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IntroductionAs adolescent smoking rates rise, its impact on cognitive function has drawn greater attention. This study explores whether exercise can mitigate the negative effects of smoking on executive function in male college students.MethodsSixty male college students were divided into four groups (n = 15 each): sedentary smokers, sedentary nonsmokers, athletic smokers, and athletic nonsmokers. All participants completed the Eriksen flanker task, with prefrontal cortex activation measured using functional near-infrared spectroscopy. After the baseline test, all sedentary students engaged in 33 min of high-intensity interval training, followed by the same procedures as in the pre-test.ResultsIn the flanker task, college athletes exhibited superior executive function compared to sedentary students, with higher accuracy (p = 0.042), faster reaction times (p = 0.002), and more pronounced brain activation (p = 0.048). Post-exercise, reaction times improved significantly in sedentary groups (p < 0.05). Smoking impaired executive function both before and after exercise, with smokers showing lower accuracy (p < 0.001), slower reaction times (p < 0.001), and diminished brain activation (p < 0.001) compared to nonsmokers.DiscussionEngaging in acute aerobic exercise may improve executive function in sedentary smokers. Exercise may help mitigate smoking-related declines in executive function among college students.

Ophiocordyceps sinensis, an entomopathogenic fungus, infects larvae from the Lepidoptera: Hepialidae family, forming the valuable Chinese cordyceps. Mycoviruses are widespread across major lineages of filamentous fungi, oomycetes, and yeasts and have the potential to influence fungal biology and ecology. This study aimed to detect mycovirus within O. sinensis by isolating double-stranded RNA from six stains for transcriptomic sequencing and analyzing publicly available transcriptome data from 13 O. sinensis representative samples. Our analysis revealed 13 mycoviruses, with nine reported for the first time in O. sinensis. These mycoviruses are distributed across five families—Partitiviridae, Mitoviridae, Narnaviridae, Botourmiaviridae, Deltaflexiviridae—and two unclassified lineages, Ormycovirus and Vivivirus. This study also revealed frequent coinfections within individual O. sinensis strains and dynamic shifts in viral composition during fungal development. These findings enhance our knowledge of mycovirus diversity within O. sinensis and provide new insights into their taxonomy.

The ladybird beetle Micraspis discolor plays an important role as a predator of various arthropods within Asia’s rice ecosystems. While pollen could serve as an alternative diet for this beetle, facilitating mass-rearing, its pollinivory might inadvertently result in attacks on crop pollen. This study aims to explore the role of gut bacteria on pollinivory of M. discolor. We found that antibiotic treatment significantly reduced the performance of M. discolor when fed Brassica campestris pollen. However, the treatment did not significantly affect their performance when fed an alternative diet of Ephestia kuehniella eggs. Further, we found that antibiotics can eliminate a strain of Serratia marcescens, SmMd, which is a specific gut bacterium in M. discolor. Moreover, the performance of M. discolor showed some degree of recovery when SmMd was reintroduced into its diet. Therefore, we propose that gut bacteria, particularly SmMd, play a significant role in pollen use by this ladybird beetle. This insight enhances our understanding of the important role of gut bacteria in insect adaptation to diverse diets and can potentially optimize the utilization of M. discolor in biological control strategies.

BackgroundPrevious studies have suggested that repetitive transcranial magnetic stimulation (rTMS) may be an effective and safe alternative treatment for post-stroke cognitive impairment (PSCI). Similarly, the application of transcranial direct current stimulation (tDCS) during stroke rehabilitation has been shown to improve cognitive function in PSCI patients. However, there have been conflicting results from some studies. Therefore, this study aims to conduct a meta-analysis to evaluate the effects of tDCS and rTMS on PSCI.MethodsThe meta-analysis search for articles published from the initial availability date to 5 February 2024 in databases. The extracted study data were entered into STATA 12.0 software for statistical analysis.ResultsThis meta-analysis provides evidence that both rTMS and tDCS have a positive impact on general cognitive function in PSCI patients [immediate effect of rTMS: standard mean difference (SMD) = 2.58, 95% confidence interval (CI) = 1.44 to 3.71; long-term effect of rTMS: SMD = 2.33, 95% CI = 0.87–3.78; immediate effect of tDCS: SMD = 2.22, 95% CI = 1.31–3.12]. Specifically, rTMS was found to significantly improve attention, language, memory, and visuospatial functions, while it did not show a significant therapeutic effect on executive function (attention: SMD = 3.77, 95% CI = 2.30–5.24; executive function: SMD = −0.52, 95% CI = −3.17–2.12; language: SMD = 3.43, 95% CI = 1.50–5.36; memory: SMD = 3.52, 95% CI = 1.74–5.30; visuospatial function: SMD = 4.71, 95% CI = 2.61–6.80). On the other hand, tDCS was found to significantly improve executive and visuospatial functions but did not show a significant improvement in attention function and memory (attention: SMD = 0.63, 95% CI = −0.30–1.55; executive function: SMD = 2.15, 95% CI = 0.87–3.43; memory: SMD = 0.99, 95% CI = −0.81–2.80; visuospatial function: SMD = 2.64, 95% CI = 1.04–4.23).ConclusionIn conclusion, this meta-analysis demonstrates that both rTMS and tDCS are effective therapeutic techniques for improving cognitive function in PSCI. However, more large-scale studies are needed to further investigate the effects of these techniques on different cognitive domains in PSCI.

Background and objectiveExtracellular adenosine (eAdo) bridges tumor metabolism and immune regulation. CD39-CD73-eAdo/A2aR axis regulates tumor microenvironment (TME) and immunotherapy response. In the era of immunotherapy, exploring the impact of the CD39-CD73-eAdo/A2aR axis on TME and developing targeted therapeutic drugs to enhance the efficacy of immunotherapy are the current research hotspots. This study summarizes and explores the research trends and hotspots of the adenosine axis in the field of TME to provide ideas for further in-depth research.MethodsLiterature information was obtained from the Web of Science core collection database. The VOS viewer and the bibliometric tool based on R were used to quantify and identify cooperation information and individual influence by analyzing the detailed information of the global annual publication volume, country/region and institution distribution, article authors and co-cited authors, and journal distribution of these articles. At the same time, the distribution of author keywords and the co-occurrence of author keywords, highly cited articles, and highly co-cited references of CD39-CD73-eAdo/A2aR in the field of TME were analyzed to determine research hotspots and trends.Result1,721 articles published in the past ten years were included in this study. Through bibliometric analysis, we found that (1) 69 countries and regions explored the effect of the CD39-CD73-eAdo/A2aR on TME, and the research was generally on the rise. Researchers in the United States dominated research in this area, with the highest total citation rate. China had the most significant number of publications. (2) Harvard University has published the most articles in this field. (3) 12,065 authors contributed to the publication of papers in this field, of which 23 published at least eight papers. STAGG J had significant academic influence, with 24 published articles and 2,776 citations. Co-cited authors can be clustered into three categories. Stagg J, Allard B, Ohta A, and Antonioli, L occupied a central position in the network. (4) 579 scholarly journals have published articles in this field. The journal FRONTIERS IN IMMUNOLOGY published the most significant number of papers, with 97 articles and a total of 2,317 citations, and the number of publications increased year by year. (5) “The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets” was the most frequently local cited article (163 times). The “A2A adenosine receptor protects tumors from antitumor T cells” was the most co-cited reference (224 times). (6) Through the analysis of author keywords, we found that the relationship between adenosine and immunotherapy was a core concept for many researchers in this field. Breast cancer, melanoma, colorectal cancer, ovarian cancer, glioblastoma, pancreatic cancer, hepatocellular carcinoma, and lung cancer were the most frequent cancer types in adenosine-related tumor studies. Immunotherapy, immunosuppression, immune checkpoint, and immune checkpoint inhibitors were the hot keywords in the research, reflecting the importance of the adenosine metabolic pathway in tumor immunotherapy. The keywords such as Immunogenic cell death, T cells, Sting, regulatory T cells, innate immunity, and immune infiltration demonstrated the pathways by which adenosine affected the TME. The famous author keywords in recent years have been immunotherapy, immunogenic cell death, inflammation, lung cancer, and gastric cancer.ConclusionThe effect of CD39-CD73-eAdo/A2aR on the infiltration and function of various immune cells in TME, tumor immunotherapy response, and patient prognosis has attracted the attention of researchers from many countries/regions. American scholars still dominate the research in this field, but Chinese scholars produce the most research results. The journal FRONTIERS IN IMMUNOLOGY has published the wealthiest research in the field. Stagg J was a highly influential researcher in this field. Further exploration of targeted inhibition of CD39-CD73-eAdo/A2aR alone or in combination with other immunotherapy, radiotherapy, and chemotherapy in treating various cancer types and developing effective clinical therapeutic drugs are continuous research hotspots in this field.

IntroductionAntibiotics frequently induce abnormal liver function. Omadacycline is a novel aminomethylcycline antibiotic, which shows potent activity against Gram-positive and Gram-negative aerobic, anaerobic, and atypical (including Legionella pneumophila) bacteria. Of note, omadacycline is tolerable in most patients with liver impairment. However, evidence regarding the application of omadacycline in patients with Legionella pneumophila pneumonia after experiencing liver dysfunction is scarce.MethodsThe current study reported 6 cases of patients with Legionella pneumophila pneumonia receiving omadacycline as subsequent antibiotics after experiencing liver dysfunction.ResultsThese 6 cases were admitted to the hospital for pneumonia and received antibiotic therapy, including piperacillin-tazobactam, imipenem, meropenem, and moxifloxacin. After receiving these antibiotics, increased liver enzymes were noted. Although hepatoprotective therapy (such as magnesium isoglycyrrhizinate and glutathione) was given, the liver function was still abnormal. According to metagenomic next-generation sequencing, these patients were diagnosed with Legionella pneumophila pneumonia. Considering the abnormal liver function, the antibiotic therapy was switched to omadacycline-containing antibiotic therapy. After that, liver function was improved, and the infection was ameliorated. Ultimately, all patients discharged from the hospital, including 2 patients who achieved complete clinical symptomatic improvement and 4 patients who achieved partial clinical symptomatic improvement.DiscussionThis study emphasizes the successful treatment of switching to omadacycline after experiencing abnormal liver function in patients with Legionella pneumophila pneumonia. This study suggests that omadacycline may serve as an optional antibiotic for patients with Legionella pneumophila pneumonia, especially when occurring liver dysfunction. However, more clinical studies are required to validate our findings.

IntroductionMicroaneurysms serve as early signs of diabetic retinopathy, and their accurate detection is critical for effective treatment. Due to their low contrast and similarity to retinal vessels, distinguishing microaneurysms from background noise and retinal vessels in fluorescein fundus angiography (FFA) images poses a significant challenge.MethodsWe present a model for automatic detection of microaneurysms. FFA images were pre-processed using Top-hat transformation, Gray-stretching, and Gaussian filter techniques to eliminate noise. The candidate microaneurysms were coarsely segmented using an improved matched filter algorithm. Real microaneurysms were segmented by a morphological strategy. To evaluate the segmentation performance, our proposed model was compared against other models, including Otsu's method, Region Growing, Global Threshold, Matched Filter, Fuzzy c-means, and K-means, using both self-constructed and publicly available datasets. Performance metrics such as accuracy, sensitivity, specificity, positive predictive value, and intersection-over-union were calculated.ResultsThe proposed model outperforms other models in terms of accuracy, sensitivity, specificity, positive predictive value, and intersection-over-union. The segmentation results obtained with our model closely align with benchmark standard. Our model demonstrates significant advantages for microaneurysm segmentation in FFA images and holds promise for clinical application in the diagnosis of diabetic retinopathy.ConclusionThe proposed model offers a robust and accurate approach to microaneurysm detection, outperforming existing methods and demonstrating potential for clinical application in the effective treatment of diabetic retinopathy.

Malignant glomus tumor (MGT) is a rare mesenchymal neoplasm. It is rarely located in the breast. We present a case of a 57-year-old female patient presenting with complaints of a progressively growing mass found in her left breast. Though multiple imaging examinations have been performed, especially multimodal ultrasound examinations, an accurate diagnosis still cannot be determined. Finally, the lesion was confirmed to be a MGT of the breast by postoperative pathological diagnosis. In conclusion, MGT originating from breast is extremely rare. No such case has ever been described before. This study demonstrates the imaging characteristics of a patient with MGT of the breast in order to provide more extensive insights to consider the differential diagnosis of breast lesions.

Introduction: The Qinnan Depression in the Bohai Bay Basin is lowly explored, where hydrocarbon generation potential of source rocks is required detailed investigation to identify hydrocarbon exploration potential and direction.Methods: This study is based on organic geochemical analysis performed on the Paleogene source rocks. After that, the burial, thermal maturity, and hydrocarbon generation histories of the Paleogene source rocks at various sags were reconstructed on BasinMod software based on reasonable geological models and geological parameters derived from geological analogy.Results: Results show that the 3rd member (Es3) and 1st member (Es1) of the Eocene Shahejie Formation are high-quality source rocks with a mixture of type I and II kerogen, whose organic matter was originated from aquatic organisms under a reducing environment. The 3rd member (Ed3) of the Oligocene Dongying Formation are fair-quality source rocks with type II kerogen and are dominated by mixed organic matter depositing in a weakly reducing environment. Clear differences in hydrocarbon generation were observed in these three source rocks owing to differential subsidence and sedimentation among the Eastern, Southeastern, and Western sags. Source rocks at the Eastern Sag were maturated early and lasted for a long time, which were currently at late mature (1.0–1.3%Ro) to high mature (1.3–2.0%Ro) stages. Two hydrocarbon generation events occurred in the Oligocene and Miocene, respectively, with intensive hydrocarbon generation capacity. Source rocks at the Southeastern Sag were maturated late and lasted for a short period, which were currently at a medium mature (0.7–1.0%Ro) stage. The major hydrocarbon generation event had occurred since the late Miocene, with intensive hydrocarbon generation capacity. Source rocks at the Western Sag were at an early mature (0.5–0.7%Ro) stage and began to generate hydrocarbon in the Pliocene, with weak hydrocarbon generation capacity. The hydrocarbon generation capacity of the Paleogene source rocks is as follows: Es3>Es1>Ed3.Discussion: The Qinnan Depression has high oil and gas exploration potential, where exploration activities should focus on effective traps around depression and slope zones located at the Eastern and Southeastern sags.

In this work, the thermal stability of four types of 18,650 lithium-ion batteries with LiCoO2 (LCO), LiFePO4 (LFP), LiNi0.8Co0.1Mn0.1O2 (NCM811) and LiNi0.8Co0.15Al0.05O2 (NCA) materials as cathodes are experimentally investigated by the accelerating rate calorimeter (ARC) and the isothermal battery testing calorimeter (iso-BTC) under adiabatic and isothermal conditions, respectively. The thermal runaway danger level of these batteries can be ranked as LCO > NCA > NCM811 >> LFP by judging from the values of Tmax and HRmax, nominal. The higher the nickel and cobalt content, the higher the lithium-ion battery capacity, but the worse the thermal stability. The Qtotal of NCA is the largest in the complete standard charge and discharge process, due to that the capacity of NCA is significantly higher than that of the other three batteries, resulting in remarkable increase in Qirre proportioned to the square of the current. When the ambient temperature rises, the energy release decreases owing to the decrease in the internal resistance of the battery. These studies are expected to have important implications for the subsequent safe design of commercial lithium-ion batteries with different cathode materials.

Background: Ailanthone, a small compound derived from the bark of Ailanthus altissima (Mill.) Swingle, has several anti-tumour properties. However, the activity and mechanism of ailanthone in colorectal cancer (CRC) remain to be investigated. This study aims to comprehensively investigate the mechanism of ailanthone in the treatment of CRC by employing a combination of network pharmacology, bioinformatics analysis, and molecular biological technique.Methods: The druggability of ailanthone was examined, and its targets were identified using relevant databases. The RNA sequencing data of individuals with CRC obtained from the Cancer Genome Atlas (TCGA) database were analyzed. Utilizing the R programming language, an in-depth investigation of differentially expressed genes was carried out, and the potential target of ailanthone for anti-CRC was found. Through the integration of protein-protein interaction (PPI) network analysis, GO and KEGG enrichment studies to search for the key pathway of the action of Ailanthone. Then, by employing molecular docking verification, flow cytometry, Transwell assays, and Immunofluorescence to corroborate these discoveries.Results: Data regarding pharmacokinetic parameters and 137 target genes for ailanthone were obtained. Leveraging The Cancer Genome Atlas database, information regarding 2,551 differentially expressed genes was extracted. Subsequent analyses, encompassing protein–protein interaction network analysis, survival analysis, functional enrichment analysis, and molecular docking verification, revealed the PI3K/AKT signaling pathway as pivotal mediators of ailanthone against CRC. Additionally, the in vitro experiments indicated that ailanthone substantially affects the cell cycle, induces apoptosis in CRC cells (HCT116 and SW620 cells), and impedes the migration and invasion capabilities of these cells. Immunofluorescence staining showed that ailanthone significantly inhibited the phosphorylation of AKT protein and suppressed the activation of the PI3K/AKT signaling pathway, thereby inhibiting the proliferation and metastasis of CRC cells.Conclusion: Therefore, our findings indicate that Ailanthone exerts anti-CRC effects primarily by inhibiting the activation of the PI3K/AKT pathway. Additionally, we propose that Ailanthone holds potential as a therapeutic agent for the treatment of human CRC.

With growing concerns about Group B streptococcal (GBS) infections and their adverse effects on perinatal pregnancies, including infection, premature delivery, neonatal septicemia, and meningitis, it is urgent to promote GBS screening at all pregnancy stages. The purpose of this study is to establish a device-independent, fast, sensitive, and visual GBS detection method. Taking advantage of the characteristics of the recombinase polymerase isothermal amplification (RPA), the activity of the nfo nuclease cleavage base analog (tetrahydrofuran, THF) site, and the advantages of visual reading of the lateral flow chromatography strip (LFS), a GBS detection method was developed. This method focused on the conservative region of the Christie–Atkins–Munch–Petersen factor encoded by the cfb gene, a virulence gene specific to GBS. Two forward primers, two biotin-labeled reverse primers, and one fluorescein isothiocyanate (FITC)-labeled and C3spacer-blocked probe were designed. The study involved optimizing the primer pair and probe combination, determining the optimal reaction temperature and time, evaluating specificity, analyzing detection limits, and testing the method on 87 vaginal swabs from perinatal pregnant women. The results showed that the visual detection method of GBS-RPA-LFS, using the cfb-F1/R2/P1 primer probe, could detect GBS within 15 min at the temperature ranging from 39°C to 42°C. Furthermore, the method specifically amplified only GBS, without cross-reacting with pathogens like Lactobacillus iners, Lactobacillus crispatus, Candida albicans, Listeria monocytogenes, Yersinia enterocolitica, Klebsiella Pneumoniae, Enterobacter cloacae, Citrobacter freundii, Vibrio alginolyticus, Vibrio parahaemolyticus, Salmonella typhimurium, Staphylococcus aureus, Pseudomonas aeruginosa, or Trichomonas vaginalis. It could detect a minimum of 100 copies per reaction. In clinical 98 samples of vaginal swabs from pregnant women, the agreement rate between the GBS-RPA-LFS method and TaqMan real-time fluorescence quantification method was 95.92%. In conclusion, this study successfully established a combined RPA and LFS GBS in situ detection platform, with short reaction time, high sensitivity, high specificity, portability, and device independence, providing a feasible strategy for clinical GBS screening.

Introduction: Yinchenzhufu decoction (YCZFD) is a traditional Chinese medicine formula with hepatoprotective effects. In this study, the protective effects of YCZFD against cholestatic liver fibrosis (CLF) and its underlying mechanisms were evaluated.Methods: A 3, 5-diethoxycarbonyl-1, 4-dihydro-collidine (DDC)-induced cholestatic mouse model was used to investigate the amelioration of YCZFD on CLF. Data-independent acquisition-based mass spectrometry was performed to investigate proteomic changes in the livers of mice in three groups: control, model, and model treated with high-dose YCZFD. The effects of YCZFD on the expression of key proteins were confirmed in mice and cell models.Results: YCZFD significantly decreased the levels of serum biochemical, liver injury, and fibrosis indicators of cholestatic mice. The proteomics indicated that 460 differentially expressed proteins (DEPs) were identified among control, model, and model treated with high-dose YCZFD groups. Enrichment analyses of these DEPs revealed that YCZFD influenced multiple pathways, including PI3K-Akt, focal adhesion, ECM–receptor interaction, glutathione metabolism, and steroid biosynthesis pathways. The expression of platelet derived growth factor receptor beta (PDGFRβ), a receptor associated with the PI3K/AKT and focal adhesion pathways, was upregulated in the livers of cholestatic mice but downregulated by YCZFD. The effects of YCZFD on the expression of key proteins in the PDGFRβ/PI3K/AKT pathway were further confirmed in mice and transforming growth factor-β-induced hepatic stellate cells. We uncovered seven plant metabolites (chlorogenic acid, scoparone, isoliquiritigenin, glycyrrhetinic acid, formononetin, atractylenolide I, and benzoylaconitine) of YCZFD that may regulate PDGFRβ expression.Conclusion: YCZFD substantially protects against DDC-induced CLF mainly through regulating the PDGFRβ/PI3K/AKT signaling pathway.

Synsepalum dulcificum exhibits high edible and medicinal value; however, there have been no reports on the exploration of its endophyte resources. Here, we conducted analyses encompassing plant metabolomics, microbial diversity, and the biological activities of endophytic metabolites in S. dulcificum. High-throughput sequencing identified 4,913 endophytic fungal amplicon sequence variants (ASVs) and 1,703 endophytic bacterial ASVs from the roots, stems, leaves, flowers, and fruits of S. dulcificum. Fungi were classified into 5 phyla, 24 classes, 75 orders, 170 families, and 313 genera, while bacteria belonged to 21 phyla, 47 classes, 93 orders, 145 families, and 232 genera. Furthermore, there were significant differences in the composition and content of metabolites in different tissues of S. dulcificum. Spearman’s correlation analysis of the differential metabolites and endophytes revealed that the community composition of the endophytes correlated with plant-rich metabolites. The internal transcribed spacer sequences of 105 isolates were determined, and phylogenetic analyses revealed that these fungi were distributed into three phyla (Ascomycota, Basidiomycota, and Mucoromycota) and 20 genera. Moreover, 16S rDNA sequencing of 46 bacteria revealed they were distributed in 16 genera in three phyla: Actinobacteria, Proteobacteria, and Firmicutes. The antimicrobial activities (filter paper method) and antioxidant activity (DPPH and ABTS assays) of crude extracts obtained from 68 fungal and 20 bacterial strains cultured in different media were evaluated. Additionally, the α-glucosidase inhibitory activity of the fungal extracts was examined. The results showed that 88.6% of the strains exhibited antimicrobial activity, 55.7% exhibited antioxidant activity, and 85% of the fungi exhibited α-glucosidase inhibitory activity. The research suggested that the endophytes of S. dulcificum are highly diverse and have the potential to produce bioactive metabolites, providing abundant species resources for developing antibiotics, antioxidants and hypoglycemic drugs.

The channel matrix of the commonly used uniform circular array-based orbital angular momentum (UCA-OAM) system reaches the full-rank state when the degree of freedom (DoF) is limited only by the number of UCA antenna elements. The rank of the channel matrix of the UCA-OAM system is equal to DoF under this condition. However, the practical DoF of the UCA-OAM system is always affected by other transmission factors, such as the transmission distance and the radius of the receiving antenna. Therefore, by exploiting the practical DoF of the UCA-OAM system affected by the transmission distance and the radii of the receiving antenna and transmission antenna, a novel channel capacity model of the UCA-OAM communication system with a deficient-rank channel (DRC) matrix is first proposed. Moreover, the formulas of the channel matrix and channel capacity for the DRC matrix are analytically derived. The results of numerical simulations indicate that when the practical transmission factors including transmission distance and radii of the receiving antenna and transmission antenna are considered, the UCA-OAM communication system with the DRC matrix has less channel capacity than that with the full-rank channel (FRC) matrix. These simulated results provide helpful guidance on the practical application of the UCA-OAM communication system.

Glucose represents the principal brain energy source. Thus, not unexpectedly, genetic glucose transporter 1 (Glut1) deficiency (G1D) manifests with encephalopathy. G1D seizures, which constitute a prominent disease manifestation, often prove refractory to medications but may respond to therapeutic diets. These seizures are associated with aberrant thalamocortical oscillations as inferred from human electroencephalography and functional imaging. Mouse electrophysiological recordings indicate that inhibitory neuron failure in thalamus and cortex underlies these abnormalities. This provides the motivation to develop a neural circuit testbed to characterize the mechanisms of thalamocortical synchronization and the effects of known or novel interventions. To this end, we used mouse thalamocortical slices on multielectrode arrays and characterized spontaneous low frequency oscillations and less frequent 30–50 Hz or gamma oscillations under near-physiological bath glucose concentration. Using the cortical recordings from layer IV among other regions recorded, we quantified oscillation epochs via an automated wavelet-based algorithm. This method proved analytically superior to power spectral density, short-time Fourier transform or amplitude-threshold detection. As expected from human observations, increased bath glucose reduced the lower frequency oscillations while augmenting the gamma oscillations, likely reflecting strengthened inhibitory neuron activity, and thus decreasing the low:high frequency ratio (LHR). This approach provides an ex vivo method for the evaluation of mechanisms, fuels, and pharmacological agents in a crucial G1D epileptogenic circuit.

ObjectivesThe advanced gastric adenocarcinoma (GAC) patients (stage III/IV) with surgery may have inconsistent prognoses due to different demographic and clinicopathological factors. In this retrospective study, we developed clinical prediction models for estimating the overall survival (OS) and cancer-specific survival (CSS) in advanced GAC patients with surgeryMethodsA retrospective analysis was conducted using the Surveillance, Epidemiology, and End Results (SEER) database. The total population from 2004 to 2015 was divided into four levels according to age, of which 179 were younger than 45 years old, 695 were 45-59 years old, 1064 were 60-74 years old, and 708 were older than 75 years old. There were 1,712 men and 934 women. Univariate and multivariate Cox regression analyses were performed to identify prognostic factors for OS and CSS. Nomograms were constructed to predict the 1-, 3-, and 5-year OS and CSS. The models’ calibration and discrimination efficiency were validated. Discrimination and accuracy were evaluated using the consistency index, area under the receiver operating characteristic curve, and calibration plots; and clinical usefulness was assessed using decision curve analysis. Cross-validation was also conducted to evaluate the accuracy and stability of the models. Prognostic factors identified by Cox regression were analyzed using Kaplan-Meier survival analysis.ResultsA total of 2,646 patients were included in our OS study. Age, primary site, differentiation grade, AJCC 6th_TNM stage, chemotherapy, radiotherapy, and number of regional nodes examined were identified as prognostic factors for OS in advanced GAC patients with surgery (P < 0.05). A total of 2,369 patients were included in our CSS study. Age, primary site, differentiation grade, AJCC 6th_TNM stage, chemotherapy, radiotherapy, and number of regional nodes examined were identified as risk factors for CSS in these patients (P < 0.05). These factors were used to construct the nomogram to predict the 1-, 3-, and 5-year OS and CSS of advanced GAC patients with surgery. The consistency index and area under the receiver operating characteristic curve demonstrated that the models effectively differentiated between events and nonevents. The calibration plots for 1-, 3-, and 5-year OS and CSS probability showed good consistence between the predicted and the actual events. The decision curve analysis indicated that the nomogram had higher clinical predictive value and more significant net gain than AJCC 6th_TNM stage in predicting OS and CSS of advanced GAC patients with surgery. Cross-validation also revealed good accuracy and stability of the models.ConclusionThe developed predictive models provided available prognostic estimates for advanced GAC patients with surgery. Our findings suggested that both OS and CSS can benefit from chemotherapy or radiotherapy in these patients.

BackgroundDyschromatosis symmetrica hereditaria (DSH) is a rare autosomal dominant inherited pigmentary dermatosis characterized by a mixture of hyperpigmented and hypopigmented freckles on the dorsal aspect of the distal extremities. To date, pathogenic mutations causing DSH have been identified in the adenosine deaminase acting on RNA1 gene (ADAR1), which is mapped to chromosome 1q21.ObjectiveThe present study aimed to investigate the underlying pathological mechanism in 14 patients with DSH from five unrelated Chinese families. Next-generation sequencing (NGS) and direct sequencing were performed on a proband with DSH to identify causative mutations. All coding, adjacent intronic, and 5′- and 3′-untranslated regions of ADAR1 were screened, and variants were identified.ResultThese mutations consisted of three missense mutations (NM_001025107: c.716G>A, NM_001111.5: c.3384G>C, and NM_001111.5: c.3385T>G), one nonsense mutation (NM_001111.5:c.511G>T), and one splice-site mutation (NM_001111.5: c.2080-1G>T) located in exon 2, exon 14, and the adjacent intronic region according to recommended Human Genome Variation Society (HGVS) nomenclature. Moreover, using polymerase chain reaction and Sanger sequencing, we identified five novel ADAR1 variants, which can be predicted to be pathogenic by in silico genome sequence analysis. Among the mutations, the missense mutations had no significant effect on the spatial structure of the protein, while the stop codon introduced by the nonsense mutation truncated the protein.ConclusionOur results highlighted that the advent of NGS has facilitated high-throughput screening for the identification of disease-causing mutations with high accuracy, stability, and specificity. Five novel genetic mutations were found in five unrelated families, thereby extending the pathogenic mutational spectrum of ADAR1 in DSH and providing new insights into this complex genetic disorder.

IntroductionDepression commonly occurs during pregnancy and has become a major public health concern. Depression not only affects the individual but also causes adverse consequences for families and children. However, little is known regarding the depression status and its influencing factors in women during late pregnancy in China. This study aimed to assess the prevalence of maternal depressive symptoms in late pregnancy during the coronavirus disease 2019 (COVID-19) pandemic and further explore the effect of biological, psychological, and social factors on depressive symptoms.MethodsAn institution-based cross-sectional survey was conducted among eligible women in the late pregnancy stage and underwent prenatal examination at Lianyungang Maternal and Child Health Hospital in Jiangsu Province, Eastern China from December 2022 to February 2023. Data regarding depressive symptoms and biological, psychological, and social factors of the pregnant women were collected via a structured questionnaire. Chi-square test, Fisher's exact tests, and binary logistics regression were used to analyze the data.ResultsIn total, 535 women in the late pregnancy stage were included in this study, 75 (14.0%) of whom exhibited depressive symptoms. A binary logistic regression analysis revealed that pregnant women who were multiparous (OR: 2.420, 95% CI: 1.188–4.932) and had moderate or severe insomnia symptoms (OR: 4.641, 95% CI: 1.787–12.057), anxiety (OR: 8.879, 95% CI: 4.387–17.971), high fear of COVID-19 (OR: 2.555, 95% CI: 1.255–5.199), moderate or severe family dysfunction (OR: 2.256, 95% CI: 1.141–4.461), and poor social support (OR: 2.580, 95% CI: 1.050–6.337) tended to show depressive symptoms. Conversely, pregnant women who received regular prenatal care (OR: 0.481, 95% CI: 0.243–0.951) and had good drinking water quality at home (OR: 0.493, 95% CI: 0.247–0.984) were more likely to avoid developing depressive symptoms.ConclusionThis study found that the prevalence of maternal depressive symptoms during late pregnancy was high and had multiple influencing factors. Thus, screening for depressive symptoms in women in the late pregnancy stage and providing special intervention programs are necessary, especially for those with risk factors.

ObjectiveTo explore the values of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), neutrophil to albumin ratio (NAR), prognostic nutritional index (PNI), systemic immune inflammatory index (SII) and red cell distribution width to albumin ratio (RA) for evaluating the risk of 30-day mortality of ischemic stroke or hemorrhagic stroke patients.MethodsIn this cohort study, the data of 1,601 patients diagnosed with stroke were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Among them, 908 were hemorrhagic stroke patients and 693 were ischemic stroke patients. Demographic and clinical variables of patients were collected. Univariate and multivariable Cox regression were performed to evaluate the predictive values of NLR, PLR, SII, NAR, RA, and PNI for 30-day mortality in hemorrhagic stroke or ischemic stroke patients. The receiver operator characteristic (ROC) curves were plotted to assess the predictive values of NLR, NAR, and RA for 30-day mortality of hemorrhagic stroke patients.ResultsAt the end of follow-up, 226 hemorrhagic stroke patients and 216 ischemic stroke patients died. The elevated NLR level was associated with increased risk of 30-day mortality in hemorrhagic stroke [hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.06–1.29]. The increased NAR level was associated with elevated risk of 30-day mortality in hemorrhagic stroke (HR = 1.16, 95% CI: 1.02–1.30). The high RA level was linked with increased risk of 30-day mortality (HR = 1.44, 95% CI: 1.23–1.69). No significant correlation was observed in these inflammation biomarkers with the risk of 30-day mortality in ischemic stroke patients. The area under the curves (AUCs) of NLR, RA, and NAR for evaluating the risk of 30-day mortality of hemorrhagic stroke patients were 0.552 (95% CI: 0.503–0.601), 0.644 (95% CI: 0.590–0.699) and 0.541 (95% CI: 0.490–0.592).ConclusionNLR, NAR, and RA were potential prognostic biomarkers for predicting 30-day mortality of hemorrhagic stroke patients, which might provide clinicians an easy and cheap way to quickly identify patients with high risk of mortality.

Objective: This study aimed to investigate the impact of varying dosages of S-ketamine on perioperative immune-inflammatory responses in patients undergoing modified radical mastectomy (MRM).Methods: This is a prospective, randomized, controlled trial. A total of 136 patients with American Society of Anesthesiologists status I/II scheduled for MRM were enrolled and randomly assigned into groups to receive the control (C) or one of three different doses [0.25 (L-Sk), 0.5 (M-Sk), or 0.75 (H-Sk) mg/kg] of S-ketamine. The primary outcomes were the cellular immune function and inflammatory factors before anesthesia and at the end of (T1) and 24 h (T2) after the surgery. Secondary outcomes included the visual analog scale (VAS) score, opioid consumption, rate of remedial analgesia, adverse events, and patient satisfaction.Results: The percentage and absolute counts of CD3+ and CD4+ cells in groups L-Sk, M-Sk, and H-Sk were higher than those of group C at T1 and T2. Moreover, a pairwise comparison revealed that the percentage in group H-Sk was higher than those in the L-Sk and M-Sk groups (p < 0.05). The ratio of CD4+/CD8+ was lower in group C at T1 and T2 than those in groups M-Sk and H-Sk (p < 0.05). There was no significant difference in the percentage and absolute counts of natural killer (NK) cells and B lymphocytes among the four groups. However, compared with group C, the concentrations of white blood cells (WBC), neutrophils (NEUT), hypersensitive C-reactive protein (hs-CRP), the neutrophil-to-lymphocyte ratio (NLR), systemic inflammation response index (SIRI), and systemic immune-inflammation index (SII) at T1 and T2 in three different doses of S-ketamine groups were significantly low, and the lymphocytes were significantly high. The ratio of SIRI and NLR at T2 in group M-Sk was lower than that in group L-Sk (p < 0.05). Additionally, a significant decrease in VAS score, opioid consumption, rates of remedial analgesia, and adverse events was observed in the M-Sk and H-Sk groups.Conclusion: Collectively, our study demonstrates that S-ketamine could reduce opioid consumption, decrease postoperative pain intensity, exert a systemic anti-inflammatory effect, and attenuate immunosuppression in patients undergoing MRM. Moreover, we found that the effects of S-ketamine are related to the dose used, with significant differences observed in 0.5 or 0.75 mg/kg of S-ketamine.Clinical Trial Registration:chictr.org.cn, identifier ChiCTR2200057226.

There are great differences in oil and gas enrichment at different locations in petroliferous basins, and faults are an important factor affecting the differential enrichment of oil and gas. In this paper, taking the No. 2 structure in the Nanpu Sag, Bohai Bay Basin, East China, as an example, based on the analysis of fault geometry and kinematics characteristics, the determination of oil source faults, the analysis of fault trap origin and effectiveness, and the analysis of fault caprock combinations are carried out to study the differences and mechanisms of oil and gas enrichment east and west of the Nanpu No. 2 structure. The results show that the fault-source contact relationship affects the direction of oil and gas migration. The No. 2 structure in the Nanpu Sag has a dual-source hydrocarbon supply. The western structure supplies hydrocarbons from the north and east, with oil and gas migrating along the direction parallel and perpendicular to the fault strike. The east structure supplies hydrocarbons from the south and north, with oil and gas migrating along the direction perpendicular to the fault strike. The effectiveness of fault traps affects the scale of oil and gas accumulation. Most of the traps of the Nanpu No. 2 structure formed before hydrocarbon expulsion, which are all effective traps and are conducive to oil and gas accumulation. The relationship between fault and caprock determines the vertical accumulation layers of oil and gas: The faulted thickness of the east structure is large, the fault is vertically closed, and oil and gas are enriched mainly in the deep layer. The faulted thickness of the west structure is small, and oil and gas are enriched in both deep and shallow layers.

IntroductionHepatocellular carcinoma (HCC) is a common malignant cancer with a poor prognosis. Cuproptosis and associated lncRNAs are connected with cancer progression. However, the information on the prognostic value of cuproptosis-related lncRNAs is still limited in HCC.MethodsWe isolated the transcriptome and clinical information of HCC from TCGA and ICGC databases. Ten cuproptosis-related genes were obtained and related lncRNAs were correlated by Pearson’s correlation. By performing lasso regression, we created a cuproptosis-related lncRNA prognostic model based on the cuproptosis-related lncRNA score (CLS). Comprehensive analyses were performed, including the fields of function, immunity, mutation and clinical application, by various R packages.ResultsTen cuproptosis-related genes were selected, and 13 correlated prognostic lncRNAs were collected for model construction. CLS was positively or negatively correlated with cancer-related pathways. In addition, cell cycle and immune related pathways were enriched. By performing tumor microenvironment (TME) analysis, we determined that T-cells were activated. High CLS had more tumor characteristics and may lead to higher invasiveness and treatment resistance. Three genes (TP53, CSMD1 and RB1) were found in high CLS samples with more mutational frequency. More amplification and deletion were detected in high CLS samples. In clinical application, a CLS-based nomogram was constructed. 5-Fluorouracil, gemcitabine and doxorubicin had better sensitivity in patients with high CLS. However, patients with low CLS had better immunotherapeutic sensitivity.ConclusionWe created a prognostic CLS signature by machine learning, and we comprehensively analyzed the signature in the fields of function, immunity, mutation and clinical application.

BackgroundCancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) are critical for immune suppression by restricting immune cell infiltration in the tumor stromal zones from penetrating tumor islands and changing their function status, particularly for CD8+ T cells. However, assessing and quantifying the impact of CAFs on immune cells and investigating how this impact is related to clinical outcomes, especially the efficacy of immunotherapy, remain unclear.Materials and methodsThe TME was characterized using immunohistochemical (IHC) analysis using a large-scale sample size of gene expression profiles. The CD8+ T cell/CAF ratio (CFR) association with survival was investigated in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) lung cancer cohorts. The correlation between CFR and immunotherapeutic efficacy was computed in five independent cohorts. The correlation between CFR and objective response rates (ORRs) following pembrolizumab monotherapy was investigated in 20 solid tumor types. To facilitate clinical translation, the IHC-detected CD8/α-SMA ratio was applied as an immunotherapeutic predictive biomarker in a real-world lung cancer cohort.ResultsCompared with normal tissue, CAFs were enriched in cancer tissue, and the amount of CAFs was overwhelmingly higher than that in other immune cells. CAFs are positively correlated with the extent of immune infiltration. A higher CFR was strongly associated with improved survival in lung cancer, melanoma, and urothelial cancer immunotherapy cohorts. Within most cohorts, there was no clear evidence for an association between CFR and programmed death-ligand 1 (PD-L1) or tumor mutational burden (TMB). Compared with TMB and PD-L1, a higher correlation coefficient was observed between CFR and the ORR following pembrolizumab monotherapy in 20 solid tumor types (Spearman’s r = 0.69 vs. 0.44 and 0.21). In a real-world cohort, patients with a high CFR detected by IHC benefited considerably from immunotherapy as compared with those with a low CFR (hazard ratio, 0.37; 95% confidence interval, 0.19–0.75; p < 0.001).ConclusionsCFR is a newly found and simple parameter that can be used for identifying patients unlikely to benefit from immunotherapy. Future studies are needed to confirm this finding.

BackgroundEffectively predicting the risk of adverse pregnancy outcome (APO) in women with systemic lupus erythematosus (SLE) during early and mid-pregnancy is a challenge. This study was aimed to identify potential markers for early prediction of APO risk in women with SLE.MethodsThe GSE108497 gene expression dataset containing 120 samples (36 patients, 84 controls) was downloaded from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA) was performed, and differentially expressed genes (DEGs) were screened to define candidate APO marker genes. Next, three individual machine learning methods, random forest, support vector machine-recursive feature elimination, and least absolute shrinkage and selection operator, were combined to identify feature genes from the APO candidate set. The predictive performance of feature genes for APO risk was assessed using area under the receiver operating characteristic curve (AUC) and calibration curves. The potential functions of these feature genes were finally analyzed by conventional gene set enrichment analysis and CIBERSORT algorithm analysis.ResultsWe identified 321 significantly up-regulated genes and 307 down-regulated genes between patients and controls, along with 181 potential functionally associated genes in the WGCNA analysis. By integrating these results, we revealed 70 APO candidate genes. Three feature genes, SEZ6, NRAD1, and LPAR4, were identified by machine learning methods. Of these, SEZ6 (AUC = 0.753) showed the highest in-sample predictive performance for APO risk in pregnant women with SLE, followed by NRAD1 (AUC = 0.694) and LPAR4 (AUC = 0.654). After performing leave-one-out cross validation, corresponding AUCs for SEZ6, NRAD1, and LPAR4 were 0.731, 0.668, and 0.626, respectively. Moreover, CIBERSORT analysis showed a positive correlation between regulatory T cell levels and SEZ6 expression (P < 0.01), along with a negative correlation between M2 macrophages levels and LPAR4 expression (P < 0.01).ConclusionsOur preliminary findings suggested that SEZ6, NRAD1, and LPAR4 might represent the useful genetic biomarkers for predicting APO risk during early and mid-pregnancy in women with SLE, and enhanced our understanding of the origins of pregnancy complications in pregnant women with SLE. However, further validation was required.

ObjectiveSeveral clinical trials have indicated that statins stabilize and reverse atherosclerotic plaque. However, different studies have provided inconsistent findings regarding mechanisms and influencing factors of plaque regression under statin therapy. Apart from lipid-lowering effect, statins have pleiotropic effects including anti inflammation in humans. In this study, meta-analysis and meta-regression were used to determine the effects of statin medications on coronary plaque volume. Meanwhile, to assess whether statins promote plaque regression effect was related to their anti-inflammatory ability, the impact of CRP/hsCRP reduction during statin therapy on plaque regression was investigated.MethodsUp to June 15, 2022, a systematic PubMed, EMBASE, and Cochrane search was performed for randomized controlled trials that assessed treatment effect using total atheroma volume (TAV), percent atheroma volume (PAV), or plaque volume (PV). Only CRP/hsCRP and LDL-C values reported before and after treatment were considered.Results12 studies (2,812 patients with heart and/or vascular disease) fulfilled the inclusion criteria and were included in the systematic review. A meta-analysis of 15 statin-treated arms reported a significant reduction in change of TAV/PV [standardized mean difference (SMD): –0.27, 95% confidence intervals (–CI): –0.42, –0.12, p < 0.001], compared with the control arms. Another meta-analysis of 7 trials also found that patients in the intervention group had a significant reduction in change of PAV (SMD: -0.16, 95% CI: –0.29, –0.03, p = 0.019), compared with those in the control group. Meta-regressionanalysis revealed that the percent change of CRP/hsCRP was significantly associated with SMD in change of TAV/PV after adjusting for percent change of LDL-C, age, gender and study duration. Meta-regression analysis showed that percent change of CRP/hsCRP statistically influenced SMD in change of PAV, when percent change of CRP/hsCRP was included separately. However, the percent change of CRP/hsCRP was not significantly associated with SMD of PAV change after adjusting for all covariates.ConclusionIn conclusion, statin therapy is beneficial for plaque regression. Statins promote plaque regression, which might be associated to their anti-inflammatory ability.

ObjectiveTo estimate the burden of potential productivity losses due to uncorrected and under-corrected presbyopia in LMICs among the working-age population in both the cross-sectional and longitudinal manner.MethodsWe extracted data for the prevalence of presbyopia from the Global Burden of Diseases (GBD), Injuries, and Risk Factors Study 2019. Data for the gross domestic product (GDP) per capita were extracted from the World Bank database and Central Intelligence Agency's World Factbook. We introduced life table models to construct age cohorts (in 5-year age groups) of the working-age population (aged from 40 to 64 years old) in LMICs, with simulated follow-up until 65 years old in people with and without uncorrected presbyopia. The differences in productivity-adjusted life years (PALYs) lived and productivity between these two cohorts were calculated. The potential productivity loss was estimated based on GDP per capita. The WHO standard 3% annual discount rate was applied to all years of life and PALYs lived.ResultsIn 2019, there were 238.40 million (95% confidence interval [CI]: 150.92–346.78 million) uncorrected and under-corrected presbyopia cases in LMICs, resulting in 54.13 billion (current US dollars) (95% confidence interval [CI]: 34.34–79.02 billion) potential productivity losses. With simulated follow-up until retirement, those with uncorrected and under-corrected presbyopia were predicted to experience an additional loss of 155 million PALYs (an average loss of 0.7 PALYs per case), which was equivalent to a total loss of US$ 315 billion (an average loss of US$ 1453.72 per person).ConclusionsOur findings highlight the considerable productivity losses due to uncorrected and under-corrected presbyopia in LMICs, especially in a longitudinal manner. There is a great need for the development of enabling eye care policies and programs to create access to eye care services, and more healthcare investment in the correction of presbyopia in the working-age population in LMICs. This study could provide evidences for some potential health-related strategies for socio-economic development.

An atomistic modeling tool is essential to an in-depth understanding upon surface reactions of transition metal dichalcogenides (TMDs), such as molybdenum disulfide (MoS2), with the presence of compositing agents, including Ti and Au, under different environmental exposures. We report a new ReaxFF reactive force field parameter set for Mo, Ti, Au, O, S, and H interactions. We apply the force field in a series of molecular dynamics (MD) simulations to unravel the impact of the Ti dopant on the oxidation/hydrogenation behaviors of MoS2 surface. The simulation results reveal that, in the absence of Ti clusters, the MoS2 surface is ruptured and oxidized at elevated temperatures through a process of adsorption followed by dissociation of the O2 molecules on the MoS2 surface during the temperature ramp. When the MoS2 surface is exposed to H2O molecules, surface hydrogenation is most favored, followed by oxidation, then hydroxylation. The introduction of Ti clusters to the systems mitigates the oxidation/hydrogenation of MoS2 at a low or intermediate temperature by capturing the O2/H2O molecules and locking the O/H-related radicals inside the clusters. However, OH− and H3O+ are emitted from the Ti clusters in the H2O environment as temperature rises, and the accelerating hydrogenation of MoS2 is consequently observed at an ultra-high temperature. These findings indicate an important but complex role of Ti dopants in mitigating the oxidation and hydrogenation of MoS2 under different environmental exposures. The possible mechanisms of oxidation and hydrogenation revealed by MD simulations can give an insight to the design of oxidation resistant TMDs and can be useful to the optical, electronic, magnetic, catalytic, and energy harvesting industries.

Quasi-zero stiffness (QZS) metamaterials and metastructures have great advantages of being highly integrable and lightweight for vibration isolation in aerospace and aviation applications. However, the geometric uncertainty introduced from additive manufacturing (AM) significantly affects the metamaterial/metastructure’s vibration isolation performance and therefore, needs to be evaluated accurately and efficiently in the design process. In this study, a high-order sparse Chebyshev polynomial expansion (HOSPSCPE) method is first utilized to quantify the influence of AM-induced geometric uncertainty in the QZS microstructure. Excellent accuracy and much higher efficiency (about 470 times faster) of the proposed method are observed when compared to the widely used Monte Carlo method (MCM). Uncertainty analyses are then conducted for vibration isolation performance of the QZS metastructures and band gap properties of the QZS locally resonant metamaterials, respectively. The numerical results demonstrate that the geometric uncertainty analysis can provide useful guidance and recommendations for the manufacturing-influenced design of QZS metastructures and metamaterials.

Cotton is an important natural fiber crop worldwide. Cotton fiber cell is regarded as an ideal material for studying the growth and development of plant cells. Sphingolipids are important components of biomembrane and bioactive molecules which participate in many processes such as plant growth, development regulation, stimulus sensing, and stress response. However, the functions of sphingolipids in the cotton fiber development are still unclear. In the present study, we identified a cotton ceramide synthase gene, GhCS1, which is predominantly expressed in fiber cell. The GhCS1 is located in the endoplasmic reticulum and has the conserved domains of ceramide synthase. Overexpression of GhCS1 gene inhibited both vegetative and reproductive growth in cotton. Importantly, the fiber cell initiation and elongation were severely inhibited when compared with control. Comparison of the sphingolipid profile in the 0-DPA (days past anthesis) ovule (with fiber cell) between control and transgenic cotton plants showed that the content of sphingosines (Sph) decreased significantly in transgenic ovules, whereas the content of phyto-sphingosines (Phyto-Sph) had no change. Meanwhile, the content of ceramide containing Sph and very-long-chain fatty acid (VLCFA) increased significantly in transgenic ovules, while ceramide containing Phyto-Sph and long-chain fatty acids (LCFA)/VLCFA significantly decreased. These results indicated that GhCS1 was a functional ceramide synthase, which preferentially used Sph and VLCFA as substrates and was different from the Arabidopsis ceramide synthase AtLOH1/AtLOH3, which preferentially used Phyto-Sph and VLCFA as substrates, and also different from AtLOH2, which preferentially used Sph and LCFA as substrates. It is suggested that GhCS1 might be a new ceramide synthase gene in the plant, play some roles in the development of fiber cells and cotton plants.

Chinese cordyceps is a well-known and valuable traditional Chinese medicine that forms after Ophiocordyceps sinensis parasitizes ghost moth larvae. The low natural infection rate of O. sinensis limits large-scale artificial cultivation of Chinese cordyceps, and the invasion process is unclear. To investigate the temporal and spatial regulation when O. sinensis enters ghost moths, we constructed an O. sinensis transformant that stably expresses green fluorescent protein (GFP). Inoculating Thitarodes xiaojinensis larvae with a high concentration of GFP-labeled O. sinensis, we observed that O. sinensis conidia could adhere to the host cuticle within 2 days, germinate penetration pegs within 4 days, and produce blastospores in the host hemocoel within 6 days. The reconstructed three-dimensional (3D) structures of the invasion sites showed that penetration pegs germinated directly from O. sinensis conidia at the joining site with the larval cuticle. Differentiated appressoria or hyphae along the host epicuticle are not required for O. sinensis to invade ghost moths. Overall, the specific invasion process of O. sinensis into its host is clarified, and we provided a new perspective on the invasion process of entomopathogenic fungi.

We previously found that leflunomide combined with low-dose prednisone rapidly improved the clinical symptoms of myasthenia gravis (MG), but we had not investigated the mechanism of this phenomenon. This study documents the effect of leflunomide combined with low-dose prednisone on pro-inflammatory T cells in MG patients. We compared 32 treated MG patients with 18 controls. We collected peripheral blood before treatment and 4, 8, and 12 weeks after treatment. We extracted peripheral blood mononuclear cells (PBMCs) and stimulated them with phorbol 12-myristate 13-acetate (PMA) + ionomycin and quantified IFN-γ, IL-4, IL-17, and IL-9 secretion through ELISA. We quantified T helper (Th) cells Th1 (CD3+CD4+IFN-γ+), Th2 (CD3+CD4+IL-4+), Th17 (CD3+CD4+IL-17A+) and Th9 (CD3+CD4+IL-9+) among PBMCs. The treatment significantly reduced IL-17 and IL-9 secretion in peripheral blood but did not affect IFN-γ levels. Significant decreases in IL-17 and IL-9 appeared at week 12, and the trend of change was similar to that of the MG composite score. Flow cytometry indicated that leflunomide combined with low-dose prednisone significantly reduced the frequency of Th1 and Th17 cells. These findings demonstrate the potential of this treatment as an alternative immunosuppressive therapy for MG.

Previous studies have demonstrated that TRIB3 is closely related to insulin resistance, metabolic disorders and vascular diseases. Recently, it was reported that a 33 bp variable number of tandem repeats (VNTR) located in the TRIB3 promoter could considerably alter its transcriptional activity. Nonetheless, whether the shift of TRIB3 transcriptional activity has the effect of inducing diabetic vascular complications is still unclear. Therefore, in our study, we aimed to explore the relationship between the TRIB3 33bp VNTR and diabetic vascular complications. The TRIB3 33bp VNTR polymorphisms were determined by PCR and Sanger sequencing, a total of 798 eligible Chinese patients with type 2 diabetes (T2DM) were included in our study and then evaluated with clinical data. After adjusting for age, gender, BMI, smoking history, drinking history and duration of diabetes, we found that the high number of 33 bp tandem repeats (repeats>8) was significantly associated with an increase in the risk of cerebrovascular diseases compared with the low number of 33 bp tandem repeats (repeats≤6) in patients with T2DM(OR 2.66, 95% CI 1.29–5.47, p = 0.008). The intermediate number of 33bp tandem repeats (6 < repeat≤8) was markedly associated with a decreased risk of diabetic retinopathy compared with the low number of tandem repeats (OR 0.65, 95% CI 0.46–0.91, p = 0.012). Adjusting for gender, age and BMI, there was a significant difference in DBP levels among patients with the number of different 33 bp tandem repeats (Low vs. Intermediate vs. High, 81.6 ± 12.8 vs. 79.8 ± 12.4 vs. 78.7 ± 12.6 mmHg; p = 0.045). Subgroup analysis found that TRIB3 VNTR was significantly correlated with the difference in systolic blood pressure (SBP) in T2DM patients taking ACEI/ARB drugs (Low vs. Intermediate vs. High, 146.27 ± 18.23 vs. 140.01 ± 19.91 vs. 140.77 ± 18.64 mmHg; p = 0.018). Our results indicated that TRIB3 promoter 33bp VNTR is related to vascular diseases in T2DM patients, and may serve as a new biomarker for individualized prevention and therapy of T2DM.

The performance of the actuator is becoming increasingly important in the ultra-precision stage. However, the traditional Lorentz motors with given mechanical parameters cannot provide enough force for the next-generation motion stage in the semiconductor industry since they achieve a physical limit of power factor. To tackle this problem, this study develops a novel-driven approach and its control strategy for high-dynamic stages. Explicitly, the proposed method utilizes a linear reluctance motor as an actuator, which could promote the continuous thrust significantly. A heuristic optimization-based Bouc–Wen model is established to describe the nonlinear behavior of the novel actuator. Also, a flux control algorithm based on the integral sliding mode is derived and adjusted for precision thrust generation. Comparative simulations on a specific linear reluctance motor confirm the effectiveness and superiority of the proposed method and show that it has the ability to conquer the force nonlinearity of the novel actuator.

Newcastle disease (ND) is an acute and highly contagious disease caused by the Newcastle disease virus (NDV) infecting poultry, which has caused great harm to the poultry industry around the world. Rapid diagnosis of NDV is important to early treatment and early institution of control measures. In this review, we comprehensively summarize the most recent research into NDV, including historical overview, molecular structure, and infection mechanism. We then focus on detection strategies for NDV, including virus isolation, serological assays (such as hemagglutination and hemagglutination-inhibition tests, enzyme linked immunosorbent assay, reporter virus neutralization test, Immunofluorescence assay, and Immune colloidal gold technique), molecular assays (such as reverse transcription polymerase chain reaction, real-time quantitative PCR, and loop-mediated isothermal amplification) and other assays. The performance of the different serological and molecular biology assays currently available was also analyzed. To conclude, we examine the limitations of currently available strategies for the detection of NDV to lay the groundwork for new detection assays.

Lung adenosquamous carcinoma (ASC) is an uncommon histological subtype. We aimed to characterize the tumor immune microenvironment (TIME) in lung ASC and estimate patient response to immune checkpoint inhibitors (ICIs), which have never been systematically investigated. In cohort I, we collected 30 ASCs from a single center for analysis of TIME characteristics, including immuno-phenotyping, tumor mutation burden (TMB), T-cell receptor (TCR) repertoires, tumor-infiltrating lymphocytes (TILs), and immune checkpoint expression. Twenty-two (73.3%) patients were EGFR-positive. The TIME was defined by immune-excluded (60%) and immune-desert phenotype (40%). Strikingly, programmed cell death-ligand 1 (PD-L1) and programmed cell death-1 (PD-1) were predominantly expressed in squamous cell carcinoma components (SCCCs) versus adenocarcinoma components (ACCs), where enhanced CD4+ FOXP3+ regulatory T cell and attenuated CD57+ natural killer cell infiltration were present, consistent with a landscape of fewer innate immune cells, more immunosuppressive cells. SCCCs had higher TMB, higher TCR clonality, and lower TCR diversity than ACC. In cohort III, the efficacy of ICI-based therapy was estimated using a real-world data of 46 ASCs from 11 centers. Majority of 46 patients were driver genes negative and unknown mutation status, 18 (39%) and 18 (39%), respectively. The overall objective response rate of 28%, median progression-free survival of 6.0 months (95% confidence interval [CI] 4.3–7.7), and median overall survival of 24.7 months (95% CI 7.2–42.2) were observed in the ICI-based treatment. This work ascertains suppressive TIME in lung ASC and genetic and immuno-heterogeneity between ACCs and SCCCs. Lung ASC patients have a moderate response to ICI-based immunotherapy.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are emerging as a crucially important protein family in tumors. However, it is unclear which family members are essential for cancer progression, and their diverse expression patterns and prognostic values are rarely reported. In this work, we found that the expression levels of hnRNPs were all upregulated in colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ) tissues. Immunohistochemical staining revealed that hnRNPA1, hnRNPA2B1, hnRNPC, hnRNPK, hnRNPR, and hnRNPU are overexpressed in colorectal adenocarcinoma. Additionally, the promoter methylation levels of hnRNPs were significantly elevated or decreased, and multiple genetic alterations of hnRNPs were found in colorectal adenocarcinoma patients. Correlation analysis showed that the expression levels of hnRNPs were positively correlated with each other. Furthermore, we demonstrated that high expressions of hnRNPA1, hnRNPK, hnRNPR, and hnRNPU were associated with better overall survival rates for colorectal adenocarcinoma patients. The co-expression network and functional prediction analysis indicated that hnRNPK/A1/R/U was involved in cellular gene transcription and translation. Moreover, hnRNPK/A1/R/U complex was identified and confirmed by mass spectrometry and co-immunoprecipitation. RNA sequencing analysis revealed that the transcription factor hnRNPK regulated transcription and translation of related genes. Finally, through establishment of stable cell lines in vitro, we verified that hnRNPK was a favorable factor in human colorectal adenocarcinoma which promoted immune cell infiltration and inhibited tumor growth. Our findings illustrate that the hnRNPK/A1/R/U complex is a favorable prognostic biomarker for human colorectal adenocarcinoma. Targeting hnRNPK during transcription and translation could be a promising therapeutic strategy for colorectal adenocarcinoma treatment.

BackgroundTo newly describe the vault measurement by using a widely used swept-source OCT-based optical biometer (IOLMaster700) and accessd the accuracy of vault measurement.MethodsThis was a retrospective, cross-sectional study. All patients underwent implantable Collamer lens (ICL) implantation surgery without complications. IOLMaster700 and AS-OCT analyses were conducted for each eye on the same day in the same condition. Measurements of anterior chamber depth (ACD), corneal-ICL (C-ICL), and vault values were made and recorded. The repeatability of the IOL Master700 measurements was quantified based upon intraclass correlation coefficient (ICC) values. Correlations between IOL Master700 and AS-OCT measurements made with these different analytical approaches were assessed. The agreement of instruments was evaluated using Bland-Altman plots.ResultsThe IOLMaster700 instrument yielded highly reliable measurements of vault, C-ICL, and ACD (ICC = 0.996, 0.995, 0.995, respectively). Vault, C-ICL and ACD values as measured using the IOLMaster700, was slightly smaller than that measured via AS-OCT, but these differences were not significant (p = 0.652, p = 0.121 and p = 0.091, respectively). The vault, C-ICL, and ACD measurements by these two instruments were strongly correlated (r = 0.971, r = 0.944, and r = 0.963, respectively; all p < 0.001). The 95% limits of agreement for vault, C-ICL, and ACD measurements between the two devices were−0.08 to 0.08 mm,−0.14 to 0.11 mm, and−0.13 to 0.10 mm, respectively.ConclusionsThe IOLMasrer700 can measure implanted ICL vault with a high degree of accuracy and repeatability. Good correlations and agreement were observed between IOLMaster700 and AS-OCT in measuring vault, C-ICL, and ACD measurements.

The diversity of bacteria and their ability to acquire drug resistance lead to many challenges in traditional antibacterial methods. Photothermal therapies that convert light energy into localized physical heat to kill target microorganisms do not induce resistance and provide an alternative for antibacterial treatment. However, many photothermal materials cannot specifically target bacteria, which can lead to thermal damage to normal tissues, thus seriously affecting their biological applications. Here, we designed and synthesized bacteria-affinitive photothermal carbon dots (BAPTCDs) targeting MurD ligase that catalyzes the synthesis of peptidoglycan (PG) in bacteria. BAPTCDs presented specific recognition ability and excellent photothermal properties. BAPTCDs can bind to bacteria very tightly due to their chiral structure and inhibit enzyme activity by competing with D-glutamic acid to bind to MurD ligases, thus inhibiting the synthesis of bacterial walls. It also improves the accuracy of bacteria treatment by laser irradiation. Through the synergy of biochemical and physical effects, the material offers outstanding antibacterial effects and potentially contributes to tackling the spread of antibiotic resistance and facilitation of antibiotic stewardship.

Extramammary Paget’s disease (EMPD) is a rare cutaneous neoplasm with distant metastases and a poor prognosis. We report the case of a 63-year-old male patient exhibiting stage IV primary EMPD with neuroendocrine differentiation, and harboring a somatic mutation in AMER1. After four cycles of Anlotinib combined with Tislelizumab, the patient achieved partial response for the metastatic lesions according to mRECIST1.1 criteria. Total positron emission tomography and computed tomography (PET-CT) scans revealed a significant reduction in SUV from 18.9 to 5.3, and the serum CEA decreased to normal levels after the treatment regimen. However, the patient developed fractures of the fourth and fifth thoracic vertebrae during the treatment. Therefore, percutaneous vertebroplasty was performed, and the patient experienced severe postoperative pneumonia and died from pulmonary encephalopathy and respiratory failure in June 2021. The overall and progression-free survival of the patient after diagnosis were 9 and 8 months, respectively. During the systemic treatment, the patient suffered grade 1 rash in the back and thigh and grade 1 hypertension. Nevertheless, the combination treatment of anlotinib and tislelizumab had a favorable clinical outcome and provided a survival advantage, and should be considered a therapeutic option for patients with AMER1-mutant metastatic EMPD.

Objective:To analyze the etiology of chest diffuse radiological changes (DRC) in children older than 2 years.MethodsA retrospective study was conducted on a primary cohort of children with DRC underwent high resolution computed tomography (HRCT).ResultsDRC mainly included bronchial wall thickening, interlobular septal thickening, pleural thickening, ground glass opacity, mosaic perfusion, reticular & linear opacities, nodular opacity, and tree-in-bud. Of the identified 457 children with DRC, 83 of children older than 2 years with DRC were included in the present study. Ground glass opacity (53, 63.9%) and reticular & linear opacities (44, 53.0%) were frequently identified findings of HRCT, and no tree-in-bud pattern was observed. By contrast, among children with DRC by M. pneumoniae (n = 64), bronchial wall thickening (33, 51.6%), and mosaic perfusion (17, 26.6%) were common patterns of HRCT in addition to ground glass opacity (36, 56.3%). Most of etiologies were connective tissue disease (24, 28.9%), followed by diffuse alveolar hemorrhage syndrome (9, 10.8%), Langerhans cell histiocytosis (7, 8.4%), and recurrent aspiration (6, 7.2%).ConclusionsThis study adds further insights into the role of HRCT in diagnosing childhood interstitial lung diseases, indirectly reflecting disease compositions.

Foxtail millet has gradually become a model gramineous C4 crop owing to its short growth period and small genome. Research on the development of its spikelets is not only directly related to the yield and economic value of foxtail millet but also can provide a reference for studying the fertility of other C4 crops. In this study, a hybrid population containing 200 offspring was constructed from the Xinong8852 and An15 parental lines, and two extreme trait populations were constructed from the F2 generation for analysis of the spikelet sterility. The F2 population conformed to a 3:1 Mendelian segregation ratio, and it was thus concluded that this trait is likely controlled by a single recessive gene. Bulk segregant analysis sequencing (BSA-Seq) was used to determine the candidate regions and candidate genes related to the development of foxtail millet spikelets. Additionally, the functional analysis of differentially expressed genes in populations with different traits was conducted by bulk segregant RNA sequencing (BSR-Seq). Finally, conjunctive analysis of BSA-Seq and BSR-Seq results, combined with biological information analysis, revealed six genes on chromosome VII that were ultimately identified as candidate genes controlling foxtail millet spikelet development. This study provides a new reference for research on foxtail millet sterility and lays a solid foundation for the examination of fertility in other gramineous crops.

ObjectiveTo assess the diagnostic performance of US and MRI in predicting malignancy of soft tissue masses by using a scoring system.MethodsA total of 120 cases of pathologically confirmed soft tissue masses (71 cases of malignant lesions and 49 cases of benign lesions) were enrolled. All patients underwent ultrasound and MRI examination prior to biopsy or surgical excision. A scoring system based on the parameters of conventional US and MRI to distinguish malignant and benign masses was established by the regression model. The receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of US and MRI.ResultsMultivariate analysis showed that margin, maximum diameter, and vascular density were independent predictors for malignancy found by US, while maximum diameter, margin, and affected peripheral soft tissue were independent predictors for malignancy found by MRI. The mean scores of the benign and malignant groups were 2.8 ± 1.6, 5.1 ± 1.1 on US and 1.3 ± 1.2, 3.5 ± 0.9 on MRI. Based on the cut-off score of 3.5 and 2.5 calculated by ROC analysis, US and MRI had 92% and 87% sensitivity, 72% and 76% specificity, 86% and 89% accuracy, respectively. The combination of these two modalities achieved the sensitivity of 91%, specificity of 82%, and accuracy of 93%.ConclusionsBoth US and MRI can provide valuable information about the differential diagnosis between benign and malignant soft tissue masses. The combination of the two imaging-based scoring systems can increase the diagnostic performance, especially in specificity.

Cisplatin-based chemotherapy is dominated in several cancers; however, insufficient therapeutic outcomes and systemic toxicity hamper their clinical applications. Controlled release of cisplatin and reducing inactivation remains an urgent challenge to overcome. Herein, diselenide-bridged mesoporous organosilica nanoparticles (MON) coated with biomimetic cancer cell membrane were tailored for coordination responsive controlled cisplatin delivery and GSH depletion to strengthen Pt-based chemotherapy. Cisplatin-loaded MON (MON-Pt) showed high loading capacity due to robust coordination between selenium and platinum atoms and preventing premature leakage in normal tissue. MON-Pt exhibited a controlled release of activated cisplatin in response to the redox tumor microenvironment. Meanwhile, MON-Pt containing redox-responsive diselenide bonds could efficiently scavenge intracellular inactivation agents, such as GSH, to enhance Pt-based chemotherapy. 4T1 breast cancer cell membranes cloaked MON-Pt (MON-Pt@CM) performed efficient anticancer performance and low in vivo system toxicity due to long blood circulation time and high tumor accumulation benefiting from the tumor targeting and immune-invasion properties of the homologic cancer cell membrane. These results suggest a biomimetic nanocarrier to control release and reduce the inactivation of cisplatin for efficient and safe Pt-based chemotherapy by responding and regulating the tumor microenvironment.

Pleomorphic adenoma gene like-2 (PLAGL2) has been implicated in the development and progression of diverse malignancies, including glioblastoma. An increasing number of studies have reported that dysregulated expression of PLAGL2 is a common phenomenon in different malignancies. However, the mechanism and biological functions of PLAGL2 in patients with high-grade glioma (HGG) remain unclear. In addition, the expression and clinical significance of PLAGL2 in HGG have not yet been reported. Herein, we investigated the expression patterns and prognostic values of PLAGL2 in patients with HGG by using various databases, including Tumor Immune Estimation Resource 2.0 (TIMER2.0), GENT2, ONCOMINE, GEPIA, Human Protein Atlas, and Gene Expression Omnibus datasets. In the present study, we analyzed the relationship between PLAGL2 mRNA expression and clinical parameters in 184 HGG cases and found that PLAGL2 presented positively high expression and was relevant to poor prognosis. Immunohistochemistry analysis confirmed the overexpression of PLAGL2 protein, which is mainly expressed in the nucleus of glioma. Additionally, a high level of expression of the PLAGL2 gene was associated with lower survival in progression-free survival and overall survival in GBM patients. The correlation analysis between PLAGL2 and immune infiltration related to the abundance of B cells, CD8+ T cells, CD4+ T cells, macrophages, DCs, and neutrophils was also performed using TIMER2.0. GSEA results showed that high PLAGL2 expression was associated with cell migration, proliferation, actin cytoskeletal, and angiogenesis. To sum up, our findings indicated that PLAGL2 could serve as an independent prognostic biomarker and might be a potential therapeutic target for HGG, which should be further investigated.

Cell-laden hydrogel microspheres with uniform size show great potential for tissue repair and drug screening applications. Droplet microfluidic systems have been widely used for the generation of cell-laden hydrogel microspheres. However, existing droplet microfluidic systems are mostly based on complex chips and are not compatible with well culture plates. Moreover, microspheres produced by droplet microfluidics need demulsification and purification from oil, which requires time and effort and may compromise cell viability. Herein, we present a simple one-step approach for producing and purifying hydrogel microspheres with an easily assembled microfluidic device. Droplets were generated and solidified in the device tubing. The obtained hydrogel microspheres were then transferred to a tissue culture plate filled with cell culture media and demulsified through evaporation of the oil at 37°C. The removal of oil caused the gelled microspheres to be released into the cell culture media. The encapsulated cells demonstrated good viability and grew into tumor spheroids in 12–14 days. Single cell-laden hydrogel microspheres were also obtained and grown into spheroid in 14 days. This one-step microsphere generation method shows good potential for applications in automated spheroid and organoid cultures as well as drug screening, and could potentially offer benefits for translation of cell/microgel technologies.

Computer-aided diagnosis of pathological images usually requires detecting and examining all positive cells for accurate diagnosis. However, cellular datasets tend to be sparsely annotated due to the challenge of annotating all the cells. However, training detectors on sparse annotations may be misled by miscalculated losses, limiting the detection performance. Thus, efficient and reliable methods for training cellular detectors on sparse annotations are in higher demand than ever. In this study, we propose a training method that utilizes regression boxes' spatial information to conduct loss calibration to reduce the miscalculated loss. Extensive experimental results show that our method can significantly boost detectors' performance trained on datasets with varying degrees of sparse annotations. Even if 90% of the annotations are missing, the performance of our method is barely affected. Furthermore, we find that the middle layers of the detector are closely related to the generalization performance. More generally, this study could elucidate the link between layers and generalization performance, provide enlightenment for future research, such as designing and applying constraint rules to specific layers according to gradient analysis to achieve “scalpel-level” model training.

Macrophage activation syndrome (MAS) and widespread brain lesions are rare and severe complications of childhood-onset systemic lupus erythematosus (SLE). We report an 11-year-old girl who presented with recurrent rashes for half a year and fever for 2 weeks. Clinical and laboratory features at admission pointed to the diagnosis of SLE and SLE-associated MAS. Cerebral magnetic resonance imaging taken on day 4 after admission showed abnormal signals. Glucocorticoid therapy was started on day 5. Two days later, the patient appeared weak and ill, then the next day she exhibited dizziness, drowsiness, apathia, and dysarthria. High-dose methylprednisolone, cyclophosphamide, and intravenous immunoglobulin were used to treat the patient, and intrathecal dexamethasone was given. The patient was discharged on day 30 after admission and showed complete clinical resolution and improved magnetic resonance imaging resolution.