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Abstract Objectives To develop radiomics models based on multi-sequence MRI from two centers for the preoperative prediction of the WHO/ISUP grade of Clear Cell Renal Cell Carcinoma (ccRCC). Methods This retrospective study included 334 ccRCC patients from two centers. Significant clinical factors were identified through univariate and multivariate analyses. MRI sequences included Dynamic contrast-enhanced MRI, axial fat-suppressed T2-weighted imaging, diffusion-weighted imaging, and in-phase/out-of-phase images. Feature selection methods and logistic regression (LR) were used to construct clinical and radiomics models, and a combined model was developed using the Rad-score and significant clinical factors. Additionally, seven classifiers were used to construct the combined model and different folds LR was used to construct the combined model to evaluate its performance. Models were evaluated using receiver operating characteristic (ROC) curves, area under the curve (AUC), and decision curve analysis (DCA). The Delong test compared ROC performance, with p

Abstract Alkenyl sulfides have gained increasing prominence in medicinal chemistry and materials. Hydrothiolation of alkynes for the diverse synthesis of alkenyl sulfides is an appealing method. Herein, we report a cobalt-catalyzed Markovnikov hydromethylthiolation of alkynes to afford branched alkenyl methylsulfanes with good yields and high regioselectivity. This method also enables the diverse synthesis of branched alkenyl sulfides. The reaction shows good functional group tolerance and could be scaled up. The mechanistic studies including control experiments, deuterium-labeling experiments, and Hammett plot indicated alkynes insertion followed by electrophilic thiolation pathway.

Abstract Objective High‐risk types of diffuse gliomas in adults include isocitrate dehydrogenase (IDH) wild‐type glioblastomas and grade 4 astrocytomas. Achieving noninvasive prediction of high‐risk molecular subtypes of gliomas is important for personalized and precise diagnosis and treatment. Methods We retrospectively collected data from 116 patients diagnosed with adult diffuse gliomas. Multiple high‐risk molecular markers were tested, and various habitat models and whole‐tumor models were constructed based on preoperative routine and diffusion kurtosis imaging (DKI) sequences to predict high‐risk molecular subtypes of gliomas. Feature selection and model construction utilized Least absolute shrinkage and selection operator (LASSO) and support vector machine (SVM). Finally, the Wilcoxon rank‐sum test was employed to explore the correlation between habitat quantitative features (intra‐tumor heterogeneity score，ITH score) and heterogeneity, as well as high‐risk molecular subtypes. Results The results showed that the habitat analysis model based on DKI performed remarkably well (with AUC values reaching 0.977 and 0.902 in the training and test sets, respectively). The model's performance was further enhanced when combined with clinical variables. (The AUC values were 0.994 and 0.920, respectively.) Additionally, we found a close correlation between ITH score and heterogeneity, with statistically significant differences observed between high‐risk and non‐high‐risk molecular subtypes. Interpretation The habitat model based on DKI is an ideal means for preoperatively predicting high‐risk molecular subtypes of gliomas, holding significant value for noninvasively alerting malignant gliomas and those with malignant transformation potential.

Abstract Objectives The present study aimed to investigate the relationship between male hormones and metabolic dysfunction-associated fatty liver disease (MAFLD) in males. Methods Data from the Fangchenggang Area Male Health and Examination Survey (FAMHES) were used to analyze the male hormone levels between MAFLD patients and controls. Univariate and multivariate logistic regression analyses were performed to identify risk factors for MAFLD. Receiver operating characteristic curve analysis was used to assess the diagnostic performance of male hormones for MAFLD. Result A total of 1578 individuals were included, with 482 individuals (30.54%) of MAFLD, including 293 (18.57%) with mild disease and 189 (11.98%) with moderate-to-severe disease. The MAFLD patients were significantly older than those without MAFLD. The LH, FSH, and SHBG levels in the MAFLD patients were significantly greater than those in the control group. Age, FSH, LH, SHBG, and estradiol were all risk factors for MAFLD. Age, FSH, and LH were risk factors for moderate-to-severe MAFLD. FSH was an independent risk factor for MAFLD and moderate-to-severe MAFLD. FSH showed an excellent diagnostic value, with an AUC of 0.992 alone and 0.996 after adjusting age. Conclusions Our findings indicate that FSH may be a potential diagnostic and predictive biomarker for MAFLD.

Abstract Background Nasopharyngeal carcinoma (NPC) is a type of malignant tumor with high morbidity. Aberrant levels of N7-methylguanosine (m7G) are closely associated with tumor progression. However, the characteristics of the tumor microenvironment (TME) in NPC associated with m7G modification remain unclear. Methods A total of 68,795 single cells from single-cell RNA sequencing data derived from 11 NPC tumor samples and 3 nasopharyngeal lymphatic hyperplasia (NLH) samples were clustered using a nonnegative matrix factorization algorithm according to 61 m7G RNA modification regulators. Results The m7G regulators were found differential expression in the TME cells of NPC, and most m7G-related immune cell clusters in NPC tissues had a higher abundance compared to non-NPC tissues. Specifically, m7G scores in the CD4+ and CD8+ T cell clusters were significantly lower in NPC than in NLH. T cell clusters differentially expressed immune co-stimulators and co-inhibitors. Macrophage clusters differentially expressed EIF4A1, and high EIF4A1 expression was associated with poor survival in patients with head and neck squamous carcinoma. EIF4A1 was upregulated in NPC tissues compared to the non-NPC tissues and mainly expressed in CD86+ macrophages. Moreover, B cell clusters exhibited tumor biological characteristics under the regulation of m7G-related genes in NPC. The fibroblast clusters interacted with the above immune cell clusters and enriched tumor biological pathways, such as FGER2 signaling pathway. Importantly, there were correlations and interactions through various ligand-receptor links among epithelial cells and m7G-related TME cell clusters. Conclusion Our study revealed tumor-associated characteristics and immune dysregulation in the NPC microenvironment under the regulation of m7G-related TME cells. These results demonstrated the underlying regulatory roles of m7G in NPC.

Ecosystems are vulnerable to accelerated climate change, population pressure, and urbanization, so ecological vulnerability assessments and impact analyses are essential if regional development is to be managed sustainably. This study develops a novel assessment framework based on resilience-sensitivity. Various techniques—including the landscape index, the ecological elasticity limit model, and the soil erosion equation—are incorporated to examine spatiotemporal variation characteristics across diverse ecological systems of China’s Jiangsu province through the decade 2010–2020, to reveal mechanisms by which various factors influence vulnerability. We arrived at a stable average yearly ecological vulnerability index value of 0.56–0.57, and found high vulnerability concentrated in cities and townships, areas along the Yangtze River, and the province’s northern coast. Results also show that vulnerability is affected more by ecological sensitivity than by ecological resilience. Stepping up from one ecological sensitivity class to another has the greatest impact on the probability of an upward step in ecological vulnerability class, accounting for 16.2% of the total area undergoing such a change. Urbanization rates and differences in human-induced landscape composition were the main factors, and their cumulative contribution to ecological vulnerability variations ranged from 59.3% to 65.8%. We found our proposed framework capable of enhancing the strength and applicability of ecological vulnerability assessments, specifically in areas with extensive river and lake networks. The framework could be used in assessments throughout China, and very likely beyond.

The efficacy of PD-1 therapy in non-small cell lung cancer (NSCLC) patients remains unsatisfactory. Activating the STING pathway is a promising strategy to improve PD-1 inhibitor efficacy. Here, we found tetrandrine (TET), an anti-tumor compound extracted from a medicinal plant commonly used in traditional Chinese medicine, has the ability to inhibit NSCLC tumor growth. Mechanistically, TET induces nuclear DNA damage and increases cytosolic dsDNA, thereby activating the STING/TBK1/IRF3 pathway, which in turn promotes the tumor infiltration of dendritic cells (DCs), macrophages, as well as CD8+ T cells in mice. In vivo imaging dynamically monitored the increased activity of the STING pathway after TET treatment and predicted the activation of the tumor immune microenvironment. We further revealed that the combination of TET with αPD-1 monoclonal antibody (αPD-1 mAb) yields significant anti-cancer effects by promoting CD8+ T cell infiltration and enhancing its cell-killing effect, which in turn reduced the growth of tumors and prolonged survival of NSCLC mice. Therefore, TET effectively eliminates NSCLC cells and enhances immunotherapy efficacy through the activation of the STING pathway, and combining TET with anti-PD-1 immunotherapy deserves further exploration for applications.

Abstract The contrast-enhanced ultrasound (CEUS) has been mainly applied to adults to differentiate benign and malignant renal lesions, however, the characteristics of CEUS in pediatric has not been as well studied as in adults. In the present work, the eligible pediatric patients who underwent renal CEUS between March 2016 and February 2023 were retrospectively analyzed. It included 20 lesions (median diameter, 8.4 cm; range, 1.8–18.0 cm) from 20 patients (median age, 28.0 months; range, 3.0–212.0 months; 9 boys) in malignant group and 5 lesions (median diameter, 3.8 cm; range, 1.3–7.5 cm) from 5 patients (median age, 25.0 months; range, 0.7–216.0 months; 2 boys) in benign group. The diagnostic performance was assessed. Nonparametric and Chi-square tests were performed. With hyperenhancement plus wash-out, CEUS showed a sensitivity of 95.0% [95% confidence interval (CI): 75.1%, 99.9%], a specificity of 80.0% (CI: 28.4%, 99.5%), a positive predictive value of 95.0% (CI: 75.1%, 99.9%) and a negative predictive value of 80.0% (CI: 28.4%, 99.5%). It suggested that CEUS is a valuable technique for identifying between malignant and benign renal lesions in children.

ObjectiveSAF-189s is a potent ALK/ROS1 inhibitor that is currently in clinical development for treating advanced ALK+/ROS1+ non-small cell lung cancer (NSCLC). Comprehensive population pharmacokinetics (PopPK) and exposure–response models were developed to evaluate the efficacy and safety of SAF-189s by integrating data from two clinical studies.MethodsThe PopPK model was developed using plasma concentration data collected from patients with ALK+/ROS1+ advanced NSCLC (n = 299) and healthy subjects (n = 24). The covariates (demographics, laboratory values, subject types, and concomitant medications) were evaluated to determine their potential influence on the between-patient variability in the pharmacokinetics of SAF-189s. Individual exposure values were then used to investigate the relationships with the efficacy endpoints (overall response rate (ORR), progression-free survival (PFS), and duration of response (DOR)) and key safety endpoints (adverse events of interest).ResultsThe final PopPK model of SAF-189s was described by a one-compartment model with delayed first-order absorption and time-dependent elimination by allowing the clearance to decrease stepwise over time. Age was included as a covariate for apparent clearance (CL/F), while prior anti-cancer therapy in ALK+ patients (ALKPOT) was included for apparent volume of distribution (V/F). There were no apparent exposure–response relationships for any of the efficacy endpoints at doses of 80–210 mg. The relationship between exposure and safety suggested that a higher steady-state exposure was associated with more frequent incidences of hyperglycemia and proteinuria; the 210-mg dose group was also less tolerated than the other low-dose groups.ConclusionPopPK and exposure–response models were developed for SAF-189s, and their results demonstrate that SAF-189s exposures are at the plateau of exposure–response for efficacy. The 210-mg dose group had a significantly higher safety risk, while the 160-mg dose group was well-tolerated. Thus, 160 mg of SAF-189s once daily was selected as the recommended phase III dose for the ALK+/ROS1+ or ROS1+ NSCLC patients.

Engineered cementitious composites (ECC), which are a kind of novel composite building material with high ductility and high toughness, can be utilized in areas susceptible to salt-freezing damage, such as that caused by snowmelt agents, seawater, and saline soils. In this paper, engineered cementitious composites reinforced with polyethylene fibers (PE) are analyzed to study the changes in the flexural static load properties, and flexural fatigue life of PE-ECC specimens after four different freeze-thaw cycles (0, 50, 100 and 150) in fresh water and a 3.5 % mass fraction NaCl solution. The results show that upon reaching 150 freeze-thaw cycles, there was a notable disparity in the relative equivalent flexural strength between specimens subjected to chloride salt freeze-thaw and freshwater freeze-thaw environments, with the former exhibiting a 1.07-fold increase in damage compared to the latter specimens. Using the relative dynamic elastic modulus as the damage variable, a relationship model was made between the relative equivalent flexural strength and the freeze-thaw damage degree of PE-ECC in two freeze-thaw environments. The flexural fatigue life of PE-ECC after freeze-thaw obeyed a two-parameter Weibull distribution, and the P-S-N curves at various reliability probabilities correlated well with the test results. The safety coefficient of PE-ECC varied with changes in freeze-thaw conditions, necessitating an increase in the safety coefficient to assure structural safety in locations with more severe freeze-thaw damage. The results of this study can serve as a reference for the development of freeze-thaw-resistant designs for PE-ECC structures in future applications.

ABSTRACT Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by social communication deficiencies and stereotypic behaviors influenced by hereditary and/or environmental risk factors. There are currently no approved medications for treating the core symptoms of ASD. Human fecal microbiota transplantation (FMT) has emerged as a potential intervention to improve autistic symptoms, but the underlying mechanisms are not fully understood. In this study, we evaluated the effects of human-derived FMT on behavioral and multi-omics profiles of the BTBR mice, an established model for ASD. FMT effectively alleviated the social deficits in the BTBR mice and normalized their distinct plasma metabolic profile, notably reducing the elevated long-chain acylcarnitines. Integrative analysis linked these phenotypic changes to specific Bacteroides species and vitamin B6 metabolism. Indeed, vitamin B6 supplementation improved the social behaviors in BTBR mice. Collectively, these findings shed new light on the interplay between FMT and vitamin B6 metabolism and revealed a potential mechanism underlying the therapeutic role of FMT in ASD.IMPORTANCEAccumulating evidence supports the beneficial effects of human fecal microbiota transplantation (FMT) on symptoms associated with autism spectrum disorder (ASD). However, the precise mechanism by which FMT induces a shift in the microbiota and leads to symptom improvement remains incompletely understood. This study integrated data from colon-content metagenomics, colon-content metabolomics, and plasma metabolomics to investigate the effects of FMT treatment on the BTBR mouse model for ASD. The analysis linked the amelioration of social deficits following FMT treatment to the restoration of mitochondrial function and the modulation of vitamin B6 metabolism. Bacterial species and compounds with beneficial roles in vitamin B6 metabolism and mitochondrial function may further contribute to improving FMT products and designing novel therapies for ASD treatment.

Abstract Objectives In the current study, for the first time, we reported a novel HCV molecular diagnostic approach termed reverse transcription loop-mediated isothermal amplification integrated with a gold nanoparticles-based lateral flow biosensor (RT-LAMP-AuNPs-LFB), which we developed for rapid, sensitive, specific, simple, and visual identification of HCV. Methods A set of LAMP primer was designed according to 5’untranslated region (5’UTR) gene from the major HCV genotypes 1b, 2a, 3b, 6a, and 3a, which are prevalent in China. The HCV-RT-LAMP-AuNPs-LFB assay conditions, including HCV-RT-LAMP reaction temperature and time were optimized. The sensitivity, specificity, and selectivity of our assay were evaluated in the current study. The feasibility of HCV-RT-LAMP-AuNPs-LFB was confirmed through clinical serum samples from patients with suspected HCV infections. Results An unique set of HCV-RT-LAMP primers were successfully designed targeting on the 5’UTR gene. The optimal detection process, including crude nucleic acid extraction (approximately 5 min), RT-LAMP reaction (67℃, 30 min), and visual interpretation of AuNPs-LFB results (~ 2 min), could be performed within 40 min without specific instruments. The limit of detection was determined to be 20 copies per test. The HCV-RT-LAMP-AuNPs-LFB assay exhibited high specificity and anti-interference. Conclusions These preliminary results confirmed that the HCV-RT-LAMP-AuNPs-LFB assay is a sensitive, specific, rapid, visual, and cost-saving assay for identification of HCV. This diagnostic approach has great potential value for point-of-care (POC) diagnostic of HCV, especially in resource-challenged regions.

Objective: In this study, we assessed the efficacy and safety of various thrombolytic treatment protocols in patients with hyperacute cerebral infarction. Methods: Patients diagnosed with acute ischemic stroke within 6 h of symptom onset and with brain computer tomography angiography confirming the absence of major vessel stenosis or occlusion were eligible for this study. The enrolled patients were subsequently randomized into two groups: all the groups received the standard intravenous thrombolysis treatment with rt-PA (0.9 mg/kg), and the experimental group underwent sequential intra-arterial thrombolysis treatment with alteplase (0.3 mg/kg, with a maximum dose of 22 mg), administered directly into the target vessel via a microcatheter. Both groups were closely monitored for changes in their National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin scale score, hemorrhage rate, all-cause mortality rate, and the rate of favorable outcomes at 90 ± 7 days. Results: Ninety-four participants were enrolled in this study, with both the control and experimental groups initiating intravenous injection of rt-PA at a median time of 29 min. For the experimental group, the median time for arterial puncture was 123 min. Baseline data for both groups were similar (P > 0.05). Hemorrhagic transformation occurred in 24.47 % (23 patients), with a lower intracranial hemorrhage rate observed in the experimental group compared to the control group (15.2 % vs 33.3 %, P 0.05). A higher proportion of patients in the experimental group achieved favorable outcomes compared to the control group (87.0 % vs 43.8 %, P

ABSTRACTPrevious studies have profiled the gut microbiota among psoriatic patients compared to that among healthy individuals. However, a comprehensive understanding of the magnitude, direction, and detailed compositional and functional profiles remains limited. Additionally, research exploring the gut microbiota in the context of both plaque psoriasis (PsO) and psoriatic arthritis (PsA) is lacking. To assess the taxonomic and functional characteristics of the gut microbiota in PsO and PsA patients and investigate potential links between the gut microbiota and disease pathogenesis. We collected fecal samples from 70 psoriatic patients (44 PsO and 26 PsA) and 25 age- and gender-matched healthy controls (HC) and employed deep metagenomic sequencing to characterize their gut microbiota. We noted significant alternations in the gut microbiota compositions of both PsO and PsA patients compared to those of HC. Despite limited effect sizes in alpha diversity (12.3% reduction of microbial richness but unchanged evenness in psoriatic patients) and beta diversity (disease accounts for 3.5% of total variations), we consistently observed substantial reductions of Eubacterium rectale in both PsO and PsA patients, with PsA patients exhibiting even lower levels of E. rectale than PsO patients. Additionally, two Alistipes species were also depleted in psoriatic patients. These microorganisms are known to play crucial roles in carbohydrate metabolism pathways, mainly producing short-chain fatty acids with anti-inflammatory effects. Overall, our observations supplemented the profiling of altered gut microbiota in patients with PsO and PsA at the species level and described a link between the dominant short-chain fatty acid-producing bacterial species and systemic immunity in psoriatic patients.IMPORTANCEIn this observational clinical study with sufficient sample size and metagenomic sequencing to profile the gut microbiota, we identified consistent signals of the depleted abundance of Eubacterium rectale and related functional genes among psoriatic patients, including those with psoriatic arthritis. E. rectale may serve as an ecologically important functional unit in the gut microbiota, holding potential as a diagnostic marker and target for therapeutic interventions to achieve lasting effects. Our findings provide comprehensive gut microbiota profiling in psoriasis, resolving previous contradictions and generating new hypotheses for further investigation. These insights may significantly impact psoriasis management and related conditions.

Thanks to the advancements in bioinformatics, drugs, and other interventions that modulate microbes to treat diseases have been emerging continuously. In recent years, an increasing number of databases related to traditional Chinese medicine (TCM) or gut microbes have been established. However, a database combining the two has not yet been developed. To accelerate TCM research and address the traditional medicine and micro ecological system connection between short board, we have developed the most comprehensive micro-ecological database of TCM. This initiative includes the standardization of the following advantages: (1) A repeatable process achieved through the standardization of a retrieval strategy to identify literature. This involved identifying 419 experiment articles from PubMed and six authoritative databases; (2) High-quality data integration achieved through double-entry extraction of literature, mitigating uncertainties associated with natural language extraction; (3) Implementation of a similar strategy aiding in the prediction of mechanisms of action. Leveraging drug similarity, target entity similarity, and known drug-target entity association, our platform enables the prediction of the effects of a new herb or acupoint formulas using the existing data. In total, MicrobeTCM includes 171 diseases, 725 microbes, 1468 herb-formulas, 1032 herbs, 15780 chemical compositions, 35 acupoint-formulas, and 77 acupoints. For further exploration, please visit https://www.microbetcm.com.

Abstract Background and Objectives This study was conducted to investigate the effect of high-fat meals on the pharmacokinetics (PK) and safety profile of SAF-189s, a novel ALK/ROS1 inhibitor. Methods This was a single-center, phase I, open-label, crossover study in which healthy adults (≥18 years) were randomized (1:1) to two sequences of SAF-189s administration (fasted-fed or fed-fasted) separated by a 14-day washout. After a ≥10-h overnight fast, volunteers received SAF-189s 160 mg orally in a fasted state or 30 min after a high-fat, high-calorie meal. Similarity of pharmacokinetic parameters was concluded if the 90% CI for the geometric mean ratio (GMR) between the fed and fasted group fell within the predefined range of 0.80–1.25. Results In total, 24 subjects were enrolled and 23 completed the study. SAF-189s maximum plasma concentration (C max; GMR: 109.1% [90% CI 103.1–115.4]) was comparable under fed (high-fat meal, n = 24) versus fasted (n = 23) conditions, with no effect on area under the plasma concentration–time curve from time 0 to t (AUC0-t; GMR: 105.1% [90% CI 100.3–110.2]) and AUC from time 0 to infinity (AUC0-∞; GMR: 105.5% [90% CI, 100.6–110.6]). In both groups, the median time to maximum plasma concentration (t max) was around 6 h and mean plasma half-life (t ½) was around 35 h. Fed administration led to a lower incidence of treatment-emergent adverse events (TEAEs; 29.2% vs 54.2%), including gastrointestinal disorders (4.2% vs 41.7%) and headache (0.0% vs 12.5%), versus fasted administration. Conclusions A high-fat meal had minimal effect on the pharmacokinetic profile of SAF-189s compared with a fasted state following a single dose of 160 mg. Administration with a high-fat meal led to a lower incidence of TEAEs.

Objective: To illustrate the cerebral protective effect of scalp mechanical stimulation (SMS), similar to scalp acupuncture in basic mechanism, on cerebral edema in rats with cerebral hypoperfusion. Methods: First, we screened the strength of SMS by measuring skin temperature and blood perfusion using laser speckle contrast imaging. Next, we observed the cerebral protective effects on cerebral blood perfusion, cerebral edema, and pathological changes in rats with modified two-vessel carotid artery occlusion (2-VO). Furthermore, the apoptosis-related proteins (caspase-3, cleaved-caspase-3) and cerebral edema related proteins [antiglial fibrillary acidic protein (GFAP) and antiaquaporin-4 (AQP4)] were measured via immunohistochemistry and Western blot analysis. Additionally, the correlation between neural apoptosis and AQP4 protein levels was analyzed. Results: We found that 0.5 N was the best SMS intensity suitable for our study. Compared with the control group, 0.5, 1, and 2 N maintained the scalp temperature and improved scalp blood flow (all P

Abstract Background An increasing number of studies on physicians’ professionalism have been done since the 2002 publication of Medical Professionalism in the New Millennium: A Physician Charter. The Charter proposed three fundamental principles and ten responsibilities. However, most studies were done in developed countries, and few have been done in China. Additionally, few studies have examined the effect of patient-centered hospital culture (PCHC) on physicians’ professionalism. We aimed to investigate physicians’ medical professionalism in public hospitals in China, and to assess mediating effect of professional attitudes in the relationship of PCHC with professional behaviours. Methods Self-administered questionnaires including professional attitudes (20 items) and behaviours (10 items) survey and PCHC scale (22 items) were given to clinical physicians in five public hospitals, China. The mediating effect of professional attitudes in the relationship of PCHC with professional behaviours was tested. Result 232 valid questionnaires were collected. More than 90% (208) respondents agreed with 15 of 20 specific statements on medical professionalism. As for the responsibility of improving quality of care, 54 (23%) respondents disagreed with reporting of incompetent colleagues and as for the responsibility of maintaining professional competence, 49 (21%) disagreed with recertification. More than 185 (83%) respondents reported that they sometimes, usually, or always showed the four positive behaviours on the questionnaire, and 173 (77%) reported that they never showed the six negative behaviours. Mediating effect analysis revealed that two dimensions of PCHC (i.e. value/institution culture and behaviour/material culture) had a significant positive impact on physicians’ professional behaviour, and professional attitude played a complete mediation role between them, but another dimension of PCHC (i.e. negative evaluation of hospital) directly affected professional behaviour without influencing professional attitude. Conclusion Chinese physicians showed positive professional attitudes and behaviours. Different dimensions of PCHC affected physicians’ attitudes and behaviours in different ways.

Abstract Background Surgery is a common treatment strategy for patients with neurofibromatosis type 1 (NF1)-related plexiform neurofibroma (PN) and has limited efficacy. FCN-159 is a novel anti-tumorigenic drug via selective inhibition of MEK1/2. This study assesses the safety and efficacy of FCN-159 in patients with NF1-related PN. Methods This is a multicenter, open-label, single-arm, phase I dose-escalation study. Patients with NF1-related PN that was non-resectable or unsuitable for surgery were enrolled; they received FCN-159 monotherapy daily in 28-day cycles. Results Nineteen adults were enrolled in the study, 3 in 4 mg, 4 in 6 mg, 8 in 8 mg, and 4 in 12 mg. Among patients included in dose-limiting toxicity (DLT) analysis, DLTs (grade 3 folliculitis) were reported in 1 of 8 patients (16.7%) receiving 8 mg and 3 of 3 (100%) patients receiving 12 mg. The maximum tolerated dose was determined to be 8 mg. FCN-159-related treatment-emergent adverse events (TEAEs) were observed in 19 patients (100%); most of which were grade 1 or 2. Nine (47.4%) patients reported grade 3 study-drug–related TEAEs across all dose levels, including four experiencing paronychia and five experiencing folliculitis. Of the 16 patients analyzed, all (100%) had reduced tumor size and six (37.5%) achieved partial responses; the largest reduction in tumor size was 84.2%. The pharmacokinetic profile was approximately linear between 4 and 12 mg, and the half-life supported once daily dosing. Conclusions FCN-159 was well tolerated up to 8 mg daily with manageable adverse events and showed promising anti-tumorigenic activity in patients with NF1-related PN, warranting further investigation in this indication. Trial registration ClinicalTrials.gov, NCT04954001. Registered 08 July 2021.

Abstract Metabolic associated fatty liver disease (MAFLD) is rising in incidence and is an increasingly common cause of cirrhosis and hepatocellular carcinoma (HCC). Alterations in the gut microbiota have been shown to correlate with the development and progression of MAFLD. However, little is known regarding differences in the gut microbiomes of MAFLD patients and healthy cohorts, and subgroups at the abnormal activity of hepatic enzymes in China. In this study, we enrolled 81 MAFLD patients and 25 healthy volunteers. The fecal microbiota was assessed using 16S rRNA gene sequencing and metagenomic sequencing. The results suggested that Ruminococcus obeum and Alistipes were most enriched in healthy individuals when compared with MAFLD patients. Microbe‐set Enrichment Analysis (MSEA) results showed Dorea, Lactobacillus and Megasphaera are enriched in MAFLD group. We also found that Alistipes has negatively related to serum glucose (GLU), gamma-glutamyl transferase (GGT), and alanine aminotransferase (ALT). Moreover, the abundance of Dorea was found to be significantly overrepresented in the MAFLD patients and the degree of enrichment increased with the increasing abnormal liver enzyme. An increase in Dorea, combined with decreases in Alistipes appears to be characteristic of MAFLD patients. Further study of microbiota may provide a novel insight into the pathogenesis of MAFLD as well as a novel treatment strategy.

Abstract Traditional Chinese medicine (TCM) is widely used in clinical practice, including skin and gastrointestinal diseases. Here, a potential TCM QY305 (T‐QY305) is reported that can modulate the recruitment of neutrophil in skin and colon tissue thus reducing cutaneous adverse reaction and diarrhea induced by epidermal growth factor receptor inhibitors (EGFRIs). On another hand, the T‐QY305 formula, through regulating neutrophil recruitment features would highlight the presence of N‐QY305, a subunit nanostructure contained in T‐QY305, and confirm its role as potentially being the biomaterial conferring to T‐QY305 its pharmacodynamic features. Here, the clinical records of two patients are analyzed expressing cutaneous adverse reaction and demonstrate positive effect of T‐QY305 on the simultaneous inhibition of both cutaneous adverse reaction and diarrhea in animal models. The satisfying results obtained from T‐QY305, lead to further process to the isolation of N‐QY305 from T‐QY305, in order to demonstrate that the potency of T‐QY305 originates from the nanostructure N‐QY305. Compared to T‐QY305, N‐QY305 exhibits higher potency upon reducing adverse reactions. The data represent a promising candidate for reducing cutaneous adverse reaction and diarrhea, meanwhile proposing a new strategy to highlight the presence of nanostructures being the “King” of Chinese medicine formula as the pharmacodynamic basis.

Wound infection is a major problem faced during wound healing. Therefore, it is necessary to develop wound dressings with excellent antimicrobial properties. Here, a smart response system of PVA-TPE/HA-AMP/SF/ALG wound dressing was prepared by a combination of chemical cross-linking and freeze-drying methods. We grafted AMP onto HA to endow the wound dressing with bacterial resistance and slow release of AMP. At the same time, the system detects bacterial activity in real time for precise antimicrobial activity (through the use of PVA-TPE) and modulates inflammation to reduce bacterial infection (through the use of AMP). In addition, the PVA-TPE/HA-AMP/SF/ALG wound dressing has a good three-dimensional mesh structure, which promotes cell proliferation, enhances collagen deposition and angiogenesis, and thus effectively promotes rapid healing of infected wounds. Moreover, it can induce the expression of inflammatory factors such as VEGF, TNF-α, IFN-γ, IL-4 and TGF-β1 in infected wounds through the Wnt/CAMK/p-PKC signaling pathway, inhibit inflammatory responses, promote wound healing and reduce scar formation. Therefore, the PVA-TPE/HA-AMP/SF/ALG wound dressing smart response system shows great promise in infected wound healing.

As human progress forges ahead in the domain of ultra-low temperature advancements, conventional concrete materials have been inadequate in addressing the exigencies of practical engineering demands, Engineered Cementitious Composites (ECC), an emerging class of novel composite materials, whose investigation concerning performance under ultra-low temperature environments assumes profound significance. This paper employed Polyethylene (PE) fibers to fabricate Engineered Cementitious Composites (ECC) and investigated the impact of varying ultra-low temperature freezing-thawing cycles lower limit temperatures, as well as the number of freezing-thawing cycles, on the bending static load strength and bending fatigue properties of PE-ECC specimens. The results show that changes in lower limit temperatures and the number of freezing-thawing cycles have a substantial effect on the flexural static load strength of PE-ECC, the flexural strength and bending deflection of the specimens exhibit a notable decrease in values. Across various freezing-thawing conditions, the toughness value is consistently lower than that of the control group unaffected by freezing-thawing, thereby indicating a compromised energy absorption capacity of the matrix. The strength of the interfacial bonding between the fibers and the matrix is reduced, leading to a conspicuous increase in fiber pullout damage when the specimen fails. The fatigue life of PE-ECC subjected to freezing-thawing in ultra-low temperatures follows the two-parameter Weibull distribution, the fatigue life equations of PE-ECC under different freezing-thawing conditions with different probabilities of reliability are obtained by regression analysis. The results of this study can serve as a reference for analyzing the fatigue life of PE-ECC at ultra-low temperatures freezing-thawing cycles.

Introduction Acute kidney injury (AKI) is a common complication in patients with community-acquired pneumonia (CAP) and negatively affects both short-term and long-term prognosis in patients with CAP. However, no study has been conducted on developing a clinical tool for predicting AKI in CAP patients. Therefore, this study aimed to develop a predictive tool based on a dynamic nomogram for AKI in CAP patients.Methods This retrospective study was conducted from January 2014 to May 2017, and data from adult inpatients with CAP at Nanjing First Hospital were analysed. Demographic data and clinical data were obtained. The least absolute shrinkage and selection operator (LASSO) regression model was used to select important variables, which were entered into logistic regression to construct the predictive model for AKI. A dynamic nomogram was based on the results of the logistic regression model. Calibration and discrimination were used to assess the performance of the dynamic nomogram. A decision curve analysis was used to assess clinical efficacy.Results A total of 2883 CAP patients were enrolled in this study. The median age was 76 years (IQR 63–84), and 61.3% were male. AKI developed in 827 (28.7%) patients. The LASSO regression analysis selected five important factors for AKI (albumin, acute respiratory failure, CURB-65 score, Cystatin C and white cell count), which were then entered into the logistic regression to construct the predictive model for AKI in CAP patients. The dynamic nomogram model showed good discrimination with an area under the receiver operating characteristics curve of 0.870 and good calibration with a Brier score of 0.129 and a calibration plot. The decision curve analysis showed that the dynamic nomogram prediction model had good clinical decision-making.Conclusion This easy-to-use dynamic nomogram may help physicians predict AKI in patients with CAP.

AbstractBackground Acute kidney injury (AKI) is common in patients with community-acquired pneumonia (CAP), and is associated with poor prognosis. Therefore, in this study, we evaluated whether AKI in Chinese patients with CAP could be well predicted by serum Cystatin C within 24 h after admission.Methods Univariate and multivariate logistic regression analyses were used to investigate independent factors of AKI in patients with CAP.Results Totally, 2716 patients with CAP were included in this study. 766 (28%) patients developed AKI. After multivariate logistic regression analysis, serum Cystatin C (odds ratio [OR] 4.27, 95% confidence interval [CI] 3.36–5.44; p

Objective: To explore the mechanism and related active components of Yishen Daluo decoction (YSDLD) in treating multiple sclerosis (MS). Methods: Targets of YSDLD were collected through the TCMSP, Chemistry, and TCMID databases. The MS targets were collected through OMIM, DrugBank, Gencards, TTD, and Pharmgkb databases. We built “component–target” network diagrams and protein–protein interaction (PPI) diagrams and performed topological analysis. The targets were subjected to GO and KEGG enrichment analysis. Molecular docking verification was conducted on selected targets and molecules. Finally, in vitro experiments were conducted. BV2 cells were induced by lipopolysaccharide for model establishment. CCK8 experiment was conducted to explore the effect of YSDLD and RT-qPCR technology was used to explore the expression of key targets. Results: There were 184 active components in YSDLD and 898 targets of its action. There were 940 MS targets, and 215 targets were shared by YSDLD and MS. According to the “component–target” diagram, the top five key components included quercetin, kaempferol, beta-sitosterol, stigmasterol, and naringenin. IL-6, IL-1β, TNF-α, AKT1, and VEGFA were the important targets identified by PPI network topology analysis. A total of 564 functions were identified by GO enrichment analysis (P

By considering the uncertainties in the initial field, model physical processes, and lateral boundary conditions, the Shanghai Weather And Risk Model System-Ensemble Prediction System (SWARMS-EN) is constructed. According to the prediction results of typhoon Muifa (2022), the daily track error of SWARMS-EN within 5 days is 70.6 km, 142.2 km, 129.1 km, 174.5 km, and 203.5 km, respectively. When compared with the Typhoon Ensemble Data Assimilation and Prediction System (TEDAPS) and the Global Ensemble Forecast System (GEFS) of the National Centers for Environmental Prediction (NCEP) in homogeneous conditions, SWARMS-EN performs better than TEDAPS within 72 h and better than GEFS beyond 72 h in track forecasting. This indicates an improvement in forecasting accuracy. The ensemble spread within two days is less than the root mean square error (RMSE), according to an analysis of the relationship between ensemble RMSE and spread, which shows that SWARMS-EN has no apparent systematic bias overall. The system has improved the ensemble RMSE and spread, indicating that it can better represent the uncertainty of the forecast and produce more reliable forecasts. Additionally, SWARMS-EN provides the landfall forecast five days in advance. The ensemble-based analysis suggests that the large-scale circulation is the primary factor contributing to the forecast differences among members, and the strong steering flow provides an indication of the landfalling forecast. The analysis of the ensemble characteristics of the initial field indicates that the initial perturbation between the wind field and the temperature field in the dynamically unstable region (such as near a tropical cyclone) exhibits flow dependence, and the small perturbation shows continuity throughout the entire troposphere. The distribution of ensemble spread and disturbance energy exhibited a reasonable growth stage as the forecast lead time increased. Disturbance internal energy dominated the lower troposphere, while the upper troposphere was mainly characterized by disturbance kinetic energy. Disturbance kinetic energy played a leading role in the evolution process. This conclusion further confirms the importance of paying attention to the initial small perturbations near TC in order to optimize the initial perturbation.

Objective: Diminished ovarian reserve (DOR) refers to the decreased number and quality of oocytes in the ovary. Acupuncture and moxibustion has a certain effect on DOR; however, the number of studies and reports of research evidence are limited. This study aimed to conduct a scoping review of the clinical research status of acupuncture and moxibustion for treating patients with DOR. Method: PubMed, Cochrane Library, Excerpta Medica database, Allied and Complementary Medicine Database, Chinese Biological Medicine, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, and Wanfang database were searched from January 2010 to May 2022 using keywords and medical subject heading terms. After applying the inclusion and exclusion criteria, relevant studies were selected. Structured tables and descriptive charts were made to visually express research features by using Excel, Original, IBM SPSS Model 18.0, Adobe Illustrator and other software packages. Report quality was evaluated for Cochrane bias using Review Manager 5.3. Results: Overall, 851 studies were identified; of these, 90 met the inclusion criteria. The results extracted from these studies were classified into four categories: research characteristics, study type, acupuncture and moxibustion prescriptions, and efficacy observation. Conclusions: The quality assessment of acupuncture and moxibustion for DOR is not ideal. Therefore, standardisation and normalisation should be strengthened, and high-quality evidence is needed to further demonstrate the effectiveness of this approach. Due to heterogeneity in DOR diagnosis, the observation index should be updated with reference to the latest research to improve efficacy evaluation.

Using a large sample of data on insiders’ stock selling and rumors about A-share listed companies in China, this study empirically tests whether and how rumors about companies are used to manipulate the market in the context of insiders’ stock selling. We find that the probability of a rumor’s occurrence, especially that of a favorable rumor, significantly increases in the 30 days before the first transaction in a round of insiders’ stock selling and remains high for 30 days afterward, showing clear signs of manipulation. These results are robust to several endogeneity tests. The probability of manipulation via rumor increases with a company’s degree of information asymmetry. In addition, large-scale stock selling, centralized bidding, and transactions involving CEOs or chairmen (or their relatives) have a significantly higher probability of manipulation via rumor, while transactions made by directors, supervisors, or senior executives (but not their relatives) have a significantly lower probability of manipulation via rumor. Further examination shows that using rumor to manipulate the market increases insiders’ transaction returns but leads to stock price reversal in the long term.

Abstract The human gut microbiome has been extensively explored, while the archaeal viruses remain largely unknown. Here, we present a comprehensive analysis of the archaeal viruses from the human gut metagenomes and the existing virus collections using the CRISPR spacer and viral signature-based approach. This results in 1279 viral species, of which, 95.2% infect Methanobrevibacteria_A, 56.5% shared high identity (>95%) with the archaeal proviruses, 37.2% have a host range across archaeal species, and 55.7% are highly prevalent in the human population (>1%). A methanogenic archaeal virus-specific gene for pseudomurein endoisopeptidase (PeiW) frequently occurs in the viral sequences (n = 150). Analysis of 33 Caudoviricetes viruses with a complete genome often discovers the genes (integrase, n = 29; mazE, n = 10) regulating the viral lysogenic-lytic cycle, implying the dominance of temperate viruses in the archaeal virome. Together, our work uncovers the unexplored diversity of archaeal viruses, revealing the novel facet of the human gut microbiome.

Abstract Background Common treatments for metastatic/unresectable HER2‐negative gastric cancer include chemotherapy, immune checkpoint inhibitor monotherapy and chemotherapy plus immune checkpoint inhibitor. However, significant drug resistance exists regardless of the treatment regimen. Methods Patients with metastatic/unresectable HER2‐negative gastric/gastroesophageal junction adenocarcinoma were enrolled. All patients were divided into three groups according to the treatment regimen and were further divided into responders and non‐responders according to efficacy evaluation. Metagenomics sequencing were performed to analyze gut microbiome signature of patients receiving different treatments at baseline and throughout treatment. Results One hundred seventeen patients with HER2‐negative advanced gastric or gastroesophageal junction adenocarcinoma receiving chemotherapy alone, anti PD‐1/PD‐L1 immunotherapy alone or combined regimen were included in this study. Microbiome signatures related to clinical response are distinct among the three treatment groups. Among which, 14, 8 and 13 species were significantly different between responders and non‐responders in immunotherapy, immunotherapy plus chemotherapy and chemotherapy group, respectively. Patients with higher relative abundance of Lactobacillus possessed higher microbiome diversity and significantly better response to anti‐PD‐1/PD‐L1 immunotherapy and had a trend to achieve better progression‐free survival. Another cohort of 101 patients has been used as an external validation set to confirm the stability and reliability of these findings. Conclusions Gut microbiome affects response of treatments in HER2‐negative advanced gastric cancer in a treatment‐specific way, immunotherapy plus chemotherapy did not equal to a simple superposition of immunotherapy and chemotherapy. Lactobacillus is expected to become a novel choice as an adjuvant agent in promoting the efficacy of immunotherapy in gastric cancer.

Elemental mercury impaction in the appendix can cause subsequent local and systemic complications. We present a case of a teenage boy who ingested approximately 10 mL of elemental mercury, resulting in residual mercury sequestration in the appendix after conservative management. We performed laparoscopic appendectomy to remove the residual mercury. The patient made a complete clinical recovery without adverse events related to mercury poisoning over the 6-month follow-up. We highlight the advantages of laparoscopic appendectomy, abdominal computed tomography (CT), negative pressure operating rooms, and surgeon protection to improve surgical success rates. This case report adds to the literature on the management of elemental mercury impaction in the appendix and provides valuable insights for clinical decision-making.

In this paper, new third-order finite volume unequal-sized weighted essentially non-oscillatory (US-WENO) Lagrangian schemes are designed to solve Euler equations in two and three dimensions. The spatial reconstruction procedures are implemented by using a convex combination of a quadratic polynomial with several linear polynomials specified on unequal-sized stencils, so the new US-WENO Lagrangian schemes can achieve the designed third-order accuracy and maintain an essentially non-oscillatory property near strong discontinuities in multi-dimensions. Unlike the traditional WENO reconstruction procedures specified on unstructured meshes, the linear weights of these new two-dimensional and three-dimensional US-WENO spatial reconstructions can be selected as any positive numbers as long as their summation equals one and they are not related to the local mesh topology or the location of quadrature points. Moreover, the linear weights do not have to be recalculated even if the grid moves with the fluid, avoiding the appearance of negative linear weights, thus improving computation efficiency and robustness in multi-dimensional Lagrangian numerical simulations. Finally, extensive benchmark numerical cases are employed to display the excellent capability of the presented US-WENO Lagrangian schemes.

The Method for Object-based Diagnostic Evaluation (MODE) is applied to evaluate the SMS-WARMS, ECMWF, and GFS models for spatial verification of their performance of rainstorm forecast for three landing typhoons in East China in 2018. The results show that: (1) The MODE method is more advanced than the traditional method in typhoon precipitation verification. It can provide more diagnostic information to reflect the prediction error of the model through various verification indices such as centroid distance, area, and axis angle etc. (2) The results of MODE indicate that the SMS-WARMS prediction is superior to the ECMWF and GFS predictions in terms of spatial predictions of heavy rainfall over 50 mm for the three landing typhoons, particularly for the rainfall over 100 mm. (3) The predicted intensity of rainfall by the regional model is stronger than that by the global models, reflecting the advantages of regional model in predicting typhoon heavy rainfall. (4) The SMS-WARMS model tends to over-predict the area of typhoon heavy rainfall, while ECMWF and GFS tend to under-predict.

Impact of the Zr58Nb3Cu12Ni12Al15 bulk metallic glasses (BMG) fragment on shield plate generates a debris cloud and causes great damage to the hindside witness target. However, conventional FEM and experimental methods are difficult to track the complex formation process and damage behavior of debris cloud. In this study, such process of a 10 mm spherical metallic glasses fragment penetrating into two LY12 separated plates is investigated, both experimentally and computationally. By introducing JH-2 constitutive model, the mechanical properties of Zr-base BMG with high strength and low plasticity are reproduced; Meanwhile, by introducing the FEM/SPH coupling method, the failed element is converted into SPH, thereby simulating the impacting and fragmentation process of the fragment, as well as the characteristics of the transiently generated debris cloud. The simulation results are in good agreement with the experimental observations. During the penetrating process, a large number of stress concentration areas are found inside the fragment, thus promoting the forming process of the debris; the mass and velocity loss rates of the residual fragment at different stages are clarified quantitatively. Further, the debris cloud in space can be divided into three zones according to the morphology, i.e. the reverse motion zone, the debris-dispersion zone and the debris-concentration zone, and the debris-concentration zone is the main factor causing damage efficiency of the witness target.

The natural marshland and forest landscapes in the Lower Yangtze region have undergone a long history of human-induced destruction; however, little is known about the beginning and process of this destruction. In this study, we investigate the anthropogenic impact on the marsh and forest using cores collected from the vicinity of the Neolithic Luotuodun site, employing palaeoenvironmental and palaeovegetation methods. Our results indicate that the marsh was disturbed by the Neolithic community at 7500 cal yr BP and was completely destroyed at 6500 cal yr BP. Deforestation began at 6500 cal yr BP, and the original mixed broadleaf evergreen and deciduous forest was completely cleared at 4800 cal yr BP. Our findings demonstrate that the Neolithic community in the Luotuodun site prioritized the transformation of marsh in low-lying areas before deforestation. Given that most recent research has focused on pollen-based forest dynamics to study terrestrial landscape changes, the emergence and evolution of anthropogenic landscapes may be greatly underestimated.

BackgroundPicosecond lasers are widely used in dermatologic and cosmetic practice. In clinical practice, informed consent for laser treatments is critical to ensure patients’ understanding of health information.ObjectivesTo evaluate whether video-based informed consent improves patient comprehension and satisfaction.MethodsThe study was performed from August 1 to November 30, 2022. Solar lentigines patients who fulfilled the inclusion criteria were included. Before October 1, 2022, traditional informed consent methods were performed. In the subsequent 2 months, a video-based informed consent was used as an adjunct to traditional consenting methods. Finally, patient comprehension of relevant knowledge about laser treatment and client satisfaction were assessed.ResultsA total of 106 patients were included. The mean number of correct answers in the comprehension assessment in the video-based informed consent group was significantly higher than that in the traditional informed consent group (4.4 ± 1.2 vs. 3.4 ± 1.1, p < 0.001). Compared to the traditional informed consent group, more correct answers in the video-based informed consent group were provided by older patients (3.9 ± 1.2 vs. 2.9 ± 1.1, p = 0.004) and patients with lower education levels (4.1 ± 1.1 vs. 3.0 ± 1.2, p < 0.001). The mean satisfaction score in the video-based informed consent group was significantly higher than that in the traditional informed consent (27.8 ± 5.7 vs. 24.3 ± 6.2, p = 0.003).ConclusionVideo-based informed consent helps patients learn clinical literacy more effectively and improves patient satisfaction, especially in those with lower education levels and older ages.

IntroductionThe wide application of immune checkpoint inhibitors has significantly improved the survival expectation of cancer patients. While immunotherapy brings benefits to patients, it also results in a series of immune-related adverse events (irAEs). Increasing evidence suggests that the gut microbiome is critical for immunotherapy response and the development of irAEs.MethodsIn this prospective study, we recruited 95 patients with advanced/unresectable gastrointestinal cancers treated with immunotherapy and report a comprehensive analysis of the association of the gut microbiome with irAEs. Metagenome sequencing was used to analyze the differences in bacterial composition and metabolic pathways of baseline fecal samples.ResultsIn summary, we identified bacterial species and metabolic pathways that might be associated with the occurrence of irAEs in gastric, esophageal, and colon cancers. Ruminococcus callidus and Bacteroides xylanisolvens were enriched in patients without severe irAEs. Several microbial metabolic pathways involved in the urea cycle, including citrulline and arginine biosynthesis, were associated with irAEs. We also found that irAEs in different cancer types and toxicity in specific organs and the endocrine system were associated with different gut microbiota profiles. These findings provide the basis for future mechanistic exploration.

Herein, an ultrasensitive DNAzyme-based fluorescence biosensor for detecting Cu2+ was designed using the cascade signal amplification strategy, coupling λ-exonuclease-assisted target recycling and mismatched catalytic hairpin assembly (MCHA). In the designed detection system, the target, Cu2+, can activate the Cu2+-dependent DNAzyme to cause a cleavage reaction, releasing ssDNA (tDNA). Then, tDNA binds to hairpin DNA (H0) with an overhanging 5′-phosphorylated terminus to form dsDNA with a blunt 5′-phosphorylated terminus, which activates the dsDNA to be digested by λ-Exo and releases tDNA along with another ssDNA (iDNA). Subsequently, the iDNA initiates MCHA, which can restore the fluorescence of carboxyfluorescein (FAM) previously quenched by tetramethylrhodamine (TAMRA), resulting in a strong fluorescent signal. Furthermore, MCHA efficiently improves the signal-to-noise ratio of the detection system. More importantly, tDNA recycling can be achieved with the λ-Exo digestion reaction to release more iDNA, efficiently amplifying the fluorescent signal and further improving the sensitivity to Cu2+ with a detection limit of 60 fM. The practical application of the developed biosensor was also demonstrated by detecting Cu2+ in real samples, proving it to be an excellent analytical strategy for the ultrasensitive quantification of heavy metal ions in environmental water sources.

Vibrations are like the heartbeat of an aero-engine. In order to better understand the pulse pattern of aero-engines, we must look deep into its nature. Instead of choosing mature themes for research such as bearing vibration fault diagnosis and fault classification, this paper creatively explores vibration forecast, a subject that is hardly ever brought up in the aero-engine field. Meanwhile, an enhanced ConvNeXt model using a sliding window mechanism, which is a highly accurate forecasting method, is proposed. On the basis of using real flight datasets gathered by aircraft acquisition systems, this powerful method can track and forecast the vibration of aero-engines very precisely in a specific condition. Due to the complexity of aero-engine vibration, our method uses the sliding window to add future information on non-target parameters in order to increase the prediction accuracy of the target parameters. In some cases, forecasted values are almost identical to true values. The application of this innovative method on various vibration parameters has also been tested, in addition to its applicability to various types of aero-engines being confirmed. Finally, experiments on noise immunity and several aero-engine states involving the transition state and the steady state are conducted to strengthen the plausibility and credibility of our theories.

For understanding the vibration states of aero-engines deeply and acquiring warning signs in real-time, a T-step forecast method of aero-engine vibration is proposed based on a powerful and advanced deep learning model, the MAE (Masked Autoencoders) model. Unlike previous common algorithms, the MAE model performs pre-training tasks by reconstructing information to achieve the purpose of analyzing and learning the latent information among parameters. Through the use of this technique, downstream tasks will be able to fine-tune and better suit the objective function, increasing the forecast’s accuracy. Compared with simulation data and open-source datasets, this paper uses the real flight data recorded by aircraft data acquisition systems. This implies that the real vibration states of aero-engines can be learned and built. And from this, fairly practical conclusions can be reached. The result shows that it is feasible to forecast the vibration signal of aero-engines. This means that not only is that the first time series forecasting application of Transformer models that has a pre-training mechanism with masked code, but it also takes the lead in exploring the feasibility of vibration signal forecast in the aero-engine area. In addition, the possibility of forecasting in different types of aero-engines is also tested. Finally, to make our theories more reasonable and convincing, experiments on different aero-engine states involving the transition state and the steady state are carried out.

Study region: The Yellow River basin (YRB), China. Study focus: To alleviate flood risks and safeguard human well-being, understanding the spatiotemporal pattern of and factors influencing flood-regulating ecosystem service capacity and demand relationship is crucial. This study quantifies the capacity-demand ratio and identifies the regions where capacity did not meet demand from 2000 to 2020. The spatial Durbin models (SDM) were employed to detect the spillovers and assess the direct and indirect effects of factors influencing the capacity-demand relationship in the YRB and across different reaches. New hydrological insights for the region: The results show that regions with unmet demand has increased since 2000 due to a dramatic increase in demand and a reduction in capacity in the YRB. The SDM results reveal that wetlands and forests had positive direct effects, and cropland and built-up land had adverse effects on the capacity-demand ratios. Heterogeneity tests show that wetland, forest and low-coverage grassland were the biggest contributors to the capacity-demand ratios across upper-, mid- and downstream areas, respectively. Forest in the upper reach had positive direct effects and spillovers on the capacity-demand ratio. Cropland and low-coverage grassland negatively affected the capacity-demand ratio in the middle reach. The capacity-demand relationship in the lower reach needs to be improved by restoring ecologically functional land and enhancing the capacity of artificial hydro facilities.

The compressor geometric variable system is vital for aeroengines, as it affects their performance and design. To monitor the compressor geometric variable system states and detect anomalies in real time, a t-step forecasting method based on the MAE (masked autoencoders) model was proposed in this article. Unlike previous studies that used simulated or lab-generated data, we use actual flight data recorded by the aircraft data acquisition system to make our results more realistic. Through our experimental efforts, the feasibility of forecasting the compressor geometric variable system based on the MAE model is verified. That is not only the first application of transformer models with a masked pretraining mechanism in time series forecasts but also taking the lead in exploring the possibility of this key system forecast. We also test the generalizability of our method across different types of aeroengines. Finally, to make our theories more reasonable and convincing, experiments on different aeroengine states, including the transition state and the steady state, are carried out.

BackgroundWith the development of metagenomic sequencing technologies, more and more cases of pneumonia caused with Chlamydia psittaci (C. psittaci) have been reported. However, it remains unknown about the characteristics of patients with pneumonia caused by different strains of C. psittaci. Here, we shared the clinical characteristics of two cases of pneumonia caused with C. psittaci strains SZ18-2 and SZ15 which were rarely identified in humans.Case presentationCase 1: A 69-year-old male farmer who fed ducks presented to hospital for cough, diarrhea and lethargy with the temperature of 39.8°C. Case 2: A 48-year-old male worker who slaughtered ducks was transferred to hospital for high fever, cough, myalgia, diarrhea and loss of appetite. Both patients did not take any protective measures (wearing face masks or gloves) while processing ducks. C. psittaci pneumonia was diagnosed by metagenomic next-generation sequencing and polymerase chain reaction. After treatment with doxycycline and azithromycin individually, they recovered well and discharged from hospital. Through OmpA sequencing, two different strains of SZ18-2 and SZ15 were identified in case 1 and case 2, respectively.ConclusionsPatients infected with different strains of C. psittaci may own different clinical manifestations. C. psittaci infection should be suspected when pneumonia appears, accompanied by digestive symptoms and multiple organ dysfunction, especially under the exposure of specific birds.

Objective: FCN-159 is a highly active mitogen-activated extracellular signal-regulated kinase 1/2 (MEK1/2) inhibitor in patients with advanced melanoma and neurofibromatosis type 1 (NF1). We report a population pharmacokinetic (PopPK) model-based analysis of FCN-159 and its application to inform dose selection for NF1 pediatric trials.Methods: PK data collected from patients with advanced melanoma and NF1 in two clinical studies (NCT03932253 and NCT04954001) were analyzed using a non-linear mixed effects model. The adult model was adapted by incorporating allometric scaling for PK projection in 2–17 years old children. Pediatric exposure in different body surface area (BSA) bins was simulated to identify nominal doses (i.e., dose amounts given as integers) and BSA bin cutoffs to achieve exposure comparable to adults’ optimal exposure across the entire pediatric BSA range.Results: The final dataset consisted of 45 subjects with a total of 1030 PK samples. The PK of FCN-159 was well-described by a 2-compartment model with first-order linear elimination and delayed first-order absorption. Covariates, including BSA, age, sex, albumin, total protein, and cancer type, were identified as statistically significant predictors of FCN-159 disposition. Simulations based on the final model projected daily doses of 4 mg/m2 QD with optimized BSA bin cutoffs would allow fixed nominal doses within each bin and result in steady state exposure approximating the adult exposure observed at the recommended phase 2 dose (RP2D) in NF1, which is 8 mg QD.Conclusion: The developed population PK model adequately described the PK profile of FCN-159, which was adapted using allometric scaling to inform dose selection for NF1 pediatric trials.