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Abstract Objective We compare the efficacy of intranasal dexmedetomidine (DEX) and DEX-esketamine sedation on pediatric acceptance of face mask. Methods This single-center double-blind randomized controlled study was conducted at a tertiary hospital affiliated with Shanghai Jiao Tong University. Ninety children aged 1 year to 6 years old and scheduled for elective surgery were randomly allocated in a 1:1 ratio into receiving DEX alone (n = 45) and DEX-esketamine (n = 45). DEX and esketamine were used intranasally at doses of 2 µg/kg and 2.0 mg/kg respectively. Children were assessed by an attending anesthesiologist with modified observer’s assessment of alertness and sedation (MOAA/S), pediatric separation anxiety scale (PSAS) and mask acceptance scale (MAS). Perioperative adverse events (bradycardia, hypotension, hypoxia, emergence delirium etc.) were recorded. Results Of 95 patients enrolled, 90 completed the study. The proportion of children who accepted facemask was significantly higher in the DEX-esketamine group compared to the DEX group (86.7% (39/45) vs. 62.2% (28/45), p = 0.008). Within 30 min after intranasal administration of agents, PSAS scores were similar between the two groups. Children in the DEX group were easily aroused when repositioned from the transferring bed to the operation table. In contrast, those in the DEX-esketamine group maintained a stable level of sedation (MOAA/S scores, median [25th– 75th interquartile range], 1 [1, 1] for DEX-esketamine vs. 2 [1, 4] for DEX, p 0.05). Conclusions For preoperative sedation, combination of DEX with esketamine improved mask acceptance than dexmedetomidine alone, likely due to its superior anxiolytic effect in children with high anxiety. Trial registration This study was registered in the Chinese Clinical Trial Register (registration no. ChiCTR2400087873, registration date on 6/8/2024).

Abstract Background Colorectal cancer (CRC) ranks among the frequently occurring malignant neoplasms affecting the gastrointestinal tract. This study aimed to explore JAK-STAT signaling pathway related genes in CRC and establish a new prognostic model. Methods The data set used in this study is from a public database. JAK-STAT-differentially expressed genes (DEGs) were identified through differential expression analysis and weighted gene co-expression network analysis (WGCNA). Prognostic genes were selected from JAK-STAT-DEGs through Mendelian randomization (MR), univariate Cox regression, and least absolute shrinkage and selection operator (LASSO) analyses. The expressions of prognostic genes were verified by RT-qPCR. Then, a risk model was built and validated by the GSE39582. Independent prognostic factors were screened underlying risk scores and different clinical indicators, resulting in the construction of a nomogram. Additionally, immune infiltration, immune scores and immune checkpoint inhibitors analyses and gene set enrichment analysis (GSEA) were carried out. Results The 3,668 JAK-STAT-DEGs were obtained by intersection of 5826 CRC-DEGs and 9766 JAK-STAT key module genes. Five prognostic genes were selected (ANK3, F5, FAM50B, KLHL35, MPP2), and their expressions were significantly different between CRC and control groups. A risk model was constructed according to prognostic genes and verified by GSE39582. In addition, the nomogram exhibited superior predictive accuracy for CRC. Furthermore, immune analysis results indicated a notable positive correlation between risk score and the scores of immune (R = 0.486), stromal (R = 0.309), and ESTIMATE (R = 0.422). Immune checkpoint inhibitor ADORA2A (Cor = 0.483263) exhibited the strongest positive correlation with risk score. And MPP2 exhibited the most potent activating influence on the cell cycle pathway, whereas ANK3 demonstrated the most significant inhibitory effect within the apoptosis pathway. Conclusions A new JAK-STAT related CRC prognostic model was constructed and validated, which possessed an underlying predictive potential for CRC patients’ prognosis and could potentially enhance tailored guidance for immunotherapy.

Abstract Background Drug-target binding affinity (DTA) prediction is vital in drug discovery and repositioning, more and more researchers are beginning to focus on this. Many effective methods have been proposed. However, some current methods have certain shortcomings in focusing on important nodes in drug molecular graphs and dealing with complex structural molecules. In particular, when considering important nodes and complex substructures in molecules, they may not be able to fully explore the potential relationships between different parts. In addition, when dealing with protein structures, some methods ignore the connections between amino acid fragments that are far apart in sequence but may work synergistically in function. Results In this paper, we propose a new method, called GS-DTA, for predicting DTA based on graph and sequence models. GS-DTA takes simplified molecular input line input system (SMILES) of the drug and the protein amino acid sequence as input. First, each drug is modeled as a graph, in which a vertex is an atom and an edge represents interaction between atoms. Then GATv2-GCN and the three-layer GCN networks are used to extract the features of the drug. GATv2-GCN enhances the model’s ability to focus on important nodes by assigning dynamic attention scores, which improves the learning of the graph structure’s intricate patterns. Besides, The three-layer GCN can captures hierarchical features of the drug through deeper propagation and feature transformation. Meanwhile, for each protein, a framework combining CNN, Bi-LSTM, and Transformer is used to extract the contextual and structural information of the protein amino acid sequences, and this combination can help to understand a comprehensive and detailed features of the protein. Finally, the obtained drug and protein feature vectors are combined to predict DTA through the fully connected layer. The source code can be downloaded from https://github.com/zhuziguang/GS-DTA . Conclusions The results show that GS-DTA achieves good performance in terms of MSE, CI, and r2 m on the Davis and KIBA datasets, improving the accuracy of DTA prediction.

Abstract This study aims to analyze changes in the disease burden of cystic echinococcosis in China from 1990 to 2019 and to predict trends from 2020 to 2044. Using the Global Burden of Disease 2019 (GBD 2019) database, we analyzed the trends in annual percentage change (APC) and average annual percentage change (AAPC) for incidence, prevalence, death, and disability-adjusted life years (DALY) rates of cystic echinococcosis in China via the Joinpoint Regression Program 4.8.0.1 software. Additionally, we applied Nordpred modeling to predict future trends in disease burden over the next 25 years. From 1990 to 2019, the incidence and prevalence of cystic echinococcosis in the Chinese population showed an overall increasing trend, whereas the death and DALY rates exhibited an overall decreasing trend. The disease burden of cystic echinococcosis was greater in males than in females, with significant differences across age groups. The highest incidence and prevalence rates were observed in the 10–24 years age group, whereas the lowest occurred in the 0–9 years age group. Fatalities and DALY rates increased with age, particularly in the 70 and older age groups. According to the Nordpred modeling results, the incidence, prevalence, and DALY rates of cystic echinococcosis in China are expected to rise slightly over the next 25 years. The overall disease burden of cystic echinococcosis is projected to increase gradually between 2020 and 2044, with men exhibiting higher incidence, prevalence, and DALY rates than women.

Abstract A large number of SpCas9 orthologs has been computationally identified, but their genome editing potential remains largely unknown. In this study, a GFP-activation assay was used to screen a panel of 18 SpCas9 orthologs, ten of which demonstrated activity in human cells. Notably, these orthologs had a preference for purine-rich PAM sequences. Four of the tested orthologs displayed enhanced specificity compared to SpCas9. Of particular interest is SeqCas9, which recognizes a simple NNG PAM and displays activity and specificity comparable to SpCas9-HF1. In addition, SeqCas9 exhibits superior base editing efficiency compared to SpCas9-NG and SpCas9-NRRH at multiple endogenous loci. This research sheds light on the diversity of SpCas9 orthologs and their potential for specific and efficient genome editing, especially in cases involving base editing.

Abstract Prion diseases are a group of fatal neurodegenerative disorders characterized by the abnormal folding of cellular prion proteins into pathogenic forms. The development of these diseases is intricately linked to oxidative stress and mitochondrial dysfunction. Irisin, an endogenous myokine, has demonstrated considerable neuroprotective potential due to its antioxidative properties. However, the protective effects of irisin against prion diseases have yet to be clarified. Our findings indicate that treatment with exogenous irisin can mitigate the apoptosis induced by PrP106–126. Additionally, irisin significantly reduces oxidative stress and alleviates the mitochondrial dysfunction triggered by PrP106–126. Furthermore, irisin treatment targets uncoupling protein 2 (UCP2) and activates the AMPK-Nrf2 pathway, substantially improving oxidative stress and mitochondrial dysfunction in N2a cells induced by PrP106–126. These results suggest that irisin represents a novel and promising therapeutic approach for treating prion diseases.

To derive critical signal features from intracranial electroencephalograms of epileptic patients in order to design instructions for feedback-type electrical stimulation systems. The Detrended Fluctuation Analysis (DFA) exponent is chosen as the classification exponent, and the disparities between indicators representing distinct seizure states and the classification efficacy of rudimentary machine learning models are computed. The DFA exponent exhibited a statistically significant variation among the pre-ictal, ictal period, and post-ictal stages. The Linear Discriminant Analysis model demonstrates the highest accuracy among the three basic machine learning models, whereas the Naive Bayesian model necessitates the least amount of computational and storage space. The set of DFA exponents is employed as an intermediary variable in the machine learning process. The resultant model possesses the capability to function as a feedback trigger program for electrical stimulation systems of the feedback variety, specifically within the domain of neural modulation in epilepsy.

Abstract Several modifiable health factors in Life’s Essential 8 (LE8) are linked to nutritional anemia and can assess overall cardiovascular health (CVH). This study explored the associations of CVH measured by LE8 score with nutritional anemia and iron deficiency anemia (IDA), including the mediating role of inflammatory biomarkers. This prospective cohort study included 181,069 participants from UK Biobank. CVH was categorized into low (0–49), medium (50–79), and high (80–100) based on the LE8 score. Weibull regression models were used to quantify the association between CVH and nutritional anemia and IDA. During a median follow-up of 8.6 years, 6749 cases of nutritional anemia occurred, including 92% (6223/6749) IDA cases. After adjusting for covariates, participants with moderate CVH and high CVH had a 44% and 54% lower risk of nutritional anemia (Moderate: hazard ratio [HR] 0.56; 95% confidence interval [CI], 0.51–0.60; High: HR 0.46; 95% CI, 0.41–0.51), and a 46% and 54% lower risk of IDA (Moderate: HR 0.54; 95% CI, 0.50–0.59; High: HR 0.46; 95% CI, 0.41–0.51), respectively, compared to those with low CVH. An L-shaped association was observed between CVH score and both types of anemia. Inflammatory biomarkers explained 22.1% and 21.6% of the associations between CVH and nutritional anemia and IDA, respectively. Higher CVH scores were associated with lower risk of nutritional anemia and IDA, and these associations may be partially mediated by inflammatory biomarkers. These findings emphasize the importance of CVH and inflammation in preventing nutritional anemia.

Abstract Background DNA methylation (DNAm) has been shown in multiple studies to be associated with the estimated glomerular filtration rate (eGFR). However, studies focusing on Chinese populations are lacking. We conducted an epigenome-wide association study to investigate the association between DNAm and eGFR in Chinese monozygotic twins. Methods Genome-wide DNAm level was detected using Reduced Representation Bisulfite Sequencing test. Generalized estimation equation (GEE) was used to examine the association between Cytosine-phosphate-Guanines (CpGs) DNAm and eGFR. Inference about Causation from Examination of FAmiliaL CONfounding was employed to infer the causal relationship. The comb-p was used to identify differentially methylated regions (DMRs). GeneMANIA was used to analyze the gene interaction network. The Genomic Regions Enrichment of Annotations Tool enriched biological functions and pathways. Gene expression profiling sequencing was employed to measure mRNA expression levels, and the GEE model was used to investigate the association between gene expression and eGFR. The candidate gene was validated in a community population by calculating the methylation risk score (MRS). Results A total of 80 CpGs and 28 DMRs, located at genes such as OLIG2, SYNGR3, LONP1, CDCP1, and SHANK1, achieved genome-wide significance level (FDR

ABSTRACT: Nutritional and metabolic state in dairy cows are important determinants of the immune response. During the periparturient period, a state of negative energy balance in the cow increases plasma concentrations of fatty acids (FA), which are associated with inflammation. Among immune cells, CD4+ T are able to function under high-FA conditions, but the underlying mechanisms regulating these events remain unclear. The objective of this study was to clarify the functional mechanisms of CD4+ T cells under high-FA conditions. The effects of glycolysis and calcium release-activated calcium modulator 1 (ORAI1) on migration of CD4+ T cells exposed to high FA were investigated in vivo and in vitro. The CD4+ T cells were isolated from peripheral blood of healthy (n = 9) and high-FA (n = 9) Holstein cows (average 2.5 ± 0.2 lactations [SE], 12.3 ± 0.8 DIM). In the first experiment, real-time quantitative PCR was used to assess chemokine receptors in isolated CD4+ T cells and migration capacity. The relative mRNA measurements results revealed downregulation of CCR1 and CXCR2, and upregulation of CCR2, CCR4, CCR5, CCR7, CCR8, CCR10, CXCR1, CXCR3, CXCR4, and CX3CR1. Among them, the expression of CXCR4 was relatively high. Therefore, CXCL12, a ligand chemokine of CXCR4, was an inducer of CD4+ T cell migration. The CD4+ T cells were inoculated in the upper chamber and CXCL12 (100 ng/mL, Peprotech) in RPMI1640 was added to the lower chamber and transmigrated for 3 h at 37°C and 5% CO2. The cell migration assay revealed that the migration capacity of CD4+ T cells from high-FA cows was greater. Real-time-qPCR indicated greater abundance of the glycolysis-related targets HIF1A, HK2, PKM2, Glut1, GAPDH, and LDHA and Western blotting indicated greater abundance of the glycolysis-related targets HIF1A, HK2, PKM2, Glut1, GAPDH, and LDHA in CD4+ T cells of high-FA cows. To characterize specific mechanisms of CD4+ T cell migration in vitro, cells from the spleens of 3 newborn (1 d old, 40–50 kg) healthy female Holstein calves were isolated after euthanasia. Inhibition of glycolysis attenuated the migration ability of cells, but had no effect on the protein and mRNA abundance of store-operated Ca2+ entry (SOCE)-associated calcium release-activated calcium modulator 1 (ORAI1) and stromal interaction molecule 1 (STIM1). In contrast, ORAI1 was upregulated in CD4+ T cells of cows exposed to high FA. To explore the potential mechanisms whereby an active glycolytic metabolism affects CD4+ T cells under high-FA conditions, we knocked down ORAI1 using small interfering RNA (siORAI1). Isolated CD4+ T cells from high-FA cows with the siORAI1 had an attenuated glycolytic metabolism and migration capacity. Taken together, these data suggested that calcium ions in CD4+ T cells from cows with high FA regulate glycolytic metabolism and influence cell migration at least in part by modulating ORAI1. Thus, these studies identified a novel mechanism of Ca2+ regulation of CD4+ T cell glycolytic metabolism affecting their migration through the SOCE pathway.

Background: Awake prone positioning (APP) can reportedly reduce the need for intubation and help improve prognosis of patients with acute hypoxemic respiratory failure (AHRF) infected with COVID-19. However, its physiological mechanism remains unclear. In this study, we evaluated the effect of APP on lung ventilation in patients with moderate-to-severe AHRF to better understand the effects on ventilation distribution and to prevent intubation in non-intubated patients. Methods: The prospective study was performed in the Department of Critical Care Medicine at Shanghai General Hospital, China, from January 2021 to November 2022. The study included patients with AHRF (partial pressure of oxygen [PaO2]/inspired oxygen concentration [FiO2]

Abstract The rapid advancement of quantum key distribution technology in recent years has spurred significant innovation within the field. Nevertheless, a crucial yet frequently underexplored challenge involves the comprehensive evaluation of security quantum state modulation. To address this issue, we propose a novel framework for quantum group key distribution. In the setup phase, preprocessing is introduced to monitor photon intensity and count, thereby ensuring the secure initialization of the protocol. During the measurement phase, signal consistency checks are implemented to verify that the intensity of the signal received by the measurement device corresponds precisely to the transmitted signal. In the key generation phase, error correction is employed to mitigate errors induced by noise or external interference, effectively reducing the error margin and restricting the information available to potential eavesdroppers. This systematic, multi-phase approach significantly enhances the framework’s robustness. Experimental results demonstrate that the proposed protocol not only substantially reduces the error rate under adversarial eavesdropping but also improves the efficiency and security of the key distribution process.

Objectives: This study aimed to investigate the factors associated with physical fitness and disparities in population segments among older adults, using data from the National Physical Fitness Surveilling Survey of China. Study design: A cross-sectional study. Methods: A total of 13524 older adults aged 60–79 years were involved in the study. Participants completed physical fitness assessments encompassing body fat percentage, lung capacity, high leg raise in place, grip strength, seated forward bending, 30-s sit-to-stand test, single-leg standing with eyes closed, and choice reaction time. A profile analysis model was constructed by feature extraction, label design and clustering using principal component analysis and k-prototypes. Factors associated with physical fitness were analyzed using ordered probit regression, and within-group differences were evaluated through the bootstrap method. Results: The older adults were categorized into four clusters based on the clustering results (Cluster I: n = 2728, Cluster II: n = 6067, Cluster III: n = 4189, Cluster IV: n = 540). Significant positive associations were identified between moderate-to-vigorous transport-related activities (α = 0.001, p

Abstract Background This study aims to examine the temporal changes in the incidence, prevalence, and disability-adjusted life years (DALYs) of depressive disorders as well as its association with age, period, and birth cohort among Chinese from 1990 to 2021, and forecast the future trends of incidence rates and numbers from 2022 to 2030. Methods Data for analysis were obtained from the Global Burden of Disease (GBD) 2021. Joinpoint analysis was used to calculate the annual percentage change (APC) and average annual percent change (AAPC) to describe the rates of depressive disorders. Age, period, and cohort model was utilized to disentangle age, period, and birth cohort effects on rates of depressive disorders. Bayesian age-period-cohort (BAPC) analysis was capitalized to forecast the incidence rates and numbers for different sexes and age groups from 2022 to 2030. Results The age-standardized incidence (ASIR, AAPC: -0.35 [95%CI: -0.65, -0.04]), prevalence (ASPR, AAPC: -0.20 [95%CI: -0.24, -0.16]), and DAYLs (AAPC: -0.28 [95%CI: -0.51, -0.05]) rates of both sexes showed a downward trend from 1990 to 2021, despite a volatility growth in recent years (APC in 2019–2021 of ASPR: 0.96 [95%CI: 0.70, 1.23]). Females exhibited a higher burden of depressive disorders compared to males but experienced a more rapid rate of reduction changes. The burden of depressive disorders was most owing to the age effect and period effect in recent years. The ASIR was predicted to decrease in the whole population (males in 2030: 1,546.3 per 100,000 people; females in 2030: 2,465.8 per 100,000 people), but in children, adolescents, and the elderly demonstrate unfavorable trends in the future. Conclusion The burden of depressive disorders decreased in China from 1990 to 2021 in terms of age-standardized rates, but increased in recent years. Children, adolescents, and the elderly are the risk groups for future depressive disorders. Considering the large population, the increasing fewer children, and the aging trend, as well as the possible long-term effects of COVID-19 on human psychological burden, more sex-age-sensitive social healthcare programs should be considered in the future to minimize the burden of depressive disorders in China.

Abstract Background Cardiovascular and cerebrovascular diseases (CVDs) present a significant challenge in the realm of chronic disease management in China. The objective of this study is to assess the efficacy of a health management model rooted in a three-tier prevention and control system for CVDs. Methods From August 2020 to September 2020, this study enrolled 2033 CVDs patients from 105 villages across three townships in central China. All participants underwent a 12-month health management involving monitoring, risk assessment, health education, and interventions. The primary endpoint focused on recurrence and exacerbation, while secondary outcomes encompassed health economic indicators, awareness of prevention and control knowledge, risk factor, lifestyle behavior. Data analysis was conducted using generalized estimating equation models. Results After 1 year of follow-up, the odds of recurrence and exacerbation decreased significantly compared to the baseline [odds ratio (OR) 0.30, 95% confidence interval (CI): 0.26, 0.35], accompanied by reduced hospitalization frequency [mean difference (MD) -0.61, 95% CI: -0.66, -0.56] and a monthly average reduction in medication costs (MD, -69.80, 95% CI: -104.55, -35.05). Moreover, patients’ awareness of CVDs prevention and treatment knowledge markedly improved (P

Abstract Background Nursing interns, the future nurses, often find it challenging to interact with trauma survivors due to their lack of experience and training. Assessing their attitudes and knowledge in trauma-informed care can improve their clinical performance. Objective To culturally adapt and assess the reliability and validity of the Attitudes Related to Trauma-Informed Care Scale in Chinese nursing interns. Design Quantitative cross-sectional design. Methods The translation of Attitudes Related to the Trauma-Informed Care (ARTIC) Scale followed guidelines for the cross-cultural adaptation process. A survey was conducted with 490 nursing interns from two colleges in China in February and May 2024, and seven experts evaluated the content equivalence of each item. Reliability and validity were assessed using item analysis, exploratory factor analysis, confirmatory factor analysis, internal consistency reliability, and test–retest reliability. Results The Chinese version of the ARTIC-C retained 35 items and demonstrated high content validity. Exploratory factor analysis revealed a 6-factor structure, explaining 61.887% of the total variance. Confirmatory factor analysis indicated that the 6-factor model adequately represented the scale structure: chi-square/degree of freedom (CMIN/DF) = 1.544, root mean square error of approximation (RMSEA) = 0.045, comparative fit index (CFI) = 0.969, incremental fit index (IFI) = 0.969, Tucker Lewis index (TLI) = 0.966, and standardized root mean square residual (SRMR) = 0.046. The scale had a Cronbach's alpha of 0.916 and test–retest reliability of 0.876. Conclusions The Chinese version of the ARTIC-C scale has demonstrated strong reliability and validity, making it an effective tool for measuring Chinese nursing interns' attitudes and knowledge regarding trauma-informed care.

Abstract Background Pueraria is an edible and medicinal raw material, which is of great value to the pharmaceutical and food industries. Nonetheless, due to morphological diversity and complex domestication history, the classification of Pueraria plants is ambiguous. As the varieties on the market are mixed, the species are difficult to distinguish, and their morphological characteristics are similar to the physical and chemical properties. It is difficult to accurately identify them by traditional identification methods. Chloroplast (cp) genomes are widely used in species identification and phylogenetic studies to achieve accurate identification of medicinal plants, and can also provide more reference information for phylogenetic studies. Based on interspecific and intraspecific sampling, the cp genomes of eight species or varieties of Pueraria plants were examined in this study. Results The study unveiled that the cp genome size varied from 151,555 to 153,668 base pairs (bp), with the total GC content ranging from 35.4 to 37.0%. Moreover, it was discerned that the cp genome contained between 128 and 135 genes. Comparative analysis indicated that the highest number of Simple Sequence Repeats (SSRs) was identified in P. montana and P. alopecuroides, with a preponderance of these SSRs being rich in Adenine (A) and Thymine (T) nucleotides. Complete comparison and sliding window analysis of the cp genome established that the non-coding region exhibited greater sequence differences than the coding region, and that the large single copy (LSC) region demonstrated higher nucleotide polymorphism levels. Fourteen highly variable loci such as rpoB,ycf1,rbcL,trnF-GAA-trnL,psbC-psbD, and ycf4-cemA were detected as potential molecular markers for Pueraria species identification. Moreover, the phylogenetic tree demonstrated that other Pueraria species had the most distant relationship with Haymondia wallichii and Toxicopueraria peduncularis, thereby offering fresh perspectives into the species classification of Pueraria. The molecular clock analysis results indicate that the divergence time of Pueraria may occur at ∼6.46 Ma. It is speculated that the cold climate may be the cause of Pueraria species diversity and promote the radiation of the genus. Conclusion This research provides theoretical backing and serves as a reference point for the identification and taxonomical classification of Pueraria species. The findings will prove beneficial in future studies on the preservation of medicinal resources, phylogenetic relationships, and genetic engineering of Pueraria plants.

Abstract Despite a lot of efforts devoted to construct efficient microbiomes, there are still major obstacles to moving from the lab to industrial applications due to the inapplicability of existing technologies or limited understanding of microbiome variation regularity. Here we show a domestication strategy to cultivate an effciient and resilient functional microbiome for addressing phenolic wastewater challenges, which involves directional domestication in shaker, laboratory water test in small-scale, gas test in pilot scale, water test in pilot scale, and engineering application in industrial scale. The domestication process includes the transition from water to gas, which provided complex transient environment for screening of a more adaptable and robust microbiome, thereby mitigating the performance disparities encountered when transitioning from laboratory experimentation to industrial engineering applications. Within the domestication and application processes for treating phenolic resin wastewater, a powerful functional microbiome was built by self-assembly. This leads to an augmented biodiversity and the development of more intricate phenol and formaldehyde metabolic pathways. The incorporation of increased stochastic processes and random network characteristics further suggested the stability of the microbial community during the application phase. This study elucidates the self-assembly process of microbial communities during the artificial construction process, showcasing their adaptive evolution under different adverse conditions. It serves as a noteworthy case study for the artificial construction of a microbiome for the engineering application of treating industrial wastewater.

Abstract Background We aimed to analyze the correlation between serum lipid levels [total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C)] and recurrence after uterine fibroids (UF) resection, and explore the predictive value of serum lipid levels in determining recurrence after myomectomy. Methods In this retrospective cohort study, 323 patients undergoing first myomectomy who came from Li Huili Hospital, Ningbo Medical Center between December 2019 and January 2023 were included. The primary endpoint was the recurrence of UF within 12 months following surgery. Univariate and multivariate logistic regression analyses were adopted to evaluate the association between four serum lipid parameters and the risk of UF recurrence. All included patients were randomly assigned to the training group for nomogram development and the testing group for nomogram validation, with a ratio of 7:3. Receiver operator characteristic, calibration curves, and decision curve analysis were used to assess the predicting performance of constructed nomograms. Results Totally, 98 developed the recurrence of UF within 12 months following surgery. Multivariate logistic regression analyses indicated that high levels of TC [odds ratio (OR) = 9.98, 95% confidence interval (CI): 4.28–23.30], LDL-C (OR = 11.31, 95% CI: 4.66–27.47) and HDL-C (OR = 2.37, 95% CI: 1.21–4.64) were associated with recurrence of UF risk. The association between TG level and UF recurrence risk did not statistical significance (P > 0.05). Four online prediction nomograms by integrating serum lipid levels and clinical features for predicting the risk of recurrence of UF were developed (TC-model, TG-model, LDL-C-model and HDL-C-model). Through verification, these models may have good prediction performance for predicting the recurrence of UF risk. Conclusion This study developed and validated prediction nomograms for predicting the risk of UF recurrence. These nomograms can provide individual risk assessment for UF recurrence.

Abstract Gastrointestinal polyps are early indicators of many significant diseases within the digestive system, and timely detection of these polyps is crucial for preventing them. Although clinical gastrointestinal endoscopy and interventions help reduce the risk of malignancy, most current methods fail to adequately address the uncertainties and scale issues associated with the presence of polyps, posing a threat to patients’ health. Therefore, this paper proposes a novel single-stage method for polyp detection. Specifically, by designing the CRFEM, the network’s ability to perceive contextual information about polyp targets is enhanced. Additionally, the RSPPF is designed to assist the network in more meticulously completing the fusion of multi-scale polyp features. Finally, one detection head is removed from the original model to reduce a substantial number of parameters, and a high-dimensional feature compensation structure is designed to address the decline in recall rate caused by the absence of the detection head. Experiments were conducted using public datasets such as Kvasir-seg, which includes gastric and intestinal polyps. The results indicate that CRH-YOLO achieves 88.8%, 86.0%, and 90.7% on three key metrics: Precision (P), Recall (R), and mean average precision at 0.5 (map@.5), significantly outperforming current mainstream detection models like YOLOv8n. Notably, CRH-YOLO improves the map@.5 metric by 2.4% compared to YOLOv8n. Furthermore, the model demonstrates excellent performance in detecting smaller or less obvious polyps, providing an effective solution for the early detection and prediction of polyps.

Abstract Reduction of power consumption is the key target for modern electronic devices. To this end, a lot of attention is paid to zero-static power switches, being able to change their state between highly resistive and highly conductive and remain in this state even in the absence of external voltage. Still, the implementation of such switches is slow because of compatibility issues of new materials with CMOS technology. At the same time, printable technology enables low-cost processes at ambient temperature and integration of devices onto flexible substrates. Here we demonstrate that printed Ag/MoS2/Ag heterostructures can be used as zero-static power switches in radiofrequency/microwave spectrum and fully-integrated reconfigurable metasurfaces. Combined with graphene, our printed platform enables reconfigurable metasurface for electromagnetic wave manipulation and control for wireless communications, sensing, and holography. In addition, it is also demonstrated that the localised MoS2 phase change may have promoted Ag diffusion in forming conductive filaments.

Abstract Background With the extensive utilization of immune checkpoint inhibitors (ICIs) across various cancers, ICIs-related thyroid dysfunction (ICI-TD) has become a growing concern in clinical practice. This study aimed to devise an individualized management strategy for ICI-TD to enhance the early identification and proactive management in cancer patients. Methods We designed and conducted a three-phase study. Initially, we analyzed the influencing factors through a systematic review and meta-analysis, which adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Moreover, the study protocol was registered with PROSPERO (CRD42019131133). Subsequently, prediction models for ICI-TD were developed utilizing 11 algorithms based on the real-world cohort data from July 20, 2018 (the approval date of the first ICIs, Pembrolizumab in China), to October 31, 2022. Considering discrimination, calibration, and clinical utility, we selected the model with the best performance for web calculator development. Finally, individualized management strategies for ICI-TD were proposed by combining evidence-based analysis with practical considerations. Results The systematic review encompassed 21 observational studies involving 4,145 patients, revealing associations between ICI-TD and factors such as female gender, age, receipt of Pembrolizumab (versus other ICIs), and baseline levels of thyroid-stimulating hormone, free thyroxine, and antithyroid antibodies. In the prediction model development phase, 621 participants were enrolled, with 36 patients developing ICI-TD. The model based on the LightGBM algorithm demonstrated superior performance, leading to the development of a web calculator. Based on these findings and existing guidelines, individualized monitoring and treatment pathways for pharmacists were devised. Conclusion This study offers comprehensive insights into managing ICI-TD, potentially enhancing tailored cancer immunotherapy management.

Abstract As the electromagnetic environment becomes increasingly complex, radar encounters more intricate jamming patterns. Accurate and real‐time jamming recognition is crucial for effective radar anti‐jamming decisions. For scenarios with limited data, a rapid active jamming recognition method based on the Hybrid 3_CNN‐Transformer model is proposed. To thoroughly evaluate and validate this method, we simulated nine jamming types and used pulse compression for preprocessing. Combining the strengths of CNNs and Transformers, we constructed the Hybrid 3_CNN‐Transformer model, which employs three CNNs to extract local features from the complex domain, real part, and imaginary part of the jamming signals. After concatenating these features and performing position encoding, the model utilises Transformers to capture global features, enhancing recognition accuracy and reducing training time. To enhance computational efficiency and reduce storage, we applied an L1 norm‐based unstructured pruning algorithm for model compression, achieving an 82% pruning rate and cutting inference time to 33 ms. Experiments show that the Hybrid 3_CNN‐Transformer model significantly boosts recognition accuracy and speed over other models. On a small dataset with nine jamming types, it achieved 95.1% accuracy after 25 epochs and 100% after 90 epochs. This approach enhances training speed and accuracy, allowing rapid and reliable jamming recognition in resource‐limited environments.

Abstract Background Cancer-associated fibroblasts (CAFs), a predominant stromal cell type in the tumor microenvironment, significantly affect the progression of oral squamous cell carcinoma (OSCC). Results The specific mechanisms through which CAFs influence the cancer stem cell phenotype in OSCC are not fully understood. This study explored the effects of lactic acid produced by CAFs on the cancer stem cells (CSCs) phenotype of OSCC cells. Our results demonstrated that CAFs exhibit increased glycolysis and lactic acid production. Lactic acid treatment enhances CSCs-related markers expression, sphere formation, and clonogenic ability of OSCC cells. RNA sequencing revealed that lactic acid treatment elevates Discs Large Homolog 5 (DLG5) expression and markedly affects the Hippo pathway. Further investigation revealed that DLG5 mediates the effects of lactic acid on the CSCs phenotype. DLG5 knockdown results in elevated expression of E3 ubiquitin ligase Cullin 3, which can promote the ubiquitination and degradation of MST1, but the expression of phosphorylated MST1 remains unchanged. This leads to enhanced binding of phosphorylated MST1 to YAP1, increasing YAP1 phosphorylation and activating the Hippo pathway. Conclusion Collectively, our findings suggest that lactic acid from CAFs promotes the CSCs phenotype in OSCC through the DLG5/CUL3/MST1 axis. Therefore, targeting lactic acid exchange between CAFs and tumor cells may provide a novel therapeutic approach to suppress the CSCs phenotype in OSCC.

We first describe a photoinduced decatungstate-catalyzed direct coupling of cycloalkanes and cyclic aldimines. The desired products were generated in moderate to good yields with wide substrate scope under mild reaction conditions. The mechanistic study revealed a radical process. In addition, the usefulness of the reaction in organic synthesis was proved by the scale-up synthesis as well as the late-stage modification of drug-like molecules.

Abstract In this study, a novel type of diamond grinding wheel with linear cooling channels (GWLCC) is proposed, and an innovative manufacturing process is employed to develop this new grinding wheel. Grinding experiments conducted on four types of hard and brittle materials demonstrate that the grinding performance of GWLCC is better than that of conventional dense grinding wheels. Furthermore, the grinding performance of GWLCC was further investigated by comparing the abrasive ratio and working current under various grinding process parameters. The results indicate that the grinding efficiency of the grinding wheel is positively correlated with the rotating speed, achieving maximum efficiency at a rotating speed of 300 r/min. Additionally, variations in feed speed significantly affect the grinding force, but to protect the grinding equipment, the value shouldn’t be too large.

Abstract Background This study aimed to understand the vision health status of adolescents in the Western Pacific Region (WPR) using Global Burden of Disease (GBD) data from 1990 to 2019. Methods We conducted a comprehensive analysis of blindness and vision loss using GBD data from 1990 to 2019, analyzed trends in the prevalence and burden of blindness and vision loss over time using joinpoint regression, and analyzed their independent effects on blindness and vision loss in three dimensions using age-period-cohort (APC) modeling. Results The prevalence of blindness and vision loss among adolescents in the WPR showed an increasing trend between 1990 and 2019 (AAPC: 0.56%) and a slight increase in YLD (AAPC: 0.11%). The joinpoint regression showed a decreasing trend after 2017 (AAPC: -2.45%). The prevalence and burden trended downward in most Western Pacific countries, with only China rising significantly (AAPC prevalence: 0.57%). Refractive disorders had the highest prevalence among the subgroups. The risk of blindness and vision loss in adolescents reduced with age but grew later in time and at later birth. In addition, prevalence and burden were generally higher in females than males. Conclusions In the context of a declining global trend in the prevalence and burden of blindness and vision loss among adolescents, there is an increasing trend among adolescents in WPR, with the most pronounced rise in China. This finding has important implications for WPR, suggesting that more attention should be given to adolescent eye health in the region.

Abstract Background Exosomes (Exos) from adipose-derived stem cells (ADSCs) have a high inclusion content and low immunogenicity, which helps to control inflammation and accelerate the healing of wounds. Unfortunately, the yield of exosomes is poor, which raises the expense and lengthens the treatment period in addition to impairing exosomes’ therapeutic impact. Thus, one of the key problems that needs to be resolved in the current exosome study is increasing the exosome yield. Methods Tetraspanin-6 (TSPAN6) overexpression and knockdown models of ADSCs were constructed to determine the number of exosomes secreted by each group of cells as well as the number of multivesicular bodies (MVBs) and intraluminal vesicles (ILVs) within the cells. Subsequently, the binding region of the interaction between TSPAN6 and syntenin-1 was identified using the yeast two-hybrid assay, and the interaction itself was identified by immunoprecipitation. Finally, cellular and animal studies were conducted to investigate the role of each class of exosomes. Results When compared to the control group, the number of intracellular MVBs and ILVs was significantly larger, and the number of ADSCsTSPAN6+-Exos was more than three times higher. However, TSPAN6’s ability to stimulate exosome secretion was reduced as a result of syntenin-1 knockdown. Additional yeast two-hybrid assay demonstrated that the critical structures for their interaction were the N-terminal, Postsynaptic density protein 95/Discs large protein/Zonula occludens 1 (PDZ1), and PDZ2 domains of syntenin-1, and the C-terminal of TSPAN6. In animal trials, the wound healing rate was best in the ADSCsTSPAN6+-Exos group, while cellular experiments demonstrated that ADSCsTSPAN6+-Exos better enhanced the proliferation and migration of human skin fibroblasts (HSFs) and human umbilical vein endothelial cells (HUVECs). Conclusion TSPAN6 stimulates exosome secretion and formation, as well as the creation of MVBs and ILVs in ADSCs. Syntenin-1 is essential for TSPAN6’s stimulation of ADSCs-Exos secretion. Furthermore, ADSCsTSPAN6+-Exos has a greater ability to support wound healing, angiogenesis, and the proliferation and migration of a variety of cells.

Abstract Certain immune-checkpoint inhibitors have a narrow therapeutic window (TW) as cancer therapeutics, and engineered dual-/multi-targeting agents could potentially widen the TW to bring true clinical benefits. We report a new rationally-designed bispecific-antibody (BsAb), HX009, simultaneously targeting PD1 and CD47 to improve both the efficacy and safety over the respective single-targeting agents by grafting the extracellular domain of SIRPα onto the parental anti-PD1-monoclonal antibody, HX008. This resulted in an IgG4-based “2 × 2” symmetric structure but with an intentionally-reduced CD47-binding affinity, suggesting a novel candidate cancer immunotherapy. Specifically, HX009 has binding affinity constant of 8.951 × 10–9 M for human PD1 and 2.557 × 10–8 M for human CD47, respectively, where the CD47 binding is significantly weaker as compared to the binding affinity of HX008 to PD1 as well as the binding affinity of SIRPα-Fc to CD47, leading to little binding to RBCs and platelets and is contrasting to many CD47-agents in development. However, HX009 effectively and simultaneously binds to the PD1 and CD47 on PD1+CD47+ T-cells via cis-binding and elicits enhanced T cell activation compared to the parental HX008. HX009 caused little cytokine-release in human peripheral blood mononuclear cells. HX009 cross-species binds to cynomolgus monkey PD1/CD47 but not to rodents, making cynomolgus monkeys the choice of species to investigate the pharmacokinetics (PK) and toxicology of HX009. HX009’s anti-tumor activities were confirmed in several humanized preclinical mouse models by determining either its anti-PD1 (humanized hu-CD47-MC38 models) or anti-CD47 (HuT-102 lymphoma CDX and three PDX-AML models) functions, although limited available humanized models have hindered broadly demonstration of enhanced anti-tumor activities contributed from the dual targeting of the BsAb. The expanded DLBCL-PDX trial data suggested that both EBV-status and OX40 expression could potentially be two positive predictors for response to HX009. An intravenous (IV) infusion PK study in cynomolgus monkey revealed its largely vasculature distribution, terminal half-life (T1/2) of ~ 50 h, and dose-proportional exposure without accumulation. The anti-drug antibody (ADA) was observed in all monkeys as expected, affecting the PK parameters of repeated administration. The IV single-dose toxicology study with a 14-day observation revealed a maximum tolerated dose of 150 mg/kg, while the repeated-dose (once weekly for 4 weeks, 5 doses in total) study showed a highest non-severely toxic dose (HNSTD) of 15 mg/kg. The desired preclinical PK and safety profiles, along with its antitumor activity, support HX009’s candidacy for its clinical development.

Abstract Objective Oral health is a critical area in healthy aging. Oral health literacy (OHL) plays an important role in improving oral health behaviors and oral health status. However, few studies have investigated OHL among community-dwelling older adults and the influential mechanism of OHL on oral health behaviors has not been clarified. The aim of this study is to explore the interaction pathways through which OHL influences oral health behaviors among community-dwelling older adults. Methods This is a cross-sectional study. 429 community-dwelling older adults were recruited by a convenience sampling method from the activity service center in Zhenjiang, Southern China. The data were collected between September and November 2021 using the Oral Health Literacy Adult Questionnaire (OHL-AQ) and other sophisticated scale assessments. A theoretical model based on the information-motivation-behavioral skills model (IMB model) and previous research was developed and then validated using a structural equation model with AMOS v24.0. Results The proposed model revealed a good fit to the data (χ2/df = 3.349, goodness of fit index = 0.957, adjusted goodness of fit index = 0.921, root mean squared error of approximation = 0.074, comparative fit index = 0.955, normed fit index = 0.938). Oral health information (β = 0.23) and motivation (β = 0.56) positively affected OHL. OHL (β = 0.20) and motivation (β = 0.25) positively affected self-efficacy; self-efficacy (β = 0.98) had a direct effect on oral health behavior. OHL had an indirect effect on oral health behaviors through self-efficacy (β = 0.19). Motivation can both directly influence oral health behavior (β = 0.18) and indirectly influence oral health behavior through OHL and self-efficacy(β = 0.35). Conclusions The study findings make a valuable contribution to the influential mechanism of OHL on oral health behaviors. OHL improved oral health behaviors through self-efficacy among community-dwelling older adults. Oral health information directly affected OHL. Motivation directly affected oral health behaviors as well as influence oral health behaviors by changing OHL.

Abstract Social anxiety is highly prevalent among nursing students and is associated with poor mental health. However, the underlying mechanism in such an association remains unclear. This study aimed to examine the potential mediating role of social intelligence in the association between social anxiety and mental health using the Stress-Coping Model (SCM) as the theoretical framework. A cross-sectional study was conducted among 748 nursing students recruited from a Chinese University from December 2022 to March 2023. Students completed an online questionnaire to assess their social anxiety, social intelligence, and mental health. The PROCESS SPSS Macro (model 4) was used to test the mediation effect of social intelligence on the association between social anxiety and mental health. The results showed that nursing students had moderate levels of social anxiety, social intelligence, and mental health, which varied according to their profile characteristics. Social anxiety was negatively associated with mental health, and the association was partially mediated by social intelligence. Our study offers fresh insights into the impact of social anxiety on mental health and sheds light on the intricate mediating role of social intelligence. These findings offer valuable insights for research and clinical endeavors aimed at formulating psychosocial interventions to enhance the mental health of nursing students.

Abstract The recognition of the transient dominant instability mode is of great significance for rapidly and accurately formulating transient emergency decisions in power systems. In response to the challenge of accurately distinguishing between angle instability and voltage instability, which are coupled in actual power grids, this paper explores the mapping relationship between simulation data and the stable state of the system, as well as the dominant instability mode. The method enables real‐time identification of the dominant instability mode, which bypasses complex physical mechanisms. Firstly, spatio‐temporal feature mining is conducted, where convolutional neural networks are employed to learn crucial local features of transient curves, and bidirectional gated recurrent unit s utilized to learn transient features over time sequences. Next, a multihead attention mechanism is introduced to enhance sensitivity to important time steps in the sequence data. Finally, the transit search optimization algorithm optimizes the global model parameters, further increasing the accuracy of the model. Using the IEEE 10‐machine and 39‐node system as an example for simulation, the results validate that the proposed method exhibits significant advantages in terms of accuracy and applicability compared with other machine learning methods.

Abstract The rise of object detection models has brought new breakthroughs to the development of clinical decision support systems. However, in the field of gastrointestinal polyp detection, there are still challenges such as uncertainty in polyp identification and inadequate coping with polyp scale variations. To address these challenges, this paper proposes a novel gastrointestinal polyp object detection model. The model can automatically identify polyp regions in gastrointestinal images and accurately label them. In terms of design, the model integrates multi-channel information to enhance the ability and robustness of channel feature expression, thus better coping with the complexity of polyp structures. At the same time, a hierarchical structure is constructed in the model to enhance the model’s adaptability to multi-scale targets, effectively addressing the problem of large-scale variations in polyps. Furthermore, a channel attention mechanism is designed in the model to improve the accuracy of target positioning and reduce uncertainty in diagnosis. By integrating these strategies, the proposed gastrointestinal polyp object detection model can achieve accurate polyp detection, providing clinicians with reliable and valuable references. Experimental results show that the model exhibits superior performance in gastrointestinal polyp detection, which helps improve the diagnostic level of digestive system diseases and provides useful references for related research fields.

Abstract This study explored the factors influencing serum 25(OH)D3 levels and the effects of Vitamin D deficiency (VDD) and VD supplementation on 25(OH)D3 levels and neuropsychobehavioral development in premature infants, to provide a theoretical basis for improving their prognosis. Physical examination, neuropsychobehavioral development and serum 25(OH)D3 levels were assessed regularly in 158 preterm infants supplemented with VD formulation. 25(OH)D3 levels were analyzed at 3, 6, 9, 12, and 18 months after birth. The Gesell neuropsychological development test was conducted at 6, 9, 12, and 18 months after birth to obtain the developmental quotient (DQ). Based on the serum 25(OH)D3 levels at 42 days of age, the infants were divided into VDD and non-VDD groups. Preterm infants in the VDD group were supplemented with more VD until their 25(OH)D3 levels were normal, and were divided into sustained VDD (SVDD) and corrected VDD (CVDD) groups according to serum 25(OH)D3 levels at 3 months of age. Appropriate statistical methods were chosen to compare differences in 25(OH)D3 and DQ between or among different groups, screen for the factors influencing 25(OH)D3 levels in preterm infants at 42 days of age, and analyze the relationship between 25(OH)D3 and DQ. The 25(OH)D3 levels of preterm infants at 42 days of age were positively correlated with VD supplementation during pregnancy, and before 42 days after birth (P

Abstract Aims The primary aim of this study was to characterize the health-related quality of life (HRQoL) and identify the associated factors among children aged 2 to 18 in China diagnosed with idiopathic nephrotic syndrome (INS). Additionally, the study aimed to evaluate the HRQoL and caregiving burden of their caregivers and investigate the correlation between the HRQoL of the children and that of their caregivers. Methods This study recruited 181 children diagnosed with INS from Children’s Hospital, Zhejiang University School of Medicine in China. The proxy-reported PedsQL Generic Core Module (PedsQL™ 4.0 GCM) was used to measure the HRQoL of children, and the EuroQol five-dimensional questionnaire, five-level version (EQ-5D-5L) was applied to measure caregivers’ HRQoL. Differences in scale scores and total scores of PedsQL™ 4.0 GCM were assessed using t-tests and one-way ANOVA. Multivariate linear regression analysis was used to identify the factors associated with children’s HRQoL. Pearson correlation analysis evaluated the correlation between children’s HRQoL and caregiver’s HRQoL. Results HRQoL of Children with INS declines with increasing age, and children aged 5-18 had lower scores in physical functioning, emotional functioning, school functioning, psychosocial health summary score, and total PedsQL™ 4.0 GCM score compared to healthy children. Various factors, including the mother filling out the questionnaire, the father being unemployed, and the use of other medications except for steroids, were associated with worse HRQoL of children (p values

Background: As a chronic inflammatory process, chronic osteomyelitis is caused by bacterial infections that lead to bone destruction. This disease is more common in patients with open fractures and those undergoing multiple surgical procedures after trauma. We aimed to provide a comprehensive overview and critical assessment of the therapeutic efficacy of the anterolateral thigh (ALT) perforator flap in the management of chronic osteomyelitis with dermatologic and soft tissue imperfections localized in the lower extremity. Methods: A retrospective analysis involving a cohort of 16 patients who underwent ALT perforator flap reconstruction for the management of chronic osteomyelitis in the calf region that manifested with integumentary deficiencies was conducted. Results: During the follow-up period spanning from 4 months to 2 years, all 16 patients who underwent ALT perforator flap transplantation exhibited flap viability. Among these cases, 15 patients made a full recovery from the infection and 1 patient had partial survival. Among the 15 cases, 2 patients developed vascular crisis (owing to venous thrombosis during surgical exploration). One patient had a relapse of the disease 1-year post-surgery. The success rate of this surgical method was 15/16, and the surgical complications included flap crisis, flap necrosis, delayed wound healing, and recurrence of infection. Conclusion: The ALT perforator flap, which can cover bone and soft tissues and effectively control infections, can be applied to the treatment of chronic osteomyelitis of the lower limbs with skin defects. Overall, the muscle flap fills the dead space and medullary cavity and skin flap covers the skin defect.

Abstract Background Chlorophenoxy compounds represent a group of selective herbicides widely used around the world. Chlorophenoxy herbicides are toxic, chemically stable, and can migrate into groundwater through soil leaching, posing a significant threat to drinking water safety and human health. Chlorophenoxy herbicides in groundwater aquifers are subject to anaerobic processes; however, the pathway and microbiology involved in the attenuation of chlorophenoxy herbicides under anaerobic condition are largely unknown. Here, the anaerobic degradation process of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), a typical chlorophenoxy herbicide, was investigated. Results The initial 52.5 ± 2.3 μM 2,4,5-T was completely degraded by a sediment-derived microbial consortium, with 3,4-dichlorophenol, 2,5-dichlorophenol, 3-chlorophenol (3-CP) and phenol being identified as the intermediate products. Reductive dechlorination of 3-CP to phenol and the subsequent elimination of phenol were the key transformation steps in the overall degradation process of 2,4,5-T. Amplicon sequencing suggested that Dehalobacter, Sulfuricurvum, Bacteroides, Acetobacterium, and Clostridium sensu stricto 7 might contribute to the transformation of 2,4,5-T to phenol, and Smithella, Syntrophorhabdus, Methanofollis and Methanosaeta likely cooperated to accomplish the complete mineralization of phenol. Conclusions This study reported the anaerobic degradation of 2,4,5-T via reductive dechlorination and the subsequent syntrophic metabolization of phenol, an intermediate product transformed from 2,4,5-T. Dehalobacter was identified as the organohalide-respiring population catalyzing the reductive dechlorination reaction. Syntrophorhabdus and methanogenic populations were likely involved in anaerobic phenol oxidation and facilitated the complete mineralization of 2,4,5-T.

The solution-treated second-generation single crystal (SX) superalloys underwent hot isostatic pressing (HIP) at 1316 °C and 105 MPa for varying durations. This study investigates the effect of HIP on micropores and stress-rupture behavior under conditions of 980 °C and 250 MPa. The results illustrate that the application of HIP treatment significantly reduces the porosity and volume of micropores, thereby increasing the rupture life of the alloys. With the disappearance of micropores, the crack initiation site shifts from the micropores to the γ/γʹ interface, resulting in reduced crack dimensions and decelerated propagation. Consequently, the smaller size of cracks in HIPed specimens slow down fracture. Nonetheless, the crack propagation pattern remains consistent: cracks expand perpendicular to the stress axis, connecting with cracks at other heights via secondary cracks along the direction.

Nuclear energy is essential for the future development of countries. However, both structural and functional components of nuclear power equipment are facing severe challenges of nuclear irradiation damage after experiencing irradiation growth and irradiation creep. How to avoid irradiation damage to nuclear power equipment has become a hotspot in international research and development of surface protection technology. Deposition of protective coatings on the underlying object surface or in bulk materials has been considered as a near-term solution to enhanc functional components. Different substrate materials are selected according to other service conditions within the reactor. Suitable material selection combined with relevant optimization can significantly increase the service life of materials. This review summarizes recent research on several categories of anti-irradiation coatings prepared by physical vapor deposition technology for current industrial applications. These includes metallic, ceramic, composite and high entropy alloy coatings. The review endeavors to impart a thorough understanding of the properties of these selected anti-irradiation coatings, from the fundamental aspects of their substrate materials to their practical applications across diverse settings. It explores not only the current research progress but also the potential avenues for future advancements. Additionally, the intricate relationships between coating formulations, their resistance to irradiation, and their ultimate performance in various environments are illuminated in this paper.

Objective To evaluate the quality of laboratory testing using anti-HIV ELISA quality monitoring indicators and continuously improve laboratory testing capabilities. Methods The data of our blood testing laboratory from July 1, 2020 to December 31, 2022 using laboratory quality monitoring indicators were analyzed, including the reaction sample size and reaction rate of initial test and the reaction sample size and compliance rate of retest. The indoor quality control data of two anti HIV ELISA reagents (Xinchuang and Wantai) during the above time period were collected. A line chart or scatter box chart was drawn to monitor the long-term trends and identify the reasons. Inter-laboratory capability comparison and evaluation with the data from the quality monitoring index evaluation report of the National Health Commission′s Clinical Inspection Center and the National Blood Station Blood Testing Laboratory during the same period was conducted. Results From July 1, 2020 to December 31, 2022, the initial reaction rates of Xinchuang and Wantai anti HIV ELISA reagents were 0.052% and 0.080%, respectively (P

Abstract Background Cell and gene therapy products (CGTPs) often receive accelerated approvals, lacking comprehensive long-term safety and efficacy data, which can raise significant safety concerns. This research aims to study the post-marketing surveillance (PMS) of CGTPs in the European Union (EU), the United States (US), Japan, South Korea, and China, to offer insights for the development of a secure and standardized post-marketing regulatory framework for CGTPs. Methods Related regulations and the implementation effect of PMS for approved CGTPs were studied searching PubMed, CNKI, and the official websites of the European Medicines Agency, the US Food and Drug Administration, Japan’s Pharmaceuticals and Medical Device Agency, South Korea’s Ministry of Food and Drug Safety, and the National Medical Products Administration of China. Results Compared to those in China, the guidelines of PMS for CGTPs in the EU, the US, Japan, and South Korea was more comprehensive. Notably, the EU had dedicated regulations and supporting guidelines of PMS. Of the 26 CGTPs approved in the EU, 88% were under additional monitoring, 38% received conditional marketing authorization, and 12% were authorized under exceptional circumstances, with 77% designated as orphan drugs. The US had released 34 guidelines specifically for CGTPs which, forming the foundation of post-marketing risk management. Among the 27 CGTPs approved in the US, 22% were required to perform risk evaluation and mitigation strategies, 37% added black box warnings in the package inserts, 63% mandated to post-marketing requirements, and 15% subject to post-marketing commitments. In Japan, stringent supervision measures encompassing all-case surveillance (79%) and re-examination (53%) were applied to the 19 approved CGTPs, with 21% approved through conditional and time-limited approval. The PMS for CGTPs in South Korea, mainly included PSUR, re-examination, and re-evaluation. China had introduced several relevant regulations, which consisted of general statements and lacked detailed guidance. Conclusions This study demonstrates that the regulatory policies of PMS for CGTPs in the EU, the US, Japan, and South Korea were comprehensive. The implementation of PMS for CGTPs in the EU, the US, and Japan was well developed. This knowledge holds valuable insights for China’s future learning and development in this field.

Abstract Background With the release of the coronavirus disease 2019 (COVID-19) pandemic in late 2022 in China, the number of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) roared, including neonatal cases. However, there were few studies on neonatal COVID-19, especially multi-center case reports. This study aimed to explore clinical characteristics and short-term outcomes of neonatal COVID-19 in China. Methods We reviewed 187 cases of neonatal COVID-19 between December 11, 2022, and January 12, 2023. The diagnosis was assessed by symptoms, laboratory tests, X-ray manifestations, and diagnosis code. Clinical characteristics and outcomes were evaluated. Results In 187 neonatal cases with COVID-19, 84 (44.9%) had severe SARS-CoV-2 infection. Most patients had confirmed exposure to SARS-CoV-2. Fever and respiratory symptoms were common (75.4% and 71.7%, respectively). Severe patients were more likely to have high alanine transaminase (ALT) (> 40U/L) (11.9% vs. 3.9%) and high N-terminal pro-brain natriuretic peptide (NT-proBNP) (> 2000pg/mL) (38.0% vs. 19.6%), compared with nonsevere ones (P

IntroductionThis study aims to clarify the development characteristics, differences, and convergence trends of environmental efficiency in China’s pig industry, which helps promote the sustainable development of the pig industry.MethodsBased on the data of 30 provinces (municipalities and autonomous regions) in China from 2008 to 2020, this article used the super-SBM model, log (t) test, and ordered probit model to estimate the environmental efficiency and convergence trend of pig farming in China and analyzed the driving factors affecting the convergence trend.ResultsThe results showed that: (1) In recent years, the environmental efficiency of pig farming in China did not reach the optimal state, and the environmental efficiency of the potential growth region was the highest, reaching 71.6%. Scale efficiency is still the key to improving the environmental efficiency of pig farming, and in the future, it is necessary to focus on improving pure technical efficiency. (2) The environmental efficiency of pig farming across China’s 30 provinces (including municipalities and autonomous regions) converges to four clubs. Most provinces within constrained development regions and potential growth regions converge to the high-level club, while the disparities in environmental efficiency of pig farming are most pronounced in key development regions. (3) The research results of driving factors show that scale level exhibits a “U-shaped” effect on the convergence of environmental efficiency in pig farming toward high-level clubs in China, and most provinces have surpassed the inflection point. The scale level of pig farming should be appropriately improved. In addition, improving the quality of the labor force can help the environmental efficiency of pig farming converge to a high-level club.DiscussionWe propose suggestions aimed at enhancing the efficiency of pig farming, promoting the scale processes of pig farming, and strengthening regional cooperation.

BackgroundTension-type headache (TTH) is the most common type of headache and the second most common health-related complaint among children and adults. Traditional Chinese medicine (TCM) offers unique therapeutic benefits in treating TTH. However, the lack of standardized evidence—such as inconsistencies in outcome selection and reporting in clinical studies, a lack of consensus on outcomes and measures, high risks of selective reporting bias, and missing data—has limited the development of robust evidence supporting the efficacy of TCM in treating TTH. Therefore, establishing a core outcome set (COS) is crucial for standardizing TCM clinical studies for TTH, thereby enhancing the quality and comparability of research findings. ObjectiveThis study aims to develop a COS for future clinical studies on the treatment of TTH with TCM. MethodsThe COS will be developed through the following 3 stages. First, systematic reviews and semistructured interviews will be conducted to identify potential essential outcomes, which will be evaluated by the steering committee to finalize a preliminary list of outcomes. Data will be processed using thematic analysis to ensure comprehensive coverage of relevant outcomes. Second, a 2-round Delphi survey will be conducted, inviting stakeholders, including health care experts and patients with tension-type headaches, to determine the importance of each outcome. Statistical analysis will be used to assess the level of consensus and prioritize outcomes based on predefined criteria. Third, a face-to-face consensus meeting will be held to finalize the COS and recommend measurement times for each outcome. Key outcomes will be interpreted based on their clinical relevance and feasibility of measurement, ensuring the COS is comprehensive and applicable in clinical settings. ResultsThe protocol has been registered in PROSPERO, with the review commencing on October 1, 2024, and anticipated results by November 15, 2024. The systematic reviews will be finalized, followed by the Delphi survey and consensus conference in late 2024 and early 2025. The COS findings will be reported per COS-STAR (Core Outcome Set–STAndards for Reporting) guidelines, published in an international journal, presented at conferences, and disseminated to participants for clinical application. ConclusionsThis study is necessary as developing a COS for future TCM clinical studies in the treatment of TTH can maximize the value of data from individual trials and provide high-quality research evidence. Trial RegistrationCore Outcome Measures in Effectiveness Trials Initiative 1473; https://tinyurl.com/3ts62s2p International Registered Report Identifier (IRRID)PRR1-10.2196/63481

Background: Despite the widespread availability of antihypertensive medications, residual cardiovascular risk of hypertension remained high. Limited studies have investigated the link between air pollution, particularly joint exposure to multiple air pollutants, with residual cardiovascular risk of hypertension. Methods: 1981 hypertensive patients (≥ 18 years) from an ongoing longitudinal cohort in China, were enrolled between 2013 and 2019. Using high-quality datasets from China, the ground-level air pollutants concentrations, including PM2.5, PM2.5–10, SO2, O3, CO and NO2, at each participant’s residence were calculated. The relationships between individual and multiple air pollutants with the residual cardiovascular risk were assessed by Cox proportional hazards models, air pollution score analyses and Bayesian Kernel Machine Regression model. Results: Over an average follow-up period of 2.24 years (SD, 1.25), 706 hypertensive patients developed cardiovascular disease. In the single-pollutant analysis, higher concentrations of PM2.5, PM2.5–10, SO2 and CO were linked to increased residual cardiovascular risk. The air pollution score analyses and Bayesian kernel machine regression suggested that combined exposure to multiple air pollutants had a positive association with the residual cardiovascular risk, and NO2 played a dominant role. With higher NO2 concentrations, the hazard ratio of individual pollutants to residual cardiovascular risk increased. Conclusions: Prolonged exposure to a mixture of various air pollutants is linked to elevated residual cardiovascular risk in individuals with hypertension. Apart from taking antihypertensive medication and adopting healthy lifestyle behaviors, hypertensive patients should lower air pollutant exposure to decrease residual cardiovascular risk.

Abstract Acetylation is critically required for p53 activation, though it remains poorly understood how p53 acetylation is regulated in glioblastoma (GBM). This study reveals that p53 acetylation is a favorable prognostic marker for GBM, regardless of p53 status, and that Smad1, a key negative regulator of p53 acetylation, is involved in this process. Smad1 forms a complex with p53 and p300, inhibiting p300's interaction with p53 and leading to reduced p53 acetylation and increased Smad1 acetylation in GBM. This results in enhanced tumor growth and resistance to chemotherapy, particularly in tumors with missense mutant p53. Acetylation of K373 is found to be essential for Smad1's oncogenic function but does not confer chemoresistance in the absence of p53. Through molecular docking, it is discovered that Smad1 and p53 both interact with the acetyltransferase domain of p300, but at different amino acid sites. Disturbing the interface of Smad1 through amino acid mutations abolishes the Smad1‐p300 complex and promotes p53 acetylation. Therefore, a small molecule is identified through virtual screening that specifically disrupts the Smad1‐p300 interaction, offering a promising strategy for inhibiting GBM and increasing chemosensitivity by inhibiting Smad1 acetylation and restoring p53 acetylation.

The monkeypox (MPXV) outbreak in 2022 is more prevalent among individuals with human immunodeficiency virus (HIV). While it is plausible that HIV-induced immunosuppression could result in a more severe progression, the exact mechanisms remain undetermined. To better understand the immunopathology of MPXV in patients with and without HIV infection, we employed single-cell RNA sequencing (scRNA-seq) to analyze peripheral blood mononuclear cells (PBMCs) from 6 patients hospitalized for MPXV, 3 of whom had HIV infection (HIV antibody positive & HIV RNA level below the detection limit), and 3 patients only infected with MPXV (HIV-). We map the peripheral immune response in both the acute phase and the recovery period, showing the reconfiguration of peripheral immune cell phenotypes in acute stage compared with recovery stage of 6 patients, characterized by disturbed cell subsets and intense cell interactions mediated by monocytes and neutrophils. Importantly, besides different Mono/DC dynamic between HIV + and HIV- patients, HIV + patients showed decreased NK cells subsets and expansion of some CD8 T cell subsets, we also found obviously dysregulated gene expression in B cells, thus proposing mechanism underlying serious condition underlying HIV + patients. In conclusion, our findings provide a comprehensive cell atlas of MPXV patients, shed light on the mechanisms underlying the severe disease progression and longer recovery time in HIV + individuals.