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Abstract Depression is a common psychiatric disorder among patients undergoing maintenance haemodialysis (MHD). Depression may reportedly contribute to poor prognosis in several ways, including its effects on platelet function. We hypothesised that depression contributes to the occurrence of cardiocerebral vascular events (CCVE) and dysfunction of arteriovenous fistula (DAVF) in patients undergoing MHD through its effects on platelets. In this prospective cohort study, patients undergoing MHD were recruited and divided into depression and non-depression groups according to their Hamilton Depression Scale (HAMD) scores. The 286 enrolled patients had 103 occurrences of depressive symptoms (prevalence = 36.01%). Compared with the non-depression group, depression group had a significantly higher cumulative prevalence of CCVE and DAVF during follow-up. Cox regression analysis indicated that higher HAMD scores and lower plasma platelet distribution width (PDW) were common risk factors for CCVE and DAVF. Furthermore, HAMD scores were significantly negatively correlated with plasma PDW and was the main variable affecting changes in PDW, as indicated by multiple linear regression analysis. Depression may increase the risk of CCVE and DAVF in patients undergoing MHD by activating platelets. Plasma PDW may be a convenient indicator of platelet activation status and may predict the risk of CCVE and DAVF.

Abstract A 28 days pesticide degradation experiment was conducted for broccoli (Brassica oleracea L. var. italica Planch) and pakchoi (Brassica chinensis L.) with three pesticides (chlorantraniliprole (CAP), haloxyfop-etotyl (HPM), and indoxacarb (IXB)) to explore the effects of biochar on pesticide environmental fate and rhizosphere soil diversity. Rice straw biochar (RB) was applied to soil at a 25.00 t ha−1 dosage under greenhouse conditions, and its effects on the degradation of three pesticides in vegetables and in soil were investigated individually. Overall, RB application effectively facilitated CAP and HPM degradation in broccoli by 13.51–39.42% and in broccoli soil by 23.80–74.10%, respectively. RB application slowed the degradation of CAP, HPM and IXB in pakchoi by 0.00–57.17% and slowed the degradation of CAP in pakchoi by 37.32–43.40%. The results showed that the effect of RB application on pesticide degradation in crops and soil was related to biochar properties, pesticide solubility, plant growth status, and soil characteristics. Rhizosphere soil microorganisms were also investigated, and the results showed that biochar application may be valuable for altering bacterial richness and diversity. The effect of biochar application on pesticide residues in crops and soil was influenced by the vegetable variety first, and the second was pesticide characteristics. RB applied to soil at a 25.00 t ha−1 dosage under greenhouse conditions is recommended for broccoli production to ensure food safety. Our results suggested that biochar application in soil could reduce pesticide non-point source pollution, especially for highly soluble pesticides, and could affect soil microorganisms.

Abstract Packetized energy encapsulates energy into modulated, routable, and trackable energy packets, enhancing the flexibility of managing distributed energy resources and expediting prosumers’ participation in transactive energy markets. In the context of packetized energy trading (PET), energy prosumers are naturally deemed as self‐interested agents seeking to obtain their own benefits. To align with prosumers’ demand, supply, quality of service (QoS), and system‐level social welfare, it is necessary to explore the design of prosumers’ bidding strategies and the market clearing methods, considering prosumers’ utility and the best demand response to markets. This study addresses challenges arising from prosumers’ selfishness and asymmetric preferences by proposing a PET‐oriented iterative double auction (IDA‐PET) design, where prosumers are allowed to iteratively change the bids before the auctioneer clears the market. Moreover, IDA‐PET accommodates system capacity constraints, energy balance, and economic constraints, providing cooperative strategies for both prosumers and the auctioneer. To validate the effectiveness of IDA‐PET, a novel and dedicated co‐simulation platform based on the hierarchical engine for large‐scale infrastructure co‐simulation platform is developed and case studies are conducted within a residential microgrid. The simulation results demonstrate that IDA‐PET can efficiently enhance the revenue of the auction market while meeting prosumers’ QoS requirements.

Abstract Objective Inadequate tuberculosis (TB) knowledge and awareness of proper TB control practices among health care workers (HCWs) may increase the risk of nosocomial TB transmission. This study aimed to assess HCWs’ TB-related knowledge and control practices to guide the development of more effective targeted TB health education and training programs. Methods In January 2023 a cross-sectional survey was administered to 323 HCWs employed by five primary health care centers and three secondary comprehensive medical institutions in Beijing, China. Survey data were collected using a standard questionnaire. Results Analysis of survey responses revealed TB knowledge and practices awareness rates of 60.4% and 90.6%, respectively. The overall average awareness rate across all 19 TB knowledge- and practice-related questions was 70.0%. Intermediate- and senior-level HCW’s average TB knowledge score was respectively 2.225 and 8.175 times higher than that of primary-level HCWs, while the average TB knowledge score of HCWs in secondary comprehensive medical institutions was 3.052 times higher than that of HCWs in primary health care centers. Higher average TB knowledge score correlated with higher-level professional titles and higher level work units, but higher average TB control practices score correlated with employment at primary health care center rather than secondary comprehensive medical institution. Notably, 13.6% of HCWs had not received TB training during the past three years, while 86.1% expressed willingness to undergo online TB training. Conclusion These findings highlight inadequate TB knowledge and awareness of proper TB control practices among HCWs in primary health care centers and secondary comprehensive medical institutions in Beijing, underscoring the urgent need for targeted educational and training initiatives to improve TB awareness and control efforts.

Abstract Community detection is an important method to analyze the characteristics and structure of community networks, which can excavate the potential links between nodes and further discover subgroups from complex networks. However, most of the existing methods only unilaterally consider the direct link topology without comprehensively considering the internal and external characteristics of the community as well as the result itself, which fails to maximize the access to the network information, thus affecting the effectiveness of community detection. To compensate for this deficiency, we propose a new community detection method based on multi-constraint non-negative matrix factorization, named orthogonal regular sparse constraint non-negative matrix factorization (ORSNMF). Based on the network topology, the ORSNMF algorithm models the differences of the outside of the community, the similarities of the nodes inside the community, and the sparseness of the community membership matrices at the same time, which together guides the iterative learning process to better reflect the underlying information and inherent attributes of the community structure in order to improve the correct rate of dividing subgroups. An algorithm with convergence guarantee is also proposed to solve the model, and finally a large number of comparative experiments are conducted, and the results show that the algorithm has good results.

Abstract Purpose This study aimed to analyse the correlation between blood glucose control and the severity of COVID-19 infection in patients with diabetes. Methods Clinical and imaging data of a total of 146 patients with diabetes combined with COVID-19 who visited our hospital between December 2022 and January 2023 were retrospectively collected. The patients were divided into the ‘good blood glucose control’ group and the ‘poor blood glucose control’ group based on an assessment of their blood glucose control. The clinical data, computed tomography (CT) appearance and score and the severity of COVID-19 infection of the two groups were compared, with the severity of COVID-19 infection being the dependent variable to analyse other influencing factors. Results The group with poor blood glucose control showed a higher lobar involvement degree and total CT severity score (CTSS) than the group with good blood glucose control (13.30 ± 5.25 vs. 10.38 ± 4.84, p 0.05). The area under the curve (AUC) of CTSS prediction of critical COVID-19 was 0.895 with sensitivity of 79.3% and specificity of 88.1% when the threshold value is 12. Conclusion Blood glucose control is significantly correlated with the CTSS; the higher the blood glucose is, the more severe the lung manifestation. The CTSS can also be used to evaluate and predict the clinical severity of COVID-19.

Abstract Background Predicting patient mortality risk facilitates early intervention in intensive care unit (ICU) patients at greater risk of disease progression. This study applies machine learning methods to multidimensional clinical data to dynamically predict mortality risk in ICU patients. Methods A total of 33,798 patients in the MIMIC-III database were collected. An integrated model NIMRF (Network Integrating Memory Module and Random Forest) based on multidimensional variables such as vital sign variables and laboratory variables was developed to predict the risk of death for ICU patients in four non overlapping time windows of 0–1 h, 1–3 h, 3–6 h, and 6–12 h. Mortality risk in four nonoverlapping time windows of 12 h was externally validated on data from 889 patients in the respiratory critical care unit of the Chinese PLA General Hospital and compared with LSTM, random forest and time-dependent cox regression model (survival analysis) methods. We also interpret the developed model to obtain important factors for predicting mortality risk across time windows. The code can be found in https://github.com/wyuexiao/NIMRF . Results The NIMRF model developed in this study could predict the risk of death in four nonoverlapping time windows (0–1 h, 1–3 h, 3–6 h, 6–12 h) after any time point in ICU patients, and in internal data validation, it is suggested that the model is more accurate than LSTM, random forest prediction and time-dependent cox regression model (area under receiver operating characteristic curve, or AUC, 0–1 h: 0.8015 [95% CI 0.7725–0.8304] vs. 0.7144 [95%] CI 0.6824–0.7464] vs. 0.7606 [95% CI 0.7300–0.7913] vs 0.3867 [95% CI 0.3573–0.4161]; 1–3 h: 0.7100 [95% CI 0.6777–0.7423] vs. 0.6389 [95% CI 0.6055–0.6723] vs. 0.6992 [95% CI 0.6667–0.7318] vs 0.3854 [95% CI 0.3559–0.4150]; 3–6 h: 0.6760 [95% CI 0.6425–0.7097] vs. 0.5964 [95% CI 0.5622–0.6306] vs. 0.6760 [95% CI 0.6427–0.7099] vs 0.3967 [95% CI 0.3662–0.4271]; 6–12 h: 0.6380 [0.6031–0.6729] vs. 0.6032 [0.5705–0.6406] vs. 0.6055 [0.5682–0.6383] vs 0.4023 [95% CI 0.3709–0.4337]). External validation was performed on the data of patients in the respiratory critical care unit of the Chinese PLA General Hospital. Compared with LSTM, random forest and time-dependent cox regression model, the NIMRF model was still the best, with an AUC of 0.9366 [95% CI 0.9157–0.9575 for predicting death risk in 0–1 h]. The corresponding AUCs of LSTM, random forest and time-dependent cox regression model were 0.9263 [95% CI 0.9039–0.9486], 0.7437 [95% CI 0.7083–0.7791] and 0.2447 [95% CI 0.2202–0.2692], respectively. Interpretation of the model revealed that vital signs (systolic blood pressure, heart rate, diastolic blood pressure, respiratory rate, and body temperature) were highly correlated with events of death. Conclusion Using the NIMRF model can integrate ICU multidimensional variable data, especially vital sign variable data, to accurately predict the death events of ICU patients. These predictions can assist clinicians in choosing more timely and precise treatment methods and interventions and, more importantly, can reduce invasive procedures and save medical costs.

Abstract Introduction The lack of safe, effective, and simple short-course regimens (SCRs) for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment has significantly impeded TB control efforts in China. Methods This phase 4, randomized, open-label, controlled, non-inferiority trial aims to assess the efficacy and safety of a 9-month all-oral SCR containing bedaquiline (BDQ) versus an all-oral SCR without BDQ for adult MDR-TB patients (18–65 years) in China. The trial design mainly mirrors that of the “Evaluation of a Standardized Treatment Regimen of Anti-Tuberculosis Drugs for Patients with MDR-TB” (STREAM) stage 2 study, while also incorporating programmatic data from South Africa and the 2019 consensus recommendations of Chinese MDR/RR-TB treatment experts. Experimental arm participants will receive a modified STREAM regimen C that replaces three group C drugs, ethambutol (EMB), pyrazinamide (PZA), and prothionamide (PTO), with two group B drugs, linezolid (LZD) and cycloserine (CS), while omitting high-dose isoniazid (INH) for confirmed INH-resistant cases. BDQ duration will be extended from 6 to 9 months for participants with Mycobacterium tuberculosis-positive sputum cultures at week 16. The control arm will receive a modified STREAM regimen B without high-dose INH and injectable kanamycin (KM) that incorporates experimental arm LZD and CS dosages, treatment durations, and administration methods. LZD (600 mg) will be given daily for ≥ 24 weeks as guided by observed benefits and harm. The primary outcome measures the proportion of participants with favorable treatment outcomes at treatment completion (week 40), while the same measurement taken at 48 weeks post-treatment completion is the secondary outcome. Assuming an α = 0.025 significance level (one-sided test), 80% power, 15% non-inferiority margin, and 10% lost to follow-up rate, each arm requires 106 participants (212 total) to demonstrate non-inferiority. Discussion PROSPECT aims to assess the safety and efficacy of a BDQ-containing SCR MDR-TB treatment at seventeen sites across China, while also providing high-quality data to guide SCRs administration under the direction of the China National Tuberculosis Program for MDR-TB. Additionally, PROSPECT will explore the potential benefits of extending the administration of the 9-month BDQ-containing SCR for participants without sputum conversion by week 16. Trial registration ClinicalTrials.gov NCT05306223. Prospectively registered on 16 March 2022 at https://clinicaltrials.gov/ct2/show/NCT05306223?term=NCT05306223&draw=1&rank=1 {2}.

Purpose: To investigate the therapeutic effect and underlying mechanism of tetrahydrocurcumin (THC) on nonalcoholic steatohepatitis (NASH) induced by high-fat diet (HFD). Methods: NASH rat model was established through long-term feeding HFD, and the steatosis cell model was stimulated via palmitate acid (PA). The therapeutic effect of THC was evaluated in terms of liver function, lipid metabolism, liver pathophysiology, inflammation and oxidative stress in vivo, and lipid accumulation in vitro. The alteration in lipophagy was identified by using western blot and immunofluorescence. mTORC1-TFEB signaling pathway was measured by qRT-PCR, western blot and protein-ligand docking. In addition, chloroquine and MHY1485 were further introduced to validate the effect of THC on lipophagy and mTORC1-TFEB signaling pathway, respectively. Results: THC effectively improved hepatic steatosis, inflammation and oxidative stress in NASH rats, and reduced lipid accumulation in steatosis L02 cells and Hep G2 cells. THC promoted lipophagy with increasing LC3B-II as well as decreasing P62 expression via lysosomal biogenesis upregulation, which was greatly weakened after chloroquine intervention. mTORC1-TFEB is a critical pathway for regulating lysosome in autophagy, THC treatment induced TFEB nucleus translocation via inhibiting mTORC1 to upregulate lysosomal biogenesis. However, these effects were partly eliminated by mTORC1 activator MHY1485. Conclusion: THC restored lipophagy to reduce lipid accumulation by regulating mTORC1-TFEB pathway in NASH rats and steatosis hepatocytes. These findings suggested that THC represents a therapeutic candidate for NASH treatment.

Recently, a rapid advancement in using unmanned aerial vehicles (UAVs) for yield prediction (YP) has led to many YP research findings. This study aims to visualize the intellectual background, research progress, knowledge structure, and main research frontiers of the entire YP domain for main cereal crops using VOSviewer and a comprehensive literature review. To develop visualization networks of UAVs related knowledge for YP of wheat, maize, rice, and soybean (WMRS) crops, the original research articles published between January 2001 and August 2023 were retrieved from the web of science core collection (WOSCC) database. Significant contributors have been observed to the growth of YP-related research, including the most active countries, prolific publications, productive writers and authors, the top contributing institutions, influential journals, papers, and keywords. Furthermore, the study observed the primary contributions of YP for WMRS crops using UAVs at the micro, meso, and macro levels and the degree of collaboration and information sources for YP. Moreover, the policy assistance from the People’s Republic of China, the United States of America, Germany, and Australia considerably advances the knowledge of UAVs connected to YP of WMRS crops, revealed under investigation of grants and collaborating nations. Lastly, the findings of WMRS crops for YP are presented regarding the data type, algorithms, results, and study location. The remote sensing community can significantly benefit from this study by being able to discriminate between the most critical sub-domains of the YP literature for WMRS crops utilizing UAVs and to recommend new research frontiers for concentrating on the essential directions for subsequent studies.

Abstract Background and aim Two oral antivirals (Nirmatrelvir- ritonavir and Azvudine) are widely used in China practice during the Omicron wave of the pandemic. However, little evidence regarding the real-world effectiveness of these two oral antivirals in in-hospital patients. We aimed to evaluate the clinical effectiveness of nirmatrelvir-ritonavir versus azvudine among adult hospitalized patients with COVID-19. Methods This retrospective cohort study used data from three Chinese PLA General Hospital medical centres. Hospitalized patients with COVID-19 treated with azvudine or nirmatrelvir-ritonavir from Dec 10, 2022, to February 20, 2023, and did not require invasive ventilation support on admission were eligible for inclusion. Results After exclusions and propensity-score matching, the final analysis included 486 azvudine recipients and 486 nirmatrelvir-ritonavir recipients. By 28 days of initiation of the antivirus treatment, the crude incidence rate of all-cause death was similar in both types of antivirus treatment (nirmatrelvir-ritonavir group 2.8 events 1000 person-days [95% CI, 2.1–3.6] vs azvudine group 3.4 events/1000 person-days [95% CI, 2.6–4.3], P = 0.38). Landmark analysis showed that all-cause death was lower in the nirmatrelvir-ritonavir (3.5%) group than the azvudine (6.8%, P = 0.029) within the initial 10-day admission period, while no significant difference was observed for results between 10 and 28 days follow-up. There was no significant difference between the nirmatrelvir-ritonavir group and the azvudine group in cumulative incidence of the composite disease progression event (8.6% with nirmatrelvir-ritonavir vs. 10.1% with azvudine, HR, 1.22; 95% CI 0.80–1.86, P = 0.43). Conclusion Among patients hospitalized with COVID-19 during the omicron wave in Beijing, similar in-hospital clinical outcomes on 28 days were observed between patients receiving nirmatrelvir-ritonavir and azvudine. However, it is worth noticing that nirmatrelvir-ritonavir appears to hold an advantage over azvudine in reducing early mortality. Further randomized controlled trials are needed to verify the efficacy of those two antivirus medications especially in early treatment.

AbstractBackground The effectiveness of nirmatrelvir–ritonavir has mainly been shown in non-hospitalized patients with mild-to-moderate coronavirus disease 2019 (COVID-19). The real-world effectiveness of nirmatrelvir-ritonavir urgently needs to be determined using representative in-hospital patients with COVID-19 during the Omicron wave of the pandemic.Methods We performed a multicentre, retrospective study in five Chinese PLA General Hospital medical centers in Beijing, China. Patients hospitalized with COVID-19 from 10 December 2022 to 20 February 2023 were eligible for inclusion. A 1:1 propensity score matching was performed between the nirmatrelvir-ritonavir group and the control group.Results 1010 recipients of nirmatrelvir-ritonavir and 1010 matched controls were finally analyzed after matching. Compared with matched controls, the nirmatrelvir-ritonavir group had a lower incidence rate of all-cause death (4.6/1000 vs. 6.3/1000 person-days, p = 0.013) and a higher incidence rate of clinical improvement (47.6/1000 vs. 45.8/1000 person-days, p = 0.012). Nirmatrelvir-ritonavir was associated with a 22% lower all-cause mortality and a 14% higher incidence of clinical improvement. Initiation of nirmatrelvir-ritonavir within 5 days after symptom onset was associated with a 50% lower mortality and a 26% higher clinical improvement rate. By contrast, no significant associations were identified among patients receiving nirmatrelvir-ritonavir treatment more than 5 days after symptom onset. Nirmatrelvir-ritonavir was also associated with a 50% increase in survival days and a 12% decrease in days to clinical improvement.Conclusion Among hospitalized patients with COVID-19 during the Omicron wave in Beijing, China, the early initiation of nirmatrelvir-ritonavir was associated with clinical benefits of lowering mortality and improving clinical recovery.

Berberine (BBR) is a major active component of traditional Chinese medicine Rhizoma Coptidis and Cortex Phellodendri, which have been frequently used to treat liver diseases. Oxidative stress and inflammation are two pivotal hepatic pathological hallmarks. This study aimed to explore the potential effect and underlying mechanism of BBR on fructose-induced rat liver injury model, and hepatocyte damage in HepG2 and BRL-3A cells. Our results indicated that BBR effectively reversed fructose-induced body weight gain, glucose intolerance, and insulin resistance, observably attenuated abnormal histopathological alterations and ameliorated serum activities of ALT and AST. In vivo and in vitro, BBR significantly alleviated the secretion of pro-inflammatory cytokines IL-6 and TNF-α, and elevated levels of anti-inflammatory cytokine IL-10. BBR also attenuated oxidative stress by markedly decreasing intracellular contents of ROS and MDA, and increasing SOD enzymatic activity and GSH level. Furthermore, BBR substantially upregulated the protein expression of Nrf2, HO-1 and p-AMPK, and the fluorescence level of p-AMPK. In addition, BBR significantly increased the level of AMP, the ratio of AMP/ATP, and promoted the expression of ADK. Nevertheless, siADK abolished the benefits exerted by BBR on HepG2 and BRL-3A cells. Conclusively, the hepatoprotective effect of BBR was believed to be intimately associated with anti-inflammatory and antioxidant action mediated, at least partially, via ADK/AMPK/Nrf2 signaling. This work provided further support for the traditional application of Rhizoma Coptidis and Cortex Phellodendri in liver protection and might shed novel dimension to the clinical application of BBR, providing a promising lead compound for drug design.

Background In adult patients with high myopia (HM), progressive axial elongation poses a significant risk for the development of subsequent ocular complications that may lead to visual impairment. Effective strategies to reduce or prevent further axial elongation in highly myopic adult patients have not been available so far. Recent studies suggested that medically lowering intraocular pressure (IOP) may reduce axial elongation.Objective This clinical randomised controlled trial (RCT) aims to evaluate the efficacy of medical IOP reduction in adult patients with progressive HM (PHM).Trial design Single-centre, open-label, prospective RCT.Methods This RCT will recruit 152 participants with PHM at the Zhongshan Ophthalmic Center (ZOC). Randomised in a ratio of 1:1, participants will receive IOP-lowering eyedrops (intervention group) or will be followed without treatment (control group) for 12 months. Follow-up visits will be conducted at 1, 6 and 12 months after baseline. Only one eye per eligible participant will be included for analysis. The primary outcome is the change in axial length (AL) within the study period of 12 months. Secondary outcomes include the incidence and progression of visual field (VF) defects, changes in optic disc morphology and incidence and progression of myopic maculopathy. Difference in AL changes between the two groups will be analysed using linear regression analysis. For the secondary outcomes, a multifactor Poisson regression within a generalised linear model will be used to estimate the relative risk of progression in VF defects and myopic maculopathy, and the rate of thinning in retinal nerve fibre layer and ganglion cell-inner plexiform will be assessed through Kaplan-Meier curves and log-rank tests.Ethics and dissemination Full ethics approval for this trial has been obtained from the Ethics Committee of ZOC, Sun Yat-sen University, China (ID: 2023KYPJ110). Results of this trial will be disseminated through peer-reviewed journals and conference presentations.Trial registration number NCT05850936.

BackgroundTuberculosis (TB) remains a significant public health challenge in China. Early detection and diagnosis of TB cases are crucial to interrupt disease transmission and prevent its progression. This study aims to describe the delay in seeking care and diagnosis among patients with pulmonary tuberculosis (PTB) and identify the influencing factors in two counties in Beijing.MethodsA retrospective analysis was carried out to investigate care-seeking and diagnosis delay in two counties in Beijing. Basic information of PTB patients from January 1 to December 31, 2021, was extracted from the Tuberculosis Information Management System of China (TBIMS), and all enrolled patients were interviewed via telephone using a standard questionnaire. Statistical description was performed using the median and interquartile range (IQR). Chi-square test and multivariate logistic regression model were used to analyze the influencing factors.Results537 patients were enrolled. The median duration of care-seeking and diagnosis delay was 11 (IQR: 5–26) days and 8 (IQR: 0–18) days, with 41.71 and 35.20% of patients experiencing delays (>14 days). The study found that being asymptomatic (OR = 2.791, 95%CI: 1.710–4.555) before seeking medical care and not attending work during treatment (OR = 2.990, 95%CI: 1.419–6.298) were identified as risk factors for care-seeking delay. Patients who were tracked (OR = 2.632, 95%CI: 1.062–6.521) and diagnosed at tuberculosis control and prevention institutions (OR = 1.843, 95%CI: 1.061–3.202) had higher odds of diagnostic delays. 44.69% of patients presented a total delay (>28 days), with a median duration of 25 (IQR: 13–39) days. A multivariate logistic regression analysis showed that healthy examination (OR = 0.136, 95%CI: 0.043–0.425) was a protective factor for total delay.ConclusionPublic interventions are necessary to improve the efficiency of PTB patients detection and treatment in Beijing. Medical services should focus on the target population and improve access to medical care to further reduce delays for PTB patients.

ABSTRACT: Semen volume is an important economic trait of broilers and one of the important indices for continuous breeding. The objective of this study was to identify genes related to semen volume through transcriptome analysis of the testis tissue of white feather broilers. The testis samples with the highest semen volume (H group, n = 5) and lowest semen volume (L group, n = 5) were selected from 400-day-old roosters for transcriptome analysis by RNA sequencing. During the screening of differentially expressed genes (DEGs) between the H and L groups, a total of 386 DEGs were identified, among which 348 were upregulated and 38 were downregulated. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the immune response, leukocyte differentiation, cell adhesion molecules and collagen binding played vital roles in spermatogenesis. The results showed that 4 genes related to spermatogenesis, namely, COL1A1, CD74, ARPC1B and APOA1, were significantly expressed in Group H, which was consistent with the phenotype results. Our findings may provide a basis for further research on the genetic mechanism of semen volume in white feather broilers.

Abstract Background Respiratory Syncytial Virus (RSV) stands out as a primary contributor to lower respiratory tract infections and hospitalizations, particularly in infants. Lonicerae japonicae flos (LJF), a traditional Chinese medicine renowned for its efficacy against various viral infections, including RSV, has been widely employed. Despite its common use, the precise therapeutic mechanism of LJF against RSV remains elusive. This study aimed to investigate the underlying mechanism of LJF against RSV through network pharmacology and metabolomics. Methods In this study, based on network pharmacology, potential targets related to LJF and RSV were obtained from PubChem and Swiss Target Prediction. The core targets and pathways were established and verified by enrichment analysis and molecular docking. The anti-RSV efficacy of LJF was determined by in vitro experiments. Additionally, metabolomics analysis was integrated, allowing for the identification of differential metabolites and their correlation with targets following LJF treatment in the context of RSV infection. Results A total of 23 active ingredients and 780 targets were obtained, of which 102 targets were associated with LJF anti-RSV. The construction of the corresponding Protein–Protein Interaction (PPI) network unveiled potential core targets, including STAT3, TNF, and AKT1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that LJF's anti-RSV effects primarily involve key pathways such as the PI3K-Akt signaling pathway, EGFR tyrosine kinase inhibitor resistance, and FoxO signaling pathway. Molecular docking showed that ZINC03978781, 4,5'-Retro-.beta.,.beta.-Carotene -3,3'-dione, 4',5'-didehydro and 7-epi-Vogeloside had better binding ability. The cellular assay showed that the therapeutic index of LJF against RSV was 4.79. Furthermore, 18 metabolites were screened as potential biomarkers of LJF against RSV, and these metabolites were mainly involved in the pathways of purine metabolism, linoleic acid metabolism, alpha-linolenic acid metabolism, and other related pathways. Conclusions The intergration of network pharmacology and metabolomics can clarify the active targets and related pathways of LJF against RSV, which could provide a valuable reference for further research and clinical application of LJF.

In the pathological process of Alzheimer’s disease, neuronal cell death is closely related to the accumulation of reactive oxygen species. Our previous studies have found that oxidative stress can activate microtubule affinity-regulating kinases, resulting in elevated phosphorylation levels of tau protein specifically at the Ser262 residue in N1E-115 cells that have been subjected to exposure to hydrogen peroxide. This process may be one of the pathogenic mechanisms of Alzheimer’s disease. Vitamin E is a fat-soluble, naturally occurring antioxidant that plays a crucial role in biological systems. This study aimed to examine the probable processes that contribute to the inhibiting effect on the abnormal phosphorylation of tau protein and the neuroprotective activity of a particular type of vitamin E, α-tocotrienol. The experimental analysis revealed that α-tocotrienol showed significant neuroprotective effects in the N1E-115 cell line. Our data further suggest that one of the mechanisms underlying the neuroprotective effects of α-tocotrienol may be through the inhibition of microtubule affinity-regulated kinase activation, which significantly reduces the oxidative stress-induced aberrant elevation of p-Tau (Ser262) levels. These results indicate that α-tocotrienol may represent an intriguing strategy for treating or preventing Alzheimer’s disease.

Salmonella has been one of the most important factors restricting the development of the poultry industry and also poses great threat to public health. To get insight into molecular alterations that occur during bacterial infection, we sequenced the cecal tonsil transcriptome in 2 chicken breeds (Beijing-You and Cobb) known to have differing resistance to Salmonella. The 28-day-old chickens were orally challenged by 1.83 × 1011 CFU Salmonella Typhimurium, and the cecal tonsil transcriptome was sequenced 3 d postinfection. Analysis identified 201 and 170 differentially expressed genes response to Salmonella in 2 chicken breeds, respectively. They were involved in the Toll-like receptor signaling pathway and activated the production of pro-inflammatory cytokines and chemokines. The protein–protein interaction (PPI) network suggested MMP9 as a crucial protein that may be involved in extracellular matrix breakdown and leukocyte migration in the resistant breed (Beijing-You). Meanwhile, in susceptible chickens (Cobb), ACOD1 was the key gene in the PPI network and might promote the expression of genes related to oxidative stress response and gastrointestinal tract function. These findings provide insight into the differing resistance of these 2 chicken breeds.

Background Small conductance calcium‐activated potassium (SK) channels are largely responsible for endothelium‐dependent coronary arteriolar relaxation. Endothelial SK channels are downregulated by the reduced form of nicotinamide adenine dinucleotide (NADH), which is increased in the setting of diabetes, yet the mechanisms of these changes are unclear. PKC (protein kinase C) is an important mediator of diabetes‐induced coronary endothelial dysfunction. Thus, we aimed to determine whether NADH signaling downregulates endothelial SK channel function via PKC. Methods and Results SK channel currents of human coronary artery endothelial cells were measured by whole cell patch clamp method in the presence/absence of NADH, PKC activator phorbol 12‐myristate 13‐acetate, PKC inhibitors, or endothelial PKCα/PKCβ knockdown by using small interfering RNA. Human coronary arteriolar reactivity in response to the selective SK activator NS309 was measured by vessel myography in the presence of NADH and PKCβ inhibitor LY333531. NADH (30–300 μmol/L) or PKC activator phorbol 12‐myristate 13‐acetate (30–300 nmol/L) reduced endothelial SK current density, whereas the selective PKCᵦ inhibitor LY333531 significantly reversed the NADH‐induced SK channel inhibition. PKCβ small interfering RNA, but not PKCα small interfering RNA, significantly prevented the NADH‐ and phorbol 12‐myristate 13‐acetate–induced SK inhibition. Incubation of human coronary artery endothelial cells with NADH significantly increased endothelial PKC activity and PKCβ expression and activation. Treating vessels with NADH decreased coronary arteriolar relaxation in response to the selective SK activator NS309, and this inhibitive effect was blocked by coadministration with PKCβ inhibitor LY333531. Conclusions NADH‐induced inhibition of endothelial SK channel function is mediated via PKCβ. These findings may provide insight into novel therapeutic strategies to preserve coronary microvascular function in patients with metabolic syndrome and coronary disease.

Objective: Protein kinase C (PKC) influences myocardial contractility and susceptibility to long-term cardiac dysfunction after ischemia–reperfusion injury. In diabetes, PKC inhibition has a protective effect in terms of microvascular dysfunction. SK-channel dysfunction also influences endothelial dysfunction in cardioplegic hypoxia–reoxygenation (CP-H/R). Here, we examine whether acute inhibition of PKC beta protects against CP-H/R–induced coronary endothelial and SK channel dysfunction. Methods: Isolated mouse coronary arterioles, half pretreated with selective PKC inhibitor ruboxistaurin (RBX), were subjected to hyperkalemic, cardioplegic hypoxia (1 hour), and reoxygenation (1 hour) with Krebs buffer. Sham control vessels were continuously perfused with oxygenated Krebs buffer without CP-H/R. After 1 hour of reoxygenation, responses to the endothelium-dependent vasodilator adenosine-diphosphate (ADP) and the SK-channel activator NS309 were examined. Endothelial SK-specific potassium currents from mouse heart endothelial cells were examined using whole-cell path clamp configurations in response to NS309 and SK channel blockers apamin and TRAM34. Results: CP-H/R significantly decreased coronary relaxation responses to ADP (P = .006) and NS309 (P = .0001) compared with the sham control group. Treatment with selective PKC beta inhibitor RBX significantly increased recovery of coronary relaxation responses to ADP (P = .031) and NS309 (P = .004) after CP-H/R. Treatment with RBX significantly increased NS309-mediated potassium currents following CP-H/R (P = .0415). Apamin and TRAM34 sensitive currents were significantly greater in CP-H/R + RBX versus CP-H/R mouse heart endothelial cells (P = .0027). Conclusions: Acute inhibition of PKC beta significantly protected mouse coronary endothelial function after CP-H/R injury. This suggests that acute PKC beta inhibition may be a novel approach for preventing microvascular dysfunction during CP-H/R.

Abstract Introduction The mortality rate of hospitalized patients with severe hospital-acquired pneumonia (SHAP) remains high. Empirical broad-spectrum antibiotic coverage and the misuse of high-grade antibiotics could lead to the emergence of multi-drug and even pandrug-resistant bacteria. In addition to metagenomic next-generation sequencing (mNGS), microbiological rapid on-site evaluation (M-ROSE) might be a useful technique to identify the pathogens in the early stage; however, the effect of M-ROSE guiding anti-infection treatment on prognostic outcomes of SHAP patients is still unclear. Methods/design This is a multicenter, single-blind, prospective, randomized controlled trial to evaluate the effect of M-ROSE guiding anti-infection treatment in SHAP patients, which will provide new strategies for the prevention and control of clinical multi-drug resistance bacteria. A total of 166 patients with SHAP, aged 18 years and over, will be recruited from seven centers in Beijing and randomly assigned to the intervention group (M-ROSE combined with mNGS) or the control group (mNGS only) in a 1:1 ratio using the central randomization system. Patients in the intervention group will accept M-ROSE and mNGS analysis, and the control group will accept mNGS analysis. Individualized anti-infective treatment and routine treatment will be selected according to the analysis results. The primary outcome is the ICU outcome (mortality). The safety of the intervention measures will be evaluated during the entire trial period. This trial will be the first randomized controlled trial to evaluate the effect of M-ROSE guiding treatment on mortality in patients with SHAP and may change the prevalence of multi-drug resistant bacteria. Ethics and dissemination This trial adheres to the Declaration of Helsinki and guidelines of Good Clinical Practice. Signed informed consent will be obtained from all participants. The trial has been approved by the Chinese PLA General Hospital (Approval Number: 20220322001). Trial registration ClinicalTrials.gov NCT05300776. Registered on 25 March 2022.

Abstract Raman spectroscopy, as a label-free optical technology, has widely applied in tumor diagnosis. Relying on the different Raman technologies, conventional diagnostic methods can be used for the diagnosis of benign, malignant and subtypes of tumors. In the past 3 years, in addition to traditional diagnostic methods, the application of artificial intelligence (AI) in various technologies based on Raman technologies has been developing at an incredible speed. Based on this, three technical methods from single spot acquisition (conventional Raman spectroscopy, surface-enhanced Raman spectroscopy) to Raman imaging are respectively introduced and analyzed the diagnosis process of these technical methods. Meanwhile, the emerging AI applications of tumor diagnosis within these methods are highlighted and presented. Finally, the challenges and limitations of existing diagnostic methods, and the prospects of AI-enabled diagnostic methods are presented.

Hyperuricemia exhibits a high incidence among individuals with diabetes; however, the significance of hyperuricemia and gout is often underestimated. This study aimed to assess the knowledge, attitude, and practice of hyperuricemia and gout among community health workers and patients with diabetes. Two questionnaires were designed to investigate knowledge, attitudes, and practices of hyperuricemia and gout among community health workers and patients with diabetes in Chenghua District, Chengdu, from August 2021 to January 2022. A total of 709 community health workers were included, whose average score was 17.74/30. Approximately half of general practitioners (GPs) demonstrated knowledge regarding the target serum uric acid levels for hyperuricemia and gout. Only 11.2% of GPs were fully aware of the preferred medicine for acute gout. The majority of GPs (86.7%) demonstrated limited awareness regarding the contraindications associated with colchicine, while a significant proportion (65.1%) lacked knowledge about the specific classes of drugs that inhibit uric acid synthesis. Among the 508 patients with diabetes included in this survey, 32.3% demonstrated awareness of hyperuricemia, while 60.8% exhibited knowledge regarding gout. The average score attained by these individuals was recorded at 7.21 out of a total of 26 points. The majority of patients with diabetes (87.8%) held the mistaken belief that hyperuricemia definitely led to the development of gout. Almost 66% agreed that a massage or a hot compress could be used when acute gouty arthritis attacks. The knowledge rate of hyperuricemia and gout among community health workers was moderate, while it was low in patients with diabetes.

Bei-dou-gen, the dried rhizome of Menispermum dauricum from the Menispermaceae family, is an important Chinese medicinal material. In order to clarify the pharmacodynamic substance basis, the methanol extract of the rhizome in M. dauricum was systematically isolated and purified using various chromatographic methods and the structures of isolated compounds were identified. The potential anti-inflammatory activity of obtained compounds from M. dauricum was measured in vitro. In this study, the chemical constituents were separated via silica gel column chromatography, macroporous adsorption resin and preparative HPLC, and their structures were determined on the basis of MS, 1H-NMR, 13C-NMR and other spectroscopic data analysis, as well as comparison with relevant literatures. Meanwhile, the anti-inflammatory activities of against NO and IL-6 production from LPS-induced RAW264.7 cells of the chemical components were evaluated in vitro. The results were as follows: (1) Fifteen compounds were isolated from the rhizome of M. dauricum, and identified as p-hydroxybenzaldehyde (1), vanillic acid (2), syringaldehyde (3), 2-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone (4), methyl 4-hydroxyphenylacetate (5), 2-(4-hydroxyphenyl)-1-nitroethane (6), 4-hydroxyphenylacetonitrile (7), dibutyl phthalate (8), fragransin B2 (9), 7-hydroxy-3,6-dimethoxy-1,4-phenanthraquinone (10), palmitic acid (11), arachidic acid (12), β-sitosterol (13), β-stigmasterol (14) and daucosterol (15). Among them, compounds 4-7, 9 and 12 were isolated from Menispermaceae for the first time, while compounds 1, 3-11 and 14 were first reported from Menispermum genus. The above compounds were all non-alkaloids components, including phenols, lignans, phenanthraquinones, fatty acids and sterols. (2) Anti-inflammatory assay in vitro showed that Compound 12 could significantly inhibited releases of NO and IL-6 induced by LPS from RAW264.7 cells at the concentrations of 25 and 50 μg·mL-1, indicating potential anti-inflammatory activity. The results of this study enrich the chemical diversity of the rhizome of M. dauricum and clarifies the active ingredients of its anti-inflammatory activity, and provide effective reference for the rational utilization of medicinal plant resources.

ObjectivesThis papers aims to analyze the impact resistance of honeycomb structure with different Poisson's ratio. MethodsBased on the explicit dynamic finite element method, this paper analyzes the dynamic mechanical properties of honeycomb structures with different Poisson's ratios under in-plane impact load, and explores the influence laws of Poisson's ratios on their impact resistance. Three typical honeycomb structures with negative/zero/positive Poisson's ratios (reentrant hexagon, hexagon and semi-reentrant hexagon) are selected, their geometric parameters are changed to give them the same relative density and different Poisson's ratios (−2.76 – +3.63), and their dynamic mechanical properties under low/medium/high-speed dynamic displacement loads are analyzed. ResultsThe results show that the zero Poisson's ratio semi-reentrant honeycomb structure has the best structural stability without transverse deformation under compression deformation; without structural instability, the platform stress has little correlation with the Poisson's ratio; and the compact strain and total energy absorbtion increases with the absolute value of the Poisson's ratio. Negative Poisson's ratio honeycomb structures with large t/l and small θ are suitable for applications with high platform stress (strong deformation resistance), and negative Poisson's ratio honeycomb structures with small t/l and small θ are suitable for high total energy absorbtion applications, while zero Poisson's ratio semi-reentrant honeycomb structures are suitable for applications with high platform stress (strong deformation resistance). ConclusionsThis study can provide references for the type selection and geometric parameter design of side impact honeycomb structures.

BackgroundIn the fight against tuberculosis, besides chemotherapy, the regulation of oxidative stress (OS) has also aroused people’s interest in host-oriented therapy. However, there is limited research on the genes involved in reactive oxygen species (ROS) production and clearance in macrophages infected with Mycobacterium tuberculosis (MTB). This study analyzes and explores this to provide a basis for exploring new targets for antituberculosis treatments.MethodsWe established a macrophage model infected with MTB, counted intracellular bacteria, and determined the ROS produced using flow cytometry. We conducted ribonucleic acid sequencing, screened differentially expressed genes through transcriptomic methods, and validated the expression of them through reverse transcription-quantitative polymerase chain reaction.ResultsThe ROS of macrophages increased with intracellular bacteria at 4 h after infection with MTB and reached its peak at 48 h, surpassing the uninfected macrophages (p < 0.05). A total of 1,613 differentially expressed genes were identified after infection with MTB, of which 458 were associated with ROS, with over 50% involved in the response of organelles and biological processes to stimuli. We analyzed and identified six genes. After macrophage infection with MTB, the expression of CAMK2B increased, whereas the expression of CYBB decreased (p < 0.05). The expression of GPX3 and SOD2 increased, whereas the expression of CAT decreased (p < 0.05).ConclusionThe ROS-related differentially expressed genes between MTB infected and uninfected macrophages may be related to some organelles and involved in various biological processes, molecular functions, and signaling pathways. Among them, CAMK2B, GPX3, and SOD2 may be related to ROS.

AbstractObjective To explore a machine learning model for the early prediction of acute kidney injury (AKI) and to screen the related factors affecting new-onset AKI in the ICU.Methods A retrospective analysis was performed used the MIMIC-III data source. New onset of AKI defined based on the serum creatinine changed. We included 19 variables for AKI assessment using four machine learning models: support vector machines, logistic regression, and random forest. and XGBoost, using accuracy, specificity, precision, recall, F1 score, and AUROC (area under the ROC curve) to evaluate model performance. The four models predicted new-onset AKI 3–6–9–12 h ahead. The SHapley Additive exPlanation (SHAP) value is used to evaluate the feature importance of the model.Results We finally respectively extracted 1130 AKI patients and non-AKI patients from the MIMIC-III database. With the extension of the early warning time, the prediction performance of each model showed a downward trend, but the relative performance was consistent. The prediction performance comparison of the four models showed that the XGBoost model performed the best in all evaluation indicators in all the time point at new-onset AKI 3–6–9–12 h ahead (accuracy 0.809 vs 0.78 vs 0.744 vs 0.741, specificity 0.856 vs 0.826 vs 0.797 vs 0.787, precision 0.842 vs 0.81 vs 0.775 vs 0.766, recall 0.759 vs 0.734 vs 0.692 vs 0.694, Fl score 0.799 vs 0.769 vs 0.731 vs 0.729, AUROC 0.892 vs 0.857 vs 0.827 vs 0.818). In the prediction of AKI 6, 9 and 12 h ahead, the importance of creatinine, platelets, and height was the most important based on SHapley.Conclusions The machine learning model described in this study can predict AKI 3–6–9–12 h before the new-onset of AKI in ICU. In particular, platelet plays an important role.Key messageThe new-onset of AKI in ICU is a common and important problem, which early be identified the risk of AKI can improve patients’ outcomes.We explored MIMIC-III and determined the exact time point of occurrence of AKI as the basis for the new-onset of AKI in ICU.XGBoost model performed the best prediction in all the time point at new-onset AKI 3–6–9–12 h ahead.For patients with the new-onset of AKI in ICU, platelets become an important factor associated with AKI.

In many shallow water lakes of China, as the numbers of tourists observing waterflow increases, the amount of supplemental food provided to waterflow also increases. However, little attention has been paid to the role of waterfowl’s behavior perturbation in N and P nutrients releasing from the sediment. In this study, five feeding experiments were undertaken in the Swan Lake (Shandong Province, northern China) during the wintering season and a noticeable release of nutrients in all experiments was found by the disturbance of the swan behaviors. The release of TN and TP was through three stages including the non-release stage, the rapid release stage, and the stable release stage. Moreover, supplemental food also influenced the swan behavior changes and triggered the frequency of the swans’ grazing and aggression. The aggressive behaviors among the swans stirred nutrient (N & P) releasing from sediments and altered TN and TP concentrations in the water columns, indicating that the aggressive behaviors may be a significant factor in affecting the TN and TP releasing from the sediment. Human feeding intensity (HFI) suggested > 850 g of supplemental corn can be an optimal way to aid in avoiding foraging competition among the swans to control nutrient release by three levels of human feeding intensity assessment. Our findings demonstrate that under the swans’ optimal foraging need in natural versus artificial feeding scenarios, the swans acted as biological pumps to increase nutrient release. There is a need for a systematic and evidence-based feeding strategy for swans, with greater restrictions on the provision of small food items scattered by visitors. Our study provided novel insights into the release mechanism of N and P from bioturbation and could help to inform a whooper swan conservation strategy in coastal wetlands and nature reserves.

Summary: Background: China has the highest prevalence of spontaneous intracerebral hemorrhage (sICH) worldwide. To date, no national-level report has revealed sICH surgical performance. We aimed to investigate the current status and short-term outcomes of patients who underwent surgical treatment for sICH between 2019 and 2021. Methods: Data from 7451 patients undergoing sICH surgical treatment in China between 2019 and 2021, including demographic information, disease severity, surgical treatments for sICH, complications, and follow-up information, were retrieved from the Bigdata Observatory Platform for Stroke of China. Propensity score matching (PSM) was applied to balance the baseline characteristics. The surgical treatment performance on 3-month mortality and functional outcome were then explored by regression analysis. The influence of stroke center level and region on surgical performance was then explored. Findings: The numbers of sICH patients undergoing open craniotomy (OC), cranial puncture (CP), decompressive craniectomy (DC) and endoscopic evacuation (EE) were 2404 (32.3%), 3030 (40.7%), 1700 (22.8%) and 317 (4.3%), respectively. The 3-month mortality rate was 20.2%. Among the surviving patients, the 3-month poor functional prognosis (mRS 3–5) rate was 46.5%. After PSM, regression analysis showed that DC was associated with a higher mortality risk (OR = 1.31, 95% CI 1.06–1.61) than OC. CP was associated with a lower risk of poor mRS scores than OC (OR = 0.84, 95% CI 0.70–1.01), especially in stroke prevention centers and specific regions. Interpretation: Outcome improvements in Chinese sICH patients undergoing surgical treatment are worth expecting. Inconsistent surgical performance, especially functional outcome, affected by inhomogeneity of the hospital should be addressed. Funding: This work was supported by the Beijing Hospitals Authority Youth Programme (QML20230804), the National Natural Science Foundation of China (81701796, 82030037, 81871009), Capital Health Research and Development of Special Fund (2020-2Z-2019), Science and Technology Innovation 2030-Major Project (2021ZD0201801), and the Translational and Application Project of Brain-inspired and Network Neuroscience on Brain Disorders (11000022T000000444685).

Abstract Background The Western Pacific Region has one of the fastest-growing populations of older adults (≥ 65 years) globally, among whom tuberculosis (TB) poses a particular concern. This study reports country case studies from China, Japan, the Republic of Korea, and Singapore reflecting on their experiences in managing TB among older adults. Findings Across all four countries, TB case notification and incidence rates were highest among older adults, but clinical and public health guidance focused on this population was limited. Individual country reports illustrated a range of practices and challenges. Passive case finding remains the norm, with limited active case finding (ACF) programs implemented in China, Japan, and the Republic of Korea. Different approaches have been trialled to assist older adults in securing an early diagnosis, as well as adhering to their TB treatment. All countries emphasised the need for person-centred approaches that include the creative application of new technology and tailored incentive programs, as well as reconceptualisation of how we provide treatment support. The use of traditional medicines was found to be culturally entrenched among older adults, with a need for careful consideration of their complementary use. TB infection testing and the provision of TB preventive treatment (TPT) were underutilised with highly variable practice. Conclusion Older adults require specific consideration in TB response policies, given the burgeoning aging population and their high TB risk. Policymakers, TB programs and funders must invest in and develop locally contextualised practice guidelines to inform evidence-based TB prevention and care practices for older adults.

As resource-constrained Internet-of-Things (IoT) devices become popular targets of various malicious attacks, frequent updates to keep their software up to date are essential to their security. However, state-of-the-art software delivery and payment systems incorporate multiple services in a client-server structure requiring multiple transits of information between client and server, while also creating a wide attack surface. We propose a blockchain-based end-to-end secure software update delivery framework for Internet of Things (IoT) devices, which aims to ensure confidentiality, integrity, availability, efficiency, and audit-ability for verified software delivery, while offloading the cryptographic computation from resource-constrained IoT devices to a decentralized blockchain system. In particular, we leverage Ciphertext-Policy Attribute-Based Encryption (CP-ABE) and design a customized authorization policy to not only ensure that software updates can only be decrypted and installed on authorized IoT devices but also significantly reduce the computational overhead for key generation and key delivery on the manufacturer side. Furthermore, secure and atomic software delivery and payments between IoT devices and the manufacturer are assured through smart contracts. The authenticity of the delivered software is guaranteed by offloading the computation-based signature validation to smart contracts. Compliance audits are satisfied through immutable records on the blockchain’s public ledger, and the smart contracts efficiently guarantee the delivery of software updates in exchange for payment. Security analysis and experiments are performed to compare the proposed framework with state-of-the-art studies and validate its effectiveness.

Abstract In this study, TCA–n‐butanol was chosen as the best deproteinization method for Lonicera japonica polysaccharide (LJP) by comparing the polysaccharide retention rate and the protein clearance rate of five different methods. The response surface methodology (RSM) based on the Box–Behnken design (BBD) was used to optimize the deproteinization conditions as follows: TCA: n‐butanol = 1: 5.1, polysaccharide solution: (TCA–n‐butanol) = 1: 2.8, and shook for 33 min. LJP could promote the thymus and spleen indexes of cyclophosphamide (CTX)‐induced immune‐deficient mice. Besides, the contents of cytokine interleukin‐2 (IL‐2) and hemolysin in mice serum were augmented after treatment with LJP. Based on serum metabolomics analysis, a total of 14 metabolites (VIP >1.0, FC >2 or FC

Objective: With the rising number of clinical trials conducted in China, the role of clinical research nurses (CRNs) within clinical trial organizations has become increasingly crucial. However, in the absence of industry guidelines, the management of CRNs lacks clarity. This study aims to address this gap by establishing a consensus on CRN management. Methods: The International Association of Clinical Research Nurses (IACRN)-Shanghai Chapter assembled a panel of experts to develop a consensus on the management of clinical research nurses. This consensus was formulated through an extensive literature review, expert evaluations, and collaborative conference discussions. Results: The consensus document offers a comprehensive professional definition of CRNs and provides detailed insights into their management. It covers aspects such as job settings, qualifications, responsibilities, training, assessment, workload management, staffing allocation, performance evaluation, and career progression. Conclusions: Establishing a professional definition for CRNs creates a standardized reference point for clinical trial institutions to effectively manage these professionals. Consistency in CRNs’ roles, training, staffing, and corresponding assessments is essential for promoting their sustainable and healthy development within the field of clinical research.

Berberine (BBR) has extremely low concentration and high tissue distribution. However, current pharmacokinetic studies predominantly focus on its concentration in plasma, which could hardly make a comprehensive understanding of its pharmacokinetic process. This study made a pioneering endeavor to explore the erythrocyte-hemoglobin (Hb) self-assembly system of BBR by exploring the interaction of BBR with erythrocyte and the combination of BBR with Hb. Results showed that BBR had a low bioavailability (C0 = 2.833 μg/mL via intravenous administration of 2.5 mg/kg BBR and Cmax = 0.260 μg/mL via oral administration of 400 mg/kg BBR). Besides, BBR achieved higher concentrations in erythrocytes than plasma, and the erythrocytes count and Hb content were significantly decreased after intravenous administration. Hemolysis rate indicated the BBR-erythrocyte system (with 2% erythrocytes) was relatively stable without hemolysis at the concentration of 1.00 mg/mL. And the maximum percentage of drug loading was 100% when the BBR-erythrocyte concentration was 0.185 μg/mL. Furthermore, incubation of BBR and erythrocytes resulted in internalization of the erythrocyte membrane and the formation of intracellular vacuoles. The thermodynamic parameters indicated that the binding process of bovine hemoglobin (BHB) and BBR was spontaneous. UV-vis absorption spectra, synchronous fluorescence, circular dichroism and Raman spectra collectively indicated that BBR showed strong binding affinity toward BHB and affected the molecular environment of residues like tryptophan and tyrosine in BHB, resulting in the conformational changes of its secondary and tertiary structure. Molecular docking indicated BBR interacted with Arg-141 residue of BHB via hydrogen bond with the bond length of 2.55 Å. The ΔG value of the BHB-BBR system was −31.79 kJ/mol. Molecular dynamics simulation indicated the root mean square derivation of BBR-BHB was

Abstract There are still some challenges in the task of single image rain removal, such as artefact remnant, background over‐smooth, and increasingly complex and heavy‐weight network architecture. Especially too heavy‐weight network to fit outdoor detection devices or mobile devices. To address the above challenges, we propose a lightweight single image Deraining algorithm incorporating visual attention saliency mechanisms (LDVS). The proposed network consists of five blocks and two convolution operations, where each block consists of a dilation convolution module and a convolutional block attention module (CBAM). Specifically, visual saliency module CBAM is used for accurate localization of rain streak, and further the combinations of dilated convolution with CBAM is used to extract feature maps of rain streaks faithfully, which is able to remove artefact remnant while maintaining background details. A good tradeoff is presented between the network's weight size and effect of rain removal. Specifically, with only 48,268 parameters, the proposed model can achieve a guaranteed performance. Extensive experiments on a few typical rainy scenarios on synthetic and real‐world datasets have demonstrated that to achieve the same level of performance, the proposed method has far smaller size than most of the baselines under both qualitative and quantitative analyses.

Post-operative adhesions are a major complication from surgical intervention. Here, the authors develop a technique to grow a super-lubricating layer over electrospun nanofibers which was demonstrated to prevent postoperative adhesions with better outcomes than commercial products when compared in two in vivo models.

Abstract Polyalkylene glycol (PAG) aqueous solutions have recently been demonstrated to exhibit an ultralow friction coefficient (COF, μ < 0.01). However, the prolonged running-in period and low bearing capacity have limited its widespread application. In this study, we determined that the running-in period can be decreased by more than 75% when the pH value of the lubricant is controlled at 3 by introducing various acid solutions. Additionally, less time was required to realize stable superlubricity with inorganic acid at lower pH values. This was mainly attributed to the acceleration effect of hydrogen ions around the contact region. In case of PAG aqueous solution with organic acid, the wear loss between sliding solid surfaces was reduced, and thus the bearing pressure during the superlubricity period was significantly improved from approximately 30 to 160 MPa. Furthermore, the organic acid molecules were considered to form strong hydrogen bonds with PAG macromolecules and solid surfaces. This in turn strengthened the structure of the adsorption layers. The unique effect of different acids in aqueous polymer lubrication can potentially significantly aid in advancing the study of polymer tribology and broadening industrial applications.

Abstract Spinal and bulbar muscular atrophy (SBMA) is an X-linked, neuromuscular neurodegenerative disease for which there is no cure. The disease is characterized by a selective decrease in fast-muscle power (e.g., tongue pressure, grip strength) accompanied by a selective loss of fast-twitch muscle fibers. However, the relationship between neuromuscular junction (NMJ) pathology and fast-twitch motor unit vulnerability has yet to be explored. In this study, we used a cross-model comparison of two mouse models of SBMA to evaluate neuromuscular junction pathology, glycolytic-to-oxidative fiber-type switching, and cytoskeletal alterations in pre- and postsynaptic termini of tibialis anterior (TA), gastrocnemius, and soleus hindlimb muscles. We observed significantly increased NMJ and myofiber pathology in fast-twitch, glycolytic motor units of the TA and gastrocnemius compared to slow-twitch, oxidative motor units of the soleus, as seen by decreased pre- and post-synaptic membrane area, decreased pre- and post-synaptic membrane colocalization, increased acetylcholine receptor compactness, a decrease in endplate area and complexity, and deficits in neurofilament heavy chain. Our data also show evidence for metabolic dysregulation and myofiber atrophy that correlate with severity of NMJ pathology. We propose a model in which the dynamic communicative relationship between the motor neuron and muscle, along with the developmental subtype of the muscle, promotes motor unit subtype specific vulnerability, metabolic alterations, and NMJ pathology.

IntroductionXuanhuang Pill (XHP) is a traditional Chinese medicine oral formula composed of 10 herbs. This study aims to verify the hepatoprotective activity of XHP and explain its possible mechanism.MethodsThe hepatoprotective activity of XHP was evaluated by constructing a mouse model of alcoholic liver disease, and the mechanism of XHP was preliminarily explained by utilizing ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC-QTOF/MS), proteomics and network pharmacology.ResultsThe current study demonstrated that treatment with XHP ameliorated acute alcohol-induced liver injury in mice by significantly reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and triglycerides (TGs) and malondialdehyde (MDA) content. Remarkably, treatment also increased superoxide dismutase (SOD) activity and glutathione (GSH) content. UPLC-QTOF/MS, 199 compounds were identified as within the make-up of the XHP. Network pharmacology analysis showed that 103 targets regulated by 163 chemical components may play an important role in the protective liver effect mediated by XHP. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggest that the HIF-1, FoxO, PI3K-Akt, insulin, and thyroid hormone signaling pathways are key modulators of XHP’s effects. Finally, eight key targets including Mapk1, Mapk3, Akt1, Map2k1, Pik3ca, Pik3cg, Raf1, and Prkca were verified by molecular docking and proteomics analysis, which provide insight into the hepatoprotective effect observed with XHP treatment.ConclusionIn summary, these results improved upon knowledge of the chemical composition and the potential mechanisms of hepatoprotective action of oral XHP treatment, providing foundational support for this formulation as a viable therapeutic option for alcoholic liver disease.

The number of patients with valvular heart disease is increasing yearly, and valve replacement is the most effective treatment, during which bioprosthetic heart valves (BHVs) are the most widely used. Commercial BHVs are mainly prepared with glutaraldehyde (Glut) cross-linked bovine pericardial or porcine aortic valves, but the residual free aldehyde groups in these tissues can cause calcification and cytotoxicity. Moreover, insufficient glycosaminoglycans (GAGs) in tissues can further reduce biocompatibility and durability. However, the anti-calcification performance and biocompatibility might be improved by blocking the free aldehyde groups and increasing the GAGs content in Glut-crosslinked tissues. In our study, adipic dihydrazide (ADH) was used to neutralize the residual free aldehyde groups in tissues and provide sites to blind with oligohyaluronan (OHA) to increase the content of GAGs in tissues. The modified bovine pericardium was evaluated for its content of residual aldehyde groups, the amount of OHA loaded, physical/chemical characteristics, biomechanical properties, biocompatibility, and in vivo anticalcification assay and endothelialization effects in juvenile Sprague-Dawley rats. The results showed that ADH could completely neutralize the free aldehyde groups in the Glut-crosslinked bovine pericardium, the amount of OHA loaded increased and the cytotoxicity was reduced. Moreover, the in vivo results also showed that the level of calcification and inflammatory response in the modified pericardial tissue was significantly reduced in a rat subcutaneous implantation model, and the results from the rat abdominal aorta vascular patch repair model further demonstrated the improved capability of the modified pericardial tissues for endothelialization. Furthermore, more α-SMA+ smooth muscle cells and fewer CD68+ macrophages infiltrated in the neointima of the modified pericardial patch. In summary, blocking free-aldehydes and loading OHA improved the anti-calcification, anti-inflammation and endothelialization properties of Glut-crosslinked BHVs and in particularly, this modified strategy may be a promising candidate for the next-generation of BHVs.

Land use/land cover changes (LULCCs) and biological invasions significantly impact coastal wetlands (CWs) and their ecosystem services and functions. The exact impacts, however, are difficult to quantify and are often neglected in policymaking. The evaluation of ecological service value (ESV) is conducive to clarifying the ecological and environmental changes caused by LULCCs and biological invasions. The objective of this study was to investigate their impact on CWs in Jiangsu Province, China, and provide useful information and advice for policymakers concerned with sustainable development. In this paper, basic data were obtained through geographic information system technology, and CW ecosystems’ services were calculated via the ESV coefficients per unit area of different wetland types. Accordingly, this study found the current land use methods responsible for significant ecosystem disruption and reductions in the area of natural vegetation. Currently, the area of natural vegetation only accounts for 43% of the total area recorded in 1987. In 2018, the total ESV of wetland vegetation (Spartina, Phragmites, and Suaeda) was estimated to be USD 14.10 million, while that of farmland was USD 8.58 million, and that of forests was USD 2.09 million. Natural vegetation only covered 9% of the total land area but produced 60% of the total ESV. Spartina alterniflora exhibited the highest ESV per unit area, with USD 1.35 million. However, the CWs of Jiangsu Province have recently shown a shift in vegetation composition due to the invasion of Spartina alterniflora. Currently, the dominant species in these CWs are Spartina alterniflora and Phragmites australis, while the local population of Suaeda salsa has significantly declined. Therefore, it is necessary to strengthen the preservation and restoration of wetland vegetation, control the invasive potential of Spartina alterniflora, and consider the implementation of suitable protective measures for native plants.

Abstract Background Type 1 diabetes (T1D) is a T lymphocyte-mediated and B lymphocyte-assisted autoimmune disease. We aimed to identify abnormally expressed genes in peripheral blood mononuclear cells (PBMCs) of T1D and explore their possible molecular regulatory network. Methods Expression datasets were downloaded from the Gene Expression Omnibus (GEO) database. Then, the differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRNAs) were identified, and functional enrichment and immune cell infiltration analysis were performed. The starBase, miRTarBase, TarBase, JASPAR, ENCODE, and TRRUST databases constructed the miRNA-mRNA-TF regulatory network. The ROC curves were plotted to evaluate the sensitivity and specificity of miRNAs and mRNAs. Result A total of 216 DEGs directly or indirectly related to type I diabetes mellitus, natural killer cell-mediated cytotoxicity, Th1, and Th2 cell differentiation, and the IL-17 and TNF signaling pathways were obtained. The miRNA-mRNA-TF network indicates that miR-320a and SOX5 are the only miRNAs and TFs that both target ADM and RRAGD. The ROC curves showed that ADM (0.9375), RRAGD (0.8958), and hsa-mir-320a (0.9417) had high accuracy in T1D diagnosis. Conclusion The constructed regulatory networks, including miR-320a/ADM/SOX5 and miR-320a/RRAGD/SOX5, may provide new insight into the mechanisms of development and progression in T1D.

The Daihai Lake, the third largest lake in Inner Mongolia Autonomous Region, is the cornerstone to maintain the ecosystem balance in this region, which is facing some problems including size shrinking, water quality declining and biodiversity decreasing largely in recent years. In order to quantify the N purification amount of submerged plants, Stella software was used in this study to construct a nitrogen dynamic model to simulate the nitrogen cycle process in the Daihai Lake and the participation of submerged plants in this cycle process. The results showed that based on the submerged plant growth area in 2019 in the Daihai Lake, the N uptake by submerged plants this year was 5.13t, accounting for 4.8% of all exogenous pollution (107.895t), Moreover, our model also predicted that the purification capacity of the restored submerged plants with a large area of 9.91 km2 in the Daihai Lake was significantly higher than before restoration. And the N pollution load of 107.892t in the Daihai Lake could be purified by this stored pattern in 12 years, while during this process a regular cleaning of submerged plant residues was required. Therefore, only large area restoration of submerged plant would benefit for improving water quality.

The durability of bioprosthetic heart valves is always compromised by the inherent antigenicity of biomaterials. Decellularization has been a promising approach to reducing the immunogenicity of biological valves. However, current methods are insufficient in eliminating all immunogenicity from the biomaterials, necessitating the exploration of novel techniques. In this study, we investigated using a novel detergent, fatty alcohol polyoxyethylene ether sodium sulfate (AES), to remove antigens from bovine pericardium. Our results demonstrated that AES treatment achieved a higher pericardial antigen removal rate than traditional detergent treatments while preserving the mechanical properties and biocompatibility of the biomaterials. Moreover, we observed excellent immune tolerance in the in vivo rat model. Overall, our findings suggest that AES treatment is a promising method for preparing biological valves with ideal clinical application prospects.

Anodic TiO2 nanotubes (ATNTs) have received much attention, but the classic field-assisted dissolution (FAD) mechanism involving the participation of fluoride ions has been questioned. Up to now, the relationship between the concentration of fluoride ions in the electrolyte and the growth rate of nanotubes has not been explained. In the same electrolyte with the same fluoride ion concentration, the growth rates of nanotubes obtained at 55 V, 60 V and 65 V are 156 nm/min, 215 nm/min and 402 nm/min. This paper considers why the FAD model involving fluoride ions cannot explain the huge differences in the growth rates. The huge difference is first interpreted reasonably in terms of the electronic current and the oxygen bubble model. The results show that the dissolution of oxide by fluoride ions is weak, and the role of fluoride ions is rather to form an anion-contaminated layer, which promotes the generation of electronic current and oxygen evolution. This theory was then tested by adding boric acid to the electrolyte. Borate can inhibit the penetration of fluoride ions into the contaminated layer, resulting in a significant reduction in electronic current, thus greatly reducing the growth rate of the nanotubes.

Miaoxi yellow peach, lanxi loquat, qingyuan sweet spring tangelo and haining pear are characteristic fruits in Zhejiang Province, China. This study investigated the levels of pesticides in these fruits in Zhengjiang Province, China, along with the associated risk of dietary exposure for consumer. In total, 25 pesticides were detected in the 68 samples. The pesticide detection rate of the samples was 95.59%, and the level of prochloraz in a pear sample was found to be higher than the maximum residue limit (MRL) in China. Overall, the pesticide residues were very low, and residue levels ranged from 0.001 to 1.06 mg/kg, of which 80.88% simultaneously occurred with 2–8 mixed residues. Acetamiprid (54.55%), carbendazim (64.71%), prochloraz (94.74%) and pyraclostrobin (85.71%) had the highest detection rate in the four fruits, respectively. A risk assessment of human exposure to pesticides via the intake of the four fruit types was performed, and the chronic intake risk (HQc) and acute intake risk (HQa) of a single pesticide and the hazard index (HI) of the mixture of pesticides for adults and children from the four fruit types were found to be less than 1, the exposure assessment showed that the levels of pesticides in the four fruit types were safe for human consumption. In addition, the quality of the four fruit types was analyzed and found to be not stable enough. We suggest strengthening standardized planting and management technology to improve product quality and safety, in particular, cultivators should use pesticides reasonably and control the pre-harvest interval (PHI) in order to better protect consumer health.

Chinese yam (Dioscorea polystachya Turczaninow) by-product produced in the water extraction process is commonly directly discarded resulting in a waste of resources and environmental pollution. However, the value of Chinese yam by-product which still contains effective ingredients is far from being fully realized; hence, it has the potential to be a safe and effective feed additive in aquaculture. To investigate the impacts of Chinese yam by-product on growth performance, antioxidant ability, histomorphology, and intestinal microbiota of Micropterus salmoides, juvenile fish (initial weight 13.16±0.05 g) were fed diets supplemented with 0% (control), 0.1% (S1), 0.4% (S2), and 1.6% (S3) of Chinese yam by-product for 60 days. The results showed that no significant difference was found in weight gain, specific growth rate, and survival among all the experimental groups (P>0.05). Feed conversion ratios of the S1 and S3 groups were significantly lower than those in the control group (P