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Abstract Long‐term exposure to moisture leads to a gradual deterioration of performance and reduced service life of glass fibre‐reinforced epoxy resin (GFRP) material in composite insulators. Therefore, it is necessary to analyse the moisture absorption characteristics of GFRP material and the evolution of damage to their internal interface properties. Moisture absorption tests on GFRP rod material used in composite insulators to obtain their three‐dimensional diffusion coefficients are conducted. Atomic force microscopy was then employed to obtain the composite material system's fibre/matrix interfacial phase parameters. Furthermore, a finite element model incorporating representative volume elements with interfacial phases and a mesoscale transient moisture absorption finite element model for the composite material was established. Finally, the moisture absorption characteristics of GFRP material and the evolution of damage to the interfacial phase under thermal‐humidity cycling conditions were investigated. The results showed that the diffusion coefficient along the fibre direction in GFRP material was higher than that in the perpendicular direction. The moisture diffusion finite element model, incorporating an anisotropic interfacial phase, fitted the anisotropic diffusion coefficients of GFRP material more accurately. As moisture invaded the GFRP material, the mismatch stresses continuously increased during the moisture absorption. Moreover, the non‐uniform arrangement of fibres resulted in uneven distribution of moisture‐induced stresses inside the material, leading to higher mismatch stresses in areas with dense fibre arrangements in the matrix. Prolonged high and low humidity cycles led to the development of micro‐cracks, micro‐porosity, and interface debonding along the fibre direction at the GFRP material interfaces, thereby affecting the anisotropic moisture absorption characteristics of the material. The findings of this study provide valuable insights into the mechanisms underlying the deterioration of GFRP material in composite insulator rods due to moisture degradation.

Nowadays, biopolymer stabilization as a promising eco-friendly approach in soft ground improvement has attracted wide attentions. However, the feasibility of using biopolymer as a green additive of cement-stabilized dredged sediment (CDS) with high water content is still unknown. In this study, guar gum (GG) and xanthan gum (XG) were adopted as typical biopolymers, and a series of unconfined compressive strength (UCS), splitting tensile strength (STS) and scanning electron microscopy (SEM) tests were performed to evaluate the mechanical and microstructural properties of XG- and GG-modified CDSs considering several factors including biopolymer modification, binder–soil ratio and water–solid ratio. Furthermore, the micro-mechanisms revealing the evolutions of mechanical properties of biopolymer-modified CDS were analyzed. The results indicate that the addition of XG can effectively improve the strength of CDS, while the GG has a side effect. The XG content of 9% was recommended, which can improve the 7 d- and 28 d-UCSs by 196% and 51.8%, together with the 7 d- and 28 d-STSs by 118.3% and 42.2%, respectively. Increasing the binder–soil ratio or decreasing the water–solid ratio significantly improved the strength gaining but aggravated the brittleness characteristics of CDS. Adding XG to CDS contributed to the formation of microstructure with more compactness and higher cementation degrees of ordinary Portland cement (OPC)-XG-stabilized DS (CXDS). The micro-mechanism models revealing the interactions of multiple media including OPC cementation, biopolymer film bonding and bridging effects inside CXDS were proposed. The key findings confirm the feasibility of XG modification as a green and high-efficiency mean for improving the mechanical properties of CDS.

Abstract In recent years, A series of environmental problems caused by air pollution have attracted widespread attention. Air quality forecasting has become an indispensable part of people’s daily life. However, the traditional air quality prediction (AQP) model WRF-CMAQ simulation system faces several challenges: (1) the fuzziness of pollutant formation mechanism; (2) the hardness of integrating the features of meteorological conditions; (3) the difficulty of cooperating among monitoring stations. To deal with these challenges, we propose a multi-task station cooperative air quality prediction (MTSC-AQP) system for sustainable development. The MTSC-AQP system contains three modules: air quality analysis, a WRF-LSTM module for initial pollutant prediction, and multi-station cooperative AQP. Through air quality analysis, it can calculate the air quality index (AQI) and analyze the correlation between pollutants and meteorological conditions. Then, the WRF-LSTM module integrates spatio-temporal multi-source data to forecast the initial concentration of pollutants. Finally, the system incorporates the gravity model to predict the final AQI. Extensive experiments conducted on real-world datasets show the effectiveness of forecasting the AQI by using the MTSC-AQP system.

Abstract Background Although recent studies provide mechanistic understanding to the pathogenesis of radiation induced lung injury (RILI), rare therapeutics show definitive promise for treating this disease. Type II alveolar epithelial cells (AECII) injury in various manner results in an inflammation response to initiate RILI. Results Here, we reported that radiation (IR) up-regulated the TNKS1BP1, causing progressive accumulation of the cellular senescence by up-regulating EEF2 in AECII and lung tissue of RILI mice. Senescent AECII induced Senescence-Associated Secretory Phenotype (SASP), consequently activating fibroblasts and macrophages to promote RILI development. In response to IR, elevated TNKS1BP1 interacted with and decreased CNOT4 to suppress EEF2 degradation. Ectopic expression of EEF2 accelerated AECII senescence. Using a model system of TNKS1BP1 knockout (KO) mice, we demonstrated that TNKS1BP1 KO prevents IR-induced lung tissue senescence and RILI. Conclusions Notably, this study suggested that a regulatory mechanism of the TNKS1BP1/CNOT4/EEF2 axis in AECII senescence may be a potential strategy for RILI.

Abstract Background Acute gouty arthritis (AGA) is classified as ‘arthritis’ in traditional Chinese medicine (TCM) theory. Shirebi granules (SGs), derived from the classic prescription SiMiaoWan, exerts satisfying therapeutic efficacy in ameliorating AGA clinically. However, the underlying mechanisms of SGs against AGA remain unclarified. Methods AGA-related biological processes, signal pathways and biomarker genes were mined from the GEO database through bioinformatics. SGs components were systematically recognized using the UPLC-Q-TOF–MS/MS. A correlation network was established based on the biomarker genes and the chemical components, from which the signal pathway used for further study was selected. Finally, we established an AGA model using SD rats injected with monosodium urate (MSU) in the ankle joint for experimental validation. A combination of behavioral tests, H&E, safranin O- fast green, western blotting, and immunofluorescence were employed to reveal the mechanism of action of SGs on AGA. Results The deterioration of AGA was significantly related to the imbalance between immunity and inflammation, neutrophil chemotaxis and inflammatory factor activation. HDAC5, PRKCB, NFκB1, MPO, PRKCA, PIK3CA were identified to be the candidate targets of SGs against AGA, associated with neutrophil extracellular traps (NETs) signal pathway. Animal experiments demonstrated that SGs effectively repaired cartilage damage, blocked TLR4 activation, and inhibited the expression of NETs indicators and inflammatory factors. In addition, SGs prominently alleviated joint redness and swelling, improved joint dysfunction, inhibited inflammatory infiltration of AGA rats. Conclusion Our data reveal that SGs may effectively alleviate the disease severity of AGA by suppressing NETs-promoted imbalance between immunity and inflammation.

Obesity is a major risk factor and pathological basis for several chronic diseases such as diabetes, cardiovascular diseases, and tumors. It has now become a global public health issue. With the increasing prevalence of obesity, research and application of natural anti-obesity drugs have become a continuous focus of attention. Tea polyphenols (TP), collectively known as polyphenolic substances in tea, are abundant and significant in their effects in tea. Numerous studies have shown that tea polyphenols have good anti-obesity effects and promising prospects. This article reviews the research progress on tea polyphenols and their anti-obesity effects in recent years, focusing on in vitro, animal, and clinical studies. It discusses the mechanisms of preventing and treating obesity through tea polyphenols, including the regulation of intestinal microbiota composition, modulation of inflammatory response, promotion of energy expenditure, regulation of enzyme activity, and inhibition of lipid synthesis and absorption. The aim is to lay a foundation for the development of natural tea polyphenol-based weight-loss foods or drugs.

Tumor metastasis, the apex of cancer progression, poses a formidable challenge in therapeutic endeavors. Circulating tumor cells (CTCs), resilient entities originating from primary tumors or their metastases, significantly contribute to this process by demonstrating remarkable adaptability. They survive shear stress, resist anoikis, evade immune surveillance, and thwart chemotherapy. This comprehensive review aims to elucidate the intricate landscape of CTC formation, metastatic mechanisms, and the myriad factors influencing their behavior. Integral signaling pathways, such as integrin-related signaling, cellular autophagy, epithelial-mesenchymal transition, and interactions with platelets, are examined in detail. Furthermore, we explore the realm of precision nanomedicine design, with a specific emphasis on the anoikis‒platelet interface. This innovative approach strategically targets CTC survival mechanisms, offering promising avenues for combatting metastatic cancer with unprecedented precision and efficacy. The review underscores the indispensable role of the rational design of platelet-based nanomedicine in the pursuit of restraining CTC-driven metastasis.

Abstract Glioma is the most common primary brain tumor, and targeting glioma stem cells (GSCs) has become a key aspect of glioma treatment. In this study, we discovered a molecular network in which circRNA forms an R-loop structure with its parental gene to regulate the biological behavior of GSCs. Genes with abnormal expression in GSCs were screened using RNA-seq and circRNA microarray analyses. The study results showed that high expression of YTHDC1 in GSCs promoted the transportation of N6-methyladenosine (m6A)-modified circPOLR2B from the nucleus to the cytoplasm. Decreased circPOLR2B levels in the nucleus resulted in fewer R-loop structures formed with its parental gene POLR2B. This reduction in R-loop structures relieved the inhibitory effect on POLR2B transcription and upregulated PBX1 expression through alternative polyadenylation (APA) action, thereby promoting the malignant biological behavior of GSCs. Knockdown of YTHDC1, POLR2B, and PBX1 reduced xenograft tumor volume and prolonged the survival of nude mice. The YTHDC1/circPOLR2B/POLR2B/PBX1 axis plays a regulatory role in the biological behavior of GSCs, offering potential targets and novel strategies for the treatment of glioma.

Penaeus vannamei is an important shrimp species that is farmed globally, owing to its fast growth and good environmental adaptability. However, vibriosis outbreaks, such as acute hepatopancreatic necrosis disease and translucent post-larva disease, have become a considerable constraint on the development of the shrimp aquaculture industry globally in recent years. Due to the negative consequences associated with the use of antibiotics to control bacterial diseases, alternative technologies, such as improving shrimp immunity, the nutrition level of shrimp diets, and the ecological environment of shrimp ponds by using probiotics, have been developed. Owing to the limitations related to the sourcing and cost of fish meal, a large amount of vegetable protein is often used as a fish meal substitute in shrimp artificial feed, which is not only difficult for the shrimp to digest and absorb but can also lead to nutritional antagonism. In order to improve the health status of aquaculture animals by providing high-quality feed, the development and optimization of fermented feed have received extensive attention. Probiotics in fermented feed can produce exogenous cellulase, protease, amylase, and other digestive enzymes in the digestive tract of farmed animals, which can improve the feed utilization rate, promote growth performance, and enhance the immunity of shrimp.In this study, in order to explore the application effects of shrimp feed fermented by different probiotic bacteria, probiotic strains, including Bacillus subtilis, Saccharomyces cerevisiae, and Lactobacillus acidophilus, were used individually and in combination for the fermentation of commercial feed and fed to shrimp (P. vannamei) for 28 days. The survival, body length growth, specific growth, and feed conversion rates of the shrimp were analyzed, and the density of Vibrio in vitro and in vivo, as well as relevant immune indicators in the serum, were analyzed. Furthermore, ammonia nitrogen and nitrite nitrogen concentrations in the water column were compared between the groups.The results demonstrated that the survival rates of shrimp in the fermented feed groups of B. subtilis, L. acidophilus, and complex bacteria were 8.54%, 8.54%, and 9.76%, respectively, which were significantly higher than that of the control group (P < 0.05). The body length growth rates in the B. subtilis and L. acidophilus groups were significantly higher than that of the control group (P < 0.05), while the feed conversion rate in the L. acidophilus group was significantly decreased compared with that of the control group (P < 0.05). There was no significant difference in the specific growth rate of shrimp between the experimental groups and the control group (P > 0.05). Fermented feed can affect the composition of bacteria in the hepatopancreas of shrimp. The density of Vibrio in the hepatopancreas of shrimp in each experimental group was significantly lower than that in the control group on days 14 and 21 of the experiment (P < 0.05). The feeding of different fermented feed in the short term (within 14 days) had no significant effect on reducing the total density of Vibrio in the water. However, feeding B. subtilis and L. acidophilus fermented feed significantly reduced the Vibrio density in the water body on day 21 (P < 0.05). In addition, the serum total protein concentration in each experimental group was significantly higher than that in the control group (P < 0.05). The activities of serum peroxidase, superoxide dismutase, and phenoloxidase in the L. acidophilus fermented feed group increased significantly compared with those of the other experimental and control groups (P < 0.05). The activities of serum peroxidase and phenoloxidase in the serum of shrimp fed S. cerevisiae fermented feed were significantly higher than those of the control group (P < 0.05). Complex bacteria-fermented feed could significantly increase the activities of serum lysozyme, peroxidase, and phenoloxidase (P < 0.05). However, the activity of the detected immune-related enzymes in the B. subtilis group did not increase significantly compared with that of the control group (P > 0.05), except for the activity of total serum protein, which was higher than that of the control group. The results also revealed that the concentration of ammonia nitrogen and nitrite nitrogen in the water group of each experimental group at the end of the experiment was significantly lower compared to that of the control group. S. cerevisiae and L. acidophilus groups had the best effect in reducing the concentration of ammonia nitrogen and nitrite nitrogen in the water, respectively.In summary, shrimp feed fermented by B. subtilis, S. cerevisiae, and L. acidophilus singly or in combination could improve the survival rate, growth performance, and immunity of shrimp to a degree, and reduce the concentration of ammonia nitrogen and nitrite nitrogen in aquaculture water. Moreover, L. acidophilus shows great potential as a candidate probiotic for shrimp feed fermentation. The results of this study provide a theoretical basis for the development of shrimp fermentation feed, which can improve the feed utilization and survival rates of shrimp in aquaculture.

Abstract Antifungal echinocandins inhibit the biosynthesis of β−1,3-glucan, a major and essential polysaccharide component of the fungal cell wall. However, the efficacy of echinocandins against the pathogen Aspergillus fumigatus is limited. Here, we use solid-state nuclear magnetic resonance (ssNMR) and other techniques to show that echinocandins induce dynamic changes in the assembly of mobile and rigid polymers within the A. fumigatus cell wall. The reduction of β−1,3-glucan induced by echinocandins is accompanied by a concurrent increase in levels of chitin, chitosan, and highly polymorphic α−1,3-glucans, whose physical association with chitin maintains cell wall integrity and modulates water permeability. The rearrangement of the macromolecular network is dynamic and controls the permeability and circulation of the drug throughout the cell wall. Thus, our results indicate that echinocandin treatment triggers compensatory rearrangements in the cell wall that may help A. fumigatus to tolerate the drugs’ antifungal effects.

Abstract Background Parkinson’s disease (PD) is a serious neurodegenerative disease that brings great stress to the physical and mental health of patients. At the same time, long-term treatment will also bring great economic losses and social burden to the family and society, especially after COVID-19 pandemic. The aim of this study is to analyze the current status of stress perception and anxiety in patients with PD and explore the influencing factors after the COVID-19 pandemic. Methods This study used the convenient sampling method to select the research objects of patients with PD who were outpatients or inpatients in a general public hospital in Hangzhou, Zhejiang Province, and the survey time was from February 2023 to March 2023. The measurements included the General information questionnaire, The Perceived Stress Scale (PSS) and The Self Rating Anxiety Scale (SAS). SPSS 21.0 software was used for data statistical analysis. Result 394 out of 420 patients with PD completed the questionnaire. The stress perception score of PD was (16.41 ± 6.435) and the anxiety score was (54.77 ± 10.477). The stress perception scores of patients with PD were significantly different in gender, age, educational, occupation, nature of costs, time of sleep, quality of sleep, duration of disease, way of medical treatment and anxiety level (p

Abstract The primary catalyst for nonalcoholic fatty liver disease (NAFLD) is widely recognized as the induction of lipotoxicity in hepatocytes by an excess of fatty acids. In China, Penthorum chinense Pursh (PcP) is commonly employed as a functional food due to its known hepatoprotective properties. The present study aimed to investigate the influence of PcP extract on in vivo and in vitro models of NAFLD. We found that PcP extract can attenuate palmitic acid (PA)‐induced lipotoxicity in HepG2 cells. PA was observed to trigger pyroptosis, as indicated by the increased expression of NLRP3 and GSDMD/N, activation of Caspase‐1, and subsequent release of IL‐1β and IL‐18. However, these changes were reversed after PcP was administered. Furthermore, the application of an NLRP3 agonist inhibited the protective effects of PcP on lipotoxicity, indicating that PcP decreased lipotoxicity by inhibiting the NLRP3/Caspase‐1/GSDMD pathway. Ultimately, we established a rat model of NAFLD through the administration of a high‐fat diet (HFD), followed by the oral delivery of PcP extracts. The results demonstrated that the administration of PcP extract effectively decreased dyslipidemia and hepatic steatosis, which coincided with a decrease in hepatic pyroptosis through modulation of the NLRP3/Caspase‐1/GSDMD pathway in liver tissues. Overall, our findings provide insight into the mechanism by which PcP extracts alleviate hepatic steatosis, highlighting the potential significance of modulating the NLRP3/Caspase‐1/GSDMD pathway in the context of pyroptosis.

Abstract Hyperbilirubinaemia is a prevalent condition during the neonatal period, and if not promptly and effectively managed, it can lead to severe bilirubin-induced neurotoxicity. Sunflower seeds are a nutrient-rich food source, particularly abundant in linoleic acid. Here, we provide compelling evidence that lactating maternal mice fed a sunflower seed diet experience enhanced neurological outcomes and increased survival rates in hyperbilirubinemic offspring. We assessed histomorphological indices, including cerebellar Nissl staining, and Calbindin staining, and hippocampal hematoxylin and eosin staining. Furthermore, we observed the transmission of linoleic acid, enriched in sunflower seeds, to offspring through lactation. The oral administration of linoleic acid-rich sunflower seed oil by lactating mothers significantly prolonged the survival time of hyperbilirubinemic offspring mice. Mechanistically, linoleic acid counteracts the bilirubin-induced accumulation of ubiquitinated proteins and neuronal cell death by activating autophagy. Collectively, these findings elucidate the novel role of a maternal linoleic acid-supplemented diet in promoting child health.

Abstract The orientation and shape of ceramics grains was always neglected, resulting in a lot of information during sintering has not been excavated. In this study, a modified phase-field model in order to express the anisotropy of grain boundary energy is developed. The effects of the anisotropy of grain boundary energy on the grain orientation and shape evolution are investigated in detail. The ferroelectric ceramic thick films are prepared by tape casting. The comparison of experiment and simulation results shows that the anisotropy of grain boundary energy results in uneven grain orientation and bimodal grain size distribution. The quantitative analysis of grain microstructures helps to establish a relationship with the degree of anisotropy of grain boundary energy. Our findings provide a new way to judge the degree of anisotropy by calculating the relevant parameters in the SEM images of ceramics materials.

Abstract Modern radar systems often face various interference signals in complex and rapidly changing electronic environments. The task of suppressing this interference in the radar echo signal to extract vital information is challenging. A radar interference suppression method is proposed based on a generative adversarial network (GAN). This method effectively recovers the target signal from the echo signal, which contains interference and noise, by leveraging the powerful fitting ability of GAN. Specifically, this method was tested using coherent suppression interference, smart noise interference, and noise frequency modulation suppression interference. We compared the proposed GAN method with recurrent neural network, short‐time Fourier transform time‐varying filtering, short‐time fractional Fourier transform time‐varying filtering algorithms and RNN approach. The results show that the interference suppression algorithm based on GAN is superior to the other three algorithms.

Abstract Background Recently, the application of deep learning (DL) has made great progress in various fields, especially in cancer research. However, to date, the bibliometric analysis of the application of DL in cancer is scarce. Therefore, this study aimed to explore the research status and hotspots of the application of DL in cancer. Methods We retrieved all articles on the application of DL in cancer from the Web of Science database Core Collection database. Biblioshiny, VOSviewer and CiteSpace were used to perform the bibliometric analysis through analyzing the numbers, citations, countries, institutions, authors, journals, references, and keywords. Results We found 6,016 original articles on the application of DL in cancer. The number of annual publications and total citations were uptrend in general. China published the greatest number of articles, USA had the highest total citations, and Saudi Arabia had the highest centrality. Chinese Academy of Sciences was the most productive institution. Tian, Jie published the greatest number of articles, while He Kaiming was the most co-cited author. IEEE Access was the most popular journal. The analysis of references and keywords showed that DL was mainly used for the prediction, detection, classification and diagnosis of breast cancer, lung cancer, and skin cancer. Conclusions Overall, the number of articles on the application of DL in cancer is gradually increasing. In the future, further expanding and improving the application scope and accuracy of DL applications, and integrating DL with protein prediction, genomics and cancer research may be the research trends.

A method for the simultaneous determination of benzimidazoles and their metabolites in dairy products was established using ultra high performance liquid chromatography-tandem mass spectrometry (MS). After extracting the samples with acetonitrile containing 0.2% formic acid, the extracts were centrifuged and purified by solid phase extraction column, and then separated by UPLC HSS T3 chromatographic column, determined in multi reaction monitoring (MRM) method with a positive ESI mode. The results showed that the linear correlation coefficient (r) within the range of 1.0~50 μg/L was greater than 0.995 (except for triclabendazole, which was 0.9578). The method had a limit of detection (LOD) (S/N=3) of 0.002 mg/kg (except for albendazole-2-aminosulfone, thiabendazole, and thiabendazole-5-hydroxy, which were 0.003 mg/kg). The limit of quantitation (LOQ) (S/N=10) was 0.005 mg/kg (except for albendazole-2-aminosulfone, thiabendazole, and thiabendazole-5-hydroxy, which were 0.010 mg/kg). The recoveries at three spiked levels of 0.005, 0.01 and 0.05 mg/kg ranged from 62.5% to 117.6%, with relative standard deviations (RSD) between 1.92% and 12.17%. The method is simple to operate, highly sensitive, and suitable for the quantitative analysis of benzimidazoles and their metabolites in dairy products.

The problem of surface deformation caused by coal mining is acute and usually lasts for a long time. During coal mining, the movement of the overlying strata has a broad range of influences, which may cause surface deformation, surface cracking, and damage to structures (buildings). However, continuous deformation monitoring data are often scarce in practice, making it challenging to predict the surface deformation caused by coal mining. In this context, this paper takes Sichuan’s Guanshan coalfield as the research object and proposes a comprehensive method integrating interferometric synthetic aperture radar (InSAR) technology, the FLAC3D finite difference software, and the probability integral method to predict the surface deformation caused by mining a thin seam of coal. The results show that the trend of surface deformation estimated by the numerical simulation agrees well with the results of InSAR data and the probability integral model when using InSAR historical deformation data to invert the parameters of rock mechanics in the numerical simulation, which is beneficial to improving the reliability of the simulation results. The calculations of the probability integral method are close to the predictions of the FLAC3D numerical simulation, and a settlement deformation of 0.68 ​m is expected to occur in the Guanshan coalfield area. The comprehensive prediction method proposed in this paper effectively enhances the accuracy of surface deformation prediction under the action of mining and can provide a reference for predicting the surface subsidence of similar coal mines.

Abstract Background Percutaneous coronary intervention (PCI) with primary stenting, which stands for stent implantation regardless of obtaining satisfactory results with balloon angioplasty, has superseded conventional plain old balloon angioplasty with provisional stenting. With drug-coated balloon (DCB), primary DCB angioplasty with provisional stenting has shown non-inferiority to primary stenting for de novo coronary small vessel disease. However, the long-term efficacy and safety of such a strategy to the primary stenting on clinical endpoints in de novo lesions without vessel diameter restrictions remain uncertain. Study design The REC-CAGEFREE I is an investigator-initiated, multicenter, randomized, open-label trial aimed to enroll 2270 patients with acute or chronic coronary syndrome from 43 interventional cardiology centers in China to evaluate the non-inferiority of primary paclitaxel-coated balloons angioplasty to primary stenting for the treatment of de novo, non-complex lesions without vessel diameter restrictions. Patients who fulfill all the inclusion and exclusion criteria and have achieved a successful lesion pre-dilatation will be randomly assigned to the two arms in a 1:1 ratio. Protocol-guided DCB angioplasty and bailout stenting after unsatisfactory angioplasty are mandatory in the primary DCB angioplasty group. The second-generation sirolimus-eluting stent will be used as a bailout stent in the primary DCB angioplasty group and the treatment device in the primary stenting group. The primary endpoint is the incidence of Device-oriented Composite Endpoint (DoCE) within 24 months after randomization, including cardiac death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularization. Discussion The ongoing REC-CAGEFREE I trial is the first randomized trial with a clinical endpoint to assess the efficacy and safety of primary DCB angioplasty for the treatment of de novo, non-complex lesions without vessel diameter restrictions. If non-inferiority is shown, PCI with primary DCB angioplasty could be an alternative treatment option to primary stenting. Trial registration Registered on clinicaltrial.gov (NCT04561739).

Abstract Background With advancements in chronic total coronary occlusion (CTO) recanalization techniques and concepts, the success rate of recanalization has been steadily increasing. However, the current data are too limited to draw any reliable conclusions about the efficacy and safety of drug-coated balloons (DCBs) in CTO percutaneous coronary intervention (PCI). Herein, we conducted a meta-analysis to confirm the efficacy of DCB in CTO PCI. Methods We systematically searched PubMed, Web of Science and Embase from inception to July 25, 2023. The primary outcome was major advent cardiovascular events (MACE), including cardiac death, nonfatal myocardial infarction (MI), target lesion revascularization (TLR), and target vessel revascularization (TVR). The follow-up angiographic endpoints were late lumen enlargement (LLE), reocclusion and restenosis. Results Five studies with a total of 511 patients were included in the meta-analysis. Across studies, patients were predominantly male (72.9-85.7%) and over fifty years old. The summary estimate rate of MACE was 13.0% (95% CI 10.1%-15.9%, I2 = 0%, p = 0.428). The summary estimate rates of cardiac death and MI were 2.2% (95% CI 0.7%-3.7%, I2 = 0%, p = 0.873) and 1.2% (95% CI -0.2-2.6%, I2 = 13.7%, p = 0.314), respectively. Finally, the pooled incidences of TLR and TVR were 10.1% (95% CI 5.7%-14.5%, I2 = 51.7%, p = 0.082) and 7.1% (95% CI 3.0%-11.2%, I2 = 57.6%, p = 0.070), respectively. Finally, the summary estimate rates of LLE, reocclusion and restenosis were 59.4% (95% CI 53.5–65.3%, I2 = 0%, p = 0.742), 3.3% (95% CI 1.1–5.4%, I2 = 0%, p = 0.865) and 17.5% (95% CI 12.9–22.0%, I2 = 0%, p = 0.623), respectively. Conclusion Accordingly, DCB has the potential to be used as a treatment for CTO in suitable patients.

Abstract Localized magnetic moments in non-magnetic materials, by interacting with the itinerary electrons, can profoundly change the metallic properties, developing various correlated phenomena such as the Kondo effect, heavy fermion, and unconventional superconductivity. In most Kondo systems, the localized moments are introduced through magnetic impurities. However, the intrinsic magnetic properties of materials can also be modulated by the dimensionality. Here, we report the observation of Kondo effect in a heterodimensional superlattice VS2-VS, in which arrays of the one-dimensional (1D) VS chains are encapsulated by two-dimensional VS2 layers. In such a heterodimensional Kondo superlattice, we observe the typical Kondo effect but with intriguing anisotropic field dependence. This unique anisotropy is determined to originate from the magnetic anisotropy which has the root in the unique 1D chains in the structure, as corroborated by the first-principles calculation. Our results open up a novel avenue of studying exotic correlated physics in heterodimensional materials.

Abstract The Tibetan Plateau contains the largest numbers of glaciers outside the polar regions, yet the initiation times of glacial advances remain unclear. The potential relics of original moraines might be preserved in the sedimentary basins. Here, we present sedimentological and geochronological data from five boreholes located upstream of the Tsangpo Gorge, Eastern Himalayan Syntaxis. Our findings reveal that fluvial sediment accumulation began over 2.5 million of years ago due to enhanced rock uplift downstream, and extensive glacial advances occurred after ~0.75 million of years. Notably, the earliest extensive glacial advance (~0.75 million of years) is considerably younger than the formation of the Tsangpo Gorge (>2.5 million of years). Following the initiation of this glacial advance, the Eastern Himalayan Syntaxis experienced rapid exhumation of approximately 1.3–1.6 kilometers. Such geomorphological processes and exhumation history suggest that rock uplift, rather than glacial damming, played a pivotal role in maintaining the stability of the knickpoints on the southeastern margins of the Tibetan Plateau.

Abstract Background Calcified lesions are one of the most challenging cases for PCI, where optimal angiographic results and satisfying outcomes are hard to achieve. Methods We evaluated the baseline clinical, procedures characteristics and outcomes of patients with severe coronary artery calcification (CAC) who underwent coronary intravascular lithotripsy (IVL) and rotational atherectomy (RA). Results Respectively 152 and 238 patients who underwent IVL and RA are enrolled from January 2023 to November 2023. Regarding demographic characteristics, the gender proportion, medical history of PCI and smoke history among groups reach statistical significance. Left anterior descending and right coronary artery were the main vessels treated in both groups. The 2.5 and 3.0 mm IVL balloons and 1.5 mm burr were the most commonly used. 99.3% cases were successfully implanted drug-eluting stents after IVL balloon pre-treatment, which was higher than in the group treated with RA. During hospitalization, there were no serious adverse events in the IVL group, but there were two adverse events in the RA group. Procedural complications were higher in the RA group than the IVL group (5.5% vs. 0.7%, P = 0.027). Conclusions IVL appears to be safe and effective for the treatment of severe CAC lesions compared to RA.

To prepare bioactive peptides from rapeseed cake directly, the superfine grinding technology was used，and the resulting rapeseed cake superfine powder was used as the material. Single-factor experiments and response surface analysis were used to optimize the preparation extraction. The active peptides were purified by membrane separation and Sephadex G-15 membrane separation, and their antioxidant activity and structure were evaluated. The results showed that the optimal preparation conditions were as follows: grinding time 30 min, solid-to-liquid ratio 1:20(g/mL), pH2.94, enzyme dosage 6300 U/g, temperature 55 ℃, and enzymatic hydrolysis time 2.25 h. Under these conditions, the yield of peptides could reach 83.28%. The F-2 fraction from hydrolysates with molecular mass less than 1000 Da showed good antioxidant activity, with an ABTS+ free radical eliminating rate of 71.62% at a concentration of 1 mg/mL. Furthermore, five peptides were identified, namely PF, SF, TF, IAIPF, and PLDLL which were predicted to have much higher activity. Overall, the results of this study can provide a theoretical basis for the exploration of bioactive peptides directly from rapeseed cakes.

In order to explore the effects of grinding strength on the physicochemical properties and protein extraction of rapeseed meal powder, cryogenic superfine milling was used to prepare six kinds of rapeseed meal powders according to the grinding time (5, 10, 15, 20, 30, 40, and 60 min), namely SGR-5, SGR-10, SGR-15, SGR-20, SGR-30, SGR-40, SGR-60, and conventional crushing one was used as a control, named GR. The results showed that the structure of the rapeseed meal powder was easily destroyed by a moderate superfine grinding compared with the conventional crushing, which was followed by a reduction in their particle size distribution, insoluble dietary fiber content, and water/oil holding capacity, thereby increasing the protein extraction rate. While the grinding process had almost no effect on their total dietary fiber content. Specially, a minimum particle size of the powder would be gotten when grinding for 40 min, about 16 μm (D50), and further grinding would cause the aggregation of powder particles. Moreover, 30 min of superfine grinding was the optimal condition for the extraction of rapeseed meal protein by alkali-extraction. In addition, the alkali pH was another important parameter for the extraction of rapeseed meal protein.

Abstract Background The optimal timing of performing ICSI on immature oocytes for POSEIDON patients is still unknown to get better early embryonic development outcomes. The purpose of this study was to implore the most appropriate time to carry out ICSI on in vitro maturation GV and MI oocytes for POSEIDON patients. Methods Two hundred thirty-nine immature oocytes from 163 POSEIDON patients were prospectively performed ICSI at different timings: P-ICSI (ICSI was performed on in vitro matured oocytes 4–6 h after the first polar body extrusion, N = 81), R-ICSI (ICSI was performed on in vitro matured oocytes less than 4 h after the first polar body extrusion, N = 80), and E-ICSI (ICSI was performed on in vitro matured oocytes the next day after oocytes retrieval, N = 78). Fertilization and embryonic development outcomes were collected and statistically analyzed. Mitochondria distribution of cytoplasm of in vitro matured oocytes with different time cultures after the first polar body (PB1) extrusion was stained. Results Compared to the E-ICSI group, more day 3 embryos from P-ICSI became blastocysts after sequential culture though without statistical significance (OR = 3.71, 95% CI: 0.94—14.63, P = 0.061). Compared to the E-ICSI group, more embryos from both P-ICSI and R-ICSI groups were clinically used with statistical significance (OR = 5.67, 95% CI: 2.24—14.35, P = 0.000 for P-ICSI embryos; OR = 3.23, 95% CI: 1.23—8.45, P = 0.017 for R-ICSI embryos). Compared to the E-ICSI group, transferred embryos from P-ICSI and R-ICSI had a higher implantation rate though without statistical significance (35.3% for P-ICSI embryos; 9.1% or R-ICSI embryos and 0% for E-ICSI embryos, P = 0.050). Among the three group, there were most healthy babies delivered from the P-ICSI group (5, 1 and 0 for P-ICSI, R-ICSI and E-ICSI respectively). The mitochondria in the cytoplasm of in vitro matured oocytes with a less than 4 h and 4–6 h culture after PB1 extrusion presented semiperipheral and diffused distribution patterns, respectively. Conclusions Our results revealed P-ICSI (ICSI was performed on in vitro matured oocytes 4–6 h after the first polar body extrusion) provided the most efficient method to utilize the immaturation oocytes basing on embryos utilization and live birth outcome for low prognosis patients under the POSEIDON classification. The mitochondria distribution of the in vitro matured oocytes’ cytoplasm from P-ICSI varied that from R-ICSI.

Background: Immunotherapy has emerged as a novel strategy for cancer treatment following surgery, radiotherapy, and chemotherapy. Immune checkpoint blockade and Chimeric antigen receptor (CAR)-T cell therapies have been successful in clinical trials. Cancer cells evade immune surveillance by hijacking inhibitory pathways via overexpression of checkpoint genes. The Cluster of Differentiation 47 (CD47) has emerged as a crucial checkpoint for cancer immunotherapy by working as a “don’t eat me” signal and suppressing innate immune signaling. Furthermore, CD47 is highly expressed in many cancer types to protect cancer cells from phagocytosis via binding to SIRPα on phagocytes. Targeting CD47 by either interrupting the CD47-SIRPα axis or combing with other therapies has been demonstrated as an encouraging therapeutic strategy in cancer immunotherapy. Antibodies and small molecules that target CD47 have been explored in pre- and clinical trials. However, formidable challenges such as the anemia and palate aggregation cannot be avoided because of the wide presentation of CD47 on erythrocytes. Aim of view: This review summarizes the current knowledge on the regulation and function of CD47, and provides a new perspective for immunotherapy targeting CD47. It also highlights the clinical progress of targeting CD47 and discusses challenges and potential strategies. Key scientific concepts of review: This review provides a comprehensive understanding of targeting CD47 in cancer immunotherapy, it also augments the concept of combination immunotherapy strategies by employing both innate and adaptive immune responses.

Plumbagin (PLB), a naphthoquinone compound, has been proven to have anti-cancer properties in different types of cancers. However, the anti-tumor actions as well as molecular processes in osteosarcoma (OS) remain unclear. This study investigates the underlying mechanisms of PLB in human OS cells in vitro. Our study showed that PLB significantly inhibited the proliferation of human OS cells in a time- and dosage-dependent manner. RNA sequencing data revealed that the efficacy of PLB is related to cell cycle, cell death, and p38 MAPK signaling pathway in KHOS-240S cells. Further studies indicated that PLB triggers G2/M phase arrest, mitochondrial-dependent apoptosis, as well as ferroptosis in human OS cells. Mechanistically, PLB treatment increased ROS generation that activates the p38 MAPK signaling pathway. BIRB 796, a p38 MAPK inhibitor, partly reversed PLB-induced phase arrest of G2/M and cell death. Furthermore, N-acetylcysteine (NAC), a ROS scavenger, significantly decreased G2/M phase arrest and cell death and reversed p38 MAPK activation caused by PLB. In conclusion, PLB induces arrest G2/M arrest, apoptosis as well as ferroptosis in human OS cells via ROS generation and p38 MAPK activation. There is potential for PLB to be an effective treatment for OS.

Spheroids and organoids have attracted significant attention as innovative models for disease modeling and drug screening. By employing diverse types of spheroids or organoids, it is feasible to establish microphysiological systems that enhance the precision of disease modeling and offer more dependable and comprehensive drug screening. High-throughput microphysiological systems that support optional, parallel testing of multiple drugs have promising applications in personalized medical treatment and drug research. However, establishing such a system is highly challenging and requires a multidisciplinary approach. This study introduces a dynamic Microphysiological System Chip Platform (MSCP) with multiple functional microstructures that encompass the mentioned advantages. We developed a high-throughput lung cancer spheroids model and an intestine-liver-heart-lung cancer microphysiological system for conducting parallel testing on four anti-lung cancer drugs, demonstrating the feasibility of the MSCP. This microphysiological system combines microscale and macroscale biomimetics to enable a comprehensive assessment of drug efficacy and side effects. Moreover, the microphysiological system enables evaluation of the real pharmacological effect of drug molecules reaching the target lesion after absorption by normal organs through fluid-based physiological communication. The MSCP could serves as a valuable platform for microphysiological system research, making significant contributions to disease modeling, drug development, and personalized medical treatment.

The fatigue crack propagation (FCP) behavior of a new Al–Cu–Li alloy under different aging treatments including T3, T8, and non-isothermal aging (NIA) was investigated. It was detected that the T8-24h sample exhibited the highest FCP resistance and the best mechanical performance. Compared with the T3-40D sample, the crack paths of the T8-24h sample and the C150 (non-isothermal peak-aged) sample were more tortuous and the crack width was narrower. Furthermore, the T8-24 sample had the lowest decreased FCP rate by an order of magnitude at the stress intensity factor (ΔK) of 30 MPa·m1/2. A large number of nano-scale T1 phases were precipitated in the T8-24h sample and their number density was also increased compared with the other sample. The presence of the tiny T1 phase plays a crucial role in impeding crack propagation as it can be sheared by dislocations without accumulating damage. This resulted in a substantial improvement both in the mechanical and fatigue properties of the alloy. Moreover, in the Paris stage of FCP, factors such as the size and concentration of precipitates within the grain and grain boundary play a vital role in determining the extent of crack growth. The results of transmission electron microscopy (TEM) bright field images on grain boundaries (GBs) analysis show that the variations in strength between the grain boundary and intragranular regions have a direct influence on the alloy's susceptibility to fatigue and corrosion resistance.

Abstract Background To evaluate the hemodynamic characteristics of normal upper extremity arteries from the brachial artery to the fingertip arterioles. Methods We analyzed the characteristics and changes in the regularities of ultrasonic parameters in the upper extremity arteries of 104 healthy volunteers using color Doppler flow imaging and Angio Planewave UltraSensitive™ imaging. The measured ultrasonic parameters included the vessel diameter, blood-flow spectrum waveform, peak systolic velocity, end-diastolic velocity, resistance index, pulsatility index, ratio of PSV to EDV, blood-flow volume, along with systolic acceleration of each BA, radial artery, superficial palmar arch artery, palmar proper digital artery, and third-grade artery arch of the fingernail bed. Results From BA to FN3AA, the diameter, PSV, RI, S/D, VFlow, and slope of the artery significantly decreased (P

Abstract Drug screening based on in-vitro primary tumor cell culture has demonstrated potential in personalized cancer diagnosis. However, the limited number of tumor cells, especially from patients with early stage cancer, has hindered the widespread application of this technique. Hence, we developed a digital microfluidic system for drug screening using primary tumor cells and established a working protocol for precision medicine. Smart control logic was developed to increase the throughput of the system and decrease its footprint to parallelly screen three drugs on a 4 × 4 cm2 chip in a device measuring 23 × 16 × 3.5 cm3. We validated this method in an MDA-MB-231 breast cancer xenograft mouse model and liver cancer specimens from patients, demonstrating tumor suppression in mice/patients treated with drugs that were screened to be effective on individual primary tumor cells. Mice treated with drugs screened on-chip as ineffective exhibited similar results to those in the control groups. The effective drug identified through on-chip screening demonstrated consistency with the absence of mutations in their related genes determined via exome sequencing of individual tumors, further validating this protocol. Therefore, this technique and system may promote advances in precision medicine for cancer treatment and, eventually, for any disease.

Abstract Granulation of juice sacs is a physiological disorder, which affects pomelo fruit quality. Here, the transcriptome and ubiquitinome of the granulated juice sacs were analyzed in Guanxi pomelo. We found that lignin accumulation in the granulated juice sacs was regulated at transcription and protein modification levels. In transcriptome data, we found that the genes in lignin biosynthesis pathway and antioxidant enzyme system of the granulated juice sacs were significantly upregulated. However, in ubiquitinome data, we found that ubiquitinated antioxidant enzymes increased in abundance but the enzyme activities decreased after the modification, which gave rise to reactive oxygen species (ROS) contents in granulated juice sacs. This finding suggests that ubiquitination level of the antioxidant enzymes is negatively correlated with the enzyme activities. Increased H2O2 is considered to be a signaling molecule to activate the key gene expressions in lignin biosynthesis pathway, which leads to the lignification in granulated juice sacs of pomelo. This regulatory mechanism in juice sac granulation of pomelo was further confirmed through the verification experiment using tissue culture by adding H2O2 or dimethylthiourea (DMTU). Our findings suggest that scavenging H2O2 and other ROS are important for reducing lignin accumulation, alleviating juice sac granulation and improving pomelo fruit quality.

Polymer matrix syntactic foams made of hollow glass microspheres (HGMs) and epoxy resin are widely used in underwater vehicles providing buoyancy due to their advantages of low density and high mechanical strength. When HGMs is strong enough, surface modification of HGMs is an effective method to improve the compressive strength of syntactic foams. However, the effects of different surface modifiers on the physical properties of HGMs and the compressive strength of syntactic foams have rarely been systematically studied. It is of great significance to enhance the interfacial strength of syntactic foams. Herein, the T40 HGMs was treated by different modifiers (HCl, NaOH, Li2SiO3, Me3SiONa, KH550, KH560, KH570, and Volan), physical properties of modified HGMs were studied, including true density, angle of repose, isostatic compressive strength, specific surface area, and contact angle. Furthermore, the effects of modified HGMs on the compressive strength of syntactic foams were also studied. The results showed that the compressive strength depend largely on the interface bonding between HGMs and resin matrix. This work can provide some references for mechanical property reinforcement of syntactic foams with high filling ratio and plenty of interface zones.

Introduction Despite the existence of numerous studies highlighting the adverse effects of smoking on kidney function, the investigation of the correlation between serum cotinine and chronic kidney disease (CKD) remains inconclusive due to insufficient evidence. Consequently, the primary objective of this study was to ascertain the association between serum cotinine levels and CKD. Methods This study analyzed data from 10900 Americans participating in the National Health and Nutrition Examination Survey between 2005 and 2016. The independent variable under investigation was log serum cotinine, while the dependent variable was the presence of CKD. To investigate the potential linear and non-linear correlations between serum cotinine and CKD, logistic regression models and generalized additive models (GAM) were employed. Furthermore, stratified analyses and interaction tests were conducted to evaluate potential disparities in the relationship between serum cotinine and CKD, based on sex. Results The median age in the study participants was 49.28 ± 17.96 years, and the median log serum cotinine (ng/mL) was -0.54 ± 1.68. The prevalence of CKD was found to be 17.04%. Multifactorial regression analysis did not show a statistically significant association between log serum cotinine and CKD (OR=1.02; 95% CI: 0.98–1.06, p=0.4387). A statistically significant non-linear association between log serum cotinine and CKD was also not observed in the GAM analysis (p nonlinear value=0.091). Subgroup analyses revealed sex differences in the association between log serum cotinine and CKD. Briefly, males had a positive association between log serum cotinine and incident CKD (OR=1.08; 95% CI: 1.02–1.15, p=0.0049). In females, there was a U-shaped association between log serum cotinine and CKD, with an optimal inflection point for log serum cotinine of -0.30 (serum cotinine=0.5 ng/mL). Conclusions Cross-sectional analyses of NHANES data showed gender differences in the association between serum cotinine and the development of CKD.

Abstract Transformers may suffer multiple short‐circuit impacts during long‐term operation, and axial instability is one of the typical types of serious accidents caused by short‐circuit faults. The axial instability form of the winding‐block structure is analysed, and the dynamic solution of the winding short‐circuit electromagnetic force is obtained by establishing the three‐dimensional magnetic‐circuit‐force multi‐physical field coupling simulation model. The influence of strain rate on the cushion block constitutive equation is corrected, and the modified model is verified by short‐circuit impact test and quasi‐static test. The research results show that for 110 kV 31.5 MVA transformers, the maximum electromagnetic axial resultant force of winding is 363.16 kN, and the ultimate tilt force is 1214.2 kN. The pre‐tightening force configuration is accordingly recommended to range from 363.16 to 608.28 kN, which is narrowed by 18.49% compared with the static calculation method; Meanwhile, adding a logarithmic strain rate correction term to the classical constitutive equation of the cushion block can achieve a good correction of the stress‐strain relationship with the coefficient of determination above 0.99, and the cushion block has a larger elastic modulus under high strain rate load. The research results provide an important theoretical reference for the axial stability structure of transformers.

Abstract Selective molecular recognition is an important alternative to the energy-intensive industrial separation process. Porous coordination polymers (PCPs) offer designing platforms for gas separation because they possess precise controllability over structures at the molecular level. However, PCPs-based gas separations are dominantly achieved using strong adsorptive sites for thermodynamic recognition or pore-aperture control for size sieving, which suffer from insufficient selectivity or sluggish kinetics. Developing PCPs that work at high temperatures and feature both high uptake capacity and selectivity is urgently required but remains challenging. Herein, we report diffusion-rate sieving of propylene/propane (C3H6/C3H8) at 300 K by constructing a PCP material whose global and local dynamics cooperatively govern the adsorption process via the mechanisms of the gate opening for C3H6 and the diffusion regulation for C3H8, respectively, yielding substantial differences in both uptake capacity and adsorption kinetics. Dynamic separation of an equimolar C3H6/C3H8 mixture reveals outstanding sieving performance with a C3H6 purity of 99.7% and a separation factor of 318.

Background: Cancer-associated cachexia is a multi-organ disorder associated with progressive weight loss due to a variable combination of anorexia, systemic inflammation and excessive energy wasting. Considering the importance of immunoregulation in cachexia, it still lacks a complete understanding of the immunological mechanisms in cachectic progression. Aim of review: Our aim here is to describe the complex immunoregulatory system in cachexia. We summarize the effects and translational potential of the immune system on the development of cancer-associated cachexia and we attempt to conclude with thoughts on precise and integrated therapeutic strategies under the complex immunological context of cachexia. Key Scientific Concepts of Review: This review is focused on three main key concepts. First, we highlight the inflammatory factors and additional mediators that have been identified to modulate this syndrome. Second, we decipher the potential role of immune checkpoints in tissue wasting. Third, we discuss the multilayered insights in cachexia through the immunometabolic axis, immune-gut axis and immune-nerve axis.

In this study, the extruded Mg-Zn-Mn-Ce-Ca alloy tube with a low compression anisotropy along the ED, 45ED and TD was prepared. The effect of the second phases, initial texture and deformation behavior on this low mechanical anisotropy was investigated. The results revealed that the alloy tube contains the high content (Mg1-xZnx)11Ce phase and the low content of Mg12Ce phase. These second phases are respectively incoherent and coherent with the Mg matrix, and their influence can be ignored. Additionally, the alloy tube exhibited a weak basal fiber texture, where the c-axis was aligned along the 0° ∼ 30° tilt from TD to ED. Such a texture made the initial deformation (at 1.0% ∼ 1.6% strain) of the three samples controlled by comparable basal slip. As deformation progressed (1.6∼9.0% strain), larger amounts of ETWs nucleated and gradually approached saturation in the three samples, re-orienting the c-axis to a 0°∼±30° deviation with respect to the loading directions. Meanwhile, the prismatic 〈a〉 and pyramidal slips replaced the dominant deformation progressively until fracture. Eventually, the similar deformation mechanisms determined by the weak initial texture in the three samples contribute to the comparable strain hardening rates, resulting in the low compressive anisotropy of the alloy tube.

Emerging research suggests a potential association of progression of Alzheimer's disease (AD) with alterations in synaptic currents and mitochondrial dynamics. However, the specific associations between these pathological changes remain unclear. In this study, we utilized Aβ42-induced AD rats and primary neural cells as in vivo and in vitro models. The investigations included behavioural tests, brain magnetic resonance imaging (MRI), liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis, Nissl staining, thioflavin-S staining, enzyme-linked immunosorbent assay, Golgi-Cox staining, transmission electron microscopy (TEM), immunofluorescence staining, proteomics, adenosine triphosphate (ATP) detection, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) assessment, mitochondrial morphology analysis, electrophysiological studies, Western blotting, and molecular docking. The results revealed changes in synaptic currents, mitophagy, and mitochondrial dynamics in the AD models. Remarkably, intervention with Dengzhan Shengmai (DZSM) capsules emerged as a pivotal element in this investigation. Aβ42-induced synaptic dysfunction was significantly mitigated by DZSM intervention, which notably amplified the frequency and amplitude of synaptic transmission. The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions, including the hippocampal CA3, primary cingular cortex, prelimbic system, and dysgranular insular cortex. DZSM intervention led to increased IDE levels, augmented long-term potential (LTP) amplitude, and enhanced dendritic spine density and length. Moreover, DZSM intervention led to favourable changes in mitochondrial parameters, including ROS expression, MMP and ATP contents, and mitochondrial morphology. In conclusion, our findings delved into the realm of altered synaptic currents, mitophagy, and mitochondrial dynamics in AD, concurrently highlighting the therapeutic potential of DZSM intervention.

The Daniudi Gas Field is one of the typical tight sandstone gas fields in the Ordos Basin. In order to better understand the genetic types and source of natural gas and reveal the migration phase of natural gas, the geochemical analysis of light hydrocarbons in the Upper Paleozoic tight gas from the Daniudi Gas Field has been conducted in this study. The results indicate that, the C5-7 light hydrocarbons in the Upper Paleozoic tight gas are dominated by iso-alkanes, and the C6-7 light hydrocarbons display low contents of aromatics (< 10%), which are even undetectable. The C7 light hydrocarbons are dominated by methylcyclohexane (MCH) with the relative MCH contents exceeding 50%. The K1 and K2 values of natural gas from the Lower Shihezi Formation (P1x) are consistent with those from the Shanxi (P1s) and Taiyuan (C3t) formations, respectively. The δ13C1 values of the P1x gas are consistent with those of the P1s gas and significantly different from those of the C3t gas. Compared with the P1s gas, the P1x gas mainly displays lower benzene/n-hexane, benzene/cyclohexane and toluene/n-heptane ratios, as well as significantly higher n-heptane/methylcyclohexane ratios. Geochemical characteristics of light hydrocarbons and carbon and hydrogen isotopic compositions of alkanes indicate that, the Upper Paleozoic natural gas from the Daniudi Gas Field is typical coal-derived gas. The P1s and C3t gases were in-situ self-generated and self-accumulated, whereas the P1x gas was mainly derived from the underlying P1s source rocks and accumulated via vertical migration in free phase, with insignificant contributions of the C3t source rocks. Due to the effect of migration and water solution of natural gas, the deviation exists in the identification of thermal maturity for tight gas from the Daniudi Gas Field using the light hydrocarbon indexes such as heptane and isoheptane values and benzene/n-hexane ratios.

Abstract Acral melanoma (AM) is a subtype of melanoma with high prevalence in East Asians. AM is characterized by greater aggressiveness and lower survival rates. However, there are still fewer studies on immune mechanisms of AM especially subungual melanoma (SM) versus non-subungual melanoma (NSM). In order to explore tumor heterogeneity and immune microenvironment in different subtypes of AM, we applied single-cell RNA sequencing to 24,789 single cells isolated from the SM and plantar melanoma (PM) patients. Aspects of tumor heterogeneity, melanocytes from PM and SM had significant differences in gene expression, CNV and pathways in which tumor-associated such as NF-kb and Wnt were involved. Regarding the immune microenvironment, PM contained more fibroblasts and T/NK cells. The EPHA3-EFNA1 axis was expressed only in cancer-associated fibroblast (CAF) and melanocytes of PM, and the TIGIT-NECTIN2 axis was expressed in both AM subtypes of T/NK cells and melanocytes. Altogether, our study helps to elucidate the tumor heterogeneity in AM subpopulations and provides potential therapeutic targets for clinical research.

Abstract Mental disorders are the leading contributors to the globally nonfatal burden of disease. This study was aimed to estimate the burden of mental disorders in Asian countries. Based on GBD 2019, the prevalence and disability-adjusted life of years (DALYs) rates with 95% uncertainty intervals (UI) were estimated in Asian countries. Predictions for the future burden of 8 selected countries, ranks of the burden of mental disorders and correlations with Sociodemographic Index (SDI) were also estimated. During the past 3 decades, while the number of DALYs of mental disorders increased from 43.9 million (95% UI: 32.5–57.2) to 69.0 million (95% UI: 51.0–89.7), the age-standardized rates of DALYs of mental disorders remained largely consistent from 1452.2 (95% UI: 1080.16–1888.53) per 100,000 population in 1990 to 1434.82 (95% UI: 1065.02–1867.27) per 100,000 population in 2019, ranked as the eighth most significant disease burden in Asia in 2019. Depressive disorders (37.2%) were the leading contributors to the age-standardized DALY rates of mental disorders in Asia, followed by anxiety disorders (21.5%). The age-standardized DALY rates in females were higher than their male counterparts, both peaked at 30-34 years. The age-standardized DALY rates were predicted to remain stable, with the number of DALYs presented an upward trend in the future. There was no significant correlation between the burden of mental disorders and SDI. All mental disorders ranked higher in 2019, compared in 1990. To reduce this burden, urgent measures for prevention, treatment, and rehabilitation for mental disorders need to be taken by Asian governments.

Abstract Background Autoimmune responses have been suggested to involvement in patients with Behcet’s syndrome (BS). There has been growing attention towards the roles of cutaneous lymphocyte antigen (CLA)+ regular T cells (Tregs) in autoimmune diseases. The role of CLA+ Tregs in BS is still uncertain. This study aims to clarify the impact of CLA+ Tregs on BS. Methods We collected peripheral blood from a total of 107 patients with BS and 114 healthy controls (HCs). The number of CLA+ Tregs, natural killer (NK) cells, B cells, and several subtypes of CD4+ T cells were detected using flow cytometry and compared between patients and HCs. Results The absolute number and proportion of CLA+ Tregs among CD4+ T lymphocytes and CD4+ Tregs were lower in patients with BS than in HCs. CLA+ Tregs were positively related with NK cells (r = 0.500, P

Abstract In plant immunity, a well-orchestrated cascade is initiated by the dimerization of receptor-like kinases (RLKs), followed by the phosphorylation of receptor-like cytoplasmic kinases (RLCKs) and subsequent activation of NADPH oxidases for ROS generation. Recent findings by Zhong et al. illustrated that a maize signaling module comprising ZmWAKL-ZmWIK-ZmBLK1-ZmRBOH4 governs quantitative disease resistance to grey leaf spot, a pervasive fungal disease in maize worldwide, unveiling the conservation of this signaling quartet in plant immunity.

Abstract In this study we aimed to investigate the prevalence of SARS-CoV-2 infection in psoriasis patients, and outcomes of SARS-CoV-2 infection and associated risk factors. A cross-sectional survey was conducted from February 2023 to March 2023. Information was obtained with online questionnaire about psoriasis patients on demographic characteristics, clinical characteristics, SARS-CoV-2 infection and outcomes, vaccination, and routine protection against COVID-19. Logistic regression analysis was used to explore risk factors with SARS-CoV-2 infection and exacerbation of psoriasis. A total of 613 participants were recruited. 516 (84.2%) were infected, and associated factors were sex, working status, routine protection against COVID-19, COVID-19 vaccination, impaired nail, infection exacerbate psoriasis, and severity of psoriasis. Among the patients infected with SARS-CoV-2, 30 (5.8%) required hospitalization, 122 (23.6%) had psoriasis exacerbation due to SARS-CoV-2 infection, and associated factors were subtype of psoriasis, discontinuation of psoriasis treatment during SARS-CoV-2 infection, response following COVID-19 vaccination, and severity of psoriasis. Booster dose vaccination contributed a low probability of COVID-19 sequelae. COVID-19 vaccine’s effectiveness was unsatisfactory, while booster dose vaccination reduced the occurrence of COVID-19 sequelae in psoriasis patients of Southwest China. Patients treated with psoriasis shown to be safe, without a higher incidence of SARS-CoV-2 infection or COVID-19hospitalization compared to untreated patients. Stopping treatment during SARS-CoV-2 infection led to psoriasis exacerbation, so psoriasis treatment could be continued except severe adverse reaction.

transformer is a switch gene for sex determination in many insects, which cooperates with transformer-2 that is expressed in both sexes to regulate female differentiation, particularly in dipterans. Zeugodacus cucurbitae (Coquillett) is a very destructive pest worldwide, however, its sex determination pathway remains largely uncharacterized. Here, we show that the female sex ratio is sharply reduced with knockdown of either transformer or transformer-2 by RNA interference in early embryos of Z. cucurbitae. Most of the males grown from the embryos with transient transformer and transformer-2 suppression mated with wild-type females and produced mixed sex progeny, with one exception that produced only female progeny, and all of the few remaining males failed to mate with wild-type females and produced no progeny. The exceptional male and those males with mating failure were XX pseudomales as determined by the detection of Y chromosome-linked Maleness-on-the-Y, indicating that most XX pseudomales are not viable. The phenotypes of transformer and transformer-2 suggest that they play a key role in regulating sex determination and are required for female sexual development of Z. cucurbitae. Our results will be beneficial to the understanding of sex determination in Z. cucurbitae and can facilitate the development of genetic sexing strains for its biological control.

Abstract Recent studies have identified a previously uncharacterized protein C11orf53 (now named POU2AF2/OCA-T1), which functions as a robust co-activator of POU2F3, the master transcription factor which is critical for both normal and neoplastic tuft cell identity and viability. Here, we demonstrate that POU2AF2 dictates opposing transcriptional regulation at distal enhance elements. Loss of POU2AF2 leads to an inhibition of active enhancer nearby genes, such as tuft cell identity genes, and a derepression of Polycomb-dependent poised enhancer nearby genes, which are critical for cell viability and differentiation. Mechanistically, depletion of POU2AF2 results in a global redistribution of the chromatin occupancy of the SWI/SNF complex, leading to a significant 3D genome structure change and a subsequent transcriptional reprogramming. Our genome-wide CRISPR screen further demonstrates that POU2AF2 depletion or SWI/SNF inhibition leads to a PTEN-dependent cell growth defect, highlighting a potential role of POU2AF2-SWI/SNF axis in small cell lung cancer (SCLC) pathogenesis. Additionally, pharmacological inhibition of SWI/SNF phenocopies POU2AF2 depletion in terms of gene expression alteration and cell viability decrease in SCLC-P subtype cells. Therefore, impeding POU2AF2-mediated transcriptional regulation represents a potential therapeutic approach for human SCLC therapy.