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Extracting uranium from seawater is an effective strategy for sustainable nuclear fuel supplementation. Uranium in seawater mainly exists in the form of hexavalent uranyl(U(Ⅵ)), although the total amount is large, the mass fraction of U(Ⅵ) is only 3.3×10−9, and many metal ions coexist with uranium. Extracting uranium from seawater is extremely challenging. Electrochemical seawater uranium extraction has become an emerging method for seawater uranium extraction due to its advantages over physical and chemical adsorption processes, such as fast reaction rate, strong anti-interference ability, and simple desorption. However, due to the lack of research on the structure-activity relationship between catalysts and uranium extraction performance, the rational design of highly active electrocatalysts remains a challenge. In this work, we proposed an interface bonding strategy by using a simple hydrothermal method to bond the {2 2 2} fact of octahedral Fe3O4 to the {0 0 2} fact of MoS2. This significantly improves the electron transfer rate at the interface and the cycling stability of Fe3O4, verifying the feasibility of interface bonding for the electrochemical extraction of uranium from seawater. After 7 hours of electrochemical extraction in a simulated solution, the extraction efficiency of uranium can reach 96%. Meanwhile, the experimental results of coexisting ion extraction of uranium indicated that MoS2/Fe3O4 has good selectivity for uranium and anti-interference ability against coexisting ions. Electrochemical extraction is also performed in 10 L natural seawater with a yield of 27.2 μg. The extraction amount of uranium is 5.44 mg/g. A series of characterizations such as XPS and HRTEM, show that Fe3O4 is dispersed on the surface of MoS2 and effectively bound through interfacial interactions. This dispersion effectively solves the aggregation problem of Fe3O4, and the stability of MoS2 structure ensures the cycling stability of Fe3O4. By combining the MoS2 and Fe3O4 at the interface, an efficient electron transfer channel can be constructed, accelerating electron transfer and achieving the goal of simultaneously improving the selectivity, stability, and electron transfer rate of the catalyst. Therefore, the interfacial regulation strategy proposed in this work utilizes the synergistic effects of different components in the composite material to achieve stability and the cyclicity of the catalyst in seawater uranium extraction. At the same time, the interface control strategy will also provide a feasible solution for achieving efficient reduction and extraction of uranyl in a series of complex environments such as seawater. And the electron transfer path and the species change of uranium during catalytic reduction need to be further explored in the mechanism analysis in this work.

Uranium, as the most important fuel for nuclear power operation, is crucial to ensure the sustainable development of nuclear power. However, the supply-demand contradiction of uranium resources in China has become increasingly prominent, and the gap needs to be filled by overseas development and international market procurement. The photoreduction and electroreduction of uranium under complex conditions are mainly targeted at uranium containing radioactive wastewater, real seawater, and other systems. Uranium containing radioactive wastewater comes from the processes of uranium mining, uranium enrichment, uranium conversion, and manufacture of nuclear fuel elements, with the characteristics of complex interfering ions. Although the total amount of uranium in seawater is very large, the concentration of uranium in seawater is low, making the extraction of uranium from seawater extremely challenging. On the one hand, the reserves of uranium in seawater are nearly a thousand times higher than those on land; on the other hand, the entire application process of the nuclear industry produces a large amount of uranium containing radioactive wastewater. If efficient separation of uranium from seawater and uranium containing radioactive wastewater can be achieved, it can promote the secondary supply of uranium resources and alleviate the supply-demand contradiction of uranium resources in China. Therefore, the development of uranium recovery and extraction technology from seawater and uranium containing radioactive wastewater is important for the sustainable development of the nuclear industry. This paper reviews the recent research progress in separating uranium in complex environments such as seawater and uranium containing radioactive wastewater. In terms of uranium speciation analysis, it describes the coordination environment of complex environmental uranyl and summarizes the advantages of photocatalysis and electrocatalysis in the fields of uranium extraction from uranium containing radioactive wastewater and seawater. In terms of designing photocatalysts, strategies such as element doping, metal loading, defect engineering, and introducing heterojunctions have been summarized for the preparation of photocatalytic semiconductor materials. The modification of functional groups on heterojunctions to regulate their energy band structure had introduced, which improved the overall performance of the material. The integration of selective adsorption and catalytic reduction, electrochemical methods can reduce soluble uranyl ions to neutral and insoluble products for separation, with advantages such as fast kinetics, wide extraction concentration range, and large separation capacity. However, there are also many key technical challenges in the practical application process, such as the competition between multiple cations and uranyl ions in complex systems, and the problem of excessive energy consumption caused by the competing reaction of water splitting during the cathodic uranium extraction process. In terms of electrocatalysis, various aspects such as electrode carrier selection, electrochemical device design, defect engineering, surface engineering, interface engineering, and microbial electrochemistry have been summarized to design electrocatalytic materials. In terms of key technical bottlenecks, combining photocatalysis and electrocatalysis technology with challenges in complex scenarios such as uranium speciation analysis, material functionalization design, intermediate reaction species analysis, uranium extraction mechanism analysis, cost control, and real-world application outcomes, relevant research have focused on challenges such as efficient photocatalytic reduction of uranium under natural light, identification of intermediate uranium species, uranium extraction from uranium containing radioactive wastewater, and seawater extraction from real ocean environments.

Abstract Osteoarthritis (OA) is the most common degenerative joint disorder that causes disability in aged individuals, caused by functional and structural alterations of the knee joint. To investigate whether metabolic drivers might be harnessed to promote cartilage repair, a liquid chromatography–mass spectrometry (LC–MS) untargeted metabolomics approach was carried out to screen serum biomarkers in osteoarthritic rats. Based on the correlation analyses, α-ketoglutarate (α-KG) has been demonstrated to have antioxidant and anti-inflammatory properties in various diseases. These properties make α-KG a prime candidate for further investigation of OA. Experimental results indicate that α-KG significantly inhibited H2O2-induced cartilage cell matrix degradation and apoptosis, reduced levels of reactive oxygen species (ROS) and malondialdehyde (MDA), increased superoxide dismutase (SOD) and glutathione (GSH)/glutathione disulfide (GSSG) levels, and upregulated the expression of ETV4, SLC7A11 and GPX4. Further mechanistic studies observed that α-KG, like Ferrostatin-1 (Fer-1), effectively alleviated Erastin-induced apoptosis and ECM degradation. α-KG and Fer-1 upregulated ETV4, SLC7A11, and GPX4 at the mRNA and protein levels, decreased ferrous ion (Fe2+) accumulation, and preserved mitochondrial membrane potential (MMP) in ATDC5 cells. In vivo, α-KG treatment inhibited ferroptosis in OA rats by activating the ETV4/SLC7A11/GPX4 pathway. Thus, these findings indicate that α-KG inhibits ferroptosis via the ETV4/SLC7A11/GPX4 signaling pathway, thereby alleviating OA. These observations suggest that α-KG exhibits potential therapeutic properties for the treatment and prevention of OA, thereby having potential clinical applications in the future.

Abstract Electrochemical uranium extraction from nuclear wastewater represents an emerging strategy for recycling uranium resources. However, in nuclear fuel production which generates the majority of uranium-containing nuclear wastewater, fluoride ion (F−) co-exists with uranyl (UO2 2+), resulting in the complex species of UO2Fx and thus decreasing extraction efficiency. Herein, we construct Tiδ+-PO4 3− ion pair extraction sites in Ti(OH)PO4 for efficient electrochemical uranium extraction in wastewater from nuclear fuel production. These sites selectively bind with UO2Fx through the combined Ti-F and multiple O-U-O bonds. In the uranium extraction, the uranium species undergo a crystalline transition from U3O7 to K3UO2F5. In real nuclear wastewater, the uranium is electrochemically extracted with a high efficiency of 99.6% and finally purified as uranium oxide powder, corresponding to an extraction capacity of 6829 mg g−1 without saturation. This work paves an efficient way for electrochemical uranium recycling in real wastewater of nuclear production.

Objective: This study investigated sex-specific pathogenesis mechanisms in Alzheimer's disease (AD) using single-nucleus RNA sequencing (snRNA-seq) data. Methods: Data from the Gene Expression Omnibus (GEO) were searched using terms “Alzheimer's Disease”, “single cell”, and “Homo sapiens”. Studies excluding APOE E4 and including comprehensive gender information with 10× sequencing methods were selected, resulting in GSE157827 and GSE174367 datasets from human prefrontal cortex samples. Sex-stratified analyses were conducted on these datasets, and the outcomes of the analysis for GSE157827 were compared with those of GSE174367. The findings were validated using expression profiling from the mouse dataset GSE85162. Furthermore, real-time PCR experiments in mice further confirmed these findings. The Seurat R package was used to identify cell types, and batch effects were mitigated using the Harmony R package. Cell proportions by sex were compared using the Mann-Whitney-Wilcoxon test, and gene expression variability was displayed with an empirical cumulative distribution plot. Differentially expressed genes were identified using the FindMarkers function with the MAST test. Transcription factors were analyzed using the RcisTarget R package. Results: Seven cell types were identified: astrocytes, endothelial cells, excitatory neurons, inhibitory neurons, microglia, oligodendrocytes, and oligodendrocyte progenitor cells. Additionally, five distinct subpopulations of both endothelial and microglial cells were also identified, respectively. Key findings included: (1) In endothelial cells, genes involved in synapse organization, such as Insulin Like Growth Factor 1 Receptor (IGF1R) and Fms Related Receptor Tyrosine Kinase 1(FLT1), showed higher expression in females with AD. (2) In microglial cells, genes in the ribosome pathway exhibited higher expression in males without AD compared to females (with or without AD) and males with AD. (3) Chromodomain Helicase DNA Binding Protein 2 (CHD2) negatively regulated gene expression in the ribosome pathway in male microglia, suppressing AD, this finding was further validated in mice. (4) Differences between Asians and Caucasians were observed based on sex and disease status stratification. Conclusions: IGF1R and FLT1 in endothelial cells contribute to AD in females, while CHD2 negatively regulates ribosome pathway gene expression in male microglia, suppressing AD in humans and mice.

Introduction Non-communicable diseases (NCDs) are the leading cause of death worldwide, and NCDs account for 61.4% of all disability-adjusted life years worldwide. The global cost of NCDs is estimated to exceed 30 trillion dollars over the period 2011–2030, representing 48% of the global gross domestic product. Older adults are the common group affected by NCDs, characterised by an insidious onset, a long course, and a protracted illness. The incidence of these diseases is increasing every year, posing a severe threat to human health and quality of life. E-educational programmes about NCDs are essential for older adults because they are the main body of patients with NCDs, and their understanding of health is uneven and inaccurate. This protocol describes a systematic review to determine the effectiveness of e-educational programme methods for NCDs in older adults. This protocol aims to summarise and critically evaluate the impact of e-educational programmes on older adult patients with NCDs and to provide direction for developing interventions to improve their quality of life and NCD health management programmes.Methods and analysis The search was performed in the databases PubMed, Cochrane Library, Web of Science, EMBASE, MEDLINE, China Biology Medicine, China National Knowledge Infrastructure and Wan Fang Data using established search terms. All randomised controlled trials on e-educational programmes for patients with NCDs published in recent 10 years (2013–2023) will be included. The risk of bias in the included study will be assessed using the Cochrane risk of bias tool after two authors have independently screened the literature. With regard to the quality of the evidence, Grading of Recommendations Assessment, Development and Evaluation analysis will be used. If the data are aggregated, then meta-analysis will be performed using RevMan V.5.4.PROSPERO registration number CRD42023455272.

Background Few small‐sample studies have quantified the T‐wave alternans (TWA) value by 24‐hour ambulatory recordings or exercise stress tests in patients with long QT syndrome (LQTS). The cutoff point of TWA ≥47 μV was based on patients with myocardial infarction. In our study, we aimed to (1) evaluate the association of TWA with life‐threatening arrhythmic events (LAEs); (2) compare the predictive model of LAEs according to the TWA value measured by 24‐hour ambulatory recordings and exercise stress tests; and (3) propose a cutoff point for the high risk of LAEs in patients with LQTS. Methods and Results The study cohort included 110 patients with LQTS referred to our hospital, and the primary outcome was LAEs. Thirty‐one patients with LQTS (31/110 [28.2%]) developed LAEs during the following 24 (12–47) months. Peak TWA value quantified from 12 leads by 24‐hour ambulatory recordings in patients with LQTS with LAEs (LQTS–LAEs group) was significantly higher than LQTS without LAEs (LQTS–non‐LAEs group) (64.0 [42.0–86.0] μV versus 43.0 [36.0–53.0] μV; P

The family Tephritidae in the order Diptera, known as true fruit flies, are agriculturally important insect pests. However, the phylogenetic relationships of true fruit flies, remain controversial. Moreover, rapid identification of important invasive true fruit flies is essential for plant quarantine but is still challenging. To this end, we sequenced the genome of 16 true fruit fly species at coverage of 47–228×. Together with the previously reported genomes of nine species, we reconstructed phylogenetic trees of the Tephritidae using benchmarking universal single-copy ortholog (BUSCO), ultraconserved element (UCE) and anchored hybrid enrichment (AHE) gene sets, respectively. The resulting trees of 50% taxon-occupancy dataset for each marker type were generally congruent at 88% nodes for both concatenation and coalescent analyses. At the subfamily level, both Dacinae and Trypetinae are monophyletic. At the species level, Bactrocera dorsalis is more closely related to Bactrocera latifrons than Bactrocera tryoni. This is inconsistent with previous conclusions based on mitochondrial genes but consistent with recent studies based on nuclear data. By analyzing these genome data, we screened ten pairs of species-specific primers for molecular identification of ten invasive fruit flies, which PCR validated. In summary, our work provides draft genome data of 16 true fruit fly species, addressing the long-standing taxonomic controversies and providing species-specific primers for molecular identification of invasive fruit flies.

Larix gmelinii is an important ecological construction tree species in northern China, and its carbon storage and distribution characteristics are of great significance for evaluating the carbon balance and climate effect of forest ecosystems. However, at present, there is a lack of systematic research on the carbon storage of L. gmelinii forests and its change with forest age. In this paper, the biomass and carbon density of L. gmelinii forests at different ages and the distribution of carbon storage in vegetation and soil were analyzed by means of sample plot investigation and model simulation in the northern forest area of Daxing’anling, Inner Mongolia. The influence of forest age on the carbon storage and carbon pool distribution characteristics of L. gmelinii forests and the mechanism of influencing factors were also discussed. Results show that: (1) As forest age increased, the total amount of carbon pools initially increased and then decreased, and the distribution structure of carbon pools showed a trend of transferring from soil to trees. The proportion of soil carbon pools gradually decreased (72.72–51.87%), while the proportion of tree carbon pools gradually increased (23.98–39.33%). The proportion of shrub and grass carbon pools was also relatively stable (0.51–0.53%). (2) Soil carbon pool was affected by the input and output of soil organic matter, soil depth, soil carbon content, and soil bulk density, shrub–grass carbon pool was affected by undergrowth light conditions and soil moisture, litter carbon pool was affected by litter input and output, and the carbon pool of trees was affected by the growth rate and carbon balance of trees. This study provides scientific basis and management suggestions for the carbon storage capacity of L. gmelinii forests and the mitigation of climate change.

To address the alerting issue of energy demand, lithium-ion capacitors (LICs) have been widely studied as promising electrochemical energy storage devices, which can deliver higher energy density than supercapacitors (SCs), and have higher power density with longer cycling life than lithium-ion batteries (LIBs). In this work, the active material lithium nickel cobalt manganese oxide LiNi0.5Co0.2Mn0.3O2 (NCM523) is grown on a cotton textile template and building a 3-dimensional (3D) integrity to improve capacitance and energy density of LICs by enhancing the interfacial ion-exchange process. With the 3D structure, the specific discharge capacitance is increased to 718.67 F g−1 at 0.1 A g−1 from that of non-textile NCM523 (265.97 F g−1), and remains a high capacitance of 254.48 Fg−1 at 10 A g−1 in the half-cell capacitors. In addition, the energy density can achieve up to 36.17 Wh kg−1 at the power density of 1,200 W kg−1 in the full-cell capacitor. The textile NCM can maintain an energy density of 28.26 Wh kg−1 at the current density of 10 A g−1 and power density of 6,000 W kg−1. Our results present promising applications of electrodes with the 3D porous structure for high energy density LICs.

ObjectiveMajor pathological response (MPR) helps evaluate the prognosis of patients with lung squamous cell carcinoma (LUSC). However, the clinical factors that affect the achievement of MPR after neoadjuvant chemoimmunotherapy (NCIO) in patients with LUSC remain unclear. This study aimed to explore the clinical factors affecting the MPR after NCIO in patients with potentially resectable LUSC.MethodsThis retrospective study included patients with stage IIB-IIIC LUSC who underwent surgical resection after receiving NCIO at a center between March 2020 and November 2022. In addition to the postoperative pathological remission rate, sex, age, body mass index (BMI), smoking history, TNM stage, hematological and imaging test results, and other indicators were examined before NCIO. According to the pathological response rate of the surgically removed tumor tissue, the patients were split into MPR and non-MPR groups.ResultsIn total, 91 LUSC patients who met the study’s eligibility criteria were enrolled: 32 (35%) patients in the non-MPR group and 59 (65%) in the MPR group, which included 43 cases of pathological complete remission (pCR). Pre-treatment lymphocyte level (LY) (odds ratio [OR] =5.997), tumor burden (OR=0.958), N classification (OR=15.915), radiographic response (OR=11.590), pulmonary atelectasis (OR=5.413), and PD-L1 expression (OR=1.028) were independently associated with MPR (all P < 0.05). Based on these six independent predictors, we developed a nomogram model of prediction having an area under the curve (AUC) of 0.914 that is simple to apply clinically to predict the MPR. The MPR group showed greater disease-free survival (DFS) than the non-MPR group, according to the survival analysis (P < 0.001).ConclusionThe MPR rate of NCIO for potentially resectable LUSC was 65%. LY, tumor burden, N classification, radiographic response, pulmonary atelectasis, and PD-L1 expression in patients with LUSC before NCIO were the independent and ideal predictors of MPR. The developed nomogram demonstrated a good degree of accuracy and resilience in predicting the MPR following NCIO, indicating that it is a useful tool for assuring customized therapy for patients with possibly resectable LUSC.

Background: This study aims to evaluate the efficacy and safety associated with ibrexafungerp in the treatment of vulvovaginal candidiasis infection patients. Methods: We conducted a comprehensive search of the PubMed, Embase, Cochrane Library, and Clinical Trials databases up to December 25, 2022. The primary outcomes were clinical cure rate and mycological eradication rate, whereas the secondary outcomes were the risk of an adverse events. Results: In total of four studies encompassing 880 patients diagnosed with vulvovaginal candidiasis (VVC) were included in the analysis. The findings demonstrated that ibrexafungerp exhibited superior clinical cure ratio (RR = 1.33 [1.07, 1.66]), mycological eradication rate (RR = 1.72 [1.00, 2.95]), and overall success ratio (RR = 1.64 [0.92, 2.92]) when compared to the fluconazole/placebo in the treatment of VVC. Furthermore, patients treated with ibrexafungerp demonstrated significantly higher clinical cure rates, mycological eradication, and overall success ratio compared to those receiving other treatments for vulvovaginal candidiasis caused by C. albicans. When ibrexafungerp was compared to fluconazole/placebo, the duration of any treatment-related treatment-emergent adverse events (TEAE), nausea, and diarrhea during therapy was significantly longer. Conclusion: In summary, the use of ibrexafungerp was linked to superior clinical cure ratio, and mycological eradication when compared to fluconazole/placebo.

Phthalic acid esters (PAEs) are widely used as plasticizers and have been suggested to engender adverse effects on glucose metabolism. However, epidemiological data regarding the PAE mixture on type 2 diabetes (T2DM), as well as the mediating role of oxidative stress are scarce. This case-control study enrolled 206 T2DM cases and 206 matched controls in Guangdong Province, southern China. The concentrations of eleven phthalate metabolites (mPAEs) and the oxidative stress biomarker 8-hydroxy-2′-deoxyguanosine (8-OHdG) in urine were determined. Additionally, biomarkers of T2DM in paired serum were measured to assess glycemic status and levels of insulin resistance. Significantly positive associations were observed for mono-(2-ethylhexyl) phthalate (MEHP) and Mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) with T2DM (P < 0.001). Restricted cubic spline modeling revealed a non-linear dose-response relationship between MEHHP and T2DM (Pnon-linear = 0.001). The Bayesian kernel machine regression and quantile g-computation analyses demonstrated a significant positive joint effect of PAE exposure on T2DM risk, with MEHHP being the most significant contributor. The mediation analysis revealed marginal evidence that oxidative stress mediated the association between the mPAEs mixture and T2DM, while 8-OHdG respectively mediated 26.88 % and 12.24 % of MEHP and MEHHP on T2DM risk individually (Pmediation < 0.05). Di(2-ethylhexyl) phthalate (DEHP, the parent compound for MEHP and MEHHP) was used to further examine the potential molecular mechanisms by in silico analysis. Oxidative stress may be crucial in the link between DEHP and T2DM, particularly in the reactive oxygen species metabolic process and glucose import/metabolism. Molecular simulation docking experiments further demonstrated the core role of Peroxisome Proliferator Activated Receptor alpha (PPARα) among the DEHP-induced T2DM. These findings suggest that PAE exposure can alter oxidative stress via PPARα, thereby increasing T2DM risk.

Abstract Objective To investigate the expression of TTC7B and its prognostic significance, biological roles, and impact on the immune system in patients with head and neck squamous cell carcinoma (HNSCC). Materials and Methods Clinical and genomic data were obtained from TCGA (The Cancer Genome Atlas), GEO (Gene Expression Omnibus), GEPIA2 (Gene Expression Profiling Interactive Analysis 2.0), and TIMER2.0 (Tumor Immune Estimation Resource 2.0) databases. R software was utilized to process the retrieved data. qPCR and immunohistochemical assays were performed to validate the findings obtained from the databases. Results High expression of TTC7B was observed in HNSCC, and this heightened expression is significantly associated with reduced overall survival (OS) in patients, making it an independent risk factor impacting OS. TTC7B is correlated with focal adhesions and cell migration pathways based on functional enrichment analysis. CIBERSORT analysis and TIMER2.0 show a positive link between TTC7B and multiple immune cells, particularly macrophages. Pearson's analysis reveals a significant correlation between TTC7B and ferroptosis‐related genes. Conclusion In all, TTC7B could serve as a promising prognostic indicator of HNSCC, and is closely associated with focal adhesions, immune infiltration, and ferroptosis.

This study investigated the impact of Lactiplantibacillus plantarum PC-004 (PL) and Kazachstania bulderi PY-1 (PY), selected from home-made Paocai, on the physicochemical properties and volatile flavor compounds of fermented Pleurotus eryngii. P. eryngii, fermented by PY, was maintained at about pH 5 throughout fermentation, while co-fermentation exhibited a higher acid production rate and lower post-acidification value compared to mono-fermentation by PL. The viable cell counts of PY exhibited no difference between the mono- and co-fermentation, while PL significantly decreased in the co-fermentation after 168 h. Compared to mono-fermented P. eryngii, co-fermentation had lower levels of certain biogenic amines. Co-fermented P. eryngii had a higher value of nitrite in the early fermentation stage, but this decreased during mono-fermentations. Additionally, among the three different groups, PY fermentation had more esters, PL fermentation had more ketones and aldehydes, and co-fermentation had more abundance and diverse volatile flavor compounds than mono-fermentations. Our results suggest that co-fermentation with K. bulderi and L. plantarum is suitable for producing fermented P. eryngii, highlighting their potential for the fermentation of edible mushrooms.

About one-third of the global food supply is wasted. Brewers’ spent grain (BSG), being produced in enormous amounts by the brewery industry, possesses an eminence nutritional profile, yet its recycling is often neglected for multiple reasons. We employed integrated metagenomics and metabolomics techniques to assess the effects of enzyme treatments and Lactobacillus fermentation on the antioxidant capacity of BSG. The biotreated BSG revealed improved antioxidant capability, as evidenced by significantly increased (p < 0.05) radical scavenging activity and flavonoid and polyphenol content. Untargeted metabolomics revealed that Lactobacillus fermentation led to the prominent synthesis (p < 0.05) of 15 novel antioxidant peptides, as well as significantly higher (p < 0.05) enrichment of isoflavonoid and phenylpropanoid biosynthesis pathways. The correlation analysis demonstrated that Lactiplantibacillus plantarum exhibited strong correlation (p < 0.05) with aucubin and carbohydrate-active enzymes, namely, glycoside hydrolases 25, glycosyl transferases 5, and carbohydrate esterases 9. The fermented BSG has potential applications in the food industry as a culture medium, a functional food component for human consumption, and a bioactive feed ingredient for animals.

The revised 4th edition of the World Health Organization (WHO4R) classification lists myelodysplastic syndromes with ring sideroblasts (MDS-RS) as a separate entity with single lineage (MDS-RS-SLD) or multilineage (MDS-RS-MLD) dysplasia. The more recent International Consensus Classification (ICC) distinguishes between MDS with SF3B1 mutation (MDS-SF3B1) and MDS-RS without SF3B1 mutation; the latter is instead included under the category of MDS not otherwise specified. The current study includes 170 Mayo Clinic patients with WHO4R-defined MDS-RS, including MDS-RS-SLD (N=83) and MDS-RS-MLD (N=87); a subset of 145 patients were also evaluable for the presence of SF3B1 and other mutations, including 126 with (87%) and 19 (13%) without SF3B1 mutation. Median overall survival for all 170 patients was 6.6 years with 5- and 10-year survival rates of 59% and 25%, respectively. A significant difference in overall survival was apparent between MDS-RS-MLD and MDS-RS-SLD (p

To realize the high-value utilization of Rushan cheese by-product, Rushan cheese whey was used as a raw material to prepare angiotensin-Ⅰ-converting enzyme inhibitory peptides (ACEIPs). After enzymatic hydrolysisn and ultrafiltration, the sequences of peptides were identified by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Two novel ACE inhibitory peptides Phe-Asp-Arg-Pro-Phe-Leu (FDRPFL) and Lys-Trp-Glu-Lys-Pro-Phe (KWEKPF) were identified. Additionally, both of the peptides exhibited good water-solubility and no toxicity according to in-silico prediction. Fourier transform infrared spectroscopy results show that both FDRPFL and KWEKPF were enriched in β-turn and β-sheet structures. Lineweaver-Burk plots revealed that FDRPFL and KWEKPF exhibited non-competitive and mixed inhibition patterns, respectively. Molecular docking and MD simulation showed that hydrogen bonds and ionic bonds forces allowed FDRPFL and KWEKPF to form stable and compact complexes with ACE. In conclusion, enzymatic hydrolysis of Rushan cheese by-products yields bioactive peptides, increases the added value of whey and reduces environmental pollution.

The BCL6-corepressor (BCOR) is a tumor-suppressor gene located on the short arm of chromosome X. Data are limited regarding factors predicting survival in BCOR-mutated (mBCOR) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We evaluated 138 patients with mBCOR myeloid disorders, of which 36 (26.1%) had AML and 63 (45.6%) had MDS. Sixty-six (47.8%) patients had a normal karyotype while 18 (13%) patients had complex karyotype. BCOR-mutated MDS/AML were highly associated with RUNX1 and U2AF1 co-mutations. In contrast, TP53 mutation was infrequently seen with mBCOR MDS. Patients with an isolated BCOR mutation had similar survival compared to those with high-risk co-mutations by European LeukemiaNet (ELN) 2022 criteria (median OS 1.16 vs. 1.27 years, P=0.46). Complex karyotype adversely impacted survival among mBCOR AML/MDS (HR 4.12, P

The Genhe River Basin is an ecological barrier and water conservation area in northern China, but its hydrological process has undergone significant changes due to climate change and human activities, endangering ecosystem functions and water resource security. Systematic research on the influencing mechanisms and laws of hydrological processes in different ecosystems in this region remains lacking. Therefore, this study analyzed the effects of different anthropogenic factors on the hydrological processes of typical ecosystems in the Genhe River Basin. The Soil and Water Assessment Tool distributed hydrological model was used to simulate the surface runoff, evapotranspiration, and soil water content of the three ecosystems of forest, grassland, and farmland in four different periods of 1980, 1990, 2000, and 2010. The spatial and temporal changes in water resources in typical ecosystems under the influence of historical climate change were demonstrated. Results showed that under different land use scenarios, the surface runoff of the farmland ecosystem increased, the evapotranspiration remained unchanged, and the soil water content decreased. The surface runoff of forest and grassland ecosystems did not change significantly, the evapotranspiration increased, and the soil water content decreased. This study reveals the influence of different human factors on the hydrological processes of typical ecosystems in the Genhe River Basin and provides a scientific basis for water resources management and ecological protection in the region.

BackgroundTumor immune microenvironment (TiME) is prognostically instructive in Pancreatic adenocarcinoma (PAAD). However, the potential value of TiME-related genes in the individualized immunotherapy of PAAD has not been clarified.MethodsCorrelation between Immune-Related Genes (IRGs) and immune-related transcription factors (TFs) was performed to prove the immune correlation of selected genes. Immune-related molecular subtypes were identified by consensus clustering. The TiME-score, an immune microenvironment-related prognostic signature for PAAD, was constructed using minimum absolute contraction and selection operator regression (Lasso-Cox). The International Cancer Genome Consortium (ICGC) dataset validated the reliability of TiME-score as external validation. Single-cell samples from GSE197177 confirmed microenvironment differences of TiME-score hub genes between tumor and its paracancer tissues. Then, RARRES3, a hub gene in TiME-score, was further analyzed about its upstream TP53 mutation and the specific immune landscape of itself in transcriptome and Single-cell level. Eventually, TiME-score were validated in different therapeutic cohorts of PAAD mice models.ResultsA 14-genes PAAD immune-related risk signature, TiME-score, was constructed based on IRGs. The differences of TiME-score hub genes in single-cell samples of PAAD cancer tissues and adjacent tissues were consistent with the transcriptome. Single-cell samples of cancer tissues showed more pronounced immune cell infiltration. The upstream mutation factor TP53 of RARRES3 was significantly enriched in immune-related biological processes. High RARRES3 expression was correlated with a worse prognosis and high macrophages M1 infiltration. Additionally, the immunohistochemistry of hub genes AGT, DEFB1, GH1, IL20RB, and TRAF3 in different treatment cohorts of mice PAAD models were consistent with the predicted results. The combination of immunotherapy, chemotherapy and targeted therapy has shown significantly better therapeutic effects than single drug therapy in PAAD.ConclusionTiME-score, as a prognostic signature related to PAAD-specific immune microenvironment constructed based on RARRES3, has predictive value for prognosis and the potential to guide individualized immunotherapy for PAAD patients.

Objective: This study aimed to conduct a systematic review and meta-analysis of randomized controlled trials to evaluate the effects of elexacaftor–tezacaftor–ivacaftor (ELX-TEZ-IVA) on patients with cystic fibrosis (CF). Methods: A systematic search was performed in PubMed, Embase, and the Cochrane Library from inception to August 1, 2022. Meta-analysis was conducted using Review Manager 5.3 software. Results: Six studies comprising seven reports involving a total of 1125 CF patients were included. The meta-analyses indicated that ELX-TEZ-IVA significantly improved the percentage predicted forced expiratory volume in 1 s (ppFEV1) by 10.29% (95% confidence interval (CI) (6.44, 14.14), p

Pectic oligosaccharides have been proposed as a novel prebiotic to prevent obesity and associated with metabolic disorders by regulating gut microbiota, but their various probiotic functions in the gut depended on their complex and heterogeneous sugar composition. This study aimed to obtain specific oligogalacturonic acids (POAS) from pectin and investigate the effects of POAS on high-fat diet-induced obesity in mice. The results showed that POAS improved body weight gain, serum lipids and hepatic steatosis in obese mice. POAS notably enhanced intestinal barrier function, reduced inflammatory response and regulated the expression of key genes in lipid synthesis and metabolism. Besides, POAS also promoted short-chain fatty acids (SCFAs) production. Furthermore, POAS alleviated the gut microbiota dysbiosis caused by HFD with significantly increasing beneficial gut microbiota such as Akkermansia and Lactobacillus. Spearman's correlation analysis indicated that these bacteria were strongly correlated with obesity-related parameters. We conclude that POAS is a potential prebiotic to treat obesity and related complications.

Markerless pose estimation based on computer vision provides a simpler and cheaper alternative to human motion capture, with great potential for clinical diagnosis and remote rehabilitation assessment. Currently, the markerless 3D pose estimation is mainly based on multi-view technology, while the more promising single-view technology has defects such as low accuracy and reliability, which seriously limits clinical application. This study proposes a high-resolution graph convolutional multilayer perception (HGcnMLP) human 3D pose estimation framework for smartphone monocular videos and estimates 15 healthy adults and 12 patients with musculoskeletal disorders (sarcopenia and osteoarthritis) gait spatiotemporal, knee angle, and center-of-mass (COM) velocity parameters, etc., and compared with the VICON gold standard system. The results show that most of the calculated parameters have excellent reliability (VICON, ICC (2, k): 0.853–0.982; Phone, ICC (2, k): 0.839–0.975) and validity (Pearson r: 0.808–0.978, p

Abstract We have previously recognized the genotypic and prognostic heterogeneity of U2AF1 mutations (MT) in myelofibrosis (MF) and myelodysplastic syndromes (MDS). In the current study, we considered 179 U2AF1-mutated patients with clonal cytopenia of undetermined significance (CCUS; n = 22), MDS (n = 108), MDS/acute myeloid leukemia (AML; n = 18) and AML (n = 31). U2AF1 variants included S34 (60%), Q157 (35%), and others (5%): corresponding mutational frequencies were 45%, 55%, and 0% in CCUS; 57%, 39%, and 4% in MDS; 61%, 33%, and 6% in MDS/AML; and 55%, 35% and 10% in AML (P = 0.17, 0.36 and 0.09), respectively. Concurrent mutations included ASXL1 (37%), BCOR (19%), RUNX1 (14%), TET2 (15%), DNMT3A (10%), NRAS/KRAS (8%), TP53 (8%), JAK2 (5.5%) and SETBP1 (5%). The two most frequent U2AF1 MT were S34F (n = 97) and Q157P (n = 46); concurrent MT were more likely to be seen with the latter (91% vs 74%; P = 0.01) and abnormal karyotype with the former (70% vs 62%; P = 0.05). U2AF1 S34F MT clustered with BCOR (P = 0.04) and Q157P MT with ASXL1 (P = 0.01) and TP53 (P = 0.03). The median overall survival (OS) in months was significantly worse in AML (14.2) vs MDS/AML (27.3) vs MDS (33.7; P = 0.001); the latter had similar OS with CCUS (30.0). In morphologically high-risk disease (n = 49), defined by ≥10% blood or bone marrow blasts (i.e., AML or MDS/AML), median OS was 14.2 with Q157P vs 37.1 months in the presence of S34F (P = 0.008); transplant-adjusted multivariable analysis confirmed the detrimental impact of Q157P (P = 0.01) on survival and also identified JAK2 MT as an additional risk factor (P = 0.02). OS was favorably affected by allogeneic hematopoietic stem cell transplantation (HR: 0.16, 95% CI; 0.04-0.61, P = 0.007). The current study defines the prevalence and co-mutational profiles of U2AF1 pathogenic variants in AML, MDS/AML, MDS, and CCUS, and suggests prognostic heterogeneity in patients with ≥10% blasts.

Abstract Background This study investigates the accuracy of 3D-printed dental stents in intensity-modulated radiotherapy (IMRT) for oropharyngeal cancer (OPC) and their dosimetric effects on normal tissues. Methods We selected 60 patients with OPC who underwent IMRT in the Department of Oncology, Special Medical Center of Army Medical University. These patients were randomly assigned into 3D-printed oral stent, simple glass bottle, and nonstent groups (20 patients/group). The positioning error was analyzed with the onboard imaging system once a week after 5 fractions of IMRT. The conformity index (CI), homogeneity index (HI), radiation dose of organs at risk (OARs), and oral mucosal reaction were compared among the three groups. Results No significant difference was observed in the conformity and uniformity of the target dose and the dose received by the spinal cord, larynx, and bilateral parotid glands among the three groups (P > 0.05). Meanwhile, the dose received by the upper cheek, hard palate, and soft palate of patients was significantly lower in the 3D-printed oral stent group than in the nonstent group (P 0.05). When compared with the nonstent group, the simple glass bottle group showed a markedly lower dose received by the upper cheek (P 0.05). According to Common Terminology Criteria for Adverse Events v.5.0, the adverse response rate of the hard palate mucosa was lower in the 3D-printed oral stent group than in the simple glass bottle and nonstent groups (P

Regulating the interface structure and bonding ability is one of the main means to improve the mechanical properties of the composite plate. Therefore, the aluminum (Al)/magnesium (Mg)/aluminum (Al) composite plate was rolled by adding a hard plate, and the influence of the interface bonding morphology on the mechanical properties of the composite plate was studied. The results show that under the same conditions, the corrugated bonding morphology is formed at the Al/Mg interface by hard plate, while the traditional rolling (TR) tends to be flat. The ultimate tensile strength (UTS) of the composite plate is 232.16 MPa, and the percentage of total elongation at fracture (At) is 14.3%, which is 7.36% and 45.22% higher than that of the traditional rolling. The texture intensity of the Mg and Al sides of the corrugated interface is greatly weakened compared to the flat interface, and the strong non-substrate slip provides a strong condition for its subsequent plastic deformation. At the same time, a large number of twins at the interface hinder the dislocation movement and improve the tensile strength of the composite plate, which realizes the double increase of strength and plasticity of the composite plate. It provides scientific advice for interface structure and optimized performance of high-performance composite plates, and has good industrial production and application potential.

The serious problem of soil erosion not only has a profound impact on people’s lives but also results in a series of ecological and environmental challenges. To determine the impact of changes in land use type on soil erosion in the urban agglomeration on the northern slopes of the Tianshan Mountains, this study commences by employing the InVEST-SDR (integrated valuation of ecosystem services and tradeoffs–sediment delivery ratio) model to calculate soil erosion levels spanning from 2000 to 2020. Subsequently, it forecasts land use and land cover (LULC) conditions for the year 2030 under three scenarios: Q1 (natural development), Q2 (ecological protection), and Q3 (economic priority). This projection is accomplished through the integration of a coupled Markov chain and multi-objective planning model (MOP) alongside patch-generating land use simulation (PLUS) models. Ultimately, based on these outcomes, the study predicts soil erosion levels for the year 2030. There has been a consistent decline in soil erosion from 2000 to 2020 with high-intensity erosion concentrated in the Tianshan Mountain region. Grasslands, glaciers, and permafrost are identified as the most erosion-prone land types in the study area, with forests exhibiting the highest capacity for soil retention. Converting from grassland and barren land to forest within the same area results in a substantial reduction in soil erosion, specifically by 27.3% and 46.3%, respectively. Furthermore, the transformation from barren land to grassland also leads to a noteworthy 19% decrease in soil erosion. Over the past two decades, the study area has witnessed a significant decline in the area of grasslands, with a notable shift towards barren and impervious surfaces due to economic development and mining activities. The three predicted scenarios depict significant expansion towards barren land, grassland, and impervious area, respectively. Soil erosion decreases under different shared socio-economic pathway (SSP) scenarios relative to 2020. There is an increase in soil erosion in the Q1 scenario and in the Q3 scenario, whereas the amount of soil erosion in the Q2 scenario exhibits a continued decrease when only the effect of land change on soil erosion is considered. Persistently rapid economic development can exacerbate soil erosion problems, underscoring the need to find a balance between economic growth and ecological conservation. As economic expansion slows down, greater emphasis should be placed on environmental protection to maintain ecological stability.

Abstract Janus particles with anisotropic surfaces possess considerable potential for biological functionalization. However, little is known about the effect of surface anisotropy of Janus particles on the shelf life of perishable food. Herein, plant protein–based nanogels prepared by acylated rapeseed protein isolate (ARPI) are exploited as novel building blocks to decorate the surface of latex particles for Janus particle synthesis. The surface anisotropy of patchy latex particles can be facilely tailored via the suspension polymerization of the Pickering emulsion using ARPI nanogels as stabilizers. The surface distribution of ARPI nanogel on latex particles can be controlled by varying the aqueous phase conditions, and thus, the tunable hydrophilic–lipophilic balance (viz., Janus balance) varied from 0.78 to 1.76 for resulting patchy latex particles. Patchy latex particles with varied Janus balance were further investigated for the effects of their anti‐perishable coatings on perishable fruit preservation. The anisotropic patchy latex particles can act as a novel type of antibacterial agent to inhibit Ascomycota microorganisms’ growth on the surface of fruits and reduce the dehydration and respiration of fruits, all of which devote to a lengthened shelf life while being safe. Furthermore, it is found that the patchy latex particle with a spatial pattern of a hydrophobic area on its surface occupying 51.3% (Janus balance = 0.95) extends the shelf life of perishable food more effectively than that of other spatial arrangements. Overall, the exploration of anisotropic Janus particles offers an alternative strategy to preserve perishable food without using antimicrobial agents.

The optimal configuration of strength and ductility was the first choice in Mg-alloys plate forming. A rolling method with adding the hard plate and unique component structure design was proposed to achieve a symmetrical gradient structure from two upmost surfaces to the center of the AZ31 Mg-alloys plate during a single rolling pass. The microstructure evolution and mechanical properties of symmetrical gradient structure plates were studied. The results indicate that Mg-alloy plates' strength and tensile ductility reached 267 MPa and 26.1%, respectively. In the fine-grain region, the proportion of high-angle grain boundary was 56.4%, and the recrystallization structure was 57.3%. In the coarse-grain region, high-grain boundaries and recrystallization decreased to 42.9% and 42.1%, respectively. Both prismatic slip and pyramidal slip in the CG region were easier to initiate, which leads the interaction of multidirectional twins. The geometrically necessary dislocations mainly accumulate at the boundary of the different region. The fracture morphology showed a gradient distribution of dimples. The crack was deflected in the process of extension, which also leads high ductility of Mg-alloy. The design strategy provides a new idea for producing the high-performance plate with through-thickness symmetrical gradient structure.

Neutrophil elastase (NE), a major protease in the primary granules of neutrophils, is involved in microbicidal activity. NE is an important factor promoting inflammation, has bactericidal effects, and shortens the inflammatory process. NE also regulates tumor growth by promoting metastasis and tumor microenvironment remodeling. However, NE plays a role in killing tumors under certain conditions and promotes other diseases such as pulmonary ventilation dysfunction. Additionally, it plays a complex role in various physiological processes and mediates several diseases. Sivelestat, a specific NE inhibitor, has strong potential for clinical application, particularly in the treatment of coronavirus disease 2019 (COVID-19). This review discusses the pathophysiological processes associated with NE and the potential clinical applications of sivelestat.

Cell mechanics is essential to cell development and function, and its dynamics evolution reflects the physiological state of cells. Here, we investigate the dynamical mechanical properties of single cells under various drug conditions, and present two mathematical approaches to quantitatively characterizing the cell physiological state. It is demonstrated that the cellular mechanical properties upon the drug action increase over time and tend to saturate, and can be mathematically characterized by a linear time-invariant dynamical model. It is shown that the transition matrices of dynamical cell systems significantly improve the classification accuracies of the cells under different drug actions. Furthermore, it is revealed that there exists a positive linear correlation between the cytoskeleton density and the cellular mechanical properties, and the physiological state of a cell in terms of its cytoskeleton density can be predicted from its mechanical properties by a linear regression model. This study builds a relationship between the cellular mechanical properties and the cellular physiological state, adding information for evaluating drug efficacy.

Abstract Objective This study aims to assess the clinical efficacy and safety of omadacycline for the treatment of acute bacterial infections. Methods A search of PubMed, Embase, Cochrane Library, and Clinical Trials was conducted up to July 1, 2022. We included only randomized controlled trials (RCTs), in which omadacycline and other antibiotics were evaluated for treating acute bacterial infections in adults. The primary outcomes were clinical response and microbiological response, whereas the secondary outcome was the risk of adverse events (AEs). Results A total of seven RCTs involving 2841 patients with acute bacterial infection were included. Overall, our study illustrated that the clinical cure ratio of omadacycline was similar to the comparators in the treatment of acute bacterial infections (OR = 1.18, 95%CI = 0.96, 1.46, I2 = 29%). Omadacycline had a microbiological eradication rate similar to comparators in the treatment of acute bacterial infections (OR = 1.02, 95%CI = 0.81, 1.29, I2 = 42%). No statistical differences were observed between omadacycline and the comparators in terms of infection caused by Staphylococcus aureus (OR = 1.14, 95%CI = 0.80, 1.63, I2 = 0%), methicillin-resistant S. aureus (MRSA, OR = 1.28, 95%CI = 0.73, 2.24, I2 = 0%), methicillin-susceptible S. aureus (MSSA, OR = 1.12, 95%CI = 0.69, 1.81, I2 = 0%), and Enterococcus faecalis (OR = 2.47, 95%CI = 0.36, 16.97, I2 = 7%). A significant difference was found between omadacycline and the comparators for the risk of any AEs and treatment related AEs. The risk of discontinuation of the study drug due to an AEs was lower for omadacycline than for the comparators. Conclusion Omadacycline is as good as comparators in terms of efficacy and tolerance in the treatment of acute bacterial infections in adult patients. Thus, omadacycline is an appropriate option for antibiotic therapy in adult patients with acute bacterial infections.

BackgroundGram-negative bacteria is a global public health problem. Treatment options include novel beta-lactamase inhibitors.ObjectivesThe objective of this study was to collect information on the efficacy and safety of novel β-lactamase inhibitor combinations such as imipenem-cilastatin/relebactam (IMI/REL).MethodsIn order to comprehensively evaluate the clinical, microbiological, and adverse events outcomes, a meta-analysis was conducted on clinical trials comparing novel β-lactamase inhibitor combinations with existing comparator therapies.ResultsFour studies comprising 948 patients were included in the analysis. IMI/REL therapy demonstrated similar clinical responses to comparators across various treatment visits, including discontinuation of intravenously administered therapy visits [DCIV, RR = 1.00 (0.88, 1.12)], early follow-up visits [EFU, RR = 1.00 (0.89, 1.14)], late follow-up visits [LFU, RR = 1.00 (0.88, 1.13)]. Moreover, no significant difference in the microbiologic response of MITT patients was observed between IMI/REL and comparators across DCIV [RR = 0.99 (0.89, 1.11)], EFU [RR = 1.01 (0.95, 1.07)], and LFU visits [RR = 1.00 (90.94, 1.07)]. In terms of safety, therapy with IMI/REL and comparators exhibited similar risks of at least one adverse event (AE), drug-related AEs, and discontinuation due to AEs. The incidence of serious AEs (SAEs) was significantly lower in the IMI/REL group compared to the comparison groups. The predominant AEs were gastrointestinal disorders, with no significant difference observed between the IMI/REL group and comparators.ConclusionThe clinical and microbiologic response to IMI/REL in the treatment of bacterial infection was comparable to that of the comparator. Furthermore, the incidence of AEs and the tolerability of IMI/REL were similar among the comparators. Based on these findings, IMI/REL can be considered as a viable alternative treatment option.

Non-small cell lung cancer (NSCLC) is one of the main causes of cancer-related death worldwide, with a serious impact on human health and life. The identification of NSCLC at an early stage is a formidable task that frequently culminates in a belated diagnosis. LncRNA is a kind of noncoding RNA with limited protein-coding capacity, and its expression is out of balance in many cancers, especially NSCLC. A large number of studies have reported that lncRNA acts a vital role in regulating angiogenesis, invasion, metastasis, and the proliferation and apoptosis of tumor cells, affecting the occurrence and development of NSCLC. Abundant evidence demonstrates that lncRNAs may serve as potential biomarkers for NSCLC diagnosis and prognosis. In this review, we summarize the latest progress in characterizing the functional mechanism of lncRNAs involved in the development of NSCLC and further discuss the role of lncRNAs in NSCLC therapy and chemotherapy resistance. We also discuss the advantages, limitations, and challenges of using lncRNAs as diagnostic or prognostic biomarkers in the management of NSCLC.

Aiming to provide a scientific basis for the prevention and control of soil erosion in the Huaihe region, this study uses the InVEST-SDR model to estimate the temporal and spatial changes of soil erosion and soil conservation in the Huaihe region in 2010, 2015 and 2020, and the driving factors are evaluated and quantified using Random Forest and Geodetector, respectively. The major findings are as follows: (1) From 2010 to 2020, soil loss and soil retention in the Huaihe region gradually intensified, while the spatial distribution trend was consistent from year to year. (2) The results from Random Forest and Geodetector show that changes in soil loss and soil retention are mainly influenced by slope and rainfall. (3) The steepness and length of slopes are the most influencing factors for soil erosion. Soil loss and soil retention vary widely between different land uses. Forests play an important role in soil conservation.

Moringa oleifera (MO) seeds treated as a new resource food rich in protein (37.48%), but, little know the bioactive benefits and peptide composition of protein hydrolysates. In this study, ultrafiltrated peptide fractions of MO seed proteins hydrolysates (MOSPH) were analyzed for their antioxidant, anti-hypertension and sleep-promoting activities. LC-MS/MS was used to identify the peptide composition of the molecular weight (MW) 0.3) from MW

Abstract Background Kallmann syndrome (KS) is a common type of idiopathic hypogonadotropic hypogonadism. To date, more than 30 genes including ANOS1 and FGFR1 have been identified in different genetic models of KS without affirmatory genotype–phenotype correlation, and novel mutations have been found. Methods A total of 35 unrelated patients with clinical features of disorder of sex development were recruited. Custom-panel sequencing or whole-exome sequencing was performed to detect the pathogenic mutations. Sanger sequencing was performed to verify single-nucleotide variants. Copy number variation-sequencing (CNV-seq) was performed to determine CNVs. The pathogenicity of the identified variant was predicted in silico. mRNA transcript analysis and minigene reporter assay were performed to test the effect of the mutation on splicing. Results ANOS1 gene c.709 T > A and c.711 G > T were evaluated as pathogenic by several commonly used software, and c.1063-2 A > T was verified by transcriptional splicing assay. The c.1063-2 A > T mutation activated a cryptic splice acceptor site downstream of the original splice acceptor site and resulted in an aberrant splicing of the 24-basepair at the 5′ end of exon 8, yielding a new transcript with c.1063–1086 deletion. FRFR1 gene c.1835delA was assessed as pathogenic according to the ACMG guideline. The CNV of del(8)(p12p11.22)chr8:g.36140000_38460000del was judged as pathogenic according to the ACMG & ClinGen technical standards. Conclusions Herein, we identified three novel ANOS1 mutations and two novel FGFR1 variations in Chinese KS families. In silico prediction and functional experiment evaluated the pathogenesis of ANOS1 mutations. FRFR1 c.1835delA mutation and del(8)(p12p11.22)chr8:g.36140000_38460000del were assessed as pathogenic variations. Therefore, our study expands the spectrum of mutations associated with KS and provides diagnostic evidence for patients who carry the same mutation in the future.

In the traditional accumulative roll bonding (ARB) process of heterogeneous composite laminates, due to the excessive strain caused by accumulative roll bonding, many problems such as reduction of plasticity and cracks on the edge of composite plates cannot be ignored while increasing the strength. In this paper, a method of developing a Mg/Al composite sheet by hard-plate accumulative roll bonding (ARB (HPR)) is proposed. The addition of hard plate can change the stress state of the composite laminate during the rolling process, The shear stress in the rolling direction is partially converted into the compressive stress in the normal direction, which then increases the welding pressure between the heterogeneous composite laminates, the interface is closely bonded, and the warpage and edge crack caused by severe plastic deformation is significantly reduced. The results show that this method can significantly improve the tensile strength and plasticity of the composite laminate. The yield strength is 226 MPa, and the elongation is 21.5%, which is substantially higher than that of the traditional accumulative roll bonding. Many dynamically recrystallised grains were formed, the grains were uniform and delicate, and the grain boundaries were clear. To sum up, the Al/Mg composite sheet rolled by hard-plate accumulative roll bonding has improved in many aspects, such as mechanical properties and sheet formability, which provides a new idea for the research on the forming and manufacturing of heterogeneous composite laminates.

Abstract Background Systemic sclerosis (SSc; also known as “scleroderma”) is an autoimmune disorder characterized by extensive fibrosis, vascular changes, and immunologic dysregulation. Baicalein (phenolic flavonoid derived from Scutellaria baicalensis Georgi) has been used to treat the pathological processes of various fibrotic and inflammatory diseases. In this study, we investigated the effect of baicalein on the major pathologic characteristics of SSc: fibrosis, B-cell abnormalities, and inflammation. Methods The effect of baicalein on collagen accumulation and expression of fibrogenic markers in human dermal fibroblasts were analyzed. SSc mice were produced by injecting bleomycin and treated with baicalein (25, 50, or 100 mg/kg). The antifibrotic features of baicalein and its mechanisms were investigated by histologic examination, hydroxyproline assay, enzyme-linked immunosorbent assay, western blotting and flow cytometry. Results Baicalein (5–120 μM) significantly inhibited the accumulation of the extracellular matrix and fibroblast activation in transforming growth factor (TGF)-β1- and platelet derived growth factor (PDGF)-induced human dermal fibroblasts, as evidenced by abrogated deposition of total collagen, decreased secretion of soluble collagen, reduced collagen contraction capability and downregulation of various fibrogenesis molecules. In a bleomycin-induced model of dermal fibrosis in mice, baicalein (25–100 mg/kg) restored dermal architecture, ameliorated inflammatory infiltrates, and attenuated dermal thickness and collagen accumulation in a dose-dependent manner. According to flow cytometry, baicalein reduced the proportion of B cells (B220+ lymphocytes) and increased the proportion of memory B cells (B220+CD27+ lymphocytes) in the spleens of bleomycin-induced mice. Baicalein treatment potently attenuated serum levels of cytokines (interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-17A, tumor necrosis factor-α), chemokines (monocyte chemoattractant protein-1, macrophage inflammatory protein-1 beta) and autoantibodies (anti-scleroderma 70 (Scl-70), anti-polymyositis-scleroderma (PM-Scl), anti-centromeres, anti-double stranded DNA (dsDNA). In addition, baicalein treatment can significantly inhibit the activation of TGF-β1 signaling in dermal fibroblasts and bleomycin-induce mice of SSc, evidenced by reducing the expression of TGF-β1 and IL-11, as well as inhibiting both small mother against decapentaplegic homolog 3 (SMAD3) and extracellular signal-related kinase (ERK) activation. Conclusions These findings suggest that baicalein has therapeutic potential against SSc, exerting modulating B-cell abnormalities, anti-inflammatory effects, and antifibrosis.

Tobacco (Nicotiana tabacum L.) is the most important cash crop in the mountainous Chongqing region, where mini rotary tillers are widely used for land preparation. The decline in tobacco yields has been partially attributed to deteriorating soil physical properties and the formation of plough pans as a result of the repeated use of the mini rotary tiller. The objective of this study was to evaluate the effects of different tillage depths on soil physical properties and the growth and yield of tobacco. Three tillage depths were evaluated: mini rotary tillage to 15 cm (T15) as a control, medium-deep tillage to 25 cm (T25), and deep tillage to 35 cm (T35). Total porosity, capillary porosity, and soil water content were measured for each treatment, and the root distribution, agronomical traits, and dry matter accumulation were monitored at different growing stages. Tobacco yield and output value were determined following the harvest. Compared to T15, T35 significantly increased total porosity and capillary porosity in the 10–40 cm soil layer and soil water content in the 0–40 cm soil layer, while T25 improved soil physical properties but not significantly. T35 significantly promoted dry matter accumulation and root, stem, and leaf growth compared to T15, while differences in some agronomic traits between T25 and T15 were not significant. Compared to T15, T35 and T25 increased the tobacco yield by 17.2–18.9% and 8.0–10.1%, respectively, and increased the output value by 44.4–46.4% and 29.2–32.6%, respectively. The results indicate that deep tillage improves soil physical properties, breaks plough pans, stimulates root growth, and increases tobacco yield and output value.

Salix psammophila is an important tree species adapted to sand-fixing afforestation in arid areas, and its different plant type characteristics can have different ecological functions. To identify the genes affecting the plant type of S. psammophila, this study used RT-qPCR and RNA-seq technology to establish a method for screening the candidate genes of the S. psammophila plant type based on the correlation coefficient of the crown–height ratio. We then screened out the gene combination that can best control the expression of the S. psammophila plant type. The results show the following: (1) The expression levels of the FHY1 and TAC2 genes were positively correlated with the crown–height ratio, whereas those of the ATX1, RFK1, PYL1, ABF2, SPA2, TB1, ZFP4, and LAZY1b genes were negatively correlated with the crown–height ratio. (2) The ATX1 + FHY1 gene combination had the greatest influence on the plant type traits of S. psammophila, and the correlation between the gene combination and the crown–height ratio reached 0.74. (3) The double- gene combination screening method improved the screening efficiency and accuracy, as well as the sensitivity and specificity, indicating certain universality. This strategy can be used for the determination of other plants or other traits, providing a theoretical basis for the directional breeding of forest trees.

BackgroundCuproptosis, a novel mode of cell death associated with the tricarboxylic acid (TCA) cycle, is relevant to the development of cancer. However, the impact of single-cell-based Cuproptosis-associated lncRNAs on the Tumor immune microenvironment (TIME) of Pancreatic adenocarcinoma (PAAD) and its potential value for individualized immunotherapy has not been clarified.Methods14 immune-related CRGs were screened by exploring the interaction between differentially expressed Immune-Related Genes (IRGs) and Cuproptosis-Related Genes (CRGs) in PAAD. Next, the expression amount and expression distribution of CRGs in single-cell samples were analyzed by focusing on 7-CRGs with significant expressions. On the one hand, MAP2K2, SOD1, and VEGFA, which were significantly differentially expressed between PAAD sites and normal tissues adjacent to them, were subjected to immunohistochemical validation and immune landscape analysis. On the other hand, from these 7-CRGs, prognostic signatures of lncRNAs were established by co-expression and LASSO-COX regression analysis, and their prognostic value and immune relevance were assessed. In addition, this study not only validated the hub CRGs and the lncRNAs constituting the signature in a PAAD animal model treated with immunotherapy-based combination therapy using immunohistochemistry and qRT-PCR but also explored the potential value of the combination of targeted, chemotherapy and immunotherapy.ResultsBased on the screening of 7-CRGs significantly expressed in a PAAD single-cell cohort and their co-expressed Cuproptosis-Related lncRNAs (CRIs), this study constructed a prognostic signature of 4-CRIs named CIR-score. A Nomogram integrating the CIR-score and clinical risk factors was constructed on this basis to predict the individualized survival of patients. Moreover, high and low-risk groups classified according to the median of signatures exhibited significant differences in clinical prognosis, immune landscape, bioenrichment, tumor burden, and drug sensitivity. And the immunohistochemical and qRT-PCR results of different mouse PAAD treatment strategies were consistent with the trend of inter-group variability in drug sensitivity of hub CRGs and CIR-score. The combination of immunotherapy, targeted therapy, and chemotherapy exhibited a better tumor suppression effect.ConclusionCIR-score, as a Cuproptosis-related TIME-specific prognostic signature based on PAAD single cells, not only predicts the prognosis and immune landscape of PAAD patients but also provides a new strategy for individualized immunotherapy-based combination therapy.

The intricate interplay between the characteristics and properties of amorphous/nanocrystalline alloys, specifically saturation flux density (Bs) and Curie temperature (Tc), has long been a perplexing task, despite their remarkable properties. However, recent developments in the field of machine learning (ML) have offered a promising paradigm for the accelerated discovery of these elusive alloys. Notably, it has become clear that their properties depend not only on their chemical composition but also on their thickness and annealing process. To further advance this paradigm, 5 ML methods were employed to predict Bs and Tc based on original features (OFs) and polynomial features (PFs). Impressively, it was discovered that ML model with the largest R2 score on OFs displayed an outstanding capability, with interpretable method, which could be of great aid to alloy design. Further analysis revealed that the explicit formulas based on PFs quantitatively provided direction for optimization. Finally, the Fe81.4Si3.4B11.4Cu0.8Nb3 alloy, with appropriate annealing time (AT1), annealing temperature (AT2) and thickness (THK), demonstrated promising Bs = 1.79 T and Tc = 661.6 K. This work strongly suggests that the discovery paradigm has the potential to quantitatively explore the relationship between features and properties and might provide some insight into the discovery of new Fe-based amorphous/nanocrystalline alloy.

Abstract Background Citrullinemia type I (CTLN1) is a rare urea cycle disorder (UCD) with few adult cases described so far. Diagnosis of late-onset CTLN1 is difficult, and delayed treatment may increase the risk of severe hyperammonemia. Pregnancy is an important risk factor for women with CTLN1. However, the clinical manifestations of CTLN1 in a pregnant woman may be mistaken for pregnancy side effects and ultimately delay a timely diagnosis. Case presentation A 34-year-old woman developed vomiting and disturbance of consciousness after 12 weeks of gestation. A blood test showed hyperammonemia (454 μg/dL) with normal liver function tests. She fell into a deep coma, and her serum ammonia level increased to 800 μg/dL. Continuous renal replacement therapy (CRRT) was administered as a diagnostic treatment for UCD and serum ammonia. This patient’s case was complicated by co-infection; her dependents decided to withdraw life support and the patient died. She was diagnosed with CTLN1 by analyses of plasma amino acids, urinary orotic acid, and second-generation gene sequencing. Discussion and conclusion When a patient displays symptoms of emesis and disturbance of consciousness in early pregnancy, blood ammonia should be monitored, and UCD should be considered, particularly for patients with hyperammonemia in the absence of severe liver function abnormalities.