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Abstract Tobacco exposure is known to be associated with a higher prevalence and incidence of liver diseases. Cotinine, a metabolite of nicotine, is a typical indicator of tobacco exposure. However, the relationship of serum cotinine levels with hepatic steatosis and liver fibrosis remains controversial and these relationships need more research to explored in American teenagers. Cross-sectional data included 1433 participants aged 12–19 from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020 were thoroughly used for this study. The linear relationships between serum cotinine levels and the Liver Stiffness Measurement (LSM) and Controlled Attenuation Parameter (CAP) were examined using multiple linear regression models. Subgroup analysis, interaction tests, and nonlinear interactions were also carried out. Serum cotinine levels > 2.99 ng/ml [β = 0.41 (0.07, 0.76), p = 0.018] and 0.05–2.99 ng/ml [β = 0.24 (0.00, 0.49), p = 0.048] showed a significant positive connection with LSM in multivariate linear regression analysis when compared to serum cotinine levels ≤ 0.05 ng/ml (p for trend = 0.006). Moreover, we discovered an inverted U-shaped association of log2-transformed cotinine with LSM with an inflection point of 4.53 using a two-stage linear regression model. However, according to multiple regression analysis, serum cotinine and CAP did not significantly correlate (p = 0.512). In conclusion, this study demonstrated that smoking cessation and keep away from secondhand smoking may beneficial for liver health in American teenagers.

Abstract The accumulation of unfolded or misfolded proteins within the endoplasmic reticulum (ER), due to genetic determinants and extrinsic environmental factors, leads to endoplasmic reticulum stress (ER stress). As ER stress ensues, the unfolded protein response (UPR), comprising three signaling pathways—inositol-requiring enzyme 1, protein kinase R-like endoplasmic reticulum kinase, and activating transcription factor 6 promptly activates to enhance the ER’s protein-folding capacity and restore ER homeostasis. However, prolonged ER stress levels propels the UPR towards cellular demise and the subsequent inflammatory cascade, contributing to the development of human diseases, including cancer, neurodegenerative disorders, and diabetes. Notably, increased expression of all three UPR signaling pathways has been observed in these pathologies, and reduction in signaling molecule expression correlates with decreased proliferation of disease-associated target cells. Consequently, therapeutic strategies targeting ER stress-related interventions have attracted significant research interest. In this review, we elucidate the critical role of ER stress in cancer, metabolic, and neurodegenerative diseases, offering novel therapeutic approaches for these conditions.

Abstract Background The RNA profiles of tumor-educated platelets (TEPs) possess pathological features that could be used for early cancer detection. However, the utility of TEP RNA profiling in detecting early colorectal cancer (CRC) versus noncancerous colorectal diseases has not yet been investigated. This study assesses the diagnostic capacity of TEP RNA profiles in a cohort of patients with CRC and noncancerous diseases. Methods Transcriptome sequencing for platelets isolated from 132 patients with CRC at early and late stages and 190 controls consisting of healthy donors and patients with ulcerative disease, Crohn’s disease, polyps, and adenomas was performed and analyzed using binary particle swarm optimization coupled with support vector machine to identify genes that contributed to the classification of CRC patients versus controls. The area under the receiver operating curves (AUROCs) and the accuracy of TEP RNA profiles in CRC diagnosis were assessed. Results TEP RNA profiling achieved high performance in distinguishing and staging CRC patients from the controls. Using the swarm intelligence algorithm, the 921 most contributive genes that classified CRC patients from the controls were identified. AUROCs of 0.928 for the training set via leave-one-out cross-validation and 0.92 for the validation set were achieved, both of which were significantly higher than the clinically utilized serum biomarkers: carcinoembryonic antigen and cancer antigen 19-9. Notably, an AUROC of 0.915 in an external validation set was achieved. For predicting different CRC stages, an AUROC of 0.984 was achieved in the training set and 1.000 in the internal validation set. Conclusions RNA profiles of TEPs are of potential diagnostic value for identifying early CRC from noncancerous diseases. Prospective studies are needed to validate its clinical relevance.

Background: The parasitic nematode Angiostrongylus cantonensis is the primary pathogen causing eosinophilic meningitis and meningoencephalitis in nonpermissive hosts. The larval parasites are eliminated by the host's immune responses in the central nervous system (CNS) through infiltration of eosinophils and lymphocytes. This study aimed to determine primary alterations of microRNA (miRNA) during A. cantonensis infection in mice. Methods: miRNA array was used to analyze the expression of miRNA in uninfected and A. cantonensis-infected mouse brains at 21 days postinfection (dpi). Target genes were predicted by miRDB software, and protein–protein interaction network was analyzed using STRING v9.1. Expression levels of selected miRNAs and cytokine production were verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results: Twenty-five mature miRNAs showed differential expression in infected mouse brains, of which 24 were upregulated and one was downregulated compared to the uninfected control. These 25 miRNAs were divided into five clusters, and the first upregulated cluster was selected for further bioinformatics analysis. Target gene prediction and gene ontology (GO) enrichment analysis revealed that the miRNAs were mainly related to the immune response. Furthermore, six target genes of mmu-miR-146a-5p were predicted to interact with tumor necrosis factor alpha (TNF-α). The in vitro study suggested that transfected mmu-miR-146a-5p inhibitor upregulated TNF-α and its target gene Traf6 in microglia following stimulation with A. cantonensis larval antigen. Conclusion: This study suggested a critical role of miRNAs in the host defense during A. cantonensis infection, providing new insights into the molecular mechanisms underlying the interaction between mmu-miR-146a-5p and TNF-α in angiostrongyliasis in nonpermissive hosts.

Abstract The purpose of this study is to develop a nomogram model for early prediction of the severe mycoplasma pneumoniae pneumonia (SMPP) in Pediatric and Adult Patients. A retrospective analysis was conducted on patients with MPP, classifying them into SMPP and non-severe MPP (NSMPP) groups. A total of 550 patients (NSMPP 374 and SMPP 176) were enrolled in the study and allocated to training, validation cohorts. 278 patients (NSMPP 224 and SMPP 54) were retrospectively collected from two institutions and allocated to testing cohort. The risk factors for SMPP were identified using univariate analysis. For radiomic feature selection, Spearman’s correlation and the least absolute shrinkage and selection operator (LASSO) were utilized. Logistic regression was used to build different models, including clinical, imaging, radiomics, and integrated models (combining clinical, imaging, and radiomics features selected). The model’s discrimination was evaluated using a receiver operating characteristic curve, its calibration with a calibration curve, and the results were visualized using the Hosmer–Lemeshow goodness-of-fit test. Thirteen clinical features and fourteen imaging features were selected for constructing the clinical and imaging models. Simultaneously, a set of twenty-five radiomics features were utilized to build the radiomics model. The integrated model demonstrated good calibration and discrimination in the training cohorts (AUC, 0.922; 95% CI: 0.900, 0.942), validation cohorts (AUC, 0.879; 95% CI: 0.806, 0.920), and testing cohorts (AUC, 0.877; 95% CI: 0.836, 0.916). The discriminatory and predictive efficacy of the clinical model in testing cohorts increased further after clinical and radiological features were incorporated (AUC, 0.849 vs. 0.922, P = 0.002). The model demonstrated exemplary predictive efficacy for SMPP by leveraging a comprehensive set of inputs, encompassing clinical data, quantitative and qualitative radiological features, along with radiomics features. The integration of these three aspects in the predictive model further enhanced the performance of the clinical model, indicating the potential for extensive clinical applications.

Abstract Objective Since January 8, 2023, China has managed COVID-19 as a Class-B infectious disease, marking the epidemic's transition to a low-level stage. This study analyzes the relationship between the public's perceived a community with shared future for doctor-patient (PCSF), health self-consciousness, benefit finding, and anxiety in this stage. Additionally, it compares changes in these variables across different stages of COVID-19. Methods Using a repeated cross-sectional design, three surveys were conducted respectively in three different stages of COVID-19 in China. Specifically, the first survey was conducted in Beijing, Dalian, Zhengzhou, Heihe, and Shangrao from November 13 to 20, 2021 in the outbreak stage of COVID-19, yielding 1,252 valid responses out of 1,534 collected questionnaires. The second survey was conducted in Dalian, Zhengzhou, Heihe, Shangrao, and Lanzhou from December 1 to 19, 2021 in the stable stage of COVID-19, with 872 valid responses obtained from 1,075 collected questionnaires. The third survey was conducted in Beijing, Dalian, Zhengzhou, Heihe, Shangrao, Lanzhou, and Chengdu from January 29 to February 4, 2023 in the low epidemic level stage of COVID-19, achieving 2,113 valid responses from the 2,461 questionnaires collected. Results Unlike in the outbreak stage but similar to the stable stage, the public's anxiety, health self-consciousness and benefit finding decreased while PCSF was improved in the low epidemic level stage. Consistent with both the outbreak and stable stage, PCSF, health self-consciousness, benefit finding, and anxiety showed positive correlations in the low epidemic level stage, with health self-consciousness partially mediating the positive impact of PCSF on benefit finding. Unlike in the stable stage but similar to the outbreak stage, anxiety did not moderate the relationship between PCSF and health self-consciousness in the low epidemic level stage. Conclusions The public's health self-consciousness, benefit finding, and anxiety decreased, while PCSF increased in the low epidemic level stage. Furthermore, PCSF had a greater impact on benefit finding, and anxiety's impact on health self-consciousness was significantly reduced. Across different stages of COVID-19, PCSF directly increased benefit finding and also enhanced benefit finding by improving health self-consciousness. Thus, comprehensive intervention measures are beneficial in the low epidemic level stage.

The traditional treatment for small-cell lung cancer (SCLC) has been traditional systemic platinum-containing chemotherapy because the response rate is 50–90%. Durvalumab is an immune checkpoint inhibitor that blocks the binding of programmed cell death protein 1 and programmed cell death 1 ligand 1. Durvalumab combined with traditional chemotherapy agents has been recommended as the first-line treatment for extensive-stage SCLC, but its use may cause immune-related adverse events. Autoimmune encephalitis is a rare and potentially fatal neurological adverse event. This current case report describes a male patient in his late 50s with ES-SCLC who developed autoimmune encephalitis associated with durvalumab treatment after three cycles of combination chemotherapy. This current case furthers the understanding of autoimmune encephalitis caused by durvalumab treatment.

Abstract Background Asymptomatic COVID-19 carriers with normal chest computed tomography (CT) scans have perpetuated the ongoing pandemic of this disease. This retrospective study aimed to use automated machine learning (AutoML) to develop a prediction model based on CT characteristics for the identification of asymptomatic carriers. Methods Asymptomatic carriers were from Yangzhou Third People’s Hospital from August 1st, 2020, to March 31st, 2021, and the control group included a healthy population from a nonepizootic area with two negative RT‒PCR results within 48 h. All CT images were preprocessed using MATLAB. Model development and validation were conducted in R with the H2O package. The models were built based on six algorithms, e.g., random forest and deep neural network (DNN), and a training set (n = 691). The models were improved by automatically adjusting hyperparameters for an internal validation set (n = 306). The performance of the obtained models was evaluated based on a dataset from Suzhou (n = 178) using the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and F1 score. Results A total of 1,175 images were preprocessed with high stability. Six models were developed, and the performance of the DNN model ranked first, with an AUC value of 0.898 for the test set. The sensitivity, specificity, PPV, NPV, F1 score and accuracy of the DNN model were 0.820, 0.854, 0.849, 0.826, 0.834 and 0.837, respectively. A plot of a local interpretable model-agnostic explanation demonstrated how different variables worked in identifying asymptomatic carriers. Conclusions Our study demonstrates that AutoML models based on CT images can be used to identify asymptomatic carriers. The most promising model for clinical implementation is the DNN-algorithm-based model.

In multicolor fluorescence microscopy, it is crucial to orient biological structures at a single-cell resolution based on precise anatomical annotations of cytoarchitecture images. However, during synchronous multicolor imaging, due to spectral mixing, the crosstalk from the blue signals of 4′,6-diamidino-2-phenylindole (DAPI)-stained cytoarchitecture images to the green waveband hinders the visualization and identification of green signals. Here, we proposed a deep learning-based framework named the crosstalk elimination and cytoarchitecture enhancement pipeline (CECEP) to simultaneously acquire crosstalk-free signals in the green channel and high-contrast DAPI-stained cytoarchitecture images during multicolor fluorescence imaging. For the CECEP network, we proposed an unsupervised learning algorithm named the cytoarchitecture enhancement network (CENet), which increased the signal-to-background ratio (SBR) of the cytoarchitecture images from 1.5 to 15.0 at a reconstruction speed of 25 Hz for 1800 × 1800 pixel images. The CECEP network is widely applicable to images of different quality, different types of tissues, and different multicolor fluorescence microscopy. In addition, the CECEP network can also facilitate various downstream analysis tasks, such as cell recognition, structure tensor calculation, and brain region segmentation. With the CECEP network, we simultaneously acquired two specific fluorescence-labeled neuronal distributions and their colocated high-SBR cytoarchitecture images without crosstalk throughout the brain. Experimental results demonstrate that our method could potentially facilitate multicolor fluorescence imaging applications in biology, such as revealing and visualizing different types of biological structures with precise locations and orientations.

Nirmatrelvir/ritonavir is a novel drug combination that is authorized by the Food and Drug Administration for the treatment of coronavirus disease 2019 (COVID-19). Ritonavir is a cytochrome P450 3A inhibitor and a P-glycoprotein inhibitor that increases the plasma concentration of tacrolimus and other medications. We describe the cases of two patients treated with nirmatrelvir/ritonavir: a patient who had undergone kidney transplantation and another with a history of hematopoietic stem cell transplantation. Toxic concentrations of tacrolimus were induced in both. This case series highlights the risk associated with the concomitant administration of tacrolimus and nirmatrelvir/ritonavir.

ABSTRACT: The processing and analysis of massive high-dimensional datasets are important issues in precision livestock farming (PLF). This study explored the use of multivariate analysis tools to analyze environmental data from multiple sensors located throughout a broiler house. An experiment was conducted to collect a comprehensive set of environmental data including particulate matter (TSP, PM10, and PM2.5), ammonia, carbon dioxide, air temperature, relative humidity, and in-cage and aisle wind speeds from 60 locations in a typical commercial broiler house. The dataset was divided into 3 growth phases (wk 1–3, 4–6, and 7–9). Spearman's correlation analysis and principal component analysis (PCA) were used to investigate the latent associations between environmental variables resulting in the identification of variables that played important roles in indoor air quality. Three cluster analysis methods; k-means, k-medoids, and fuzzy c-means cluster analysis (FCM), were used to group the measured parameters based on their environmental impact in the broiler house. In general, the Spearman and PCA results showed that the in-cage wind speed, aisle wind speed, and relative humidity played critical roles in indoor air quality distribution during broiler rearing. All 3 clustering methods were found to be suitable for grouping data, with FCM outperforming the other 2. Using data clustering, the broiler house spaces were divided into 3, 2, and 2 subspaces (clusters) for wk 1 to 3, 4 to 6, and 7 to 9, respectively. The subspace in the center of the house had a poorer air quality than other subspaces.

Strength-ductility trade-off is a common issue in Mg alloys. This work proposed that a synergistic enhancement of strength and ductility could be achieved through tuning interlayer dwell time (IDT) in the wire and arc additive manufacturing (WAAM) process of Mg alloy. The thermal couples were used to monitor the thermal history during the WAAM process. Additionally, the effect of different IDTs on the microstructure characteristics and resultant mechanical properties of WAAM-processed Mg alloy thin-wall were investigated. The results showed that the stable temperature of the thin-wall component could reach 290 °C at IDT=0s, indicating that the thermal accumulation effect was remarkable. Consequently, unimodal coarse grains with an average size of 39.6 µm were generated, and the resultant room-temperature tensile property was poor. With the IDT extended to 60s, the thermal input and thermal dissipation reached a balance, and the stable temperature was only 170 °C, closing to the initial temperature of the substrate. A refined grain structure with bimodal size distribution was obtained. The remelting zone had fine grains with the size of 15.2 µm, while the arc zone owned coarse grains with the size of 24.5 µm. The alternatively distributed coarse and fine grains lead to the elimination of strength-ductility trade-off. The ultimate tensile strength and elongation of the samples at IDT=60s are increased by 20.6 and 75.0% of those samples at IDT=0s, respectively. The findings will facilitate the development of additive manufacturing processes for advanced Mg alloys.

Abstract Traditionally, the clinical evaluation of respiratory diseases was pulmonary function testing, which can be used for the detection of severity and prognosis through pulmonary function parameters. However, this method is limited by the complex process, which is impossible for patients to monitor daily. In order to evaluate pulmonary function parameters conveniently with less time and location restrictions, cough sound is the substitute parameter. In this paper, 371 cough sounds segments from 150 individuals were separated into 309 and 62 as the training and test samples. Short-time Fourier transform (STFT) was applied to transform cough sound into spectrogram, and ResNet50 model was used to extract 2048-dimensional features. Through support vector regression (SVR) model with biological attributes, the data were regressed with pulmonary function parameters, FEV1, FEV1%, FEV1/FVC, FVC, FVC%, and the performance of this models was evaluated with fivefold cross-validation. Combines with deep learning and machine learning technologies, the better results in the case of small samples were achieved. Using the coefficient of determination (R2), the ResNet50 + SVR model shows best performance in five basic pulmonary function parameters evaluation as FEV1(0.94), FEV1%(0.84), FEV1/FVC(0.68), FVC(0.92), and FVC%(0.72). This ResNet50 + SVR hybrid model shows excellent evaluation of pulmonary function parameters during coughing, making it possible to realize a simple and rapid evaluation for pneumonia patients. The technology implemented in this paper is beneficial in judge the patient's condition, realize early screening of respiratory diseases, evaluate postoperative disease changes and detect respiratory infectious diseases without time and location restrictions.

Wire arc additive manufacturing (WAAM) of Mg-RE (rare-earth)-Zn alloys is important for meeting the requirements of lightweight large-scale components with high manufacturing flexibility. The Mg-8.1Gd-2.6Y-0.7Zn-0.5Zr (GWZ831K, wt.%) alloys were fabricated through the use of WAAM technology, and the microstructure evolution along the building direction and corresponding mechanical properties were then studied. The as-built sample in this paper was composed of finely equiaxed ɑ-Mg grains, eutectic (Mg, Zn)3(Gd, Y) phase, cubic phase, and γʹ precipitates. Furthermore, due to the in-suit heat treatments that were induced by the multiple thermal cycles, more γʹ precipitates were observed in the middle region. The microstructures at different heights were characterized by alternatively distributed fine equiaxed grains (melt pool boundaries, MPB) and coarse equiaxed grains (melt pools, MP). The mechanical properties of the as-built component were found to exhibit yield strength (YS), ultimate tensile strength (UTS), and elongation (EL) of 159 ± 1.0 MPa, 237 ± 4.0 MPa, and 6.7 ± 0.4 % in the building direction (BD) and 163 ± 5.1 MPa, 242 ± 8.7 MPa, and 7.0 ± 0.7 % in the traveling direction (TD). This demonstrates that the WAAM-processed GWZ831K alloy has good isotropy.

The study investigated the effects of microencapsulated essential oils (MEO) on the growth performance, diarrhea, and intestinal microenvironment of weaned piglets. The 120 thirty-day-old weaned piglets (Duroc × Landrace × Yorkshire, 8.15 ± 0.07 kg) were randomly divided into four groups and were fed with a basal diet (CON) or CON diet containing 300 (L-MEO), 500 (M-MEO), and 700 (H-MEO) mg/kg MEO, respectively, and data related to performance were measured. The results revealed that MEO supplementation increased the ADG and ADFI in weaned piglets (p < 0.05) compared with CON, and reduced diarrhea rates in nursery pigs (p < 0.05). MEO supplementation significantly increased the duodenum’s V:C ratio and the jejunal villi height of weaned piglets (p < 0.05). The addition of MEO significantly increased the T-AOC activity in the jejunum of piglets (p < 0.05), but only L-MEO decreased the MDA concentration (p < 0.01). H-MEO group significantly increases the content of isobutyric acid (p < 0.05) in the piglet colon, but it does not affect the content of other acids. In addition, MEO supplementation improved appetite in the nursery and increased the diversity and abundance of beneficial bacteria in the intestinal microbiome. In conclusion, these findings indicated that MEO supplementation improves growth and intestinal health in weaned piglets.

This study investigated the simulated body fluid-assisted stress corrosion cracking (SCC) of an Al-free magnesium alloy (RS66) and a common Al-containing magnesium alloy (AZ91), the former being more suitable for temporary implant applications (however, we used AZ91 for comparison since there are considerable reports on SCC in this alloy). The investigation includes SCC tests under simultaneous conditions of mechanical loading and imposed electrochemical potential that established a combined effect of hydrogen and anodic dissolution as the embrittlement mechanism. Though the RS66 alloy possesses impressive mechanical properties in non-corrosive environments (as a result of its fine grain size), both alloys suffered significant embrittlement when tested in simulated body fluid. The susceptibility of the RS66 alloy to SCC was ~25% greater than that of AZ91, which is attributed to the greater resistance of AZ91 to corrosion/localised corrosion because of its Al content.

Background: The efficacy of acupuncture at Zusanli (ST36) in alleviating lower-limb pain is widely acknowledged in clinical practice, while its underlying mechanism remains incompletely elucidated. Our previous research had revealed that the prompt analgesia induced by needling-ST36 was accompanied by expression alterations in certain exco-nucleotidases within the sciatic nerve. Building upon this finding, the current work focused on NTPDase1, the primary ecto-nucleotidase in the human body, which converts ATP into AMP. Methods: A 20-min acupuncture was administered unilaterally at the ST36 on rats with acute ankle arthritis. The pain thresholds of the injured hind paws were determined. Pharmacological interference was carried out by introducing the corresponding reagents to the sciatic nerve. ATP levels around the excised nerve were measured using a luciferase-luciferin assay. Live calcium imaging, utilizing the Fura 2-related-F340/F380 ratio, was conducted on Schwann cells in excised nerves and cultured rat SCs line, RSC96 cells. Results: The analgesic effect induced by needling-ST36 was impaired when preventing ATP degradation via inhibiting NTPDase1 activities with ARL67156 or Ticlopidine. Conversely, increasing NTPDase1 activities with Apyrase duplicated the acupuncture effect. Similarly, preventing the conversion of AMP to adenosine via suppression of NT5E with AMP-CP hindered the acupuncture effect. Unexpectedly, impeded ATP hydrolysis ability and diminished NTPDase1 expression were observed in the treated group. Agonism at P2Y2Rs with ATP, UTP, or INS365 resulted in anti-nociception. Contrarily, antagonism at P2Y2Rs with Suramin or AR-C 118925xx prevented acupuncture analgesia. Immunofluorescent labeling demonstrated that the treated rats expressed more P2Y2Rs that were predominant in Schwann cells. Suppression of Schwann cells by inhibiting ErbB receptors also prevented acupuncture analgesia. Finally, living imaging on the excised nerves or RSC96 cells showed that agonism at P2Y2Rs indeed led to [Ca2+]i rise. Conclusion: These findings strongly suggest that the analgesic mechanism of needling-ST36 on the hypersensation in the lower limb partially relies on NTPDase1 activities in the sciatic nerve. In addition to facilitating adenosine signaling in conjunction with NT5E, most importantly, NTPDase1 may provide an appropriate low-level ATP milieu for the activation of P2Y2R in the sciatic nerve, particularly in Schwann cells.

Abstract Background Despite the growing interest in the impact of the gut microbiome on cancer, the relationship between the lung microbiome and lung cancer has received limited investigation. Additionally, the composition of the oral microbiome was found to differ from that of individuals with lung cancer, indicating that these microorganisms may serve as potential biomarkers for the detection of lung cancer. Methods Forty-three Chinese lung cancer patients were enrolled in the current retrospective study and 16 S rRNA sequencing was performed on saliva, cancerous tissue (CT) and paracancerous tissue (PT) samples. Results Diversity and species richness were significantly different between the oral and lung microbiota. Lung microbiota were largely composed of the phyla Proteobacteria, Firmicutes, Bacteroidetes and Actinobacteria. The relative abundance of Promicromonosporacea and Chloroflexi increased in CT, while Enterococcaceae and Enterococcus were enriched in PT (p

Chemosensory protein (CSP) genes significantly enriched in the female antennae are potential molecular candidates for mediating female oviposition behaviors. In this study, we presented the interaction mechanisms of a female-antenna-biased PxutCSP19 in Papilio xuthus to 47 host volatiles, four biopesticides and 24 synthetic insecticides. Using a bioinformatics-based homology search, 22 genes orthologous to PxutCSP19 were identified from 22 other Papilio butterflies with high sequence identities to each other (73.20~98.72%). Multiple alignment analyses revealed a particularly extended N-terminus of Papilio CSP19s (an average of 154 residues) compared to insects’ typical CSPs (approximately 120 residues). The expression profiles indicated that PxutCSP19 was significantly enriched in the female antennae, with a 31.81-fold difference relative to the male antennae. In ligand-binding assays, PxutCSP19 could strongly bind six host odorants with high affinities, ranging from dissociation constant (Ki) values of 20.44 ± 0.64 μM to 22.71 ± 0.73 μM. Notably, this protein was tuned to a monoterpenoid alcohol, linalool, which generally existed in the Rutaceae plants and elicited electrophysiological and behavioral activities of the swallowtail butterfly. On the other hand, PxutCSP19 was also capable of binding eight insecticides with stronger binding abilities (Ki < 12 μM) compared to host odorants. When an extended N-terminal region of PxutCSP19 was truncated into two different proteins, they did not significantly affect the binding of PxutCSP19 to ligands with high affinities, suggesting that this extended N-terminal sequences were not involved in the specificity of ligand recognition. Altogether, our study sheds light on the putative roles of PxutCSP19 enriched in the female antennae of P. xuthus in the perception of host volatiles and the sequestering of insecticides, and it complements the knowledge of butterfly CSPs in olfaction and insecticide resistance.

This research presents a new, eco-friendly, and swift method combining solid-phase extraction and hydrophobic deep eutectic solvents (DES) with high-performance liquid chromatography (SPE-DES-HPLC) for extracting and quantifying catechin and epicatechin in Shanxi aged vinegar (SAV). The parameters, such as the elution solvent type, the XAD-2 macroporous resin dosage, the DES ratio, the DES volume, the adsorption time, and the desorption time, were optimized via a one-way experiment. A central composite design using the Box–Behnken methodology was employed to investigate the effects of various factors, including 17 experimental runs and the construction of three-dimensional response surface plots to identify the optimal conditions. The results show that the optimal conditions were an HDES (tetraethylammonium chloride and octanoic acid) ratio of 1:3, an XAD-2 macroporous resin dosage of 188 mg, and an adsorption time of 11 min. Under these optimal conditions, the coefficients of determination of the method were greater than or equal to 0.9917, the precision was less than 5%, and the recoveries ranged from 98.8% to 118.8%. The environmentally friendly nature of the analytical process and sample preparation was assessed via the Analytical Eco-Scale and AGREE, demonstrating that this method is a practical and eco-friendly alternative to conventional determination techniques. In summary, this innovative approach offers a solid foundation for the assessment of flavanol compounds present in SAV samples.

Abstract This article describes a teaching strategy that synergizes computing and management, aimed at the running of complex projects in industry and academia, in the areas of civil engineering, physics, geosciences, and a number of other related fields. The course derived from this strategy includes four parts: (a) Computing with a selected set of modern paradigms—the stress is on Control Flow and Data Flow computing paradigms, but paradigms conditionally referred to as Energy Flow and Diffusion Flow are also covered; (b) Project management that is holistic—the stress is on the wide plethora of issues spanning from the preparation of project proposals, all the way to incorporation activities to follow after the completion of a successful project; (c) Examples from past research and development experiences—the stress is on experiences of leading experts from academia and industry; (d) Student projects that stimulate creativity—the stress is on methods that educators could use to induce and accelerate the creativity of students in general. Finally, the article ends with selected pearls of wisdom that could be treated as suggestions for further elaboration.

IntroductionInfectious diseases are major causes of morbidity and mortality worldwide, necessitating the rapid identification and accurate diagnosis of pathogens. While unbiased metagenomic next-generation sequencing (mNGS) has been extensively utilized in clinical pathogen identification and scientific microbiome detection, there is limited research about the application of nanopore platform-based mNGS in the diagnostic performance of various infectious fluid samples.MethodsIn this study, we collected 297 suspected infectious fluids from 10 clinical centers and detected them with conventional microbiology culture and nanopore platform–based mNGS. The objective was to assess detective and diagnostic performance of nanopore-sequencing technology (NST) in real-world scenarios.ResultsCombined with gold-standard culture and clinical adjudication, nanopore sequencing demonstrated nearly 100% positive predictive agreements in microbial-colonized sites, such as the respiratory and urinary tracts. For samples collected from initially sterile body sites, the detected microorganisms were highly suspected pathogens, and the negative predictive agreements were relatively higher than those in the microbial-colonized sites, particularly with 100% in abscess and 95.7% in cerebrospinal fluid. Furthermore, consistent performance was also observed in the identification of antimicrobial resistance genes and drug susceptibility testing of pathogenic strains of Escherichia coli, Staphylococcus aureus, and Acinetobacter baumannii.DiscussionRapid NST is a promising clinical tool to supplement gold-standard culture, and it has the potential improve patient prognosis and facilitate clinical treatment of infectious diseases.

Objective: Post-traumatic stress disorder (PTSD) is a neuropsychiatric disorder that can develop after experiencing or witnessing a traumatic event. Exposure therapy is a common treatment for PTSD, but it has varying levels of efficacy depending on sex. In this study, we aimed to compare the sexual dimorphism in brain activation during the extinction of fear conditioning in male and female rats by detecting the c-fos levels in the whole brain. Methods: Thirty-two rats (Male: n = 16; Female: n = 16) were randomly separated into the extinction group as well as the non-extinction group, and fear conditioning was followed by extinction and non-extinction, respectively. Subsequently, brain sections from the sacrificed animal were performed immunofluorescence and the collected data were analyzed by repeated two-way ANOVAs as well as Pearson Correlation Coefficient. Results: Our findings showed that most brain areas activated during extinction were similar in both male and female rats, except for the reuniens thalamic nucleus and ventral hippocampi. Furthermore, we found differences in the correlation between c-fos activation levels and freezing behavior during extinction between male and female rats. Specifically, in male rats, c-fos activation in the anterior cingulate cortex was negatively correlated with the freezing level, while c-fos activation in the retrosplenial granular cortex was positively correlated with the freezing level; but in female rats did not exhibit any correlation between c-fos activation and freezing level. Finally, the functional connectivity analysis revealed differences in the neural networks involved in extinction learning between male and female rats. In male rats, the infralimbic cortex and insular cortex, anterior cingulate cortex and retrosplenial granular cortex, and dorsal dentate gyrus and dCA3 were strongly correlated after extinction. In female rats, prelimbic cortex and basolateral amygdala, insular cortex and dCA3, and anterior cingulate cortex and dCA1 were significantly correlated. Conclusion: These results suggest divergent neural networks involved in extinction learning in male and female rats and provide a clue for improving the clinical treatment of exposure therapy based on the sexual difference.

ABSTRACT: The dysbiosis of lung microbiota and inflammatory factors play a crucial role in the occurrence of lipopolysaccharides (LPS)-induced lung injury. Recently, mogroside V (MGV) has received increasing attention due to its potential health benefits in pneumonia, but its complex mechanism needs further experimental elucidation. In this study, we established an LPS-induced chicken lung injury model to investigate the protective effect of MGV on LPS-induced acute lung injury in broiler and its related mechanisms. A total of 192 one-day-old white-finned broilers were randomly assigned into 4 groups with 6 replicates: 1) control group: basal diet (d 1–44), saline (d 43); 2) LPS group: basal diet (d 1–44), LPS (d 43); 3) MGV group: basal diet + 0.2% MGV (d 1–44), saline (d 43); 4) MGV-LPS group: basal diet + 0.2% MGV (d 1–44), LPS (d 43). The results showed that pathological examination showed that lung tissue inflammation infiltration was reduced after MGV treatment. In addition, MGV can promote the balance of Th17 and Treg cell cytokines, significantly inhibit the expression of proinflammatory cytokines (IL-1β (P < 0.01), IL-6 (P < 0.001), IL-17F (P < 0.05)), and decrease immunosuppressive target expression (PD-L1 (P < 0.01), PD-1 (P < 0.001), RORα (P < 0.001)), activating the immune system. Furthermore, 16S rRNA sequencing analysis showed that MGV treatment could increase the abundance of beneficial bacteria in the lung and reduce the abundance of bacteria associated with inflammation. Generally, MGV intervention has a preventive effect on the pathological damage induced by lipopolysaccharides. Its mechanism is related to inhibiting the inflammatory response, regulating the Th17/Treg balance, and maintaining the stability of lung microbiota.

A detailed and systematic investigation on the effect post heat treatment has on the microstructure evolution and the resultant mechanical properties of the wire arc additive manufacturing processed Mg-5.9Gd-2.8Y-0.7Zr alloy is conducted in this work. The microstructure of the as-built sample is composed mainly of fine equiaxed α-Mg grain and Mg24(Gd, Y)5 phase. The solution heat treatment (400°C × 1 h) has relatively little effect on grain size, but it can effectively reduce the content of the Mg24(Gd, Y)5 phase, which leads to a significantly improved elongation with slightly decreased strength. Further ageing heat treatment at 200°C induces prismatic βʹ precipitates formation and does not influence other phases and grain size. The samples directly following the peak ageing heat treatment process demonstrate the best tensile properties with yield strength of 227 ± 9 MPa, ultimate tensile strength of 350 ± 4 MPa and elongation of 5.5 ± 0.6%.

Background: Close contacts infected with Mycobacterium tuberculosis are at high risk of tuberculosis (TB) disease and a priority for preventive treatment. Three tests measure infection: two interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST). The objective of our study was to assess the association of positive test results in contacts with infectiousness of the presumed TB source case. Methods: Contacts in a cohort study at 10 United States sites received both IGRAs (QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB (T-SPOT)) and TST. We defined test conversion as negative for all tests at baseline and positive for at least one on retest. Risk ratios (RR) and 95% confidence intervals (CI) assessed association of positive test results with increased infectiousness of the TB case—defined as acid-fast bacilli (AFB) on sputum microscopy or cavities on chest radiographs— and contact demographics. Results: Adjusted for contacts’ age, nativity, sex, and race, IGRAs (QFT-GIT RR = 6.1, 95% CI 1.7–22.2; T-SPOT RR = 9.4, 95% CI 1.1–79.1), but not TST (RR = 1.7, 95% CI 0.8–3.7), were more likely to convert among contacts exposed to persons with cavitary TB disease. Conclusions: Because IGRA conversions in contacts are associated with infectiousness of the TB case, their use may improve efficiency of health department contact investigations by focusing efforts on those likely to benefit from preventive treatment in the United States.

ObjectivesLung adenocarcinoma (LUAD) is the most common newly diagnosed malignant tumor in older people. As older patients age, organ function decreases, leading to increased adverse reactions to treatment. The epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase tyrosine (ALK) tyrosine kinase inhibitors (TKIs) therapy are more effective and well-tolerated than chemotherapy, while the rate of genetic testing and subsequent targeted treatment among older patients remains relatively low, the clinical benefit limitation for those patients. This study aims to investigate the mutation characteristics of LUAD diver gene and its relationship with clinicopathological features in older LUAD.Materials and methodsA total of 275 patients were diagnosed as LUAD and were over sixty years old. We utilized next-generation sequencing technology to detect and analyze gene mutations in postoperative tissue specimens, including EGFR, KRAS, ALK, ROS1, RET, MET, BRAF, HER2, PIK3CA and NRAS.ResultsA total of 90.18% (248/275) of older LUAD patients experienced genetic mutations. The EGFR (192, 69.82%) had the highest mutation rate among ten genes, followed by KRAS (21, 7.64%), MET (21, 7.64%), ERBB2 (15, 5.45%), RET (9, 3.27%), ALK (8, 2.91%), ROS1 (8, 2.91%), PIK3CA (6, 2.18%), BRAF (5, 1.82%) and NRAS (1, 0.36%). We also found thirty patients (15.63%) with EGFR mutations also having other gene mutations. The L858R mutation and exon19 deletion were the predominant EGFR mutations, accounting for 84.90% of EGFR-mutated patients. In addition, fifty-one kinds of EGFR mutations were detected, distributed in the protein tyrosine kinase catalytic domain (43, 84.31%), cysteine enriched domain (4, 7.84%), receptor binding domain (3, 5.88%), and EGFR transmembrane domain (1,1.96%). Ten cases of gene fusion mutation were detected. Two rare partner genes, PKHD1 (P60:R34) and STK39 (R33:S11), were detected by ROS1 gene fusion. RET gene fusion revealed a rare companion gene KCND2 (R11:K2). The EGFR mutations were more prevalent in female, non-smoking patients (p < 0.05), and the KRAS mutations were more common in male and smoking patients (p < 0.01). In addition, the BRAF mutations were more likely to occur in the right lung (p < 0.05).ConclusionOlder LUAD populations exhibit diverse genetic mutations, which may also exist simultaneously. Simultaneous detection of multiple genes by NGS can accelerate and enhance targeted treatment benefits for older LUAD patients, ultimately improving their quality of life.

Abstract The commercialization of atomic technologies requires replacing laboratory-scale laser setups with compact and manufacturable optical platforms. Complex arrangements of free-space beams can be generated on chip through a combination of integrated photonics and metasurface optics. In this work, we combine these two technologies using flip-chip bonding and demonstrate an integrated optical architecture for realizing a compact strontium atomic clock. Our planar design includes twelve beams in two co-aligned magneto-optical traps. These beams are directed above the chip to intersect at a central location with diameters as large as 1 cm. Our design also includes two co-propagating beams at lattice and clock wavelengths. These beams emit collinearly and vertically to probe the center of the magneto-optical trap, where they will have diameters of ≈100 µm. With these devices we demonstrate that our integrated photonic platform is scalable to an arbitrary number of beams, each with different wavelengths, geometries, and polarizations.

Abstract Acute myeloid leukemia (AML) is a deadly hematological malignancy. Cellular morphology detection of bone marrow smears based on the French–American–British (FAB) classification system remains an essential criterion in the diagnosis of hematological malignancies. However, the diagnosis and discrimination of distinct FAB subtypes of AML obtained from bone marrow smear images are tedious and time-consuming. In addition, there is considerable variation within and among pathologists, particularly in rural areas, where pathologists may not have relevant expertise. Here, we established a comprehensive database encompassing 8245 bone marrow smear images from 651 patients based on a retrospective dual-center study between 2010 and 2021 for the purpose of training and testing. Furthermore, we developed AMLnet, a deep-learning pipeline based on bone marrow smear images, that can discriminate not only between AML patients and healthy individuals but also accurately identify various AML subtypes. AMLnet achieved an AUC of 0.885 at the image level and 0.921 at the patient level in distinguishing nine AML subtypes on the test dataset. Furthermore, AMLnet outperformed junior human experts and was comparable to senior experts on the test dataset at the patient level. Finally, we provided an interactive demo website to visualize the saliency maps and the results of AMLnet for aiding pathologists’ diagnosis. Collectively, AMLnet has the potential to serve as a fast prescreening and decision support tool for cytomorphological pathologists, especially in areas where pathologists are overburdened by medical demands as well as in rural areas where medical resources are scarce.

IntroductionThyroidectomy and thyrotropin suppressive therapy is the widely used surgical treatment for papillary thyroid carcinoma (PTC) patients. However, systematic metabolic changes of post-operative PTC patients were rarely reported.MethodsHere, untargeted metabolomic detection of cohorts from PTC before (t0) and 1-month-after (t1) thyroidectomy, were performed to characterize circulating metabolic signatures after surgical treatment.ResultsOur results showed PTC patients exhibited lower thyroid stimulating hormone degree, higher total thyroxine, and significant lipid-related metabolic alternations after thyroidectomy, which included 97 upregulations (including 93 lipids) and 5 downregulations (including 2 lipids and 3 nucleotides). Enrichment of metabolic pathways mainly included biosynthesis of fatty acids, purine metabolism, and linoleic acid metabolism. We also demonstrated that differential surgical approaches (hemi- and total thyroidectomy) and post-operative complication phenotypes (insomnia, fatigue), might lead to characteristic metabolic signatures.DiscussionThis study revealed dynamic changes of metabolite characteristics of PTC patients after surgical treatment, which were associated with clinical thyroid function parameters, surgical approaches, and complication occurrence. It enlightened us to pay more attention on the post-operative metabolic dysregulation of PTC patients and their long-term qualities of life, so as to provide cautious clinical decisions on surgical choices, treatments, and follow-up details.

ABSTRACT: Respiratory health problems in poultry production are frequent and knotty and thus attract the attention of farmers and researchers. The breakthrough of gene sequencing technology has revealed that healthy lungs harbor rich microbiota, whose succession and homeostasis are closely related to lung health status, suggesting a new idea to explore the mechanism of lung injury in broilers with pulmonary microbiota as the entry point. This study aimed to investigate the succession of pulmonary microbiota in healthy broilers during the growth cycle. Fixed and molecular samples were collected from the lungs of healthy broilers at 1, 3, 14, 21, 28, and 42 d of age. Lung tissue morphology was observed by hematoxylin and eosin staining, and the changes in the composition and diversity of pulmonary microbiota were analyzed using 16S rRNA gene sequencing. The results showed that lung index peaked at 3 d, then decreased with age. No significant change was observed in the α diversity of pulmonary microbiota, while the β diversity changed regularly with age during the broilers’ growth cycle. The relative abundance of dominant bacteria of Firmicutes and their subordinate Lactobacillus increased with age, while the abundance of Proteobacteria decreased with age. The correlation analysis between the abundance of differential bacteria and predicted function showed that dominant bacteria of Firmicutes, Proteobacteria and Lactobacillus were significantly correlated with most functional abundance, indicating that they may involve in lung functional development and physiological activities of broilers. Collectively, these findings suggest that the lung has been colonized with abundant microbiota in broilers when they were just hatched, and their composition changed regularly with day age. The dominant bacteria, Firmicutes, Proteobacteria, and Lactobacillus, play crucial roles in lung function development and physiological activities. It paves the way for further research on the mechanism of pulmonary microbiota-mediated lung injury in broilers.

The experience of traumatic stress can engender lasting memories associated with the trauma, often resulting in post-traumatic stress disorder (PTSD). However, only a minority of individuals develop PTSD symptoms upon exposure. The neurobiological mechanisms underlying the pathology of PTSD are poorly understood. Utilizing a rat model of PTSD, the Single Prolonged Stress (SPS) paradigm, we were able to differentiate between resilient and susceptible individuals. Fourteen days after the SPS exposure, we conducted the behavioral analyses using Elevated Plus Maze (EPM) and Open Field (OF) tests to identify male rats as trauma resilient or susceptible. We focused on the microRNA (miRNA) profiles of the infralimbic (IL) and prelimbic (PL) cortical regions, known to be crucial in regulating the stress response. Our investigation of stressed rats exposed to the SPS procedure yielded divergent response, and differential expression microRNAs (DEmiRs) analysis indicated significant differences in the IL and PL transcriptional response. In the IL cortex, the GO analysis revealed enriched GO terms in the resilient versus control comparison, specifically related to mitogen-activated protein kinase and MAP kinase signaling pathways for their molecular functions as well as cytosol and nucleoplasm for the biological process. In the susceptible versus resilient comparison, the changes in molecular functions were only manifested in the functions of regulation of transcription involved in the G1/S transition of the mitotic cell cycle and skeletal muscle satellite cell activation. However, no enriched GO terms were found in the susceptible versus control comparison. In the PL cortex, results indicated that the DEmiRs were enriched exclusively in the cellular component level of the endoplasmic reticulum lumen in the comparison between resilient and control rats. Overall, our study utilized an animal model of PTSD to investigate the potential correlation between stress-induced behavioral dysfunction and variations in miRNA expression. The aforementioned discoveries have the potential to pave the way for novel therapeutic approaches for PTSD, which could involve the targeted regulation of transcriptome expression.

This study aimed to investigate whether dietary fiber pectin can alleviate PM2.5-induced pulmonary inflammation and the potential mechanism. PM2.5 samples were collected from a nursery pig house. The mice were divided into three groups: the control group, PM2.5 group and PM2.5 + pectin group. The mice in the PM2.5 group were intratracheally instilled with PM2.5 suspension twice a week for four consecutive weeks, and those in the PM2.5 + pectin group were subject to the same PM2.5 exposure, but fed with a basal diet supplemented with 5% pectin. The results showed that body weight and feed intake were not different among the treatments (p > 0.05). However, supplementation with pectin relieved PM2.5-induced pulmonary inflammation, presenting as slightly restored lung morphology, decreased mRNA expression levels of IL-1β, IL-6 and IL-17 in the lung, decreased MPO content in bronchoalveolar lavage fluid (BLAF), and even decreased protein levels of IL-1β and IL-6 in the serum (p

Abstract Purpose Corneal collagen crosslinking (CXL) is an effective treatment for progressive keratoconus. Multiple CXL modalities are clinically available. The present study compared the 1 year outcomes of five types of CXL procedures for progressive keratoconus in a Chinese population using generalized estimating equations (GEE). Methods This retrospective study included 239 eyes in 171 patients with keratoconus who underwent CXL and were followed up for 1 year. Five CXL procedures were assessed, including Accelerated Transepithelial CXL, Iontophoresis CXL for 10 min, CXL plus phototherapeutic keratectomy (CXL-plus-PTK), High-Fluence Accelerated CXL, and Accelerated CXL. Patients treated with the Accelerated CXL procedure represented the reference group. Primary outcomes were visual acuity change, spherical equivalence, endothelial cell density, mean keratometry (Kmean), maximum keratometry (Kmax), minimum corneal thickness (MCT), and the ABCD Grading System, consisting of A (staging index for ARC; ARC = anterior radius of curvature), B (staging index for PRC, PRC = posterior radius of curvature), and C (staging index for MCT) values 1 year postoperatively compared to baseline. Secondary outcomes were corrected GEE comparisons from each procedure versus the Accelerated CXL group. Results The Accelerated Transepithelial CXL group had lower performance than the Accelerated CXL group according to Kmean and Kmax. The CXL-plus-PTK group performed significantly better than the reference group as reflected by Kmax (β = -0.935, P = 0.03). However, the CXL-plus-PTK group did not perform as well for B and C, and the Iontophoresis CXL group performed better for C. Conclusions The CXL-plus-PTK procedure was more effective than the Accelerated CXL procedure based on Kmax, and the Iontophoresis CXL procedure performed better on the C value based on the ABCD Grading System.

Objective To evaluate the necessity and rationality of setting 0.7 CO of the gray area of HBV surface antigen reagent (ELISA) in our laboratory, and to provide the basis for the grey area setting. Methods A total of 60 samples of serum plate were repeatability tested by two kinds of ELISA HBsAg reagents. Based on the test results, C50, C5, C95 concentrations and corresponding S / CO values were calculated, and whether C5 and C95 were within C50±20% was verified. At the same time, the true positive rate and the confirmed positive rate of gray area samples revealed by two reagents were calculated. Results The confirmation results of serum plate were as follows: The C50, C5 and C95 concentrations of reagent A were 0.090 IU/mL, 0.075 IU/mL, 0.105 IU/mL. The true positive rate was 99.1%(436/440), the confirmed positive rate of grey area was37.8%(136/360). The C50, C5 and C95 concentrations of reagent B were 0.112 IU/mL, 0.091 IU/mL, and 0.133 IU/mL; the true positive detection rate was 97.1%(233/240); the confirmed positive rate of grey area was 35.8%(129/360). It was verified that C5 and C95 of reagent A and reagent B were within their respective C50±20%, and the gray areas of the HBsAg ELISA were verified to be effective. Conclusion It is necessary to set the gray area for these two HBsAg ELISA reagents in our laboratory, but the gray area value setting to 0.7 CO is unreasonable. The best gray area value was 0.75 CO in reagent A and 0.63 CO in reagent B.

Abstract Background At present, the role of inactivated vaccines in viral RNA shedding among Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) breakthrough infections is still unknown. Methods We collected data of 147 coronavirus disease 2019 (COVID-19) patients with mild-to-moderate illness who were hospitalized in the Third People’s Hospital of Yangzhou from 7 to 20 August 2021 and analyzed the differences in symptoms and laboratory tests among fully vaccinated (FV), partially vaccinated (PV) and unvaccinated (UV) patients. Results The median duration of viral RNA shedding was shorter in the FV (12 [IQR, 9.5–14] days) and PV (13 [IQR, 9–16.75] days) groups than in the UV group (15 [IQR, 11.75–17.25] days) (adjusted P

PurposeTo explore and validate the utility of machine learning (ML) methods using a limited sample size to predict changes in visual acuity and keratometry 2 years following corneal crosslinking (CXL) for progressive keratoconus.MethodsThe study included all consecutive patients with progressive keratoconus who underwent CXL from July 2014 to December 2020, with a 2 year follow-up period before July 2022 to develop the model. Variables collected included patient demographics, visual acuity, spherical equivalence, and Pentacam parameters. Available case data were divided into training and testing data sets. Three ML models were evaluated based on their performance in predicting case corrected distance visual acuity (CDVA) and maximum keratometry (Kmax) changes compared to actual values, as indicated by average root mean squared error (RMSE) and R-squared (R2) values. Patients followed from July 2022 to December 2022 were included in the validation set.ResultsA total of 277 eyes from 195 patients were included in training and testing sets and 43 eyes from 35 patients were included in the validation set. The baseline CDVA (26.7%) and the ratio of steep keratometry to flat keratometry (K2/K1; 13.8%) were closely associated with case CDVA changes. The baseline ratio of Kmax to mean keratometry (Kmax/Kmean; 20.9%) was closely associated with case Kmax changes. Using these metrics, the best-performing ML model was XGBoost, which produced predicted values closest to the actual values for both CDVA and Kmax changes in testing set (R2 = 0.9993 and 0.9888) and validation set (R2 = 0.8956 and 0.8382).ConclusionApplication of a ML approach using XGBoost, and incorporation of identifiable parameters, considerably improved variation prediction accuracy of both CDVA and Kmax 2 years after CXL for treatment of progressive keratoconus.

ObjectiveThis study aims to investigate the correlation between sleep duration and all-cause and cardiovascular mortality in the general population.MethodsA total of 26,977 participants aged ≥18 years were included in the analysis from the National Health and Nutrition Examination Survey (NHANES) database covering the period from 2005 to 2014. Data on cardiovascular and all-cause deaths were collected until December 2019. Sleep duration was assessed using a structured questionnaire, and participants were categorized into five groups based on their reported sleep duration (≤5, 6, 7, 8, or ≥9 h). Kaplan-Meier survival curves were employed to examine the mortality rates across different sleep duration groups. Multivariate Cox regression models were utilized to explore the association between sleep duration and mortality. Additionally, a restricted cubic spline regression model was employed to identify the non-linear relationship between sleep duration and all-cause and cardiovascular mortality.ResultsThe average age of participants was 46.23 ± 18.48 years, with 49.9% of the subjects being male. Over a median follow-up period of 9.42 years, 3,153 (11.7%) participants died from all-cause mortality, among which 819 (3.0%) were attributed to cardiovascular causes. The groups with sleep durations of ≥9 and ≤5 h exhibited the lowest cumulative survival rates for all-cause mortality and cardiovascular mortality, respectively. When using a sleep duration of 7 h as the reference, the hazard ratios (with 95% confidence intervals) for all-cause mortality were 1.28 (1.14–1.44) for ≤5 h, 1.10 (0.98–1.23) for 6 h, 1.21 (1.10–1.34) for 8 h, and 1.53 (1.35–1.73) for ≥9 h. The hazard ratios (with 95% confidence intervals) for cardiovascular mortality were 1.32 (1.04–1.67) for ≤5 h, 1.22 (0.97–1.53) for 6 h, 1.29 (1.05–1.59) for 8 h, and 1.74 (1.37–2.21) for ≥9 h. A U-shaped non-linear relationship between sleep duration and all-cause and cardiovascular mortality was observed, with inflection point thresholds at 7.32 and 7.04 h, respectively.ConclusionThe findings suggest that the risk of all-cause and cardiovascular mortality is minimized when sleep duration is approximately 7 h.

IntroductionRoot-knot nematode disease is one of the world's most serious vegetable crop diseases. In recent years, Trichoderma spp. has been widely used in root-knot nematode disease control as a biological control agent.MethodsVirulent and attenuated strains of Trichoderma citrinoviride mediated resistance and biological control mechanism in tomato were determined.ResultsPreliminary experiments found differences in nematicidal virulence among Trichoderma citrinoviride. The 24-hour corrected mortality rate of the virulent strainT1910 was as high as 92.37%, with an LC50 of 0.5585 against the second juveniles (J2s) of Meloidogyne incognita. And the attenuated strain TC9 was 23.01%, the LC50 was 2.0615, so the virulent strain T1910 had a more substantial effect on the J2s than the attenuated strain. We found that the strong virulent strain T1910 have a good control effect on M. incognita by the pot experiment of tomato than that of the attenuated virulent strain TC9,especially the J2 and J4 numbers were inhibited inside the root knots of tomato. Theinhibition rates of virulent strains reached 85.22% and 76.91%, followed by attenuatedstrain TC9, which were 63.16% and 59.17%, respectively. To reveal the differences intomato defense pathways induced by different virulent strains, qRT-PCR was further usedto detect changes in the expression of inducement-related genes. The results showed thatthe TC9 was significantly upregulated at 5dpi, LOX1, PR1, and PDF1.2. The PR5 gene ofthe virulent strain T1910 was highly upregulated, and the JA pathway was activated laterbut weaker than the attenuated strain. The results of this study revealed that thebiocontrol mechanism of T. citrinoviride as poison killing through the virulent strain T1910 and induced resistance to M. incognita through attenuated strain, although virulence degradation also has an induced resistance effect. Moreover, the attenuated strain TC9 stimulated tomato immune response earlier than the virulent strain by nematode-associated molecular pattern-triggered (NAMP).DiscussionTherefore, the research elucidated the mechanism of multiple control of Trichoderma spp. against M. incognita.

Customized heat treatment is essential for enhancing the mechanical properties of additively manufactured metallic materials, especially for alloys with complex phase constituents and heterogenous microstructure. However, the interrelated evolutions of different microstructure features make it difficult to establish optimal heat treatment processes. Herein, we proposed a method for customized heat treatment process exploration and establishment to overcome this challenge for such kind of alloys, and a wire arc additively manufactured (WAAM) Mg-Gd-Y-Zn-Zr alloy with layered heterostructure was used for feasibility verification. Through this method, the optimal microstructures (fine grain, controllable amount of long period stacking ordered (LPSO) structure and nano-scale β ′ precipitates) and the corresponding customized heat treatment processes (520 °C/30 min + 200 °C/48 h) were obtained to achieve a good combination of a high strength of 364 MPa and a considerable elongation of 6.2%, which surpassed those of other state-of-the-art WAAM-processed Mg alloys. Furthermore, we evidenced that the favorable effect of the undeformed LPSO structures on the mechanical properties was emphasized only when the nano-scale β ′ precipitates were present. It is believed that the findings promote the application of magnesium alloy workpieces and help to establish customized heat treatment processes for additively manufactured materials.

Rice bran is a kind of agricultural by-product, which is rich in renewable organic carbon sources and mainly used in feed and fertilizer production today. It has been reported that rice bran is rich in various active ingredients such as dietary fiber, polyphenols and polysaccharides, which have significant physiological activities such as anti-oxidation, lowering blood lipid and blood sugar. This paper starts with the bioactive components of rice bran, analyzes its the functional properties of rice bran and its active components in anti-oxidation, hypoglycemia, anti-obesity, hypolipidemic, immunomodulating, antitumor, etc, in order to improve the application value of the bioactive components of rice bran and provide theoretical basis for the effective utilization and industrialization of the following agricultural by-products.

Abstract Background Aberrant alternative splicing (AS) contributes to tumor progression. Previous studies have shown that apurinic-apyrimidinic endonuclease-1 (APEX1) is involved in tumor progression. It is unknown whether APEX1 functions in tumor progression by regulation of AS. It is also unknown whether APEX1 can regulate non-small-cell lung cancer (NSCLC) proliferation and apoptosis. We analyzed APEX1 expression levels in 517 lung NSCLC samples from the TCGA (Cancer Genome Atlas) database. The impact of APEX1 over expression on A549 cell proliferation and apoptosis was detected by the methyl thiazolyl tetrazolium assay and by flow cytometry. The transcriptome of A549 cells with and without APEX1 over expression was determined by Illumina sequencing, followed by analysis of AS. RT-qPCR validated expression of APEX1-related genes in A549 cells. We have successfully applied RNA-seq technology to demonstrate APEX1 regulation of AS. Results APEX1 expression was shown to be upregulated in NSCLC samples and to reduce cell proliferation and induce apoptosis of A549 cells. In addition, APEX1 regulated AS of key tumorigenesis genes involved in cancer proliferation and apoptosis within MAPK and Wnt signaling pathways. Each of these pathways are involved in lung cancer progression. Furthermore, validated AS events regulated by APEX1 were in key tumorigenesis genes; AXIN1 (axis inhibition protein 1), GCNT2 (N-acetyl glucosaminyl transferase 2), and SMAD3 (SMAD Family Member 3). These genes encode signaling pathway transcription regulatory factors. Conclusions We found that increased expression of APEX1 was an independent prognostic factor related to NSCLC progression. Therefore, APEX1 regulation of AS may serve as a molecular marker or therapeutic target for NSCLC treatment.