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Abstract Targeted delivery and precise release of toxins is a prospective strategy for the treatment of triple-negative breast cancer (TNBC), yet the flexibility to incorporate both properties simultaneously remains tremendously challenging in the X-drug conjugate fields. As critical components in conjugates, linkers could flourish in achieving optimal functionalities. Here, we pioneered a pH-hypersensitive tumor-targeting aptamer AS1411-triptolide conjugate (AS-TP) to achieve smart release of the toxin and targeted therapy against TNBC. The multifunctional acetal ester linker in the AS-TP site-specifically blocked triptolide toxicity, quantitatively sustained aptamer targeting, and ensured the circulating stability. Furthermore, the aptamer modification endowed triptolide with favorable water solubility and bioavailability and facilitated endocytosis of conjugated triptolide by TNBC cells in a nucleolin-dependent manner. The integrated superiorities of AS-TP promoted the preferential intra-tumor triptolide accumulation in xenografted TNBC mice and triggered the in-situ triptolide release in the weakly acidic tumor microenvironment, manifesting striking anti-TNBC efficacy and virtually eliminated toxic effects beyond clinical drugs. This study illustrated the therapeutic potential of AS-TP against TNBC and proposed a promising concept for the development of nucleic acid-based targeted anticancer drugs.

Cymbidium (Orchidaceae: Epidendroideae), with around 60 species, is widely-distributed across Southeast Asia, providing a nice system for studying the processes that underlie patterns of biodiversity in the region. However, phylogenetic relationships of Cymbidium have not been well resolved, hampering investigations of species diversification and the biogeographical history of this genus. In this study, we construct a plastome phylogeny of 56 Cymbidium species, with four well-resolved major clades, which provides a framework for biogeographical and diversification rate analyses. Molecular dating and biogeographical analyses show that Cymbidium likely originated in the region spanning northern Indo-Burma to the eastern Himalayas during the early Miocene (∼21.10 Ma). It then rapidly diversified into four major clades in East Asia within approximately a million years during the middle Miocene. Cymbidium spp. migration to the adjacent regions (Borneo, Philippines, and Sulawesi) primarily occurred during the Pliocene-Pleistocene period. Our analyses indicate that the net diversification rate of Cymbidium has decreased since its origin, and is positively associated with changes in temperature and monsoon intensity. Favorable hydrothermal conditions brought by monsoon intensification in the early Miocene possibly contributed to the initial rapid diversification, after which the net diversification rate was reduced with the cooling climate after the middle Miocene. The transition from epiphytic to terrestrial habits may have enabled adaptation to cooler environments and colonization of northern niches, yet without a significant effect on diversification rates. This study provides new insights into how monsoon activity and temperature changes affected the diversification dynamics of plants in Southeast Asia.

Abstract Background Histone deacetylases (HDACs) and histone acetyltransferases (HATs) are involved in plant growth and development as well as in response to environmental changes, by dynamically regulating gene acetylation levels. Although there have been numerous reports on the identification and function of HDAC and HAT in herbaceous plants, there are fewer report related genes in woody plants under drought stress. Results In this study, we performed a genome-wide analysis of the HDAC and HAT families in Populus trichocarpa, including phylogenetic analysis, gene structure, conserved domains, and expression analysis. A total of 16 PtrHDACs and 12 PtrHATs were identified in P. trichocarpa genome. Analysis of cis-elements in the promoters of PtrHDACs and PtrHATs revealed that both gene families could respond to a variety of environmental signals, including hormones and drought. Furthermore, real time quantitative PCR indicated that PtrHDA906 and PtrHAG3 were significantly responsive to drought. PtrHDA906, PtrHAC1, PtrHAC3, PtrHAG2, PtrHAG6 and PtrHAF1 consistently responded to abscisic acid, methyl jasmonate and salicylic acid under drought conditions. Conclusions Our study demonstrates that PtrHDACs and PtrHATs may respond to drought through hormone signaling pathways, which helps to reveal the hub of acetylation modification in hormone regulation of abiotic stress.

Abstract Small cell lung cancer (SCLC) patients exhibit significant heterogeneity in tumor burden, physical condition, and responses to initial treatment. This diversity in treatment responses can result in varying treatment outcomes. The primary objective of this study was to explore the patient demographics associated with improved survival outcomes through radiotherapy. Based on the SEER database, we identified 42,824 SCLC patients enrolled between 2004 and 2015. These patients were stratified into radiotherapy (n = 20,360) and non-radiotherapy groups (n = 22,464). We controlled for confounding factors using propensity score matching (PSM) analysis. Subsequently, Kaplan–Meier (KM) analysis was employed to evaluate the impact of radiotherapy on patients’ overall survival (OS) and cancer-specific survival (CSS). Cancer-specific mortality was further analyzed using competitive risk models. Cox analysis was also conducted to examine additional variables potentially affecting the survival of SCLC patients. We identified a total of 42,824 eligible patients, and following PSM, 13,329 patients were successfully matched in both the radiotherapy and non-radiotherapy groups. The KM analysis showed that the median OS was 9 months in the radiotherapy group and 6 months in the non-radiotherapy group. The median CSS was 10 months in the radiotherapy group and 7 months in the non-radiotherapy group. The 5-year OS and 10-year OS rates were 6.2% versus 1.6% in the radiotherapy group and 2.6% versus 0.8% in the non-radiotherapy group (P

Abstract Objective There is growing evidence supporting the utilization of the radial artery as a secondary arterial graft in coronary artery bypass grafting (CABG) surgery. However, debates continue over the recovery period of the radial artery following angiography. This study aims to evaluate the clinical outcomes and experiences related to the use of the radial artery post-angiography in total arterial coronary revascularization. Methods A retrospective analysis was performed on data from patients who underwent total arterial CABG surgery at the University of Hong Kong Shenzhen Hospital from July 1, 2020, to September 30, 2022. Preoperative assessments included ultrasound evaluations of radial artery blood flow, diameter, intimal integrity, and the Allen test. Additionally, pathological examinations of the distal radial artery and coronary artery CT angiography were conducted, along with postoperative follow-up to assess the safety and efficacy of using the radial artery in patients undergoing total arterial CABG. Results A total of 117 patients, compromising 102 males and 15 females with an average age of 60.0 ± 10.0 years, underwent total arterial CABG. The internal mammary artery was used in situ in 108 cases, while in 4 cases, it was grafted to the ascending aorta due to length limitations. Bilateral radial arteries were utilized in 88 patients, and bilateral internal mammary arteries in 4 patients. Anastomoses of the proximal radial arteries to the proximal ascending aorta included 42 cases using distal T-anastomosis and 4 using sequential grafts. The interval between bypass surgery and coronary angiography ranged from 7 to 14 days. Pathological examination revealed intact intima and continuous elastic membranes with no significant inflammatory infiltration or hyperplastic lumen stenosis in the radial arteries. There were no hospital deaths, 3 cases of perioperative cerebral infarction, 1 secondary thoracotomy for hemorrhage control, 21 instances of intra-aortic balloon pump (IABP) assistance, and 2 cases of poor wound healing that improved following debridement. CT angiography performed 2 weeks post-surgery showed no internal mammary artery occlusions, but 4 radial artery occlusions were noted. Conclusion Ultrasound may be used within 2 weeks post-angiography to assess the recovery of the radial artery in some patients. Radial arteries with intact intima may be considered in conjunction with the internal mammary artery for total arterial coronary CABG. However, long-term outcomes of these grafts require further validation through larger prospective studies.

Abstract Co-immobilization of cells and enzymes is often essential for the cascade biocatalytic processes of industrial-scale feasibility but remains a vast challenge. Herein, we create a facile co-immobilization platform integrating enzymes and cells in covalent organic frameworks (COFs) to realize the highly efficient cascade of inulinase and E. coli for bioconversion of natural products. Enzymes can be uniformly immobilized in the COF armor, which coats on the cell surface to produce cascade biocatalysts with high efficiency, stability and recyclability. Furthermore, this one-pot in situ synthesis process facilitates a gram-scale fabrication of enzyme-cell biocatalysts, which can generate a continuous-flow device conversing inulin to D-allulose, achieving space-time yield of 161.28 g L−1 d−1 and high stability (remaining >90% initial catalytic efficiency after 7 days of continuous reaction). The created platform is applied for various cells (e.g., E. coli, Yeast) and enzymes, demonstrating excellent universality. This study paves a pathway to break the bottleneck of extra- and intracellular catalysis, creates a high-performance and customizable platform for enzyme-cell cascade biomanufacturing, and expands the scope of biocatalysis process intensification.

Abstract Background Monoacylglycerol lipase (MAGL) genes belong to the alpha/beta hydrolase superfamily, catalyze the terminal step of triglyceride (TAG) hydrolysis, converting monoacylglycerol (MAG) into free fatty acids and glycerol. Results In this study, 30 MAGL genes in upland cotton have been identified, which have been classified into eight subgroups. The duplication of GhMAGL genes in upland cotton was predominantly influenced by segmental duplication events, as revealed through synteny analysis. Furthermore, all GhMAGL genes were found to contain light-responsive elements. Through comprehensive association and haplotype analyses using resequencing data from 355 cotton accessions, GhMAGL3 and GhMAGL6 were detected as key genes related to lipid hydrolysis processes, suggesting a negative regulatory effect. Conclusions In summary, MAGL has never been studied in upland cotton previously. This study provides the genetic mechanism foundation for the discover of new genes involved in lipid metabolism to improve cottonseed oil content, which will provide a strategic avenue for marker-assisted breeding aimed at incorporating desirable traits into cultivated cotton varieties.

The practical applications of magnesium (Mg) alloys are usually beset by their relatively low strength and limited ductility. Herein we attempt to fabricate hexagonal BN nanoplatelet (BNNP) reinforced ZK61 magnesium composites using a combination of spark plasma sintering and friction stir processing. The resulting composites exhibit microstructural characteristics of homogeneous dispersion of BNNP in Mg matrix with refined equiaxed grains and (0002) basal texture roughly surrounding the pin column surface. Transmission electron microscopy observation illustrates that trace amounts of Mg3N2 and MgB2 form at BNNP-Mg interface, in which Mg3N2 locates at the basal plane of a BNNP and MgB2 grows at its open edge. The spatial distribution of Mg3N2 and MgB2 facilitates interfacial wetting and stronger BNNP-Mg interface in such a way that interfacial products act as anchors bonding between them. In comparison with monolithic ZK61 alloy, the BNNP/ZK61 composites display simultaneous improvements in yield strength, hardness and ductility, achieving good strength-ductility balance. This research is expected to shed some light on BNNP potentials for designing and producing magnesium composites with high strength and good ductility.

Abstract Peripheral CD8+ T cell number is tightly controlled but the precise molecular mechanism regulating this process is still not fully understood. In this study, we found that epilepsy patients with loss of function mutation of DEPDC5 had reduced peripheral CD8+ T cells, and DEPDC5 expression positively correlated with tumor-infiltrating CD8+ T cells as well as overall cancer patient survival, indicating that DEPDC5 may control peripheral CD8+ T cell homeostasis. Significantly, mice with T cell-specific Depdc5 deletion also had reduced peripheral CD8+ T cells and impaired anti-tumor immunity. Mechanistically, Depdc5-deficient CD8+ T cells produced high levels of xanthine oxidase and lipid ROS due to hyper-mTORC1-induced expression of ATF4, leading to spontaneous ferroptosis. Together, our study links DEPDC5-mediated mTORC1 signaling with CD8+ T cell protection from ferroptosis, thereby revealing a novel strategy for enhancing anti-tumor immunity via suppression of ferroptosis.

Abstract Cervical cancer is the fourth most common cancer and the leading cause of mortality among women worldwide. Tumor metastasis is an important cause of poor prognosis. Determining the exact mechanisms of metastasis and potential targeted therapies is urgently needed. Junctional adhesion molecule 3 (JAM3) is an important member of the TJ tight junction (TJ) family, and its biological function in cervical cancer needs to be further clarified. We found that JAM3 was highly expressed in cervical cancer patients with lymph node metastasis and that high expression of JAM3 promoted cervical cancer cell metastasis both in vitro and in vivo. In addition, overexpression of JAM3 induces epithelial–mesenchymal transition (EMT). Moreover, silencing JAM3 suppressed cervical cancer cell migration and invasion in vitro. Finally, JAM3 overexpression activated the HIF-1α/VEGFA pathway. In conclusion, our results suggested that JAM3 promotes cervical cancer cell migration and invasion by activating the HIF-1α/VEGFA pathway. JAM3 may be a promising biomarker and effective therapeutic target for cervical cancer.

Abstract The cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase-stimulator of interferon genes (cGAS-STING) signaling pathway, an important component of the innate immune system, is involved in the development of several diseases. Ectopic DNA-induced inflammatory responses are involved in several pathological processes. Repeated damage to tissues and metabolic organelles releases a large number of damage-associated molecular patterns (mitochondrial DNA, nuclear DNA, and exogenous DNA). The DNA fragments released into the cytoplasm are sensed by the sensor cGAS to initiate immune responses through the bridging protein STING. Many recent studies have revealed a regulatory role of the cGAS-STING signaling pathway in cardiovascular diseases (CVDs) such as myocardial infarction, heart failure, atherosclerosis, and aortic dissection/aneurysm. Furthermore, increasing evidence suggests that inhibiting the cGAS-STING signaling pathway can significantly inhibit myocardial hypertrophy and inflammatory cell infiltration. Therefore, this review is intended to identify risk factors for activating the cGAS-STING pathway to reduce risks and to simultaneously further elucidate the biological function of this pathway in the cardiovascular field, as well as its potential as a therapeutic target.

Abstract Programmed cell death (PCD) is a basic process of life that is closely related to the growth, development, aging and disease of organisms and is one of the hotspots of life science research today. PCD is a kind of genetic control, autonomous and orderly important cell death that involves the activation, expression, and regulation of a series of genes. In recent years, with the deepening of research in this field, new mechanisms of multiple PCD pathways have been revealed. This article reviews and summarizes the multiple PCD pathways that have been discovered, analyses and compares the morphological characteristics and biomarkers of different types of PCD, and briefly discusses the role of various types of PCD in the diagnosis and treatment of different diseases, especially malignant tumors.

Abstract Background This study aimed to examine the reporting quality of existing economic evaluations for negotiated glucose-lowering drugs (GLDs) included in China National Reimbursement Drug List (NRDL) using the Consolidated Health Economic Evaluation Reporting Standards 2013 (CHEERS 2013). Methods We performed a systematic literature research through 7 databases to identify published economic evaluations for GLDs included in the China NRDL up to March 2021. Reporting quality of identified studies was assessed by two independent reviewers based on the CHEERS checklist. The Kruskal–Wallis test and Mann–Whitney U test were performed to examine the association between reporting quality and characteristics of the identified studies. Results We have identified 24 studies, which evaluated six GLDs types. The average score rate of the included studies was 77.41% (SD:13.23%, Range 47.62%-91.67%). Among all the required reporting items, characterizing heterogeneity (score rate = 4.17%) was the least satisfied item. Among six parts of CHEERS, results part scored least at 0.55 (score rate = 54.79%) because of the incompleteness of characterizing uncertainty. Results from the Kruskal–Wallis test and Mann–Whitney U test showed that model choice, journal type, type of economic evaluations, and study perspective were associated with the reporting quality of the studies. Conclusions There remains room to improve the reporting quality of economic evaluations for GLDs in NRDL. Checklists such as CHEERS should be widely used to improve the reporting quality of economic researches in China.

Existing microfabricated atomic vapor cells have only one optical channel, which is insufficient for supporting the multiple orthogonal beams required by atomic devices. In this study, we present a novel wafer-level manufacturing process for fabricating multi-optical-channel atomic vapor cells and an innovative method for batch processing the inner sidewalls of millimeter glass holes to meet optical channel requirements. Surface characterization and transmittance tests demonstrate that the processed inner sidewalls satisfy the criteria for an optical channel. In addition, the construction of an integrated processing platform enables multilayer non-isothermal anode bonding, the filling of inert gases, and the recovery and recycling of noble gases. Measurements of the absorption spectra and free-induction decay signals of xenon-129 (129Xe) and xenon-131 (131Xe) under different pump-probe schemes demonstrate the suitability of our vapor cell for use in atomic devices including atomic gyroscopes, dual-beam atomic magnetometers, and other optical/atomic devices. The proposed micromolding technology has broad application prospects in the field of optical-device processing.

Abstract Objectives The risk of intracranial aneurysms (IAs) development and rupture is significantly higher in patients with periodontitis (PD), suggesting an association between the two. However, the specific mechanisms of association between these two diseases have not been fully investigated. Materials and methods In this study, we downloaded IAs and PD data from the Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified, and functional enrichment analysis was performed. The protein-protein interaction (PPI) network and weighted gene co-expression network analysis (WGCNA) was performed to identified key modules and key crosstalk genes. In addition, the immune cell landscape was assessed and the correlation of key crosstalk genes with each immune cell was calculated. Finally, transcription factors (TFs) regulating key crosstalk genes were explored. Results 127 overlapping DEGs were identified and functional enrichment analysis highlighted the important role of immune reflection in the pathogenesis of IAs and PD. We identified ITGAX and COL4A2 as key crosstalk genes. In addition, the expression of multiple immune cells was significantly elevated in PDs and IAs compared to controls, and both key crosstalk genes were significantly negatively associated with Macrophages M2. Finally, GATA2 was identified as a potential key transcription factor (TF), which regulates two key crosstalk gene. Conclusions The present study identifies key crosstalk genes and TF in PD and IAs, providing new insights for further study of the co-pathogenesis of PD and IAs from an immune and inflammatory perspective. Also, this is the first study to report the above findings.

Abstract Background Gastric cancer is one of the global health concerns. A series of studies on the stomach have confirmed the role of the microbiome in shaping gastrointestinal diseases. Delineation of microbiome signatures to distinguish chronic gastritis from gastric cancer will provide a non-invasive preventative and treatment strategy. In this study, we performed whole metagenome shotgun sequencing of fecal samples to enhance the detection of rare bacterial species and increase genome sequence coverage. Additionally, we employed multiple bioinformatics approaches to investigate the potential targets of the microbiome as an indicator of differentiating gastric cancer from chronic gastritis. Results A total of 65 patients were enrolled, comprising 33 individuals with chronic gastritis and 32 with gastric cancer. Within each group, the chronic gastritis group was sub-grouped into intestinal metaplasia (n = 15) and non-intestinal metaplasia (n = 18); the gastric cancer group, early stage (stages 1 and 2, n = 13) and late stage (stages 3 and 4, n = 19) cancer. No significant differences in alpha and beta diversities were detected among the patient groups. However, in a two-group univariate comparison, higher Fusobacteria abundance was identified in phylum; Fusobacteria presented higher abundance in gastric cancer (LDA scored 4.27, q = 0.041 in LEfSe). Age and sex-adjusted MaAsLin and Random Forest variable of importance (VIMP) analysis in species provided meaningful features; Bacteria_caccae was the most contributing species toward gastric cancer and late-stage cancer (beta:2.43, se:0.891, p:0.008, VIMP score:2.543). In contrast, Bifidobacterium_longum significantly contributed to chronic gastritis (beta:-1.8, se:0.699, p:0.009, VIMP score:1.988). Age, sex, and BMI-adjusted MasAsLin on metabolic pathway analysis showed that GLCMANNANAUT-PWY degradation was higher in gastric cancer and one of the contributing species was Fusobacterium_varium. Conclusion Microbiomes belonging to the pathogenic phylum Fusobacteria and species Bacteroides_caccae and Streptococcus_anginosus can be significant targets for monitoring the progression of gastric cancer. Whereas Bifidobacterium_longum and Lachnospiraceae_bacterium_5_1_63FAA might be protection biomarkers against gastric cancer.

Abstract Background Non-invasive techniques such as central intermittent theta burst stimulation (iTBS) and repetitive peripheral magnetic stimulation (rPMS) have shown promise in improving motor function for patients with stroke. However, the combined efficacy of rPMS and central iTBS has not been extensively studied. This randomized controlled trial aimed to investigate the synergistic effects of rPMS and central iTBS in patients with stroke. Method In this study, 28 stroke patients were randomly allocated to receive either 1200 pulses of real or sham rPMS on the radial nerve of the affected limb, followed by 1200 pulses of central iTBS on the ipsilesional hemisphere. The patients received the intervention for 10 sessions over two weeks. The primary outcome measures were the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) and the Action Research Arm Test (ARAT). Secondary outcomes for activities and participation included the Functional Independence Measure-Selfcare (FIM-Selfcare) and the Stroke Impact Scale (SIS). The outcome measures were assessed before and after the intervention. Results Both groups showed significant improvement in FMA-UE and FIM-Selfcare after the intervention (p

Abstract Steroidal glycoalkaloids (SGAs) are major plant defense metabolites against pests, while they are considered poisonous in food. The genetic basis that guides negative selection of SGAs production during tomato domestication remains poorly understood. Here, we identify a distal enhancer, GAME Enhancer 1 (GE1), as the key regulator of SGAs metabolism in tomato. GE1 recruits MYC2-GAME9 transcriptional complex to regulate the expression of GAME cluster genes via the formation of chromatin loops located in the neighboring DNA region. A naturally occurring GE1 76 allelic variant is found to be more active in stimulating GAME expression. We show that the weaker GE1 allele has been the main driver for selecting reduced SGAs levels during tomato domestication. Unravelling the “TFs-Enhancer-Promoter” regulatory mechanism operating in SGAs metabolism opens unprecedented prospects for SGAs manipulation in Solanaceae via precision breeding strategies.

Abstract Background and objectives To investigate the relationship between body mass index (BMI) and blood biochemical indicators in early adolescence, and to provide ideas for early prevention of diseases and explore possible disease-related predictors. Methods 3125 participants aged 10 ∼ 14 years were selected from China from the survey of “China Nutrition and Health Surveillance ( 2016 ∼ 2017 ) “. Employing advanced statistical methods, including generalized linear models, heatmaps, hierarchical clustering, and generalized additive models, the study delved into the associations between BMI and various biochemical indicators. Results In early adolescence, indicators including systolic pressure, diastolic pressure, weight, height, BMI, hemoglobin, blood uric acid, serum creatinine, albumin, vitamin A presented increasing trends with the increase of age ( P 1, P

In order to investigate the changes in volatile compounds of Morchella esculenta during drying treatments, the volatile compounds of fresh, vaccum freezed-dried, and hot air-dried Morchella esculenta from two different parts (the pileus and stipe) were compared and analyzed by electronic nose combined with headspace gas chromatography-ion mobility spectroscopy (HS-GC-IMS) techniques. The principal component analysis (PCA) of electronic nose data showed that the drying treatment significantly changed the volatile profiles of Morchella esculenta regardless of the sampling parts. The HS-GC-IMS analysis yielded a total of 41 volatile flavor compounds, and abundant amounts of alcohols (40.02%~50.76%), esters (15.82%~25.66%), and aldehydes (18.24%~20.33%) were observed for the fresh sample. Furthermore, the drying treatments resulted in the reduction of alcohols and esters in fresh Morchella esculenta, specifically by 27.39% to 33.51% and 62.14% to 68.51% respectively, while the total contents of ketones and pyrazines increased significantly (P

During the construction of karst tunnel, it is difficult to avoid approaching the cavern, even high pressure water cavern. Water inrush damage very easily causes safety accidents and would have irreversible impact on the tunnel. The study on damage mode is conducive to solving problems related to karst tunnel safety and has certain significance for the safety of route selection. In this study, the physical and mechanical parameters of micro-discrete particles are calibrated and verified by a three-dimensional discrete-continuous coupling numerical technology, and the important process of rock-burst collapse prevention between the underlying solution cavity and the tunnel invert under water pressure is simulated. The results show that the failure modes of outburst prevention rock mass are divided into three types: shear failure mode, bending failure mode, and composite failure mode. The bending failure mode indicates that the tensile cracks in the middle and both ends of the outburst prevention rock mass are in the form of penetration; the shear failure mode shows that the cracks at both ends of the outburst prevention rock mass are in the shear state; while the composite failure mode has the common characteristics of both. The fracture development rules caused by the three failure modes are similar and can be divided into three stages: initial development, rapid development, and gentle development. At the stage of initial development, the number of cracks in the rock body is small; the number of cracks in the rock mass maintaining water pressure and preventing outburst suddenly increases and enters the stage of rapid development; after that, the crack in the outburst prevention rock mass connect and then enter the stage of gentle development, ultimately, leading to the overall collapse of the outburst prevention rock mass. Thus, this study indicates that water inrush damage is a gradual process in karst tunnels, but it has an irreversible impact on the overall safety of karst tunnels.

Abstract Marital status is an independent prognostic factor for survival in many types of cancers, but its prognostic impact on patients with prostate cancer (PCa) has not been established. The aim of this study was to explore the independent prognostic factors of PCa and to investigate the effect of marital status on survival outcomes in patients with different stratified by PCa. Using the surveillance, epidemiology, and end results (SEER) database, we collected data on 584,655 PCa patients diagnosed between 1975 and 2019. Marital status was classified as married, divorced, widowed, and single. We used the Kaplan–Meier analysis and single multivariate Cox proportional hazards regression analysis to determine the effect of marital status on overall survival (OS) and cancer-specific survival (CSS). In addition, we performed subgroup analyses for different ages, Gleason score and PSA values, and performed a 1:1 propensity score matching (PSM) to reduce the impact of confounding factors to obtain more accurate matching results. According to our findings, marital status was an independent prognostic factor for the survival of PCa patients and a better prognosis of married patients. Moreover, we also found that factors such as age, TNM stage, Gleason score, and PSA concentration were also considered as important predictors for the prognosis of PCa. The above findings can facilitate early detection and treatment of high-risk PCa patients, prolong their life and reduce family burden.

Abstract Despite clinical and epidemiological evidence suggestive of a link between glioblastoma (GBM) and periodontitis (PD), the shared mechanisms of gene regulation remain elusive. In this study, we identify differentially expressed genes (DEGs) that overlap between the GEO datasets GSE4290 [GBM] and GSE10334 [PD]. Functional enrichment analysis was conducted, and key modules were identified using protein–protein interaction (PPI) network and weighted gene co-expression network analysis (WGCNA). The expression levels of CXCR4, LY96, and C3 were found to be significantly elevated in both the test dataset and external validation dataset, making them key crosstalk genes. Additionally, immune cell landscape analysis revealed elevated expression levels of multiple immune cells in GBM and PD compared to controls, with the key crosstalk genes negatively associated with Macrophages M2. FLI1 was identified as a potential key transcription factor (TF) regulating the three key crosstalk genes, with increased expression in the full dataset. These findings contribute to our understanding of the immune and inflammatory aspects of the comorbidity mechanism between GBM and PD.

Abstract Background Occupational exposure to artificial stone, a popular material used for countertops, can cause accelerated silicosis, but the precise relationship between silica dose and disease development is unclear. Objectives This study evaluated the impact of silica exposure on lung function and chest imaging in artificial stone manufacturing workers. Methods Questionnaire and spirometry assessments were administered to workers in two plants. A high-exposure subset underwent further evaluation, including chest CT and DLco. Weighting factors, assigned as proxies for silica exposure, were based on work tasks. Individual cumulative exposures were estimated using area concentration measurements and time spent in specific areas. Exposure-response associations were analyzed using linear and logistic regression models. Results Among 65 participants, the mean cumulative silica exposure was 3.61 mg/m3-year (range 0.0001 to 44.4). Each 1 mg/m3-year increase was associated with a 0.46% reduction in FVC, a 0.45% reduction in FEV1, and increased lung function abnormality risk (aOR = 1.27, 95% CI = 1.03–1.56). Weighting factors correlated with cumulative exposures (Spearman correlation = 0.59, p

Abstract Background Trauma has been identified as one of the risk factors for acute respiratory distress syndrome. Respiratory support can be further complicated by comorbidities of trauma such as primary or secondary lung injury. Conventional ventilation strategies may not be suitable for all trauma-related acute respiratory distress syndrome. Airway pressure release ventilation has emerged as a potential rescue method for patients with acute respiratory distress syndrome and hypoxemia refractory to conventional mechanical ventilation. However, there is a lack of research on the use of airway pressure release ventilation in children with trauma-related acute respiratory distress syndrome. We report a case of airway pressure release ventilation applied to a child with falling injury, severe acute respiratory distress syndrome, hemorrhagic shock, and bilateral hemopneumothorax. We hope this case report presents a potential option for trauma-related acute respiratory distress syndrome and serves as a basis for future research. Case presentation A 15-year-old female with falling injury who developed severe acute respiratory distress syndrome, hemorrhagic shock, and bilateral hemopneumothorax was admitted to the surgical intensive care unit. She presented refractory hypoxemia despite the treatment of conventional ventilation with deep analgesia, sedation, and muscular relaxation. Lung recruitment was ineffective and prone positioning was contraindicated. Her oxygenation significantly improved after the use of airway pressure release ventilation. She was eventually extubated after 12 days of admission and discharged after 42 days of hospitalization. Conclusion Airway pressure release ventilation may be considered early in the management of trauma patients with severe acute respiratory distress syndrome when prone position ventilation cannot be performed and refractory hypoxemia persists despite conventional ventilation and lung recruitment maneuvers.

Abstract Soft tissue filler injections are among the most popular facial rejuvenation methods. Cerebral infarction and ophthalmic artery occlusion are rare and catastrophic complications, especially when facial cosmetic fillers are injected by inexperienced doctors. Radiologists and plastic surgeons need to increase their awareness of the complications associated with fillers, which allows early diagnosis and intervention to improve patient prognosis. Regarding the mechanism by which vascular occlusion occurs after facial filler injections, a retrograde embolic mechanism is currently the predominant theory. Numerous case reports have been presented regarding complications associated with injections of facial aesthetics. However, the small sample sizes of these studies did not allow for an adequate assessment of the clinical and imaging manifestations based on the location of the occlusion and the type of filler, and detailed elaboration of multiple cerebral infarctions is also lacking. Therefore, this study aimed to investigate the clinical and radiological features of severe cerebral and ocular complications caused by cosmetic facial filler injections. In addition, we discuss the pathogenesis, treatment, and prognosis of these patients. The clinical, computed tomography (CT), magnetic resonance imaging (MRI), and digital subtraction angiography (DSA) findings were described and analysed. Radiological examinations are crucial for demonstrating severe complications, and brain MRI is especially strongly suggested for patients with cosmetic filler-induced vision loss to identify asymptomatic cerebral infarctions. Extreme caution and care should be taken during facial injections by plastic surgeons.

Abstract Intracellular signaling dynamics play a crucial role in cell function. Protein kinase A (PKA) is a key signaling molecule that has diverse functions, from regulating metabolism and brain activity to guiding development and cancer progression. We previously developed an optical reporter, FLIM-AKAR, that allows for quantitative imaging of PKA activity via fluorescence lifetime imaging microscopy and photometry. However, using viral infection or electroporation for the delivery of FLIM-AKAR is invasive and results in variable expression. Here, we developed a reporter mouse, FL-AK, which expresses FLIM-AKAR in a Cre-dependent manner from the ROSA26 locus. FL-AK provides robust and consistent expression of FLIM-AKAR over time. Functionally, the mouse line reports an increase in PKA activity in response to activation of both Gαs and Gαq-coupled receptors in brain slices. In vivo, FL-AK reports PKA phosphorylation in response to neuromodulator receptor activation. Thus, FL-AK provides a quantitative, robust, and flexible method to reveal the dynamics of PKA activity in diverse cell types.

Abstract Accurate annotation of vertebral bodies is crucial for automating the analysis of spinal X-ray images. However, manual annotation of these structures is a laborious and costly process due to their complex nature, including small sizes and varying shapes. To address this challenge and expedite the annotation process, we propose an ensemble pipeline called VertXNet. This pipeline currently combines two segmentation mechanisms, semantic segmentation using U-Net, and instance segmentation using Mask R-CNN, to automatically segment and label vertebral bodies in lateral cervical and lumbar spinal X-ray images. VertXNet enhances its effectiveness by adopting a rule-based strategy (termed the ensemble rule) for effectively combining segmentation outcomes from U-Net and Mask R-CNN. It determines vertebral body labels by recognizing specific reference vertebral instances, such as cervical vertebra 2 (‘C2’) in cervical spine X-rays and sacral vertebra 1 (‘S1’) in lumbar spine X-rays. Those references are commonly relatively easy to identify at the edge of the spine. To assess the performance of our proposed pipeline, we conducted evaluations on three spinal X-ray datasets, including two in-house datasets and one publicly available dataset. The ground truth annotations were provided by radiologists for comparison. Our experimental results have shown that the proposed pipeline outperformed two state-of-the-art (SOTA) segmentation models on our test dataset with a mean Dice of 0.90, vs. a mean Dice of 0.73 for Mask R-CNN and 0.72 for U-Net. We also demonstrated that VertXNet is a modular pipeline that enables using other SOTA model, like nnU-Net to further improve its performance. Furthermore, to evaluate the generalization ability of VertXNet on spinal X-rays, we directly tested the pre-trained pipeline on two additional datasets. A consistently strong performance was observed, with mean Dice coefficients of 0.89 and 0.88, respectively. In summary, VertXNet demonstrated significantly improved performance in vertebral body segmentation and labeling for spinal X-ray imaging. Its robustness and generalization were presented through the evaluation of both in-house clinical trial data and publicly available datasets.

Abstract An unexpected surge of osteoporosis outpatients occurred after COVID-19 lockdown was lifted in China. To confirm the observation and identify possible reasons driving patients care seeking behaviors post-pandemic, we compared the outpatient volumes at the osteoporosis clinic in January through May, 2019–2022 and surveyed seven osteoporosis specialists across China to validate the phenomenon before devising an online questionnaire to collect patients’ characters and physical activity levels. Univariate and binary logistic regression analyses were calculated to identify predictors of post-lockdown care-seeking. We received 480 valid responses, including 397 (82.7%) patients having visited the clinic after lockdown and 83 (17.3%) having not. Four significant predictors were identified, including being female, experiencing pain, aggravating symptoms, and heightened anxiety during lockdown (P

Abstract The purpose of the present study is to predict and draw up non-grain cultivated land (NCL) susceptibility map based on optimized Extreme Gradient Boosting (XGBoost) model using the Particle Swarm Optimization (PSO) metaheuristic algorithm. In order to, a total of 184 NCL areas were identified based on historical records, and a total of 16 NCL susceptibility conditioning factors (NCLSCFs) were considered, based on both a systematic literature survey and local environmental conditions. The results showed that the XGBoost model optimized by PSO performed well in comparison to other machine learning algorithms; the values of sensitivity, specificity, PPV, NPV, and AUC are 0.93, 0.89, 0.88, 0.93, and 0.96, respectively. Slope, rainfall, fault density, distance from fault and drainage density are most important variables. According to the results of this study, the use of meta-innovative algorithms such as PSO can greatly enhance the ability of machine learning models.

Abstract Background For patients with steroid-refractory acute graft-versus-host disease (SR-aGVHD), effective second-line regimens are urgently needed. Mesenchymal stromal cells (MSCs) have been used as salvage regimens for SR-aGVHD in the past. However, clinical trials and an overall understanding of the molecular mechanisms of MSCs combined with basiliximab for SR-aGVHD are limited, especially in haploidentical haemopoietic stem cell transplantation (HID HSCT). Methods The primary endpoint of this multicentre, randomized, controlled trial was the 4-week complete response (CR) rate of SR-aGVHD. A total of 130 patients with SR-aGVHD were assigned in a 1:1 randomization schedule to the MSC group (receiving basiliximab plus MSCs) or control group (receiving basiliximab alone) (NCT04738981). Results Most enrolled patients (96.2%) received HID HSCT. The 4-week CR rate of SR-aGVHD in the MSC group was obviously better than that in the control group (83.1% vs. 55.4%, P = 0.001). However, for the overall response rates at week 4, the two groups were comparable. More patients in the control group used ≥ 6 doses of basiliximab (4.6% vs. 20%, P = 0.008). We collected blood samples from 19 consecutive patients and evaluated MSC-derived immunosuppressive cytokines, including HO1, GAL1, GAL9, TNFIA6, PGE2, PDL1, TGF-β and HGF. Compared to the levels before MSC infusion, the HO1 (P = 0.0072) and TGF-β (P = 0.0243) levels increased significantly 1 day after MSC infusion. At 7 days after MSC infusion, the levels of HO1, GAL1, TNFIA6 and TGF-β tended to increase; however, the differences were not statistically significant. Although the 52-week cumulative incidence of cGVHD in the MSC group was comparable to that in the control group, fewer patients in the MSC group developed cGVHD involving ≥3 organs (14.3% vs. 43.6%, P = 0.006). MSCs were well tolerated, no infusion-related adverse events (AEs) occurred and other AEs were also comparable between the two groups. However, patients with malignant haematological diseases in the MSC group had a higher 52-week disease-free survival rate than those in the control group (84.8% vs. 65.9%, P = 0.031). Conclusions For SR-aGVHD after allo-HSCT, especially HID HSCT, the combination of MSCs and basiliximab as the second-line therapy led to significantly better 4-week CR rates than basiliximab alone. The addition of MSCs not only did not increase toxicity but also provided a survival benefit.

Abstract Background Kabuki syndrome (KS) is a monogenic disorder leading to special facial features, mental retardation, and multiple system malformations. Lysine demethylase 6A, (KDM6A, MIM*300128) is the pathogenic gene of Kabuki syndrome type 2 (KS2, MIM#300867), which accounts for only 5%–8% of KS. Previous studies suggested that female patients with KS2 may have a milder phenotype. Method We summarized the phenotype and genotype of KS2 patients who were diagnosed in Shanghai Children’s Medical Center since July 2017 and conducted a 1:3 matched case–control study according to age and sex to investigate sex-specific differences between patients with and without KS2. Results There were 12 KS2 cases in this study, and 8 of them matched with 24 controls. The intelligence quotient (IQ) score of the case group was significantly lower than that of the control group (P