Search

Objective: This study was aimed at analyzing the efficacy and safety of an injectable form of chlorogenic acid (CGA) in patients with recurrent high-grade glioma after standard of care treatments, through a first-in-human, open-label, dose-escalation phase I trial. Methods: A total of 26 eligible patients were enrolled, received intramuscular CGA injections at 5 dose levels, and were followed up for 5 years. CGA was well tolerated, and the maximum tolerated dose was 5.5 mg/kg. Results: The most common treatment-related adverse events occurred at the sites of injection. No grade 3 or 4 adverse events (e.g., drug allergy) were reported for these patients except for induration at the injection sites. A clinical pharmacokinetic study showed that CGA was rapidly eliminated from the plasma, with a t1/2 of 0.95–1.27 h on day 1 and 1.19–1.39 h on day 30, and no detectable CGA was observed on days 9, 11, 13, 23, 25, 27, and 29 before CGA administration. After the first treatment cycle, 52.2% of patients (12 of 23) achieved stable disease. Long-term follow-up indicated an estimated median overall survival of 11.3 months for all 23 evaluable patients. Of the 18 patients with grade 3 glioma, the median overall survival was 9.5 months. Two patients remained alive at the cutoff day. Conclusions: This phase I study demonstrated that CGA has a favorable safety profile (with no severe toxicity), and provides preliminary clinical benefits for patients with high grade glioma relapsing after prior standard therapies, thus shedding light on the potential clinical application of CGA for recurrent grade 4 glioma.

Wheat tiller angle (TA) is an important agronomic trait that contributes to grain production by affecting plant architecture. It also plays a crucial role in high-yield wheat breeding. An association panel and a recombinant inbred line (RIL) population were used to map quantitative trait loci (QTL) for TA. Results showed that 470 significant SNPs with 10.4%–28.8% phenotypic variance explained (PVE) were detected in four replicates by a genome-wide association study (GWAS). Haplotype analysis showed that the TA_Hap_4B1 locus on chromosome 4B was a major QTL to regulate wheat TA. Ten QTL were totally detected by linkage mapping with the RIL population, and QTA.hau-4B.1 identified in six environments with the PVE of 7.88%–18.82% was a major and stable QTL. A combined analysis demonstrated that both TA_Hap_4B1 and QTA.hau-4B.1 were co-located on the same region. Moreover, QTA.hau-4B.1 was confirmed by bulked segregant RNA-Seq (BSR-Seq) analysis. Phenotypic analysis showed that QTA.hau-4B.1 was also closely related to yield traits. Furthermore, TraesCS4B02G049700 was considered as a candidate gene through analysis of gene sequence and expression. This study can be potentially used in cloning key genes modulating wheat tillering and provides valuable genetic resources for improvement of wheat plant architecture.

Abstract Background The causal role of high-risk Human papillomavirus (HR-HPV) in the pathogenesis of anogenital cancers is well established. In contrast, information on HR-HPV distribution of continuous anatomic sites within the female genital tract is limited, and the impact of sample type on the clinical performance in HPV-based cervical cancer screening warrants investigation. Methods A total of 2,646 Chinese women were enrolled in the study from May 2006 to April 2007. We analyzed the infection features by infection status and pathological diagnoses of 489 women with complete HR-HPV type and viral load data on the cervix, upper vagina, lower vagina, and perineum samples. Additionally, we assessed the clinical performance for detecting high-grade cervical intraepithelial neoplasia of grade two or worse (≥ CIN2) among these four types of samples. Results HR-HPV positivity rate was lower in the cervix (51.53%) and perineum (55.83%), higher in the upper (65.64%) and lower vagina (64.42%), and increased with the severity of cervical histological lesions (all P

Abstract Objective The drug‐refractory epilepsy (DRE) in children is commonly observed but the underlying mechanisms remain elusive. We examined whether fatty acids (FAs) and lipids are potentially associated with the pharmacoresistance to valproic acid (VPA) therapy. Methods This single‐center, retrospective cohort study was conducted using data from pediatric patients collected between May 2019 and December 2019 at the Children's Hospital of Nanjing Medical University. Ninety plasma samples from 53 responders with VPA monotherapy (RE group) and 37 non‐responders with VPA polytherapy (NR group) were collected. Non‐targeted metabolomics and lipidomics analysis for those plasma samples were performed to compare the potential differences of small metabolites and lipids between the two groups. Plasma metabolites and lipids passing the threshold of variable importance in projection value >1, fold change >1.2 or

Geological observation and thermal simulation experiments have revealed that the peak period of hydrocarbon generation of gypsum-bearing mudstone is often advanced in sedimentary basins, but the correlation between the amount of advance and the content of gypsum is still not clear. In this study, the source rock powder samples with different gypsum content in the Lower Ganchaigou Formation from well S49-1 in the western Qaidam Basin were selected and extracted to remove soluble organic matter (SOM). Part of the extracted residue was pickled to remove carbonate. Rock pyrolysis analysis was performed on the original samples and the solid residue after two-step pretreatment. Compared to the Tmax of original samples, the Tmax was higher in the SOM-free residue but lower in the SOM-free and carbonate-free residue, showing that SOM and sulfate minerals (gypsum and anhydrite) in gypsum-bearing mudstone can promote the thermal evolution of organic matter. Although the latter has a more significant effect, it is not proportional to its sulfate content, indicating that the contact area of sulfate minerals and organic matter is more important to Tmax. The hypothesis was verified by the Tmax values of different proportions of kerogen and magnesium sulfate powder mixtures. Therefore, the occurrence state of sulfate minerals will directly affect the contact relationship between organic matter and sulfate, which in turn will affect the process of hydrocarbon generation in thermal evolution.

Temozolomide (TMZ) is an anticancer agent used to treat glioblastoma, typically following radiation therapy and/or surgical resection. However, despite its effectiveness, at least 50% of patients do not respond to TMZ, which is associated with repair and/or tolerance of TMZ-induced DNA lesions. Studies have demonstrated that alkyladenine DNA glycosylase (AAG), an enzyme that triggers the base excision repair (BER) pathway by excising TMZ-induced N3-methyladenine (3meA) and N7-methylguanine lesions, is overexpressed in glioblastoma tissues compared to normal tissues. Therefore, it is essential to develop a rapid and efficient screening method for AAG inhibitors to overcome TMZ resistance in glioblastomas. Herein, we report a robust time-resolved photoluminescence platform for identifying AAG inhibitors with improved sensitivity compared to conventional steady-state spectroscopic methods. As a proof-of-concept, this assay was used to screen 1440 food and drug administration-approved drugs against AAG, resulting in the repurposing of sunitinib as a potential AAG inhibitor. Sunitinib restored glioblastoma (GBM) cancer cell sensitivity to TMZ, inhibited GBM cell proliferation and stem cell characteristics, and induced GBM cell cycle arrest. Overall, this strategy offers a new method for the rapid identification of small-molecule inhibitors of BER enzyme activities that can prevent false negatives due to a fluorescent background.

Abstract Light-based 3D bioprinting is now employed widely to fabricate geometrically complex constructs for various biomedical applications. However, the inherent light scattering defect creates significant challenges in patterning dilute hydrogels to form high-fidelity structures with fine-scale features. Herein, we introduce a photoinhibiting approach that can effectively suppress the light scattering effect via a mechanism of simultaneous photoabsorption and free-radical reaction. This biocompatible approach significantly improves the printing resolution (~1.2 - ~2.1 pixels depending on swelling) and shape fidelity (geometric error less than 5%), while minimising the costly trial-and-error procedures. The capability in patterning 3D complex constructs using different hydrogels is demonstrated by manufacturing various scaffolds featuring intricate multi-sized channels and thin-walled networks. Importantly, cellularised gyroid scaffolds (HepG2) are fabricated successfully, exhibiting high cell proliferation and functionality. The strategy established in this study promotes the printability and operability of light-based 3D bioprinting systems, allowing numerous new applications for tissue engineering.

Abstract Background Based on our previous studied on different provenances of Pistacia chinensis, some accessions with high quality and quantity of seed oils has emerged as novel source of biodiesel. To better develop P. chinensis seed oils as woody biodiesel, a concurrent exploration of oil content, FA profile, biodiesel yield, and fuel properties was conducted on the seeds from 5 plus germplasms to determine superior genotype for ideal biodiesel production. Another vital challenge is to unravel mechanism that govern the differences in oil content and FA profile of P. chinensis seeds across different accessions. FA biosynthesis and oil accumulation of oil plants are known to be highly controlled by the transcription factors. An integrated analysis of our recent transcriptome data, qRT-PCR detection and functional identification was performed as an attempt to highlight LEC1/WRI1-mediated transcription regulatory mechanism for high-quality oil accumulation in P. chinensis seeds. Results To select ideal germplasm and unravel high oil accumulative mechanism for developing P. chinensis seed oils as biodiesel, five plus trees (accession PC-BJ/PC-AH/PC-SX/PC-HN/PC-HB) with high-yield seeds were selected to assess the variabilities in weight, oil content, FA profile, biodiesel yield and fuel property, revealing a variation in the levels of seed oil (50.76–60.88%), monounsaturated FA (42.80–70.72%) and polyunsaturated FA (18.78–43.35%), and biodiesel yield (84.98–98.15%) across different accessions. PC-HN had a maximum values of seed weight (26.23 mg), oil (60.88%) and biodiesel yield (98.15%), and ideal proportions of C18:1 (69.94%), C18:2 (17.65%) and C18:3 (1.13%), implying that seed oils of accession PC-HN was the most suitable for ideal biodiesel production. To highlight molecular mechanism that govern such differences in oil content and FA profile of different accessions, a combination of our recent transcriptome data, qRT-PCR detection and protein interaction analysis was performed to identify a pivotal role of LEC1/WRI1-mediated transcription regulatory network in high oil accumulation of P. chinensis seeds from different accessions. Notably, overexpression of PcWRI1 or PcLEC1 from P. chinensis seeds in Arabidopsis could facilitate seed development and upregulate several genes relevant for carbon flux allocation (plastidic glycolysis and acetyl-CoA generation), FA synthesis, TAG assembly and oil storage, causing an increase in seed oil content and monounsaturated FA level, destined for biodiesel fuel property improvement. Our findings may present strategies for better developing P. chinensis seed oils as biodiesel feedstock and bioengineering its high oil accumulation. Conclusions This is the first report on the cross-accessions assessments of P. chinensis seed oils to determine ideal accession for high-quality biodiesel production, and an effective combination of PcWRI1 or PcLEC1 overexpression, morphological assay, oil accumulation and qRT-PCR detection was applied to unravel a role of LEC1/WRI1-mediated regulatory network for oil accumulation in P. chinensis seeds, and to highlight the potential application of PcWRI1 or PcLEC1 for increasing oil production. Our finding may provide new strategies for developing biodiesel resource and molecular breeding.

Abstract Background Ulcerative colitis (UC) is a common type of inflammatory bowel disease. Due to the elusive pathogenesis, safe and effective treatment strategies are still lacking. Fraxini Cortex (FC) has been widely used as a medicinal herb to treat some diseases. However, the pharmacological mechanisms of FC for UC treatment are still unclear. Methods An integrated platform combining network pharmacology and experimental studies was introduced to decipher the mechanism of FC against UC. The active compounds, therapeutic targets, and the molecular mechanism of action were acquired by network pharmacology, and the interaction between the compounds and target proteins were verified by molecular docking. Dextran sulfate sodium (DSS)-induced colitis model was employed to assess the therapeutic effect of FC on UC, and validate the molecular mechanisms of action predicted by network pharmacology. Results A total of 20 bioactive compounds were retrieved, and 115 targets were predicted by using the online databases. Ursolic acid, fraxetin, beta-sitosterol, and esculetin were identified as the main active compounds of FC against UC. PPI network analysis identified 28 FC-UC hub genes that were mainly enriched in the IL-17 signaling pathway, the TNF signaling pathway, and pathways in cancer. Molecular docking confirmed that the active compounds had high binding affinities to the predicted target proteins. GEO dataset analysis showed that these target genes were highly expressed in the UC clinical samples compared with that in the healthy controls. Experimental studies showed that FC alleviated DSS-induced colitis symptoms, reduced inflammatory cytokines release, and suppressed the expression levels of IL1β, COX2, MMP3, IL-17 and RORγt in colon tissues. Conclusion FC exhibits anti-UC properties through regulating multi-targets and multi-pathways with multi-components. In vivo results demonstrated that FC alleviated DSS-induced colitis.

Abstract Formalin-fixed paraffin-embedded (FFPE) tissues constitute a vast and valuable patient material bank for clinical history and follow-up data. It is still challenging to achieve single cell/nucleus RNA (sc/snRNA) profile in FFPE tissues. Here, we develop a droplet-based snRNA sequencing technology (snRandom-seq) for FFPE tissues by capturing full-length total RNAs with random primers. snRandom-seq shows a minor doublet rate (0.3%), a much higher RNA coverage, and detects more non-coding RNAs and nascent RNAs, compared with state-of-art high-throughput scRNA-seq technologies. snRandom-seq detects a median of >3000 genes per nucleus and identifies 25 typical cell types. Moreover, we apply snRandom-seq on a clinical FFPE human liver cancer specimen and reveal an interesting subpopulation of nuclei with high proliferative activity. Our method provides a powerful snRNA-seq platform for clinical FFPE specimens and promises enormous applications in biomedical research.

Epidural angiolipoma is a rare benign tumor consisting of mature adipocytes, blood sinuses, capillaries, and small blood vessels. It constitutes about 0.04%-1.2% of spinal axis tumors and about 2%-3% of extradural spinal tumors. We report a case of thoracic epidural angiolipoma and review the literature. We describe a 42-year-old woman who had weakness and numbness in her lower extremities prior to diagnosis and had an onset of approximately 10 months. The patient was misdiagnosed as schwannoma on preoperative imaging, possibly because neurogenous tumor is the most common intramedullary subdural tumor, and the lesion grew into bilateral intervertebral foramina. However, the lesion demonstrated high signal on the T2-weighted and T2 fat suppression sequences, and the linear low signal at the lesion edge was ignored, leading to misdiagnosis. The patient underwent posterior thoracic 4-6 laminectomy, pathectomy, and spinal decompression/vertebroplasty under general anesthesia. The final pathologic diagnosis was intradural epidural angiolipoma of the thoracic vertebra. Spinal epidural angiolipoma is a rare benign tumor that occurs frequently in middle-aged women and is mostly located on the dorsal side of the thoracic spinal canal. Magnetic resonance imaging findings of spinal epidural angiolipoma depend on the ratio of fat to blood vessels. Most angiolipomas show equal or high signal on T1-weighted images and high intensity on T2-weighted images, with significant enhancement after injection of gadolinium. The treatment of spinal epidural angiolipoma is complete surgical resection with good prognosis.

Abstract Ensuring the traceability of Pu-erh tea products is crucial in the production and sale of tea, as it is a key means to ensure their quality and safety. The common approach used in traceability systems is the utilization of bound Quick Response (QR) codes or Near Field Communication (NFC) chips to track every link in the supply chain. However, counterfeiting risks still persist, as QR codes or NFC chips can be copied and inexpensive products can be fitted into the original packaging. To address this issue, this paper proposes a tea face verification model called TeaFaceNet for traceability verification. The aim of this model is to improve the traceability of Pu-erh tea products by quickly identifying counterfeit products and enhancing the credibility of Pu-erh tea. The proposed method utilizes an improved MobileNetV3 combined with Triplet Loss to verify the similarity between two input tea face images with different texture features. The recognition accuracy of the raw tea face dataset, ripe tea face dataset and mixed tea face dataset of the TeaFaceNet network were 97.58%, 98.08% and 98.20%, respectively. Accurate verification of tea face was achieved using the optimal threshold. In conclusion, the proposed TeaFaceNet model presents a promising approach to enhance the traceability of Pu-erh tea products and combat counterfeit products. The robustness and generalization ability of the model, as evidenced by the experimental results, highlight its potential for improving the accuracy of Pu-erh tea face recognition and enhancing the credibility of Pu-erh tea in the market. Further research in this area is warranted to advance the traceability of Pu-erh tea products and ensure their quality and safety.

Abstract Mesenchymal gastrointestinal cancers are represented by the gastrointestinal stromal tumors (GISTs) which occur throughout the whole gastrointestinal tract, and affect human health and economy globally. Curative surgical resections and tyrosine kinase inhibitors (TKIs) are the main managements for localized GISTs and recurrent/metastatic GISTs, respectively. Despite multi-lines of TKIs treatments prolonged the survival time of recurrent/metastatic GISTs by delaying the relapse and metastasis of the tumor, drug resistance developed quickly and inevitably, and became the huge obstacle for stopping disease progression. Immunotherapy, which is typically represented by immune checkpoint inhibitors (ICIs), has achieved great success in several solid tumors by reactivating the host immune system, and been proposed as an alternative choice for GIST treatment. Substantial efforts have been devoted to the research of immunology and immunotherapy for GIST, and great achievements have been made. Generally, the intratumoral immune cell level and the immune-related gene expressions are influenced by metastasis status, anatomical locations, driver gene mutations of the tumor, and modulated by imatinib therapy. Systemic inflammatory biomarkers are regarded as prognostic indicators of GIST and closely associated with its clinicopathological features. The efficacy of immunotherapy strategies for GIST has been widely explored in pre-clinical cell and mouse models and clinical experiments in human, and some patients did benefit from ICIs. This review comprehensively summarizes the up-to-date advancements of immunology, immunotherapy and research models for GIST, and provides new insights and perspectives for future studies.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been reapproved for heart failure (HF) therapy in patients with and without diabetes. However, the initial glucose-lowering indication of SGLT2i has impeded their uses in cardiovascular clinical practice. A challenge of SGLT2i then becomes how to separate their anti-HF activity from glucose-lowering side-effect. To address this issue, we conducted structural repurposing of EMPA, a representative SGLT2 inhibitor, to strengthen anti-HF activity and reduce the SGLT2-inhibitory activity according to structural basis of inhibition of SGLT2. Compared to EMPA, the optimal derivative JX01, which was produced by methylation of C2–OH of the glucose ring, exhibited weaker SGLT2-inhibitory activity (IC50 > 100 nmol/L), and lower glycosuria and glucose-lowering side-effect, better NHE1-inhibitory activity and cardioprotective effect in HF mice. Furthermore, JX01 showed good safety profiles in respect of single-dose/repeat-dose toxicity and hERG activity, and good pharmacokinetic properties in both mouse and rat species. Collectively, the present study provided a paradigm of drug repurposing to discover novel anti-HF drugs, and indirectly demonstrated that SGLT2-independent molecular mechanisms play an important role in cardioprotective effects of SGLT2 inhibitors.

Abstract Background The processes of fertilization and egg activation are vital for early embryogenesis. However, while the mechanisms associated with key events during these processes differ among species and modes of spawning, the signal pathways underlying these processes are opaque for many fishes, including economically important species. Results We investigated phenotypic traits, ultrastructure and protein expression levels in the eggs of the topmouth culter (Culter alburnus), a protected and economically important freshwater fish that exhibits two spawning modes, producing semi-buoyant eggs and adhesive eggs. Unfertilized eggs of C. alburnus were examined, as well as eggs at fertilization and 30 min post fertilization. Our results showed that in semi-buoyant eggs, energy metabolism was activated at fertilization, followed by elevated protein expression of cytoskeleton and extracellular matrix (ECM)-receptor interactions that resulted in rapid egg swelling; a recognized adaptation for lotic habitats. In contrast, in adhesive eggs fertilization initiated the process of sperm-egg fusion and blocking of polyspermy, followed by enhanced protein expression of lipid metabolism and the formation of egg envelope adhesion and hardening, which are adaptive in lentic habitats. Conclusion Our findings indicate that alternative signal pathways differ between modes of spawning and timing during the key processes of fertilization and egg activation, providing new insights into the molecular mechanisms involved in adaptive early embryonic development in teleost fishes.

Introduction: Recent studies suggested that sarcopenia may be a significant comorbidity of diabetes mellitus (DM). Nonetheless, studies with nationally representative data are scarce, and the changing trend of sarcopenia prevalence over time is largely unknown. Therefore, we aimed to estimate and compare the prevalence of sarcopenia in diabetic and nondiabetic US older population, and to explore the potential predictors of sarcopenia as well as the trend of sarcopenia prevalent in the past decades. Methods: Data were retrieved from the National Health and Nutrition Examination Survey (NHANES). Sarcopenia and DM were defined according to corresponding diagnosis criteria. Weighted prevalence was calculated and compared between diabetic and nondiabetic participants. The differences among age and ethnicity groups were explored. Results: A total of 6,381 US adults (>50 years) were involved. The overall prevalence of sarcopenia was 17.8% for US elders, and the prevalence was higher (27.9% vs. 15.7%) in those with diabetes ones than those without. Stepwise regression revealed that sarcopenia was significantly associated with DM (adjusted odds ratio = 1.37, 95% CI: 1.08–1.22; p < 0.05) after controlling for potential confounders including gender, age, ethnicity, educational level, BMI, and muscle strengthening activity. A slight fluctuation but overall increasing trend of sarcopenia prevalence was observed among diabetic elders, while no obvious changing trend was observed in their counterparts in recent decades. Conclusion: Diabetic US older adults face significantly higher risk of sarcopenia when compared with their nondiabetic counterparts. Gender, age, ethnicity, educational level, and obesity were important influencing factors of sarcopenia development.

Abstract Background Up to 85% of hepatocellular carcinoma (HCC) cases in China can be attributed to infection of hepatitis B virus (HBV). Lipid metabolism performs important function in hepatocarcinogenesis of HBV–related liver carcinoma. However, limited studies have explored the prognostic role of lipid metabolism in HBV–related HCC. This study established a prognostic model to stratify HBV–related HCC based on lipid metabolisms. Methods Based on The Cancer Genome Atlas HBV–related HCC samples, this study selected prognosis-related lipid metabolism genes and established a prognosis risk model by performing uni- and multi-variate Cox regression methods. The final markers used to establish the model were selected through the least absolute shrinkage and selection operator method. Analysis of functional enrichment, immune landscape, and genomic alteration was utilized to investigate the inner molecular mechanism involved in prognosis. Results The risk model independently stratified HBV-infected patients with liver cancer into two risk groups. The low–risk groups harbored longer survival times (with P

Glyphosate [N-(phosphonomethyl)-glycine] is a non-selective herbicide with a broad spectrum activity that is commonly used to control perennial vegetation in agricultural fields. The widespread utilization of glyphosate in agriculture leads to soil, water, and food crop contamination, resulting in human and environmental health consequences. Therefore, it is imperative to devise techniques for enhancing the degradation of glyphosate in soil. Rhizobacteria play a crucial role in degrading organic contaminants. Limited work has been done on exploring the capabilities of indigenously existing glyphosate-degrading rhizobacteria in Pakistani soils. This research attempts to discover whether native bacteria have the glyphosate-degrading ability for a sustainable solution to glyphosate contamination. Therefore, this study explored the potential of 11 native strains isolated from the soil with repeated glyphosate application history and showed resistance against glyphosate at higher concentrations (200 mg kg−1). Five out of eleven strains outperformed in glyphosate degradation and plant growth promotion. High-pressure liquid chromatography showed that, on average, these five strains degraded 98% glyphosate. In addition, these strains promote maize seed germination index and shoot and root fresh biomass up to 73 and 91%, respectively. Furthermore, inoculation gave an average increase of acid phosphatase (57.97%), alkaline phosphatase (1.76-fold), and dehydrogenase activity (1.75-fold) in glyphosate-contaminated soil. The findings indicated the importance of using indigenous rhizobacteria to degrade glyphosate. Therefore, by maintaining soil health, indigenous soil biodiversity can work effectively for the bioremediation of contaminated soils and sustainable crop production in a world facing food security.

It is unclear whether the health equity of autism spectrum disorders (ASDs) has changed in different years, regions, and gender. The aims of this study were to provide a comprehensive description of the ASDs burden and provide evidence for improvement in health policies regarding ASDs inequality. This study is a population-based cross-sectional study based on the Global Burden of Disease datasets 1990–2019. We collected detailed information on ASDs between 1990 and 2019 in 204 countries worldwide, derived from the Global Burden of Disease study in 2019. Burden was calculated in terms of the incidence, prevalence and years lived with disability (YLDs). Concentration curves and concentration indices were used to summarize the degree of income-related inequality in the burden of ASDs. The overall age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR) and age-standardized YLDs rate (ASYR) of ASDs was 9.3 (95 %UI 7.7–11.1), 369.4 (95 %UI 305.9–441.2), 56.3 (95 %UI 36.8–81.5) per 100,000 people, respectively. The ASIR, ASPR and ASYR of ASDs affected three times as many males as females. The changing trends of age-standardized rates of ASDs showed that the ASIR of ASDs a slow growing trend globally. However, the ASPR and ASYR of ASDs showed a slow decreasing trend globally. All the concentration curves were below the line of equality and statistically significant. There was no significant difference in the age-standardized rate for different years in socio-demographic index-related inequality happened over 29 years (p > 0.05). The global burden of ASDs has remained higher in males and pro-rich, the income-related inequality tended not to change between 1990 and 2019.

Rising social media use over the past decade has been linked with increasing suicide rates among young people. Previous studies that assessed the impact of social media on suicide have typically focused on single social media platforms, such as Twitter, and assumed unidirectional associations, where social media posts leads to suicide. Our study focused on the past decade (2012–2021) which has witnessed a rapid increase of social media platforms and use. Poisson and negative binominal auto-regression models were employed to examine the dynamic reciprocity between social media, traditional media and youth suicides in Taiwan. Increased volume in suicide-related social media posts positively correlated with increased youth suicide rates (β = 2.53 × 10-5, 95% CI= (0.83 × 10-5, 4.24 × 10-5), P

AbstractHeat shock protein 70 (Hsp70) is a crucial member of the Hsp family, which is present in many animals, and acts as a chaperone to protect the organism from damage caused by various environmental stresses, particularly unfavorable temperatures. In this study, we used homologous gene search and domain analysis to identify sixteen Hsp70 genes (named as CiHSP genes) from the genome of grass carp (Ctenopharyngodon idella). These genes were classified into ten subfamilies based on their conserved structures and phylogenetic analysis. To investigate the biological functions of CiHSP genes in grass carp, we analyzed public RNA-Seq data, and found that most members of the CiHSP gene family were highly expressed in the brain and kidney, suggesting potential roles in protecting brain cells and participating in fish immunological processes. Additionally, these CiHSP genes were characterized as responding to high density and high temperature stress, with most members significantly upregulated under high temperature conditions. These findings demonstrate the critical roles of CiHSP genes in grass carp development and their response to environmental stress, which will provide valuable insights for determining their function and potential application in fish production in the future.

AbstractCalciphylaxis is a rare cutaneous vascular disease that manifests with intolerable pains, non-healing skin wounds, histologically characterized by calcification, fibrointimal hyperplasia, and microvessel thrombosis. Currently, there are no standardized guidelines for this disease. Recent studies have recognized a high prevalence of thrombophilias and hypercoagulable conditions in calciphylaxis patients. Here, we report a case of uremic calciphylaxis patient whom was refractory to conventional treatments and then received a salvage strategy with intravenous and local hAMSC application. In order to investigate the therapeutic mechanism of hAMSCs from the novel perspective of hypercoagulability, coagulation-related indicators, wound status, quality of life and skin biopsy were followed up. Polymerase chain reaction (PCR) was performed to determine the distribution of hAMSCs in multiple tissues including lung, kidney and muscle after infusion of hAMSCs for 24 h, 1 week and 1 month in mice aiming to investigate whether hAMSCs retain locally active roles after intravenous administration. Improvement of hypercoagulable condition involving correction of platelet, D-dimer and plasminogen levels, skin regeneration and pain alleviation were revealed after hAMSC administration over one-year period. Skin biopsy pathology suggested regenerative tissues after 1 month hAMSC application and full epidermal regeneration after 20 months hAMSC treatment. PCR analysis indicated that hAMSCs were homing in lung, kidney and muscle tissues of mice even until tail vein injection of hAMSCs for 1 month. We propose that hypercoagulability is a promising therapeutic target of calciphylaxis patients, which can be effectively improved by hAMSC treatment.

Abstract The inhomogeneous native oxide shells on the surfaces of III–V group semiconductors typically yield inferior and unstable electrical properties metrics, challenging the development of next‐generation integrated circuits. Herein, the native GaOx shells are profitably utilized by a simple in‐situ thermal annealing process to achieve high‐performance GaSb nanowires (NWs) field‐effect‐transistors (FETs) with excellent bias‐stress stability and synaptic behaviors. By an optimal annealing time of 5 min, the as‐constructed GaSb NW FET demonstrates excellent stability with a minimal shift of transfer curve (ΔVth ≈ 0.54 V) under a 60 min gate bias, which is far more stable than that of pristine GaSb NW FET (ΔVth ≈ 8.2 V). When the high bias‐stress stability NW FET is used as the chargeable‐dielectric free synaptic transistor, the typical synaptic behaviors, such as short‐term plasticity, long‐term plasticity, spike‐time‐dependent plasticity, and reliable learning stability are demonstrated successfully through the voltage tests. The mobile oxygen ion in the native GaOx shell strongly offsets the trapping states and leads to enhanced bias‐stress stability and charge retention capability for synaptic behaviors. This work provides a new way of utilizing the native oxide shell to realize stable FET for chargeable‐dielectric free neuromorphic computing systems.

Abstract Here, a sucrose non‐fermenting‐1‐related protein kinase alpha subunit (TaSnRK1α‐1A) is identified as associated with cold stress through integration of genome‐wide association study, bulked segregant RNA sequencing, and virus‐induced gene silencing. It is confirmed that TaSnRK1α positively regulates cold tolerance by transgenes and ethyl methanesulfonate (EMS) mutants. A plastid‐lipid‐associated protein 6, chloroplastic‐like (TaPAP6L‐2B) strongly interacting with TaSnRK1α‐1A is screened. Molecular chaperone DJ‐1 family protein (TaDJ‐1‐7B) possibly bridged the interaction of TaSnRK1α‐1A and TaPAP6L‐2B. It is further revealed that TaSnRK1α‐1A phosphorylated TaPAP6L‐2B. Subsequently, a superior haplotype TaPAP6L‐2B30S/38S is identified and confirmed that both R30S and G38S are important phosphorylation sites that influence TaPAP6L‐2B in cold tolerance. Overexpression (OE) and EMS‐mutant lines verified TaPAP6L positively modulating cold tolerance. Furthermore, transcriptome sequencing revealed that TaPAP6L‐2B‐OE lines significantly increased jasmonic acid (JA) content, possibly by improving precursor α‐linolenic acid contributing to JA synthesis and by repressing JAR1 degrading JA. Exogenous JA significantly improved the cold tolerance of wheat plants. In summary, TaSnRK1α profoundly regulated cold stress, possibly through phosphorylating TaPAP6L to increase endogenous JA content of wheat plants.

Cyanophages affect the abundance, diversity, metabolism, and evolution of picocyanobacteria in marine ecosystems. Here we report an estuarine Synechococcus phage, S-CREM2, which represents a novel viral genus and leads to the establishment of a new T4-like cyanophage clade named cluster C. S-CREM2 possesses the longest tail (~418 nm) among isolated cyanomyoviruses and encodes six tail-related proteins that are exclusively homologous to those predicted in the cluster C cyanophages. Furthermore, S-CREM2 may carry three regulatory proteins in the virion, which may play a crucial role in optimizing the host intracellular environment for viral replication at the initial stage of infection. The cluster C cyanophages lack auxiliary metabolic genes (AMGs) that are commonly found in cyanophages of the T4-like clusters A and B and encode unique AMGs like an S-type phycobilin lyase gene. A variation in the composition of tRNA and cis-regulatory RNA genes was observed between the marine and freshwater phage strains in cluster C, reflecting their different modes of coping with hosts and habitats. The cluster C cyanophages are widespread in estuarine and coastal regions and exhibit equivalent or even higher relative abundance compared to those of clusters A and B cyanophages in certain estuarine regions. The isolation of cyanophage S-CREM2 provides new insights into the phage–host interactions mediated by both newly discovered AMGs and virion-associated proteins and emphasizes the ecological significance of cluster C cyanophages in estuarine environments.

IntroductionThis study aimed to develop and assess a deep-learning model based on CT images for distinguishing infectivity in patients with pulmonary tuberculosis (PTB).MethodsWe labeled all 925 patients from four centers with weak and strong infectivity based on multiple sputum smears within a month for our deep-learning model named TBINet's training. We compared TBINet's performance in identifying infectious patients to that of the conventional 3D ResNet model. For model explainability, we used gradient-weighted class activation mapping (Grad-CAM) technology to identify the site of lesion activation in the CT images.ResultsThe TBINet model demonstrated superior performance with an area under the curve (AUC) of 0.819 and 0.753 on the validation and external test sets, respectively, compared to existing deep learning methods. Furthermore, using Grad-CAM, we observed that CT images with higher levels of consolidation, voids, upper lobe involvement, and enlarged lymph nodes were more likely to come from patients with highly infectious forms of PTB.ConclusionOur study proves the feasibility of using CT images to identify the infectivity of PTB patients based on the deep learning method.

To understand the occurrence state of fracturing fluid in shale gas matrix-fracture system, an experimental method for evaluating fracturing fluid flow characteristics in matrix-fracture system was established. By using Nuclear Magnetic Resonance method, the flow characteristics of fracturing fluid were investigated from three processes of filtration, well shut-in and flowback. The T2 spectrum of fracturing fluid flow process and fracturing fluid saturation in matrix-fracture core model were clarified. The results demonstrate that the peak area of T2 spectra increases gradually during the filtration process, and the fracturing fluid quickly fills the fractures and matrix pores. During the well shut-in process, the fracturing fluid gradually flows from the fracture space to the matrix pores, and the signal of the matrix pores increases by 50.5%. During the flowback process, fracturing fluid flows out of the matrix and fracture. And when it reaches a stable state, the peak signal in the fracture decreases by 64.5% and the matrix signal reduces by 18.8%. The better the porosity and permeability characteristics of the core, the more likely the fracturing fluid is to stay in the formation and cannot be discharged. This paper would contribute to basic parameters for shale gas fracturing design and production strategy optimization.

Abstract The properly applied pressure between the skin and hemostasis devices is an essential parameter for preventing bleeding and postoperative complications after a transradial procedure. However, this parameter is usually controlled based on the subjective judgment of doctors, which might cause insufficient hemostatic effect or thrombosis. Here this study develops a compact and wireless sensing system for continuously monitoring the pressure applied on the radial artery and wrist skin in clinical practice. A liquid metal (LM)‐based all‐soft pressure sensor is fabricated to enable conformal attachment between the device and skin even under large deformation conditions. The linear sensitivity of 0.007 kPa−1 among the wide pressure range of 0–100 kPa is achieved and the real‐time detection data can be wirelessly transmitted to mobile clients as a reference pressure value. With these devices, detailed pressure data can be collected, analyzed, and stored for medical assistance as well as to improve surgery quality.

BackgroundIn recent years, the role of ferroptosis in Parkinson’s disease (PD) has become a research hotspot based on evidence of abnormal iron deposition and lipid peroxidation damage in the brains of PD patients. This study aims to examine the relevant research on ferroptosis and PD from a bibliometric perspective.MethodsOriginal research and review articles related to ferroptosis and PD were retrieved from the Web of Science Core Collection (WOSCC) database. Statistical analysis and visualization of information including countries, institutions, authors, journals, and keywords of the included studies were conducted using the R software package “bibliometrix.”ResultsA total of 414 articles met the inclusion criteria, averaging 37.86 citations per article. From 2012 to 2022, the average annual growth rate of research in this area was 63.44%. The corresponding authors of published articles were mainly affiliated with institutions in China, the United States, and Australia. Shanghai Jiao Tong University in China and the University of Melbourne in Australia emerged as the most active and influential institutions. The journal with the highest H-index and publication output was Free Radical Biology and Medicine. “Ferroptosis,” “immunotherapy,” “prognosis” and “microenvironment” were identified as high-frequency keywords, indicating current and future research directions in this field.ConclusionThis bibliometric study provides insights into current research hotspots and emerging trends in the growing field of ferroptosis research related to PD. The high-frequency keywords identified highlight active areas of investigation involving methods, mechanisms, and populations of interest.

Alzheimer’s disease (AD) is a common neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aβ), hyperphosphorylation of tau, and neuroinflammation in the brain. The blood–brain barrier (BBB) limits solutes from circulating blood from entering the brain, which is essential for neuronal functioning. Focusing on BBB function is important for the early detection of AD and in-depth study of AD pathogenic mechanisms. However, the mechanism of BBB alteration in AD is still unclear, which hinders further research on therapeutics that target the BBB to delay the progression of AD. The exact timing of the vascular abnormalities in AD and the complex cause-and-effect relationships remain uncertain. Thus, it is necessary to summarize and emphasize this process. First, in this review, the current evidence for BBB dysfunction in AD is summarized. Then, the interrelationships and pathogenic mechanisms between BBB dysfunction and the risk factors for AD, such as Aβ, tau, neuroinflammation, apolipoprotein E (ApoE) genotype and aging, were analyzed. Finally, we discuss the current status and future directions of therapeutic AD strategies targeting the BBB. We hope that these summaries or reviews will allow readers to better understand the relationship between the BBB and AD.

Reflux esophagitis (RE), an esophageal inflammation caused by reflux of gastric contents, often damages the lower esophagus, seriously affecting the quality of life of patients. This study aims to investigate the therapeutic effects and underlying molecular mechanisms of atractylenolide III (ATL III) on RE model rats. In this research, the RE rat model is established sequentially following hemipyloric ligation, cardia transection, and hydrochloric acid perfusion. Further, the RE-induced rats are intragastrically administrated with ATL III (0.6, 1.2, and 2.4 mg/kg/D) for 28 days to evaluate ATL III therapeutic effects. To study the molecular mechanism, RE rats are treated with a phosphoinositide-3 kinase (PI3K) agonist (740 Y–P) combined with ATL III. The histopathological changes in the esophagus are eventually observed by hematoxylin & eosin (H&E) staining. In addition to changes in gastric pH and levels of reactive oxygen species (ROS), enzyme-linked immunosorbent assay (ELISA) and Western blot analyses are used to detect the expression levels of tumor necrosis factor-α (TNF-α, mmol/L), interleukin (IL)-8, IL-6, IL-1β in the esophageal tissues. As a result, the lesions in the esophageal tissues of RE rats are alleviated, decreasing the macroscopic observation scores of the esophageal mucosa after ATL III treatment,. The experimental results indicated significantly increased pH value of the gastric contents and reduced ROS, thiobarbituric acid reactants (TBARS), TNF-α, IL-8, IL-6, and IL-1β levels, as well as expression levels of p-PI3K, p-AKT, iNOS, and nuclear NF-κB proteins in esophageal tissues. In conclusion, the study indicated that ATL III could efficiently treat RE in rats by inhibiting oxidative stress and inflammatory damage through the PI3K/AKT/NF-κB/iNOS pathway.

Objective: The objective of this study was to evaluate the whole-brain pattern of oxygen extraction fraction (OEF), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen consumption (CMRO2) perturbation in Alzheimer's disease (AD) and investigate the relationship between regional cerebral oxygen metabolism and global cognition. Methods: Twenty-six AD patients and 25 age-matched healthy controls (HC) were prospectively recruited in this study. Mini-Mental State Examination (MMSE) was used to evaluate cognitive status. We applied the QQ-CCTV algorithm which combines quantitative susceptibility mapping and quantitative blood oxygen level-dependent models (QQ) for OEF calculation. CBF map was computed from arterial spin labeling and CMRO2 was generated based on Fick's principle. Whole-brain and regional OEF, CBF, and CMRO2 analyses were performed. The associations between these measures in substructures of deep brain gray matter and MMSE scores were assessed. Results: Whole brain voxel-wise analysis showed that CBF and CMRO2 values significantly decreased in AD predominantly in the bilateral angular gyrus, precuneus gyrus and parieto-temporal regions. Regional analysis showed that CBF value decreased in the bilateral caudal hippocampus and left rostral hippocampus and CMRO2 value decreased in left caudal and rostral hippocampus in AD patients. Considering all subjects in the AD and HC groups combined, the mean CBF and CMRO2 values in the bilateral hippocampus positively correlated with the MMSE score. Conclusion: CMRO2 mapping with the QQ-CCTV method - which is readily available in MR systems for clinical practice - can be a potential biomarker for AD. In addition, CMRO2 in the hippocampus may be a useful tool for monitoring cognitive impairment.

ABSTRACT: Mycoplasma gallisepticum (MG) is one of the important pathogens in poultry industry and has led to major economic losses. Understanding the epidemiology is crucial to improve the control and eradication program of MG. This study collected 1,250 chicken samples, including trachea and lung, from China in 2022 to investigate the epidemiology of MG. Among the collected samples, 938 samples were positive for MG infection, resulting in an average positive rate of 75.04%. Additionally, 570 samples were positive for both MG and Mycoplasma synoviae (MS) coinfection, with an average positive rate of 45.60%. A total of 183 MG infection positive samples in this study were selected for genotyping, and the multilocus sequence typing (MLST) method based on 7 housekeeping genes was used. As a result, 183 samples belonged to 11 sequence types (STs), with ST-78 being the most prevalent. After BURST analysis, all 183 sequences were divided into group 3. Besides, 119 reference sequences from database and 183 sequences of this study were selected to construct the phylogenetic tree using the neighbor-joining method. The results revealed that the sequences from China, total 196 sequences, were classified into 4 branches. The findings suggest that the MG strains in China exhibit diverse genotypes, which may be related to international trade and the use of live vaccines. Furthermore, we detected the drug susceptibility of 10 isolated strains randomly, which may be helpful to guide the clinical use of drugs to control MG infection.

PurposeThis study aims to explore novel biomarkers related to the coagulation process and tumor-associated macrophage (TAM) infiltration in lung adenocarcinoma (LUAD).MethodsThe macrophage M2-related genes were obtained by Weighted Gene Co-expression Network Analysis (WGCNA) in bulk RNA-seq data, while the TAM marker genes were identified by analyzing the scRNA-seq data, and the coagulation-associated genes were obtained from MSigDB and KEGG databases. Survival analysis was performed for the intersectional genes. A risk score model was subsequently constructed based on the survival-related genes for prognosis prediction and validated in external datasets.ResultsIn total, 33 coagulation and macrophage-related (COMAR) genes were obtained, 19 of which were selected for the risk score model construction. Finally, 10 survival-associated genes (APOE, ARRB2, C1QB, F13A1, FCGR2A, FYN, ITGB2, MMP9, OLR1, and VSIG4) were involved in the COMAR risk score model. According to the risk score, patients were equally divided into low- and high-risk groups, and the prognosis of patients in the high-risk group was significantly worse than that in the low-risk group. The ROC curve indicated that the risk score model had high sensitivity and specificity, which was validated in multiple external datasets. Moreover, the model also had high efficacy in predicting the clinical outcomes of LUAD patients who received anti-PD-1/PD-L1 immunotherapy.ConclusionThe COMAR risk score model constructed in this study has excellent predictive value for the prognosis and immunotherapeutic clinical outcomes of patients with LUAD, which provides potential biomarkers for the treatment and prognostic prediction.

ABSTRACT The N4-like viruses, which were recently assigned to the novel viral family Schitoviridae in 2021, belong to a podoviral-like viral lineage and possess conserved genomic characteristics and a unique replication mechanism. Despite their significance, our understanding of N4-like viruses is primarily based on viral isolates. To address this knowledge gap, this study has established a comprehensive N4-like viral data sets comprising 342 high-quality N4-like viruses/proviruses (144 viral isolates, 158 uncultured viruses, and 40 integrated N4-like proviruses). These viruses were classified into 97 subfamilies (89 of which are newly identified), 148 genera (100 of which are newly identified), and 253 species (177 of which are newly identified). The study reveals that N4-like viruses inhibit the polar region, oligotrophic open oceans, and the human gut, where they infect various bacterial lineages, such as Alpha/Beta/Gamma/Epsilon-proteobacteria in the Proteobacteria phylum. Although N4-like viral endogenization appears to be prevalent in Proteobacteria, it has also been observed in Firmicutes. Additionally, the phylogenetic analysis has identified evolutionary divergence within the hallmark genes of N4-like viruses, indicating a complex origin of the different conserved parts of viral genomes. Moreover, 1,101 putative auxiliary metabolic genes (AMGs) were identified in the N4-like viral pan-proteome, which mainly participate in nucleotide and cofactor/vitamin metabolisms. Of these AMGs, 27 were found to be associated with virulence, suggesting their potential involvement in the spread of bacterial pathogenicity. Importance The findings of this study are significant, as N4-like viruses represent a unique viral lineage with a distinct replication mechanism and a conserved core genome. This work has resulted in a comprehensive global map of the entire N4-like viral lineage, including information on their distribution in different biomes, evolutionary divergence, genomic diversity, and the potential for viral-mediated host metabolic reprogramming. As such, this work significantly contributes to our understanding of the ecological function and viral-host interactions of bacteriophages.

In recent years, the Alzheimer’s disease (AD) epidemic has become one of the largest global healthcare crises. Besides, the available systemic therapies for AD are still inadequate. Due to the insufficient therapeutic options, new treatment strategies are urgently needed to achieve a satisfactory therapeutic effect. Marine bio-resources have been accepted as one of the most economically viable and sustainable sources with potential applications for drug discovery and development. In this study, a marine cyanobacteria–Synechococcus sp. XM-24 was selected as the object of research, to systematically investigate its therapeutic potential mechanisms for AD. The major active compounds derived from the Synechococcus sp. biomass were identified via pyrolysis-gas chromatography-mass spectrometry (GC-MS), and 22 compounds were identified in this strain. The most abundant chemical compounds was (E)-octadec-11-enoic acid, with the peak area of 30.6%. Follow by tridecanoic acid, 12-methyl- and hexadecanoic acid, with a peak area of 23.26% and 18.23%, respectively. GC-MS analysis also identified indolizine, isoquinoline, 3,4-dihydro- and Phthalazine, 1-methyl-, as well as alkene and alkane from the strain. After the chemical toxicity test, 10 compounds were finally collected to do the further analysis. Then, network pharmacology and molecular docking were adopted to systematically study the potential anti-AD mechanism of these compounds. Based on the analysis, the 10 Synechococcus-derived active compounds could interact with 128 related anti-AD targets. Among them, epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGFA) and mitogen-activated protein kinase 3 (MAPK3) were the major targets. Furthermore, the compounds N-capric acid isopropyl ester, (E)-octadec-11-enoic acid, and 2H-Pyran-2,4(3H)-dione, dihydro-6-methyl- obtained higher degrees in the compounds-intersection targets network analysis, indicating these compounds may play more important role in the process of anti-AD. In addition, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that these active compounds exert the anti-AD effects mainly through PI3K-Akt signaling pathway, neuroactive ligand-receptor interaction and ras signaling pathway. Our study identified Synechococcus-derived bioactive compounds have the potential for application to AD by targeting multiple targets and related pathways, which will provide a foundation for future research on applications of marine cyanobacteria in the functional drug industry.

BackgroundEndodermal sinus tumors are rare, especially extragonadal endodermal sinus tumors, which often occur in the midline of the brain, neck, chest, and abdomen.Case summaryWe present the case of a 37-year-old woman with a mass on the right edge of the liver. Color Doppler ultrasound, computed tomography, and magnetic resonance imaging examinations were performed before the operation. Given these results and the elevation of alpha-fetoprotein, the diagnosis of hepatocellular carcinoma was made. Postoperative pathological examination indicated an endodermal sinus tumor on the abdominal wall near the right liver. The causes of misdiagnosis were analyzed, and the related literature was reviewed.ConclusionPrimary endodermal sinus tumors on the abdominal wall near the right liver are easily misdiagnosed as hepatocellular carcinoma due to liver compression and elevated alpha-fetoprotein. The key point of differentiation is the wide basal connection between the tumor and the abdominal wall near the liver. In addition, the enhancement mode of endodermal sinus tumors is different from the enhancement pattern of hepatocellular carcinoma.Core tipExtragonadal endodermal sinus tumors often occur in the midline of the body. Here, we present a case of a primary endodermal sinus tumor on the abdominal wall near the right liver for the first time.

ObjectivesTo develop a scoring system based on independent predictors of the need for ventriculoperitoneal (VP) shunt after brain tumor resection in pediatric patients.MethodsA total of 416 pediatric patients (≤ 14 years old) with brain tumors who underwent surgery were randomly assigned to the training (n = 333) and validation cohorts (n = 83). Based on the implementation of VP shunt, the training cohort was divided into the VP shunt group (n = 35) and the non-VP shunt group (n = 298). Univariate and multivariate logistic analyses were performed. A scoring system was developed based on clinical characteristics and operative data, and scores and corresponding risks were calculated.ResultsAge < 3 (p = 0.010, odds ratio [OR] = 3.162), blood loss (BL) (p = 0.005, OR = 1.300), midline tumor location (p < 0.001, OR = 5.750), preoperative hydrocephalus (p = 0.001, OR = 7.044), and total resection (p = 0.025, OR = 0.284) were identified as independent predictors. The area under the curve (AUC) of the scoring system was higher than those of age < 3, BL, midline tumor location, preoperative hydrocephalus, and total resection (0.859 vs. 0.598, 0.717, 0.725, 0.705, and 0.555, respectively; p < 0.001). Furthermore, the scoring system showed good performance in the validation cohort (AUC = 0.971). The cutoff value for predictive scores was 5.5 points, which categorized patients into low risk (0-5 points) and high risk (6-14 points) groups.ConclusionsOur scoring system, integrating age < 3, BL, midline tumor location, preoperative hydrocephalus, and total resection, provides a practical evaluation. Scores ranging from 6 to 14 points indicate high risk.

The carbon–nitrogen double bond (C=N) is a fundamentally important functional group in organic chemistry. This is largely due to the fact that C=N acts as electrophilic synthon to give nitrogen-containing compounds. Here, we report the condensation of primary amine or hydrazine with very electron-deficient aldehyde to form C=N bond in the absence of any catalysts (metals and acids). The protocol performs at room temperature and applies water as co-solvent. Two hundred examples are presented here. With its intrinsic advantages of wide substrate scopes, excellent efficiency (high yields and short reaction time), operational simplicity, mild condition (room temperature as reaction temperature, no catalysts, no additions, water as co-solvent and opening to air) and available starting materials, the protocol can be compatible with various drugs, prodrugs, dyes and pharmacophores containing primary amino group. In addition, we also successfully apply this protocol to rapidly synthesize the core scaffolds of bioactive molecules.

The separation and transport of photogenerated carriers is regarded as a curial factor in photocatalytic H2 production. As known in solar cells and photoelectron-chemistry, to strengthen the electron conduction for effective utilization of carriers, the electron transport material (ETM) is widely applied. Herein, inspired by the function of ETM, we adopted barium stannate (BaSnO3, labeled as BSO) as an excellent ETM which had the merits of high electron mobility, suitable conduction band position and simple preparation, to adjust the carrier kinetics of dye Eosin Y (EY)-sensitized photocatalytic system. Detailly, the photocatalytic system with the spatial separation sites of photogenerated carriers excitation and water reduction reaction was elaborately constructed, that was, dye EY-sensitized BSO (EY/BSO) for photocatalytic H2 production. The photocatalytic H2-production rate of EY/BSO (257 μmol·h−1·gEY−1) in the absence of noble metals was 28.6 times higher than that of single EY (∼9 μmol·h−1·gEY−1) under visible-light irradiation. With systematic and comprehensive characterizations, the formed electron transport channel by the bidentate bridging of EY on BSO could accelerate the transfer of photogenerated electrons from EY to BSO, promoting the effective separation of photogenerated carriers for the enhanced photocatalytic performance. Moreover, the water reduction reaction for H2 production proceeded on the surface of BSO that acted as the H2-evolution cocatalyst, avoiding the use of high-cost noble metals. Furthermore, based on the well-proved ETM-based concept in the EY/BSO system, La-doped BaSnO3 (LBSO) with better electron transport ability was adopted to construct EY/LBSO system (344 μmol·h−1·gEY−1) which showed better photocatalytic activity than EY/BSO.

Abstract Identifying tumor-cell-specific markers and elucidating their epigenetic regulation and spatial heterogeneity provides mechanistic insights into cancer etiology. Here, we perform snRNA-seq and snATAC-seq in 34 and 28 human clear cell renal cell carcinoma (ccRCC) specimens, respectively, with matched bulk proteogenomics data. By identifying 20 tumor-specific markers through a multi-omics tiered approach, we reveal an association between higher ceruloplasmin (CP) expression and reduced survival. CP knockdown, combined with spatial transcriptomics, suggests a role for CP in regulating hyalinized stroma and tumor-stroma interactions in ccRCC. Intratumoral heterogeneity analysis portrays tumor cell-intrinsic inflammation and epithelial-mesenchymal transition (EMT) as two distinguishing features of tumor subpopulations. Finally, BAP1 mutations are associated with widespread reduction of chromatin accessibility, while PBRM1 mutations generally increase accessibility, with the former affecting five times more accessible peaks than the latter. These integrated analyses reveal the cellular architecture of ccRCC, providing insights into key markers and pathways in ccRCC tumorigenesis.

Abstract Background The development of multidrug resistance (MDR) during postoperative chemotherapy for colorectal cancer substantially reduces therapeutic efficacy. Nanostructured drug delivery systems (NDDSs) with modifiable chemical properties are considered promising candidates as therapies for reversing MDR in colorectal cancer cells. Selenium-doped manganese phosphate (Se-MnP) nanoparticles (NPs) that can reverse drug resistance through sustained release of selenium have the potential to improve the chemotherapy effect of colorectal cancer. Results Se-MnP NPs had an organic–inorganic hybrid composition and were assembled from smaller-scale nanoclusters. Se-MnP NPs induced excessive ROS production via Se-mediated activation of the STAT3/JNK pathway and a Fenton-like reaction due to the presence of manganese ions (Mn2+). Moreover, in vitro and in vivo studies demonstrated Se-MnP NPs were effective drug carriers of oxaliplatin (OX) and reversed multidrug resistance and induced caspase-mediated apoptosis in colorectal cancer cells. OX@Se-MnP NPs reversed MDR in colorectal cancer by down-regulating the expression of MDR-related ABC (ATP binding cassette) transporters proteins (e.g., ABCB1, ABCC1 and ABCG2). Finally, in vivo studies demonstrated that OX-loaded Se-MnP NPs significantly inhibited proliferation of OX-resistant HCT116 (HCT116/DR) tumor cells in nude mice. Conclusions OX@Se-MnP NPs with simple preparation and biomimetic chemical properties represent promising candidates for the treatment of colorectal cancer with MDR.

To solve the problems of low consolidation strength and high energy consumption of vanadium-titanium magnetite (VTM) pellets, high-pressure grinding rolls (HPGR) technology can be used to pretreat the raw materials (VTM concentrate). Compared with other technologies, HPGR pretreatment has the advantages of high efficiency and low energy consumption. This study discovered that the quantities of titaniferous magnetite particles with coarse size and regular shape were dominant in VTM concentrate. Lower surface area resulted in lower microcrystalline and recrystallization bonding strength of titaniferous hematite in VTM pellets. In this study, HPGR pretreatment technology was used in the preparation of VTM pellets. Experiments confirmed that the high pressure supplied by HPGR could increase the total contact area between particles in VTM pellets, which was conducive to form more microcrystalline and recrystallization connections of titaniferous hematite. The performance of VTM green pellets was greatly improved by HPGR pretreatment, the preheating temperature could be reduced about 100 °C, the roasting temperature could be decreased 60–80 °C, the preheating and roasting time could also be correspondingly shortened. These research results will provide important insights to solve the problems of low strength and high energy consumption of VTM pellets.

Abstract Epithelial–mesenchymal transition (EMT) of the retinal pigment epithelium (RPE) is a hallmark of the pathogenesis of proliferative vitreoretinopathy (PVR) that can lead to severe vision loss. Nevertheless, the precise regulatory mechanisms underlying the pathogenesis of PVR remain largely unknown. Here, we show that the expression of death-associated protein-like 1 (DAPL1) is downregulated in PVR membranes and that DAPL1 deficiency promotes EMT in RPE cells in mice. In fact, adeno-associated virus (AAV)-mediated DAPL1 overexpression in RPE cells of Dapl1-deficient mice inhibited EMT in physiological and retinal-detachment states. In a rabbit model of PVR, ARPE-19 cells overexpressing DAPL1 showed reduced ability to induce experimental PVR, and AAV-mediated DAPL1 delivery attenuated the severity of experimental PVR. Furthermore, a mechanistic study revealed that DAPL1 promotes P21 phosphorylation and its stabilization partially through NFκB (RelA) in RPE cells, whereas the knockdown of P21 led to neutralizing effects on DAPL1-dependent EMT inhibition and enhanced the severity of experimental PVR. These results suggest that DAPL1 acts as a novel suppressor of RPE-EMT and has an important role in antagonizing the pathogenesis of experimental PVR. Hence, this finding has implications for understanding the mechanism of and potential therapeutic applications for PVR.

Abstract Gliomas refer to a group of complicated human brain tumors with a low 5‐year survival rate and limited therapeutic options. Extremely low‐frequency pulsed electromagnetic field (ELF‐PEMF) is a specific magnetic field featuring almost no side effects. However, the application of ELF‐PEMF in the treatment of gliomas is rare. This review summarizes five significant underlying mechanisms including calcium ions, autophagy, apoptosis, angiogenesis, and reactive oxygen species, and applications of ELF‐PEMF in glioma treatment from a clinical practice perspective. In addition, the prospects of ELF‐PEMF in combination with conventional therapy for the treatment of gliomas are reviewed. This review benefits any specialists, especially oncologists, interested in this new therapy because it can help treat patients with gliomas properly.

To investigate the effect of different structures of MOF on the catalytic performance of ammonium perchlorate (AP) thermal decomposition. By adding 2-methylimidazole (2-MI) as an inhibitor during the synthesis of MOF-5, a two-dimensional (2D) MOF material was prepared and characterized by SEM, EDS, XRD, FT-IR and other means. The prepared two-dimensional material was added to the AP raw material to investigate its effect on the AP thermal decomposition process. After DSC and TG test, it was found that the addition of this kind of 2D MOF material can completely eliminate the low-temperature decomposition peak of the AP-based composite and advance the high temperature decomposition peak to 296.5 °C, and the apparent heat of decomposition increase to 905.6 J/g, which has a better catalytic effect than the bulk MOF-5. In addition, through the combustion test, it was found that 2D MOF, as a burning rate catalyst, can effectively enhance the burning rate of AP based solid propellant.

Abstract Background Recent numerous epidemiology and clinical association studies reported that ApoE polymorphism might be associated with the risk and severity of coronavirus disease 2019 (COVID-19), and yielded inconsistent results. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection relies on its spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptor expressed on host cell membranes. Methods A meta-analysis was conducted to clarify the association between ApoE polymorphism and the risk and severity of COVID-19. Multiple protein interaction assays were utilized to investigate the potential molecular link between ApoE and the SARS-CoV-2 primary receptor ACE2, ApoE and spike protein. Immunoblotting and immunofluorescence staining methods were used to access the regulatory effect of different ApoE isoform on ACE2 protein expression. Results ApoE gene polymorphism (ε4 carrier genotypes VS non-ε4 carrier genotypes) is associated with the increased risk (P = 0.0003, OR = 1.44, 95% CI 1.18–1.76) and progression (P

Abstract Cognitive dysfunction is a common postoperative neurological complication in patients undergoing valve replacement surgery. This study aimed to compare the effects of sevoflurane versus propofol‐based total intravenous anesthesia on the incidence of cognitive dysfunction following valve replacement surgery. This multicenter, randomized, controlled double‐blinded study was conducted in three teaching hospitals in China. Patients receiving on‐pump valve replacement surgery were enrolled. Stratified block randomization was used to randomly assign patients 1:1 to receive sevoflurane (1.0–1.5 MAC) or propofol (2.0–3.0 mg/kg/h) for anesthesia maintenance. The primary outcome was the incidence of cognitive dysfunction assessed by four cognitive tests before, as well as 7–14 days after surgery. Patients were randomly assigned to receive sevoflurane anesthesia (n = 144) or propofol‐based total intravenous anesthesia (n = 145). The incidence of postoperative cognitive dysfunction in the sevoflurane anesthesia group (31.9%) was significantly lower than that in the total intravenous anesthesia group (43.4%; relative risk 0.61, 95% confidence interval [CI]: 0.38–0.97, p = 0.044). There was no difference in the incidence of delirium between patients receiving sevoflurane and total intravenous anesthesia (27.8% [35/144] vs. 25.9% [35/145], 1.10, 95% CI: 0.64 to 1.90, p = 0.736). There was a significant difference in the Katz Index on day 3 after surgery (3 [0.9) vs. 3 (1.0], 0.095, 95% CI: 0.05 to 0.43, p = 0.012). No difference was observed in other outcomes between the two groups. For patients undergoing on‐pump valve replacement surgery, sevoflurane anesthesia had a smaller effect on cognitive function and independence in daily life activities compared with propofol anesthesia.