Search

With the development of computer technology, machine learning method has become an important technology for the prediction of water inrush in coal seam floor. However, the prediction accuracy of many machine learning algorithms requires a high number of samples, which restricts the practical application. In this paper, by using the nearest neighbor algorithm (KNN) and the combination algorithm of gradient boosting decision tree (GBDT) and logistic regression (LR), a water inrush prediction model was established based on the sample data of six indexes, including water pressure, mining height, water-barrier thickness, fault drop, coal seam inclination, and fault distance from the working face. The influence rule of sample number on prediction accuracy was discussed, and the comparison study was conducted with the commonly used particle swarm, support vector machine, BP neural network, random forest and convolutional neural network. The results show that when the number of samples reaches 18, the prediction accuracy of KNN and GBDT+LR remains stable. The prediction accuracy of KNN and GBDT+LR is higher than that of conventional models under small sample conditions. The predicted results of the model agree with the actual situation.

In this study, a new sludge-based biochar loaded with Fe species (Fe/SSBC) was prepared by a two-step process involving hydrothermal treatment and low-temperature air calcination, and used to degrade tetracycline (TC) by activating peroxymonosulfate (PMS). After 30 min reaction, more than 98 % TC (50 mg/L) could be removed by optimized Fe/SSBC/PMS system (k = 0.166 min−1), which was 2.18 times compared with individual hydrothermal treatment (k = 0.076 min−1). Besides, it also exhibited good stabilization. Detailed characterizations revealed the effect of hydrothermal treatment on the Fe–O coordination of the biochar surface and the change of the Fe valence state by air calcination. The electron paramagnetic resonance (EPR), electrochemical analysis and quenching experiments confirmed that singlet oxygen (1O2) was the main active substance. We further elucidated the influence of grafting Fe–O on the surface electron distribution of biochar by DFT calculations. Moreover, two possible pathways were proposed based on LC-MS analysis. In this study, a method of preparing high catalytic performance sludge-based carbon materials under low energy consumption has been proposed, which provides a new strategy for sludge recycling.

Abstract Kidney Chromophobe (KICH) is the third most prevalent renal malignancy, with research challenges due to a dearth of cell lines and clinical samples. There is no specific treatment regimen tailored exclusively for KICH. This study employed gene expression analysis, immunohistochemistry (IHC), Spearman’s correlation, immune cell infiltration assessment, and molecular network construction to investigate the autophagy gene ATG10 in KICH. ATG10 was uniquely downregulated in KICH, predominantly regulated by RNA m6A methylation. This downregulation correlated with patient survival, suggesting a potential tumor-regulatory role. ATG10’s involvement in the protein lipidation pathway, essential for cuproptosis, was identified. B cells and CD8 + T cells were key immune cells in KICH tumorigenesis associated with ATG10. Examination of molecular networks identified several key molecules and mechanisms, including ceRNA, interplaying proteins, and transcription factors. Additionally, drug targeting analysis pointed to specific amino acids and metabolites as potential therapeutic agents. This study elucidates the significance of ATG10 in KICH, implicating m6A methylation and cuproptosis as novel targets for therapeutic intervention. The identification of B cells and CD8 + T cells as key immune components, along with specific amino acids, suggests that a combination of targeted immune therapies and dietary interventions could provide a multifaceted approach to KICH treatment. Given the limited understanding of KICH pathogenesis, our analysis has unveiled new theoretical insights and potential clinical significances for KICH, expected to broaden the research horizon in this field.

Background/purpose: South Asia and Southeast Asia are the regions with relatively high and increased disease burden of oral cancer. The purpose of this study was to analyze the scientometric characteristics of oral cancer research in these regions. Materials and methods: There are 8 countries from South Asia and 11 countries from Southeast Asia. All the articles on oral cancer from these countries were retrieved in the Scopus database. Results: A total of 5660 articles originated from South Asia (n = 4718) and Southeast Asia (n = 942). India (n = 4302; 91.2%) was the country publishing most articles on oral cancer in South Asia, and Malaysia (n = 355; 37.7%) was first in Southeast Asia. Tobacco smoking, alcohol consumption, and areca nut as risk factors were common keywords, attention should be paid to them while developing polices for oral cancer control. In India, the most topic including distinctive keywords was diagnostics (sensitivity/specificity, saliva, and predictive value), followed by molecular biology (antioxidants, lipid peroxidation, and glutathione), experimental in vivo (hamster and cheek pouch), and risk factor (smokeless tobacco). In Malaysia, the most topic containing keywords was molecular biology followed by epidemiology and drug research. Conclusion: This study for the first time reported the scientometric characteristics of oral cancer research in South Asia (India) and Southeast Asia (Malaysia). It is essential to improve the public awareness of risk factors control to reduce the oral cancer burden, especially in low-and middle-income countries.

Protein kinase C α (PKCα) regulates diverse biological functions of cancer cells and is a promising therapeutic target. However, clinical trials of PKC-targeted therapies have not yielded satisfactory results. Recent studies have also indicated a tumor-suppressive role of PKCs via unclear molecular mechanisms. In this study, we found that PKCα inhibition enhances CD8+ T-cell-mediated tumor evasion and abolishes antitumor activity in immunocompetent mice. We further identified PKCα as a critical regulator of programmed cell death-ligand 1 (PD-L1) and found that it enhances T-cell-dependent antitumor immunity in breast cancer by interacting with PD-L1 and suppressing PD-L1 expression. We demonstrated that PKCα-mediated PD-L1 phosphorylation promotes PD-L1 degradation through β transducin repeat-containing protein. Notably, the efficacy of PKCα inhibitors was intensified by synergizing with anti-PD-L1 mAb therapy to boost antitumor T-cell immunity in vivo. Clinical analysis revealed that PKCα expression is positively correlated with T-cell function and the interferon-gamma signature in patients with breast cancer. This study demonstrated the antitumor capability of PKCα, identified potential therapeutic strategies to avoid tumor evasion via PKC-targeted therapies, and provided a proof of concept for targeting PKCα in combination with anti-PD-L1 mAb therapy as a potential therapeutic approach against breast cancer, especially TNBC.

ObjectiveTo screen differentially-expressed circRNA in plasma exosomes of patients with non-small cell lung cancer (NSCLC) and verify its diagnostic value for NSCLC. MethodsThe plasma exosomes of six patients with NSCLC and six healthy people were analyzed by circRNA sequencing. The expression of hsa_circ_0052513 in plasma exosomes of 60 NSCLC patients and 60 healthy controls was detected by qRT-PCR. The expression level of hsa_circ_0052513 in plasma exosomes of NSCLC patients before and after surgery was detected by qRT-PCR. The correlation between the expression of plasma exosomal hsa_circ_0052513 and clinical data of patients with NSCLC was statistically analyzed. ResultsSequencing results showed that the expression of hsa_circ_0052513 in the plasma exosomes of NSCLC patients was higher than that of healthy controls, and the results were confirmed by qRT-PCR. Hsa_circ_0052513 was decreased in patients with NSCLC after tumor resection (P

Abstract Low-frequency repetitive transcranial magnetic stimulation (rTMS) has emerged as an effective intervention for alleviating symptoms of psychiatric disorders, particularly schizophrenia characterized by persistent auditory verbal hallucinations (AVH). However, the underlying mechanism of its action remain elusive. This study employed a randomized controlled design to investigate the impact of low-frequency rTMS on the neural connectivity at the stimulate site, specifically left temporoparietal junction (TPJ), in schizophrenia patients with suffering from AVH. Using Dynamic Causal Modeling (DCM), this study assessed changes in directed connectivity patterns and their correlations with clinical symptomatology. The results demonstrated significant improvements in AVH. Notably, significant changes in connectivity were observed, including both abnormal functional connectivity and effective connectivity among multiple brain regions. Particularly, the inhibition effects from the left precentral gyrus and left medial superior frontal gyrus to the left TPJ were closely associated with improvements in AVH. These findings underscore the potential of rTMS to effectively modulate neural pathways implicated in hallucinations in schizophrenia, thereby providing a neurobiological foundation for its therapeutic effects.

In areas with large temperature differences, the uneven distribution of temperatures in the CRTS III ballastless track slab due to daytime sunlight can cause warpage deformation, leading to periodic rail irregularities that increase the wheel-rail impact of high-speed vehicles and accelerate track structure damage. Therefore, it is necessary to study the dynamic contact relationship between the composite slab and the base plate during vehicle running. The results of the study show that: 1) Under the influence of temperature gradients, the composite slab tends to deform elliptically. With a positive temperature gradient, the middle part of the track slab bulges upward, causing the slab to be supported by its four corners. Conversely, with a negative temperature gradient, the four corners of the track slab bulge upward, resulting in the slab being supported by its center. 2) Temperature gradients can lead to separation between the composite slab and the base plate, reducing the contact area between layers. During vehicle running, the contact area between layers gradually increases, but the separation cannot be completely closed. 3) The temperature gradient significantly affects the vertical displacement of the track. The vertical displacement in the middle of the slab increases with a positive temperature gradient. In contrast, the vertical displacement at the ends of the slab increases with a negative temperature gradient. 4) The stress of self-compacting concrete at the side position significantly increases under a positive temperature gradient, with the vertical stress increasing by 2.7 times when the temperature gradient increases from 0 to 90 ℃·m−1.

Psoriasis is a chronic inflammatory skin condition characterized by erythematous plaques with white scales. Its pathogenesis is closely linked to oxidative stress and an imbalance in Th1/Th2 immune responses. Current treatments for psoriasis, such as topical agents, systemic therapies and phototherapy, frequently fail to achieve complete remission in clinical settings. Monomethyl fumarate (MMF), which has been approved by the US Food and Drug Administration in 2020 for multiple sclerosis, has demonstrated efficacy in psoriasis management. Additionally, our previous studies have identified aluminum ions as beneficial in psoriasis treatment. This present study investigates the combined therapeutic effects of MMF and aluminum ions and observed that the combination treatment achieves superior efficacy compared to either treatment alone in a psoriasis mouse model through the modulation of the Nrf2/NF-κB signaling pathway, as demonstrated in cellular models. The combination first activates Nrf2 nuclear translocation and induces antioxidant gene expression, followed by the inhibition of NF-κB nuclear translocation and phosphorylation, which reduces Th1 cytokine production and cellular chemotaxis. Concurrently, the treatment elevates Th2 cytokine secretion, thereby increasing the anti-inflammatory response in HaCaT cells. Overall, these findings support the MMF and aluminum ions combination (MMFAL) as a potential therapeutic strategy for psoriasis, effectively diminishing inflammation and oxidative stress.

IntroductionMethicillin-resistant Staphylococcus aureus (MRSA) exhibits diverse genotypes with varying virulence and resistance profiles, particularly in the context of bloodstream infections (BSI). This study investigates the prevalence of the sasX, mupA, and qacA/B genes among MRSA isolates from bloodstream infections in southern China and analyzes their genetic relatedness.MethodsA polymerase chain reaction (PCR) assay was developed to detect the presence of the sasX gene, which is associated with nasal colonization, immune evasion, and virulence, the mupirocin resistance gene mupA, and the chlorhexidine tolerance gene qacA/B in a total of 77 MRSA isolates. Multilocus sequence typing (MLST) was performed to determine the sequence types (STs) and assess the genetic relatedness of the isolates. The resistance of these strains to 16 antibiotics was also analyzed. The distribution of these genes and their association with epidemic STs were analyzed.ResultsA total of 26 STs were identified, with notable prevalence in five epidemic clones: ST59, ST5, and ST764. The prevalence of the sasX, mupA, and qacA/B genes across all isolates was 23.4%, 33.8%, and 79.2%, respectively. Specifically, the frequency of the sasX gene was highest in ST59 (29.4%), ST239 (100%), and ST764 (37.5%); mupA was most prevalent in ST5 (66.7%), ST59 (17.6%), ST764 (37.5%), and ST15 (100%); qacA/B was predominantly found in ST59 (88.2%), ST5 (66.7%), ST398 (85.7%), ST764 (50.0%), and ST239 (100%). The gene distribution patterns revealed that sasX+ qacA/B+ mupA+ strains were closely associated with epidemic clones ST6290 and ST88, whereas sasX+ qacA/B+ mupA- strains were linked to ST59, ST239, and ST764. DiscussionNotably, forty-seven (61%) MRSA BSI strains were multidrug-resistant, with the majority exhibiting resistance to penicillin, erythromycin, and clindamycin. Major MRSA clones in southern China include ST59, ST5, ST764, and ST398. In this study, sasX, mupA and qacA/B genes were present in the MRSA isolates, with the mupA gene being the most prevalent. Variations in the prevalence of virulence and resistance genes among these epidemic strains underscore the need for targeted infection control measures. These findings contribute to a better understanding of the genetic epidemiology of MRSA in the region, facilitating the development of effective prevention and control strategies for BSI.

Abstract It is a complex disease with multiple pathogenesis that causes pulmonary hypertension (PH). In addition to the commonly used drugs for treating PH, pharmacogenomic therapies are facilitating the innovation of personalized medicine to treat PH. Meanwhile, gene therapy has been extensively studied but is a quite challenging task. Furthermore, the gradual widespread application of omics analyses, big data and machine learning is a trend to improve the efficacy of drugs and gene therapy of PH. They are widely used in the screening of drug therapeutic targets and predicting drugs therapeutic effect. The emergence of innovative diagnosis and treatment approaches for PH opens pathways for combining personalized medicine with established pharmacological and gene therapies to achieve effective treatment strategies and further decrease the mortality rate associated with this disease.

BackgroundDiabetes, a chronic disease necessitating long-term treatment and self-management, presents significant challenges for patients who spend most of their treatment time outside of hospitals. The potential of digital therapeutics for diabetes has garnered recognition from different organizations. Although some prior studies have demonstrated successful reductions in patients’ blood glucose levels and body weight through digital diabetes programs, many studies were limited by including patients with prediabetes, including patients treated with mostly premixed insulin, or evaluating user engagement outcomes rather than clinical outcomes. Consequently, limited evidence remains regarding the effectiveness of health management mobile apps specifically designed for patients with type 2 diabetes mellitus (T2DM) initiating basal insulin (BI). Based on this, a data-based and artificial intelligence management system named “TRIO” was developed to provide patients with more personalized intervention methods in stages, in groups, and around the clock. TRIO assists doctors and nurses in achieving better blood glucose controls, truly carries out standardized management around patients, and allows them to have a higher quality of life. TRIO represents the 3 essential pillars in comprehensive diabetes management: physician, nurse, and patient. ObjectiveThis prospective observational study evaluated the effectiveness and safety of the TRIO optimal health management program for patients with T2DM initiating BI therapy in a real-world setting. MethodsPatients aged 18-85 years with inadequate glycemic control (baseline hemoglobin A1c [HbA1c] ≥7%) starting BI therapy were enrolled in outpatient and inpatient settings. The study lasted 3 months, with health education and phone-based follow-up assessments. Data collected included patient characteristics, medical history, baseline diabetes conditions, treatment compliance, glycemic control, and safety indicators. ResultsA total of 199,431 patients were included, and 118,134 patients completed the 3-month follow-up between December 1, 2019, and December 31, 2021, involving 574 hospitals in China. The mean baseline HbA1c was 9.2%, the mean duration of diabetes was 7.3 years, and 80.4% (1,59,930/1,98,969) of patients were using BI with oral antihyperglycemic drugs. After the intervention, mean HbA1c decreased by –2.59% from baseline, with 55.6% (28,858/51,912) achieving the target HbA1c level of

Objective: The relationship between serum lipids and prognosis of pancreatic cancer has not been confirmed. Our purpose in the study was to investigate the associations between serum lipids level and prognosis in patients with pancreatic cancer. Methods: A retrospective study was performed on 286 pancreatic cancer patients who admitted to our hospital from January 1, 2017 to December 31, 2021. Serum lipids level were recorded. Clinical-pathological characteristics, oncologic outcomes, progression free survival (PFS) and overall survival (OS) were collected. The prognostic significance was determined by Kaplan-Meier analysis and Cox proportional hazards regression model. Results: Regarding serum lipids level, compared to normal apolipoprotein B/ apolipoprotein A (ApoB/ApoA1), high ApoB/ApoA1 level indicated a shorter OS (HR:2.028, 95% CI: 1.174–2.504, P = 0.011) and a shorter PFS (HR:1.800, 95% CI: 1.076–3.009, P = 0.025). Other serum lipid molecules were not associated with PFS and OS. Conclusion: ApoB/ApoA1 might be an independent prognostic factor of pancreatic cancer.

Oral squamous cell carcinoma (OSCC) is a highly aggressive and malignant tumor of oral cavity with a poor prognosis and high mortality due to the limitations of existing therapies. The significant role of tumor microenvironment (TME) in the initiation, development, and progression of OSCC has been widely recognized. Various cells in TME, including tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), T lymphocytes, tumor-associated neutrophils (TANs), myeloid-derived suppressor cells (MDSCs) and dendritic cells (DCs), form a complicated and important cellular network to modulate OSCC proliferation, invasion, migration, and angiogenesis by secreting RNAs, proteins, cytokines, and metabolites. Understanding the interactions among cells in TME provides the foundation for advanced clinical diagnosis and therapies. This review summarizes the current literature that describes the role of various cellular components and other TME factors in the progression of OSCC, hoping to provide new ideas for the novel OSCC treatment strategies targeting the complicated cellular network and factors that mediate the interactive loops among cells in TME.

Abstract Exposure to nanoparticles (NPs) is frequently associated with adverse cardiovascular effects. In contrast, NPs in nanomedicine hold great promise for precise lung‐specific drug delivery, especially considering the extensive pulmonary capillary network that facilitates interactions with bloodstream‐suspended particles. Therefore, exact knowledge about effects of engineered NPs within the pulmonary microcirculation are instrumental for future application of this technology in patients. To unravel the real‐time dynamics of intravenously delivered NPs and their effects in the pulmonary microvasculature, we employed intravital microscopy of the mouse lung. Only PEG‐amine‐QDs, but not carboxyl‐QDs triggered rapid neutrophil recruitment in microvessels and their subsequent recruitment to the alveolar space and was linked to cellular degranulation, TNF‐α, and DAMP release into the circulation, particularly eATP. Stimulation of the ATP‐gated receptor P2X7R induced expression of E‐selectin on microvascular endothelium thereby mediating the neutrophilic immune response. Leukocyte integrins LFA‐1 and MAC‐1 facilitated adhesion and decelerated neutrophil crawling on the vascular surface. In summary, this study unravels the complex cascade of neutrophil recruitment during NP‐induced sterile inflammation. Thereby we demonstrate novel adverse effects for NPs in the pulmonary microcirculation and provide critical insights for optimizing NP‐based drug delivery and therapeutic intervention strategies, to ensure their efficacy and safety in clinical applications.

ABSTRACTHigh-quality samples for training and validation are crucial for land cover classification, especially in some complex scenarios. The reliability, representativeness, and generalizability of the sample set are important for further researches. However, manual interpretation is subjective and prone to errors. Therefore, this study investigated the following questions: (1) How much difference is there in the interpreters’ performance across educational levels? (2) Do the accuracies of human and AI (Artificial Intelligence) improve with increased training and supporting material? (3) How sensitive are the accuracies of land cover types to different supporting material? (4) Does interpretation accuracy change with interpreters’ consistency? The experiment involved 50 interpreters completing five cycles of manual image interpretation. Higher educational background interpreters showed better performance: accuracies pre-training at 52.22% and 58.61%, post-training at 61.13% and 70.21%. Accuracy generally increased with more supporting material. Ultra-high-resolution images and background knowledge contributed the most to accuracy improvement, while the time series of normalized difference vegetation index (NDVI) contributed the least. Group consistency was a reliable indicator of volunteer sample reliability. In the case of limited samples, AI was not as good as manual interpretation. To ensure quality in samples through manual interpretation, we recommend inviting educated volunteers, providing training, preparing effective support material, and filtering based on group consistency.

Objective To determine whether ultrasonic manifestations of Hashimoto’s thyroiditis (HT) related to embryo qualities or pregnancy outcomes in women with thyroid autoimmunity (TAI) undergoing in vitro fertilization/intracytoplasmic sperm injection.Methods Our study was a retrospective cohort study. A total of 589 euthyroid women enrolled from January 2017 to December 2019. 214 TAI women and 375 control women were allocated in each group according to serum levels of thyroid peroxidase antibodies (TPOAb) and/or anti-thyroglobulin antibodies (TgAb). Basal serum hormone levels and thyroid ultrasound were assessed, embryo qualities, pregnancy outcomes were collected from medical records. Diagnosis of thyroid ultrasound was used for subanalysis. Logistic regression was used to evaluate outcomes of embryo development and pregnancy.Results Implantation rate was significantly lower in euthyroid women with TAI compared with control group (TAI group: 65.5% vs. Control group: 73.0%, adjusted OR (95% CI): 0.65 (0.44, 0.97), p = 0.04). We further stratified TAI group into two groups: one group with HT features under ultrasound and another group with normal thyroid ultrasound. After regression analysis, TAI women with HT morphological changes had a lower chance of implantation compared with control group (TAI group with HT: 64.1% vs. Control group: 73.0%, adjusted OR (95% CI): 0.63 (0.41, 0.99), p = 0.04), while there was no significant difference on implantation rate between TAI women with normal thyroid ultrasound and control group. Other outcomes, such as embryo qualities and pregnancy rate, were comparable between TAI and control groups.Conclusions A higher risk of implantation failure was seen among euthyroid women with TAI, especially women with HT morphological changes under ultrasound. The underlying mechanisms of implantation failure among euthyroid HT patients need further research.

Abstract Complicated associations between multiplexed environmental factors and aging are poorly understood. We manipulated aging using multidimensional metrics such as phenotypic age, brain age, and brain volumes in the UK Biobank. Weighted quantile sum regression was used to examine the relative individual contributions of multiplexed environmental factors to aging, and self-organizing maps (SOMs) were used to examine joint effects. Air pollution presented a relatively large contribution in most cases. We also found fair heterogeneities in which the same environmental factor contributed inconsistently to different aging metrics. Particulate matter contributed the most to variance in aging, while noise and green space showed considerable contribution to brain volumes. SOM identified five subpopulations with distinct environmental exposure patterns and the air pollution subpopulation had the worst aging status. This study reveals the heterogeneous associations of multiplexed environmental factors with multidimensional aging metrics and serves as a proof of concept when analyzing multifactors and multiple outcomes.

Abstract Background Dexmedetomidine and midazolam are commonly used sedatives in children. We conducted a systematic review and meta-analysis to compare the safety and effectiveness of sedation provided by dexmedetomidine combined with midazolam versus other sedatives including chloral hydrate, midazolam and other sedatives in pediatric sedation. Methods The Embase, Web of Science, Cochrane Library, and PubMed databases, and Clinicaltrials.gov register of controlled trials were searched from inception to June 2022. All randomized controlled trials used dexmedetomidine-midazolam in pediatric sedation were enrolled. The articles search, data extraction, and quality assessment of included studies were performed independently by two researchers. The success rate of sedation was considered as the primary outcome. The secondary outcomes included onset time of sedation, recovery time of sedation and occurrence of adverse events. Results A total of 522 studies were screened and 6 RCTs were identified; 859 patients were analyzed. The administration of dexmedetomidine combined with midazolam was associated with a higher sedation success rate and a lower incidence of nausea and vomiting in computed tomography, magnetic resonance imaging, Auditory Brainstem Response test or fiberoptic bronchoscopy examinations than the other sedatives did (OR = 2.92; 95% CI: 1.39–6.13, P = 0.005, I2 = 51%; OR = 0.23, 95% CI: 0.07–0.68, P = 0.008, I2 = 0%, respectively). Two groups did not differ significantly in recovery time and the occurrence of adverse reactions (WMD = − 0.27, 95% CI: − 0.93 to − 0.39, P = 0.42; OR 0.70; 95% CI: 0.48–1.02, P = 0.06, I2 = 45%. respectively). However, the results of the subgroup analysis of ASA I-II children showed a quicker onset time in dexmedetomidine-midazolam group than the other sedatives (WMD=−3.08; 95% CI: −4.66 to − 1.49, P = 0.0001, I2 = 30%). Conclusions This meta-analysis showed that compared with the control group, dexmedetomidine combined with midazolam group provided higher sedation success rates and caused a lower incidence of nausea and vomiting in completing examinations, indicating a prospective outpatient clinical application for procedural sedation.

Objectives: Respiratory infections are among the most common infectious diseases, resulting in significant morbidity and mortality. C-reactive protein (CRP), serum amyloid A (SAA), procalcitonin (PCT), and interleukin-6 (IL-6) are advantageous for diagnosing respiratory tract infections. This study assessed the analytical performance and accuracy of new kits for Eu3+-based CRP/SAA and PCT/IL-6 lateral flow immunoassay and its diagnostic value in respiratory tract infections. Methods: This study evaluated the detection performance of a test kit using guidelines from the Center for Medical Device Evaluation (CMDE) and the Clinical and Laboratory Standards Institute (CLSI). The test results were compared to those of the commercial kits (CRP: Mindray; SAA: Norman; PCT: Shanghai Upper; IL-6: Wantai BioPharm). A total of 156 patients with respiratory tract infections (53 with bacterial infections (Bac group); 50 with viral infections (Vir group); and 53 with co-infections (Bac + Vir group)) were enrolled, along with 50 healthy controls (HC group). Venous blood samples were collected to measure levels of SAA, PCT, CRP, and IL-6 using both the test and commercial kits. The diagnostic value of these biomarkers was assessed using receiver operating characteristic (ROC) curves. Results: Correlation analysis demonstrated a strong concordance between the test kits and commercial kits (CRP: r = 0.9396, P

Abstract Phenotypic switching of smooth muscle cells (SMC) is a crucial process in the pathogenesis of pulmonary arterial hypertension (PAH). However, the underlying mechanism is unclear. Here, we performed single‐cell RNA sequencing on pulmonary arteries obtained from lung transplantation to explore the cellular heterogeneity and gene expression profile of the main cell types. We identified three distinct SMC phenotypes, namely contractile, fibroblast‐like, and chondroid‐like, and observed an enhanced transition from contractile to fibroblast‐like phenotype in PAH by pseudo‐time analysis and in vitro. We also revealed a classically activated (M1) polarization of macrophages and an increased pro‐inflammatory macrophage‐SMC crosstalk in PAH via intercellular communication. Notably, Nicotinamide phosphoribosyltransferase (NAMPT) emerges as a key player in macrophage polarization. The macrophages overexpress Nampt in Sugen/hypoxia (Su/Hx) ‐induced PAH mice and significantly downregulate the pro‐inflammation secretion pattern with Nampt interference. In a cellular coculture system, Nampt knockdown in macrophages significantly inhibits the fibroblast‐like phenotypic switching of SMCs. Finally, we identified Ccl2/5 as a key cytokine for SMC phenotypic modulation. Collectively, these findings provide a cell atlas of normal human pulmonary arteries and demonstrate that NAMPT‐driven M1 macrophage polarization promotes the fibroblast‐like phenotypic switching of SMCs through CCR2/CCR5 cellular crosstalk in PAH.

Background: Adults with cognitive impairment are prone to living alone in large numbers but receive relatively little attention. This study aimed to evaluate whether living alone with cognitive impairment was associated with a higher burden of functional disability but lack of informal care. Methods: 982 observations of adults living alone with cognitive impairment and 50,695 observations of adults living with others and with normal cognition were identified from 4 waves (2011/2012, 2013, 2015, and 2018) of the China Health and Retirement Longitudinal Study (CHARLS). A matched comparator was selected using propensity score matching (1:2). Functional disability included disability in Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), and mobility. The time of receiving informal care was measured in monthly hours. Results: Adults living alone with cognitive impairment demonstrated significantly higher odds ratio of ADL disability (OR = 1.59, 95 % CI: 1.30, 1.95), IADL disability (OR = 1.19, 95 % CI: 1.00, 1.44), mobility disability (OR = 1.38, 95 % CI: 1.12, 1.70), but received fewer hours of informal care (β = −127.7 h per month, standard error = 25.83, P

Hyperimmunoglobulin D syndrome (HIDS) is a rare but severe autoinflammatory disease with a poor prognosis if not diagnosed and treated early. Here, we report three cases of HIDS in children with typical clinical manifestations and a clear genetic diagnosis. Patient 1 experienced recurrent fever flares with a maculo-papular skin rash. Patient 2 presented with periodic fever, cholestasis, lymphadenopathy, aphthous stomatitis, arthralgia, and abdominal pain and underwent surgery for intestinal obstruction. Patient 3, a sibling of patient 2, presented with periodic fever and underwent a surgical procedure for intussusception. All three patients were administered interleukin (IL)-6 receptor antagonist (tocilizumab). The results showed that tocilizumab effectively reduced inflammatory flares. Early diagnosis and tocilizumab treatment are effective at improving the prognosis of HIDS patients.

Working memory (WM) is an essential cognitive function that underpins various higher-order cognitive processes. Improving WM capacity through targeted training interventions has emergered as a potential approach for enhancing cognitive abilities. The present study employed an 8-week regimen of computerized WM training (WMT) to investigate its effect on neuroplasticity in healthy individuals, utilizing neuroimaging data gathered both before and after the training. The key metrics assessed included the amplitude of low-frequency fluctuations (ALFF), voxel-based morphometry (VBM), and the spatial distribution correlations of neurotransmitter. The results indicated that post-training, compared to baseline, there was a reduction in ALFF in the medial superior frontal gyrus and an elevation in ALFF in the left middle occipital gyrus within the training group. In comparison to the control group, the training group also exhibited decreased ALFF in the anterior cingulate cortex, angular gyrus, and superior parietal lobule, along with increased ALFF in the postcentral gyrus post-training. VBM analysis revealed a significant increase in gray matter volume (GMV) in the right dorsal superior frontal gyrus after the training period, compared to the initial baseline measurement. Furthermore, the training group showed GMV increases in the dorsal superior frontal gyrus, Rolandic operculum, precentral gyrus, and postcentral gyrus when compared to the control group. In addition, significant associations were identifed between neuroimaging measurements (AFLL and VBM) and the spatial patterns of neurotransmitters such as serotonin (5-HT), dopamine (DA), and N-methyl-D-aspartate (NMDA), providing insights into the underlying neurochemical processes. These findings clarify the neuroplastic changes caused by WMT, offering a deeper understanding of brain plasticity and highlighting the potential advantages of cognitive training interventions.

BackgroundAccurate identification of infectious diseases using molecular techniques, such as PCR and NGS, is well-established. This study aims to assess the utility of Bactfast and Fungifast in diagnosing bloodstream infections in ICU settings, comparing them against traditional culture methods. The objectives include evaluating sensitivity and specificity and identifying a wide range of pathogens, including non-culturable species.MethodsWe collected 500 non-duplicate blood samples from ICU patients between January 2023 and December 2023. Specimens underwent traditional culture, MALDI-TOF, VITEK®2 compact system, and NGS-based Bactfast and Fungifast analyses.ResultsOut of the 500 samples, 26.8% (n=134) showed bacterial growth via traditional culture methods, while 4.8% (n=24) were positive for fungal growth. MALDI-TOF and VITEK®2 compact system yielded comparable results, identifying 26.4% (n=132) of specimens with bacterial growth. NGS-based Bactfast detected bacterial presence in 38.2% (n=191) of samples, including non-culturable bacteria missed by traditional methods. However, NGS-based Fungifast showed concordant fungal detection rates with culture methods. Among identified pathogens by culture method included Klebsiella pneumoniae 20.89% (n=28), Enterococcus faecalis 18.65% (n=25), Escherichia coli 15.67% (n=21), Pseudomonas aeruginosa 12.68% (n=17), Acinetobacter baumannii 10.44% (n=14), various Streptococcus species 7.46% (n=10), Mycobacterium tuberculosis 6.71% (n=9), Mycobacterium abscessus 4.47% (n=6), and Salmonella spp 2.98% (n=4). Non-culture-based NGS identified additional (n=33) pathogens, including Klebsiella pneumoniae 27.27% (n=9), Bacteroides fragilis 21.21% (n=7), Aerococcus viridans 15.15% (n=5), Elizabethkingia anopheles 12.12% (n=4), Aeromonas salmonicida 9% (n=3), Clostridium 9% (n=3), and Bacteroides vulgatus 6% (n=2). Candida albicans was reported in 5% (n=24) of samples by both methods.ConclusionNGS-based Bactfast and Fungifast demonstrate high sensitivity in identifying a wide array of bacterial and fungal pathogens in ICU patients, outperforming traditional culture methods in detecting non-culturable organisms. These molecular assays offer rapid and comprehensive diagnostic capabilities, potentially improving clinical outcomes through timely and accurate pathogen identification.

Abstract Background While there is an understanding of the association between the expression of Porphyromonas gingivalis (P. gingivalis) and prognosis of oral squamous cell carcinoma (OSCC), significance specially to address the relevance between different immunohistochemical intensities of P. gingivalis and tumor-associated macrophages (TAMs) in OSCC tissue and related clinicopathologic characteristics has not been well investigated. The present study aimed to investigate the pathological features related to M2-TAM in P. gingivalis-infected OSCC and ascertain its clinical relevance with patients’ prognosis. Methods A prospective cohort study was designed to comparatively analyze 200 patients from June 2008 to June 2020. Bioinformatics analyses were implemented to identify DOK3 as a key molecule and to appraise immunocyte infiltration using Gene Expression Omnibus and The Cancer Genome Atlas databases. Immunohistochemical evaluation was performed to analyze the association between the expression levels of P. gingivalis, DOK3, and M2-TAM and clinicopathological variables using Fisher’s exact test or Pearson’s chi-square test. Cox analysis was used to calculate hazard ratios (HR) with corresponding 95% confidence interval (CI) for various clinicopathological features. The Kaplan–Meier approach and log-rank test were used to plot the survival curves. Results The expression level of P. gingivalis was positively associated with DOK3 and M2-TAMs expression level (P

General type-2 fuzzy logic systems (GT2 FLSs) on the basis of alpha-plane representation of GT2 fuzzy sets (FSs) have attracted considerable attention in recent years. For the kernel type-reduction (TR) block of GT2 FLSs, the enhanced Karnik-Mendel (EKM) algorithm is the most popular approach. This paper proposes the sensible beginning divided-search EKM (SBDEKM) algorithms for completing the centroid TR of GT2 FLSs. Computer simulations are provided to show the performances of the SBDEKM algorithms. Compared with EKM algorithms and sensible beginning EKM (SBEKM) algorithms, the SBDEKM algorithms have almost the same accuracies and better computational efficiency.

Recent advances in high-temperature gas-cooled reactor fuel research have captured the global spotlight, as modern operating contexts demand innovative responses to unprecedented challenges. This article offers an overview of contemporary directions in high-temperature gas-cooled reactor fuel design worldwide, pinpointing the shared operational demands and development patterns characteristic of these advanced fuels. It presents an innovative advanced fuel design, which incorporates multi-layer coated particles to boost safety and employs high-temperature-resistant silicon carbide (SiC) ceramics, seamlessly integrated with cutting-edge additive manufacturing (AM) techniques. This design heralds a shift toward modular fuel element solutions that are easily scalable, supporting the diverse array of advanced reactors and marking a significant step forward in the quest for high-temperature gas-cooled reactor fuel technologies.

Brown planthoppers (BPHs, Nilaparvata lugens Stål) are a major threat to rice cultivation in Asia, necessitating the development of pest-resistant varieties for effective management. However, the adaptability of BPHs has resulted in the development of virulent populations, such as biotype Y BPHs, which exhibit significant virulence against the rice variety YHY15 that harbors the resistance gene Bph15. The various response mechanisms of BPH populations to resistant rice varieties are critical yet underexplored. Via RNA sequencing, the present study identified distinct transcriptional profiles in avirulent (biotype 1) and virulent (biotype Y) BPH nymphs both before and after feeding on YHY15 rice. Our findings revealed differential expression patterns of gene clusters involved in protein synthesis, hydrolysis, fatty acid biosynthesis, metabolism, cuticle composition, and translocation. Further analysis elucidated changes in the expression of genes associated with longevity and structural components of cuticles, highlighting specific disruptions in both biotype 1 and biotype Y BPHs. Moreover, the two biotypes showed differences in the expression level of genes involved in ATP-binding cassette (ABC) transporters. A functional assessment of ABC transporter genes revealed a role of NlABCG14 in the honeydew production of biotype Y BPHs to YHY15 rice, without impacting their survival and developmental dynamics. These insights deepen our understanding of the mechanisms of virulent BPHs response to resistant rice varieties and highlight potential targets for improving pest management strategies.