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Abstract Late-stage specific and selective diversifications of peptides and proteins performed at target residues under ambient conditions are recognized to be the most facile route to various and abundant conjugates. Herein, we report an orthogonal modification of cysteine residues using alkyl thianthreium salts, which proceeds with excellent chemoselectivity and compatibility under mild conditions, introducing a diverse array of functional structures. Crucially, multifaceted bioconjugation is achieved through clickable handles to incorporate structurally diverse functional molecules. This “two steps, one pot” bioconjugation method is successfully applied to label bovine serum albumin. Therefore, our technique is a versatile and powerful tool for late-stage orthogonal bioconjugation.

Drought, which is severe and recurring in Northern China, is the most significant meteorological disaster on a worldwide scale. However, a definitive conclusion has not yet been reached on the multi-scale drought features in Northern China under a warming context. Drought is affected by several circulation-related variables and a deeper scientific comprehension of their synergistic effects is required. This research addresses the spatiotemporal aspects of summer drought and its causes in the northern drought-prone belt of China (NDPB), based on meteorological observation and data reanalysis. The primary findings indicate that the NDPB is very vulnerable to drought, with the uniform mode being the region’s most significant spatial mode associated with summer droughts. Inter-annual variations are the primary cause of the summer drought in the NDPB when considering multi-scale changes. Regional drought has typically declined during this century because of the effect of multi-decadal scale changes, which cannot be disregarded. Considering the circulation background field, during summer drought years in the NDPB, the South Asian high is weaker and moves eastward, while the high-level westerly jet is weaker and more northerly. From Lake Baikal to Northern China, there is an anomalous anticyclonic circulation, and the mid-level subtropical high in the western Pacific is more southerly and easterly. As a result, the NDPB is governed by the unusual northerly circulation. The Mongolian and northeastern surface cyclone activity is decreasing, the low-level warm and humid airflow is feeble, and the NDPB is not experiencing anomalous water vapor transport. In the high-, middle-, and low-level arrangement, the NDPB circulations diverge at low levels and converge at high levels—unusual sinking in the vertical field results in regular droughts. Multiple circulation parameters on inter-annual, inter-decadal, and multi-decadal scales interact synergistically to impact summer droughts in NDPB. However, the synergistic elements that mainly impact various timescales differ. They are primarily influenced by northerly circulation, westerly winds, and the combined effect of the South Asian summer monsoon on inter-annual timescales. The combined impact of the upper westerly winds, northerly circulation, and East Asian, South Asian, and plateau summer monsoons significantly influences their inter-decadal timescales. The westerly winds, northerly circulation, and East Asian, plateau summer monsoons are the primary multi-decadal factors.

Objective: Cannabis use has been linked to physical, psychological, and behavioral changes. Although research indicates separately that informal social support and formal social engagement – which are correlated measures – serve as protective factors in cannabis use, much of this research focuses on youth and more urban samples, limiting our understanding of if these findings are true for rural populations where social support and social engagement are particularly important for health and health behaviors. To fill the research gap, this study examines the effects of informal social support (tangible support and emotional support) and formal social engagement on cannabis use among rural working-age adults. Methods: This research analyzed 1,122 observations from a cross-sectional online survey conducted in 2022 of working-age adults (18–64) from rural America. Multilevel logistic regression models were used to predict cannabis use in the past 12 months using informal social support (tangible support and emotional support) and formal social engagement and other sociodemographic covariates and state legalization status. Results: Multilevel logistic modeling indicates that low emotional support and low formal social engagement are associated with a higher odds of reporting cannabis use in the past 12 months among rural working-age adults, net of other sociodemographic variables and state legalization status. Conclusions: The study suggests that emotional support and social engagement may contribute to cannabis use prevention among rural working-age adults. These findings should inform future research as well as the development of tailored health interventions targeting rural working-age adults.

Fine-grained classification of tree species by using high-spectral image data has garnered considerable attention from scholars. In this study, through field measurements from Maguan County, Wenshan Prefecture, Yunnan Province, China, high-spectral image data from the Chinese Resource-1 02D satellite were used as the data source. Various analyses were conducted on the original image’s spectral curve, the spectral curve after envelope removal, the spectral curve after first-order differential transformation, and the spectral curve after second-order differential transformation. A spectral angle mapping classification method was employed to classify and identify four dominant tree species in Maguan County, and the accuracy of the classification results was validated using a confusion matrix. Results indicate that the highest accuracy in tree species classification was achieved when first-order differential transformation and envelope removal were used for the spectral curve; the overall accuracy exceeded 95%, and the kappa value was approximately 0.95. The classification results for the spectral curve after second-order differential transformation were the lowest, with an overall accuracy of 81.69% and a kappa value of 0.76. This research demonstrates that applying first-order differential transformation or envelope removal in combination with spectral angle mapping classification considerably reduces data processing time and improves tree species classification accuracy.

IntroductionIn 2023, a comprehensive survey was conducted at Qiziwan National Marine Park (QZW) to assess marine environmental variables, coral communities, and ecosystem parameters. This study aimed to evaluate the current state of coral ecosystems across different regions within the park.MethodsThe survey covered 19 sampling stations distributed among four regions: Xiaojiao Park, Zhongjiao Park, Dajiao Park, and Shayutang Village. Various marine environmental parameters were measured, and coral species were identified and recorded.ResultsA total of 67 species of reef-building corals belonging to 25 genera were identified. Dominant species included Porites lutea, Goniopora columna, Platygyra sinensis, Favites flexuosa, Galaxea fascicularis, and Acropora millepora. Coral coverage was found to be low at Xiaojiao Park, with high levels of turbidity and dissolved inorganic nitrogen, likely due to the nearby Changhua Port. Dajiao Park's sandy substrate made it unsuitable for coral survival. In contrast, Zhongjiao Park and Shayutang Village exhibited the best coral ecosystems. Redundancy analysis indicated that turbidity and substrate types were significant factors influencing coral distribution.DiscussionThe live coral coverage at Xiaojiao Park, parts of Zhongjiao Park, and Dajiao Park declined from 14.03% in 2017 to 11.73% in 2023. This decline is potentially attributed to frequent marine construction and land use changes. Anthropogenic disturbances appear to have worsened environmental conditions, undermining coral reef survival at QZW.

The presence of trace organic pollutants in the effluent of wastewater treatment plants (WWTPs) poses considerable risks to aquatic organisms and human health. A large-scale survey of 302 trace organic pollutants in the effluent of 46 Chinese WWTPs was conducted to gain an improved understanding of their occurrence and ecological risks. The survey data showed that 216 compounds in 11 chemical classes had been detected in effluents. The sum concentrations of the trace contaminants in effluent ranged from 1,392 ng/L to 35,453 ng/L, with the maximum concentration of perfluoroalkyl substances (PFASs) recorded as the highest (30,573 ng/L), which was markedly less than the reported 185,000 ng/L for the 38 American WWTPs. The concentration of bisphenol analogs (BPs) was up to 4,422 ng/L, significantly higher than those reported in France, Germany, Japan, Korea, and the U.S. PFASs and BPs were the major pollutants, accounting for 59% of the total pollution. Additionally, a total of 119 contaminants were found to have ecological risks (RQ > 0.01). Among these, 23 contaminants (RQ > 1.0) warrant higher attention and should be prioritized for removal. This study lists valuable information for controlling contaminants with higher priority in WWTP effluent in China.

Abstract Ageing exhibits common and distinct features in various tissues, making it critical to decipher the tissue-specific ageing mechanisms. MiRNAs are essential regulators in ageing and are recently highlighted as a class of intercellular messengers. However, little is known about the tissue-specific transcriptomic changes of miRNAs during ageing. C. elegans is a well-established model organism in ageing research. Here, we profile the age-dependent miRNAomic changes in five isolated worm tissues. Besides the diverse ageing-regulated miRNA expression across tissues, we discover numerous miRNAs in the tissues without their transcription. We further profile miRNAs in the extracellular vesicles and find that worm miRNAs undergo inter-tissue trafficking via these vesicles in an age-dependent manner. Using these datasets, we uncover the interaction between body wall muscle-derived mir-1 and DAF-16/FOXO in the intestine, suggesting mir-1 as a messenger in inter-tissue signalling. Taken together, we systematically investigate worm miRNAs in the somatic tissues and extracellular vesicles during ageing, providing a valuable resource to study tissue-autonomous and nonautonomous functions of miRNAs in ageing.

Abstract Systemic lupus erythematosus (SLE), a severe autoimmune disorder, is characterized by systemic inflammatory response, autoantibody accumulation and damage to organs. The dysregulation of double-negative (DN) T cells is considered as a crucial commander during SLE. Neddylation, a significant type of protein post-translational modification (PTM), has been well-proved to regulate T cell-mediated immune response. However, the function of neddylation in SLE is still unknown. Here, we reported that neddylation inactivation with MLN4924, a specific inhibitor of NEDD8-activating enzyme E1 (NAE1), or genetic abrogation of Ube2m in T cells decreased DN T cell accumulation and attenuated murine lupus development. Further investigations revealed that inactivation of neddylation blocked Bim ubiquitination degradation and maintained Bim level in DN T cells, contributing to the apoptosis of the accumulated DN T cells in lupus mice. Then double knockout (KO) lupus-prone mice (Ube2m -/- Bim -/- lpr) were generated and results showed that loss of Bim reduced Ube2m deficiency-induced apoptosis in DN T cells and reversed the alleviated lupus progression. Our findings identified that neddylation inactivation promoted Bim-mediated DN T cell apoptosis and attenuated lupus progression. Clinically, we also found that in SLE patients, the proportion of DN T cells was raised and their apoptosis was reduced. Moreover, compared to healthy groups, SLE patients exhibited decreased Bim levels and elevated Cullin1 neddylation levels. Meantime, the inhibition of neddylation induced Bim-dependent apoptosis of DN T cells isolated from SLE patients. Altogether, our findings provide the direct evidence about the function of neddylation during lupus, suggesting a promising therapeutic approach for this disease.

Abstract Peptide and protein postmodification have gained significant attention due to their extensive impact on biomolecule engineering and drug discovery, of which cysteine‐specific modification strategies are prominent due to their inherent nucleophilicity and low abundance. Herein, the study introduces a novel approach utilizing multifunctional 5‐substituted 1,2,3‐triazine derivatives to achieve multifaceted bioconjugation targeting cysteine‐containing peptides and proteins. On the one hand, this represents an inaugural instance of employing 1,2,3‐triazine in biomolecular‐specific modification within a physiological solution. On the other hand, as a powerful combination of precision modification and biorthogonality, this strategy allows for the one‐pot dual‐orthogonal functionalization of biomolecules utilizing the aldehyde group generated simultaneously. 1,2,3‐Triazine derivatives with diverse functional groups allow conjugation to peptides or proteins, while bi‐triazines enable peptide cyclization and dimerization. The examination of the stability of bi‐triazines revealed their potential for reversible peptide modification. This work establishes a comprehensive platform for identifying cysteine‐selective modifications, providing new avenues for peptide‐based drug development, protein bioconjugation, and chemical biology research.

Cardiovascular diseases (CVD) persist as a prominent cause of mortality worldwide, with oxidative stress constituting a pivotal contributory element. The oxidative modification of guanosine, specifically 8-oxoguanine, has emerged as a crucial biomarker for oxidative stress, providing novel insights into the molecular underpinnings of CVD. 8-Oxoguanine can be directly generated at the DNA (8-oxo-dG) and RNA (8-oxo-G) levels, as well as at the free nucleotide level (8-oxo-dGTP or 8-oxo-GTP), which are produced and can be integrated through DNA replication or RNA transcription. When exposed to oxidative stress, guanine is more readily produced in RNA than in DNA. A burgeoning body of research surrounds 8-oxoguanine, exhibits its accumulation playing a pivotal role in the development of CVD. Therapeutic approaches targeting oxidative 8-Oxoguanine damage to DNA and RNA, encompassing the modulation of repair enzymes and the development of small molecule inhibitors, are anticipated to enhance CVD management. In conclusion, we explore the noteworthy elevation of 8-oxoguanine levels in patients with various cardiac conditions and deliberate upon the formation and regulation of 8-oxo-dG and 8-oxo-G under oxidative stress, as well as their function in CVD.

Abstract The inflammatory damage caused by thrombus formation and dissolution can increase the risk of thrombotic complications on top of cell death and organ dysfunction caused by thrombus itself. Therefore, a rapid and precise thrombolytic therapy strategy is in urgent need to effectively dissolve thrombus and resist oxidation simultaneously. In this study, Ce‐UiO‐66, a cerium‐based metal–organic framework (Ce‐MOF) with reactive oxygen species (ROS) scavenging properties, encapsulated by low‐immunogenic mesenchymal stem cell membrane with inflammation‐targeting properties, is used to construct a targeted nanomedicine Ce‐UiO‐CM. Ce‐UiO‐CM is applied in combination with external ultrasound stimulation for thrombolytic therapy in rat femoral artery. Ce‐UiO‐66 has abundant Ce (III)/Ce (IV) coupling sites that react with hydrogen peroxide (H2O2) to produce oxygen, exhibiting catalase (CAT) activity. The multi‐cavity structure of Ce‐UiO‐66 can generate electron holes, and its pore channels can act as micro‐reactors to further enhance its ROS scavenging capacity. Additionally, the porous structure of Ce‐UiO‐66 and the oxygen produced by its reaction with H2O2 may enhance the cavitation effects of ultrasound, thereby improving thrombolysis efficacy.

Abstract With the widespread development of chest computed tomography (CT), the detection rate of pulmonary nodules has increased; therefore, the classification of benign vs. malignant nodules has become a common problem in the clinic. MicroRNA, a potential tool, is expected to become a good choice for diagnosing and studying the occurrence and development of diseases through the vector of bronchoalveolar lavage fluid extracellular vesicles (BALF-EVs). In this study, radial endobronchial ultrasound (R-EBUS) was used to locate pulmonary nodules in patients. BALF was obtained, EVs were isolated, and small RNA sequencing was performed to screen differentially expressed miRNAs between benign and malignant pulmonary nodules. The binding targets and underlying mechanisms of the differentially expressed miRNAs were verified by in vitro and in vivo experiments. R-EBUS localization and sampling was used to obtain BALF, and EVs were successfully isolated and characterized. Differentially expressed miRNAs in BALF-EVs of patients with benign vs. malignant pulmonary nodules were screened by high-throughput small RNA sequencing. A new miRNA, miR-1246b, was identified. We found that FGF14 was the binding target of miR-1246b by luciferase assay. Subsequent mechanistic studies showed that miR-1246b inhibited the expression of FGF14 in lung cancer cells, further leading to ERK phosphorylation and epithelial-to-mesenchymal transition (EMT), which ultimately contributed to lung cancer cell proliferation, migration and invasion. In summary, our study demonstrates that the detection of miRNAs in BALF-EVs, a means of liquid biopsy, could assist in distinguishing malignant nodules from benign nodules. miR-1246b, which was extracted from BALF-EVs, targets FGF14 to promote lung cancer cell proliferation, migration and invasion.

Introduction:Rana dybowskii Guenther (RDG), as a traditional Chinese medicine, has been shown to have antioxidant effects. However, studies on the anti-aging effect of RDG are still limited.Methods: In this study, we prepared polysaccharides from the skin of RDG (RDGP) by hot water extraction, alcohol precipitation, ion-exchange chromatography and gel chromatography. The proteins were removed using the Sevage method in combination with an enzymatic method. The structural features were analyzed using high-performance gel permeation chromatography, β-elimination reaction and Fourier transform infrared spectra. The anti-aging effect of RDGP was investigated by using D-Gal to establish an aging model in mice, and pathological changes in the hippocampus were observed under a microscope.Results: We obtained the crude polysaccharide DGP from the skin of RDG, with a yield of 61.8%. The free protein was then removed by the Sevage method to obtain DGPI and deproteinated by enzymatic hydrolysis combined with the Sevage method to further remove the bound protein to obtain the high-purity polysaccharide DGPII. Then, DGPIa (1.03 × 105 Da) and DGPIIa (8.42 × 104 Da) were obtained by gel chromatography, monosaccharide composition analysis showed that they were composed of Man, GlcA, GalNAc, Glc, Gal, Fuc with molar ratios of 1: 4.22 : 1.55: 0.18 : 8.05: 0.83 and 0.74 : 1.78: 1: 0.28: 5.37 : 0.36, respectively. The results of the β-elimination reaction indicated the presence of O-glycopeptide bonds in DGPIa. The Morris water maze test indicated that mice treated with DGPIIa exhibited a significantly shorter escape latency and increased time spent in the target quadrant as well as an increase in the number of times they traversed the platform. Pathologic damage to the hippocampus was alleviated in brain tissue stained with hematoxylin-eosin. In addition, DGPIIa enhanced the activities of SOD, CAT, and GSH-Px and inhibited the level of MDA in the serum and brain tissues of aging mice.Discussion: These results suggest that RDGP has potential as a natural antioxidant and provide useful scientific information for anti-aging research.

Background: Hepatitis C virus (HCV) vaccines are an urgent need to prevent hepatitis C and its further progression of hepatocellular carcinoma. Since the promising T cell based chimpanzee adenovirus and modified vaccinia virus Ankara vectorial HCV vaccines were failed in clinical phase II trial, the vaccine designs to improve protection efficacy in combination of cellular and humoral immunity have been hypothesized against multi-genotypic HCV. Methods: Eight HCV vaccine strains were constructed with two novel adenovirus vectors (Sad23L and Ad49L) encoding E1E2 or NS3–5B proteins of HCV genotype (Gt) 1b and 6a isolates, covering 80 % HCV strains prevalent in south China and south-east Asia. Eight HCV vaccine strains were grouped into Sad23L-based vaccine cocktail-1 and Ad49L-based vaccine cocktail-2 for vaccinating mice, respectively. Results: The immunogenicity of a single dose of 107-1010 PFU HCV individual vaccines was evaluated in mice, showing weak specific antibody to E1 and E2 protein but a dose-dependent T cell response to E1E2/NS3–5B peptides, which could be significantly enhanced by boosting with an alternative vector vaccine carrying homologous antigen. Prime-boost vaccinations with vaccine cocktail-1 and cocktail-2 induced significantly higher cross-reactive antibody and stronger T cell responses to HCV Gt-1b/6a. The high frequency of intrasplenic and intrahepatic NS31629–1637 CD8+ T cell responses were identified, in which the high proportion of TRM and TEM cells might play an important role against HCV infection in liver. Conclusions: Prime-boost regimens with HCV vaccine cocktails elicited the broad cross-reactive antibody and robust T cell responses against multi-genotypic HCV in mice.

Objective There is currently no consensus on proximal humerus fractures with an initial deformity in the coronal plane who are better off with plates or nails, so we designed this study. To compare the effect of the initial deformity in the coronal plane of proximal humerus fractures on postoperative outcomes, we compare the maintenance of reduction in procedures utilizing plates and nails, and analyzed the subsequent occurrence of complications to explore whether the initial deformity should dictate the fixation approach. Methods The clinical data of patients with proximal humerus fractures who were hospitalized and underwent surgical treatment in our hospital from January 2016 to December 2020 were reviewed. Postoperative functional scores (American Shoulder and Elbow Surgeons, ASES; Constant‐Murley Score, CMS), Neck‐shaft angle (NSA), Quality of fracture reduction, Deltoid Tuberosity Index (DTI), and complications were compared among cases with initial varus, normal, or valgus deformities. Results We included 131 patients, 56 males and 75 females, with a mean age of 60.89 ± 5.53 years (range 50–76) and a mean follow‐up duration of 16.63 ± 6.78 months (range 12–48). Of these, 29 cases had initial varus displacement, 71 had a normal NSA, and 31 had initial valgus displacement. Seventy‐five were treated with a locking plate and 56 with a nail. After open reduction and internal fixation, the NSA was restored to normal (−135°) in all patients in all groups (P > 0.05). There was a significant difference in NSA changes at the last follow‐up; 2.93° ± 2.12° in the varus group, 1.77° ± 1.18° in the normal group, and 2.32° ± 1.64° in the valgus group, with the highest change occurring in the varus group. There was no significant difference in the range of motion or functional scores including ASES and CMS among the three groups (P > 0.05). The complication rate of 20.7% in the varus group was significantly higher than the complication rates of 12.7% in the normal and 12.9% in the valgus groups (P

Objectives Rotator cuff injury caused by subacromial impingement presents different morphologies. This study aims to investigate the correlation between various shoulder anatomical indexes on X‐ray with subacromial impingement and morphology of rotator cuff tears to facilitate surgical management. Method This retrospective study was carried out between January 2020 and May 2022. Patients who were diagnosed as sub‐acromial impingement associated with rotator cuff tears (without tendon retraction) and received arthroscopic surgery were enrolled in this study. The radiographic indexes of acromial slope (AS), acromial tilt (AT), lateral acromial angle (LAA), acromial Index (AI), and sub‐acromial distance (SAD) were measured on preoperative true AP view and outlet view. The location of rotator cuff tear (anterior, middle, posterior, medial, and lateral) and morphology of tear (horizontal, longitudinal, L‐shaped, and irregular shaped) were evaluated by arthroscopy. Groups were set up due to different tear location and tear morphologies, by comparing the various radiographic indices between each group (one‐way analysis of variance and t‐test), the correlation between radiographic indices and tear characteristics was investigated. Results We analyzed 92 shoulders from 92 patients with a mean age of 57.23 ± 8.45 years. The AS in anterior tear group (29.32 ± 6.91°) was significantly larger than that in middle tear group (18.41 ± 6.13°) (p = 0.000) and posterior tear group (24.01 ± 7.69°) (p = 0.041). The AS in posterior tear group (24.01 ± 7.69°) was significantly larger than that in middle tear group (18.41 ± 6.13°) (p = 0.029). The LAA in middle tear group (67.41 ± 6.54°) was significantly smaller than that in posterior group (72.74 ± 8.78°) (p = 0.046). The AS in longitudinal tear group (26.86 ± 8.41°) was significantly larger than that in horizontal tear group (22.05 ± 9.47°) (p = 0.035) and L‐shaped group (21.56 ± 6.62°) (p = 0.032). The LAA in horizontal group (70.60 ± 6.50°) was significantly larger than that in L‐shaped group (66.39 ± 7.31°) (p = 0.033). The AI in L‐shaped tear group (0.832 ± 0.074) was significantly larger than that in horizontal tear group (0.780 ± 0.084) (p = 0.019) and irregular tear group (0.781 ± 0.068) (p = 0.047). Conclusion Acromion with a larger AS and a smaller LAA tend to cause anterior or posterior rotator cuff tears rather than middle tears in sub‐acromial impingement. Meanwhile acromion with a larger AS tends to cause a longitudinal tear, a larger LAA tends to cause horizontal tears and a larger AI tends to cause L‐shaped tears.

BackgroundAberrant metabolism is a major hallmark of cancers and hereditary diseases. Genes associated with inborn metabolic errors may also play roles in cancer development. This study evaluated the overall impact of these genes on gastric cancer (GC).MethodsIn total, 162 genes involved in 203 hereditary metabolic diseases were identified in the Human Phenotype Ontology database. Clinical and multi-omic data were acquired from the GC cohort of the Affiliated Hospital of Jiangsu University and other published cohorts. A 4-gene and 32-gene signature was established for diagnosis and prognosis or therapeutic prediction, respectively, and corresponding abnormal metabolism scores (AMscores) were calculated.ResultsThe diagnostic AMscore showed high sensitivity (0.88-1.00) and specificity (0.89-1.00) to distinguish between GC and paired normal tissues, with area under the receiver operating characteristic curve (AUC) ranging from 0.911 to 1.000 in four GC cohorts. The prognostic or predictive AMscore was an independent predictor of overall survival (OS) in five GC cohorts and a predictor of the OS and disease-free survival benefit of postoperative chemotherapy or chemoradiotherapy in one GC cohort with such data. The AMscore adversely impacts immune biomarkers, including tumor mutation burden, tumor neoantigen burden, microsatellite instability, programmed death-ligand 1 protein expression, tumor microenvironment score, T cell receptor clonality, and immune cell infiltration detected by multiplex immunofluorescence staining. The AUC of the AMscore for predicting immunotherapy response ranging from 0.780 to 0.964 in four cohorts involving GC, urothelial cancer, melanoma, and lung cancer. The objective response rates in the low and high AMscore subgroups were 78.6% and 3.2%, 40.4% and 7%, 52.6% and 0%, and 72.7% and 0%, respectively (all p

Abstract Background Many studies have shown effective protection from myocardial ischemia–reperfusion injury (MIRI) in animal models, but few, if any, treatments have yielded a substantial reduction in clinical. Several studies showed significant therapeutic effects for the Chinese patent medicine Suxiao Jiuxin Pill (SJP) in MIRI, although the specific molecular mechanisms remain undefined. Recently, increasing evidence indicates an important role for m6A modification in autophagy regulation in MIRI, and SJP has not been investigated in this regard. Methods In vivo experiments were performed in a Wistar rat MIRI model. In vitro assays were conducted in hypoxia/reoxygenation (H/R)-treated H9c2 cells. H9c2 cells with ALKBH5 and GSK3β silencing were constructed by lentivirus transfection. TUNEL and Annexin V/PI assays were carried out for apoptosis detection. Then, m6A modification was detected with the EpiQuik m6A RNA methylation quantification kit, and GFP-RFP-LC3B was used to observe dynamic changes in autophagy. The autophagosome structure was assessed by Transmission electron microscopy. qPCR and immunoblot were performed for mRNA and protein analyses, receptively. Results SJP significantly mitigated MIRI in rats, reducing infarct size and myocardial apoptosis, and improving left ventricular function. In addition, SJP inhibited autophagy through the GSK3β/mTOR pathway in MIRI rats. In cultured H9c2 cells, SJP significantly inhibited H/R- related apoptosis and autophagic activity through the GSK3β/mTOR pathway. Additionally, SJP enhanced ALKBH5 expression in H/R cardiomyocytes, which is important in impaired m6A modification. Interestingly, ALKBH5 knockdown enhanced autophagy and apoptosis in H/R-induced cells, whereas SJP reversed these effects. Further experiments showed that autophagic activity and apoptosis enhanced by ALKBH5 deficiency are GSK3β/mTOR pathway dependent in H/R-treated H9c2 cells. After SJP administration the above effects were alleviated, suggesting SJP inhibited autophagy through the ALKBH5/GSK3β/mTOR pathway in H/R-induced cardiomyocytes. These effects of SJP were common to its two main constituents, including tetra-methylpyrazine (TMP) and borneol (BOR). Conclusion SJP improves MIRI in rats and alleviates autophagy and apoptosis in H9c2 cells through the ALKBH5/GSK3β/mTOR pathway, thanks to its two major constituents TMP and BOR.

Resonant scattering (RS) of X-ray line emission in supernova remnants (SNRs) may modify the observed line profiles and fluxes and has a potential impact on estimating the physical properties of the hot gas and hence on understanding the SNR physics, but has not been theoretically modeled ever. Here we present our Monte Carlo simulation of the RS effect on X-ray resonant-line emission, typified by the O vii He α r line, from SNRs. We employ the physical conditions characterized by the Sedov–Taylor solution and some basic parameters similar to those in Cygnus Loop. We show that the impact of the RS effect is most significant near the edge of the remnant. The line profiles are predicted to be asymmetric because of different temperatures and photon production efficiencies of the expanding gas at different radii. We also predict the surface brightness of the line emission would decrease in the outer projected region but is slightly enhanced in the inner. The G-ratio of the O vii He α triplet can be effectively elevated by RS in the outer region. We show that the RS effect of the O vii He α r line in the southwestern boundary region of Cygnus Loop is nonnegligible. The observed O vii G-ratio of ∼1.8 of the region could be achieved with RS taken into account for properly elevated O abundance from the previous estimates. Additional simulation performed for the SNRs in ejecta-dominated phases like Cas A shows that RS in the shocked ejecta may have some apparent effects on the observational properties of oxygen-resonant lines.

Crisis communication plays a crucial role in preserving the national reputation during significant national crises. From the perspective of Situational Crisis Communication Theory (SCCT), this research paper analyzed over 1,790,816 YouTube comments from Chinese-speaking audiences, using sentiment analysis alongside the Difference-in-Differences (DiD) model, in order to investigate the influence of strategic crisis communication on public perceptions during public health crises. The study findings indicate that during this public health crisis, YouTube Chinese media, whose audience mainly consists of overseas Chinese-speaking users, primarily incorporated the enhancing strategies, succeeded by the diminish strategies, with limited application of deny strategies, while the use of rebuild strategies was virtually absent in this context. In addition, the research analysis confirms that Chinese media effectively increased the public’s positive perceptions of crisis events through crisis communication. Particularly, enhancing strategies proved most effective in improving public perceptions, followed by diminish strategies. In contrast, deny strategies failed to influence public perceptions of the crisis, and rebuild strategies demonstrated a negative impact on public perception. Thus, the research findings of this paper extend essential insights for effectively managing potential public health crises in the future.

Compound hot extremes (CHEs) are receiving increasing attention due to their significant impacts on human health, ecosystems, and society compared to individual hot days or nights. While previous studies have focused on the characteristics of CHEs at individual points or stations, assessments of features for regional CHEs (RCHEs), which have a specific impact area and duration, are still lacking. This study aimed to investigate the climatic characteristics of RCHEs in mainland China by applying an objective identification technique for regional extreme events based on a compound index. The results show that 379 RCHEs were identified during 1961–2020, most of the events had a duration of 5–11 d and a maximum impacted area of approximately 460 10 ^4 km ^2 . Long-duration RCHEs were found to have vigorous extreme intensity and large maximum impacted area. The middle and lower reaches of the Yangtze River were most susceptible to RCHEs, while the Yellow River Valley had the most robust positive trend of frequency for RCHEs, suggesting a significant risk of compound temperature disasters in this region. Furthermore, RCHEs in mainland China showed significant increasing trends in several aspects, such as annual frequency, integrated index, and single indices (e.g. duration, accumulated intensity, accumulated impacted area, and extreme intensity). These upward trends were accompanied by evident interdecadal variations, with low values before 1992 and high values after 1992. This study provides valuable insights into understanding and monitoring CHEs in China from the perspective of regional extremes.

Conventional clinical monotherapies for advanced hepatocellular carcinoma (HCC) have numerous limitations. Integrated oncology approaches can improve cancer treatment efficacy, and photothermal-chemotherapy drug delivery nanosystems (DDS) based on nanotechnology and biotechnology have piqued the interest of researchers. This study developed an aptamer-modified graphene quantum dots (GQDs)/magnetic chitosan DDS for photothermal-chemotherapy of HCC. The HCC aptamer and the EPR effect of nanoparticles, in particular, enable active and passive targeting of DDS to HCC. GQDs functioned as photosensitizers, effectively moderating photothermal therapy and inhibiting drug release during blood circulation. Magnetic chitosan demonstrated excellent drug encapsulation, acid sensitivity, and tumor imaging capabilities. Proper assembly of the units mentioned above enables precise combined therapy of HCC. This study indicates that DDS can significantly inhibit tumor growth while also extending the survival duration of tumor-bearing mice. The DDS (DOX-Fe3O4@CGA) shows strong synergistic tumor treatment potential, allowing for the exploration and development of novel HCC therapies.

Objective: The glycation inhibition of 8 different non-Camellia teas was evaluated by detecting the content of non-enzymatic advanced glycation end-products (AGEs) and the inhibition mechanism of different teas with good inhibition effect on AGEs formation at various stages were investigated. Methods: Firstly, the total flavonoid content of the water extracts of 8 non-Camellia teas water extracts were detected, then all teas were tested by constructing an in vitro protein non-enzymatic glycation model experiment to evaluate the ability of inhibit the production of AGEs. Finally, the inhibitory ability of fructosamine (early glycation product), active carbonyl compound (intermediate glycation product), and the protein cross-linking were determined to explore the inhibitory mechanism of the non-enzymatic glycation reaction. Results: The inhibitory effect of Ilex latifolia tea and Rubus suavissimus tea on AGEs showed more prominent among the eight non-Camellia teas, and the inhibitory rate of AGEs reached at 76.31%±0.87% and 81.75%±0.41% at 50 µg/mL respectively. Further experimental results showed that Ilex latifolia tea and Rubus suavissimus tea mainly reduced the production of AGEs by inhibiting the formation of early and intermediate products of glycation, and 500 μg/mL Rubus suavissimus tea had the highest inhibition rate of fructosamine(59.12%) and protein cross-linking inhibition rate (81.41%), 5000 μg/mL Ilex latifolia tea had the highest inhibition rate of active carbonyl compounds (94.24%). Conclusion: Ilex latifolia tea and Rubus suavissimus tea could be used as functional foods to inhibit glycation reaction. This study could provide a theoretical basis for the comprehensive development and utilization of anti-glycation diet materials.

Abstract Background Salvia-Nelumbinis naturalis (SNN), the extract of Chinese herbal medicine, has shown effects on NAFLD. This study aims to explore the underlying mechanism of SNN for regulating the lipid metabolism disorder in NAFLD based on the SIRT1/AMPK signaling pathway. Methods Male C57BL/6J mice fed with a high-fat diet (HFD) were used to establish the NAFLD model. Dynamic changes of mice including body weight, liver weight, serological biochemical indexes, liver histopathological changes, and protein level of AMPK and SIRT1 were monitored. After18 weeks, SNN treatment was administrated to the NAFLD mice for another 4 weeks. Besides the aforementioned indices, TC and TG of liver tissues were also measured. Western blot and quantitative RT-PCR were used to detect the expression and/or activation of SIRT1 and AMPK, as well as the molecules associated with lipid synthesis and β-oxidation. Furthermore, AML12 cells with lipid accumulation induced by fatty acids were treated with LZG and EX527 (SIRT1 inhibitor) or Compound C (AMPK inhibitor ) to confirm the potential pharmacological mechanism. Results Dynamic observation found the mice induced by HFD with gradually increased body and liver weight, elevated serum cholesterol, hepatic lipid accumulation, and liver injury. After 16 weeks, these indicators have shown obvious changes. Additionally, the hepatic level of SIRT1 and AMPK activation was identified gradually decreased with NAFLD progress. The mice with SNN administration had lower body weight, liver weight, and serum level of LDL-c and ALT than those of the NAFLD model. Hepatosteatosis and hepatic TG content in the liver tissues of the SNN group were significantly reduced. When compared with control mice, the NAFLD mice had significantly decreased hepatic expression of SIRT1, p-AMPK, p-ACC, ACOX1, and increased total Acetylated-lysine, SUV39H2, and SREBP-1c. The administration of SNN reversed the expression of these molecules. In vitro experiments showed the effect of SNN in ameliorating hepatosteatosis and regulating the expression of lipid metabolism-related genes in AML12 cells, which were diminished by EX527 or Compound C co-incubation. Conclusions Taken together, the SIRT1/AMPK signaling pathway, involved in hepatic lipid synthesis and degradation, plays a pivotal role in the pathogenesis of NAFLD development. The regulation of SIRT1/AMPK signaling greatly contributes to the underlying therapeutic mechanism of SNN for NAFLD.

Abstract Background Sichuan province is one of the highest AIDS epidemic provinces in China, with a large number of floating population. The annual number of cases of HIV/AIDS reported in Sichuan has been the highest province in China for several successive years. There is a lack of widespread and representative data on the distribution of HIV genotypes in Sichuan. We aim to investigate the characteristics of HIV-1 molecular epidemiology and transmitted drug-resistance in newly diagnosed HIV-infected patients in Sichuan, China. Method Archived plasma samples (n = 1524) from HIV-1 newly-diagnosed individuals in April 2019 were selected by cross-sectional investigation from all 21 cities in Sichuan province. Phylogenetic relationship, transmission cluster, and genotypic drug resistance analyses were performed using HIV-1 polymerase (pol) gene sequences. We also analysed the association of demographic and virological factors with transmitted drug-resistance (TDR) and transmission clusters. Results Partial pol gene sequences were obtained from 1297 cases. HIV-1 epidemic strains in Sichuan province: the majority of genotypes were circulating recombinant form (CRF) 07_BC (675, 52.04%), CRF01_AE (343, 26.45%), CRF08_BC (115, 8.87%), CRF85_BC (67, 5.17%), subtype B (33, 2.54%), the other genotypes only accounted for 4.93%, and unique recombinant forms (URFs) (23, 1.77%) were observed in the study, and the difference of age, ethnicity, education, occupation, region and transmission pathway of different genotypes were statistically significant. According to WHO HIVDR surveillance threshold, the level of TDR has reached a medium level, with 72 of 1297 (5.55%) cases carrying drug-resistance mutation sites, TDR mutation frequency to nonnucleoside reverse transcriptase inhibitors (NNRTIs, 3.85%) was much higher than nucleoside reverse transcriptase inhibitors (NRTIs, 0.31%) and protease inhibitors (PIs, 1.70%), and CRF08_BC was a risk factor for TDR (odds ratio, 8.32; 95% CI 4.38–15.80 for CRF07_BC, P

Grass carp and silver carp eggs have no swimming ability in the water-hardened phase and need to drift for tens or even hundreds of hours before complete incubation. A full comprehensive understanding of the settling and transport properties of eggs is crucial for the resource protection and invasion control of Four Major Chinese Carps (FMCCs) during their early life stages. Artificial eggs have been used extensively in previous field and flume experiments; however, our understanding of the settling and transport properties of real eggs in the water-hardened phase remains limited. In the present study, a series of column and flume experiments were conducted in stagnant and moving water, respectively. In light of the differences in settling characteristics, caution should be exercised when applying research results obtained from artificial eggs having the closest diameter and specific gravity as real eggs. Compared with grass carp and silver carp eggs in the water-hardening phase, egg diameters in the water-hardened phase were 36% and 33% greater, respectively, and egg hydrostatic settling velocities were 31% and 40% lower, respectively. Significant interspecific differences between the two species exist in terms of egg size and hydrostatic settling velocity. Based on linear mixed effects analysis of dominant transport trajectories and regression analysis between suspending rate and flow velocity, 0.30 m/s can be considered as critical drifting velocity in uniform flow. Adaptive management schemes are discussed to promote resource protection and invasion control of FMCCs during the early life stages. The results of the present study enhance our understanding of drifting egg movement and provide insights that could facilitate the comprehensive management of FMCCs.

Non-alcoholic fatty liver disease (NAFLD) has become one of the main chronic liver diseases worldwide. Protopanaxadiol (PPD), an active compound derived from Gynostemma pentaphyllum, has been found able to improve free fatty acid-induced lipid accumulation in hepatocytes. However, the efficacy of PPD on NAFLD and the underlying mechanism remains unknown. In this study, the mice were fed with a high-fat diet for 22 weeks to induce the NAFLD model, and then were treated with PPD by gavage for 8 weeks. Moreover, AML12 and HepG2 cells induced by free fatty acids for 24 h, were treated with different doses of PPD and/or AMPK or SIRT1 inhibitor to explore the pharmacological mechanism of PPD. The results showed that mice with PPD treatment had significantly reduced liver weight and serum aminotransferase levels, less severe hepatosteatosis, and inflammatory cell infiltration in liver tissues when compared with the model mice. PPD also reversed the down-regulated activation of AMPK and SIRT1 expression as well as the change of lipid metabolism-related molecules in the mice liver tissues. Consistently, the in vitro experiments showed the effect of PPD in ameliorating lipid accumulation in hepatocytes. The inhibitor of AMPK or SIRT1 suppressed the AMPK and SIRT1 signaling and markedly diminished the anti-steatosis effect of PPD. In conclusion, our results prove the ameliorating impact of PPD on NAFLD and also reveal the involvement of regulation of AMPK/SIRT1 signaling pathway-mediated lipid metabolism in the underlying mechanism, suggesting PPD as a potential natural compound for the treatment of NAFLD.

Glycosyltransferase family 1 (GT1) is a large group of proteins that play critical roles in secondary metabolite biosynthesis in plants. However, the GT1 family is not well studied in maize. In this study, 107 GT1 unigenes were identified in the maize reference genome and classified into 16 groups according to their phylogenetic relationship. GT1s are unevenly distributed across all ten maize chromosomes, occurring as gene clusters in some chromosomes. Collinearity analysis revealed that gene duplication events, whole-genome or segmental duplication, and tandem duplication occurred at a similar frequency, indicating that both types of gene duplication play notable roles in the expansion of the GT1 gene family. Expression analysis showed GT1s expressing in all tissues with specific expression patterns of each GT1, suggesting that they might participate in multiple biological processes during the whole growth and development stages. Furthermore, 16 GT1s were identified to have similar expression patterns to those of anthocyanidin synthase (ANS), the critical enzyme in anthocyanin biosynthesis. Molecular docking was carried out to examine the affinity of GT1s with substrates in anthocyanin biosynthesis. This study provides valuable information on the GT1s of maize and will promote the development of research on their biological functions in the biosynthesis of other secondary metabolites.

Magnetic nanocarriers are nano-platforms that integrate multiple moieties based on magnetic nanoparticles for diagnostic and therapeutic purposes. In recent years, they have become an advanced platform for tumor treatment due to their wide application in magnetic resonance imaging (MRI), biocatalysis, magneto-thermal therapy (MHT), and photoresponsive therapy. Drugs loaded into magnetic nanocarriers can efficiently be directed to targeted areas by precisely reshaping their structural properties. Magnetic nanocarriers allow us to track the location of the therapeutic agent, continuously control the therapeutic process and eventually assess the efficacy of the treatment. They are typically used in synergistic therapeutic applications to achieve precise and effective tumor treatment. Here we review their latest applications in tumor treatment, including stimuli-responsive drug delivery, MHT, photoresponsive therapy, immunotherapy, gene therapy, and synergistic therapy. We consider reducing toxicity, improving antitumor efficacy, and the targeting accuracy of magnetic nanocarriers. The challenges of their clinical translation and prospects in cancer therapy are also discussed.

Abstract Linking of ‘consumption-industrial production-surface water deterioration’ is essential for industrialised economies to understand the mechanism of industrial water pollution. However, such a connection may mislead policy decisions if sectoral details are lacking. This study investigated excess pollution discharge from 11,094 industrial enterprises comprising 22 economic sectors through setting discharge thresholds on 1338 water function zones in Jiangsu Province, the most industrialised province in China. We further evaluated the contribution of final consumption in Chinese provinces to excess pollution discharge in Jiangsu via a national multi-region input–output table. Notably, despite typically heavy polluting sectors contributing the maximum excess pollution discharge, high-tech manufacturing sectors had a higher level of risk for excess pollution discharge. This was attributed to the spatial agglomeration of these sectors, with enterprises typically located in industrial parks. The increasing final consumption of specific sectors in both Jiangsu and other provinces may further drive excess pollution discharge in Jiangsu.

The significance of CO2 emissions at the water–air interface from inland water bodies in the global carbon cycle has been recognized and is being studied more and more. Although it is important to accurately assess CO2 emission flux in a catchment, little research has been carried out to investigate the spatio-temporal variations in CO2 emissions in view of a water continuum. Here, we systematically compared the differences and control factors of CO2 degassing across the water–air interface of a spring–river–lake continuum in the discharge area of Baotuquan Spring in July 2017, which is a typical temperate karst spring area in Jinan city, northern China, using hydrogeochemical parameters, stable carbon isotope values, and CO2 degassing flux. Affected by the pCO2 concentration gradient between the water and ambient air, the spring water showed a high CO2 degassing flux (166.19 ± 91.91 mmol/(m2 d)). After the spring outlet, the CO2 degassing flux in the spring-fed river showed a slight increase (181.05 ± 155.61 mmol/(m2 d)) due to river flow rate disturbance. The river flow rate was significantly reduced by the “blockage” of the lake, which promoted the survival and reproduction of phytoplankton and provided favorable conditions for aquatic plant photosynthesis, increasing the plankton biomass in the lake to 3383.79 × 104/L. In addition, the significant decrease in the dissolved inorganic carbon (DIC) concentration and the increase in the δ13CDIC values in the lake also indicated that the photosynthesis of the lake’s aquatic plants resulted in a significant decrease in the pCO2 concentration, thus limiting the amount of CO2 off-gassing (90.56 ± 55.03 mmol/(m2 d)).

Complete mitochondrial genomes were newly sequenced for eight species of the treehopper subfamily Centrotinae (Hemiptera: Membracidae), four of which represent genera for which mitogenomes were not previously available. The new mitogenomes are generally similar in overall structure, gene order, base composition, and nucleotide content to those of previously sequenced species of the subfamily. Phylogenetic analyses were conducted using both maximum likelihood and Bayesian inference methods based on three separate nucleotide sequence datasets in which RNA gene sequences and/or third codon positions were either included or excluded from the concatenated protein-coding gene alignments. The results are consistent with previous phylogenies based on morphology and partial nuclear genome data, except for the lack of support for the monophyly of Leptocentrini. These results show that mitogenome sequences are informative of both ancient and recent divergence patterns within Centrotinae.

Silicosis is an incurable lung disease that can progress even when exposure to silica dust has ended. Lipid metabolism plays an important role in the occurrence and development of silicosis. However, the mechanistic details have not been fully elucidated. This was investigated in the current study by high-performance liquid chromatography-mass spectrometry-based lipidomic analysis of lung tissue in a mouse model of silicosis. Lipid profiles and key metabolic enzymes were compared between silica and control groups. The lipidomic analysis revealed differentially-expressed lipids in the lungs of silicosis mice compared with controls. Among the identified lipid metabolism-related enzymes, the expression of lysophosphatidylcholine acyltransferase 1 (LPCAT1) was significantly down-regulated at the transcript and protein levels. LPCAT1 overexpression in vivo using adeno-associated virus altered the balance between phosphatidylcholine and lysophosphatidylcholine and inhibited the development of silicosis in mice. These results indicate that LPCAT1 dysregulation leads to abnormal lipid metabolism and silicosis, and is a potential therapeutic target for the treatment of silica-induced pulmonary fibrosis.

At the beginning of the 21st century, micro-nano processing technology has developed rapidly, and research on wearable electronic devices has exploded. In particular, flexible thermoelectric materials and thermoelectric generators (TEGs) that have stretchable or foldable properties have been widely studied. Textile-based thermoelectric materials are more suitable for use on the human body than are film or block types of devices, and they are accordingly favoured for wearable smart devices. The design idea of textile thermoelectric materials include the preparation of thermoelectric fibres, textiles, fabric-based films and some novel methods, like using three-dimensional modules to become two-dimensional fabrics by a weaving method, which not to rely something as a base for TE modules. Investigators are thus gaining opportunities to make comfortable and effective fabric TEGs using a wider variety of materials. This article briefly introduces the common methods used to produce textile TEGs. The opportunities and challenges of fabric TEGs are discussed at the end.

With the extensive use of immune checkpoint inhibitors (ICI) in advanced-stage cancers, immune-related adverse events (irAEs) have been noted in various systems. While most irAEs are reversible and manageable, cardiac toxicities are rare but life-threatening, with high mortality rates. We present a case of a 71-year-old man with cholangiocarcinoma who developed myocarditis related to ICIs 29 days after the first infusion of teriprizumab combined with albumin-bound paclitaxel and gemcitabine. He was initially asymptomatic after admission but with substantial elevations of troponin I and myocardial enzymes. Sixteen hours after admission, he developed palpitations, dizziness, and syncope. Electrocardiography confirmed third-degree atrioventricular block and frequent ventricular premature contractions for which he received high-dose corticosteroids and a permanent pacemaker. The patient survived and permanently discontinued immunotherapy. Early identification and intervention are the keys to improving the prognosis of immune myocarditis.

Macrophage-mediated inflammation compromises bone repair in diabetic patients. Electrical signaling cues are known to regulate macrophage functions. However, the biological effects of electrical microenvironment from charged biomaterials on the immune response for regulating osteogenesis under diabetic conditions remain to be elucidated. Herein the endogeneous electrical microenvironment of native bone tissue was recapitulated by fabricating a ferroelectric BaTiO3/poly (vinylidene fluoridetrifluoroethylene) (BTO/P(VDF-TrFE)) nanocomposite membrane. In vitro, the polarized BaTiO3/poly (vinylidene fluoridetrifluoroethylene) (BTO/P(VDF-TrFE)) nanocomposite membranes inhibited high glucose-induced M1-type inflammation, by effecting changes in cell morphology, M1 marker expression and pro-inflammatory cytokine secretion in macrophages. This led to enhanced osteogenic differentiation of human bone marrow mesenchymal stem cells (BM-MSCs). In vivo, the biomimetic electrical microenvironment recapitulated by the polarized nanocomposite membranes switched macrophage phenotype from the pro-inflammatory (M1) into the pro-healing (M2) phenotype, which in turn enhanced bone regeneration in rats with type 2 diabetes mellitus. Mechanistic studies revealed that the biomimetic electrical microenvironment attenuated pro-inflammatory M1 macrophage polarization under hyperglycemic conditions by suppressing expression of AKT2 and IRF5 within the PI3K-AKT signaling pathway, thereby inducing favorable osteo-immunomodulatory effects. Our study thus provides fundamental insights into the biological effects of restoring the electrical microenvironment conducive for osteogenesis under DM conditions, and offers an effective strategy to design functionalized biomaterials for bone regeneration therapy in diabetic patients.

Abstract Background Coronary heart disease (CHD) has become one of the biggest health problems in the world. Stable angina is a common clinical type of CHD with poor prognosis and high mortality. Although there are various interventions for stable angina, none of them can significantly reduce mortality. Both basic and clinical research have shown that Suxiao Jiuxin Pill (SJP) can relieve the symptoms of angina pectoris and improve the clinical efficacy, but there is a lack of high-quality clinical research to provide research-based evidence. We design a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of SJP for stable angina. Methods/design This is a prospective, randomized, double-blind, placebo-controlled, and multicenter trial. The trial will enroll 324 participants with chronic stable angina (Qi Stagnation and Blood Stasis syndrome). All participants will have received the conventional therapy of chronic stable angina. Participants will be randomized into two groups, conventional therapy plus SJP group and conventional therapy plus placebo group. Eligible participants will receive either SJP or placebo (five pills administered orally, three times daily) in addition to conventional treatment for 24 weeks. The primary outcomes are the symptom improvement rate of angina from baseline to 4 weeks after inclusion and major adverse cardiovascular events (MACE). The secondary outcomes are angina classification (CCS), improvement of traditional Chinese medicine (TCM) syndromes, Seattle Angina Scale score, the dosage of emergency drugs and the stopping rate, and electrocardiogram (EKG) efficacy. Adverse events will be monitored throughout the trial. Discussion Integrated traditional Chinese and Western Medicine is commonly used for angina in China. This study will evaluate the clinical effectiveness and safety of SJP for angina. The results of the trial will provide high-level clinical research-based evidence for the application of SJP instable angina. Trial registration This study protocol was registered on 14 March 2019. The registration number is ChiCTR1900021876 on the Chinese Clinical Trial Registry.

In this paper, an adaptive control scheme with disturbance estimation is proposed for the station keeping and trajectory tracking of an underwater vehicle-manipulator system (UVMS) in a task space. The control of UVMSs encounters time-varying and lumped disturbances introduced by the motion of the manipulator and currents. The proposed control scheme includes an observer to identify disturbances without introducing additional sensors. Using state-of-the-art UVMS control technologies, it alleviates the restriction of the feedforward control applied to the UVMS. In addition, the proposed control scheme is not designed based on the worst case. In other words, the robustness of the controller is not achieved at the price of performance, and the performance of the controller can be recovered in the absence of disturbance. Meanwhile, the controller can also realize quick responses to attenuating disturbance and closed-loop stability when encountering an unexpected disturbance. The effectiveness of the proposed control scheme was demonstrated by a series of spatial trajectory tracking experiments under various disturbances. A limitation of this study is that the proposed control scheme is specialized for the underwater manipulation of UVMSs.

The brain–computer interface (BCI) provides direct communication between human brains and machines, including robots, drones and wheelchairs, without the involvement of peripheral systems. BCI based on electroencephalography (EEG) has been applied in many fields, including aiding people with physical disabilities, rehabilitation, education and entertainment. Among the different EEG-based BCI paradigms, steady-state visual evoked potential (SSVEP)-based BCIs are known for their lower training requirements, high classification accuracy and high information transfer rate (ITR). In this article, a filter bank complex spectrum convolutional neural network (FB-CCNN) was proposed, and it achieved leading classification accuracies of 94.85 ± 6.18% and 80.58 ± 14.43%, respectively, on two open SSVEP datasets. An optimization algorithm named artificial gradient descent (AGD) was also proposed to generate and optimize the hyperparameters of the FB-CCNN. AGD also revealed correlations between different hyperparameters and their corresponding performances. It was experimentally demonstrated that FB-CCNN performed better when the hyperparameters were fixed values rather than channel number-based. In conclusion, a deep learning model named FB-CCNN and a hyperparameter-optimizing algorithm named AGD were proposed and demonstrated to be effective in classifying SSVEP through experiments. The hyperparameter design process and analysis were carried out using AGD, and advice on choosing hyperparameters for deep learning models in classifying SSVEP was provided.

This paper proposes a centralized MTT method based on a state-of-the-art multi-sensor labeled multi-Bernoulli (LMB) filter in underwater multi-static networks with autonomous underwater vehicles (AUVs). The LMB filter can accurately extract the number of targets and trajectories from measurements affected by noise, missed detections, false alarms and port–starboard ambiguity. However, its complexity increases as the number of sensors increases. In addition, due to the time-varying underwater environment, AUV detection probabilities are time-varying, and their mismatches often lead to poor MTT performance. Consequently, we detail a robust multi-sensor LMB filter that estimates detection probabilities and multi-target states simultaneously in real time. Moreover, we derive an effective approximate form of the multi-sensor LMB filter using Kullback–Leibler divergence and develop an efficient belief propagation (BP) implementation of the multi-sensor LMB filter. Our method scales linearly with the number of AUVs, providing good scalability and low computational complexity. The proposed method demonstrates superior performance in underwater multi-AUV network MTT simulations.

Abstract Background The baculoviral IAP repeat containing 5 (BIRC5) related to epithelial-mesenchymal transition (EMT) plays a crucial role in the pathogenesis of hepatocellular carcinoma (HCC). However, it remains unclear whether BIRC5-related genes can be used as prognostic markers of HCC. Methods Kaplan-Meier (K-M) survival curve was used to assess the Overall Survival (OS) of high- and low-expression group divided by the median of BIRC5 expression. The differentially expressed genes (DEGs) between the two groups were screened using the limma package, and performed the functional enrichment analysis by the clusterProfiler package. WGCNA was used to analyze the relationship of the module and the clinical traits. The risk signature was constructed by univariate and multivariate Cox regression analyses and the enrichment analysis of genes in the risk signature was performed by the Intelligent pathway analysis (IPA). The immunophenoscore (IPS) and the tumor immune dysfunction and exclusion (TIDE) were used to estimate the clinical significance of the risk groups. Results BIRC5 was high-expressed in HCC samples and associated with a poor prognosis (p-value 0.72] and was closely associated with clinicopathological characteristics of HCC patients. IPA suggested that the 8 genes were enriched in Cancer and Immunological disease related pathways. IPS and TIDE score indicated that the genes in low-risk group could cause an immune response, and patients in the low-risk group may be more sensitive to the immune checkpoint blockade (ICB) therapy. Conclusion The risk score constructed by the 8 genes could not only predict the clinical outcome but also distinguish the cohort of ICB therapy in HCC, which exerted a vital value in treatment and prognosis of HCC.

BackgroundEvidence on the efficacy of antiretroviral therapy (ART) regimen switches on the mortality of patients with HIV drug resistance (HIVDR) is limited. ObjectiveWe aim to provide policy guidance for ART regimen selection and evaluate the effectiveness of ART regime switches for people living with HIV and HIV-1 drug resistance. MethodsThis retrospective observational cohort study included 179 people living with HIV and HIV-1 drug resistance from 2011 to 2020. The time that participants switched treatment regimens either to protease inhibitor (PI)–based ART regimens (PIs) or nonnucleoside reverse transcriptase inhibitor (NNRTI)–based ART regimens (NNRTIs) was taken as an observation starting point and followed up every 12 months. The parametric g-formula was used to estimate the 5-year risk of mortality under the situations of (1) natural course, (2) immediate switch to NNRTIs, (3) immediate switch to PIs, and (4) if CD4(+) T cells

The activated c-Jun N-terminal kinase (JNK) specifically combined with SH3 domain-binding protein 5 (Sab) may mediate damage to the mitochondrial respiratory chain. Whether mitochondrial dysfunction induced by the JNK/Sab signaling pathway plays a pivotal role in the lipotoxic injury of nonalcoholic steatohepatitis (NASH) remains a lack of evidence. Scoparone, a natural compound from Traditional Chinese Medicine herbs, has the potential for liver protection and lipid metabolism regulation. However, the effect of scoparone on NASH induced by a high-fat diet (HFD) as well as its underlying mechanism remains to be elucidated. The HepG2 and Huh7 cells with/without Sab-knockdown induced by palmitic acid (PA) were used to determine the role of JNK/Sab signaling in mitochondrial dysfunction and cellular lipotoxic injury. To observe the effect of scoparone on the lipotoxic injured hepatocytes, different dose of scoparone together with PA was mixed into the culture medium of HepG2 and AML12 cells to incubate for 24 h. In addition, male C57BL/6J mice were fed with an HFD for 22 weeks to induce the NASH model and were treated with scoparone for another 8 weeks to investigate its effect on NASH. Molecules related to JNK/Sab signaling, mitochondrial function, and lipotoxic injury were detected in in vitro and/or in vivo experiments. The results showed that PA-induced activation of JNK/Sab signaling was blocked by Sab knockdown in hepatocytes, which improved mitochondrial damage, oxidative stress, hepatosteatosis, cell viability, and apoptosis. Scoparone demonstrated a similar effect on the PA-induced hepatocytes as Sab knockdown. For the NASH mice, treatment with scoparone also downregulated the activation of JNK/Sab signaling, improved histopathological changes of liver tissues including mitochondrial number and morphology, lipid peroxide content, hepatosteatosis and inflammation obviously, as well as decreased the serum level of lipid and transaminases. Taken together, this study confirms that activation of the JNK/Sab signaling pathway-induced mitochondrial dysfunction plays a crucial role in the development of NASH. Scoparone can improve the lipotoxic liver injury partially by suppressing this signaling pathway, making it a potential therapeutic compound for NASH.

Aim: The present study aimed to explore the potential herb-drug interactions (HDI) between Shengmai injection (SMI) and losartan potassium (LOS) based on the expression profiles of cytochromes P450 (CYP450) and drug transporters in rat and in vitro.Methods: Different concentrations of SMI were used to explore the influence of SMI on the antihypertensive efficacy of LOS in the hypertension rat model established by N (omega)-nitro-L-arginine methyl ester (L-NAME) for 4 weeks. Subsequently, the serum concentration levels of LOS and losartan carboxylic acid (EXP3174) were determined by Liquid Chromatography Mass Spectrometry (LC-MS) and pharmacokinetic analysis. Human liver microsomes, human multidrug resistance protein 1 (MDR1/P-gp), and breast cancer resistance protein (BCRP) vesicles, human embryonic kidney 293 cell line with stable expression of the organic anion transporting polypeptide 1B1 (HEK293-OATP1B1 cells) and mock-transfected HEK293 (HEK293-MOCK) cells were used to verify the effects of SMI on CYP450 enzymes and drug transporters in vitro.Results: Low, medium, and high concentrations of SMI increased the antihypertensive efficacy of LOS to varying degrees. The high dose SMI increased the half-life (t1/2), the maximum plasma concentration (Cmax), the area under the plasma concentration-time curve (AUC) from time zero to the time of the last measurable plasma concentration (AUC0-t), AUC from time zero to infinity (AUC0-∞), and mean residence time (MRT) values of LOS and decreased its apparent volume of distribution (Vd) and clearance (CL) values. The AUC0-t, AUC0-∞, and MRT of LOS were increased, whereas the CL was decreased by the medium concentration of SMI. In addition, the high, medium, and low doses of SMI increased the relative bioavailability (Frel) of LOS. SMI exhibited no significant effects on the pharmacokinetics of EXP3174. In vitro, SMI exhibited different suppressive effects on the enzyme activity levels of CYP1A2 (6.12%), CYP2B6 (2.72%), CYP2C9 (14.31%), CYP2C19 (12.96%), CYP2D6 (12.26%), CYP3A4 (3.72%), CYP2C8 (10.00–30.00%), MDR1 (0.75%), OATP1B1(2.03%), and BCRP (0.15%).Conclusion: In conclusion, SMI improved the antihypertensive efficacy of LOS in the L-NAME-induced hypertension rat model by increasing the concentration of LOS, while leaving the concentration of EXP3174 intact. SMI affected the pharmacokinetic properties of LOS by decreasing the elimination of LOS. These effects might partly be attributed to the inhibition of the activities of CYP3A4, CYP2C9, and of the drug transporters (P-gp, BCRP, and OATP1B1) by SMI, which need further scrutiny.

Objectives: The weak health system, domestic political unrest, poverty, and many other factors in the Central African Republic (CAR) have left the country underprepared for the COVID-19 pandemic, resulting in a greater health threat to the entire country. Rapid measures must therefore be taken to prevent the further spread of COVID-19.Methods: This work encompassed a review of relevant literature. We aim to analyze how far Chinese COVID measures can be transferred to the context of the CAR.Results: We argue that the measure that the CAR can learn from China’s success is the involvement of community workers and that greater investment in this model may be the optimal solution. Help from the international community is urgently needed.Conclusion: The CAR can benefit from China’s successful experience in fighting the epidemic, but the disparity in the combined power of the two countries does not allow for simple replication of China’s strategy.

Fluoride (F−) is widespread in aquatic environments; however, it is not clear whether the fluctuation of F− concentrations in overlying lake water affects the composition and migration of dissolved organic matter (DOM) from sediment. A case study was presented in Sand Lake, China, and an experiment was conducted to analyze the influence of different F− concentrations in overlying water on DOM characteristics. Diffusion resulted in similarities in DOM components between overlying and pore waters, and bacterial activities and enzyme variation resulted in differences between them. Higher F− concentrations in overlying water resulted in a higher pH of pore water, which favored the enrichment of protein-like substances. Higher F− concentrations caused lower DOM concentrations and lower maximum fluorescence intensities (Fmax) of protein-like components in pore water. The F− concentrations had significantly negative correlations with Shannon indexes (P

Abstract Background Group A rotavirus (RVA), despite being a leading cause of gastroenteritis in infants and young children, is less studied in Shanxi Province, China. The current study was conducted to determine the prevalence and genetic characterization of RVA in hospitalized children younger than 10 years of age with the diagnosis of acute gastroenteritis in Shanxi Province, China. Methods A hospital-based active surveillance of rotavirus gastroenteritis was conducted at Children’s Hospital of Shanxi from Jan 1, 2015, through Dec 31, 2019. Rotavirus was detected in stool samples by real-time quantitative reverse transcription PCR (qRT-PCR). G- and P-genotypes were determined by reverse transcription PCR (RT-PCR) and nucleotide sequencing. Results A total of 961 children younger than 10 years of age was enrolled over the study period, of whom 183 (19.0%) were positive for RVA. The highest RVA-infection frequency (23.7%) was found among children aged 12–23 months, and the seasonal peak was in December. G9P[8] was most prevalent (76.0%), followed by G3P[8] (7.1%), G2P[4] (3.3%), G1P[8] (0.5%) and G9P[4] (0.5%). Conclusions These results report for the first time that RVA was one of the main causes of severe infectious gastroenteritis in children, and a high proportion of G9P[8] strains circulating in most areas of Shanxi Province. While the protective efficacy of the rotavirus vaccines has been demonstrated against G9P[8] strains, our results highlight that the dominant strains have not been effectively controlled in China.

Abstract Background Iron (Fe) and phosphorus (P) dynamics in sediments have direct and indirect impacts on water quality. However, the mobility of P and Fe in reservoir sediments in Eucalyptus plantation region remains unclear. This study examined P and Fe pollution in sediments in a Eucalyptus plantation region using the novel planar optode, the ZrO-Chelex DGT, and the DIFS model. Results Direct in situ investigations showed that the levels of labile P and Fe were smaller in the Eucalyptus species-dominated sediments (X2) compared to sediments without Eucalyptus species (X1). The mean concentration of labile P and Fe decreased by 25% and 42% from X1 to X2. The decrement was insignificant (p = 0.20) in the surface sediment concentration for labile P. The significant disparity for DGT-Fe (Fe2+) (p = 0.03) observed in the surface sediments could be attributed to the Eucalyptus species’ elevated organic matter (tannins) concentration at X2, which reacted and consumed labile Fe. For both regions, the maximum concentration of labile P and Fe occurred in November (autumn). The reductive decomposition of Fe/Mn oxides was recognized as the main driver for their high P efflux in July and November. Low concentration of labile P and Fe was observed in December (winter) due to the adsorption of Fe/Mn oxides. The concentration of labile Fe synchronizes uniformly with that of labile P in both sediments indicating the existence of a coupling relationship (r > 0.8, p < 0.01) in both regions. The positive diffusion fluxes in both regions suggested that the sediments release labile P and Fe. The fluxes of labile P and Fe in both regions were substantially higher (p < 0.05) in the summer (anoxic period) than winter (aerobic period), indicating that hypoxia and redox conditions influenced the seasonal efflux of labile P and Fe. From the DIFS model, the replenishment ability of reactive P was higher during the anoxic period (R = 0.7, k 1 = 79.4 day− 1, k - 1 = 0.2 day− 1) than the aerobic period (R = 0.4, k 1 = 14.2 day− 1 , k-1 = 0.1 day− 1), suggesting that oxygen inhibited the efflux of P in the sediments. Conclusion Our results indicated that hypoxia, Eucalyptus species (organic matter (tannins)), and redox conditions influenced the seasonal mobility of sediment labile P and Fe. Our findings provided an insight into the mobility of labile P and Fe in Eucalyptus-dominated sediments and, moreover, serves as a reference for developing future studies on Eucalyptus-dominated sediments.

The brain–computer interface (BCI), which provides a new way for humans to directly communicate with robots without the involvement of the peripheral nervous system, has recently attracted much attention. Among all the BCI paradigms, BCIs based on steady-state visual evoked potentials (SSVEPs) have the highest information transfer rate (ITR) and the shortest training time. Meanwhile, deep learning has provided an effective and feasible solution for solving complex classification problems in many fields, and many researchers have started to apply deep learning to classify SSVEP signals. However, the designs of deep learning models vary drastically. There are many hyper-parameters that influence the performance of the model in an unpredictable way. This study surveyed 31 deep learning models (2011–2023) that were used to classify SSVEP signals and analyzed their design aspects including model input, model structure, performance measure, etc. Most of the studies that were surveyed in this paper were published in 2021 and 2022. This survey is an up-to-date design guide for researchers who are interested in using deep learning models to classify SSVEP signals.

Objective To analyze if general factors such as age, gender, dominant side, fasting blood sugar level, BMI (body mass index), smoking, and drinking play a role in graft resorption after arthroscopic autologous scapular spine bone grafting. Methods From July 2016 to August 2018, patients who were diagnosed with anterior shoulder instability with subcritical bone loss (10%–15%) and underwent arthroscopic autologous scapular spine bone graft transplant were retrospectively reviewed and enrolled in this study. The age, gender, dominant side, fasting blood sugar level, BMI, smoking, and drinking conditions of the enrolled patients were recorded. The graft resorption rate at postoperative 1 year was also measured on three‐dimensional computed tomography (3D‐CT) scans. The Pearson test and the Spearman test were used to identify any significant correlation between the general factors and graft resorption rate. Results A total of 27 patients who underwent arthroscopic autologous scapular spine bone graft for recurrent shoulder instability qualified and were included in this study. There were 20 males and seven females, the mean age was 30.8 ± 9.4 years, the mean follow‐up time was 29.3 months (range, 25–39 months), during which no severe complications such as infection, neurovascular injury, or re‐dislocation were observed. The bone graft healed in all cases, the mean healing time was 2.6 ± 0.5 months (range, 2–3 months). At the last follow‐up, the mean Constant–Murley score was 89.74 ± 3.71, the mean Disabilities of Arm, Shoulder and Hand (DASH) score was 9.77 ± 5.31, and the mean visual analogue score (VAS) was 0.74 ± 0.64. The apprehension test was all negative at final follow‐up. The fasting blood sugar level was 4.78 ± 0.42 mmol/L, BMI was 23.70 ± 4.70. Five patients were “smoking” and 22 “non‐smoking”, four patients were “drinking” and 23 were “non‐drinking.” The graft resorption rate at postoperative 1 year was 19.4% ± 7.5%. The Pearson test and the Spearman test showed no significant correlation between age, gender, dominant side, fasting blood sugar level, BMI, smoking, drinking, and graft resorption rate. Conclusion Age, gender, dominant side, fasting blood sugar level, BMI, smoking, and drinking were not significantly correlated with graft resorption after the arthroscopic autologous scapular spine bone graft for recurrent shoulder instability.