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Abstract Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD.

AIM: To investigate the types of bacteria in patients with eye infections in Suzhou and their drug resistance to commonly used antibacterial drugs. METHODS: The clinical data of 155 patients were retrospectively collected in this study, and the pathogenic bacteria species and drug resistance of each pathogenic bacteria were analyzed. RESULTS: Among the 155 patients (age from 12 to 87 years old, with an average age of 57, 99 males and 56 females) with eye infections (160 eyes: 74 in the left eye, 76 in the right eye and 5 in both eyes, all of which were exogenous), 71 (45.81%) strains were gram-positive bacteria, 23 (14.84%) strains were gram-negative bacteria and 61 (39.35%) strains were fungi. Gram-positive bacteria were highly resistant to penicillin and erythromycin (78.87% and 46.48% respectively), but least resistant to vancomycin at 0. Gram-negative bacteria were highly resistant to cefoxitin and compound sulfamethoxazole (100% and 95.65% respectively), but least resistant to meropenem at 0. Comparison of the resistance of gram-positive and gram-negative bacteria to some drugs revealed statistically significant differences (P

Abstract Biliary tract infection (BTI), a commonly occurring abdominal disease, despite being extensively studied for its initiation and underlying mechanisms, continues to pose a challenge in the quest for identifying specific diagnostic biomarkers. Extracellular vesicles (EVs), which emanate from diverse cell types, serve as minute biological entities that mirror unique physiological or pathological conditions. Despite their potential, there has been a relatively restricted exploration of EV-oriented methodologies for diagnosing BTI. To uncover potent protein biomarkers for BTI patients, we applied a label-free quantitative proteomic method known for its unbiased and high-throughput nature. Furthermore, 192 differentially expressed proteins surfaced within EVs isolated from individuals afflicted with BTI. Subsequent GO and KEGG analyses pinpointed Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and Crumbs homolog 3 (CRB3) as noteworthy biomarkers. Validation via data analysis of plasma-derived EV samples confirmed their specificity to BTI. Our study leveraged an unbiased proteomic tool to unveil CEACAM1 and CRB3 as promising protein biomarkers in serum EVs, presenting potential avenues for the advancement of diagnostic systems for BTI detection.

In this study, 1.0 wt%Al element was added into the traditional 26.8Cr-3.7Mo–2Ni super-ferritic stainless steel to tailor the brittle phase precipitation, recrystallization microstructure and mechanical property via solution annealing at temperatures of 950–1150 °C. The experimental results demonstrated that hot-rolled microstructure for 1.0Al sample consisted of surface fine grain region and core elongated grains together with TiN, NbC and Laves phase, while none of these fine grains appeared in 0Al samples. After annealing below 1050 °C, both σ-phase and Laves phase were formed in Al-free samples, while only abundant Laves phase precipitated in 1.0Al sample indicating the inhibition effect of Al on the σ-phase and the promotion effect on Laves phase. When annealing above 1050 °C, recrystallization was completed and neither σ-phase nor Laves phase were observed. Relatively stable mean grain size was produced due to the Laves phase pinning effect during annealing at 1050 °C, while the Nb/Al solute drag effect bore responsibility for the situation at 1050–1150 °C. Sudden grain coarsening phenomenon appeared after annealing above 1150 °C. Al additions gave a solution strengthening and intensive Laves phase precipitation strengthening for the designed alloys, and good comprehensive mechanical properties were obtained demonstrating the probability of developing of the Al-modified ultra-super stainless steels.

The accurate prediction of urban road collapses is of paramount importance for public safety and infrastructure management. However, the complex and variable nature of road subsidence mechanisms, coupled with the inherent noise and non-stationarity in the data, poses significant challenges to the development of precise and real-time prediction models. To address these challenges, this paper develops an Adaptive Difference Least Squares Support Vector Regression (AD-LSSVR) model. The AD-LSSVR model employs a difference transformation to process the input and output data, effectively reducing noise and enhancing model stability. This transformation extracts trends and features from the data, leveraging the symmetrical characteristics inherent within it. Additionally, the model parameters were optimized using grid search and cross-validation techniques, which systematically explore the parameter space and evaluate model performance of multiple subsets of data, ensuring both precision and generalizability of the selected parameters. Moreover, a sliding window method was employed to address data sparsity and anomalies, ensuring the robustness and adaptability of the model. The experimental results demonstrate the superior adaptability and precision of the AD-LSSVR model in predicting road collapse timing, highlighting its effectiveness in handling the complex nonlinear data.

The solution treating and cooling experiments were conducted to study the microstructure and mechanical properties of Al modified super ferritic stainless steels with various cooling methods. The results demonstrated that the grain was characterized by the stratified distribution. The grain coarsened gradually with the decrease in cooling rate. And the surface grain coarsened obviously, Nb (C, N) particles were precipitated in the samples in different cooling manners. However, the Laves phase was distributed both at the grain boundaries and in the grains in the furnace-cooled specimen, and the area fraction of Laves phase increased significantly with the increase of Al content. With the cooling rate decreased, the yield strength, ultimate tensile strength and Vickers hardness of the Al-free samples increased, while the elongation decreased, and the furnace-cooled specimens showed brittle fracture during the tensile test. The addition of Al also increased yield strength, ultimate tensile strength and Vickers hardness and deteriorated plasticity of samples with different cooling manners. Meanwhile, the plasticity of furnace-cooled samples was more sensitive to addition of Al than water-quenched and air-cooled specimens. The analysis results showed that the plastic deterioration of furnace-cooled samples was mainly related to the coarsening of Laves phase at grain boundaries. Hence, the precipitation of large size Laves phase at grain boundaries should be inhibited in the process of industrial production.

An isothermal ageing experiment was carried out to investigate the influence of Al modification on the brittle phase precipitation behaviour, grain coarsening and mechanical properties of newly designed ultra-super ferritic stainless steel. Experimental results demonstrated that the modification of Al significantly inhibited the formation rate of the sigma phase, retarded the induction period of the chi phase, and promoted the growth process of the Laves phase. Meanwhile, the calculated grain growth kinetics of the surface layer and core layer were compared with the measured values. It was found that the Al modification enhanced the effect of Laves phase precipitation pinning and solid solution drag, which slowed the grain coarsening rate. With the modification of Al, the values of ultimate tensile strength, yield strength (0.2% proof stress) and total elongation increased compared to those of the Al-free alloys. The plasticity of the Al-modified alloys was improved with the retardation of sigma and chi phases at the grain boundary. This study provided valuable insights for the development of Al-modified ultra-super ferritic stainless steels with low precipitation brittleness tendency.

Abstract Background N6‐methyladenosine (m6A), the most prevalent internal mRNA modification in eukaryotes, is added by m6A methyltransferases, removed by m6A demethylases and recognised by m6A‐binding proteins. This modification significantly influences carious facets of RNA metabolism and plays a pivotal role in cellular and physiological processes. Main body Pre‐mRNA alternative splicing, a process that generates multiple splice isoforms from multi‐exon genes, contributes significantly to the protein diversity in mammals. Moreover, the presence of crosstalk between m6A modification and alternative splicing, with m6A modifications on pre‐mRNAs exerting regulatory control, has been established. The m6A modification modulates alternative splicing patterns by recruiting specific RNA‐binding proteins (RBPs) that regulate alternative splicing or by directly influencing the interaction between RBPs and their target RNAs. Conversely, alternative splicing can impact the deposition or recognition of m6A modification on mRNAs. The integration of m6A modifications has expanded the scope of therapeutic strategies for cancer treatment, while alternative splicing offers novel insights into the mechanistic role of m6A methylation in cancer initiation and progression. Conclusion This review aims to highlight the biological functions of alternative splicing of m6A modification machinery and its implications in tumourigenesis. Furthermore, we discuss the clinical relevance of understanding m6A‐dependent alternative splicing in tumour therapies.

Background: Previous studies have suggested that point-of-care ultrasound could help to evaluate and diagnose pediatric skull fracture for the closed scalp hematoma from blunt trauma. However, relevant data in Chinese children are missing, especially in children 0–6 years old. Objectives: Our study aimed to evaluate the efficacy of point-of-care ultrasound to diagnose skull fracture in children 0–6 years old with scalp hematoma in China. Methods: We performed a prospective observational study and screened children 0–6 years old with closed scalp hematoma and a Glasgow coma scale of 14–15 at Hospital in China. Enrolled children (N = 152) were first evaluated for skull fracture with point-of-care ultrasound by the emergency physician and then received a head computed tomography scan. Results: The point-of-care ultrasound examination and computed tomography scan revealed skull fracture in 13 (8.6%) and 12 (7.9%) children, respectively. The kappa test showed a satisfactory agreement between two examinations (P

Medicinal plants are the primary material basis for disease prevention and treatment in traditional Chinese medicine (TCM). The conservation and sustainable utilization of these medicinal plants is critical for the development of the TCM industry. However, wild medicinal plant resources have sharply declined in recent decades. To ameliorate the shortage of medicinal plant resources, it is essential to explore the development potential of the TCM industry in different geographical regions. For this purpose, we examined the spatial distribution of commonly used medicinal plants in China, the number of Chinese medicinal material markets, and the number of TCM decoction piece enterprises. Specifically, multispecies superimposition analysis and Thiessen polygons were used to reveal the optimal range for planting bulk medicinal plants and the ideal regions for building Chinese medicinal material markets, respectively. Furthermore, we quantitatively analyzed mismatches between the spatial distribution of commonly used medicinal plant richness, Chinese medicinal material markets, and TCM decoction piece enterprises. We found that the areas suitable for growing commonly used medicinal plants in China were mainly distributed in Hengduan Mountain, Nanling Mountain, Wuling Mountain, and Daba Mountain areas. The Thiessen polygon network based on Chinese medicinal material market localities showed there are currently fewer markets in southwestern, northwestern, and northeastern China than in central and southern China. TCM decoction piece enterprises are concentrated in a few provinces, such as Hebei and Jiangxi. We found that the distribution of commonly used medicinal plants, Chinese medicinal material markets and TCM decoction piece enterprises are mismatched in Henan, Shaanxi, Hunan, Hubei, Zhejiang, Fujian, Chongqing, and Xizang. We recommend strengthening development of the TCM industry in Henan, Hunan, Zhejiang, Shaanxi, Hubei, Chongqing, Fujian, and Xizang; building more Chinese medicinal material markets in southwestern, northwestern, and northeastern China; and establishing medicinal plant nurseries in resource-rich provinces to better protect and domesticate local medicinal plants.

Abstract Sphingosine kinase 1 (SphK1) expression and activity are elevated in human osteosarcoma (OS) and is a promising target of therapy. SKI-V is a non-competitive and highly-efficient non-lipid SphK1 inhibitor. The potential anti-OS cell activity by the SphK1 inhibitor was studied here. In primary OS cells and immortalized cell lines, SKI-V robustly suppressed cell survival, growth and proliferation as well as cell mobility, and inducing profound OS cell death and apoptosis. The SphK1 inhibitor was however non-cytotoxic nor pro-apoptotic in human osteoblasts. SKI-V robustly inhibited SphK1 activation and induced accumulation of ceramides, without affecting SphK1 expression in primary OS cells. The SphK1 activator K6PC-5 or sphingosine-1-phosphate partially inhibited SKI-V-induced OS cell death. We showed that SKI-V concurrently blocked Akt-mTOR activation in primary OS cells. A constitutively-active Akt1 (ca-Akt1, S473D) construct restored Akt-mTOR activation and mitigated SKI-V-mediated cytotoxicity in primary OS cells. In vivo, daily injection of SKI-V potently suppressed OS xenograft tumor growth in nude mice. In SKI-V-administrated OS xenograft tissues, SphK1 inhibition, ceramide increase and Akt-mTOR inhibition were detected. Together, SKI-V exerts significant anti-OS activity by inhibiting SphK1 and Akt-mTOR cascades in OS cells.

Osteosarcoma (OS) is the most common primary bone malignancy in the adolescent population. MAFG (v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog G) forms a heterodimer with Nrf2 (NF-E2-related factor 2), binding to antioxidant response element (ARE), which is required for Nrf2 signaling activation. We found that MAFG mRNA and protein expression is significantly elevated in human OS tissues as well as in established and primary human OS cells. In human OS cells, MAGF silencing or knockout (KO) largely inhibited OS cell growth, proliferation, and migration, simultaneously inducing oxidative injury and apoptosis activation. Conversely, ectopic overexpression of MAFG augmented OS cell progression in vitro. MicroRNA-4660 (miR-4660) directly binds the 3′ untranslated region (UTR) of MAFG mRNA in the cytoplasm of OS cells. MAFG 3′ UTR luciferase activity and expression as well as OS cell growth were largely inhibited with forced miR-4660 overexpression but augmented with miR-4660 inhibition. In vivo, MAGF short hairpin RNA (shRNA) or forced overexpression of miR-4660 inhibited subcutaneous OS xenograft growth in severe combined immunodeficient mice. Furthermore, MAFG silencing or miR-4660 overexpression inhibited OS xenograft in situ growth in proximal tibia of the nude mice. In summary, MAFG overexpression-driven OS cell progression is inhibited by miR-4660. The miR-4660-MAFG axis could be novel therapeutic target for human OS.

Pternopetalum paucifoliolatum, a new species from Sixigou Scenic Area, Emeishan City, Sichuan Province, is proposed and described. Diagnostic morphological characters, full description, detailed illustrations, and a distribution map are provided. The new species is similar to P. porphyronotum in possessing the 1-pinnate leaves and the abaxially purple-red leaflets, but differs from the latter by shorter stature, fewer leaflets ((1–) 3–7) and rays (5–8), the leaflet margin white-ciliate. The new species, which is assessed as Critically Endangered (CR), was only found on limestone cliffs. We also provide a new key to the species of Pternopetalum.