Search

Abstract Background Play is an indispensable and meaningful activity in children’s daily life. Research has shown that autistic children often exhibit differences in play development. The core traits of autism, such as distinct patterns in social interaction and communication, focused interests, and repetitive behaviors, frequently manifest in their play. Therefore, play may serve as an insightful measure of these differences. Unlike previous studies focusing on play behaviors only, we explored other behaviors associated with autism during free play, and constructed a clinical prediction model for effectively screening autistic children. Methods Participants, including 123 autistic children and 123 neurotypical children aged 1–6 years, engaged in a 1.5-min free play with fixed toys, which was videotaped. A novel behavior-coding scheme was used to code these videos for 19 autistic behaviors, including play. The coding details of the 19 behaviors were then converted and expanded to 81 digital behavior indicators, including counts, duration, and proportion. Results The autistic children showed less functional play and imaginative play and reduced social communication and interactions, such as eye contact, facial expressions, and vocalizations, compared to the neurotypical children during free play. Furthermore, 5 behavioral indicators were selected for the prediction model through stepwise logistic regression, including 1 on socially oriented vocalizations and 4 on count and duration of functional play. The receiver operating characteristic (ROC) curve revealed a good prediction performance with an area under the curve (AUC) of 0.826, a sensitivity of 85.4%, and a specificity of 68.3%. Conclusion Our findings highlight differences in play performance and social communication and interactions during free play among autistic children. Based on these findings, we constructed a good clinical prediction model, which might be a potential digital tool used by clinicians to effectively screen autistic children.

Abstract Background Leaves are important sites for photosynthesis and can convert inorganic substances into organic matter. Photosynthetic performance is an important factor affecting crop yield. Leaf colour is closely related to photosynthesis, and leaf colour mutants are considered an ideal material for studying photosynthesis. Results We obtained a yellow-green leaf mutant jym165, using ethyl methane sulfonate (EMS) mutagenesis. Physiological and biochemical analyses indicated that the contents of chlorophyll a, chlorophyll b, carotenoids, and total chlorophyll in the jym165 mutant decreased significantly compared with those in Jiyu47 (JY47). The abnormal chloroplast development of jym165 led to a decrease in net photosynthetic rate and starch content compared with that of JY47. However, quality traits analysis showed that the sum of oil and protein contents in jym165 was higher than that in JY47. In addition, the regional yield (seed spacing: 5 cm) of jym165 increased by 2.42% compared with that of JY47 under high planting density. Comparative transcriptome analysis showed that the yellow-green leaf phenotype was closely related to photosynthesis and starch and sugar metabolism pathways. Genetic analysis suggests that the yellow-green leaf phenotype is controlled by a single recessive nuclear gene. Using Mutmap sequencing, the candidate regions related of leaf colour was narrowed to 3.44 Mb on Chr 10. Conclusions Abnormal chloroplast development in yellow-green mutants leads to a decrease in the photosynthetic pigment content and net photosynthetic rate, which affects the soybean photosynthesis pathway and starch and sugar metabolism pathways. Moreover, it has the potentiality to increase soybean yield under dense planting conditions. This study provides a useful reference for studying the molecular mechanisms underlying photosynthesis in soybean.

Using the daily average temperature data of 125 national meteorological observation stations and NCAR/NCEP reanalysis data from 1961 to 2022, the main patterns of Asian circulation changes in winter and their impact on low-temperature events in Yunnan province were analyzed. The results show that there are two patterns of atmospheric circulation at 500 hPa in Asia during winter, namely zonal and meridional patterns, and the impact of the two patterns on low-temperature events in Yunnan province is significantly different. During the zonal circulation pattern, the stronger cold air flows directly southward from Lake Baikal to low latitudes, mainly affecting the eastern part of East Asia. The low-temperature events in Yunnan province also mainly occur in the eastern region. At this time, the low-temperature process is closely related to the strengthening of the Ural Mountains High and the Siberian High, as well as the wave trains at mid-to-high latitudes in Eurasia. During the meridional circulation pattern, the cold air flows southward along the eastern coast of the East Asian continent with the northerly airflow of the eastern side of the anomalous anticyclone in Lake Baikal, and moves southeast in the form of backflow in mid-to-low latitude areas. The activity is located southward and westward, which is beneficial for the low temperature of Yunnan province, the Tibet Plateau, and low latitude areas in Southeast Asia. At this time, the low-temperature events are mainly related to the changes in the subtropical wave train and the strengthening of positive surface level pressure (SLP) anomalies on the Tibet Plateau, but not closely related to the strengthening of High pressure in the Ural Mountain and the Siberian.

Abstract Background The mortality rate of COVID-19 patients with critical symptoms is reported to be 40.5%. Early identification of patients with poor progression in the critical cohort is essential to timely clinical intervention and reduction of mortality. Although older age, chronic diseases, have been recognized as risk factors for COVID-19 mortality, we still lack an accurate prediction method for every patient. This study aimed to delve into the cell-free DNA fragmentomics of critically ill patients, and develop new promising biomarkers for identifying the patients with high mortality risk. Methods We utilized whole genome sequencing on the plasma cell-free DNA (cfDNA) from 33 COVID-19 patients with critical symptoms, whose outcomes were classified as survival (n = 16) and death (n = 17). Mitochondrial DNA (mtDNA) abundance and fragmentomic properties of cfDNA, including size profiles, ends motif and promoter coverages were interrogated and compared between survival and death groups. Results Significantly decreased abundance (~ 76% reduction) and dramatically shorter fragment size of cell-free mtDNA were observed in deceased patients. Likewise, the deceased patients exhibited distinct end-motif patterns of cfDNA with an enhanced preference for “CC” started motifs, which are related to the activity of nuclease DNASE1L3. Several dysregulated genes involved in the COVID-19 progression-related pathways were further inferred from promoter coverages. These informative cfDNA features enabled a high PPV of 83.3% in predicting deceased patients in the critical cohort. Conclusion The dysregulated biological processes observed in COVID-19 patients with fatal outcomes may contribute to abnormal release and modifications of plasma cfDNA. Our findings provided the feasibility of plasma cfDNA as a promising biomarker in the prognosis prediction in critically ill COVID-19 patients in clinical practice.

Abstract Glomus tumor (GT) is a neoplastic lesion of mesenchymal origin arising from the neuromyoarterial canal or glomus body. Although most GT occur in the peripheral soft tissue and extremities, these tumors can grow anywhere in the body. Here, we describe an uncommon case of GT involving the prostate.

The problem of Pb pollution emission from sludge during its combustion has received a widespread attention. The migration and transformation characteristics of Pb during sludge combustion were analyzed by a combination of experimental studies and simulations with the help of inductively coupled plasma mass spectrometry (ICP-MS), specific surface and porosity analyzer (BET), and X-ray diffraction (XRD), etc. The influences of factors such as the addition of CaO, moisture, and acidic gases on the volatilization of Pb and the solid-phase enrichment were investigated, and the activity strength of the adsorption of PbCl2 molecules on different surfaces were revealed with the combination of the density-functional theory. The experimental results showed that the increase of Pb residue to 61.37% after sludge combustion at 900 °C was mainly influenced by the melting effect. The addition of 4% CaO was unfavorable to the enrichment of Pb in the solid-phase product at combustion temperatures of 700−900 °C, while the residual rate of Pb in the solid-phase product increased by 7.82% at 1 000 °C with the addition of 4% CaO. The Pb residual rate was reduced by 28.43% at 20% sludge moisture content compared to burnt dry sludge. The presence of acidic gases favored Pb immobilization, but the promotion varied inconsistently with concentration. CO2 had an obvious promotion effect on the fixation of Pb, and the larger the concentration, the more favorable to the enrichment of Pb, when the simulated flue gas was fed with 30% CO2, the residual rate of Pb increased by 23.37%. While SO2 had a weak promoting effect on Pb immobilization, and with the increase of SO2 concentration, the residual rate of Pb was firstly increased and then decreased, and in the combustion condition with 0.15% SO2, the residual rate of Pb was increased to the best extent, which was only 4.82%. The residual rate of Pb after the combustion of sludge loaded with 4% CaO at 20% H2O/20O2/80N2, 20CO2/20O2/60N2 and 0.15CO2/20O2/79.85N2 increased by −3.61%, 8.77% and 7.65%, respectively. Simulations showed that after the adsorption of PbCl2 molecules on the clean CaO(001) surface, the Pb atoms of Pb molecules underwent orbital hybridization with Osurf atoms, whereas on the surface of CaO(001) with pre-adsorbed CO2, SO2 and H2O, the Pb atoms of PbCl2 molecules would undergo orbital hybridization with OH, OC, and OS atoms, which led to an increase of adsorption energies of PbCl2 molecules after adsorption on the surface of CaO(001) with pre-adsorbed CO2, SO2, and H2O on the surface of CaO(001) with pre-adsorbed CO2, SO2 and OS atoms, which resulted in the increase of adsorption energy after adsorption by 90.069, −13.458 and −55.836 kJ/mol, respectively, compared with that on the clean surface. In summary, controlling the combustion temperature and adding an appropriate amount of CaO can effectively improve the residual rate of Pb, the presence of moisture inhibits the immobilization of Pb, and the CO2 and SO2 atmospheres are favorable for the enrichment of Pb in the solid-phase products.

Background: Streptococcus agalactiae is a recognized pathogen that primarily affects infants and pregnant women. However, its increasingly important role in causing invasive infections among non-pregnant adults has become a significant health concern due to the severity and variety of its clinical impacts. Methods: Nonduplicate S. agalactiae clinical strains associated with clinical infections (n = 139) were isolated from non-pregnant adults in Shandong, China. Antibiotic susceptibility testing, whole-genome sequencing and genomic analyses were conducted to characterize the genome and identify resistance features of these strains. Results: The strains exhibited universal susceptibility to penicillin, ampicillin, cefotaxime, meropenem, linezolid and vancomycin. Notably, high resistance rates were observed for erythromycin (91.4%), clindamycin (89.2%), levofloxacin (84.2%), tetracycline (54.0%) and, to a lesser extent, chloramphenicol (12.9%). Serotyping revealed seven serotypes and one non-typeable strain. Serotypes Ia, Ib, III and V predominated, representing 95.7% of the strains. Nineteen sequence types were categorized into seven clonal complexes, with CC10 being the most prevalent at 48.9%. The resistance genes mreA (100%), ermB (70.5%) and tetM (46.0%) were commonly detected. All the isolates carried at least one pilus backbone determinant and one alpha-like protein gene, with the PI-1+PI-2a and the bca gene being the most frequent at 84.2% and 54.7%, respectively. Conclusions: While S. agalactiae strains in non-pregnant adults retain sensitivity to β-lactam antibiotics, the elevated resistance to erythromycin, clindamycin, levofloxacin and tetracycline is concerning. Given the growing elderly population worldwide, the burden of S. agalactiae infections is significant. Continuous surveillance of serotype distribution and antibiotic resistance patterns is imperative for targeted prevention and therapeutic strategies.

After desulphurization, the trace amount of SO2 in the tail gas of coal-fired power plant will lead to the deterioration of CO2 adsorption performance of potassium-based adsorbent. Using crystalline aluminum chloride as precursor, the solid adsorbent K2CO3/Al2O3 was prepared by sol-gel method. The adsorption characteristics of CO2 in SO2 (0, 150, 250 and 400 mg/m3) atmosphere were simulated by fixed bed reaction system. Combined with the BET and XRD characterization methods, the pore structure and material composition of the adsorbent were analyzed. The influence of SO2 on the surface adsorption of CO2 by K2CO3/Al2O3(0001) was studied by using the DFT theory. The results showed that in the ideal atmosphere, the cumulative adsorption capacity of CO2 of potassium adsorbent is 1.72 mmol/g. In the presence of 150 mg/m3 SO2 in the reaction atmosphere, the potassium adsorbent reacts with SO2 to form K2SO3, resulting in a 19.77% decrease in adsorption capacity (1.38 mmol/g). When the concentration of SO2 increases to 400 mg/m3, the cumulative adsorption capacity of CO2 of potassium-based adsorbent gradually decreases to 1.26 mmol/g, the adsorption performance of CO2 of the adsorbent is deteriorated. The adsorption capacity of potassium-based adsorbent decreases to 1.1 mmol/g after seven cycles, and the cycle performance is deteriorated. The adsorption sites of CO2 and SO2 on the surface of K2CO3/Al2O3(0001) are Al-O bridge sites, and the H2O molecules are O top sites. The adsorption of SO2 on K2CO3/Al2O3(0001) surface is greater than that on H2O and CO2. When H2O and CO2 are co-adsorbed, the O-s orbitals and H-s orbitals overlap in the CO2 molecules, so that the two can promote each other during surface adsorption. Due to the active p orbitals of S and O atoms, the SO2 molecules preferentially preempt the adsorption site of CO2 and inhibit the adsorption of CO2 on the surface when co-adsorbed with CO2. The catalytic effect of H2O molecules on the adsorption of SO2 on the surface of K2CO3/Al2O3(0001) is greater than that of CO2. The presence of H2O will accelerate the reaction between SO2 and the surface, leading to the deterioration of the adsorption capacity of CO2 on the surface of the adsorbent. When CO2 and H2O are co-adsorbed on K2CO3/Al2O3(0001) surface, the carbonation mechanism is H+ and OH− in H2O molecules, which forms \begin{document}${\mathrm{HCO}}_3^- $\end{document} with \begin{document}${\mathrm{CO}}_3^{2-} $\end{document} and CO2 respectively. The reaction energy barrier is 1.12 eV, and the reaction heat is −1.47 eV.

Abstract Tissue-derived extracellular vesicles (EVs) are emerging as pivotal players to maintain organ homeostasis, which show promise as a next-generation candidate for medical use with extensive source. However, the detailed function and therapeutic potential of tissue EVs remain insufficiently studied. Here, through bulk and single-cell RNA sequencing analyses combined with ultrastructural tissue examinations, we first reveal that in situ liver tissue EVs (LT-EVs) contribute to the intricate liver regenerative process after partial hepatectomy (PHx), and that hepatocytes are the primary source of tissue EVs in the regenerating liver. Nanoscale and proteomic profiling further identify that the hepatocyte-specific tissue EVs (Hep-EVs) are strengthened to release with carrying proliferative messages after PHx. Moreover, targeted inhibition of Hep-EV release via AAV-shRab27a in vivo confirms that Hep-EVs are required to orchestrate liver regeneration. Mechanistically, Hep-EVs from the regenerating liver reciprocally stimulate hepatocyte proliferation by promoting cell cycle progression through Cyclin-dependent kinase 1 (Cdk1) activity. Notably, supplementing with Hep-EVs from the regenerating liver demonstrates translational potential and ameliorates insufficient liver regeneration. This study provides a functional and mechanistic framework showing that the release of regenerative Hep-EVs governs rapid liver regeneration, thereby enriching our understanding of physiological and endogenous tissue EVs in organ regeneration and therapy.

Abstract Infections caused by pathogenic Escherichia coli are a serious threat to human health, while conventional antibiotic susceptibility tests (AST) have a long turn-around time, and rapid antibiotic susceptibility methods are urgently needed to save lives in the clinic, reduce antibiotic misuse and prevent emergence of antibiotic-resistant bacteria. We optimized and validated the feasibility of a novel rapid AST based on SYBR Green I and Propidium Iodide (SGPI-AST) for E. coli drug susceptibility test. A total of 112 clinical isolates of E. coli were collected and four antibiotics (ceftriaxone, cefoxitin, imipenem, meropenem) were selected for testing. Bacterial survival rate of E. coli was remarkably linearly correlated with S value at different OD600 values. After optimizing the antibiotic concentrations, the sensitivity and specificity of SGPI-AST reached 100%/100%, 97.8%/100%, 100%/100% and 98.4%/99% for ceftriaxone, cefoxitin, imipenem and meropenem, respectively, and the corresponding concordances of the SGPI-AST with conventional AST were 1.000, 0.980, 1.000 and 0.979, respectively. The SGPI-AST can rapidly and accurately determine the susceptibility of E. coli clinical isolates to multiple antibiotics in 60 min, and has the potential to be applied to guide the precise selection of antibiotics for clinical management of infections caused by pathogenic E. coli.

Renal interstitial fibrosis (RIF) is a crucial and irreversible element that speeds up the advancement of diabetic nephropathy (DN) to end-stage renal disease. DN-RIF, which is mostly caused by long-lasting inflammation, is greatly affected by the NOD-like receptor thermal protein domainassociated protein 3 (NLRP3) inflammasome. This inflammasome plays a crucial role in triggering inflammatory reactions. The inflammasome has a significant impact in worsening DN-RIF by triggering processes related to inflammation, oxidative stress, and autophagy. This paper thoroughly analyzes the role of the NLRP3 inflammasome in the development of RIF and explores the possibility of traditional Chinese medicine in specifically targeting this inflammasome to reduce the severity of RIF. The primary objective is to promote progress in treatment approaches for the management of recurrent RIF.

Abstract Background A higher Life's Essential 8 (LE8)-based cardiovascular health (CVH) has been reported to be associated with a lower risk of both all-cause mortality and cardio-cerebrovascular diseases (CCVDs) related mortality in adults in the United States. At the same time, multiple studies have shown a significant negative association of CVH with the risk of stroke and CCVDs. Since no research has investigated the applicability of the LE8 in stroke patients, this study aimed to explore the association of LE8 with all-cause mortality and cardio-cerebrovascular mortality in stroke patients. Methods Data of patients were extracted from the National Health and Nutrition Examination Surveys (NHANES) database in 2007–2018 in this retrospective cohort study. Weighted univariate and multivariate COX regression analyses were utilized to investigate the associations of LE8 with all-cause mortality and cardio-cerebrovascular mortality. We further explored these relationships in subgroups of age, gender, body mass index (BMI), cancer, congestive heart failure (CHF), and coronary heart disease (CHD). The evaluation indexes were hazard ratios (HRs) and 95% confidence intervals (CIs). Results Among the eligible patients, 278 died from all-cause and 89 (8.38%) of them died due to CCVDs. After adjusting for covariates, patients with LE8 score ≥ 58.75 seemed to have both lower risk of all-cause mortality (HR = 0.46, 95%CI: 0.31–0.69) and cardio-cerebrovascular mortality (HR = 0.51, 95%CI: 0.26–0.98), comparing to those with LE8 score

Background: The prediction of response to immunotherapy mostly depends on the programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) status, and the 22C3 pharmDx assay has been approved in esophageal squamous cell carcinoma (ESCC). However, the widespread use of the 22C3 pharmDx assay is limited due to its availability. Thus, alternative PD-L1 assays are needed. We aimed to investigate the analytical and clinical diagnostic performances of four PD-L1 assays and to compare their concordances with the 22C3 pharmDx assay. Methods: The PD-L1 22C3 pharmDx assay was performed on the Dako Autostainer Link 48 platform, three testing assays (PD-L1 E1L3N XP antibody [Ab], PD-L1 BP6099 Ab and PD-L1 CST E1L3N Ab) on the Leica BOND-MAX/III platform, and one testing assay (PD-L1 MXR006 Ab) on the Roche VENTANA Benchmark Ultra platform. A total of 218 ESCC cases from four centers were included in this retrospective study. Professionals from each center stained and read the IHC slides independently and determined the combined positive score (CPS) and the tumor proportion score (TPS). Results: Regarding analytical performance, the four testing assays demonstrated good correlations with the 22C3 pharmDx assay when evaluated by the TPS or CPS (ρ > 0.8 for all four assays). Regarding diagnostic performance (CPS ≥ 10 was used as the cutoff), the four testing assays showed moderate concordances with the 22C3 pharmDx assay (kappa > 0.7 for all four assays). The overall percent agreements between each testing assay and the 22C3 pharmDx assay was at least 87.2 %. Conclusion: This study provides insight into the potential interchangeability of the four PD-L1 assays with the 22C3 pharmDx assay.

Abstract Within the Industry 4.0 landscape, humans collaborate with cyber and physical elements to form human‐cyber‐physical systems (HCPS). These environments are increasingly complex and challenging workspaces due to increasing levels of automation and data availability. An effective system design requires suitable frameworks that consider human activities and needs whilst supporting overall system efficacy. Although several reviews of frameworks for technology were identified, none of these focused on the human in the system (moving towards Industry 5). The critical literature review presented provides a summary of HCPS frameworks, maps the considerations for a human in HCPS, and provides insight for future framework and system development. The challenges, recommendations, and areas for further research are discussed.

Fine terrain classification is one of the main applications of Synthetic Aperture Radar (SAR). In the multiband fully polarized SAR operating mode, obtaining information on different frequency bands of the target and polarization response characteristics of a target is possible, which can improve target classification accuracy. However, the existing datasets at home and abroad only have low-resolution fully polarized classification data for individual bands, limited regions, and small samples. Thus, a multidimensional SAR dataset from Hainan is used to construct a multiband fully polarized fine classification dataset with ample sample size, diverse land cover categories, and high classification reliability. This dataset will promote the development of multiband fully polarized SAR classification applications, supported by the high-resolution aerial observation system application calibration and verification project. This paper provides an overview of the composition of the dataset, and describes the information and dataset production methods for the first batch of published data (MPOLSAR-1.0). Furthermore, this study presents the preliminary classification experimental results based on the polarization feature classification and classical machine learning classification methods, providing support for the sharing and application of the dataset.

Introduction: Childhood-onset asthma is a chronic respiratory disease that profoundly impacts patients, their families, and healthcare systems. This study explores the lived experiences, challenges, and perceptions of mothers in managing asthma, controlling symptoms, and maintaining the quality of life for their children with asthma in Palestine. Methods: A qualitative descriptive design through semi-structured interviews was used in this study. Purposive sampling was used to identify mothers who have children with severe uncontrolled asthma in the four public hospitals with pediatric units in the West Bank, Palestine. Mothers of children with scored below 15 on the asthma control test were included in the study. The data were analyzed using an analytical framework following a thematic analysis through the NVivo 11. Results: A total of 20 mothers participated in interviews wherein they delineated the most important challenges negatively affecting asthma management from mothers’ perspectives. These challenges encompassed frequent emergency room visits, improper medication administration practices, and limitations in physical activity. The mothers expressed concerns regarding asthma control, including anxieties concerning the chronicity of the illness, adverse effects of medications, and susceptibility to weather fluctuations. The main themes that emerged from the data included reduced quality of life for the child, parental responsibility for monitoring triggers, symptoms, and medications, challenges in asthma management, apprehensions regarding asthma control, and strategies for enhancing asthma management. Conclusion: This study emphasizes the pressing need for targeted interventions to address asthma management, environmental triggers, and psychosocial disruptions related to asthma in children with asthma to enhance the quality of life and asthma control. This study highlights the importance of developing strategies that provide mothers with the appropriate information and tools to navigate the complexities of caring for a child with asthma.

Background: Magnetic resonance enterography (MRE) has become a routine intestinal imaging examination for Crohn’s disease (CD). Sufficient bowel preparation is fundamental for MRE. Objectives: To compare the efficacy and compliance of bowel preparation between through a mid-gut tube and oral administration for MRE in CD. Design: This was an open-label, prospective, multicenter, randomized controlled trial. Methods: Eligible patients were randomized at a 1:1 ratio into an oral group (bowel preparation by oral administration) and a tubing group (bowel preparation through a mid-gut tube). Bowel preparation for MRE included bowel cleaning and bowel distention. The primary outcomes were the degree of discomfort and grade of bowel distention. The secondary outcomes were diagnostic accuracy rate through MRE, mental stress, and bowel preparation method preference. Results: A total of 95 CD patients were included in the final analysis. Subjects in the tubing group complained of less vomiting during bowel preparation than those in the oral group ( p

The pulmonary system represents a unique lipidomic environment as it contains cellular membrane-bound lipid species and a specialized reservoir of lipids in the airway epithelial lining fluid. As a major initial point of defense, airway lipids react to inhaled contaminants such as volatile organic compounds, oxides of nitrogen, or ozone (O3), creating lipokine signaling that is crucial for both the initiation and resolution of inflammation within the lung. Dietary modulation of eicosanoids has gained increased attention in recent years for improvements to cardiovascular health. The current study sought to examine how dietary supplementation with eicosanoid precursors (i.e, oils rich in saturated or polyunsaturated fatty acids) might alter the lung lipid composition and subsequently modify the inflammatory response to ozone inhalation. Our study demonstrated that mice fed a diet high in saturated fatty acids resulted in diet-specific changes to lung lipid profiles and increased cellular recruitment to the lung following ozone inhalation. Bioinformatic analysis revealed an ozone-dependent upregulation of several lipid species, including phosphoserine 37:5. Pathway analysis of lipid species revealed the process of lateral diffusion of lipids within membranes to be significantly altered due to ozone exposure. These results show promising data for influencing pulmonary lipidomic profiles via diet, which may provide a pragmatic therapeutic approach to protect against lung inflammation and damage following pulmonary insult.

Summary: Reliable blood-based tests for identifying early-stage breast cancer remain elusive. Employing single-cell transcriptomic sequencing analysis, we illustrate a close correlation between nucleotide metabolism in the breast cancer and activation of regulatory T cells (Tregs) in the tumor microenvironment, which shows distinctions between subtypes of patients with triple-negative breast cancer (TNBC) and non-TNBC, and is likely to impact cancer prognosis through the A2AR-Treg pathway. Combining machine learning with absolute quantitative metabolomics, we have established an effective approach to the early detection of breast cancer, utilizing a four-metabolite panel including inosine and uridine. This metabolomics study, involving 1111 participants, demonstrates high accuracy across the training, test, and independent validation cohorts. Inosine and uridine prove predictive of the response to neoadjuvant chemotherapy (NAC) in patients with TNBC. This study deepens our understanding of nucleotide metabolism in breast cancer development and introduces a promising non-invasive method for early breast cancer detection and predicting NAC response in patients with TNBC.

Abstract The gut microbiome (GM) modulates body weight/composition and gastrointestinal functioning; therefore, approaches targeting resident gut microbes have attracted considerable interest. Intermittent fasting (IF) and protein pacing (P) regimens are effective in facilitating weight loss (WL) and enhancing body composition. However, the interrelationships between IF- and P-induced WL and the GM are unknown. The current randomized controlled study describes distinct fecal microbial and plasma metabolomic signatures between combined IF-P (n = 21) versus a heart-healthy, calorie-restricted (CR, n = 20) diet matched for overall energy intake in free-living human participants (women = 27; men = 14) with overweight/obesity for 8 weeks. Gut symptomatology improves and abundance of Christensenellaceae microbes and circulating cytokines and amino acid metabolites favoring fat oxidation increase with IF-P (p

Abstract Background Understanding the intricate influences of risk factors contributing to suicide among young individuals remains a challenge. The current study employed interpretable machine learning and network analysis to unravel critical suicide-associated factors in Chinese university students. Methods A total of 68,071 students were recruited between Sep 2016 and Sep 2020 in China. Students reported their lifetime experiences with suicidal thoughts and behaviors, categorized as suicide ideation (SI), suicide plan (SP), and suicide attempt (SA). We assessed 36 suicide-associated factors including psychopathology, family environment, life events, and stigma. Local interpretations were provided using Shapley additive explanation (SHAP) interaction values, while a mixed graphical model facilitated a global understanding of their interplay. Results Local explanations based on SHAP interaction values suggested that psychoticism and depression severity emerged as pivotal factors for SI, while paranoid ideation strongly correlated with SP and SA. In addition, childhood neglect significantly predicted SA. Regarding the mixed graphical model, a hierarchical structure emerged, suggesting that family factors preceded proximal psychopathological factors, with abuse and neglect retaining unique effects. Centrality indices derived from the network highlighted the importance of subjective socioeconomic status and education in connecting various risk factors. Conclusions The proximity of psychopathological factors to suicidality underscores their significance. The global structures of the network suggested that co-occurring factors influence suicidal behavior in a hierarchical manner. Therefore, prospective prevention strategies should take into account the hierarchical structure and unique trajectories of factors.

Abstract The CUL3-RING E3 ubiquitin ligases (CRL3s) play an essential role in response to extracellular nutrition and stress stimuli. The ubiquitin ligase function of CRL3s is activated through dimerization. However, how and why such a dimeric assembly is required for its ligase activity remains elusive. Here, we report the cryo-EM structure of the dimeric CRL3KLHL22 complex and reveal a conserved N-terminal motif in CUL3 that contributes to the dimerization assembly and the E3 ligase activity of CRL3KLHL22. We show that deletion of the CUL3 N-terminal motif impairs dimeric assembly and the E3 ligase activity of both CRL3KLHL22 and several other CRL3s. In addition, we found that the dynamics of dimeric assembly of CRL3KLHL22 generates a variable ubiquitination zone, potentially facilitating substrate recognition and ubiquitination. These findings demonstrate that a CUL3 N-terminal motif participates in the assembly process and provide insights into the assembly and activation of CRL3s.

Abstract Background Neoadjuvant therapy followed by surgery has become the standard of care for locally advanced esophageal squamous cell carcinoma (ESCC) and accurate pathological response assessment is critical to assess the therapeutic efficacy. However, it can be laborious and inconsistency between different observers may occur. Hence, we aim to develop an interpretable deep-learning model for efficient pathological response assessment following neoadjuvant therapy in ESCC. Methods This retrospective study analyzed 337 ESCC resection specimens from 2020–2021 at the Pudong-Branch (Cohort 1) and 114 from 2021–2022 at the Puxi-Branch (External Cohort 2) of Fudan University Shanghai Cancer Center. Whole slide images (WSIs) from these two cohorts were generated using different scanning machines to test the ability of the model in handling color variations. Four pathologists independently assessed the pathological response. The senior pathologists annotated tumor beds and residual tumor percentages on WSIs to determine consensus labels. Furthermore, 1850 image patches were randomly extracted from Cohort 1 WSIs and binarily classified for tumor viability. A deep-learning model employing knowledge distillation was developed to automatically classify positive patches for each WSI and estimate the viable residual tumor percentages. Spatial heatmaps were output for model explanations and visualizations. Results The approach achieved high concordance with pathologist consensus, with an R^2 of 0.8437, a RAcc_0.1 of 0.7586, a RAcc_0.3 of 0.9885, which were comparable to two senior pathologists (R^2 of 0.9202/0.9619, RAcc_0.1 of 8506/0.9425, RAcc_0.3 of 1.000/1.000) and surpassing two junior pathologists (R^2 of 0.5592/0.5474, RAcc_0.1 of 0.5287/0.5287, RAcc_0.3 of 0.9080/0.9310). Visualizations enabled the localization of residual viable tumor to augment microscopic assessment. Conclusion This work illustrates deep learning's potential for assisting pathological response assessment. Spatial heatmaps and patch examples provide intuitive explanations of model predictions, engendering clinical trust and adoption (Code and data will be available at https://github.com/WinnieLaugh/ESCC_Percentage once the paper has been conditionally accepted). Integrating interpretable computational pathology could help enhance the efficiency and consistency of tumor response assessment and empower precise oncology treatment decisions.

Abstract Effective therapeutic targets and early diagnosis are major challenges in the treatment of gastrointestinal tract (GIT) cancers. SALL4 is a well-known transcription factor that is involved in organogenesis during embryonic development. Previous studies have revealed that SALL4 regulates cell proliferation, survival, and migration and maintains stem cell function in mature cells. Additionally, SALL4 overexpression is associated with tumorigenesis. Despite its characterization as a biomarker in various cancers, the role of SALL4 in GIT cancers and the underlying mechanisms are unclear. We describe the functions of SALL4 in GIT cancers and discuss its upstream/downstream genes and pathways associated with each cancer. We also consider the possibility of targeting these genes or pathways as potential therapeutic options for GIT cancers.

Abstract Nobiletin, a citrus polymethoxy flavonoid with antiapoptotic and antioxidative properties, could safeguard against cisplatin-induced nephrotoxicity and neurotoxicity. Cisplatin, as the pioneer of anti-cancer drug, the severe ototoxicity limits its clinical applications, while the effect of nobiletin on cisplatin-induced ototoxicity has not been identified. The current study investigated the alleviating effect of nobiletin on cisplatin-induced ototoxicity and the underlying mechanisms. Apoptosis and ROS formation were evaluated using the CCK-8 assay, Western blotting, and immunofluorescence, indicating that nobiletin attenuated cisplatin-induced apoptosis and oxidative stress. LC3B and SQSTM1/p62 were determined by Western blotting, qPCR, and immunofluorescence, indicating that nobiletin significantly activated autophagy. Nobiletin promoted the nuclear translocation of NRF2 and the transcription of its target genes, including Hmox1, Nqo1, and ferroptosis markers (Gpx4, Slc7a11, Fth, and Ftl), thereby inhibiting ferroptosis. Furthermore, RNA sequencing analysis verified that autophagy, ferroptosis, and the NRF2 signaling pathway served as crucial points for the protection of nobiletin against ototoxicity caused by cisplatin. Collectively, these results indicated, for the first time, that nobiletin alleviated cisplatin-elicited ototoxicity through suppressing apoptosis and oxidative stress, which were attributed to the activation of autophagy and the inhibition of NRF2/GPX4-mediated ferroptosis. Our study suggested that nobiletin could be a prospective agent for preventing cisplatin-induced hearing loss.

Abstract Background Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) co-producing bla KPC and bla NDM poses a serious threat to public health. This study aimed to investigate the mechanisms underlying the resistance and virulence of CR-hvKP isolates collected from a Chinese hospital, with a focus on bla KPC and bla NDM dual-positive hvKP strains. Methods Five CR-hvKP strains were isolated from a teaching hospital in China. Antimicrobial susceptibility and plasmid stability testing, plasmid conjugation, pulsed-field gel electrophoresis, and whole-genome sequencing (WGS) were performed to examine the mechanisms of resistance and virulence. The virulence of CR-hvKP was evaluated through serum-killing assay and Galleria mellonella lethality experiments. Phylogenetic analysis based on 16 highly homologous carbapenem-resistant K. pneumoniae (CRKP) producing KPC-2 isolates from the same hospital was conducted to elucidate the potential evolutionary pathway of CRKP co-producing NDM and KPC. Results WGS revealed that five isolates individually carried three unique plasmids: an IncFIB/IncHI1B-type virulence plasmid, IncFII/IncR-type plasmid harboring KPC-2 and IncC-type plasmid harboring NDM-1. The conjugation test results indicated that the transference of KPC-2 harboring IncFII/IncR-type plasmid was unsuccessful on their own, but could be transferred by forming a hybrid plasmid with the IncC plasmid harboring NDM. Further genetic analysis confirmed that the pJNKPN26-KPC plasmid was entirely integrated into the IncC-type plasmid via the copy-in route, which was mediated by TnAs1 and IS26. Conclusion KPC-NDM-CR-hvKP likely evolved from a KPC-2-CRKP ancestor and later acquired a highly transferable bla NDM-1 plasmid. ST11-KL64 CRKP exhibited enhanced plasticity. The identification of KPC-2-NDM-1-CR-hvKP highlights the urgent need for effective preventive strategies against aggravated accumulation of resistance genes.

Abstract Background Anthocyanins are the most important compounds for nutritional quality and economic values of blood orange. However, there are few reports on the pre-harvest treatment accelerating the accumulation of anthocyanins in postharvest blood orange fruit. Here, we performed a comparative transcriptome and metabolomics analysis to elucidate the underlying mechanism involved in seasonal drought (SD) treatment during the fruit expansion stage on anthocyanin accumulation in postharvest ‘Tarocco’ blood orange fruit. Results Our results showed that SD treatment slowed down the fruit enlargement and increased the sugar accumulation during the fruit development and maturation period. Obviously, under SD treatment, the accumulation of anthocyanin in blood orange fruit during postharvest storage was significantly accelerated and markedly higher than that in CK. Meanwhile, the total flavonoids and phenols content and antioxidant activity in SD treatment fruits were also sensibly increased during postharvest storage. Based on metabolome analysis, we found that substrates required for anthocyanin biosynthesis, such as amino acids and their derivatives, and phenolic acids, had significantly accumulated and were higher in SD treated mature fruits compared with that of CK. Furthermore, according to the results of the transcriptome data and weighted gene coexpression correlation network analysis (WGCNA) analysis, phenylalanine ammonia-lyase (PAL3) was considered a key structural gene. The qRT-PCR analysis verified that the PAL3 was highly expressed in SD treated postharvest stored fruits, and was significantly positively correlated with the anthocyanin content. Moreover, we found that other structural genes in the anthocyanin biosynthesis pathway were also upregulated under SD treatment, as evidenced by transcriptome data and qRT-PCR analysis. Conclusions The findings suggest that SD treatment promotes the accumulation of substrates necessary for anthocyanin biosynthesis during the fruit ripening process, and activates the expression of anthocyanin biosynthesis pathway genes during the postharvest storage period. This is especially true for PAL3, which co-contributed to the rapid accumulation of anthocyanin. The present study provides a theoretical basis for the postharvest quality control and water-saving utilization of blood orange fruit.

The global health threat posed by carbapenem-resistant Klebsiella pneumoniae (CRKP) is exacerbated by the limited availability of effective treatments. Bacteriophages are promising alternatives to conventional antimicrobial agents. However, current phage databases are limited. Thus, identifying and characterizing new phages could provide biological options for the treatment of multi-drug resistant bacterial infections. Here, we report the characterization of a novel lytic phage, vB_KpnP_23, isolated from hospital sewage. This phage exhibited potent activity against carbapenemase-producing CRKP strains and was characterised by an icosahedral head, a retractable tail, and a genome comprising 40,987 base pairs, with a G + C content of 51 %. Capable of targeting and lysing nine different capsule types (K-types) of CRKP, including the clinically relevant ST11-K64, it demonstrated both high bacteriolytic efficiency and stability in various environmental contexts. Crucially, vB_KpnP_23 lacks virulence factors, antimicrobial resistance genes, or tRNA, aligning with the key criteria for therapeutic application. In vitro evaluation of phage-antibiotic combinations revealed a significant synergistic effect between vB_KpnP_23 and meropenem, levofloxacin, or amikacin. This synergy could lead to an 8-fold reduction in the minimum inhibitory concentration (MIC), suggesting that integrated treatments combining this phage with the aforementioned antibiotics may substantially enhance drug effectiveness. This approach not only extends the clinical utility of these antibiotics but also presents a strategic advance in combating antibiotic resistance. Specifically, it underscores the potential of phage-antibiotic combinations as a powerful tool in the treatment of infections caused by CRKP, offering a promising avenue to mitigate the public health challenges of antibiotic-resistant pathogens.

Background The global prevalence of violence against children is alarmingly high, with millions facing violent discipline and physical punishment. In Mongolia, domestic violence-related criminal offenses have sharply increased, with a 46.92% surge in the first quarter of 2020 compared to 2019. Objective This study aimed to estimate the prevalence of and identify factors associated with physical punishment and/or psychological aggression experienced by children under 5 years old from their caregivers. Methods We used data from the nationally representative 2018 MICS6 dataset. To examine the association between independent and dependent variables, we used multilevel Poisson regression because it provides a better estimate and is more interpretable when the prevalence is relatively high. Results The prevalence of psychological aggression was reported at 32.3% and physical punishment at 31.6%, including severe forms. Nonviolent techniques were common, with 77.5% exclusively using nonviolent discipline. Psychological aggression was more likely to occur in older children (3 and 4 years old) and in households with Buddhist heads. Additionally, 3-year-olds are more likely to experience physical punishment compared to 2-year-olds. Conclusion These findings underscore the need for targeted policy interventions, including age-sensitive parental education programs and religious and cultural sensitivity measures. Comprehensive educational and awareness programs are essential to foster a culture of nonviolence across all educational levels, highlighting the need for context-specific policies to safeguard the well-being of children in Mongolia.

Agricultural price forecasting plays an important role in stabilising markets and ensuring food security. It provides insights for various stakeholders to optimise planting choices, allocate resources efficiently and mitigate potential risks. However, price forecasting during food safety incidents poses unique challenges. This study focused on a case of tuna fraud in Spain in 2017, which caused 105 people to fall ill and influenced consumer behaviour in fish purchases. To forecast fish prices during an incident of fraud, we used an artificial neural network model (ANN) based on the price of tuna and its substitutes, salmon and hake, as well as a communication index based on the number of posts regarding the tuna fraud from the social media platform X (formerly Twitter). ANN was compared with a threshold vector autoregressive model (TVAR), a classical time series econometric model that offers valuable insights into price dynamics. The results showed that, in the short term, TVAR offers a better price forecast for tuna and salmon, considering the impacts of the X platform. In the medium term, ANN outperformed TVAR. This study contributes to the ANN literature regarding agrifood price forecasting during food safety incidents.

Background In low- and middle-income countries, the double burden of malnutrition is prevalent. Many countries in Africa are currently confronted with overweight and obesity, particularly among women, coupled with an increase in the prevalence of non-communicable diseases. Objective This study examines trends in overweight and obesity among Ethiopian women of reproductive age from 2005 to 2016, and identifies associated factors. Methods We used three consecutive datasets from 2005 (n = 14070), 2011 (n = 16515), and 2016 (n = 15683) demographic health survey years. Multilevel logistic regression was used to identify the determinant factors among individual- and cluster-level variables. Results The prevalence of overweight and obesity among reproductive women in Ethiopia increased steadily from 6.09% in 2005 to 8.54% in 2011, and 10.16% in 2016. However, mixed patterns were observed among the regions of the country. We found that age, education, living in urban areas, and living in a rich community are associated with becoming overweight and obese. For instance, the odds of becoming overweight and obese among women aged 35–49 were higher than those among women aged 15–24 (odds ratio [OR] = 3.62, 95% Confidence Interval [CI]:2.64–4.97). Women who completed secondary school have higher odds than those without formal education (OR = 1.64, 95% CI:1.19–2.26). Conclusion To our knowledge, this is the first study to investigate trends in the nationwide prevalence of overweight and obesity and the associated factors among Ethiopian women. This study warrants further follow-up research to identify the pathways between overweight and obesity and their probable factors.

ABSTRACTThe estimation of soil moisture (SM) utilizing the data from the Cyclone Global Navigation Satellite System (CYGNSS) has attracted significant interest in recent times. However, CYGNSS’ inherent capability of variable resolution has not been fully exploited, often resulting in a loss of detailed spatial information in the raw data. In this paper, a novel downscaling scheme tailored for CYGNSS data is introduced to yield a “self-adjusting adaptive resolution” SM product, which dynamically varies the resolution of SM estimates based on the available CYGNSS data resolution at different geographic locations. Initially, a direct quantitative relationship is established between the key CYGNSS parameters reflecting SM variations and the reference SM from the Soil Moisture Active Passive (SMAP) mission with a coarse resolution of 36 km. This model is then applied to CYGNSS observations with resolutions down to 3 km to generate high-resolution, self-adjusting SM estimates that better conserve the fine-scale information linked to the original CYGNSS data. Extensive experimental results with error ratio diagrams show that the advanced geographically weighted regression (GWR)-based SM estimation method outperforms other competing estimation models and better retains localized spatial relationships and patterns. This study underscores the potential of CYGNSS as a novel and robust independent data source capable of delivering fine-resolution SM estimations by harnessing its unique multiresolution observational capability.

Release and transport of organic carbon (OC), a large portion of which is complexed with mineral colloids, can lead to long-term C sequestration. However, the role of mobile colloids in carbon cycling is not well understood. In this study, we conducted experiments using syringe columns to measure size-dependent colloid mobility and associated OC loadings under stepwise reductions of redox potential, representing existence of different electron acceptors. Colloids were extracted from both leachate and soil samples, designated as leachate colloids and soil colloids, respectively, and fractionated into different sizes: particulates (450–1000 nm), fine colloids (100–450 nm) and nano colloids (2–100 nm) using sequential centrifugation and ultrafiltration techniques. Increases in leachate solution pH and ionic strength (IS) with decreasing redox potential promoted colloid release, as indicated in the increase in turbidity values, due to increased electrostatic repulsion between colloids and soil matrix. The average OC loading by colloids, i.e., the amount of OC associated with per unit mass of colloids, in leachate colloids was up to four times that of soil colloids for the same size fraction. In addition, fine colloids had ∼2 times higher OC loading (∼0.4 mg C mg−1 colloids) than particulates (∼0.2 mg C mg−1 colloid) for leachate colloids. Moreover, measurements of C:N ratio and the natural abundance of stable δ13C and δ15N isotope signatures of soil colloids showed that the fine-colloid fraction experienced more significant fluctuations in these measurements as redox potential decreased than the other two fractions (i.e., particulates and nano colloids). The results of this study demonstrated that OC loading, composition and reactivity all varied with size and strongly influenced by redox conditions. This knowledge can help improve the understanding of how different phases of OC, e.g., dissolved vs. colloidal OC, may impact C sequestration and transport in soils.

Background: Rhabdomyosarcoma (RMS) is one of the most common soft tissue sarcomas in children and adolescents, in which PAX3-FOXO1 fusion gene positive patients have very poor prognosis. PAX3-FOXO1 has been identified as an independent prognostic predictor in RMS, with no currently available targeted therapeutic intervention. The novel tyrosine kinase inhibitor anlotinib exhibits a wide range of anticancer effects in multiple types of cancers; however, there have been no relevant studies regarding its application in RMS. Materials and methods: We investigated the effects of PAX3-FOXO1 on the therapeutic efficacy of anlotinib using the CCK-8 assay, flow cytometry, invasion assay, wound healing assay, western blotting, quantitative polymerase chain reaction(qPCR), and xenograft experiments. RNA-seq and co-immunoprecipitation assays were conducted to determine the specific mechanism by which anlotinib regulates PAX3-FOXO1 expression. Results: Anlotinib effectively inhibited RMS cell proliferation and promoted apoptosis and G2/M phase arrest while impeding tumor growth in vivo. Downregulation of PAX3-FOXO1 enhances the antitumor effects of anlotinib. Anlotinib upregulates protein kinase NEK2 and increases the degradation of PAX3-FOXO1 via the ubiquitin-proteasome pathway, leading to a reduction in PAX3-FOXO1 protein levels. Conclusion: Anlotinib effectively inhibited the malignant progression of RMS and promoted degradation of the fusion protein PAX3-FOXO1. Anlotinib could be a targeted therapeutic approach to treat PAX3-FOXO1 fusion-positive RMS.

Limited evidence has suggested a relationship between phthalate exposure and biological aging. This study investigated the association between phthalate exposure and biological aging, focusing on the mediating role of inflammation and the interaction with dietary nutrient intake. Data were analyzed from a nationwide cross-sectional survey comprising 12,994 participants aged 18 and above. Eight phthalate metabolites were detected in spot urine samples. Biological aging was assessed using the Klemera-Doubal method-biological age (KDM-BA) acceleration, phenotypic age (PA) acceleration, and homeostatic dysregulation (HD). The systemic immune-inflammation index (SII) evaluated systemic inflammation. The individual and combined associations between phthalate exposure and biological aging were assessed using linear regression, weighted quantile sum (WQS) regression, and quantile g-computation (qgcomp). The participants had a mean age of 47 years, with 50.7 % male and 44.8 % non-Hispanic white. Most phthalate metabolites were positively correlated with KDM-BA acceleration (β = 0.306–0.584), PA acceleration (β = 0.081–0.281), and HD (β = 0.016–0.026). Subgroup analysis indicated that men, older individuals, and non-Hispanic whites are particularly sensitive populations. WQS regression and qgcomp analyses consistently indicated a positive association between mixed phthalate exposure and HD, highlighting MEHHP as the most significant contributing metabolite. Mediation analyses showed inflammation partially mediated the association between phthalate metabolites and biological aging. Significant interactions regarding biological aging were found between specific phthalate metabolites and dietary nutrients (carotenoids, vitamins A, B1, B2, B6, B12, niacin, and selenium) intake. These findings indicated that the association between phthalate exposure and biological aging was mediated by inflammation, with nutrient intake mitigating this effect.

BackgroundNeuroblastoma (NB), characterized by its marked heterogeneity, is the most common extracranial solid tumor in children. The status and functionality of mitochondria are crucial in regulating NB cell behavior. While the significance of mitochondria-related genes (MRGs) in NB is still missing in key knowledge.Materials and methodsThis study leverages consensus clustering and machine learning algorithms to construct and validate an MRGs-related signature in NB. Single-cell data analysis and experimental validation were employed to characterize the pivotal role of FEN1 within NB cells.ResultsMRGs facilitated the classification of NB patients into 2 distinct clusters with considerable differences. The constructed MRGs-related signature and its quantitative indicators, mtScore and mtRisk, effectively characterize the MRGs-related patient clusters. Notably, the MRGs-related signature outperformed MYCN in predicting NB patient prognosis and was adept at representing the tumor microenvironment (TME), tumor cell stemness, and sensitivity to the chemotherapeutic agents Cisplatin, Topotecan, and Irinotecan. FEN1, identified as the most contributory gene within the MRGs-related signature, was found to play a crucial role in the communication between NB cells and the TME, and in the developmental trajectory of NB cells. Experimental validations confirmed FEN1’s significant influence on NB cell proliferation, apoptosis, cell cycle, and invasiveness.ConclusionThe MRGs-related signature developed in this study offers a novel predictive tool for assessing NB patient prognosis, immune infiltration, stemness, and chemotherapeutic sensitivity. Our findings unveil the critical function of FEN1 in NB, suggesting its potential as a therapeutic target.

ObjectiveNowadays, increasingly studies are attempting to analyze strokes in advance. The identification of brain damage areas is essential for stroke rehabilitation.ApproachWe proposed Electroencephalogram (EEG) multi-modal frequency features to classify the regions of stroke injury. The EEG signals were obtained from stroke patients and healthy subjects, who were divided into right-sided brain injury group, left-sided brain injury group, bilateral brain injury group, and healthy controls. First, the wavelet packet transform was used to perform a time-frequency analysis of the EEG signal and extracted a set of features (denoted as WPT features). Then, to explore the nonlinear phase coupling information of the EEG signal, phase-locked values (PLV) and partial directed correlations (PDC) were extracted from the brain network, and the brain network produced a second set of features noted as functional connectivity (FC) features. Furthermore, we fused the extracted multiple features and used the resnet50 convolutional neural network to classify the fused multi-modal (WPT + FC) features.ResultsThe classification accuracy of our proposed methods was up to 99.75%.SignificanceThe proposed multi-modal frequency features can be used as a potential indicator to distinguish regions of brain injury in stroke patients, and are potentially useful for the optimization of decoding algorithms for brain-computer interfaces.

Successfully transforming isolated peripheral blood mononuclear cells (PBMCs) from a healthy male into induced pluripotent stem cells (iPSCs) was achieved using non-integrating episomal vectors containing OCT4, SOX2, c-MYC, KLF4, and BCL-XL. The iPSCs exhibited a normal karyotype, expressed pluripotency markers, and demonstrated the ability to differentiate into three germ layers in vitro. This iPSC line may be employed for subsequent research purposes.

Hydraulic fracturing has become the main technology for the efficient development of geothermal energy in hot dry rock (HDR), however, few studies on the propagation behavior and mechanism of HDR hydraulic fractures under high-temperature conditions have investigated. In this paper, a large-size high-temperature true triaxial hydraulic fracturing physical modeling apparatus is designed, and hydraulic fracturing experiments with it are performed to investigate the fracture initiation and propagation behavior in natural granite samples collected from Gonghe Basin, the first HDR site in China. The experimental results show that the designed high-temperature apparatus provides a constant-temperature condition during the whole hydraulic fracturing process and the maximum temperature can reach 600 °C, showing its ability to simulate realistic temperatures and pressures in both ultra-deep and HDR formations. Although the tensile strength of the rock samples remains almost unchanged at a temperature of 200 °C, the cooling effects of the fracturing fluid in high-temperature rock can induce the formation of microfractures and significantly reduce the rock strength, thus lowering the breakdown pressure and increasing the complexity of the hydraulic fracture morphology. Compared with traditional oil and gas reservoirs, the hydraulic fractures in HDR are rougher and the specific surface area of a single fracture is larger, which can be helpful for heat extraction. This study provides a basis for understanding hydraulic fracture geometries and field construction design in HDRs.

Abstract Purpose This study aimed to characterise the whole-genome structure of two clinical Klebsiella pneumoniae strains co-harbouring mcr-8.1 and tmexCD1-toprJ1, both resistant to colistin and tigecycline. Methods K. pneumoniae strains TGC-02 (ST656) and TGC-05 (ST273) were isolated from urine samples of different patients hospitalised at separate times in 2021. Characterisation involved antimicrobial susceptibility testing (AST), conjugation assays, whole-genome sequencing (WGS), and bioinformatics analysis. Comparative genomic analysis was conducted on mcr-8.1-carrying and tmexCD1-toprJ1-carrying plasmids. Results Both K. pneumoniae isolates displayed a multidrug-resistant phenotype, exhibiting resistance or reduced susceptibility to ampicillin, ampicillin/sulbactam, cefazolin, aztreonam, amikacin, gentamicin, tobramycin, ciprofloxacin, levofloxacin, nitrofurantoin, trimethoprim/sulfamethoxazole, apramycin, tigecycline and colistin. WGS analysis revealed that clinical strain TGC-02 carried the TmexCD1-toprJ1 gene on a 200-Kb IncFII/IncFIB-type plasmid, while mcr-8 was situated on a 146-Kb IncFII-type plasmid. In clinical strain TGC-05, TmexCD1-toprJ1 was found on a 300-Kb IncFIB/IncHI1B/IncR-type plasmid, and mcr-8 was identified on a 137-Kb IncFII/IncFIA-type plasmid. Conjugation experiments assessed the transferability of these plasmids. While transconjugants were not obtained for TGC-05 despite multiple screening with tigecycline or colistin, pTGC-02-tmex and pTGC-02-mcr8 from clinical K. pneumoniae TGC-02 demonstrated self-transferability through conjugation. Notably, the rearrangement of pTGC-02-tmex and pTGC-02-mcr8 via IS26-based homologous recombination was observed. Moreover, the conjugative and fusion plasmids of the transconjugant co-harboured the tmexCD1-toprJ1 gene cluster and mcr-8.1, potentially resulting from IS26-based homologous recombination. Conclusion The emergence of colistin- and tigecycline-resistant K. pneumoniae strains is concerning, and effective surveillance measures should be implemented to prevent further dissemination.

Abstract Background Crohn’s disease (CD) is an inflammatory disease of the gastrointestinal tract. The disease behavior changes over time, and endoscopy is crucial in evaluating and monitoring the course of CD. To reduce the economic burden of patients and alleviate the discomfort associated with ineffective examination, it is necessary to fully understand the location, extent, and severity of intestinal stenosis in patients with CD before endoscopy. This study aimed to utilize imaging features of magnetic resonance enterography (MRE) to evaluate intestinal stenosis in patients with CD and to predict whether endoscopy could be passed. Methods MRE data of patients with CD were collected, while age, gender, disease duration, and laboratory test parameters were also gathered. Two radiologists analyzed the images and assessed whether endoscopy could be passed based on the imaging performance. Imaging features of MRE were analyzed in groups based on endoscopy results. Results The readers evaluated the imaging performance for 86 patients to determine if endoscopy could be passed and performed a consistency test (compared between two readers k = 0.812, p = 0.000). In the univariate analysis, statistical differences were observed in the degree of T1WI enhancement, thickness of the intestine wall at the stenosis, and diameter of the upstream intestine between the two groups of whether endoscopy was passed. In multivariate logistic regression, the diameter of the upstream intestine was identified to be an independent factor in predicting whether endoscopy was passed or not (OR = 3.260, p = 0.046). Conclusions The utilization of MRE signs for assessing the passage of an endoscope through the narrow segment revealed that the diameter of the upstream intestine emerged as an independent predictor of endoscopic passage. Before performing an endoscopy, MRE can aid in evaluating the passage of the endoscope. Critical relevance statement This retrospective study explored the imaging features of MRE to evaluate intestinal stenosis in patients with Crohn’s disease and determined that the diameter of the upstream intestine of the stenotic segment was an independent predictor in assessing endoscopic passage. Key points • Endoscopy is crucial in evaluating and monitoring the course of Crohn’s disease. • The diameter of the upstream intestine of the stenotic segment was an independent predictor in assessing endoscopic passage. • MRE can aid in evaluating the passage of the endoscope in stenotic segments of Crohn’s disease. Graphical Abstract

Global Navigation System Reflectometry (GNSS-R) is a microwave remote sensing technology that enables Earth observation by receiving GNSS signals reflected from the Earth's surface. The Cyclone Global Navigation Satellite System (CYGNSS) constellation is a satellite system that uses GNSS-R technology with high temporal resolution and has been a popular data source in soil moisture retrieval in recent years. However, the constant movement of GNSS transmitters and GNSS-R satellites results in potentially chaotic and random observations of the Earth's surface, with many unevenly distributed gaps in the observed data. In this paper, a gap-filling method based on spatial autocorrelation is proposed to interpolate the gaps within these observation datasets, with SM being estimated post-interpolation. The sample set for the model comprises points surrounding the interpolation target, with modeling conducted considering factors of spatial weighting to estimate values at the interpolation target. Different autocorrelation-based gap-filling methods using CYGNSS data can achieve good estimation accuracy, and the data coverage after interpolation is on average 1.8 times greater than before interpolation. The gap-filling method using XGBoost achieves the best performance and offers the highest accuracy in SM estimation, with an average correlation coefficient of 0.8445, and an average RMSE of 0.0457 m3/m3. The gap-filling approach can significantly enhance data coverage and facilitate the filling of daily gaps in CYGNSS data with all maintaining high SM estimation accuracy. The estimation of daily missing values using CYGNSS data can fully exploit the embedded surface features in the data's fine resolution and can provide high-resolution SM retrieval.

Pre-harvest water deficit (PHWD) plays an important role in sugar accumulation of citrus fruit. However, the mechanism is not known well. Here, it was confirmed that PHWD promoted sucrose accumulation of citrus fruit, but had limited effect on fructose, glucose and total acid. A sucrose transporter, CsSUT1, which localizes to the plasma membrane, was demonstrated to function in sucrose transport induced by PHWD. Compared to wild-type, CsSUT1 overexpression in citrus calli stimulated sucrose, fructose and glucose accumulation, while its silencing in juice sacs reduced sucrose accumulation. Increased sugar accumulation in transgenic lines enhanced plant drought tolerance, and resulted in decreased electrolyte leakage, malondialdehyde and hydrogen peroxide contents, as well as increased superoxide dismutase activity and proline contents. An abscisic acid (ABA)-responsive transcription factor, CsABF3, was found with a same expression pattern with CsSUT1 under PHWD. Yeast one-hybrid, electrophoretic mobility shift assay and dual-luciferase assays all revealed that CsABF3 directly bound with the CsSUT1 promoter by ABA responsive elements. When CsABF3 was overexpressed in citrus calli, the sucrose, fructose and glucose concentration increased correspondingly. Further, transgenic studies demonstrated that CsABF3 could affect sucrose accumulation by regulating CsSUT1. Overall, this study revealed a regulation of CsABF3 promoting CsSUT1 expression and sucrose accumulation in response to PHWD. Our results provide a detail insight into the quality formation of citrus fruit.

Satellite-based solar-induced chlorophyll fluorescence (SIF) has emerged as a valuable tool for monitoring the photosynthetic activity of vegetation at both regional and global scales. Downscaling techniques offer the opportunity to utilize coarse-spatial-resolution SIF products for investigating carbon cycles and ecological processes at finer resolutions. However, the lack of pre-2000 downscaled products and the limited utilization of residual information in existing models pose challenges in fully harnessing the potential of SIF downscaling. In this study, we generated a new monthly SIF product, DSIFRFK*_EA0.05, at a resolution of 0.05° in East Asia from July 1995 to June 2003. Random forest kriging (RFK) was employed, incorporating GOME SIF, AVHRR data, ERA5 climate data, and using the optimal explanatory variables. Compared with other downscaled results, the produced DSIFRFK*_EA0.05 has higher accuracy and more accurate details of SIF distribution with the highest mean R2 value of 0.83 and smallest root mean squared error value of 0.08 mW/m2/nm/sr. The DSIFRFK*_EA0.05 estimates showed a strong correlation with gross primary productivity data from eight flux sites (R2 = 0.73), as well as high correlation coefficient values of 0.73, 0.88, and 0.89 with three other fine-resolution products. This study addresses the gap in statistical downscaling of SIF before 2000 and demonstrates the feasibility of utilizing AVHRR data for fine-resolution SIF prediction. Our developed product offers improved detail compared to the original GOME SIF, thereby enhancing the application of satellite SIF for understanding early carbon cycles and ecological processes at a finer resolution.

The development of grain storage warehouses has low high-tech coverage because of the special features of grain products. Traditional grain warehouses are facing problems including limited land resources, increased labor costs, and poorer health indicators. Accompanied by the development of information technology and the Internet of Things, automated three-dimensional warehouses have been widely used in industry with the advantages of unmanned, informationized, intensive, high-speed and seamless. In the field of grain warehousing, the finished grain three-dimensional warehouse based on mechatronics, automation, control and logistics is expected to solve the problem of grain warehousing. The traditional grain storage industry will be driven by new technology to ensure national food security.

Abstract Anxiety-associated symptoms following acute stress usually become extinct gradually within a period of time. However, the mechanisms underlying how individuals cope with stress to achieve the extinction of anxiety are not clear. Here we show that acute restraint stress causes an increase in the activity of GABAergic neurons in the CeA (GABACeA) in male mice, resulting in anxiety-like behaviors within 12 hours; meanwhile, elevated GABACeA neuronal CX3CL1 secretion via MST4 (mammalian sterile-20-like kinase 4)-NF-κB-CX3CL1 signaling consequently activates microglia in the CeA. Activated microglia in turn inhibit GABACeA neuronal activity via the engulfment of their dendritic spines, ultimately leading to the extinction of anxiety-like behaviors induced by restraint stress. These findings reveal a dynamic molecular and cellular mechanism in which microglia drive a negative feedback to inhibit GABACeA neuronal activity, thus facilitating maintenance of brain homeostasis in response to acute stress.

Abstract Background We determined the cost-effectiveness of the anti-vascular endothelial growth factor (VEGF) intravitreal injection versus panretinal photocoagulation (PRP) for patients with proliferative diabetic retinopathy (PDR) in South Korea. Methods We simulated four treatment strategies using PRP and the anti-VEGF injection by constructing a Markov model for a hypothetical cohort of 50-year-old PDR patients: (1) PRP only; (2) anti-VEGF injection only; (3) PRP first; and (4) anti-VEGF injection first. Results In this cost-effectiveness analysis, compared with only-PRP, the incremental cost-effectiveness ratio was $95,456 per quality-adjusted life-year (QALY) for PRP first, $34,375 per QALY for anti-VEGF injection first, and $33,405 per QALY for anti-VEGF injection only from a healthcare perspective. From the societal and payer perspective, strategy (2) was more cost-saving and effective than (1). In the probabilistic sensitivity analysis, only-PRP was cost-effective up to the willingness-to-pay (WTP) of about $42,000, while anti-VEGF injection only was cost-effective from a healthcare perspective. From the societal and payer perspectives, regardless of the value of WTP, anti-VEGF injection only was the most cost-effective strategy. Conclusion In our study, the anti-VEGF injection for PDR was cost-effective from the payer and societal perspectives.

Due to numerous leakage zones, such as vugs, fractures, and caves appearing in carbonate rocks, lost circulation, the main issue, restricts safe and effective drilling. The lost circulation pattern of the vug-fractured limestone formation has been extensively studied using the Mishrif formation of the H oilfield in the Middle East as the research sample. The equivalent physical models of three different types of leakage zones, including vug, natural fracture, and induced fracture, were built based on the interpretation of FMI (Formation MicroScanner Image) logging. By embedding discrete fractures into a variable permeability matrix and solving it using the finite element method (FEM), a three-dimensional fluid–solid coupling mathematical model of mud loss rate was established. The study focused on the effects of drilling fluid performance parameters on lost circulation as well as the parameters of the single leakage zone (vug, natural fracture, or induced fracture) on lost circulation. Additionally mentioned were the variable characteristics of mud loss rate and cumulative mud loss volume in various combined ways of leakage zones. The findings indicate that there are considerable differences in how various types of leakage zones affect lost circulation properties. Fractures, particularly induced fractures, can result in more severe lost circulation than those brought on by vug for the creation of a single leaking zone. Mud loss rate and cumulative mud loss volume are greatly influenced by fracture width and dissolved radius, both of which have thresholds. Due to the enhanced flow conductivity, the lost circulation is more severe the more complicated the leakage zone combination mode is. The numerical model developed in this research provides a new perspective on how to analyze the lost circulation pattern of vug-fractured limestone formations and provides theoretical direction for lost circulation control of drilling in this kind of formation.