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Abstract Introduction The Hong Kong Poison Information Centre (HKPIC) has been providing consultation services to healthcare professionals and collecting epidemiological data on poisoning in Hong Kong since 2005. Objective To analyse and report the poisoning data from HKPIC in 2021. Methods A retrospective review was conducted on all poisoning cases recorded in the Poison Information and Clinical Management System of HKPIC in 2021. Results A total of 3973 poisoning cases were analysed. There was an increase of approximately 10% in total poisoning cases compared to 2020, bringing the total caseload back to the pre‐COVID era. Teenage (13–19 years) poisoning incidence continued to rise, reaching a recorded high of 16.2% of total poisoning cases. Notably, poisoning cases involving selective serotonin receptor inhibitors showed a significant increase, along with the use of the antidote cyproheptadine. The majority of these cases involved individuals under the age of 20 presenting with suspected self‐harm. Compared to 2020, the number of poisoning‐related deaths decreased by 25%, from 48 to 36 deaths in 2021, resulting in a case fatality rate of 1.0%. Additionally, six interesting cases and two poisoning clusters were discussed. Conclusions The 16th annual report provides valuable information on poisoning patterns in Hong Kong during the second year of the COVID‐19 pandemic, highlighting significant changes compared to previous reports.

Abstract Background Chronic inflammatory pain is a pervasive condition, and electroacupuncture (EA) is an effective treatment, but its mechanisms are not fully understood. AMP-activated protein kinase (AMPK), a key energy sensor, is involved in pain relief and EA’s effects. EA may work by increasing endocannabinoids, upregulating CB2 receptors (CB2R), and stimulating β-endorphin (β-END). This study tests if EA activates AMPK via CB2R to modulate β-END and reduce pain. Methods The inflammatory pain model was established with Complete Freund’s adjuvant (CFA), and EA was administered daily for six consecutive days, targeting the acupoints “Zusanli” (ST36) and “Shangjuxu” (ST37). Pain sensitivity was evaluated using Von Frey filaments for mechanical thresholds and a hot plate for thermal thresholds. Ultra-high Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS) was used to quantitatively determine the levels of endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA). The expression levels of the CB2R and β-END were measured by Western blotting, along with the activation of AMPK. Immunofluorescence double-labeling was applied to visualize AMPK activation and β-END expression within CD68-positive macrophages. The study encompassed both wild-type and CB2R gene knockout mice, elucidating the role of CB2R in EA-induced AMPK activation. Results CFA-induced inflammatory pain model mice exhibited mechanical allodynia and thermal hyperalgesia. EA activated AMPK in the inflamed skin tissue when it exerted analgesic effect on the inflammatory pain. Pre-administration of the AMPK inhibitor Compound C significantly inhibited the effect of EA on pain relief. EA elevated β-END expression in inflamed skin tissue, which was reversed by Compound C, indicating that AMPK has a regulatory role in EA inducing β-END expression. In addition, EA significantly upregulated the levels of 2-AG, AEA and the expression of CB2Rs in the inflamed skin tissue compared with the CFA group. In wild-type mice, EA activates AMPK in macrophages, while CB2 knockout reduced EA's ability to activate AMPK in these cells. Conclusion EA activates AMPK through CB2R, enhancing β-END expression in inflamed skin to alleviate inflammatory pain. This study reveals a new link between endocannabinoids, endorphins, and AMPK in analgesic effects of EA, highlighting the CB2R-AMPK-β-END pathway.

As a frozen dessert, ice cream is deeply loved by consumers. Not only does it offer a unique taste, but it also has great nutritional value. As healthy eating habits become more widespread, protein ice cream becomes increasingly popular among consumers. Understanding the effects of proteins on ice cream structure and quality is critical for promoting the growth of protein ice cream. This article delves into the creation of ice cream structure and the significant effect of proteins on its quality, including ice crystal recrystallization, fat partial coalescence, expansion rate, melting rate, and storage stability. It also offers a comprehensive overview of the latest research advancements in animal and plant proteins in ice cream, milk protein (whey proteins and casein) and soybean protein isolate are currently the most widely used in ice cream, and have a significant effect on improving the taste of ice cream and inhibiting the recrystallization of ice crystals. However, there is a problem of poor anti-melting effect in whey protein ice cream, and the quality of the ice cream can be improved by compounding with plant proteins. Additionally, protein as a fat substitute and natural emulsifier in ice cream becomes a new research hotspot. This review not only summarizes the current state of research in this area, but also prospects to the future application of proteins in ice cream.

Abstract Excessive exposure to ultraviolet radiation B (UVB) has been shown to contribute to the aging of human skin cells. Previous research has demonstrated that atorvastatin calcium (Ato) can mitigate the aging effects caused by chemotherapy drugs. However, it remains unclear whether Ato can alleviate skin aging induced by ultraviolet radiation. In this study, through in vitro experiments with Hacat cells, we found that Ato can significantly reduce the UVB-induced increased expression of age-related protein p16 and age-related gene p21, and also reduce the up-regulation of inflammatory factors such as IL-1 and IL-6. Besides, it can reduce the expression of metallomatrix protein (MMP1 and MMP9), and inhibit cell senescence and inflammatory damage. Similarly, we found that Ato can enhance skin collagen fiber reduction and collagen volume decrease, repair skin photoaging and damage induced by UVB rays, and speed up the rate at which the wounded location heals in vivo using Balb/c mice. In the mechanism, Ato markedly decreased the expression of p-p38, p-p65, p-mTOR in vivo and in vitro, suggesting that it may act on Mitogen-activated protein kinase (MAPK), Nuclear factor κB (NF- κB) and Mammalian target of rapamycin (mTOR) signaling pathways to produce above marked effects. In conclusion, Ato obviously relieved UVB-induced photoaging and damage, thus providing evidence for its potential in mitigating skin aging caused by ultraviolet radiation.

In order to improve the baking characteristics and nutritional quality of mung bean bread, mung bean sourdough was made by fermenting mung bean flour using Northwest leavening head, and then combined with yeast as a compound leavening agent to make mung bean bread. The microbial composition of the Northwest leavening head was analyzed to clarify the composition of its microflora, the Fourier transform infrared spectrometer and rheometer were used to analyze the changing pattern of the secondary structure and viscoelasticity of gluten proteins in the dough of the mung bean bread, and the texture meter was used in combination with the sensory assessment to evaluate the sensory quality of the mung bean bread. The results showed that the phytic acid content of the mung bean sourdough fermented in the Northwest fermentation head was reduced by 44.71% at 6 h of fermentation, and the pH and total titration acidity (TTA) were 6.29 and 11.03 mL, respectively. Compared with the control group, the bread with added mung bean sourdough showed a decrease in the modulus of elasticity and viscous modulus of the dough, an increase in the plasticity of the dough, the content of α-helices and β-folds in the secondary structure of proteins, and the stability of the dough. The antioxidant results showed that the scavenging ability of mung bean bread for both DPPH and ABTS+ free radicals also significantly increased (P

Abstract As one of the most important senses in human beings, touch can also help robots better perceive and adapt to complex environmental information, improving their autonomous decision-making and execution capabilities. Compared to other perception methods, tactile perception needs to handle multi-channel tactile signals simultaneously, such as pressure, bending, temperature, and humidity. However, directly transferring deep learning algorithms that work well on temporal signals to tactile signal tasks does not effectively utilize the physical spatial connectivity information of tactile sensors. In this paper, we propose a tactile perception framework based on graph attention networks, which incorporates explicit and latent relation graphs. This framework can effectively utilize the structural information between different tactile signal channels. We constructed a tactile glove and collected a dataset of pressure and bending tactile signals during grasping and holding objects, and our method achieved 89.58% accuracy in object tactile signal classification. Compared to existing time-series signal classification algorithms, our graph-based tactile perception algorithm can better utilize and learn sensor spatial information, making it more suitable for processing multi-channel tactile data. Our method can serve as a general strategy to improve a robot’s tactile perception capabilities.

Abstract Kagome magnets provide a fascinating platform for the realization of correlated topological quantum phases under various magnetic ground states. However, the effect of the magnetic spin configurations on the characteristic electronic structure of the kagome-lattice layer remains elusive. Here, utilizing angle-resolved photoemission spectroscopy and density functional theory calculations, we report the spectroscopic evidence for the spin-reorientation effect of a kagome ferromagnet Fe3Ge, which is composed solely of kagome planes. As the Fe moments cant from the c-axis into the a b plane upon cooling, the two kinds of kagome-derived Dirac fermions respond quite differently. The one with less-dispersive bands (k z ~ 0) containing the $$3{d}_{{z}^{2}}$$ 3 d z 2 orbitals evolves from gapped into nearly gapless, while the other with linear dispersions (k z ~ π) embracing the 3d x z /3d y z components remains intact, suggesting that the effect of spin reorientation on the Dirac fermions has an orbital selectivity. Moreover, we demonstrate that there is no signature of charge order formation in Fe3Ge, contrasting with its sibling compound FeGe, a newly established charge-density-wave kagome magnet.

Abstract Rice (Oryza sativa L.) endosperm is essential to provide nutrients for seed germination and determine grain yield. RNA editing, a post-transcriptional modification essential for plant development, unfortunately, is not fully characterized during rice endosperm development. Here, we perform systematic analyses to characterize RNA editome during rice endosperm development. We find that most editing sites are C-to-U CDS-recoding in mitochondria, leading to increased hydrophobic amino acids and changed structures of mitochondrial proteins. Comparative analysis of RNA editome reveals that CDS-recoding sites present higher editing frequencies with lower variabilities and their resultant recoded amino acids tend to exhibit stronger evolutionary conservation across many land plants. Furthermore, we classify mitochondrial genes into three groups, presenting distinct patterns in terms of CDS-recoding events. Besides, we conduct genome-wide screening to detect pentatricopeptide repeat (PPR) proteins and construct PPR-RNA binding profiles, yielding candidate PPR editing factors related to rice endosperm development. Taken together, our findings provide valuable insights for deciphering fundamental mechanisms of rice endosperm development underlying RNA editing machinery.

Abstract 5-Fluorouracil (5-FU) is used as a standard first-line drug for colorectal cancer malignancy (CRC), but it brings a series of side effects such as severe diarrhea and intestinal damage. Our previous study found that a large number of senescent cells increased while 5-Fu induced intestinal damage, and anti-senescence drugs can alleviate its side effects of inflammatory damage. Oleanolic acid (OA) is a common pentacyclic triterpenoid mainly derived from food fungi and medicinal plants, and studies have shown that it mainly possesses hepatoprotective, enzyme-lowering, anti-inflammatory, and anti-tumor effects. But its role in senescence is still unclear. In the present study, we demonstrated for the first time that OA ameliorated 5-Fu-induced human umbilical vein endothelial cells (HUVECs) and human normal intestinal epithelial cells (NCM460) in a 5-Fu-induced cellular senescence model by decreasing the activity of SA-β-gal-positive cells, and the expression of senescence-associated proteins (p16), senescence-associated genes (p53 and p21), and senescence-associated secretory phenotypes (SASPs: IL-1β, IL-6, IL-8, IFN-γ and TNF-α). Meanwhile, in this study, in a BALB/c mouse model, we demonstrated that 5-FU induced intestinal inflammatory response and injury, which was also found to be closely related to the increase of senescent cells, and that OA treatment was effective in ameliorating these adverse phenomena. Furthermore, our in vivo and in vitro studies showed that OA could alleviate senescence by inhibiting mTOR. In colon cancer cell models, OA also enhanced the ability of 5-FU to kill HCT116 cells and SW480 cells. Overall, this study demonstrates for the first time the potential role of OA in counteracting the side effects of 5-FU chemotherapy, providing a new option for the treatment of colorectal cancer to progressively achieve the goal of high efficacy and low toxicity of chemotherapy.

Anthocyanins, flavonoid pigments, are responsible for the purple and red hues in potato tubers. This study analyzed tubers from four potato cultivars—red RR, purple HJG, yellow QS9, and white JZS8—to elucidate the genetic mechanisms underlying tuber pigmentation. Our transcriptomic analysis identified over 2400 differentially expressed genes between these varieties. Notably, genes within the flavonoid biosynthesis pathway were enriched in HJG and RR compared to the non-pigmented JZS8, correlating with their higher levels of anthocyanin precursors and related substances. Hierarchical clustering revealed inverse expression patterns for the key genes involved in anthocyanin metabolism between pigmented and non-pigmented varieties. Among these, several MYB transcription factors displayed strong co-expression with anthocyanin biosynthetic genes, suggesting a regulatory role. Specifically, the expression of 16 MYB genes was validated using qRT-PCR to be markedly higher in pigmented HJG and RR versus JZS8, suggesting that these MYB genes might be involved in tuber pigmentation. This study comprehensively analyzed the transcriptome of diverse potato cultivars, highlighting specific genes and metabolic pathways involved in tuber pigmentation. These findings provide potential molecular targets for breeding programs focused on enhancing tuber color.

Background: Diabetes Mellitus (DM), a chronic metabolic disease characterized by elevated blood glucose, is caused by various degrees of insulin resistance and dysfunctional insulin secretion, resulting in hyperglycemia. The loss and failure of functional β-cells are key mechanisms resulting in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Aim of review: Elucidating the underlying mechanisms of β-cell failure, and exploring approaches for β-cell neogenesis to reverse β-cell dysfunction may provide novel strategies for DM therapy. Key scientific concepts of review: Emerging studies reveal that genetic susceptibility, endoplasmic reticulum (ER) stress, oxidative stress, islet inflammation, and protein modification linked to multiple signaling pathways contribute to DM pathogenesis. Over the past few years, replenishing functional β-cell by β-cell neogenesis to restore the number and function of pancreatic β-cells has remarkably exhibited a promising therapeutic approach for DM therapy. In this review, we provide a comprehensive overview of the underlying mechanisms of β-cell failure in DM, highlight the effective approaches for β-cell neogenesis, as well as discuss the current clinical and preclinical agents research advances of β-cell neogenesis. Insights into the challenges of translating β-cell neogenesis into clinical application for DM treatment are also offered.

Abstract Quantitatively predicting the impacts of climate change on water demands of various crops is essential for developing measures to ensure food security, sustainable agriculture, and water resources management, especially in arid regions. This study explored the water footprints (WFs) of nine major crops in the middle and downstream areas of Shule River Basin, Northwest China, from 1989 to 2020 using the WF theory and CROPWAT model and predicted the future WFs of these crops under four emission and socio-economic pathway (SSPs-RCPs) scenarios, which provides scientific support for actively responding to the negative impacts of climate change in arid regions. Results indicated: (1) an increasing trend of the overall crop WF, with blue WF accounting for 80.31–99.33% of the total WF in the last 30 years. Owing to differences of planting structure, water-conservation technologies, and other factors, the multi-year average WF per unit area of crops was 0.75 × 104 m3 hm−2 in downstream area, which was higher than that in midstream area (0.57 × 104 m3 hm−2) in the last 30 years; therefore agricultural water use efficiency in the downstream area was lower than that in the midstream area, implying that the midstream area has more efficient agricultural water utilization. (2) an initial increase and then decrease of crop WFs in the study area under SSP1-2.6, SSP2-4.5, and SSP5-8.5 scenarios by the end of the century, reaching their peak in 2030s which was higher than that from 1989 to 2020; with the maximum growth rates in the midstream area ranging from −0.85% in SSP5-8.5 to 5.33% in SSP2-4.5 and 29.74% in SSP5-8.5 to 34.71% in SSP2-4.5 in the downstream area. The local agricultural water demand would continue to increase and water scarcity issues would be more severe in the next 10–20 years, affecting downstream areas more. Under the SSP3-7.0 scenario, crop WF values of the midstream and downstream regions will be 2.63 × 108 m3 and 4.22 × 108 m3 in 2030, respectively, which is significantly higher than those of other scenarios and show a long-term growth trend. The growth rate of the midstream and downstream regions will reach 44.71% and 81.12%, respectively, by the end of this century, so the local agricultural water use would be facing more strain if this scenario materializes in the future. Therefore, the Shule River Basin should encourage development of water-saving irrigation technologies, adjust the planting ratio of high water consuming crops, and identify other measures to improve water resource utilization efficiency to cope with future water resource pressures.

Abstract There is a relative scarcity of large-scale population studies investigating the relationship between the insulin resistance index of homeostasis model assessment (HOMA-IR) and vascular damage. Therefore, we assessed the association between HOMA-IR and vascular damage in adults aged 18 years and older in China. A total of 17,985 research subjects were included. Vascular damage markers and relevant laboratory tests were measured. HOMA-IR was calculated as (fasting insulin * fasting blood glucose)/22.5. Vascular damage included arteriosclerosis (ba-PWV > 1800 cm/s), peripheral artery disease (ABI 30 mg/g). The relationship between HOMA-IR and vascular damage was analyzed using the RCS. The restricted cubic spline (RCS) analysis suggested that HOMA-IR was nonlinearly associated with arteriosclerosis (P for no-liner

Abstract Background Obesity is well-established as a significant contributor to the development of insulin resistance (IR) and diabetes, partially due to elevated plasma saturated free fatty acids like palmitic acid (PA). Grb10-interacting GYF Protein 2 (GIGYF2), an RNA-binding protein, is widely expressed in various tissues including the liver, and has been implicated in diabetes-induced cognitive impairment. Whereas, its role in obesity-related IR remains uninvestigated. Methods In this study, we employed palmitic acid (PA) exposure to establish an in vitro IR model in the human liver cancer cell line HepG2 with high-dose chronic PA treatment. The cells were stained with fluorescent dye 2-NBDG to evaluate cell glucose uptake. The mRNA expression levels of genes were determined by real-time qRT-PCR (RT-qPCR). Western blotting was employed to examine the protein expression levels. The RNA immunoprecipitation (RIP) was used to investigate the binding between protein and mRNA. Lentivirus-mediated gene knockdown and overexpression were employed for gene manipulation. In mice, an IR model induced by a high-fat diet (HFD) was established to validate the role and action mechanisms of GIGYF2 in the modulation of HFD-induced IR in vivo. Results In hepatocytes, high levels of PA exposure strongly trigger the occurrence of hepatic IR evidenced by reduced glucose uptake and elevated extracellular glucose content, which is remarkably accompanied by up-regulation of GIGYF2. Silencing GIGYF2 ameliorated PA-induced IR and enhanced glucose uptake. Conversely, GIGYF2 overexpression promoted IR, PTEN upregulation, and AKT inactivation. Additionally, PA-induced hepatic IR caused a notable increase in STAU1, which was prevented by depleting GIGYF2. Notably, silencing STAU1 prevented GIGYF2-induced PTEN upregulation, PI3K/AKT pathway inactivation, and IR. STAU1 was found to stabilize PTEN mRNA by binding to its 3’UTR. In liver cells, tocopherol treatment inhibits GIGYF2 expression and mitigates PA-induced IR. In the in vivo mice model, GIGYF2 knockdown and tocopherol administration alleviate high-fat diet (HFD)-induced glucose intolerance and IR, along with the suppression of STAU1/PTEN and restoration of PI3K/AKT signaling. Conclusions Our study discloses that GIGYF2 mediates obesity-related IR by disrupting the PI3K/AKT signaling axis through the up-regulation of STAU1/PTEN. Targeting GIGYF2 may offer a potential strategy for treating obesity-related metabolic diseases, including type 2 diabetes. Graphical Abstract

ObjectiveTo analyze the experience of Professor Chen Huanchao, a famous TCM doctor in Hubei Province, in treating breast cancer by data mining technology. MethodsThe medical records of Professor Chen Huanchao’s treatment of breast cancer were collected, and the first prescription of each patient was recorded after screening and sorting. MS Excel 2019 was used to analyze drug frequency, efficacy frequency, and the meridian distribution, and SPSS Modeler 18.0 software was adopted for association rule analysis and network display of drugs. SPSS 27.0 was employed for clustering analysis of high-frequency drugs to summarize medication patterns. ResultsA total of 185 prescriptions involving 180 traditional Chinese medicines were included, and 29 high-frequency drugs were screened. The medicinal properties were mainly neutral, cold, and warm, and the medicinal flavors were mainly sweet, bitter, and pungent. The meridians were liver, lung, spleen, and kidney meridians. The medicinal effects primarily included tonifying deficiency, clearing heat, and promoting diuresis and dampness. The association rule analysis showed 20 groups of drug pairs, and the cluster analysis mainly revealed two categories. ConclusionProfessor Chen Huanchao believes that breast cancer involves root deficiency and excessive symptoms and should be treated from the perspective of “deficiency, blood stasis, phlegm, and toxin.” Genuine-Qi should be strengthened, and Evil-Qi should be eliminated. The symptoms and root causes of this disease should be treated simultaneously while soothing the liver and qi, tonifying the spleen and kidney, promoting blood circulation, removing phlegm and preventing its accumulation, and clearing heat and detoxify. This work provides ideas for the treatment of breast cancer with traditional Chinese medicine.

PurposeFunctional near-infrared spectroscopy (fNIRS) has shown feasibility in evaluating cognitive function and brain functional connectivity (FC). Therefore, this fNIRS study aimed to develop a screening method for subjective cognitive decline (SCD) and mild cognitive impairment (MCI) based on resting-state prefrontal FC and neuropsychological tests via machine learning.MethodsFunctional connectivity data measured by fNIRS were collected from 55 normal controls (NCs), 80 SCD individuals, and 111 MCI individuals. Differences in FC were analyzed among the groups. FC strength and neuropsychological test scores were extracted as features to build classification and predictive models through machine learning. Model performance was assessed based on accuracy, specificity, sensitivity, and area under the curve (AUC) with 95% confidence interval (CI) values.ResultsStatistical analysis revealed a trend toward compensatory enhanced prefrontal FC in SCD and MCI individuals. The models showed a satisfactory ability to differentiate among the three groups, especially those employing linear discriminant analysis, logistic regression, and support vector machine. Accuracies of 94.9% for MCI vs. NC, 79.4% for MCI vs. SCD, and 77.0% for SCD vs. NC were achieved, and the highest AUC values were 97.5% (95% CI: 95.0%–100.0%) for MCI vs. NC, 83.7% (95% CI: 77.5%–89.8%) for MCI vs. SCD, and 80.6% (95% CI: 72.7%–88.4%) for SCD vs. NC.ConclusionThe developed screening method based on resting-state prefrontal FC measured by fNIRS and machine learning may help predict early-stage cognitive impairment.

Abstract High expression of cellular self‐activated immunosuppressive molecules and extensive infiltration of suppressive immune cells in the tumor microenvironment are the main factors contributing to glioma's resistance to immunotherapy. Nonetheless, technology to modify the expression of glioma cellular self‐molecules through gene editing requires further development. This project advances cell therapy strategies to reverse the immunosuppressive microenvironment of glioma (TIME). Bone marrow‐derived mesenchymal stem cells (MSCs) are engineered to express bioactive proteins and demonstrate tumor‐homing characteristics upon activation by TGF‐β. These MSCs are designed to secrete the anti‐tumor immune cytokine IL‐12 and the nCD47‐SLAMF7 fusion protein, which regulates T‐cell activity and macrophage phagocytosis. The engineered MSCs are then injected in situ into the glioma site, circumventing the blood‐brain barrier to deliver high local concentrations of bioactive proteins. This approach aims to enhance the M1 polarization of infiltrating macrophages, stimulate macrophage‐mediated tumor cell phagocytosis, activate antigen‐presenting cells, and promote effector CD8+ T cell infiltration, effectively controlling glioma. Additionally, the engineered MSCs may serve as a universal treatment for other tumors that express TGF‐β at high levels. This study proposes a novel treatment strategy for the clinical management of glioma patients.

ObjectivesThe incidence of peripheral arterial disease (PAD) in China is increasing. We aim to conduct a comprehensive analysis of the burden of PAD.MethodsWe collected information from 1990 to 2019 in the Global Burden of Disease (GBD 2019) study. Joinpoint regression analysis was used to calculate the annual percentage change (APC). Trends in incidence, mortality and DALYs were forecasted by Bayesian age-period-cohort (BAPC) analysis.ResultsIn 2019, the number of new cases and prevalence of PAD in China accounted for nearly a quarter of the global proportion. The age-standardized incidence rate (ASIR) declined after rising until 2005. The age-standardized death rate (ASDR) maintained an upward trend. The DALYs was 0.16 million. Incidence, prevalence and DALYs are predominantly female, except for mortality, which is predominantly male. Smoking predominantly affected males, while hypertension and diabetes had a greater impact on females. By 2030, ASDR is elevated, predominantly in males. ASIR and age-standardized DALY rate decline, predominantly in females.ConclusionIt is urgent for China to develop strategies based on the specific distribution characteristics of the PAD burden.

IntroductionThe Cinnamomum Camphora var. Borneol (CCB) tree is a valuable timber species with significant medicinal importance, widely cultivated in mountainous areas but susceptible to pests and diseases, making manual surveillance costly.MethodsThis paper proposes a method for detecting CCB pests and diseases using Unmanned aerial vehicle (UAV) as an advanced data collection carrier, capable of gathering large-scale data. To tackle the high cost and challenging data processing issues associated with traditional hyper-spectral/multi-spectral sensors, this method only relies on UAV visible light RGB bands. The process first involves calculating and normalizing 24 visible light vegetation indices from the UAV RGB images of the monitoring area, along with the original RGB bands. To account for the collinearity relationship between indices, the random forest variable importance and correlation coefficient iterative analysis algorithm are employed to select indices, retaining the most important or lowest collinearity multiple vegetation indices. Subsequently, the Beluga Whale Optimization (BWO) algorithm is utilized to generate a new vegetation index, which is then combined with the multi-threshold segmentation method to propose a BWO-weighted ensemble strategy for obtaining the final pests and diseases detection results.Results and discussionThe experimental results suggest that the new BWO-based vegetation index has a higher feature expression ability than single indices, and the new BWO-based ensemble strategy can yield more accurate detection results. This approach provides an effective means for low-cost pests and diseases detection of CCB trees.

Under the background of climate change and global warming, extreme drought events in China are becoming increasingly frequent. Drought is one of the primary natural causes of damage to China’s agriculture, economy, and environment, making timely, accurate, and high-resolution drought monitoring particularly crucial. The global standardized precipitation − evapotranspiration index database (SPEIbase) is a widely accepted and used global-scale drought monitoring product. However, limited by its spatial resolution of 0.5 degrees, it is difficult to describe the local spatio-temporal structure of drought. How to improve its spatial resolution while maintaining spatio-temporal consistency is one of the current research hotspots. Based on the response of vegetation growth status to drought, this paper proposes a simple and feasible SPEI prediction method, which improves the resolution of SPEIbase from 0.5 degrees to 1 km. Sixteen remote sensing inversion indices, reflectance and elevation data related to drought were selected from Google Earth Engine (GEE) as features. After preprocessing such as gridding and sample balancing, a random forest regression model was constructed to achieve high spatial resolution prediction of SPEI. SPEI with time scales of 1, 3, 6, 9, 12 and 24 months in July 2020, August 2019 and August 2018 in China was selected for experiments. The accuracy of 1 km resolution SPEI was evaluated through metrics such as root mean square error (RMSE), Pearson correlation coefficient (PCC) and determination coefficient (R2). At the same time, it was compared with the existing 1 km resolution SPEI dataset and the site-scale SPEI values. The results show that the method in this paper can obtain accurate prediction results more stably. The PCC and R2 of different months and multiple time scales are all higher than 0.9 and 0.8, and the RMSE is lower than 0.4, showing a good application prospect. Despite the good consistency between the Proposed SPEI and SPEIbase with the site-scale SPEI values, there is still significant room for improvement.

Breast cancer has become the most prevalent malignant tumor worldwide and remains one of the leading causes of cancer-related mortality among women globally. The prognosis for patients with metastatic breast cancer remains poor, necessitating the exploration of novel therapeutic strategies to improve survival rates. In the era of precision medicine, antibody-drug conjugates (ADCs) have gained significant attention as a targeted therapeutic strategy in breast cancer treatment. ADCs, a relatively new treatment for breast cancer, deliver cytotoxic drugs (payloads), directly into the tumor space, turning chemotherapy into a targeted agent, which enables patients to experience significant improvements with manageable drug toxicity. For the treatment of breast cancer, there are three ADCs approved for breast cancer treatment: Trastuzumab emtansine (T-DM1), Trastuzumab Deruxtecan (T-Dxd) targeting HER-2, and Sacituzumab Govitecan (SG) targeting Trop-2. Recent clinical studies have demonstrated that the benefits of ADC therapies extend beyond HER2-positive breast cancer toinclude hormone receptor (HR)-positive breast cancer, triple-negative breast cancer (TNBC), and HER2-low expressing breast cancer. Notably, the DESTINY-Breast series of studies, particularly focusing on T-Dxd, encompass neoadjuvant, adjuvant, and multiple lines of therapy for advanced breast cancer. This marks the advent of a comprehensive ADC era in breast cancer treatment. This review summarizes the efficacy and adverse effects of ADC therapies that have completed or are currently undergoing phase I-III clinical trials. Additionally, it analyzes potential combination strategies to overcome ADC resistance, aiming to provide clinicians with a comprehensive clinical guide to the use of ADCs in breast cancer treatment.

Background Tongue coating microbiota has aroused particular interest in profiling oral and digestive system cancers. However, little is known on the relationship between tongue coating microbiome and colorectal cancer (CRC).Methods Metagenomic shotgun sequencing was performed on tongue coating samples collected from 30 patients with CRC, 30 patients with colorectal polyps (CP), and 30 healthy controls (HC). We further validated the potential of the tongue coating microbiota to predict the CRC by a random forest model.Results We found a greater species diversity in CRC samples, and the nucleoside and nucleotide biosynthesis pathway was more apparent in the CRC group. Importantly, various species across participants jointly shaped three distinguishable fur types.The tongue coating microbiome profiling data gave an area under the receiver operating characteristic curve (AUC) of 0.915 in discriminating CRC patients from control participants; species such as Atopobium rimae, Streptococcus sanguinis, and Prevotella oris aided differentiation of CRC patients from healthy participants.Conclusion These results elucidate the use of tongue coating microbiome in CRC patients firstly, and the fur-types observed contribute to a better understanding of the microbial community in human. Furthermore, the tongue coating microbiota-based biomarkers provide a valuable reference for CRC prediction and diagnosis.

Background The mortality risk varies considerably among individual dialysis patients. This study aimed to develop a user-friendly predictive model for predicting all-cause mortality among dialysis patients.Methods Retrospective data regarding dialysis patients were obtained from two hospitals. Patients in training cohort (N = 1421) were recruited from the Fifth Affiliated Hospital of Sun Yat-sen University, and patients in external validation cohort (N = 429) were recruited from the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine. The follow-up endpoint event was all-cause death. Variables were selected by LASSO-Cox regression, and the model was constructed by Cox regression, which was presented in the form of nomogram and web-based tool. The discrimination and accuracy of the prediction model were assessed using C-indexes and calibration curves, while the clinical value was assessed by decision curve analysis (DCA).Results The best predictors of 1-, 3-, and 5-year all-cause mortality contained nine independent factors, including age, body mass index (BMI), diabetes mellitus (DM), cardiovascular disease (CVD), cancer, urine volume, hemoglobin (HGB), albumin (ALB), and pleural effusion (PE). The 1-, 3-, and 5-year C-indexes in the training set (0.840, 0.866, and 0.846, respectively) and validation set (0.746, 0.783, and 0.741, respectively) were consistent with comparable performance. According to the calibration curve, the nomogram predicted survival accurately matched the actual survival rate. The DCA showed the nomogram got more clinical net benefit in both the training and validation sets.Conclusions The effective and convenient nomogram may help clinicians quantify the risk of mortality in maintenance dialysis patients.

Land-use modeling stands as a pivotal tool in shaping sustainable development policies. With the rapid advancement of remote-sensing technology and the widespread adoption of satellite imagery-based land cover products, these datasets have emerged as primary sources for understanding land-use dynamics due to their high spatial and temporal resolutions. Yet, it remains challenging to effectively integrate such rich panel data into nonlinear econometric land-use models. This paper introduces a method to seamlessly incorporate land cover panel data into econometric models, enabling comprehensive utilization of temporal information within a single framework. - By capturing dynamic land-use patterns, the method enhances prediction accuracy while mitigating issues such as autocorrelated error terms commonly encountered in panel data analysis. - The method is straightforward to implement and applicable to many nonlinear models, making it particularly suitable for datasets with large sample sizes.

Objectives To evaluate the effectiveness and safety of different B cell-targeting biological agents combining with standard of care in patients with lupus nephritis (LN).Methods Comprehensive literature searches were conducted using PubMed, Embase, Web of Science, and Central in the Cochran Library, spanning from inception to May 20th, 2024. Randomized control trials (RCTs) comparing rituximab (RTX), belimumab, ocrelizumab, obinutuzumab, and anifrolumab in LN were selected. The primary outcomes of interest were related to complete renal remission (CRR), and partial renal remission (PRR). Additionally, we delved into safety outcomes, examining the occurrence of serious adverse events (SAEs), infections, and the discontinuation rates due to adverse events.Results A total of 6 RCTs with 1150 patients applying various B cell-targeting biological agents were included. Notably, ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that obinutuzumab (SUCRA 85.2%) has the highest potential superiority in improving CRR, followed by belimumab, ocrelizumab. Regarding the improvement in PRR, obinutuzumab (SUCRA 83.0%) has the highest potential superiority. In terms of safety, with a focus on SAEs, infections, and the discontinuation rates due to adverse events, the results were: SUCRA-based ranking indicated that RTX (SUCRA 74.1%) had the highest probability of postponing SAEs, followed by belimumab and obinutuzumab. Concerning infection reduction, anifrolumab (SUCRA 78.7%) had the highest potential superiority. Safety events monitoring infection occurred better with RTX than with standard therapy (OR = 3.57, 95% CI 1.02, 12.66) and were statistically different. For the discontinuation rates due to adverse events, RTX (SUCRA 88.6%) demonstrated the highest potential superiority.Conclusions Concerning the effectiveness and safety outcomes, obinutuzumab, belimumab, and RTX plus standard of care may be superior to the current standard therapy as treatments for LN. This study protocol has been registered with PROSPERO, with a registration number of CRD42024548522.

Background Glycyrrhiza, a perennial herbaceous medicinal plant, is extensively utilized in the pharmaceutical industry. The growth of Glycyrrhiza is frequently constrained by soil phosphorus availability, as a significant portion of arable land in China suffers from phosphorus deficiency. Method This study utilized Ural Glycyrrhiza uralensis Fisch as the subject and examined the application of GR24, a synthetic strigolactone, under three phosphorus conditions: none (P1), low (P2), and high (P3). The research aimed to ascertain the optimal concentration of GR24 for promoting licorice growth and development, thereby providing a theoretical foundation for its agricultural management. Results The optimal GR24 concentration for P3 and P2 conditions was identified as G3 (10 µM), which enhanced growth metrics, chlorophyll a and b levels, while also boosting antioxidant enzyme activities in licorice. Specifically under P3, significant increases in liquiritigenin and glycyrrhizic acid levels were observed. Under P2, increases were noted in isoliquiritigenin, liquiritigenin, and liquiritin levels. Transcriptome analysis revealed differential gene, with 137 and 270 genes up-regulated and 77 and 294 genes down-regulated in the P3 and P2 treatments, respectively. GO functional enrichment identified 132 and 436 differentially expressed genes for P3 and P2 respectively, while KEGG pathways were predominantly enriched in plant-pathogen interactions and phenylpropanoid biosynthesis. Application of GR24 in P1 conditions did not significantly affect growth indices but did enhance glycyrrhetic acid, isoliquiritin, and liquiritin accumulation. Transcriptome profiling in this treatment identified 465 up-regulated and 1,109 down-regulated genes. GO annotation involved 1,108 differentially expressed genes, and KEGG analysis was primarily enriched in the plant-pathogen interaction pathway. Furthermore, transcription factor analysis revealed alterations in the C2H2, NAC, and MYB families, which are associated with phosphorus response.

Guillain–Barré syndrome (GBS) is a heterogeneous disease, and it usually develops after an antecedent infection, while rare cases develop following a central nervous system disease. Given the indeterminacy of prodromal infection symptoms and the overlap of symptoms with other neurological disorders, a rigorous clinical and neurological examination in conjunction with history is necessary for early diagnosis and treatment of GBS. Here we present a rare case of GBS following acute ischemic stroke which was different from previous reports such as GBS following hemorrhagic stroke or head trauma. Moreover, intravenous immunoglobulin was effective in this patient after 6 months of follow-up despite the potential risk of thrombotic events.

Primary osteosarcoma of the breast (POB) is an aggressive and exceedingly rare tumor, and cases with onset during lactation are extremely rare. The exact mechanism of POB development remains unclear. They may originate from totipotent mesenchymal cells in the breast stroma or may be the result of neoplastic transformation of prior breast lesions. Here, we present the case of a 40-year-old Chinese woman who was found with a palpable tumor measuring approximately 3 cm in diameter in her right breast while breastfeeding 4 months post-partum. The lactating woman was misdiagnosed with lactational mastitis during her initial visit to a community hospital. However, due to negative bacterial cultures and ineffective anti-infective treatment, later on the patient was taken to a more advanced hospital where a tissue biopsy was taken. The superior hospital considered that it might be a malignant tumor and performed local excision of the breast mass, leading to a final pathological diagnosis of POB. This is the first reported case of primary osteosarcoma during breastfeeding. We hope that this case report will improve readers’ understanding of the diagnosis and differential diagnosis of POB, especially for patients with atypical clinical symptoms and imaging findings, which should not be taken lightly.

Abstract Background Hoylesella marshii can be isolated from human oral cavities affected by dental pulp and periodontal infections, as well as from the dental plaque of healthy individuals, making it a common bacterium within the oral microbiota. However, its role in causing pleural infections in humans is rare. Case presentation A case of purulent pleural effusion occurred shortly after discharge in an elderly patient who had undergone surgery for gastric cancer. The infection was identified as being caused by an obligate anaerobe through laboratory culture, and was further identified as Hoylesella marshii causing pleural infection through 16 S rRNA gene sequence analysis. Susceptibility testing guided precise treatment with cefoperazone-sulbactam and metronidazole. The patient’s clinical symptoms improved rapidly, laboratory test indicators gradually returned to normal, and the patient ultimately recovered. Conclusion Hoylesella marshii can cause pleural infections in humans. Clinical microbiology laboratories should pay special attention to the cultivation of obligate anaerobes when routine aerobic cultures do not show bacterial growth but bacteria are visible on smear staining, and when conventional identification methods fail to identify the bacterium, analysis based on the highly conserved 16 S rRNA gene sequence can accurately and specifically identify the bacterium, guiding clinicians in formulating precise anti-infection strategies.

The specific of functioning for artificial intelligence and digital stratum is an important direction of interdisciplinary, including linguistics, researches in the modern world. The subject of the study is the voice assistant Alice of the Yandex company with the inbuilt Yandex GPT2 neural network. The object under the study is the AI functioning on the materials of phraseological units and set phrases of the Chinese and Russian languages with the universal semantic component смерть / death. The conceptual category of смерть / death was chosen due to the existence of the Russian and Chinese cultural tradition represented on the rich background ascendant to folklore images. The novelty of the study consists in understanding the notion of “a digital stratum as a separate component of the linguistic paradigm, according to N.I. Tolstoy, and it is introduced and discussed for the first time. In course of linguistic experiment, we managed to reveal four types of generations on the AI stimulus words: 1) the absence of generation; 2) the generation of the existing phraseological units and set phrases of direct and indirect nominations; 3) the hybrid generation; 4) the digital or arbitrary generation. By means of the continuous sampling method there were identified 50 % of the AI generations both in Russian and in translated into Russian materials. The results of the study allow conclude that there takes place of forming the digital stratum of the linguistic paradigm owing to the evolution of the virtual environment of language functioning. With time, textual generations which at present seem to be antilogical, could enter the live conversational style and become widely-used ones due to the mass use of voice systems in various spheres of daily living activities.

Abstract This paper proposes and investigates a novel 4H‐SiC trench MOSFET (TMOS) with integrated high‐K deep trench and gate dielectric (INHK‐TMOS). The integrated high‐K (INHK) consists of a high‐K gate dielectric and an extended high‐K deep trench dielectric in the drift region. Firstly, the high‐K gate dielectric together with the metal‐forming high‐K metal gate structure, which increases the gate oxide capacitance (COX), reduces the threshold voltage (VTH) and the specific on‐resistance (Ron,sp). Secondly, the extended high‐K deep trench dielectric not only modulates the electric field in the drift region by introducing a new electric field peak at the bottom of the high‐K deep trench dielectric, thereby enhancing the breakdown voltage (BV), but also improves the doping concentration (ND) of the drift region by the assist depletion effect of the high‐K dielectric, further optimizing the forward conduction characteristics. Simulation results demonstrate that when compared to the conventional TMOS, the INHK‐TMOS using HfO2 exhibits a 52.6% reduction in VTH, a 52.1% reduction in Ron,sp, a 20.3% increasement in BV and a 202.3% improvement in figure of merit.

Objective Yishu fault zone geothermal field and central Shandong uplift geothermal field are typical geothermal fields in south central Shandong Province. In order to investigated the distribution characteristics and mechanisms of fluorine enrichment in the geothermal water of the this area, Methods hydrochemical diagrams, geochemical simulations and principal component analysis were employed. Results The results show that the geothermal water in the study area is mainly Na-Ca-Cl-, Na-Ca-SO4-Cl- and Na-Cl-SO4-type water, dominated by weakly alkaline water. The predominant cation is the sodium ion, with fluorine concentration between 0.38 and 4.5 mg/L. Sodium-rich and weakly alkaline environments are faciliated to the enrichment of fluorine in the geothermal water. The fluorine concentration has significant positive correlations with the Na+, Cl- and TDS concentrations in the geothermal water. In addition, it has significant positive correlations with K+ and SO42- concentrations and significant negative correlations with Mg2+ and HCO3- concentrations in the geothermal water in the Yishu fault zone. The cation exchange effect in the geothermal water of the central Shandong uplift zone is stronger than that in the Yishu fault zone, and the reaction strength of Na+ is significantly stronger than that of Mg2+. The geothermal field of the central Shandong uplift and Yishu fault zones are both fracturing types. The thermal storage lithologies are limestone, limestone in the thermal alteration zone and ansanite in the broken belt, with strong water-rock interactions. The provenance of fluorine in the geothermal water is the dissolution reprecipitation of fluorine-containing minerals, and the fluorine concentration in the geothermal water is further increased by cation exchange and other water-rock interactions. High temperature and sodium-rich have a great influence on fluorine enrichment. Conclusion This research provides a reference for the exploitation and utilization of geothermal resources.

IntroductionKnee osteoarthritis (KOA) is a chronic degenerative bone metabolic disease that primarily affects older adults, leading to chronic pain and disability that affect patients’ daily activities. Electroacupuncture (EA) is a commonly used method for the treatment of chronic pain in clinical practice. Previous studies indicate that the endocannabinoid system is involved in EA analgesia, but whether endocannabinopeptide VD-hemopressin (α) and RVD-hemopressin (α) derived from hemoglobin chains are involved in EA analgesia is unclear.MethodsRNA-seq technology was used to screen which genes involved in EA analgesia. The expression of hemoglobin α chain and 26S proteasome were determined by Western blotting. The level of VD-hemopressin (α) and RVD-hemopressin (α) were measured by UPLC-MS/MS. Microinjection VD-Hemopressin (α), RVD-Hemopressin (α) and 26S proteasome inhibitor MG-132 into vlPAG, then observe mechanical and thermal pain thresholds.ResultsTherefore, we used RNA-seq to obtain differentially expressed genes Hba-a1 and Hba-a2 involved in EA analgesia in the periaqueductal gray (PAG), which were translated into the hemoglobin α chain. EA significantly increased the expression of the hemoglobin α chain and the level of hemopressin (α) and RVD-hemopressin (α). Microinjection of VD-hemopressin (α) and RVD-hemopressin (α) into the ventrolateral periaqueductal gray (vlPAG) mimicked the analgesic effect of EA, while CB1 receptor antagonist AM251 reversed this effect. EA significantly increased the expression of 26S proteasome in KOA mice. Microinjection of 26S proteasome inhibitor MG132 before EA prevented both the anti-allodynic effect and upregulation of the concentration of RVD-hemopressin (α) by EA treatment and upregulated the expression of the hemoglobin α chain.DiscussionOur data suggest that EA upregulated the concentration of VD-hemopressin (α) and RVD-hemopressin (α) through enhancement of the hemoglobin α chain degradation by 26S proteasome in the PAG, then activated the CB1 receptor, thereby exerting inhibition of chronic pain in a mouse model of KOA. These results provide new insights into the EA analgesic mechanisms and reveal possible targets for EA treatment of chronic pain.

BackgroundDepression is a significant risk factor affecting the mental health of older adults. In the context of accelerated population aging and the policy of “delayed retirement,” self-employment has become an important alternative for older adults. Thus, studying the difference in depression levels between self-employed older adults and retirees, along with the mechanisms behind these differences, has emerged as a crucial theoretical and practical issue.MethodsThis research, based on panel data from the China Health and Retirement Longitudinal Study for the years 2011, 2013, 2015, and 2018, employed fixed-effect, instrumental variable, mediation models to analyze the difference in depression levels between self-employed older adults and retirees, as well as the mediating mechanisms involved.ResultsThe findings indicate that self-employed older adults have lower levels of depression than retirees. The results of the mediating mechanism analysis suggest that self-employment can indirectly lower the depression levels of older adults by frequent social participation and greater life satisfaction. However, heterogeneity analysis revealed significant urban–rural differences and different types of self-employment in the impact of self-employment on the depression levels of older adults.ConclusionsThe results of this study are of great significance for enhancing the mental health of older adults and provide empirical support for China and other developing countries in formulating more effective aging policies and building a more beneficial aging society.

Skin aging and wound healing have always been significant topics in the skin field. Hyaluronic acid (HA), a natural glycosaminoglycan (GAG) presenting in the extracellular matrix (ECM), is extensively applied in the fields of anti-aging therapeutics and wound repair due to its unique physicochemical and biological properties. HA is indispensable in the regulation of diverse biological processes such as cellular proliferation, differentiation, migration, signaling, inflammatory responses, angiogenesis, and tissue regeneration. Consequently, HA-based formulations, including creams, gels, serums, and dermal fillers, are instrumental in combating wrinkles, enhancing skin hydration, correcting tear trough deformity, and restoring facial volume. Additionally, the inherent biocompatibility and high biodegradability of HA facilitates its chemical modification, rendering it an ideal material for wound healing and tissue regeneration. This review summarizes the recent advances and applications of the molecular mechanisms of HA and its derivatives in the field of anti-aging and wound healing; and discusses the prospects and challenges of HA-based compounds in tissue repair and skin regeneration.

Background: Existing epidemiological studies have indicated a correlation between air pollutants and the occurrence of mental disorders. However, it is difficult to estimate the causal relationship between the two because of the limitations of traditional epidemiological research. In our study, we aimed to extensively explore the causal relationship between five types of air pollutants and four types of mental disorders. Methods: Based on the IEU OPEN GWAS database, we performed a two-sample MR analysis. The primary analysis method utilized was the inverse variance weighted (IVW) method, supplemented by the MR-Egger method and the weighted median method. Additionally, we conducted sensitivity analyses with the Cochran's Q statistic method, the leave-one-out method, and the MR-Egger intercept. We chose at least 4 GWAS datasets for each of the four psychiatric diseases and conducted a meta-analysis of our results of the MR analysis. Results: The meta-analysis's findings demonstrated a causal link between depression and PM2.5 (OR=1.020, 95 %CI: (1.010,1.030), P=0.001). PM10 and schizophrenia are also causally related (OR=1.136, 95 %CI: (1.034,1.248), P=0.008). Nitrogen oxides and bipolar disorder have a causal relationship (OR=1.002, 95 %CI: (1.000,1.003), P=0.022). Nitrogen oxides and schizophrenia have a high causal association (OR=1.439, 95 %CI: (1.183,1.752), P

ABSTRACT The COVID-19 pandemic caused by SARS-CoV-2 has had a persistent and significant impact on global public health for 4 years. Recently, there has been a resurgence of seasonal influenza transmission worldwide. The co-circulation of SARS-CoV-2 and seasonal influenza viruses results in a dual burden on communities. Additionally, the pandemic potential of zoonotic influenza viruses, such as avian Influenza A/H5N1 and A/H7N9, remains a concern. Therefore, a combined vaccine against all these respiratory diseases is in urgent need. mRNA vaccines, with their superior efficacy, speed in development, flexibility, and cost-effectiveness, offer a promising solution for such infectious diseases and potential future pandemics. In this study, we present FLUCOV-10, a novel 10-valent mRNA vaccine created from our proven platform. This vaccine encodes hemagglutinin (HA) proteins from four seasonal influenza viruses and two avian influenza viruses with pandemic potential, as well as spike proteins from four SARS-CoV-2 variants. A two-dose immunization with the FLUCOV-10 elicited robust immune responses in mice, producing IgG antibodies, neutralizing antibodies, and antigen-specific cellular immune responses against all the vaccine-matched viruses of influenza and SARS-CoV-2. Remarkably, the FLUCOV-10 immunization provided complete protection in mouse models against both homologous and heterologous strains of influenza and SARS-CoV-2. These results highlight the potential of FLUCOV-10 as an effective vaccine candidate for the prevention of influenza and COVID-19.IMPORTANCEAmidst the ongoing and emerging respiratory viral threats, particularly the concurrent and sequential spread of SARS-CoV-2 and influenza, our research introduces FLUCOV-10. This novel mRNA-based combination vaccine, designed to counteract both influenza and COVID-19, by incorporating genes for surface glycoproteins from various influenza viruses and SARS-CoV-2 variants. This combination vaccine was highly effective in preclinical trials, generating strong immune responses and ensuring protection against both matching and heterologous strains of influenza viruses and SARS-CoV-2. FLUCOV-10 represents a significant step forward in our ability to address respiratory viral threats, showcasing potential as a singular, adaptable vaccine solution for global health challenges.

Introduction Acupuncture is widely used for metabolic-associated fatty liver disease (MAFLD) treatment; however, the clinical efficacy has not been confirmed due to the lack of high-level evidence-based clinical practice. The purpose of this study is to design a research protocol that will be used to determine the efficacy of acupuncture versus sham acupuncture (SHA) for MAFLD treatment.Methods and analysis This will be a multicentre, randomised and sham-controlled trial. Ninety-eight participants with MAFLD will be enrolled in this trial. Participants will be randomly assigned in a 1:1 ratio to receive acupuncture or SHA for 12 weeks. The primary outcome is the rate of patients with a 30% relative decline in liver fat after 12 weeks of treatment in MRI-proton density fat fraction (MRI-PDFF), which will be obtained by quantitative chemical shift imaging such as the multipoint Dixon method at 0, 12 and 24 weeks. Secondary outcomes include the changes in the relative liver fat content measured by MRI-PDFF, magnetic resonance elastography, liver function, lipid metabolism, homeostatic model assessment for insulin resistance (HOMA-IR) and serum high sensitivity C reactive protein, which will be obtained at 0, 6, 12 and 24 weeks. Body measurement indicators (body mass index, waist circumference, hip circumference and waist-to-hip ratio) will be obtained at 0, 3, 6, 9, 12 and 24 weeks. The alteration in the gut microbiota composition and its metabolism will be assessed by 16S ribosomal RNA sequencing and liquid chromatography-mass spectrometry at 0 and 12 weeks.Ethics and dissemination This study protocol has been approved by the ethics committee of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (2023-1347-114-01). The results of this study will be published in a peer-reviewed journal and presented at academic conferences.Trial registration number ChiCTR2300075701.

Background: STIL is an important cell cycle-regulating protein specifically recruited to the mitotic centrosome to promote the replication of centrioles in dividing cells. However, the potential role of STIL in the regulation of the biological functions of triple-negative breast cancer remains still unclear. Methods: We screened for differentially expressed STIL in the Cancer Genome Atlas database. The expression of STIL protein in 10 pairs of breast cancer tissues and adjacent normal tissues was further assessed by western blotting. Functionally, the knockdown and overexpression of STIL have been used to explore the effects of STIL on breast cancer cell proliferation, migration, and invasion. Mechanistically, RNA-seq, dual-luciferase reporter assay, chromatin immunoprecipitation assay, mass spectrometry, immunoprecipitation assay, and DNA pull-down assay were performed. Results: Breast cancer tissues and cells have higher STIL expression than normal tissues and cells. STIL knockdown impairs breast cancer cell growth, migration, and invasion, whereas STIL overexpression accelerates these processes. STIL promotes breast cancer progression by regulating FANCD2 expression, and exploration of its molecular mechanism demonstrated that STIL interacts with KLF16 to regulate the expression of FANCD2. Conclusions: Collectively, our findings identified STIL as a critical promoter of breast cancer progression that interacts with KLF16 to regulate Fanconi anemia pathway protein FANCD2. In summary, STIL is a potential novel biomarker and therapeutic target for breast cancer.

Zizania latifolia (Griseb.) Turcz. ex Stapf has been cultivated as a popular aquatic vegetable in China due to its important nutritional, medicinal, ecological, and economic values. The complete mitochondrial genome (mitogenome) of Z. latifolia has not been previously studied and reported, which has hindered its molecular systematics and understanding of evolutionary processes. Here, we assembled the complete mitogenome of Z. latifolia and performed a comprehensive analysis including genome organization, repetitive sequences, RNA editing event, intercellular gene transfer, phylogenetic analysis, and comparative mitogenome analysis. The mitogenome of Z. latifolia was estimated to have a circular molecule of 392,219 bp and 58 genes consisting of three rRNA genes, 20 tRNA genes, and 35 protein-coding genes (PCGs). There were 46 and 20 simple sequence repeats (SSRs) with different motifs identified from the mitogenome and chloroplast genome of Z. latifolia, respectively. Furthermore, 49 homologous fragments were observed to transfer from the chloroplast genome to the mitogenome of Z. latifolia, accounting for 47,500 bp, presenting 12.1% of the whole mitogenome. In addition, there were 11 gene-containing homologous regions between the mitogenome and chloroplast genome of Z. latifolia. Also, approximately 85% of fragments from the mitogenome were duplicated in the Z. latifolia nuclear genome. Selection pressure analysis revealed that most of the mitochondrial genes were highly conserved except for ccmFc, ccmFn, matR, rps1, and rps3. A total of 93 RNA editing sites were found in the PCGs of the mitogenome. Z. latifolia and Oryza minuta are the most closely related, as shown by collinear analysis and the phylogenetic analysis. We found that repeat sequences and foreign sequences in the mitogenomes of Oryzoideae plants were associated with genome rearrangements. In general, the availability of the Z. latifolia mitogenome will contribute valuable information to our understanding of the molecular and genomic aspects of Zizania.

In China, the major water user is agriculture. Under the background of climate change and with the pressure of scarce water resources, the study of crop water footprints serves as a theoretical basis for regional optimization of water resource management, fine-tuning crop planting structures and actively addressing the negative impacts of climate change on agricultural production, among other critical issues. Leveraging meteorological and agricultural data, we employed Taiyuan which is situated in Fen River Basin as our focal research subject and calculated and analyzed the water footprint variations concerning six major food crops—wheat, corn, grain, sorghum, soybean, and potato—from 2000 to 2020. Through meticulous examination, we identified the predominant contribution of blue water (45 %) to the total water footprint, followed by green water (39 %), with grey water playing the smallest role (16 %), indicating that the use of water for crops in the Fen River Basin mainly consumes surface water and groundwater. Our investigation reveals a complementary association between blue water and green water, while both blue water and grey water exhibit an overall declining tendency from 2000 to 2020. Moreover, our predictive modeling of food crop water footprints, considering various SSPs-RCPs scenarios refered from IPCC, points towards a peak within the coming 10–20 years, with a growth rate of 16.2 % to 33.0 %, followed by a subsequent decline. Particularly, in SSP3-7.0 scenario, the water footprint of food crops presents the highest, with a growth rate of up to 33.0 % because of the continuous growth of population and the increase of crop sowing area, while in SSP1-2.6 scenario, the water footprint of food crops shows the lowest, with a growth rate of 16.2 % because of the decrease in population and crop sowing area, before the middle of the current century.

Venetoclax, a selective BCL-2 inhibitor, has shown superior efficacy in the treatment of AML. Nevertheless, some AML patients with AML1-ETO respond poorly to venetoclax treatment. In this report, a relapsed/refractory (R/R) venetoclax resistant AML1-ETO positive AML patient showed rapid tumor regression after combination therapy with gilteritinib and venetoclax. Additional laboratory findings indicated that the combined impact of the two drugs may be associated with the induction of the integrated stress response. This case presents a novel therapeutic approach for the treatment of FLT3 wild-type RR, AML1-ETO AML patients who have primary resistance to venetoclax.

The development of a Digital Intelligence Quotient (DQ) scale for primary school students is the basis for research on the DQ of primary school students, which helps to scientifically diagnose the level and the current average DQ among Chinese primary school students. This study developed and validated a scale applicable to the assessment of DQ in Chinese primary school students where, the initial scale was first constructed; Then 1109 valid datasets were collected through purposive sampling and divided into Sample A and Sample B; Sample A was subjected to exploratory factor analysis and Sample B was tested by confirmatory factor analysis; The final validated scale consists of 22 items in 7 dimensions: digital identity, digital use, digital safety, digital security, digital emotional intelligence, digital literacy and digital rights. The scale has high reliability and validity and thus can be used as a reliable instrument for assessing DQ in Chinese primary school students.

Background Emerging evidence suggests a central role for inflammation in cardiac conduction disorder (CCD). It is unknown whether habitual physical activity could modulate the inflammation‐associated risks of incident CCD in the general population. Methods and Results This population‐based cohort was derived from the China Kailuan study, including a total of 97 192 participants without prior CCD. The end points included incident CCD and its subcategories (atrioventricular block and bundle‐branch block). Systemic inflammation was indicated by the monocyte‐to‐lymphocyte ratio (MLR). Over a median 10.91‐year follow‐up, 3747 cases of CCD occurred, with 1062 cases of atrioventricular block and 2697 cases of bundle‐branch block. An overall linear dose‐dependent relationship was observed between MLR and each study end point (all P‐nonlinearity≥0.05). Both higher MLR and physical inactivity were significantly associated with higher risks of conduction block. The MLR‐associated risks of developing study end points were higher in the physically inactive individuals than in those being physically active, with significant interactions between MLR levels and physical activity for developing CCD (P‐interaction=0.07) and bundle‐branch block (P‐interaction

Background Multiple target‐organ damages (TODs) in the same patient are common and further increase the risk of cardiovascular disease. However, the relationship between ambulatory central systolic blood pressure (SBP) and multiple TODs has yet to be explored. Methods and Results MobilO‐Graph PWA was used to monitor the participants' ambulatory blood pressure, and the presence of left ventricular hypertrophy, carotid hypertrophy, and kidney injury were used to define TOD. Logistic regression analyses and receiver operating characteristic analyses were used to explore the correlation between SBP and TOD. Overall, 2018 nondialysis patients with chronic kidney disease were included and 580 (28.74%) had multiple TODs. Twenty‐four‐hour central SBP with c2 calibration exhibited a stronger correlation with the increasing number of TOD compared with 24‐hour brachial SBP in ordinal logistic regression analyses. In the multivariable analyses with the presence of multiple TODs, the odds ratios were 1.786 (95% CI, 1.474–2.165; P

Abstract Background Salt stress severely inhibits plant growth, and the WRKY family transcription factors play important roles in salt stress resistance. In this study, we aimed to characterize the role of tobacco (Nicotiana tabacum) NtWRKY65 transcription factor gene in salinity tolerance. Results This study characterized the role of tobacco (Nicotiana tabacum) NtWRKY65 transcription factor gene in salinity tolerance using four NtWRKY65 overexpression lines. NtWRKY65 is localized to the nucleus, has transactivation activity, and is upregulated by NaCl treatment. Salinity treatment resulted in the overexpressing transgenic tobacco lines generating significantly longer roots, with larger leaf area, higher fresh weight, and greater chlorophyll content than those of wild type (WT) plants. Moreover, the overexpressing lines showed elevated antioxidant enzyme activity, reduced malondialdehyde content, and leaf electrolyte leakage. In addition, the Na+ content significantly decreased, and the K+/Na+ ratio was increased in the NtWRKY65 overexpression lines compared to those in the WT. These results suggest that NtWRKY65 overexpression enhances salinity tolerance in transgenic plants. RNA-Seq analysis of the NtWRKY65 overexpressing and WT plants revealed that NtWRKY65 might regulate the expression of genes involved in the salt stress response, including cell wall component metabolism, osmotic stress response, cellular oxidant detoxification, protein phosphorylation, and the auxin signaling pathway. These results were consistent with the morphological and physiological data. These findings indicate that NtWRKY65 overexpression confers enhanced salinity tolerance. Conclusions Our results indicated that NtWRKY65 is a critical regulator of salinity tolerance in tobacco plants.

ObjectiveTo study the change trend of blood pressure among rural adults in Shanxi province from 2002 to 2019, and to provide evidence for the prevention and control of hypertension in the population. MethodsThe study included 1 095 rural adult residents (≥ 18 years) with normal blood pressure at baseline in four counties of Shanxi province as part of the Provincial Nutrition and Chronic Diseases Household Cohort Study, which began in 2002. Data were collected from participants′ blood pressure measurements in 2015 and 2019, and changes in participants′ blood pressure between 2002 and 2019 were analyzed. ResultsAmong the participants, systolic and diastolic blood pressure (both in mm Hg) showed a significant increasing trend during the period (both P < 0.05). Compared to 122.9 ± 10.4 in 2002, systolic blood pressure increased by 14.8 to 137.7 ± 18.8 in 2015 and by 15.8 to 138.7 ± 18.1 in 2019, with an increase percentage of 12.0% and 12. 9%; while compared to 72.6 ± 6.9 in 2002, diastolic blood pressure increased by 7.3 to 79.9 ± 10.9 in 2015 and by 7.5 to 80.1 ± 10.9 in 2019, with increase percentages of 10.1% and 10.3%, respectively. ConclusionThere was a significant increasing trend in both systolic and diastolic blood pressure levels among rural adults in Shanxi province from 2002 to 2019.

To investigate the effect of ultrasound assisted NaCl soaking on the structure and digestive characteristics of black beans, the scanning electron microscopy, infrared spectroscopy analysis, X-ray diffraction and other methods were used to analyze the mechanism of NaCl on the structure of black beans. And the thermal properties, water absorption, and swelling rate were used to clarify the changes in the properties of the black beans during the ripening process, and the in vitro digestive properties of starch were analyzed. The results showed that ultrasound-assisted NaCl soaking decreased the densification of black bean powder particles and made the gap between particles larger while reducing the damage to the starch crystallization region. With the increase of NaCl concentration, the swelling rate of black bean particles increased by 28%, 48%, and 56% compared to water soaking, and the hardness significantly decreased. The gelatinization degree increased to 40%, 43%, and 45%, and the hydrolysis rate of black bean starch decreased to 19.05%, 17.93%, and 17.48%, respectively. This indicated that sodium ions could inhibit starch digestion, the NaCl soaking treatment in this study would provide a theoretical basis for the development of low GI functional foods.