroalgal species and contact status with corals were the most important predictors of the impacts of macroalgae on corals, and macroalgal density was another nonnegligible parameter. Overall, macroalgae may have caused a potential functional shift in the composition of coral assemblages on the Sanya reefs by further reducing the already depauperate reef-building coral populations. The negative impacts of macroalgae in Sanya Reefs may serve as an early warning that the persistence of the invaluable ecological functions provided by coral reefs will be increasingly threatened throughout the South China Sea. Our findings could contribute to improving the scientific and effective management practices, fostering sustainable coral reef development in China and beyond.

Shallow purple soils (Entisols) were widely distributed in hilly areas of southwest China and were easily subjected to drought due to the weak soil water retention capacity, which largely reduced the crop productivity. However, the impact of solum thickness on ecological traits and water use strategies of crops remain poorly understood under the shallow Entisol environment. In this study, water use patterns and physiological adaptation of maize with different solum thicknesses were investigated to ascertain the optimum solum thickness based on an in-situ experiment. Isotopic (2H and 18O) tracing technique was used to investigate the water sources for maize growth in sloping croplands with solum of 20 cm (C1), 40 cm (C2), 60 cm (C3), 80 cm (C4), 100 cm (C5) thickness. The morphological and physiological characteristics were also discussed under different soil moisture regimes. The results showed the soil water storage capacity significantly increased with solum thickness. The isotopes of xylem water in shallow solum (≦40 cm) were more enriched, indicating more contributions from the bottom soil water, especially under dry regimes (62.3% for C1, 42.8% for C2, at Jul. 09). The water sources utilized by maize in the treatments with solum thickness greater than 60 cm were relatively evenly distributed throughout the soil profile (mean 19.3%, 19.6% and 17.6%, respectively, in the 0–10 cm, 10–20 cm, 20–40 cm soil layer), and the water niche breadth increased with the solum thickness. Maize in shallow solum (≦40 cm) had lower biomass and higher specific leaf area (SLA) to reduce transpiration rate and improved water use efficiency (WUEi) (highest for C1, P60 cm) had significantly higher yields than in shallower solum (P

The drug development process is poised for significant transformation due to the rapid advancement of modern biological and information technologies, such as artificial intelligence (AI). As these new technologies and concepts infiltrate every stage of drug development, the efficiency and success rate of research and development are expected to improve substantially. Traditional Chinese medicine (TCM), a time-honored therapeutic system encompassing herbal medicine, acupuncture, and qigong, will also be profoundly impacted by these advancements. Over the next decade, Traditional Chinese medicine research will encounter both opportunities and challenges as it integrates with modern technologies and concepts. By 2035, TCM is anticipated to merge with modern medicine through a more contemporary and open research and development model, providing substantial support for treating a broader spectrum of diseases.

Abstract Background and Objective High‐grade glioma (HGG) is known to be characterized by a high degree of malignancy and a worse prognosis. The classical treatment is safe resection supplemented by radiotherapy and chemotherapy. Tumor treating fields (TTFields), an emerging physiotherapeutic modality that targets malignant solid tumors using medium‐frequency, low‐intensity, alternating electric fields to interfere with cell division, have been used for the treatment of new diagnosis of glioblastoma, however, their administration in HGG requires further clinical evidence. The efficacy and safety of TTFields in Chinese patients with HGG were retrospectively evaluated by us in a single center. Methods We enrolled and analyzed 52 patients with newly diagnosed HGG undergoing surgery and standard chemoradiotherapy regimens from December 2019 to June 2022, and followed them until June 2023. Based on whether they used TTFields, they were divided into a TTFields group and a non‐TTFields group. Progression‐free survival (PFS) and overall survival (OS) were compared between the two groups. Results There were 26 cases in the TTFields group and 26 cases in the non‐TTFields group. In the TTFields group, the median PFS was 14.2 months (95% CI: 9.50–18.90), the median OS was 19.7 months (95% CI: 14.95–24.25) , the median interval from surgery to the start of treatment with TTFields was 2.47 months (95% CI: 1.47–4.13), and the median duration of treatment with TTFields was 10.6 months (95% CI: 9.57–11.63). 15 (57.69%) patients experienced an adverse event and no serious adverse event was reported. In the non‐TTFields group, the median PFS was 9.57 months (95% CI: 6.23–12.91) and the median OS was 16.07 months (95% CI: 12.90–19.24). There was a statistically significant difference in PFS (p = 0.005) and OS (p = 0.007) between the two groups. Conclusions In this retrospective analysis, TTFields were observed to improve newly diagnosed HGG patients' median PFS and OS. Compliance was much higher than reported in clinical trials and safety remained good.

Drug-induced liver injury is a prevalent adverse event associated with pharmaceutical agents. More significantly, there are certain drugs that present severe hepatotoxicity only during the clinical phase, consequently leading to the termination of drug development during clinical trials or the withdrawal from the market after approval. The establishment of an evaluation model that can sensitively manifest such hepatotoxicity has always been a challenging aspect in drug development. In this study, we build a liver-immune-microphysiological-system (LIMPS) to fully demonstrate the liver injury triggered by troglitazone (TGZ), a drug that was withdrawn from the market due to hepatotoxicity. Leveraging the capabilities of organ-on-chip technology allows for the dynamic modulation of cellular immune milieu, as well as the synergistic effects between drugs, hepatocytes and multiple immune cells. Through the LIMPS, we discovered that 1) TGZ can promote neutrophils to adhered hepatocytes, 2) the presence of TGZ enhances the crosstalk between macrophages and neutrophils, 3) the induction of damage in hepatocytes by TGZ at clinically relevant blood concentrations not observed in other in vitro experiments, 4) no hepatotoxicity was observed in LIMPS when exposed to rosiglitazone and pioglitazone, structurally similar analogs of TGZ, even at the higher multiples of blood drug concentration levels. As an immune-mediated liver toxicity assessment method, LIMPS is simple to operate and can be used to test multiple drug candidates to detect whether they will cause severe liver toxicity in clinical settings as early as possible.

BackgroundExposure to trauma is often associated with an increased incidence of Major Depressive Disorder (MDD), yet the mechanisms underlying MDD development post-trauma remain elusive. The microbiota-gut-brain axis has been implicated in neuropsychiatric disorders, suggesting its potential role in post-traumatic MDD (PTMDD) development. Our study aimed to assess the significance of the gut microbiome-brain interaction in PTMDD.MethodsWe conducted a bidirectional two-sample Mendelian Randomization (MR) analysis to investigate the causal relationship between the gut microbiota and both PTMDD and trauma exposure in MDD. Genome-wide association study (GWAS) summary datasets for PTMDD and trauma exposure in MDD, both derived from the UK Biobank. The PTMDD dataset included 24,090 individuals (13,393 cases and 10,701 controls), while the dataset for trauma exposure in MDD comprised 22,880 participants (13,393 cases and 9,487 controls). Additionally, gut microbiota data from the MiBioGen consortium included 14,306 European individuals across 18 diverse cohorts.ResultsOur research identified a significant negative association between the phylum Verrucomicrobia (odds ratio (OR) [95% confidence interval (CI)] =0.799 [0.684–0.933], P=0.005) and the risk of developing PTMDD, suggesting a protective role for Verrucomicrobia against PTMDD. Conversely, our findings indicate no causal effects of the gut microbiota on trauma exposure in MDD. However, reverse analysis revealed that both PTMDD and MDD influence certain bacterial traits, affecting 5 and 9 bacterial traits, respectively. Moreover, Verrucomicrobia (OR [95% CI] = 1.166 [1.051 - 1.294], P=0.004) was found to be positively impacted by trauma exposure in MDD.ConclusionOur findings provide a cause-and-effect relationship between the gut microbiota and PTMDD, contributing to our understanding of the microbiota-gut-brain axis and its role in neuropsychiatric disorder development after trauma. This information provides an opportunity for new treatment and prevention methods which are aimed at the gut-brain interaction.

AimTo evaluate the efficacy and safety of URLi (ultra rapid lispro insulin) compared to insulin lispro as bolus insulin with basal insulin using CGM in the individuals with type 2 diabetes(T2D) in China.MethodsThis was a double-blind, randomized, parallel, prospective, phase 3 study. Subjects with uncontrolled T2D were recruited and randomized 1:2 into the insulin lispro and URLi groups. Subjects received a consistent basal insulin regimen during the study and self-administered insulin lispro or URLi before each meal throughout the treatment period. Subjects underwent a 3-day continuous glucose monitoring (CGM) at the baseline and endpoint respectively, and then CGM data were analyzed. The primary endpoint was to compare the difference in postprandial glucose (PPG) control using CGM between the two groups.ResultsA total of 57 subjects with T2D completed the study. Our CGM data showed that postprandial glucose excursions after breakfast (BPPGE) in the URLi group was lower than that in the insulin lispro group (1.59 ± 1.57 mmol/L vs 2.51 ± 1.73 mmol/L, p = 0.046). 1-hour PPG was observed to decrease more in the URLi group than that in the insulin lispro group (-1.37 ± 3.28 mmol/L vs 0.24 ± 2.58 mmol/L, p = 0.047). 2-hour PPG was observed to decrease more in the URLi group than that in the insulin lispro group (-1.12 ± 4.00 mmol/L vs 1.22 ± 2.90 mmol/L, p = 0.021). The mean HbA1c level decreased by 1.1% in the URLi group and 0.99% in the insulin lispro group, with no treatment difference (p = 0.642). In the CGM profile, TBR was not significantly different between the two groups (p = 0.743). The weight gain also did not differ between the two groups (p = 0.303).ConclusionURLi can control breakfast PPG better than insulin lispro in adults with T2D in China, while it is non-inferior in improving HbA1c. The incidence of hypoglycemic and weight gain were similar between the two groups.

BackgroundGreen tea intake has been reported to improve the clinical outcomes of patients with cardiovascular diseases or cancer. It may have a certain role in the development of venous thromboembolism (VTE) among cancer patients. The current study aimed to address this issue, which has been understudied.MethodsWe carried out a retrospective study to explore the role of green tea intake in cancer patients. Patients with and without green tea intake were enrolled in a 1:1 ratio by using propensity scoring matching. The primary and secondary outcomes were VTE development and mortality 1 year after cancer diagnosis, respectively.ResultsThe cancer patients with green tea intake (n = 425) had less VTE development (10 [2.4%] vs. 23 [5.4%], p = 0.021), VTE-related death (7 [1.6%] vs. 18 [4.2%], p = 0.026), and fatal pulmonary embolism (PE) (3 [0.7%] vs. 12 [2.8%], p = 0.019), compared with those without green tea intake (n = 425). No intake of green tea was correlated with an increase in VTE development (multivariate hazard ratio (HR) 1.758 [1.476–2.040], p

In this study, the neuroprotective potential of tanshinone IIA (TIIA)-modified mesenchymal stem cells (MSC) were investigated using a murine model of lipopolysaccharide (LPS)-induced neuroinflammation. The cognitive performance of the mice was assessed using the Y-maze and Morris water maze tests, while immunofluorescence and Western blot analyses were employed to evaluate the hippocampal expression of pertinent markers and inflammatory factors, respectively. The results from the behavioral experiments demonstrated discernible differences in learning and memory abilities between the model group and the control group (P

Prothrombin time/international normalized ratio (PT/INR) is related to both antithrombotic effect and risk of bleeding. Its role in the prediction of venous thromboembolism (VTE) recurrence and bleeding for patients with acute VTE who undergo direct oral anticoagulants (DOACs) treatment is unclear, despite previous studies revealed some association between them. The predictive efficiency of INR for VTE recurrence and bleeding were analyzed in a retrospective cohort with VTE patients who underwent DOACs treatment. Then its predictive efficiency for VTE recurrence and bleeding were validated in a prospective cohort with the acquired cutoffs range, and compared with anti-Xa level, DASH and VTE-BLEED scores. In the retrospective cohort ( n = 1083), the sensitivity and specificity of INR for the prediction of VTE recurrence were 79.4% and 92.8%, respectively. The area under the curve (AUC) was 0.881 (0.803-0.960)( P = .025). The cutoff value of INR was 0.9. The sensitivity and specificity of INR for the prediction of bleeding were 85.7% and 77.9%, respectively. The AUC was 0.876 (0.786-0.967)( P 2.1)( n = 34) groups, respectively. The baseline PT/INR value at the initiation of DOACs treatment is an independent predictor for VTE recurrence and bleeding in patients with acute VTE who undergo DOACs treatment.

Abstract Background Endometriosis is a common and complex syndrome characterized by the presence of endometrial-like tissue outside the uterus. Chinese medicine has been recently found to show good efficacy in treating endometriosis. Our previous results revealed that Maqian fruit essential oil (MQEO) could inhibit the proliferation and induce apoptosis of ectopic endometrial stromal cells (EESCs), but the mechanisms remain unclear. In this study, we aim to explore the molecular mechanism of MQEO’s specific effects in EESCs. Methods We conducted a quantitative proteomics analysis by iTRAQ on EESCs treated with MQEO or DMSO. Then deep analysis was performed based on differentially expressed proteins, including Gene Ontology enrichment analysis, pathway enrichment analysis and protein interaction analysis. Candidate protein targets were subsequently verified by western blotting. Results Among 6575 identified proteins, 435 proteins exhibited altered expression levels in MQEO-treated EESCs. Of these proteins, most were distributed in signal transduction as well as immune system and the most significantly altered pathway was complement and coagulation cascades. Moreover, two differentially expressed proteins (Heme oxygenase 1 and Acyl-CoA 6-desaturase) were verified and they can be potential biomarkers for endometriosis treatment. Conclusions Our proteomic analysis revealed distinct protein expression patterns induced by MQEO treatment in EESCs, highlighting the potential of MQEO for endometriosis treatment and biomarker discovery.

Abstract Ti15Mo alloy has been regarded as one of the most potential biomedical materials due to its excellent performance. However, the low hardness and poor wear resistance of titanium alloy limit the further application. Therefore, high temperature solid carburising technology was performed on the surface of Ti15Mo alloys to prepare titanium carbide (TiC) coating with graphene (G) as the carburising agent. The microstructure, mechanical properties, and tribological properties of TiC coating under different lubricants were investigated. Results showed that TiC coating was closely bonded to the titanium substrate. The maximum thickness of TiC coating treated with 1150°C was approximately 184.02 μm, and the microhardness of alloys treated with 1100°C can achieve 1221.5 HV. All modified Ti15Mo alloys showed improved tribological performance compared to the original samples. The wear mechanisms of modified Ti15Mo alloys were abrasive wear and adhesive wear under the SBF lubricant, and the TiC coating was slightly peeled off. The overall friction coefficient and wear rate under 25% calf serum lubricant were lower than the SBF lubricant, and surface scratches were almost absent, and slight abrasive wear and adhesive wear occurred on the surface.

The utility-scale deployment of photovoltaic (PV) power plants is critical for achieving carbon peaking and carbon neutrality goals and mitigating climate change. However, the impact of a PV power plant project on the microclimate is unclear for different underlying surfaces. Therefore, PV power plants in deserts and lakes were selected to assess and compare the impact of PV array deployment on the environment by the observation. The results indicate that the PV array affected the wind pattern, the wind direction makes simple (from 10 m to 2 m), and wind speed in the PV site under two types of underlying surfaces was less than the reference site. For the PV power plant in desert, the delta (PV - REF) is increased from 0.12 m s−1 at 10 m to 0.27 m s−1 at 2 m. The counterpart in the lake is increased from 0.14 m s−1 at 10 m to 0.55 m s−1 at 2 m. However, the PV arrays had no effect on the air temperature at the center of the PV array gap. The difference in air temperature for two observation sites under two type of underlying surfaces was less than the resolution of instrument MaxiMet (0.1 °C). Instead, the heat from the PV panels is transmitted down to the land surface, causing a temperature effect in the desert and lakes. For the PV power plant in land, the arrays have heating effect on air temperature (The air temperature was 33.43 °C in the PV_land site, and 28.03 °C in the REF_land site in July, respectively). But the arrays have cooling effect on air temperature for the PV power plant in lake in the same month (PV_lake site, 28.58 °C; REF_lake site, 29.97 °C). Furthermore, evaporation is lower in the PV power plant owing to the physical shielding of PV arrays (For the land, the peak of hour evaporation (PV_land – REF_land) was 0.12 mm; for the lake, the peak of hour evaporation (PV_lake – REF_lake) was 0.32 mm). This study provides new evidence of the microclimate impact of photovoltaic array deployment on different underlying surfaces.

In the high-precision optoelectronic tracking system (OTS) based on a charge-coupled device (CCD), the boresight error extracted from the tracking image contains an undeniable delay, which directly limits the control bandwidth of visual tracking. High bandwidth means high response speed and tracking accuracy. Generally, a model-based delay compensation control method called the Smith predictor is utilized to separate time delay from the closed loop to promote the control bandwidth. However, due to the existence of errors between the established model and the real object, the improvement in the bandwidth is still limited to ensure system stability, resulting in insufficient tracking performance. In this paper, to solve the problem, a Smith predictor modified with pseudo feedforward control for the OTS is proposed. The experimental results demonstrate that the proposed method achieves significant improvements in tracking performance, reducing the maximum residual error at 1 Hz from 365 arcseconds (using the classic Smith predictor) to 283 arcseconds, a 22.5% improvement. Across the main frequency band (0.2 Hz to 2 Hz), the residual errors were consistently lower using the proposed method.

Abstract Background Alzheimer's disease (AD) and related Tauopathies are characterised by the pathologically hyperphosphorylated and aggregated microtubule‐associated protein Tau, which is accompanied by neuroinflammation mediated by activated microglia. However, the role of Tau pathology in microglia activation or their causal relationship remains largely elusive. Methods The levels of nucleotide‐binding oligomerisation domain (NOD)‐like receptor pyrin domain containing 3 (NLRP3) acetylation and inflammasome activation in multiple cell models with Tau proteins treatment, transgenic mice with Tauopathy, and AD patients were measured by Western blotting and enzyme‐linked immunosorbent assay. In addition, the acetyltransferase activity of Tau and NLRP3 acetylation sites were confirmed using the test‐tube acetylation assay, co‐immunoprecipitation, immunofluorescence (IF) staining, mass spectrometry and molecular docking. The Tau‐overexpressing mouse model was established by overexpression of human Tau proteins in mouse hippocampal CA1 neurons through the adeno‐associated virus injection. The cognitive functions of Tau‐overexpressing mice were assessed in various behavioural tests, and microglia activation was analysed by Iba‐1 IF staining and [18F]‐DPA‐714 positron emission tomography/computed tomography imaging. A peptide that blocks the interaction between Tau and NLRP3 was synthesised to determine the in vitro and in vivo effects of Tau–NLRP3 interaction blockade on NLRP3 acetylation, inflammasome activation, microglia activation and cognitive function. Results Excessively elevated NLRP3 acetylation and inflammasome activation were observed in 3xTg‐AD mice, microtubule‐associated protein Tau P301S (PS19) mice and AD patients. It was further confirmed that mimics of ‘early’ phosphorylated‐Tau proteins which increase at the initial stage of diseases with Tauopathy, including TauT181E, TauS199E, TauT217E and TauS262E, significantly promoted Tau–K18 domain acetyltransferase activity‐dependent NLRP3 acetylation and inflammasome activation in HEK293T and BV‐2 microglial cells. In addition, Tau protein could directly acetylate NLRP3 at the K21, K22 and K24 sites at its PYD domain and thereby induce inflammasome activation in vitro. Overexpression of human Tau proteins in mouse hippocampal CA1 neurons resulted in impaired cognitive function, Tau transmission to microglia and microgliosis with NLRP3 acetylation and inflammasome activation. As a targeted intervention, competitive binding of a designed Tau–NLRP3‐binding blocking (TNB) peptide to block the interaction of Tau protein with NLRP3 inhibited the NLRP3 acetylation and downstream inflammasome activation in microglia, thereby alleviating microglia activation and cognitive impairment in mice. Conclusions In conclusion, our findings provide evidence for a novel role of Tau in the regulation of microglia activation through acetylating NLRP3, which has potential implications for early intervention and personalised treatment of AD and related Tauopathies.

The introduction of new internal fixation devices and arthroscopic techniques has led to significant changes in the surgical treatment of tibial eminence fractures (TEFs) in children. In recent years, arthroscopic surgery has arisen as the gold standard for the treatment of TEFs. This popularity of arthroscopic techniques has reduced surgical complications and improved patient prognosis. In this paper, we investigate the current situation of the use of arthroscopic fixation techniques for pediatric TEFs. We searched the PubMed database using the terms “arthroscopic treatment and tibial eminence,” “arthroscopic treatment and tibial spine,” “tibial eminence avulsion”, “tibial spine fracture”, with no limit on the year of publication. From these articles, we reviewed the use of various arthroscopic TEFs fixation techniques reported in the current literature. Overall, we found that the choice of fixation method seems to have no effect on clinical outcomes or imaging results. However, if an easy, strong fixation that is less prone to epiphyseal damage is desired, as a junior practitioner, the anchor technique should be mastered first, whereas for senior practitioners, a variety of fixation techniques for TEFs should be mastered, including anchors, sutures, and screws, so that personalized fixation can be achieved with the least amount of trauma, operative time, and complications. Higher quality studies are needed in the future to provide Useful evidence to determine the optimal fixation technique in terms of clinical outcomes, function, and complications.

Engineering rock containing flaws or defects under a large water source is frequently subject to the couple influence of constant crack water pressure and geostress. To investigate the fracture behavior of precracked rock under hydromechanical coupling with constant crack water pressure, compression tests were conducted on red sandstone specimens containing a single crack of different angles using a device to realize the constant crack water pressure during loading, and the failure process of rock specimens was monitored by acoustic emission (AE) technique. The results show that the presence of constant crack water pressure has a significant promotion effect on the development of shear wing cracks, and the promotion effect is influenced by the prefabricated crack angle and water pressure. As the constant crack water pressure increases, the failure mode of the 0° precrack specimen changes from “X”- shear failure to the single oblique shear failure along the shear wing crack direction, the main failure crack of the inclined precracked specimens (precrack angles of 15°, 45°, and 60°) changes from a small acute angle with the prefabricated crack to a direction along the shear wing crack, and irregular cracks occur at the chipped prefabricated crack in the 90° precracked specimen. With an increase in the constant crack water pressure, the average energy for a single hit, cumulative AE energy, and cumulative AE hits decrease, and the proportion of the tensile cracks increases and that of the shear cracks decreases.

In this study, to investigate the factors affecting container semitrailer rollovers while driving on interchange loop ramps, a simulation model was established in TruckSim on the basis of data collected from an in-depth investigation of the vehicle, road, and driving behaviors in a real accident. The established model was validated by reproducing the accident in a simulation. The effects of vehicle speed, the height of the cargo's center of gravity, tractor-semitrailer interactions, and the radius of the circular curve on container semitrailer rollover were investigated using the established model. The results reveal that if the height of the container semitrailer is within the limits in Chinese standards and the container semitrailer is moving at a speed of less than 45.3 km/h, it can safely travel through a loop ramp with a circular curve radius of 60 m. The height of the cargo's center of gravity and the lateral load transfer ratio have a negative relationship, and a higher center of gravity reduces the safe speed for a container semitrailer traveling through a loop ramp. During rollover, the rear axle of the semitrailer first begins to roll over and then drives the tractor to overturn.

Cell culture as the cornerstone of biotechnology remains a labor-intensive process requiring continuous manual oversight and substantial time investment. In this work, we propose an integrated mini-pillar platform for in situ monitoring of multiple cellular metabolism processes, which achieves media anchoring and cell culture through an arrayed mini-pillar chip. The assembly of polyaniline (PANI)/dendritic gold-modified microelectrode biosensors exhibits high sensitivity (63.55 mV/pH) and excellent interference resistance, enabling real-time acquisition of biosensing signals. We successfully employed such integrated devices to real-time measuring pH variations in multiple cells and real-time monitoring of cell metabolism under drug interventions and to facilitate in situ assisted cultivation of 3-dimensional (3D) cell spheroids. This mini-pillar array-based cell culture platform exhibits excellent biosensing sensitivity and real-time monitoring capability, offering considerable potential for the advancement of biotechnology and medical drug development.

The power generation of bifacial photovoltaic modules is greatly related to the diffuse solar radiation component received by the rear side, but radiation component data are scarce in China, where bifacial solar market is large. Radiation components can be estimated from satellite data, but sufficient ground truth data are needed for calibrating empirical methods or training machine learning methods. In this work, a data-augmented machine learning method was proposed to estimate radiation components. Instead of using observed ground truth, far more abundant radiation component data derived from sunshine duration measured at 2,453 routine weather stations in China were used to augment samples for training a machine-learning-based model. The inputs of the model include solar radiation (either from ground observation or satellite remote sensing) and surface meteorological data. Independent validation of the model at Chinese stations and globally distributed stations demonstrates its effectiveness and generality. Using a state-of-the-art satellite product of solar radiation as input, the model is applied to construct a satellite-based radiation component dataset over China. The new dataset not only outperforms mainstream radiation component datasets, but also has significantly higher accuracy than satellite-based datasets derived from other machine learning methods trained with limited observations, indicating the superiority of our data-augmented method. In principle, this model can be applied on the global scale without additional training with local data.

Abstract Water injection, as a widely used technique to prevent coal burst, can restrain the fractured coal seam and released the energy storage. In this study, laboratory tests were firstly carried out on standard coal specimens with five different water contents (i.e., 0%, 0.6%, 1.08%, 1.5%, 2.0%, and 2.3%). The failure mode, fragment size, and energy distribution characteristics of coal specimens were investigated. Experimental results show that strength, elastic strain energy, dissipated energy, brittleness index, as well as impact energy index decrease with increasing water content. Besides, the failure mode transitions gradually from splitting ejection to tensile-shear mixed failure mode as water content increases, and average fragment size shows positively related to water content. Moreover, scanning electron microscope tests results indicate that water in coal sample mainly causes the mineral softening and defects increase. Furthermore, a numerical model containing roadway excavation was established considering the water on coal burst prevention. Modelling results revealed that water injection can reduce degree of coal burst and ejection velocity of coal blocks, while it will raise up the depth of crack zone and surface displacement of roadway. Combined with laboratory tests and numerical results, the micro mechanism, energy mechanism, and engineering significance of water injection on coal burst prevention were finally analyzed.

Abstract The “death cap”, Amanita phalloides, is the world’s most poisonous mushroom, responsible for 90% of mushroom-related fatalities. The most fatal component of the death cap is α-amanitin. Despite its lethal effect, the exact mechanisms of how α-amanitin poisons humans remain unclear, leading to no specific antidote available for treatment. Here we show that STT3B is required for α-amanitin toxicity and its inhibitor, indocyanine green (ICG), can be used as a specific antidote. By combining a genome-wide CRISPR screen with an in silico drug screening and in vivo functional validation, we discover that N-glycan biosynthesis pathway and its key component, STT3B, play a crucial role in α-amanitin toxicity and that ICG is a STT3B inhibitor. Furthermore, we demonstrate that ICG is effective in blocking the toxic effect of α-amanitin in cells, liver organoids, and male mice, resulting in an overall increase in animal survival. Together, by combining a genome-wide CRISPR screen for α-amanitin toxicity with an in silico drug screen and functional validation in vivo, our study highlights ICG as a STT3B inhibitor against the mushroom toxin.

Abstract The structure and functionality of biomacromolecules are often regulated by chemical bonds, however, the regulation process and underlying mechanisms have not been well understood. Here, by using in situ liquid-phase transmission electron microscopy (LP-TEM), we explored the function of disulfide bonds during the self-assembly and structural evolution of sulfhydryl single-stranded DNA (SH-ssDNA). Sulfhydryl groups could induce self-assembly of SH-ssDNA into circular DNA containing disulfide bonds (SS-cirDNA). In addition, the disulfide bond interaction triggered the aggregation of two SS-cirDNA macromolecules along with significant structural changes. This visualization strategy provided structure information at nanometer resolution in real time and space, which could benefit future biomacromolecules research.

Abstract Focused ultrasound ablation surgery (FUAS) is a novel therapy with a wide range of potential applications. However, synergists are crucial to the therapy process due to the ultrasonic energy's attenuation properties. As a result of the complex hypoxic environment in the tumor area and many factors, the existing synergists have limitations such as weak targeting, single imaging mode, and easy tumor recurrence after treatment. Because of the above deficiencies, this study intends to construct bio-targeted oxygen production probes consisting of Bifidobacterium that naturally target the hypoxia region of the tumor and multi-functional oxygen-producing nanoparticles equipped with IR780, perfluorohexane (PFH), CBP (carboplatin), and oxygen. The probes are expected to achieve targeted and synergistic FUAS therapy and dual-mode imaging to mediate tumor diagnosis and treatment. The oxygen and drugs carried in it are accurately released after FUAS stimulation, which is expected to alleviate tumor hypoxia, avoid tumor drug resistance, improve the effect of chemotherapy, and realize FUAS combined with chemotherapy antitumor therapy. This strategy is expected to make up for the deficiencies of existing synergists, improve the effectiveness and safety of treatment, and provide the foundation for future tumor therapy progress. Graphical Abstract

Abstract Background Achondroplasia is a congenital skeletal system malformation caused by missense variant of FGFR3 gene with an incidence of 1 per 20,000–30,000 newborns, which is an autosomal dominant inheritance disease. Despite similar imaging features, the homozygous achondroplasia is absolutely lethal due to thoracic stenosis, whereas heterozygous achondroplasia does not lead to fetal death. Case presentation A fetus with progressive rhizomelic short limbs and overt narrow chest was detected by prenatal ultrasound in the second trimester. Gene sequencing results of amniotic fluid sample indicated a rare missense variant NM_000142.4: c.1123G > T(p.Gly375Cys), leading to a glycine to cysteine substitution. Re-sequencing confirmed that it was a heterozygous variant, and thoracic stenosis was then confirmed in the corpse by radiological examination. Conclusions We identified a heterozygous variant of the FGFR3 gene as the rare pathogenic variant of severe achondroplasia in a fetus. Heterozygous variants of p.Gly375Cys may have a severe phenotype similar to homozygote. It’s crucial to combine prenatal ultrasound with genetic examination to differentiate heterozygous from homozygous achondroplasia. The p.Gly375Cys variant of FGFR3 gene may serve as a vital target for the diagnosis of severe achondroplasia.

Abstract Accurate offshore surface wind forecasting is crucial for navigation safety and disaster prevention. However, significant biases exist in forecasting sea surface winds due to the uncertainties in estimating sea surface roughness. In this study, we propose a deep learning‐based scheme (DL2023) for estimating sea surface roughness and integrate it into a regionally coupled ocean‐atmosphere‐wave model. Single‐point experiments demonstrate that DL2023 achieves a remarkable 50% reduction in the Root Mean Square Error (RMSE) compared to the four traditional schemes. During five typhoon cases in August 2020, compared to the four traditional schemes, the RMSEs of forecasted surface winds using DL2023 are reduced by 6.02%–14.75%, 11.17%–18.30%, and 11.91%–19.46% at lead times of 24, 48, and 72 hr, respectively. Thus, the DL2023 scheme, trained using data from the Atlantic Ocean, successfully improves the forecast of surface winds over the Northwest Pacific Ocean.

Drought monitoring is crucial for assessing and mitigating the impacts of water scarcity on various sectors and ecosystems. Although traditional drought monitoring relies on soil moisture data, remote sensing technology has have significantly augmented the capabilities for drought monitoring. This study aims to evaluate the accuracy and applicability of two temperature vegetation drought indices (TVDI), TVDINDVI and TVDIEVI, constructed using the Normalized Difference Vegetation Index (NDVI) and the Enhanced Vegetation Index (EVI) vegetation indices for drought monitoring. Using Guangdong Province as a case, enhanced versions of these indices, developed through Savitzky–Golay filtering and terrain correction were employed. Additionally, Pearson correlation analysis and F-tests were utilized to determine the suitability of the Standardized Precipitation Index (SPI) and the Standardized Precipitation Evapotranspiration Index (SPEI) in correlation with TVDINDVI and TVDIEVI. The results show that TVDINDVI had more meteorological stations passing both significance test levels (P

Background Extended oral anticoagulant (OA) use is recommended in patients with acute pulmonary embolism (PE) who require secondary thromboprophylaxis. Nevertheless, the optimal length of OA use for the maximum long-term benefit in this patient population has been undefined to date.Methods A retrospective study was performed to explore the role of different length of overall OA use (group 1 (≥1 year of OA use and

Dilated cardiomyopathy (DCM) is a cardiovascular disease characterized by persistent ventricular dilatation and systolic dysfunction. DCM has a variety of causes, including myocarditis; exposure to narcotics, alcohol, or other toxins; and metabolic or endocrine disorders. Genetic factors play a dominant role in 30%–40% of DCM cases. Here, we report a case of DCM with very severe heart failure. Because of the severity of heart failure, the patient underwent heart transplantation. We speculated that the patient's DCM might be due to a mutation; hence, we performed whole-exome sequencing of the patient and their parents, which showed a de novo heterozygous mutation (NM_001001431.2c.769G>A:p.E257K) in TNNT2, which was considered pathogenic according to the ACMG pathogenicity assessment. This finding expands the genetic map of DCM and TNNT2 and will be important for future studies on the genetic and disease relationships between DCM and TNNT2.

Triggering receptor expressed on myeloid cells 2 (TREM2), a pattern recognition receptor abundantly expressed on microglia, has been identified as one of the risk factors for Alzheimer’s disease (AD). Several studies have already demonstrated the relationship between TREM2 and Tau. TREM2 mutations and altered expression play an important role in Tau phosphorylation. Furthermore, the level of Tau phosphorylation is correlated with soluble TREM2 (sTREM2). However, in different stages of AD, TREM2 seems to have varying effects on Tau pathology. The explicit interaction between TREM2 and Tau, as well as how they affect AD pathology, remains unclear, and there is much evidence to the contrary that requires rational interpretation. Reviewing the dual roles of TREM2 in AD will help identify a more appropriate development strategy for targeting TREM2 to treat AD. Therefore, this review focuses on the interplay between Tau and TREM2 in relation to AD.

Ischemic stroke (IS) is a leading cause of disability, morbidity, and mortality globally. Aging affects immune function and contributes to poor outcomes of IS in elderly individuals. However, little is known about how aging-related genes (ARGs) are involved in IS. In this study, the relationship between ARGs and IS immune microenvironment biomarkers was explored by bioinformatics. Two IS microarray datasets (GSE22255, GSE16561) from human blood samples were analyzed and 502 ARGs were identified, from which 29 differentially expressed ARGs were selected. Functional analysis revealed that 7 of these ARGs (IL1B, FOS, JUN, CXCL5, PTGS2, TNFAIP3 and TLR4) were involved in five top enriched pathways (IL-17 signaling pathway, TNF signaling pathway, Rheumatoid arthritis, NF-kappa B signaling pathway and Pertussis) related to immune responses and inflammation. Five hub DE-ARGs (IL2RB, FOS, IL7R, ALDH2 and BIRC2) were identified using machine learning algorithms, and their association with immune-related characteristics was confirmed by additional tests. Single-cell sequencing dataset GSE129788 was retrieved to analyze aging molecular-related features, which was in accordance with microarray datasets. Clustering analysis revealed two subtypes of IS, which were distinguished by their differential expression of genes related to the NF-kappa B signaling pathway. These findings highlight the importance of ARGs in regulating immune responses in IS and suggest potential prevention and treatment strategies as well as guidelines for future research.

Summary: Background: Landscape fire smoke, including smoke from all vegetation burning in natural and cultural landscapes, remains a threat to the health of the population. However, the future health impacts of landscape fire smoke in China have not been sufficiently investigated. We aimed to estimate the mortality risk attributable to landscape fire-related PM2·5 under different scenarios. Methods: In this health impact assessment study, we used the projected population and landscape fire-related PM2·5 concentration to calculate deaths attributable to short-term exposure to landscape fire smoke PM2·5 during 2021–2100. We did the analysis in three defined future periods: 2021–40 (near term), 2051–70 (medium term), and 2081–2100 (long term), with 1986–2005 as the historical period. We used fire-specific short-term epidemiological functions with the regional parameters specific to China. We assessed the mortality risks of landscape fire-related smoke and further identified their spatiotemporal distribution under two shared socioeconomic pathway (SSP) scenarios: SSP1–2·6, an optimistic scenario with strict control of carbon emissions, and SSP2–4·5, an intermediate scenario with weaker control of carbon emissions. Findings: The national mortality rate attributable to short-term exposure (ie, a few days) to landscape fire-related PM2·5 is projected to increase compared with historical values. The national deaths attributable to landscape fire smoke PM2·5 could peak in 2021–40, with increases of 28·10% (95% CI 14·08–53·11) under the SSP1–2·6 scenario and 37·38% (14·08–53·11) under the SSP2–4·5 scenario. Deaths would then decrease slightly during 2051–70 and 2081–2100. The provinces with the highest projected number of deaths attributable to landscape fire-related PM2·5 are located in east and south-central China, and those with the largest percentage increase in projected deaths are located in northwest and southwest China. Interpretation: Our results suggest that global warming could increase the contribution of landscape fire smoke to the total PM2·5 concentration, leading to an increase in the mortality rate in China. Our findings could help policy makers implement effective interventions in hotspot areas during different periods to reduce the impact of landscape fire smoke on human health. Funding: The National Natural Science Foundation of China, National Key Research and Development Program of China, and the Wellcome Trust.