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To develop a new method for the sterilization of fresh-cut lettuce, plasma-activated water (PAW) combined with dielectric barrier discharge (DBD) plasma technology was applied in this study. Response surface methodological approach was performed to determine the optimal sterilization process parameters. Meanwhile, the microbial count, color, browning degree, firmness and weight loss rate were evaluated to investigate the effects of combined cold plasma treatments on the qualities of fresh-cut lettuce during the storage. Results showed that the total viable bacteria count on the surface of fresh-cut lettuce was (0.48±0.07) lg CFU/g under the optimal treatment conditions when PAW preparation time was 130 s, PAW soaking time was 5 min, and DBD plasma treatment time was 135 s. Moreover, during 7 days of storage, the combined cold plasma treatments could effectively inhibit the growth of microorganisms, maintain the color and firmness of fresh-cut lettuce, delay the increase of weight loss rate, and inhibit the occurrence of browning, which would effectively prolong the shelf life of fresh-cut lettuce.

Abstract Acute ischemic stroke (AIS) is a major global health concern due to its high mortality and disability rates. Hemorrhagic transformation, a common complication of AIS, leads to poor prognosis yet lacks effective treatments. Preclinical studies indicate that hyperbaric oxygen (HBO) treatment within 12 h of AIS onset alleviates ischemia/reperfusion injuries, including hemorrhagic transformation. However, clinical trials have yielded conflicting results, suggesting some underlying mechanisms remain unclear. In this study, we confirmed that HBO treatments beginning within 1 h post reperfusion significantly alleviated the haemorrhage and neurological deficits in hyperglycemic transient middle cerebral arterial occlusion (tMCAO) mice, partly due to the inhibition of the NLRP3 inflammasome-mediated pro-inflammatory response in microglia. Notably, reactive oxygen species (ROS) mediate the anti-inflammatory and protective effect of early HBO treatment, as edaravone and N-Acetyl-l-Cysteine (NAC), two commonly used antioxidants, reversed the suppressive effect of HBO treatment on NLRP3 inflammasome-mediated inflammation in microglia. Furthermore, NAC countered the protective effect of early HBO treatment in tMCAO mice with hyperglycemia. These findings support that early HBO treatment is a promising intervention for AIS, however, caution is warranted when combining antioxidants with HBO treatment. Further assessments are needed to clarify the role of antioxidants in HBO therapy for AIS.

Abstract The increasing amount of coal gasification fine slag (CGFS) necessitates its resource utilization. CGFS, mainly composed of porous carbonaceous particles and partially fused spherical or agglomerated ash particles, is an inexpensive and high-quality raw material for preparing adsorbent materials. However, the challenge remains in developing a simple, low-cost, and environmentally friendly method to produce high-performance porous materials from CGFS. In this study, a one-step treatment method using 2 mol/L nitric acid under hydrothermal conditions was proposed for CGFS. The adsorbent material (CGFS-2 M) prepared under a solid–liquid ratio of 2:5 and an initial concentration of 200 mg/L methylene blue (MB) exhibited an equilibrium adsorption capacity as high as 210.20 mg/g. The excellent adsorption performance of CGFS-2 M can be attributed to several factors: acid leaching for mineral removal and pore formation, resulting in a specific surface area and total pore volume 2.2 and 1.6 times that of untreated CGFS, respectively, and an optimized mesoporous pore size distribution favorable for MB adsorption; optimal mineral removal and a well-defined carbon microcrystal structure providing more space for MB adsorption; nitric acid treatment increasing the surface oxygen content and hydrophilicity, enhancing its ability to remove MB. The synergistic effect of pore structure improvement and surface modification indicates a feasible research direction for enhancing the performance of CGFS-based adsorbent materials. These results provide theoretical support for the development of efficient CGFS-based adsorbents.

Abstract Background A modified surgical technique of sutured scleral fixated intraocular lens (SSF-IOL) was applied in a patient with post-traumatic aniridia and aphakia. Case presentation A 51-year-old man was referred to our clinic with decreased vision (finger count) in his right eye. This patient had previously undergone primary repair of the ruptured globe and pars plana vitrectomy to manage ocular trauma in the same eye. On presentation, the best corrected visual acuity in his right eye was 20/40. The slit lamp examination of his right eye revealed loss of total iris and lens. Corneal endothelial cell density was 1462 cells/mm2. Fundoscopic examination of the right eye revealed a retinal attachment. For IOL implantation, a rigid poly methyl methacrylate IOL was used with a 2-point scleral fixation performed using a polypropylene suture. One year postoperatively, the uncorrected distance visual acuity was 20/32, and the manifest refraction was − 0.5/–1.5 × 130 (20/20). Pentacam revealed that the astigmatism of the anterior corneal surface and the total cornea was 1.1 D (axis: 59.8°) and 1.0 D (axis: 35.6°), respectively. The horizontal (3°–183°) cross-section image displayed an IOL with a 1° tilt and 0.425 mm decentration. The patient reported no dysphotopsia or photophobia and was satisfied with the visual results. OPD-scan III revealed that higher-order aberrations in the right eye were slightly higher than those in the left eye. No suture-related or other serious complications were observed. Conclusion The modified SSF-IOL technique can offer improved visual quality for patients with aniridia and aphakia by ensuring proper IOL positioning and reducing astigmatism.

Abstract Endometrial cancer (UCEC) is one of three major malignant tumors in women. The HOX gene regulates tumor development. However, the potential roles of HOX in the expression mechanism of multiple cell types and in the development and progression of tumor microenvironment (TME) cell infiltration in UCEC remain unknown. In this study, we utilized both the The Cancer Genome Atlas (TCGA) database and International Cancer Genome Consortium (ICGC) database to analyze transcriptome data of 529 patients with UCEC based on 39 HOX genes, combing clinical information, we discovered HOX gene were a pivotal factor in the development and progression of UCEC and in the formation of TME diversity and complexity. Here, a new scoring system was developed to quantify individual HOX patterns in UCEC. Our study found that patients in the low HOX score group had abundant anti-tumor immune cell infiltration, good tumor differentiation, and better prognoses. In contrast, a high HOX score was associated with blockade of immune checkpoints, which enhances the response to immunotherapy. The Real-Time quantitative PCR (RT-qPCR) and Immunohistochemistry (IHC) exhibited a higher expression of the HOX gene in the tumor patients. We revealed that the significant upregulation of the HOX gene in the epithelial cells can activate signaling pathway associated with tumour invasion and metastasis through single-cell RNA sequencing (scRNA-seq), such as nucleotide metabolic proce and so on. Finally, a risk prognostic model established by the positive relationship between HOX scores and cancer-associated fibroblasts (CAFs) can predict the prognosis of individual patients by scRNA-seq and transcriptome data sets. In sum, HOX gene may serve as a potential biomarker for the diagnosis and prediction of UCEC and to develop more effective therapeutic strategies.

Acute pancreatitis (AP) is a potentially fatal condition with no targeted treatment options. Although inhibiting xanthine oxidase (XO) in the treatment of AP has been studied in several experimental models and clinical trials, whether XO is a target of AP and what its the main mechanism of action is remains unclear. Here, we aimed to re-evaluate whether XO is a target aggravating AP other than merely generating reactive oxygen species that trigger AP. We first revealed that XO expression and enzyme activity were significantly elevated in the serum and pancreas of necrotizing AP models. We also found that allopurinol and febuxostat, as purine-like and non-purine XO inhibitors, respectively, exhibited protective effects against pancreatic acinar cell death in vitro and pancreatic damage in vivo at different doses and treatment time points. Moreover, we observed that conditional Xdh overexpression aggravated pancreatic necrosis and severity. Further mechanism analysis showed that XO inhibition restored the hypoxia-inducible factor 1-alpha (HIF-1α)-regulated lactate dehydrogenase A (LDHA) and NOD-like receptor family pyrin domain containing 3 (NLRP3) signaling pathways and reduced the enrichment of 13C6-glucose to 13C3-lactate. Lastly, we observed that clinical circulatory XO activity was significantly elevated in severe cases and correlated with C-reactive protein levels, while pancreatic XO and urate were also increased in severe AP patients. These results together indicated that proper inhibition of XO might be a promising therapeutic strategy for alleviating pancreatic necrosis and preventing progression of severe AP by downregulating HIF-1α-mediated LDHA and NLRP3 signaling pathways.

Abstract Glycyrrhiza stems and leaves (GSL) are waste products of Glycyrrhiza; however, it has been considered a potential source of flavonoid compounds. In this study, GSL was processed by solid-state fermentation (SSF) to improve the flavonoid content and antioxidant activity. Firstly, a near-infrared (NIR) prediction model for flavonoid content in fermented Glycyrrhiza stems and leaves (FGSL) was established. Next, the effects of SSF on the antioxidant activity and metabolite profile of GSL were investigated. Finally, the possible mechanism of ferment release of flavonoids was explored based on enzyme activity, thermogravimetric analysis, and FTIR spectroscopy. The results revealed that NIR spectroscopy can efficiently analyze flavonoid contents in GSL, with predicted determination coefficient (Rp2) and root mean square error (RMSEP) of 0.9874 and 0.125, respectively. SSF significantly increased the levels of flavonoids, and enhanced the scavenging activities of DPPH radical and hydroxyl radical and reducing power of FGSL. Widely targeted metabolomic analysis showed the detection of 461 differential metabolites were identified after SSF, with 141 metabolites remarkably up-regulated and 320 metabolites of FGSL down-regulated during fermentation. The main types of differential metabolites were phenolic acids and flavonoids, and the destruction of cellulose by SFF was crucial to the release of flavonoids. In conclusion, our study revealed that SSF remarkably improved the phytochemical components of FGSL by increasing enzyme activity and destroying cellulose structure, thereby contributing to the enhancement of antioxidant activity. This study provided a scientific basis for the production of high-value flavonoids from plant materials and offered a novel approach to elucidate the release and conversion of flavonoids. Graphical Abstract

Abstract Depressive symptoms occur commonly in Alzheimer’s disease (AD). Although abnormalities in the amygdala-frontal circuit have been linked to emotional dysregulation and cognitive impairment, the neurological basis underlying these associations in AD patients with depressive symptoms (ADD) is unclear. We aimed to investigate the relationship between the amygdala-frontal circuit and depressive symptoms and cognitive function in ADD. We recruited 60 ADD, 60 AD patients without depressive symptoms (ADND), and 60 healthy controls (HC). Functional connectivity (FC) maps of the bilateral amygdala were compared. Fractional anisotropy (FA) of the amygdala-frontal circuit connected by the uncinate fasciculus (UF) was calculated using automated fiber quantification (AFQ). In addition, mediation analysis was performed to explore the effects of the amygdala-frontal circuit on the relationship between depressive symptoms and cognitive function. We found decreased bilateral amygdala FC with the inferior frontal gyrus (IFG) in the ADD group compared to the ADND and HC groups. Moreover, FA in the left frontal UF (nodes 64–97) was significantly lower in the ADD group than ADND group. Notably, amygdala-based FC with IFG and the left frontal UF FA mediated the relationship between depressive symptoms and cognitive function in ADD, with mediating effects ranging between 15 and 18%. Our study is the first to demonstrate the mediating effect of functional and microstructural abnormalities in the amygdala-frontal circuit in ADD. The findings suggest that the amygdala-frontal circuit may underlie emotional dysregulation in ADD, providing potential targets for treatment strategies.

Abstract Intercropping systems have garnered attention as a sustainable agricultural approach for efficient land use, increased ecological diversity in farmland, and enhanced crop yields. This study examined the effect of intercropping on the kiwifruit rhizosphere to gain a deeper understanding of the relationships between cover plants and kiwifruit in this sustainable agricultural system. Soil physicochemical properties and bacterial communities were analyzed using the Kiwifruit-Agaricus blazei intercropping System. Moreover, a combined analysis of 16S rRNA gene sequencing and metabolomic sequencing was used to identify differential microbes and metabolites in the rhizosphere. Intercropping led to an increase in soil physicochemical and enzyme activity, as well as re-shaping the bacterial community and increasing microbial diversity. Proteobacteria, Bacteroidota, Myxococcota, and Patescibacteria were the most abundant and diverse phyla in the intercropping system. Expression analysis further revealed that the bacterial genera BIrii41, Acidibacter, and Altererythrobacter were significantly upregulated in the intercropping system. Moreover, 358 differential metabolites (DMs) were identified between the monocropping and intercropping cultivation patterns, with fatty acyls, carboxylic acids and derivatives, and organooxygen compounds being significantly upregulated in the intercropping system. The KEGG metabolic pathways further revealed considerable enrichment of DMs in ABC transporters, histidine metabolism, and pyrimidine metabolism. This study identified a significant correlation between 95 bacterial genera and 79 soil metabolites, and an interactive network was constructed to explore the relationships between these differential microbes and metabolites in the rhizosphere. This study demonstrated that Kiwifruit-Agaricus blazei intercropping can be an effective, labor-saving, economic, and sustainable practice for reshaping bacterial communities and promoting the accumulation and metabolism of beneficial microorganisms in the rhizosphere.

Carbon capture and storage (CCS) and geological energy storage are essential technologies for mitigating global warming and achieving China’s “dual carbon” goals. Carbon storage involves injecting carbon dioxide into suitable geological formations at depth of 800 meters or more for permanent isolation. Geological energy storage, on the other hand, involves compressing air or other gases using surplus electricity during off-peak hours and temporarily storing them in underground reservoirs. These gases are then released during peak hours for power generation. Both technologies share commonalities in reservoir selection, with aquifers, depleted oil and gas reservoirs, and salt caverns all serving as potential storage sites. Carbon storage demands long-term containment, while geological energy storage necessitates multiple cycles of storage and release, requiring careful consideration during site evaluation. CCS projects are rapidly increasing globally, evolving towards networked and clustered configurations. In China, CCS projects are primarily focused on CO2-enhanced oil recovery, with fewer dedicated storage projects. However, direct storage projects are projected to dominate in the future and are also transitioning towards clustered development. China possesses favorable geological conditions for carbon storage, with relatively accurate estimates for oil and gas reservoir storage potential. Nevertheless, significant uncertainties persist regarding the storage capacity of saline aquifers. Compressed air energy storage in salt caverns is currently the predominant type of geological energy storage projects. Germany, the USA, and China have a total of five operating compressed air salt cavern energy storage power plants. China has abundant salt cavern resources, albeit with complex geological conditions. Suitable construction sites are concentrated in the eastern regions, and numerous projects are already underway. Compared to salt caverns, porous formations such as aquifers and depleted oil and gas reservoirs are more widespread and offer higher storage potential. However, technical challenges related to multiphase flow and chemical reactions need to be addressed. However, current site selection, potential assessment, efficiency optimization, and monitoring technologies face considerable challenges in meeting the demands of large-scale practical applications. Traditional hydrogeological exploration methods prove inadequate for selecting suitable sites, highlighting the need for efficient monitoring and risk control techniques. Additionally, there is a lack of cost-effective and accurate continuous monitoring technologies specifically designed for pressure and stress changes in storage and caprock formations. The development of key equipment components, such as monitoring and power generation systems, with independent intellectual property rights remains limited. Moreover, our reservoir simulation software requires further advancements to effectively simulate complex reservoirs at large scales. It is crucial to prioritize research and development in resource exploration, site selection technologies, and engineering equipment for both carbon sequestration and geological energy storage. The establishment of diverse demonstration projects and facilities for various storage options such as saline aquifers, depleted oil/gas fields are needed in the future as well.

Abstract Background The cold tolerance of rice is closely related to its production and geographic distribution. The identification of cold tolerance-related genes is of important significance for developing cold-tolerant rice. Dongxiang wild rice (Oryza rufipogon Griff.) (DXWR) is well-adapted to the cold climate of northernmost-latitude habitats ever found in the world, and is one of the most valuable rice germplasms for cold tolerance improvement. Results Transcriptome analysis revealed genes differentially expressed between Xieqingzao B (XB; a cold sensitive variety) and 19H19 (derived from an interspecific cross between DXWR and XB) in the room temperature (RT), low temperature (LT), and recovery treatments. The results demonstrated that chloroplast genes might be involved in the regulation of cold tolerance in rice. A high-resolution SNP genetic map was constructed using 120 BC5F2 lines derived from a cross between 19H19 and XB based on the genotyping-by-sequencing (GBS) technique. Two quantitative trait loci (QTLs) for cold tolerance at the early seedling stage (CTS), qCTS12 and qCTS8, were detected. Moreover, a total of 112 candidate genes associated with cold tolerance were identified based on bulked segregant analysis sequencing (BSA-seq). These candidate genes were divided into eight functional categories, and the expression trend of candidate genes related to ‘oxidation-reduction process’ and ‘response to stress’ differed between XB and 19H19 in the RT, LT and recovery treatments. Among these candidate genes, the expression level of LOC_Os12g18729 in 19H19 (related to ‘response to stress’) decreased in the LT treatment but restored and enhanced during the recovery treatment whereas the expression level of LOC_Os12g18729 in XB declined during recovery treatment. Additionally, XB contained a 42-bp deletion in the third exon of LOC_Os12g18729, and the genotype of BC5F2 individuals with a survival percentage (SP) lower than 15% was consistent with that of XB. Weighted gene coexpression network analysis (WGCNA) and modular regulatory network learning with per gene information (MERLIN) algorithm revealed a gene interaction/coexpression network regulating cold tolerance in rice. In the network, differentially expressed genes (DEGs) related to ‘oxidation-reduction process’, ‘response to stress’ and ‘protein phosphorylation’ interacted with LOC_Os12g18729. Moreover, the knockout mutant of LOC_Os12g18729 decreased cold tolerance in early rice seedling stage signifcantly compared with that of wild type. Conclusions In general, study of the genetic basis of cold tolerance of rice is important for the development of cold-tolerant rice varieties. In the present study, QTL mapping, BSA-seq and RNA-seq were integrated to identify two CTS QTLs qCTS8 and qCTS12. Furthermore, qRT-PCR, genotype sequencing and knockout analysis indicated that LOC_Os12g18729 could be the candidate gene of qCTS12. These results are expected to further exploration of the genetic mechanism of CTS in rice and improve cold tolerance of cultivated rice by introducing the cold tolerant genes from DXWR through marker-assisted selection.

Abstract Background Neutrophils play an essential role in Alzheimer’s disease (AD) pathology. However, the extent of their heterogeneity remains poorly explored, particularly in the context of developing novel therapies targeting these cells. Results We investigate the population structure of neutrophils purified from peripheral blood samples of AD mice. Utilizing single cell RNA sequencing, we comprehensively map neutrophil populations into six distinct clusters and find that the Neu-5 subset is specially enriched in AD mice. This subset exhibits fewer specific granules and a lower mature score. Gene ontology (GO) analysis reveals that genes involved in cytokine-mediated signaling are downregulated in the Neu-5 cluster. Furthermore, we identify the Ccrl2 gene is specifically upregulated in this subgroup, which is confirmed by flow cytometry in AD mice. Finally, immunohistochemical staining indicates that CCRL2 protein is increased in the brains of AD mice. Conclusions We identify a unique CCRL2 positive neutrophil cluster, that is specifically enriched in the peripheral blood of AD mice.

Abstract Background Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease. Its pathogenesis is not fully understood, and early diagnosis is challenging owing to the lack of effective biomarkers. This study aimed to analyze different samples to identify potential biomarkers and therapeutic targets. Methods Microarray datasets of RA, osteoarthritis (OA), and healthy control (HC) were downloaded from the Gene Expression Omnibus database. R software was used to identify differentially expressed genes (DEGs), which were visualized using volcano and heat maps. Venn diagrams, principal component analysis, gene set enrichment analysis, gene ontology, and Kyoto Encyclopedia of genes and genomes were used to analyze the data. A protein–protein interaction network was constructed, and synovial tissues from patients with RA and OA were collected for verification using the collagen‐induced arthritis mouse model. Results More DEGs were found in synovial tissues than in peripheral blood mononuclear cells or fibroblast‐like synoviocytes. Principal component analysis revealed significant differences between the RA and OA samples, highlighting the unique advantages of synovial tissue. Enrichment analysis revealed that metabolic and cytokine signaling pathways play crucial roles in the development of RA. Further analysis of the four synovial datasets identified 54 DEGs, of which signaling lymphocytic activation molecule family (SLAMF) 8 was identified as the key molecule. SLAMF8 levels were increased in the synovial tissue of patients with RA compared to those of patients with OA (0.38 ± 0.19 vs. 12.40 ± 1.66), and SLAMF8 levels were similarly elevated in collagen‐induced arthritis model mice compared with those in the healthy mice (1.13 ± 0.47 vs. 9.05 ± 2.52). Conclusions This study established the unique advantages of synovial tissue for RA research and identified metabolic and cytokine signaling pathways as important for RA development. Thus, SLAMF8 may be a potential therapeutic target for RA.

Introduction: This study aimed to investigate the differences between pregnant women with chronic hepatitis B virus (HBV) infection and intrafamilial infection and those without intrafamilial infection. Methods: HBV-DNA was extracted from the sera of 16 pregnant women with chronic hepatitis B (CHB) and their family members for gene sequencing and phylogenetic analyses. A total of 74 pregnant women with CHB were followed up from the second trimester to 3 months postpartum. Viral markers and other laboratory indicators were compared between pregnant women with CHB with and without intrafamilial infection. Results: The phylogenetic tree showed that HBV lines in the mother-spread pedigree shared a node, whereas there was an unrelated genetic background for HBV lines in individuals without intrafamilial infection. From delivery to 3 months postpartum, compared with those without intrafamilial infection, pregnant women with intrafamilial infection were related negatively to HBV-DNA (β = −0.43, 95% confidence interval [CI]: −0.76 to −0.12, p = 0.009), HBeAg (β = −195.15, 95% CI: −366.35 to −23.96, p = 0.027), and hemoglobin changes (β = −8.09, 95% CI: −15.54 to −0.64, p = 0.035) and positively to changes in the levels of alanine aminotransferase (β = 73.9, 95% CI: 38.92–108.95, p < 0.001) and albumin (β = 2.73, 95% CI: 0.23–5.23, p = 0.033). Conclusion: The mother-spread pedigree spread model differs from that of non-intrafamilial infections. Pregnant women with intrafamilial HBV infection have less hepatitis flares and liver damage, but their HBV-DNA and HBeAg levels rebound faster after delivery, than those without intrafamilial infection by the virus.

Schools are important places to carry out earthquake disaster education. Earthquake prevention and disaster reduction publicity and education in colleges and universities can help improve the results of earthquake safety education in primary and secondary schools. It is important to strengthen the awareness and skills of college students in earthquake prevention and disaster reduction, so that they can change their role to provide services to the society, and take the initiative to undertake the publicity and popularization of earthquake disasters, which is conducive to improving the ability of earthquake prevention and disaster preparedness of the whole people. In view of the problems found in the practice of popular science popularization, this paper compares the differences between universities and other academic sections of earthquake popular science popularization through questionnaire survey, analyzes the reasons and summarizes the experience, and puts forward the ways to strengthen the publicity and education of earthquake prevention and disaster reduction in universities. The analysis points out that the publicity and education of earthquake prevention and disaster reduction for college students is a continuous and dynamic project, and colleges and universities need to vigorously carry out earthquake safety education in many aspects such as concept, knowledge, skills and responsibilities, and at the same time need to rely on the strength and resources of relevant departments to improve the publicity and education effect.

Abstract Background To assess the immunogenicity of the current primary polio vaccination schedule in China and compare it with alternative schedules using Sabin or Salk-strain IPV (sIPV, wIPV). Methods A cross-sectional investigation was conducted at four sites in Chongqing, China, healthy infants aged 60–89 days were conveniently recruited and divided into four groups according to their received primary polio vaccination schedules (2sIPV + bOPV, 2wIPV + bOPV, 3sIPV, and 3wIPV). The sero-protection and neutralizing antibody titers against poliovirus serotypes (type 1, 2, and 3) were compared after the last dose. Results There were 408 infants completed the protocol. The observed seropositivity was more than 96% against poliovirus types 1, 2, and 3 in all groups. IPV-only groups induced higher antibody titers(GMT) against poliovirus type 2 (Median:192, QR: 96–384, P

Abstract Background As is known, CD4 cell count is a significant parameter predicting HIV progression, opportunistic infections and death in HIV-infected individuals, as well was an important indicator for initiating antiretroviral therapy (ART). In China’s National Free Antiretroviral Treatment Program, people with HIV (PWH) on ART can receive a CD4 count test at least once every six months. Importantly, the baseline CD4 count (before ART initiation) is significantly correlated with ART and even prognosis, but the influence of the peak CD4 cell count on ART and/or clinical outcomes is still unknown. Methods A retrospective study was conducted among 7965 PWH who received ART from October 2003 to September 2022 at Yunnan Infectious Disease Hospital. Clinical features and laboratory data were collected and analyzed by Chi-square test, univariate and multivariate Cox regression analysis. After elimination of confounding variables, multivariate Cox regression analysis was performed to identify survival-related factors. Results Of a total of 7965 PWH in the ART treatment cohort who met the inclusion and exclusion criteria, 7939 were finally included in the subsequent analyses. First, it was found that the proportion of clinical variables, including sex, age distribution, interval from diagnosis to ART initiation, marital status, and others, was significantly different between the living and dead groups (P

Abstract Whether and how the reactive oxygen species generated by hepatic stellate cells (HSCs) promote immune evasion of hepatocellular carcinoma (HCC) remains mysterious. Therefore, investigating the function of superoxide anion (O2 •−), the firstly generated reactive oxygen species, during the immune evasion become necessary. In this work, we establish a novel in situ imaging method for visualization of O2 •− changes in HSCs based on a new two-photon fluorescence probe TPH. TPH comprises recognition group for O2 •− and HSCs targeting peptides. We observe that O2 •− in HSCs gradually rose, impairing the infiltration of CD8+ T cells in HCC mice. Further studies reveal that the cyclin-dependent kinase 4 is deactivated by O2 •−, and then cause the up-regulation of PD-L1. Our work provides molecular insights into HSC-mediated immune evasion of HCC, which may represent potential targets for HCC immunotherapy.

Abstract Background Premature infants commonly encounter difficulties with oral feeding, a complication that extends hospital stays, affects infants’ quality of life, and imposes substantial burdens on families and society. Enhancing preterm infants’ oral feeding skills and facilitating their transition from parenteral or nasal feeding to full oral feeding pose challenges for neonatal intensive care unit (NICU) healthcare professionals. Research indicates that oral motor interventions (OMIs) can enhance preterm infants’ oral feeding capabilities and expedite the transition from feeding initiation to full oral feeding. Nonetheless, the most suitable timing for commencing these interventions remains uncertain. Methods This is a single-blind, randomized controlled trial. Preterm with a gestational age between 29+0 to 34+6 weeks will be eligible for the study. These infants will be randomized and allocated to one of two groups, both of which will receive the OMIs. The intervention commences once the infant begins milk intake during the early OMIs. Additionally, in the late OMIs group, the intervention will initiate 48 h after discontinuing nasal continuous positive airway pressure. Discussion OMIs encompass non-nutritive sucking and artificial oral stimulation techniques. These techniques target the lips, jaw, muscles, or tongue of premature infants, aiming to facilitate the shift from tube feeding to oral feeding. The primary objective is to determine the ideal intervention timing that fosters the development of oral feeding skills and ensures a seamless transition from parenteral or nasal feeding to full oral feeding among preterm infants. Furthermore, this study might yield insights into the long-term effects of OMIs on the growth and neurodevelopmental outcomes of preterm infants. Such insights could bear substantial significance for the quality of survival among preterm infants and the societal burden imposed by preterm birth. Trial registration chictr.org.cn ChiCTR2300076721. Registered on October 17, 2023.

Guilin rice noodles belong to fresh wet rice noodles, which are difficult to be preserved due to their high moisture content and susceptibility to microbial contamination. Therefore, it is very important to analyze its putrefactive bacteria and screen bacteriostatic agents for extending the shelf life, and maintain the taste and nutritional value. In order to study the microbial growth during the storage of Guilin rice noodles, 13 strains of spoilage organism were isolated and purified from Guilin rice noodles stored at room temperature for 1 to 3 days, and six main spoilage organism MF1, MF2, MF3, MF4, MF6 and MF12 were obtained through the counterfactual experiment. Then the main spoilage organism were identified as Bacillus thuringiensis, B. cereus, B. velezensis, Citrobacter sp. and Exiguobacterium acetylicum through routine identification combined with molecular identification. Furthermore, the effective antibacterial agents and optimal inhibitory concentrations were selected from five food additives through the plate culture. The results showed that different concentrations of ascorbic acid and citric acid had good antibacterial effects on six types of spoilage bacteria, with the optimal inhibitory concentrations being 90 and 120 mg/mL, respectively. This shows that ascorbic acid and citric acid can be used as preservatives of Guilin rice noodles and have a certain application prospect in the storage and fresh-keeping of Guilin rice noodles.

Laser weeding is one of the promising weed control methods for weed management in organic agriculture. However, the complex field environments lead to low weed detection accuracy, which makes it difficult to meet the requirements of high-precision laser weed control. To overcome this challenge and facilitate precise weeding by laser weeding robots in complex fields, this study suggests the use of a dual-mode image fusion algorithm of visible light and infrared light based on machine vision. This innovative technology, introducing infrared information based on visible light images, enhances weed detection accuracy and resilience to environmental factors. The introduction of the Swin-transformer module and Slim-neck module enables the creation of a brand new weed detection model allied with the YOLOv8 model, applicable for weed meristem detection. According to the experimental results, for fusion images with a resolution of 640*640, the dual-scale fusion of RGB and NIR images on the improved network has an average accuracy (mAP) of 96.0% and a detection accuracy of 94.0%, respectively. This study builds a laser weeding robot with a mobile platform, a weed recognition module and a laser polarization transmitter module. The ROS system is utilized to effectively detect weeds and determine their geometric center position after the weed detection model is successfully installed on the robot platform. The laser vibrator demonstrates accurate deflection to the weed growth position during the weed detection and laser illumination experiment. The results show that the accuracy of weed detection has reached 82.1%, and the efficiency of laser weeding has reached 72.3%. These results prove the feasibility of the laser weeding method proposed in this study. However, the fusion strategy of these two kinds of images still has great room for improvement in terms of detection accuracy and efficiency. In the future, multiple modal information can be used to improve the identification efficiency of weeds in the field.

Lithium-ion batteries (LIBs) have become the predominant and widely used energy storage systems in portable electronic devices, such as video cameras, smartphones, laptops, and plug-in hybrid vehicles, along with in stationary energy storage applications like power banks and backup energy storage systems. Moreover, they are widely used in the latest models of all electric vehicles (EVs) and hybrid electric vehicles (HEVs). However, to meet the demand for EVs and HEVs, notable improvements in commercially available LIBs are required. These include improving energy density, cycling life, power and rate capabilities, safety, and cost. In spite of the initial commercialization of LIBs in 1990 by Sony, current commercial LIBs still rely on graphite/carbon as the anode material, providing a theoretical capacity of approximately 372 mAh g−1. The search is on for viable alternatives to graphite with higher capacity materials, and silicon (Si) has emerged as a promising candidate with a theoretical capacity of approximately 4200 mAh g−1. However, Si anodes face several challenges, such as considerable volume expansion during the lithiation/delithiation process, which leads to significant crystallographic-related phase-induced stresses, continuous formation of a solid electrolyte interface (SEI), and cycle retention decay. The volume expansion caused by stress leads to the pulverization of Si electrodes. This results in the loss of electrical contact with the substrate or current collector, causing a significant and rapid decrease in capacity and ultimately leading to battery failure. This review explores the challenges associated with Si-based anodes, their underlying causes, and their comparative advantages over conventional anodes. Furthermore, the review discusses innovative solutions to address these challenges, such as utilizing novel binders, electrolyte additives, structural, interfacial, composite engineering techniques, and prelithiation methods. Finally, considering the material cost, the suggestion to transition entirely to using up to 100% wt. silicon for anode development is proposed, streamlining practical and commercial implementation in future LIBs.

Glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) are putative non-amyloid biomarkers indicative of ongoing inflammatory and neurodegenerative disease processes. Hence, this study aimed to demonstrate the relationship between plasma biomarkers (GFAP and NfL) and 18F-AV-1451 tau PET images, and to explore their effects on cognitive function. Ninety-one participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database and 20 participants from the Shanghai Action of Prevention Dementia for the Elderly (SHAPE) cohort underwent plasma biomarker testing, 18F-AV-1451 tau PET scans and cognitive function assessments. Within the ADNI, there were 42 cognitively normal (CN) individuals and 49 with mild cognitive impairment (MCI). Similarly, in the SHAPE, we had 10 CN and 10 MCI participants. We calculated the standardized uptake value ratios (SUVRs) for the regions of interest (ROIs) in the 18F-AV-1451 PET scans. Using plasma biomarkers and regional SUVRs, we trained machine learning models to differentiate between MCI and CN subjects with ADNI database and validated in SHAPE.Results showed that eight selected variables (including left amygdala SUVR, right amygdala SUVR, left entorhinal cortex SUVR, age, education, plasma NfL, plasma GFAP, plasma GFAP/ NfL) identified by LASSO could differentiate between the MCI and CN individuals, with AUC ranging from 0.783 to 0.926. Additionally, cognitive function was negatively associated with the plasma biomarkers and tau deposition in amygdala and left entorhinal cortex. Increased tau deposition in amygdala and left entorhinal cortex were related to increased plasma biomarkers. Moreover, tau pathology mediated the effect of plasma biomarkers level on the cognitive decline. The present study provides valuable insights into the association among plasma markers (GFAP and NfL), regional tau deposition and cognitive function. This study reports the mediation effect of brain regions tau deposition on the plasma biomarkers level and cognitive function, indicating the significance of tau pathology in the MCI patients.

The purpose of this study was to investigate the effects of BOC on glioblastoma cells and its underlying mechanisms. In vitro, BOC-knockdown was performed in glioma cell lines. CCK-8 and Transwell were used to assess the impact of BOC on the viability, invasion, and migration of gliobma cells. RNA-seq technology was employed to analyze the differential gene expression between BOC-knockdown glioma cells and the control group, and qRT-PCR was used to validate the expression of downstream differential genes. SMO-overexpression was performed to investigate the effects of SMO on glioma cells. A BOC-knockdown mouse subcutaneous tumor model was to verify the effects of BOC on mouse tumors. Tissue microarray technology was used to detect the expression of BOC and SMO in samples of normal human brain tissue and glioma tissue. In vitro, BOC-knockdown inhibited the viability, invasion, and migration of glioma cells, as well as downregulated the expression of downstream differential genes SMO, EGFR, HRAS, and MRAS. Conversely, SMO-overexpression upregulated the viability, invasion, and migration abilities of BOC-knockdown cells. In vivo, BOC-knockdown suppressed tumor growth in mice and downregulated the expression of downstream differential genes SMO, EGFR, HRAS, and MRAS. Tissue microarray results showed that both BOC and SMO were highly expressed in glioma tissues. BOC is aberrantly overexpressed in glioma patients and promotes glioma development. Mechanistically, BOC activates the Hedgehog (Hh) and RAS signaling pathways by upregulating the expression of SMO, EGFR, HRAS, and MRAS, thereby facilitating the Proliferation, invasion and migration of glioma cells.

Abstract Background Podiatry enrolments at Australian and New Zealand universities have decreased by 17.3% since 2015, which threatens the profession's sustainability and the health and wellbeing of Australian and New Zealand people and communities. Reasons for this decline remain unclear due to insufficient evidence on factors influencing career choices. The overarching aim of this study was to identify motivators and barriers for studying podiatry in Australia and New Zealand. Methods This study used a convergent mixed methods design. Students enrolled in (i) podiatry and (ii) relevant non‐podiatry health, sport or science programs at nine Australian and one New Zealand university, were invited to participate in an online survey. First‐year podiatry students were also invited to participate in an online workshop. Quantitative data were analysed using descriptive statistics and linear/logistic regression models. Three independent assessors used inductive thematic analysis for the qualitative data. Results Overall, 278 podiatry students (mean age 24.9 ± 8.5 years, 65.1% female) and 553 non‐podiatry students (mean age 24.8 ± 8.2 years, 75.4% female; 32.2% from physiotherapy and 29.1% from occupational therapy) responded to the survey. Interest in a health‐related career, wanting to make a difference to people's health, and opportunity to care for people from different backgrounds/age groups were key motivating factors among podiatry students. Barriers to studying podiatry were encountered by 28.1% of podiatry students. Thematic analysis identified seven themes concerning career choice, which are as follows: (i) awareness of profession and scope of practice; (ii) stereotypes and negative perceptions of the profession; (iii) awareness of career pathways; (iv) job prospects and earning potential; (v) working with people and building relationships; (vi) podiatry is not the first preference; and (vii) barriers which limit student enrolment. Conclusions There are a variety of factors that motivate and influence students to study podiatry, however, altruistic reasons are most highly rated. Allied health students have limited understanding of the scope of practice and career opportunities in podiatry. Additionally, the podiatry profession often faces negative stereotypes. Further work is required to reverse the negative stereotypes and perceptions of podiatry and build knowledge of the profession's scope of practice, career pathways/opportunities, job prospects and earning potential.

Background: BET family proteins are important epigenetic and transcriptional regulators involved in the control of tumorigenesis and development and have become important targets for cancer therapy. However, there is no systematic bibliometric analysis in this field. A visual analysis of the research hotspots and trends of BET is helpful to understand the future development direction. Method: We used CiteSpace, VOSviewer, and Excel to visualize and analyze the trends regarding authors, journals, countries or regions, highly cited papers, and keywords in the field. Result: The results included a total of 946 publications. There are many more papers on BET proteins published since 2013. The papers are mainly from 44 countries, led by the U.S. and China. A total of 7381 authors were identified, among which Bradner, J.E. had the greatest number of articles and the greatest influence. Cancer Discovery was the journal with the most citations per article. Our analysis identified the most influential papers in the field, including highly cited papers and citation burst references. The most frequent keywords included ‘expression’, ‘c-Myc’, ‘cancer’, ‘BRD4’, ‘BET inhibition’, ‘resistance’, ‘differentiation’, and ‘JQ1’, which represent the focus of current and developing research fields. Conclusion: Research on BET is thriving. Collaboration and exchanges between countries and institutions must be strengthened in the future, and the mechanisms of BET-related pathways, the relationship between BET and various diseases, and the development of new BET inhibitors have become the major focus of current research and the trend of future research.

DNA hydrogels are three-dimensional polymer networks constructed using DNA as the structural building block. Due to the tight binding between hydrophilic groups on DNA chains and water molecules, they exhibit outstanding plasticity and fluid thermodynamic properties, making them one of the best choices for mimicking natural biological tissues. By controlling the backbone building blocks, gelation conditions, and cross-linking methods of DNA hydrogels, hydrogels with different mechanical strengths can be obtained, thus expanding their applications in the field of biology. This review first introduces the relationship between the mechanical properties of DNA hydrogels and their structure, elucidates the approaches and strategies for mechanical property modulation, and focuses on the scheme of controllable design to modulate the mechanical properties of DNA hydrogels for applications in biosensing, cellular function regulation, and bone tissue engineering. Furthermore, this review outlines the future development directions and challenges faced in the mechanical property modulation of DNA hydrogels, providing useful information for the precise design of DNA hydrogels for biological research.

The de Winter electrocardiogram (ECG) pattern indicates severe stenosis or occlusion of the left anterior descending artery (LAD). We present a 72-year-old female with 1.5-h chest pain. Angiography and optical coherence tomography (OCT) revealed 90 % LAD stenosis with plaque rupture, but no ST-segment elevation in the precordial leads. The de Winter pattern, characterized by upsloping ST-segment depression in V1-V6, appeared only in lead V2. Following successful percutaneous coronary intervention (PCI), the de Winter pattern disappeared. This case underscores the significance of the de Winter pattern in one precordial lead, necessitating prompt angiography and PCI for improved patient outcomes.

ABSTRACT Growing evidence have indicated the crucial role of intratumor microbiome in a variety of solid tumor. However, the intratumoral microbiome in gynecological malignancies is largely unknown. In the present study, a total of 90 Han patients, including 30 patients with cancer in cervix, ovary, and endometrium each were enrolled, the composition of intratumoral microbiome was assessed by 16S rDNA amplicon high throughput sequencing. We found that the diversity and metabolic potential of intratumoral microbiome in all three cancer types were very similar. Furthermore, all three cancer types shared a few taxa that collectively take up high relative abundance and positive rate, including Pseudomonas sp., Comamonadaceae gen. sp., Bradyrhizobium sp., Saccharomonospora sp., Cutibacterium acnes, Rubrobacter sp., Dialister micraerophilus, and Escherichia coli. Additionally, Haemophilus parainfluenzae and Paracoccus sp. in cervical cancer, Pelomonas sp. in ovarian cancer, and Enterococcus faecalis in endometrial cancer were identified by LDA to be a representative bacterial strain. In addition, in cervical cancer patients, alpha-fetoprotein (AFP) (correlation coefficient = −0.3714) was negatively correlated (r = 0.4, 95% CI: 0.03 to 0.7) with Rubrobacter sp. and CA199 (correlation coefficient = 0.3955) was positively associated (r = 0.4, 95% CI: 0.03 to 0.7) with Saccharomonospora sp.. In ovarian cancer patients, CA125 (correlation coefficient = −0.4451) was negatively correlated (r = −0.4, 95% CI: −0.7 to −0.09) with Porphyromonas sp.. In endometrial cancer patients, CEA (correlation coefficient = −0.3868) was negatively correlated (r = −0.4, 95% CI: −0.7 to −0.02) with Cutibacterium acnes. This study promoted our understanding of the intratumoral microbiome in gynecological malignancies.IMPORTANCEIn this study, we found the compositional spectrum of tumor microbes among gynecological malignancies were largely similar by sharing a few taxa and differentiated by substantial species owned uniquely. Certain species, mostly unreported, were identified to be associated with clinical characteristics. This study prompted our understanding of gynecological malignancies and offered evidence for tumor microbes affecting tumor biology among cancers in the female reproductive system.

The agricultural sector constitutes a pivotal component of China’s economy. Considering China’s substantial population, alterations in cultivated land hold considerable potential to influence agricultural output, consequently impacting the livelihoods of a substantial portion of the populace. Therefore, understanding the dynamics of cultivated land is crucial for ensuring food security.From 2000 to 2020, this research amalgamates county-level land cover, environmental variables, and socio-economic indicators to examine the spatiotemporal dynamics of cultivated land expansion across diverse agricultural sectors in China, elucidating associated causal factors. The following deduction is presented: (1) Variations in the extent of cultivated land exhibit diversity across distinct agricultural regions. It has spatial heterogeneity. (2) From 2000 to 2020, among China’s nine primary agricultural regions, those east of the Hu Line mainly experienced an expansion trend in cultivated land. The intensity of cultivated land expansion was highest in the northern arid and semi-arid regions, followed by the Qinghai-Tibet Plateau, albeit with a predominant slow expansion. In the agricultural areas west of the Hu line, except for the Northeast Plain, the expansion intensity of cultivated land was not significant, and the cultivated land was mainly contracted, with a patchy distribution. (3) Both natural and socio-economic factors influence cultivated land changes in China. Altitude and precipitation stand out as the dominant natural influencers, whereas within the realm of socio-economic considerations, population density, the disposable income per capita among rural inhabitants, the total power of agricultural machinery, the gross value of primary industry output, and the total power of agricultural machinery collectively exert influence on alterations in cultivated land. Different indicators have varying positive or negative effects on cultivated land.

Background: The elevated long-term cardiovascular disease (CVD) risks associated with pneumonia have been observed among inpatients, yet the risks associated with outpatients are less understood. Methods: We used register-based data and a matched cohort design, including 98,354 pneumonia inpatients and 44,486 outpatients, as well as a 5-fold number of matched healthy controls. Associations between pneumonia presentation (in inpatient and outpatient settings) and long-term CVD risks were measured by rate difference and hazard ratio (HR) using Poisson and Cox regressions in a time-dependent manner. Results: During a maximum follow-up period of 5.7 years of ischemic heart disease (IHD), heart failure (HF), and stroke were documented among pneumonia inpatients.Relative to healthy controls, pneumonia patients showed increased risks of IHD, HF, and stroke. Women and young inpatients demonstrated stronger associations of CVD with pneumonia; inpatients aged 60 years or older showed the highest excessive CVD risks. Conclusions: Pneumonia demanding outpatient and inpatient cares are intermediate-term and long-term risk factors of incident CVDs respectively, underscoring the need to plan setting-specific and time-dependent CVD-preventive cares following pneumonia presentation.

In this study, a systematic analysis was conducted to investigate the efficiency and mechanism of methylene blue (MB) removal from water using blue coke-based activated carbon (AC) as an adsorbent. The investigation encompassed several critical parameters, including adsorbent dosage, contact time, pH, temperature, initial MB concentration, and the regeneration capacity of the adsorbent. The adsorption mechanism of MB by AC was elucidated through instrumental analysis and theoretical models such as adsorption kinetics, isotherm models, and thermodynamic analysis. The experimental results demonstrated several key findings: the removal efficiency of MB increased with the adsorbent dosage, although the unit adsorption capacity decreased; the removal rate of MB rose rapidly with increasing contact time and reached equilibrium after 90 min; the highest removal efficiency was achieved at pH 6; the adsorption capacity increased with higher initial MB concentrations. The adsorption kinetics conformed to the pseudo-second-order model, indicating that chemical adsorption was the predominant control step. The adsorption process was identified as a spontaneous reaction, with the Langmuir model suggesting a maximum adsorption capacity of 2040.696 mg/g at 318 K. Furthermore, AC exhibited an abundant mesoporous structure and surface functional groups, contributing to the efficient removal of MB. The adsorption mechanism involved pore-filling, hydrogen bonding, π-π interactions, and electrostatic attraction. Additionally, AC demonstrated excellent regeneration performance. These findings suggest that AC prepared from blue coke holds significant potential for industrial applications in MB removal, owing to its high removal efficiency, low cost, and good regenerative properties, making it highly valuable for practical use.

Cropland resources are crucial for food security and economic development. As a populous nation that considers cropland a valuable strategic resource, China has faced challenges of the phenomenon of the cropland non-agriculturalization (CLNA) in recent years. Studying the spatial and temporal patterns of CLNA in different regions and its driving factors is of great significance for formulating and improving cropland protection policies. Based on remotely sensed land use data, the spatial and temporal evolution characteristics of CLNA and its underlying influencing factors in three typical regions of China (Jilin, Henan, and the Guangdong-Hong Kong-Macao Greater Bay Area) from 2000 to 2020 were revealed by using Moran’s index, Lorenz’s curve, and XGBoost-SHAP model. The results of the study show that: (1). There was a certain amount of CLNA phenomenon in all three regions during the past 20 years, and the phenomenon in the Guangdong-Hong Kong-Macao Greater Bay Area (GHM) was the most serious, with the CLNA area exceeding 6 % of the total cropland in the peak period. The average Gini coefficients of Jilin (JL), Henan (HN) and the GHM were 0.39, 0.45 and 0.77, respectively, and the spatial imbalance of CLNA was the most serious in the GHM, which seriously threatened the food security of the region. (2). In the three study areas, socio-economic factors contributed 68 % (JL), 86 % (HN) and 84 % (GHM) to the CLNA, significantly higher than natural factors, and were the dominant factors influencing the CLNA. (3) Although socio-economic factors played a dominant role in non-agriculturalization, the role of natural factors such as elevation and slope should not be overlooked. These natural factors not only directly affect land usability and suitability but also interact with socio-economic factors, jointly shaping the trends and patterns of CLNA. In specific regions, natural constraints may hinder the conversion of cropland to non-agricultural uses, thus playing a protective role. Conversely, in some areas, favorable natural conditions may combine with strong economic development needs, accelerating the transformation of cropland to non-agricultural uses. This interactive effect of socio-economic factors and natural conditions revealed that the CLNA is a complex process influenced by multiple factors. Overall, this study not only provides an in-depth perspective for understanding the spatiotemporal evolution characteristics and complex driving mechanisms of CLNA but also offers a scientific basis for precisely formulating policies for cropland protection and promoting sustainable land use.

IntroductionPre-HSCT disease control, suboptimal long-term prognosis, and a high recurrence incidence (RI) continue to pose significant challenges for hematopoietic stem cell transplantation (HSCT) in juvenile myelomonocytic leukemia (JMML) patients.MethodsThis retrospective cohort study assessed the effectiveness of a decitabine (DAC)-based protocol in JMML patients undergoing HSCT. The pre-HSCT treatment includes initial and bridging treatment. The efficacy of DAC monotherapy versus DAC combined with cytotoxic chemotherapy(C-DAC) as initial treatment was compared, followed by DAC plus FLAG (fludarabine, cytarabine, and GCSF) as bridging treatment. The HSCT regimens were based on DAC, fludarabine, and busulfan. Post-HSCT, low-dose DAC was used as maintenance therapy. The study endpoints focused on pretransplantation simplified clinical response and post-HSCT survival.ResultsThere were 109 patients, including 45 receiving DAC monotherapy and 64 undergoing C-DAC treatment. 106 patients completed bridging treatment. All patients were administered planned HSCT regimens and post-HSCT treatment. The initial treatment resulted in 88.1% of patients achieving clinical remission without a significant difference between the DAC and C-DAC groups (p=0.769). Clinical remission rates significantly improved following bridging treatment (p=0.019). The 5-year overall survival, leukemia-free survival, and RI were 92.2%, 88.4%, and 8.0%, respectively. A poor clinical response to pre-HSCT treatment emerged as a risk factor for OS (hazard ratio: 9.8, 95% CI: 2.3-41.1, p=0.002).ConclusionImplementing a DAC-based administration strategy throughout the pre-HSCT period, during HSCT regimens, and in post-HSCT maintenance significantly reduced relapse and improved survival in JMML patients. Both DAC monotherapy and the DAC plus FLAG protocol proved effective as pre-HSCT treatments.

Plant-derived exosome-like nanoparticles (ELNs) have demonstrated cross-kingdom capabilities in regulating intercellular communication, facilitating drug delivery, and providing therapeutic interventions in humans. However, the functional attributes of konjac-derived ELNs (K-ELNs) remain largely unexplored. This study investigates the isolation, characterization, and functional analysis of K-ELNs, along with the profiling and differential expression analysis of associated miRNAs in both K-ELNs and Konjac tissues. K-ELNs were successfully isolated and characterized from two konjac species using ultracentrifugation, followed by Transmission Electron Microscopy (TEM) and Nanoparticle Tracking Analysis (NTA). Small RNA sequencing identified a total of 3,259 miRNAs across all samples. Differential expression analysis revealed significant differences in miRNA profiles between K-ELNs and tissue samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis of target genes provided insights into their roles in modulating pathways associated with diseases such as cancer and neurodegenerative disorders. Additionally, six miRNAs were selected for validation of sequencing results via RT-qPCR. The 5’RLM-RACE method was employed to validate the cleavage sites between differentially expressed miRNAs (DEMs) and their predicted target genes, further substantiating the regulatory roles of miRNAs in konjac. The findings of this study enhance our understanding of the molecular mechanisms underlying the biological functions and applications of K-ELNs, laying the groundwork for future research into their potential therapeutic roles in human health.

ObjectiveThis study aims to assess the effectiveness of the National Early Warning Score 2 (NEWS2) versus Glasgow Coma Scale (GCS) in predicting hospital mortality among patients with stroke and traumatic brain injury (TBI).LocationThis multicenter study was conducted at two anonymized tertiary care hospitals in distinct climatic regions of China, with a combined annual emergency admission exceeding 10,000 patients.PatientsThe study included 2,276 adult emergency admissions diagnosed with stroke (n = 1,088) or TBI (n = 1,188) from January 2021 to December 2023, excluding those with chronic pulmonary disease, severe cardiac conditions, or a history of brain surgery.Measuring and main outcomesThe receiver operating characteristic (ROC) curve and the area under the curve (AUC) were utilized to analyze the predictive accuracy of NEWS2 and GCS for hospital mortality at 24, 48, and 72 h post-admission and at discharge.ResultsOut of 2,276 patients (mean age 61.4, 65.6% male), 1855 survived while 421 succumbed. NEWS2 demonstrated superior predictive accuracy (AUC = 0.962) over GCS (AUC = 0.854) for overall hospital mortality. Specifically, NEWS2 outperformed GCS in predicting mortality at 24 h (0.917 vs. 0.843), 48 h (0.893 vs. 0.803), and 72 h (0.902 vs. 0.763). Notably, despite a higher AUC for NEWS2 at predicting 24-h hospital mortality, the sensitivity and specificity of GCS were considerably lower (12 and 31%, respectively) compared to NEWS2 (sensitivity of 95% and specificity of 81%). Subgroup analysis showed NEWS2 outperforming GCS in predicting in-hospital mortality for TBI and stroke patients. For TBI patients (n = 260), NEWS2 had an AUC of 0.960 (95% CI: 0.948–0.973) vs. GCS’s AUC of 0.811 (95% CI: 0.781–0.840). For stroke patients (n = 161), NEWS2 had an AUC of 0.930 (95% CI: 0.908–0.952) vs. GCS’s AUC of 0.858 (95% CI, 0.823–0.892). NEWS2 showed greater sensitivity in both groups, highlighting its effectiveness in identifying high-risk neurological patients.ConclusionNEWS2 scores are more precise and effective in predicting hospital mortality in stroke and TBI patients compared to GCS scores, although slightly less so within the first 24 h. Combining NEWS2 with GCS and clinical findings within the initial 24 h is recommended for a comprehensive prognosis evaluation.

Summary: Background: Sleep disturbances are widespread but usually overlooked health risk factors for coronavirus disease 2019 (COVID-19). We aimed to investigate the influence of pre-existing sleep disturbances on the susceptibility, severity, and long-term effects of COVID-19. Methods: We searched PubMed, Web of Science, and Embase for relevant articles from inception to October 27, 2023 and updated at May 8, 2024. Sleep disturbances included obstructive sleep apnea (OSA), insomnia, abnormal sleep duration, night-shift work, and any other sleep disturbances. Outcomes were COVID-19 susceptibility, hospitalization, mortality, and long COVID. The effect sizes were pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). This study is registered with PROSPERO (CRD42024503518). Findings: A total of 48 observational studies (n = 8,664,026) were included. Pre-existing sleep disturbances increased the risk of COVID-19 susceptibility (OR = 1.12, 95% CI 1.07–1.18), hospitalization (OR = 1.25, 95% CI 1.15–1.36), mortality (OR = 1.45, 95% CI 1.19–1.78), and long COVID (OR = 1.36 95% CI 1.17–1.57). Subgroup analysis showed that younger individuals with sleep disturbances were associated with higher susceptibility and hospitalization and a lower risk of mortality than older individuals. Males with sleep disturbances were associated with higher mortality. For specific sleep disturbances, the susceptibility and hospitalization of COVID-19 were associated with OSA, abnormal sleep duration, and night-shift work; mortality of COVID-19 was linked to OSA; risk of long COVID was related to OSA, abnormal sleep duration and insomnia. Interpretation: Pre-existing sleep disturbances, especially OSA, increased the risk of COVID-19 susceptibility, hospitalization, mortality, and long COVID. Age and sex played important roles in the effect of sleep disturbances on COVID-19. Funding: The National Natural Science Foundation of China and the Key Laboratory of Respiratory Diseases of Liaoning Province.

Lung cancer remains a leading cause of cancer-related deaths globally, and a significant number of patients are ineligible for surgery, while chemoradiotherapy often shows limited efficacy, a systemic distribution, a low drug concentration at tumor sites, severe side effects, and the emergence of drug resistance. In this context, a nanodrug delivery system (NDDS) has emerged as a promising approach for lung cancer treatment, offering distinct advantages such as targeted delivery, responsiveness to the tumor microenvironment, site-specific release, and enhanced induction of apoptosis in cancer cells, ultimately leading to tumor growth inhibition or even elimination. This review aims to provide an overview of the physiological characteristics of lung cancer, highlight the limitations of conventional treatment methods, and extensively examine recent significant advancements in NDDS utilized for lung cancer therapy. The findings from this review lay the foundation for further development and optimization of NDDSs in the treatment of lung cancer.

Abstract The insufficient abundance and weak activity of tumour-infiltrating lymphocytes (TILs) are two important reasons for the poor efficacy of PD-1 inhibitors in hepatocellular carcinoma (HCC) treatment. The combined administration of tanshinone IIA (TSA) and astragaloside IV (As) can up-regulate the abundance and activity of TILs by normalising tumour blood vessels and reducing the levels of immunosuppressive factors respectively. For enhancing the efficacy of PD-1 antibody, a magnetic metal–organic framework (MOF) with a homologous tumour cell membrane (Hm) coating (Hm@TSA/As-MOF) is established to co-deliver TSA&As into the HCC microenvironment. Hm@TSA/As-MOF is a spherical nanoparticle and has a high total drug-loading capacity of 16.13 wt%. The Hm coating and magnetic responsiveness of Hm@TSA/As-MOF provide a homologous-magnetic dual-targeting, which enable Hm@TSA/As-MOF to counteract the interference posed by ascites tumour cells and enhance the precision of targeting solid tumours. Hm coating also enable Hm@TSA/As-MOF to evade immune clearance by macrophages. The release of TSA&As from Hm@TSA/As-MOF can be accelerated by HCC microenvironment, thereby up-regulating the abundance and activity of TILs to synergistic PD-1 antibody against HCC. This study presents a nanoplatform to improve the efficacy of PD-1 inhibitors in HCC, providing a novel approach for anti-tumour immunotherapy in clinical practice.

The application of a male-sterile line is an ideal approach for hybrid seed production in non-heading Chinese cabbage (Brassica rapa ssp. chinensis). However, the molecular mechanisms underlying male sterility in B. rapa are still largely unclear. We previously obtained the natural male sterile line WS24-3 of non-heading Chinese cabbage and located the male sterile locus, Bra2Ms, on the A2 chromosome. Cytological observations revealed that the male sterility of WS24-3 resulted from disruption of the meiosis process during pollen formation. Fine mapping of Bra2Ms delimited the locus within a physical distance of about 129 kb on the A2 chromosome of B. rapa. The Bra039753 gene encodes a plant homeodomain (PHD)-finger protein and is considered a potential candidate gene for Bra2Ms. Bra039753 was significantly downregulated in sterile line WS24-3 compared to the fertile line at the meiotic anther stage. Sequence analysis of Bra039753 identified a 369 bp fragment insertion in the first exon in male sterile plants, which led to an amino acid insertion in the Bra039753 protein. In addition, the 369 bp fragment insertion was found to cosegregate with the male sterility trait. This study identified a novel locus related to male sterility in non-heading Chinese cabbage, and the molecular marker obtained in this study will be beneficial for the marker-assisted selection of excellent sterile lines in non-heading Chinese cabbage and other Brassica crops.

Abstract Background This study aimed to develop and validate a machine learning (ML)-based fusion model to preoperatively predict Ki-67 expression levels in patients with head and neck squamous cell carcinoma (HNSCC) using multiparametric magnetic resonance imaging (MRI). Methods A total of 351 patients with pathologically proven HNSCC from two medical centers were retrospectively enrolled in the study and divided into training (n = 196), internal validation (n = 84), and external validation (n = 71) cohorts. Radiomics features were extracted from T2-weighted images and contrast-enhanced T1-weighted images and screened. Seven ML classifiers, including k-nearest neighbors (KNN), support vector machine (SVM), logistic regression (LR), random forest (RF), linear discriminant analysis (LDA), naive Bayes (NB), and eXtreme Gradient Boosting (XGBoost) were trained. The best classifier was used to calculate radiomics (Rad)-scores and combine clinical factors to construct a fusion model. Performance was evaluated based on calibration, discrimination, reclassification, and clinical utility. Results Thirteen features combining multiparametric MRI were finally selected. The SVM classifier showed the best performance, with the highest average area under the curve (AUC) of 0.851 in the validation cohorts. The fusion model incorporating SVM-based Rad-scores with clinical T stage and MR-reported lymph node status achieved encouraging predictive performance in the training (AUC = 0.916), internal validation (AUC = 0.903), and external validation (AUC = 0.885) cohorts. Furthermore, the fusion model showed better clinical benefit and higher classification accuracy than the clinical model. Conclusions The ML-based fusion model based on multiparametric MRI exhibited promise for predicting Ki-67 expression levels in HNSCC patients, which might be helpful for prognosis evaluation and clinical decision-making.

Although all walks of life are paying less attention to COVID-19, the spread of COVID-19 has never stopped. As an infectious disease, its transmission speed is closely related to the atmosphere environment, particularly the temperature (T) and PM2.5 concentrations. However, How T and PM2.5 concentrations are related to the spread of SARS-CoV-2 and how much their cumulative lag effect differ across cities is unclear. To identify the characteristics of cumulative lag effects of environmental exposure under city differences, this study used a generalized additive model to investigate the associations between T/PM2.5 concentrations and the daily number of new confirmed COVID-19 cases (NNCC) during the outbreak period in the second half of 2021 in Shaoxing, Shijiazhuang, and Dalian. The results showed that except for PM2.5 concentrations in Shaoxing, the NNCC in the three cities generally increased with the unit increase of T and PM2.5 concentrations. In addition, the cumulative lag effects of T/PM2.5 concentrations on NNCC in the three cities reached a peak at lag 26/25, lag 10/26, and lag 18/13 days, respectively, indicating that the response of NNCC to T and PM2.5 concentrations varies among different regions. Therefore, combining local meteorological and air quality conditions to adopt responsive measures is an important way to prevent and control the spread of SARS-CoV-2.

Purpose: Little is known about the role of gut microbiota in the pathogenesis of erectile dysfunction (ED). We performed a study to compare taxonomic profiles of gut microbiota of ED and healthy males. Materials and Methods: A total of 43 ED patients and 16 healthy controls were enrolled in the study. The 5-item version of the International Index of Erectile Function (IIEF-5) with a cutoff value of 21 was used to evaluate erectile function. All participants underwent nocturnal penile tumescence and rigidity test. Samples of stool were sequenced to determine the gut microbiota. Results: We identified a distinct beta diversity of gut microbiome in ED patients by unweighted UniFrac analysis (R2=0.026, p=0.036). Linear discriminant analysis effect size (LEfse) analysis showed Actinomyces was significantly enriched, whereas Coprococcus_1, Lachnospiraceae_FCS020_group, Lactococcus, Ruminiclostridium_5, and Ruminococcaceae_UCG_002 were depleted in ED patients. Actinomyces showed a significant negative correlation with the duration of qualified erection, average maximum rigidity of tip, average maximum rigidity of base, tip tumescence activated unit (TAU), and base TAU. Coprococcus_ 1, Lachnospiraceae_FCS020_group, Ruminiclostridium_5, and Ruminococcaceae_UCG_002 were significantly correlated with the IIEF-5 score. Ruminiclostridium_5 and Ruminococcaceae_UCG_002 were positively related with average maximum rigidity of tip, average maximum rigidity of base, ΔTumescence of tip, and Tip TAU. Further, a random forest classifier based on the relative abundance of taxa showed good diagnostic efficacy with an area under curve of 0.72. Conclusions: This pilot study identified evident alterations in the gut microbiome composition of ED patients and found Actinomyces was negatively correlated with erectile function, which may be a key pathogenic bacteria.

Abstract Background Rheumatoid arthritis (RA) is an autoimmune disease characterized by destructive polyarthritis, and abnormal T–B‐cell interactions may contribute to its pathogenesis. This study aimed to investigate the characteristics and roles of CD4+ programmed death 1 (PD‐1)+Foxp3− T cells in relation to the B‐cell response in patients with RA. Methods This study included 155 patients with RA and 36 age‐ and sex‐matched healthy controls (HCs) from the Second Hospital of Dalian Medical University in China. Flow cytometry was used to assess the proportion and properties of peripheral CD4+PD‐1+Foxp3+ T cells, including their proliferation, activation, cytokine production, and capacity to induce B‐cell differentiation. Results The proportion of CD4+PD‐1+Foxp3− T cells was increased in patients with RA compared with HCs ([10.78 ± 0.60]% vs. [5.67 ± 0.40]%, p

Abstract Background Regulatory T cells (Tregs) are involved in the maintenance of immune homeostasis and immune regulation. Clinical trials on the adoptive transfer of Tregs have been ongoing for > 10 years. However, many unresolved issues remain in the production of readymade Treg products and selection of patients. Hence, this study aimed to develop a method to expand off-the-shelf Tregs derived from umbilical cord blood (UCB-Tregs) in vitro without changing their phenotype and inhibitory function. In addition, the study intended to design an approach to precisely select patients who are more likely to benefit from the adoptive Treg transfer therapy. Methods UCB-Tregs were isolated and cultured in a medium containing human recombinant IL-2 and rapamycin and then multiply restimulated with human T-activator CD3/CD28 dynabeads. The phenotype and suppressive capacity of Tregs were assessed on days 18 and 42. The relationship between the suppressive function of UCB-Tregs in vitro and clinical indicators was analyzed, and the ability of the in vitro suppressive capacity to predict the in vivo therapeutic effects was evaluated. Results UCB-Tregs expanded 123-fold and 5,981-fold at 18 and 42 days, respectively. The suppressive function of UCB-Tregs on the proliferation of immune cells at 42 days was not significantly different compared with that of UCB-Tregs obtained at 18 days. The suppression rate of UCB-Tregs to PBMCs was negatively correlated with the course of diabetes. Moreover, the high-suppression group exhibited a better treatment response than the low-suppression group during the 12-month follow-up period. Conclusions Multiply restimulated UCB-Tregs expanded at a large scale without any alterations in their classical phenotypic features and inhibitory functions. The suppressive function of Tregs in vitro was negatively correlated with the disease duration. The present study revealed the possibility of predicting the in vivo therapeutic effects via the in vitro inhibition assay. Thus, these findings provided a method to obtain off-the-shelf Treg products and facilitated the selection of patients who are likely to respond to the treatment, thereby moving toward the goal of precision treatment.

Abstract Esophageal squamous cell carcinoma (ESCC) remains an important health concern in developing countries. Patients with advanced ESCC have a poor prognosis and survival rate, and achieving early diagnosis remains a challenge. Metabolic biomarkers are gradually gaining attention as early diagnostic biomarkers. Hence, this multicenter study comprehensively evaluated metabolism dysregulation in ESCC through an integrated research strategy to identify key metabolite biomarkers of ESCC. First, the metabolic profiles were examined in tissue and serum samples from the discovery cohort (n = 162; ESCC patients, n = 81; healthy volunteers, n = 81), and ESCC tissue-induced metabolite alterations were observed in the serum. Afterward, RNA sequencing of tissue samples (n = 46) was performed, followed by an integrated analysis of metabolomics and transcriptomics. The potential biomarkers for ESCC were further identified by censoring gene-metabolite regulatory networks. The diagnostic value of the identified biomarkers was validated in a validation cohort (n = 220), and the biological function was verified. A total of 457 dysregulated metabolites were identified in the serum, of which 36 were induced by tumor tissues. The integrated analyses revealed significant alterations in the purine salvage pathway, wherein the abundance of hypoxanthine/xanthine exhibited a positive correlation with HPRT1 expression and tumor size. A diagnostic model was developed using two purine salvage–associated metabolites. This model could accurately discriminate patients with ESCC from normal individuals, with an area under the curve (AUC) (95% confidence interval (CI): 0.680–0.843) of 0.765 in the external cohort. Hypoxanthine and HPRT1 exerted a synergistic effect in terms of promoting ESCC progression. These findings are anticipated to provide valuable support in developing novel diagnostic approaches for early ESCC and enhance our comprehension of the metabolic mechanisms underlying this disease.

Abstract Background Mesenchymal stem/stromal cells (MSCs) are of great therapeutic value due to their role in maintaining the function of hematopoietic stem/progenitor cells (HSPCs). MSCs derived from human pluripotent stem cells represent an ideal alternative because of their unlimited supply. However, the role of MSCs with neural crest origin derived from HPSCs on the maintenance of HSPCs has not been reported. Methods Flow cytometric analysis, RNA sequencing and differentiation ability were applied to detect the characteristics of stromal cells from 3D human brain organoids. Human umbilical cord blood CD34+ (UCB-CD34+) cells were cultured in different coculture conditions composed of stromal cells and umbilical cord MSCs (UC-MSCs) with or without a cytokine cocktail. The hematopoietic stroma capacity of stromal cells was tested in vitro with the LTC-IC assay and in vivo by cotransplantation of cord blood nucleated cells and stroma cells into immunodeficient mice. RNA and proteomic sequencing were used to detect the role of MSCs on HSPCs. Results The stromal cells, derived from both H1-hESCs and human induced pluripotent stem cells forebrain organoids, were capable of differentiating into the classical mesenchymal-derived cells (osteoblasts, chondrocytes, and adipocytes). These cells expressed MSC markers, thus named pluripotent stem cell-derived MSCs (pMSCs). The pMSCs showed neural crest origin with CD271 expression in the early stage. When human UCB-CD34+ HSPCs were cocultured on UC-MSCs or pMSCs, the latter resulted in robust expansion of UCB-CD34+ HSPCs in long-term culture and efficient maintenance of their transplantability. Comparison by RNA sequencing indicated that coculture of human UCB-CD34+ HSPCs with pMSCs provided an improved microenvironment for HSC maintenance. The pMSCs highly expressed the Wnt signaling inhibitors SFRP1 and SFRP2, indicating that they may help to modulate the cell cycle to promote the maintenance of UCB-CD34+ HSPCs by antagonizing Wnt activation. Conclusions A novel method for harvesting MSCs with neural crest origin from 3D human brain organoids under serum-free culture conditions was reported. We demonstrate that the pMSCs support human UCB-HSPC expansion in vitro in a long-term culture and the maintenance of their transplantable ability. RNA and proteomic sequencing indicated that pMSCs provided an improved microenvironment for HSC maintenance via mechanisms involving cell–cell contact and secreted factors and suppression of Wnt signaling. This represents a novel method for large-scale production of MSCs of neural crest origin and provides a potential approach for development of human hematopoietic stromal cell therapy for treatment of dyshematopoiesis.

Abstract Immune disorders have become one of the public health problems and imposes a serious economic and social burden worldwide. Ginsenosides, the main active constituents of ginseng, are regarded as a novel supplementary strategy for preventing and improving immune disorders and related diseases. This review summarized the recent research progress of ginsenosides in immunomodulation and proposed future directions to promote the development and application of ginsenosides. After critically reviewing the immunomodulatory potential of ginsenosides both in vitro and in vivo and even in clinical data of humans, we provided a perspective that ginsenosides regulated the immune system through activation of immune cells, cytokines, and signaling pathways such as MAPK, PI3K/Akt, STAT, and AMPK, as well as positively affected immune organs, gut flora structure, and systemic inflammatory responses. However, the evidence for the safety and efficacy of ginsenosides is insufficient, and the immune pathways of ginsenosides remain incompletely characterized. We believe that this review will provide a valuable reference for further research on ginsenosides as dietary supplements with immunomodulatory effects.