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ABSTRACT Renovascular hypertension (RVH) is a primary cause of secondary hypertension, primarily driven by the activation of the renin–angiotensin–aldosterone system activation. Recently, growing studies suggested accessory renal artery (ARA) might also contribute to RVH. However, the treatment of ARA‐related hypertension and whether to take interventional treatment lack consensus. Herein, we report two cases of ARA‐related hypertension in our hospital. Imaging studies of both patients showed ARA stenosis. One patient had ARA occlusion well‐compensated through tortuous collateral branches, achieving normal blood pressure by medical treatment alone. The other patient had ARA stenosis coexisted with main renal artery stenosis, and revascularization of both arteries led to a significant postoperative reduction in blood pressure. A literature review was conducted to summarize overall treatment strategies for ARA‐related hypertension and clarify the relationship between ARA and hypertension. Recent research supported an association between ARA and hypertension. While medical therapy remains the first‐line treatment for ARA‐related hypertension, interventional procedures should be considered for patients whose blood pressure remains uncontrolled despite conservative management.

In order to explore the future development strategy of telemetry system, a research on the development strategy of telemetry system is conducted based on the SWOT-AHP model. Firstly, based on the structural characteristics and functional attributes of the telemetry system, the advantages, disadvantages, opportunities and challenges of the telemetry system, the qualitative and quantitative analysis provides the optimal development strategy. The results show that the telemetry system development priorities the SO strategy, and thus formulates the long-term plan of the telemetry system development strategy, so as to provide a reference for the upgrading and transformation and frontier deployment of the telemetry system.

Abstract To investigate the response of post-installed rebar connectors in steel frame retrofitted concrete structures under combined shear and tension, seven shear-and-tensile tests were conducted. The bearing capacity, stiffness, and hysteresis behavior of the connectors were investigated during the tests. Both Monotonic and cyclic load regimes were applied in the loading process. The results show that with the increase of the loading angle, the deformation capacity, the yield force, ultimate tensile force, and tensile stiffness of the specimen decrease, while the maximum shear force and shear stiffness of the specimen increase. The bearing capacity, stiffness, and energy dissipation performance of the specimen under a monotonic load is greater than that under the coupled shear-and-pull load. The bearing capacity, stiffness, hysteresis curve, and failure status of the specimens are not affected by different loading regimes. At the end, the design formula of anchor bolt for this type of connectors from the design code of China, United States, and Japan were compared. Formulas to calculate the shear strength under combined shear and tension is developed.

Abstract Our study investigated the causal relationship between immune cells, metabolites, and epilepsy using two-sample Mendelian Randomization (MR) and mediation MR analysis of 731 immune cell traits and 1400 metabolites. Our core methodology centered on inverse-variance weighted MR, supplemented by other methods. This approach was crucial in clarifying the potential intermediary functions of metabolites in the genetic links between traits of immune cells and epilepsy. We found a causal relationship between immune cells and epilepsy. Specifically, the genetically predicted levels of CD64 on CD14-CD16- are positively correlated with the risk of epilepsy (p

Abstract The marine ecological red lines (MERLs) is an institutional innovation of the Chinese government to seek a balance between ecological protection and social development. China’s MERLs was designated in 2017, but there are problems such as insufficient consideration of areas of high ecological importance and lack of convergence with marine functional zoning. This paper carries out the adjustment of the MERLs in China by constructing the methods of marine ecological importance assessment and human activities disposal assessment, and the results show that after the adjustment, the type and distribution pattern of China’s MERLs is more reasonable, the areas of high ecological importance in the MERLs increases significantly, the intensity of human activities in the MERLs declines significantly, and the unification with the use of marine space is realized. China’s adjustment of the MERLs is based on scientific assessment and realizes the coordination of development and protection, which can provide a reference for global marine ecological protection.

Abstract Small extracellular vesicles (sEVs) have the ability to transfer genetic material between cells, but their role in mediating HBV infection and regulating M1 macrophages to promote immune evasion remains unclear. In this study, we utilized PMA + LPS + IFN-γ to induce THP-1 into M1 macrophages. We then extracted sEVs from HepG2.2.15 cell and treated the M1 macrophages with these sEVs. QPCR detection revealed the presence of HBV-DNA in the M1 macrophages. Additionally, RT-qPCR and WB analysis demonstrated a significantly decreased in the expression of TLR4, NLRP3, pro-caspase-1, caspase-1p20, IL-1β and IL-18 in the M1 macrophages (P

BackgroundThere are few literatures comprehensively analyzed the global research in hip prosthesis joint infections (HPJI). We aim to clarify the global research trends and analysis the top 10 cited articles in the HPJI field.MethodsWe identified the core collection of articles/reviews in the HPJI field from 2001 to 2021 through the Web of Science Core Collection (WOSCC). VOSviewer and online bibliometric tool were used to conduct the visualized and knowledge maps. Annual trends of publications, research hotspots and the top 10 cited articles were analyzed.ResultsA total of 5,477 publications were finally included. Generally, an increasing trend was observed in the number of publications from 2001 to 2021. The authors, journals and institutions with largest number of publications all belong to the USA. Co-occurrence analysis of keywords showed that surgical techniques, risk factors, revision surgery strategy, epidemiology, diagnoses and prevention were the 6 major research directions. Total hip arthroplasty, replacement, outcomes, risk factors and diagnosis were the keywords that occurred most frequently. The top 10 cited articles were all published in Journal Citation Reports (JCR) Q1 journals, providing valuable reference value from the perspectives of clinical guidelines, perioperative management, causes and diagnostic methods of infection, epidemiological investigation, risk factors and prognostic analysis.ConclusionsThe number of publications in HPJI field had been on the rise over the past 20 years, from disease management to prevention. An intensive reading of the top 10 cited articles is beneficial to understand the focus of HPJI research comprehensively.

IntroductionMRTX1133 is a selective and reversible small molecule inhibitor of KRAS (G12D), which significantly delays the progression of solid tumors. However, no study on the absorption, distribution, and excretion of MRTX1133.MethodsA fast ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry method was developed for the determination of MRTX1133 in rat plasma, tissue homogenate, and urine. The method applied to the pharmacokinetics, bioavailability, tissue distribution, and excretion of MRTX1133 after oral administration (25 mg/kg) and intravenous administration (5 mg/kg).ResultsThe calibration curve for MRTX1133 in plasma and other homogenates was linear, with r2 > 0.99. The intra- and inter-day accuracies were ranged from 85% to 115% and precision were within ± 10%. The matrix effect and recovery were within ± 15 %. The Cmax of MRTX1133 was 129.90 ± 25.23 ng/mL at 45 min after oral administration. The plasma half-life (t1/2) of MRTX1133 was 1.12 ± 0.46 h after oral administration and 2.88 ± 1.08 after intravenous administration. Its bioavailability was 2.92%. Furthermore, MRTX1133 was widely distributed in all the main organs, including liver, kidney, lung, spleen, heart, pancreas, and intestine. MRTX1133 was still detectable in liver, kidney, lung, spleen, heart, and pancreas after 24 h. The excretion ratio of prototype MRTX1133 through kidney was 22.59% ± 3.22% after 24 h.ConclusionsMRTX1133 was quickly absorbed, and widely distributed in the main organs. This study provided a reference for the quantitative determination of MTRX1133 in preclinical or clinical trials.

BackgroundSkeletal muscle atrophy significantly affects quality of life and has socio-economic and health implications. This study evaluates the effects of entacapone (ENT) on skeletal muscle atrophy linked with oxidative stress and proteolysis.MethodsC2C12 cells were treated with dexamethasone (Dex) to simulate muscle atrophy. Four murine models were employed: diaphragm atrophy from mechanical ventilation, Dex-induced atrophy, lipopolysaccharide (LPS)-induced atrophy, and hyperlipidemia-induced atrophy. Each model utilized entacapone (10 mg/kg), with sample sizes: Control (9), MV (11), MV + ENT (5) for diaphragm atrophy; Control (4), Dex (4), Dex + ENT (5) for Dex model; Control (4), LPS (4), LPS + ENT (5) for LPS model; and similar for hyperlipidemia. Measurements included muscle strength, myofiber cross-sectional area (CSA), proteolysis, oxidative stress markers [uperoxide dismutase 1 (SOD1), uperoxide dismutase 2 (SOD2), 4-hydroxynonenal (4-HNE)], and lipid levels.ResultsOur findings confirm Dex-induced muscle atrophy, evidenced by increased expression of muscle atrophy-associated proteins, including Atrogin-1 and Murf-1, along with decreased diameter of C2C12 myotubes. Atrogin-1 levels rose by 660.6% (p < 0.05) in the Dex group compared to control, while entacapone reduced Atrogin-1 by 84.4% (p < 0.05). Similarly, Murf-1 levels increased by 365% (p < 0.05) in the Dex group and were decreased by 89.5% (p < 0.05) with entacapone. Dexamethasone exposure induces oxidative stress, evidenced by the upregulation of oxidative stress-related proteins Sod1, Sod2, and 4-HNE. Entacapone significantly reduced the levels of these oxidative stress markers, enhancing GSH-PX content by 385.6% (p < 0.05) compared to the Dex-treated group. Additionally, ENT effectively reduced the Dex-induced increase in MDA content by 63.98% (p < 0.05). Furthermore, entacapone effectively prevents the decline in diaphragm muscle strength and myofiber CSA in mice. It also mitigates diaphragm oxidative stress and protein hydrolysis. Additionally, entacapone exhibits the ability to attenuate lipid accumulation in the gastrocnemius muscle of hyperlipidemic mice and alleviate the reduction in muscle fiber CSA.ConclusionOur findings suggest that entacapone is a promising therapeutic candidate for muscle atrophy, functioning through the reduction of oxidative stress, proteolysis, and lipid aggregation. Future research should explore the underlying mechanisms and potential clinical applications of entacapone in muscle-wasting conditions.

The opinions of individuals within a group about an ongoing epidemic play a crucial role in the dynamics of epidemic spread. People’s acceptance of others' opinions also changes with the changing epidemic situation and the dynamics of communication between individuals, how individuals' opinions and acceptance of others' views on epidemics affect the spread of epidemics has become an unresolved issue. In this study, we construct a two-layer coupled network that integrates the Hegselmann-Krause (HK) continuous opinion model with an epidemic model. This framework takes into account the evolutionary game of opinion acceptance among individuals within the group. We investigate the dynamic interaction between opinion exchange among individuals and the spread of the epidemic and derive the epidemic spread threshold of the model using the Quasi-Mean-Field (QMF) approach. The results indicate that under different infection rates, individuals in the group spontaneously form varying levels of opinion about the epidemic, which in turn evolve into different final infection states for the group. The higher the infection rate, the faster a positive and unified opinion forms. Promoting communication among individuals within the group can, to some extent, inhibit the spread of the epidemic. However, due to the diversity and complexity of information in the real world, the phenomenon of “delayed epidemic prevention” often occurs.

C12H13NO5S, triclinic, P1̄ (no. 2), a = 9.7095(6) Å, b = 11.9632(6) Å, c = 12.4335(5) Å, α = 86.456(4)°, β = 73.532(4)°, γ = 69.272(5)°, V = 1294.15(12) Å3, Z = 4, Rgt (F) = 0.0445, wRref (F 2) = 0.1113, T = 296(2) K.

Abstract Background Airway epithelial cell (AEC) necroptosis contributes to airway allergic inflammation and asthma exacerbation. Targeting the tumor necrosis factor-like ligand 1 A (TL1A)/death receptor 3 (DR3) axis has a therapeutic effect on asthmatic airway inflammation. The role of TL1A in mediating necroptosis of AECs challenged with ovalbumin (OVA) and its contribution to airway inflammation remains unclear. Methods We evaluated the expression of the receptor-interacting serine/threonine-protein kinase 3(RIPK3) and the mixed lineage kinase domain-like protein (MLKL) in human serum and lung, and histologically verified the level of MLKL phosphorylation in lung tissue from asthmatics and OVA-induced mice. Next, using MLKL knockout mice and the RIPK3 inhibitor GSK872, we investigated the effects of TL1A on airway inflammation and airway barrier function through the activation of necroptosis in experimental asthma. Results High expression of necroptosis marker proteins was observed in the serum of asthmatics, and necroptosis was activated in the airway epithelium of both asthmatics and OVA-induced mice. Blocking necroptosis through MLKL knockout or RIPK3 inhibition effectively attenuated parabronchial inflammation, mucus hypersecretion, and airway collagen fiber accumulation, while also suppressing type 2 inflammatory factors secretion. In addition, TL1A/ DR3 was shown to act as a death trigger for necroptosis in the absence of caspases by silencing or overexpressing TL1A in HBE cells. Furthermore, the recombinant TL1A protein was found to induce necroptosis in vivo, and knockout of MLKL partially reversed the pathological changes induced by TL1A. The necroptosis induced by TL1A disrupted the airway barrier function by decreasing the expression of tight junction proteins zonula occludens-1 (ZO-1) and occludin, possibly through the activation of the NF-κB signaling pathway. Conclusions TL1A-induced airway epithelial necroptosis plays a significant role in promoting airway inflammation and barrier dysfunction in asthma. Inhibition of the TL1A-induced necroptosis pathway could be a promising therapeutic strategy.

Abstract The paper presents a fault region identification method for the active distribution network (ADN) with limited PMU. First, PMU configuration and region division strategies are proposed based on the network topology. Next, the difference in three-phase current variations between the normal and fault regions of the ADN is analyzed. A multi-dimensional state monitoring matrix is built using the measured current data. The spectral norm ratio coefficient is constructed based on the 2-norm to lower the complexity of the multi-dimensional state monitoring matrix and quantify the difference in state changes before and after the fault occurs in each region. Then, the fault region is identified by combining each region’s spectral norm ratio coefficient and the change of the current phase. Finally, an IEEE 33-node simulation model is created to simulate faults under different working conditions. According to the simulation results, the suggested approach is less impacted by fault type, neutral point grounding mode, and transition resistance. Furthermore, even if the communication does not match the rigorous synchronization requirements, the proposed method can still complete the fault identification of the distribution network correctly and has high robustness.

Abstract Background Airway epithelium is an important component of airway structure and the initiator of airway remodeling in asthma. The changes of extracellular matrix (ECM), such as collagen deposition and structural disturbance, are typical pathological features of airway remodeling. Thus, identifying key mediators that derived from airway epithelium and capable of modulating ECM may provide valuable insights for targeted therapy of asthma. Methods The datasets from Gene Expression Omnibus database were analyzed to screen differentially expressed genes in airway epithelium of asthma. We collected bronchoscopic biopsies and serum samples from asthmatic and healthy subjects to assess lysyl oxidase like 2 (LOXL2) expression. RNA sequencing and various experiments were performed to determine the influences of LOXL2 knockdown in ovalbumin (OVA)-induced mouse models. The roles and mechanisms of LOXL2 in bronchial epithelial cells were explored using LOXL2 small interfering RNA, overexpression plasmid and AKT inhibitor. Results Both bioinformatics analysis and further experiments revealed that LOXL2 is highly expressed in airway epithelium of asthmatics. In vivo, LOXL2 knockdown significantly inhibited OVA-induced ECM deposition and epithelial-mesenchymal transition (EMT) in mice. In vitro, the transfection experiments on 16HBE cells demonstrated that LOXL2 overexpression increases the expression of N-cadherin and fibronectin and reduces the expression of E-cadherin. Conversely, after silencing LOXL2, the expression of E-cadherin is up-regulated. In addition, the remodeling and EMT process that induced by transforming growth factor-β1 could be enhanced and weakened after LOXL2 overexpression and silencing in 16HBE cells. Combining the RNA sequencing of mouse lung tissues and experiments in vitro, LOXL2 was involved in the regulation of AKT signaling pathway. Moreover, the treatment with AKT inhibitor in vitro partially alleviated the consequences associated with LOXL2 overexpression. Conclusions Taken together, the results demonstrated that epithelial LOXL2 plays a role in asthmatic airway remodeling partly via the AKT signaling pathway and highlighted the potential of LOXL2 as a therapeutic target for airway remodeling in asthma.

Abstract An arc is the high‐temperature discharge plasma produced in the opening process of mechanical switches, which directly affects the breaking capability of a hybrid DC circuit breaker. According to the physical mechanism of an electric arc, the construction of an arc model for simulation analysis is an important technical means in the electrical field. In this study, based on the theory of magneto hydrodynamics (MHD), a gas mechanical switch model of a natural commutation DC circuit breaker with a compound gap is established. The arc motion process under different conditions is simulated and calculated. The influence of different initial pressures, different opening speeds, and different striking currents on the arc voltage characteristics is analysed. The results show that the larger the gas pressure, the smaller the arc volume and the higher the arc voltage. The faster the opening speed, the longer the arc and the higher the arc voltage; with the increase of the current, the arc voltage increases rapidly at a low current, while the arc voltage increases slowly at a high current.

Abstract Background Previous studies have shown that protein kinase MoKin1 played an important role in the growth, conidiation, germination and pathogenicity in rice blast fungus, Magnaporthe oryzae. ΔMokin1 mutant showed significant phenotypic defects and significantly reduced pathogenicity. However, the internal mechanism of how MoKin1 affected the development of physiology and biochemistry remained unclear in M. oryzae. Result This study adopted a multi-omics approach to comprehensively analyze MoKin1 function, and the results showed that MoKin1 affected the cellular response to endoplasmic reticulum stress (ER stress). Proteomic analysis revealed that the downregulated proteins in ΔMokin1 mutant were enriched mainly in the response to ER stress triggered by the unfolded protein. Loss of MoKin1 prevented the ER stress signal from reaching the nucleus. Therefore, the phosphorylation of various proteins regulating the transcription of ER stress-related genes and mRNA translation was significantly downregulated. The insensitivity to ER stress led to metabolic disorders, resulting in a significant shortage of carbohydrates and a low energy supply, which also resulted in severe phenotypic defects in ΔMokin1 mutant. Analysis of MoKin1-interacting proteins indicated that MoKin1 really took participate in the response to ER stress. Conclusion Our results showed the important role of protein kinase MoKin1 in regulating cellular response to ER stress, providing a new research direction to reveal the mechanism of MoKin1 affecting pathogenic formation, and to provide theoretical support for the new biological target sites searching and bio-pesticides developing.

Abstract Evidence about associations of phthalates metabolites with increased serum uric acid (SUA) levels in pregnant women remains unknown. To address this, we conducted a cross-sectional population-based study including 851 pregnant women from Zunyi birth cohort in southwest China. Multiple linear regression models were used to explore single relationships between ten urinary phthalate metabolites with SUA and estimated glomerular filtration rate (eGFR). And then, the overall relationship of phthalate mixture with SUA and eGFR were determined by principal component analysis (PCA) and quantile g-computation (Q-g) analysis. The multivariable linear regression showed that mono-butyl phthalate (MBP), mono-octyl phthalate (MOP) and mono-benzyl phthalate (MBzP) were positively associated with SUA, while mono (2-ethylhexyl) phthalate (MEHP) and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were associated with increased eGFR level. Moreover, PCA analysis suggested that phthalate mixture was positively associated with SUA, and MOP, MBzP and MEHP appeared to be the major contributors. Furthermore, Q-g regression showed that each quantile increase in phthalate mixture was associated with 3.27% higher SUA (95% CI 0.21%, 6.41%). Our results imply that phthalate metabolites were associated with higher SUA in late pregnant women, and MBP, MBzP and MOP might be the major drivers. So, a health perinatal duration should be seriously taken to counteract the environment-related dysregulated kidney function.

Abstract Background Postmenopausal osteoporosis is a chronic metabolic bone disease caused by excessive osteoclast formation and function. Targeting osteoclast differentiation and activity can modulate bone resorption and alleviate osteoporosis. Cirsilineol, an active constituent of Vestita Wall, has shown numerous biological activities and has been used to treat many metabolic diseases. However, whether cirsilineol inhibits osteoclast activity and prevents postmenopausal osteoporosis still remain unknown. Materials and methods Primary bone marrow macrophages (BMMs) and RAW264.7 cells were used. Osteoclast activity was measured by TRAP staining, F-actin staining, and bone resorption assay after BMMs were treated with cirsilineol at concentrations of 0, 1, 2.5 and 5 µM. RT-PCR and western blotting were performed to evaluate the expression of osteoclast-related genes. In addition, female C57BL/6 mice underwent OVX surgery and were treated with cirsilineol (20 mg/kg) to demonstrate the effect of cirsilineol on osteoporosis. Results Cirsilineol significantly inhibited receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast differentiation in a concentration- and time-dependent manner, respectively. Additionally, cirsilineol inhibited F-actin ring formation, thus reducing the activation of bone resorption ability. Cirsilineol suppressed the expression of osteoclast-related genes and proteins via blocking nuclear factor (NF)-κb, ERK, and p38 signaling cascades. More importantly, cirsilineol treatment in mice with osteoporosis alleviated osteoclasts hyperactivation and bone mass loss caused by estrogen depletion. Conclusion In this study, the protective effect of cirsilineol on osteoporosis has been investigated for the first time. In conclusion, our findings prove the inhibitory effect of cirsilineol on osteoclast activity via NF-κb/ERK/p38 signaling pathways and strongapplication of cirsilineol can be proposed as a potential therapeutic strategy.

Abstract The noncovalent interactions of ammonium ion with multidentate oxygen-based host has never been reported as a reacting center in catalytic reactions. In this work, we report a reactivity enhancement process enabled by non-covalent interaction of ammonium ion, achieving the C–H functionalization of polyethylene glycols with acrylates by utilizing photoinduced co-catalysis of iridium and quinuclidine. A broad scope of alkenes can be tolerated without observing significant degradation. Moreover, this cyano-free condition respectively allows the incorporation of bioactive molecules and the PEGylation of dithiothreitol-treated bovine serum albumin, showing great potentials in drug delivery and protein modification. DFT calculations disclose that the formed α-carbon radical adjacent to oxygen-atom is reduced directly by iridium before acrylate addition. And preliminary mechanistic experiments reveal that the noncovalent interaction of PEG chain with the formed quinuclidinium species plays a unique role as a catalytic site by facilitating the proton transfer and ultimately enabling the transformation efficiently.

A two-year long-term workshop centered around a phenotypic whole-cell screening strategy for integrating cutting-edge knowledge and discovery-based laboratory experiences was developed to serve as a preparatory course for enhancing the teaching quality of the upper-level discovery-based research internship curriculum for pharmacy major undergraduates. The workshop comprises four modules that integrate lessons and experiments into a genuine research project, which initiates with a medicinal-chemistry course, run concurrently in the second year and culminates with the discovery-based research internship curriculum for pharmacy major students as a corequisite in the last year. The effective implementation of the featured pedagogical approaches in the modules is detailed as described. A group of students (N = 4) passed the instructor-student two-way choice and were enrolled in the senior-level phenotypic hit discovery laboratory project. The students synthesized a small library of molecules, tested them in an antibacterial assay, and further designed new compounds to analyze structure-activity relationships. Furthermore, positive feedback from students revealed that the phenotypic hit discovery oriented workshop enabled them to gain in-depth cutting-edge knowledge and provided an understanding of how medicinal chemists engage in new drug discovery research. The student's early exposure to troubleshooting or exploring unexpected results in an authentic scientific environment inspired them with ambition and confidence to engage with new drug discovery. We hope that this workshop will serve as a springboard for those wishing to educate medicinal chemists at an undergraduate level with modern strategies that are relevant to the current and future drug discovery landscape.

Many studies have indicated that individual exposure to phthalates (PAEs) or polycyclic aromatic hydrocarbons (PAHs) affects pregnancy outcomes. However, combined exposure to PAEs and PAHs presents a more realistic situation, and research on the combined effects of PAEs and PAHs on gestational age and newborn size is still limited. This study aimed to assess the effects of combined exposure to PAEs and PAHs on neonatal gestational age and birth size. Levels of 9 PAE and 10 PAH metabolites were measured from the urine samples of 1030 women during early pregnancy from the Zunyi Birth Cohort in China. Various statistical models, including linear regression, restricted cubic spline, Bayesian kernel machine regression, and quantile g-computation, were used to study the individual effects, dose–response relationships, and combined effects, respectively. The results of this prospective study revealed that each ten-fold increase in the concentration of monoethyl phthalate (MEP), 2-hydroxynaphthalene (2-OHNap), 2-hydroxyphenanthrene (2-OHPhe), and 1-hydroxypyrene (1-OHPyr) decreased gestational age by 1.033 days (95 % CI: −1.748, −0.319), 0.647 days (95 % CI: −1.076, −0.219), 0.845 days (95 % CI: −1.430, −0.260), and 0.888 days (95 % CI: −1.398, −0.378), respectively. Moreover, when the concentrations of MEP, 2-OHNap, 2-OHPhe, and 1-OHPyr exceeded 0.528, 0.039, 0.012, and 0.002 µg/g Cr, respectively, gestational age decreased in a dose–response manner. Upon analyzing the selected PAE and PAH metabolites as a mixture, we found that they were significantly negatively associated with gestational age, birth weight, and the ponderal index, with 1-OHPyr being the most important contributor. These findings highlight the adverse effects of single and combined exposure to PAEs and PAHs on gestational age. Therefore, future longitudinal cohort studies with larger sample sizes should be conducted across different geographic regions and ethnic groups to confirm the impact of combined exposure to PAEs and PAHs on birth outcomes.

Tumor stands as one of the principal contributors to global mortality. As research into tumor treatments advances, tumor inhibitors emerge as pivotal milestones in tumor therapy. Among these inhibitors, Anaplastic Lymphoma Kinase (ALK), a receptor tyrosine kinase, is critical owing to its close association with tumor cell proliferation and growth, which renders it a critical therapeutic target. This work systematically explores the relationship between the chemical structures of 36 piperidine carboxamide derivatives and their efficacy in inhibiting Karpas-299 tumor cell activity by employing a rigorous 3D-QSAR modeling approach. A robust Topomer CoMFA model was generated and was meticulously validated through ANN neural network analysis (q2 = 0.597, r2 = 0.939, F = 84.401, N = 4, SEE = 0.268). Based on the model, 60 new compounds with desirable inhibitory activities were successfully designed. Combined with Lipinski’s rule and ADMET criteria alongside molecular docking and dynamics simulations, a lead compound with high inhibitory activity and good drug-likeness was selected. Further computational analyses, encompassing free energy landscape and binding free energy calculations, provided compelling evidence of the stable binding conformation of the lead compound and the superior affinity with the target protein at the active site, underscoring its potential therapeutic utility. In summary, this investigation offers valuable insights and methodological guidance for advancing tumor therapy and underscores the promise of piperidine carboxamide derivatives as prospective ALK inhibitors.

Abstract Discerning weak electric fields has important implications for cosmology, quantum technology, and identifying power system failures. Photonic integration of electric field sensors is highly desired for practical considerations and offers opportunities to improve performance by enhancing microwave and lightwave interactions. Here, we demonstrate a high-Q microcavity electric field sensor (MEFS) by leveraging the silicon chip-based thin film lithium niobate photonic integrated circuits. Using the Pound-Drever-Hall detection scheme, our MEFS achieves a detection sensitivity of 5.2 μV/(m $$\sqrt{{{{{{{{\rm{Hz}}}}}}}}}$$ Hz ), which surpasses previous lithium niobate electro-optical electric field sensors by nearly two orders of magnitude, and is comparable to atom-based quantum sensing approaches. Furthermore, our MEFS has a bandwidth that can be up to three orders of magnitude broader than quantum sensing approaches and measures fast electric field amplitude and phase variations in real-time. The ultra-sensitive MEFSs represent a significant step towards building electric field sensing networks and broaden the application spectrum of integrated microcavities.

Abstract Photoexcitation of the electron-donor-acceptor complexes have been an effective approach to achieve radicals by triggering electron transfer. However, the catalytic version of electron-donor-acceptor complex photoactivation is quite underdeveloped comparing to the well-established utilization of electronically biased partners. In this work, we utilize 4-nitrophthalonitrile as an electron acceptor to facilitate the efficient π-stacking with electron-rich aromatics to form electron-donor-acceptor complex. The characterization and energy profiles on the cocrystal of 4-nitrophthalonitrile and 1,3,5-trimethoxybenzene disclose that the electron transfer is highly favorable under the light irradiation. This electron acceptor catalyst can be efficiently applied in the benzylic C−H bond photoactivation by developing the Giese reaction of alkylanisoles and the oxidation of the benzyl alcohols. A broad scope of electron-rich aromatics can be tolerated and a mechanism is also proposed. Moreover, the corresponding π-anion interaction of 4-nitrophthalonitrile with potassium formate can further facilitate the hydrocarboxylation of alkenes efficiently.

Seamounts are prominent seafloor features that make inhomogeneous oceanic crust, carried by some moving plates and eventually accreted or subducted at convergent margins. These seamounts contribute to subduction dynamics, continental crustal growth, and chemical mantle heterogeneities. We present a review of seamount subduction and accretion in the West Junggar based on available geological, geochronological, and geochemical data of the ophiolitic mélanges. Several ophiolitic mélanges with ages ranging from 572 Ma to 332 Ma developed in West Junggar, including the Mayile, Tangbale, Chagantaolegai, Barleik, Hebukesaier, Kujibai, Emin, Hongguleleng, Karamay, and Durbut ophiolitic mélanges, and displayed some typical block-in-matrix structures. The mafic rocks from these ophiolitic mélanges can be divided into MORB and OIB types. The MORB type likely to have formed in arc related setting were derived from a depleted mantle source that had been metasomatized by slab-derived fluids. However, the OIB type was formed in seamounts/oceanic plateaus related to mantle plume activities. Many seamounts with different ages developed in the Junggar Ocean as well as the Paleo-Asian Ocean, and had three different destinations: accretion in the accretionary prism, underplating to the overriding plate, and collision, resulting in different geological effects. The subducting and accreting seamounts in West Junggar are mainly involved in deformation of the overriding plate, magmatism of the volcanic arc and plate tectonics. Particularly, seamounts/oceanic plateaus accretion probably induced subduction initiation in West Junggar, namely subduction polarity-reversal and/or subduction transference. This will provide new insights into understanding the tectonic evolution of the West Junggar as well as the CAOB.

BackgroundMechanical ventilation (MV) is often required in critically ill patients. However, prolonged mechanical ventilation can lead to Ventilator-induced diaphragmatic dysfunction (VIDD), resulting in difficulty in extubation after tracheal intubation, prolonged ICU stay, and increased mortality. At present, the incidence of diabetes is high in the world, and the prognosis of diabetic patients with mechanical ventilation is generally poor. Therefore, the role of diabetes in the development of VIDD needs to be discovered.MethodsMV modeling was performed on C57 mice and DB mice, and the control group was set up in each group. After 12 h of mechanical ventilation, the muscle strength of the diaphragm was measured, and the muscle fiber immunofluorescence staining was used to verify the successful establishment of the MV model. RNA sequencing (RNA-seq) method was used to detect mRNA expression levels of the diaphragms of each group, and then differential expressed gene analysis, Heatmap analysis, WGCNA analysis, Venn analysis, GO and KEGG enrichment analysis were performed. qRT-PCR was used to verify the expression of the selected mRNAs.ResultsOur results showed that, compared with C57 control mice, the muscle strength and muscle fiber cross-sectional area of mice after mechanical ventilation decreased, and DB mice showed more obvious in this respect. RNA-seq showed that these differential expressed (DE) mRNAs were mainly related to genes such as extracellular matrix, collagen, elastic fiber and Fbxo32. GO and KEGG enrichment analysis showed that the signaling pathways associated with diabetes were mainly as follows: extracellular matrix (ECM), protein digestion and absorption, PI3K-Akt signaling pathway, calcium signaling pathway, MAPK signaling pathway and AGE-RAGE signaling pathway in diabetic complications, etc. ECM has the closest relationship with VIDD in diabetic mice. The key genes determined by WGCNA and Venn analysis were validated by quantitative real-time polymerase chain reaction (qRT-PCR), which exhibited trends similar to those observed by RNA-seq.ConclusionVIDD can be aggravated in diabetic environment. This study provides new evidence for mRNA changes after mechanical ventilation in diabetic mice, suggesting that ECM and collagen may play an important role in the pathophysiological mechanism and progression of VIDD in diabetic mice, and provides some clues for the research, diagnosis, and treatment of VIDD in diabetic context.

Abstract Chiglitazar is a novel peroxisome proliferator-activated receptor (PPAR) pan-agonist, which passed phase III clinical trials and was newly approved in China for use as an adjunct to diet and exercise in glycemic control in adult patients with Type 2 Diabetes (T2D). To explore the circulating protein signatures associated with the administration of chiglitazar in T2D patients, we conducted a comparative longitudinal study using plasma proteome profiling. Of the 157 T2D patients included in the study, we administered chiglitazar to a specific group, while the controls were given either placebo or sitagliptin. The plasma proteomes were profiled at baseline and 12 and 24 weeks post-treatment using data-independent acquisition mass spectrometry (DIA-MS). Our study indicated that 13 proteins were associated with chiglitazar treatment in T2D patients, including 10 up-regulated proteins (SHBG, TF, APOA2, APOD, GSN, MBL2, CFD, PGLYRP2, A2M, and APOA1) and 3 down-regulated proteins (PRG4, FETUB, and C2) after treatment, which were implicated in the regulation of insulin sensitivity, lipid metabolism, and inflammation response. Our study provides insight into the response of chiglitazar treatment from a proteome perspective and demonstrates the multi-faceted effects of chiglitazar in T2D patients, which will help the clinical application of chiglitazar and further study of its action mechanism.

Abstract Chronic risk factors for pseudoaneurysm (PSA) or penetrating aortic ulcer (PAU) have not been fully clarified. This study aims to evaluate the association of aortic calcification with PSA or PAU of different etiologies. Totally 77 pseudoaneurysms, 80 PAU, and 160 healthy controls (HCs) were retrospectively included, of which 30 were infected, 34 were immunological, and 93 were atherosclerotic etiologies. The aortic calcification status, position of aortic tears/ulcers, and risk factors for disease or acute aortic syndrome (AAS) were identified. Atherosclerotic patients aged more than 65 and infective patients aged more than 60 had significantly higher calcification scores. The immunological group had a lower level of calcification in the infrarenal aorta. For patients of infective or atherosclerotic etiology, 60% (18/30) and 60.22% (56/93) of the tears/ulcers occurred at the aortic parts with the highest level of calcification. Patients with longitudinal calcification exceeding 1/3 of the aortic arch had an increased risk of acquiring diseases (OR = 13.231). The presence of longitudinal calcification of the descending aorta or cross-sectional calcification of the infrarenal aorta increased the risks of acquiring diseases (OR = 8.484 and 8.804). After adjusting for age, longitudinal calcification of the descending aorta exceeding 1/3 length was found to be associated with AAS (OR = 4.662). Tears/ulcers of pseudoaneurysm and PAU were both generally found at the part of the aorta with most calcification. Distinct aorta calcification characteristics were observed for lesions of different etiologies. Longitudinal thoracic and cross-sectional infrarenal abdominal aortic calcification increased the risk of acquiring diseases, and descending aortic calcification was associated with symptomatic patients.

Abstract Indocyanine green (ICG) fluorescence imaging-guided lymphadenectomy has been demonstrated to be effective in increasing the number of lymph nodes (LNs) retrieved in laparoscopic gastrectomy for gastric cancer (GC). Previously, we reported the primary outcomes and short-term secondary outcomes of a phase 3, open-label, randomized clinical trial (NCT03050879) investigating the use of ICG for image-guided lymphadenectomy in patients with potentially resectable GC. Patients were randomly (1:1 ratio) assigned to either the ICG or non-ICG group. The primary outcome was the number of LNs retrieved and has been reported. Here, we report the primary outcome and long-term secondary outcomes including three-year overall survival (OS), three-year disease-free survival (DFS), and recurrence patterns. The per-protocol analysis set population is used for all analyses (258 patients, ICG [n = 129] vs. non-ICG group [n = 129]). The mean total LNs retrieved in the ICG group significantly exceeds that in the non-ICG group (50.5 ± 15.9 vs 42.0 ± 10.3, P

Abstract Introduction Renal artery stenosis (RAS) is a significant reason for secondary hypertension. Impaired renal function and subsequent cardiopulmonary dysfunction could also occur. Patients of non-atherosclerotic RAS has a relatively young age and long life expectancy. Revascularization with percutaneous transluminal angioplasty (PTA) is a viable treatment option. However, restenosis is unavoidable which limits its use. Drug-coated balloon (DCB) has been proven to be effective in restenosis prevention in femoropopliteal arterial diseases and in patients with renal artery stenosis. And PTA for Renal artery fibromuscular dysplasia is safe and clinically successful. Therefore, we could speculate that DCB might have potential efficacy in non-atherosclerotic RAS treatment. Methods and analysis This will be a randomized multi-center-controlled trial. Eighty-four eligible participants will be assigned randomly in a 1:1 ratio to the control group (plain old balloon, POB) and the experimental group (DCB). Subjects in the former group will receive balloon dilatation alone, and in the latter group will undergo the DCB angioplasty. The DCB used in this study will be a paclitaxel-coated balloon (Orchid, Acotec Scientific Holdings Limited, Beijing, China). Follow-up visits will be scheduled 1, 3, 6, 9, and 12 months after the intervention. Primary outcomes will include controlled blood pressure and primary patency in the 9-month follow-up. Secondary outcomes will include technical success rate, complication rate, and bail-out stenting rate. Trial registration ClinicalTrials.gov (number NCT 05858190). Protocol version V.4 (3 May 2023).

Introduction: CircRNAs are closely related to many human diseases; however, their role in acne remains unclear. This study aimed to determine the role of hsa_circ_0102678 in regulating inflammation of acne. Methods: First, microarray analysis was performed to study the expression of circRNAs in acne. Subsequently, RNase R digestion assay and fluorescence in situ hybridization assay were utilized to confirm the characteristics of hsa_circ_0102678. Finally, qRT-PCR, Western blotting analysis, immunoprecipitation, luciferase reporter assay, circRNA probe pull-down assay, biotin-labeled miRNA pull-down assay, RNA immunoprecipitation assay, and m6A dot blot assay were utilized to reveal the functional roles of hsa_circ_0102678 on inflammation induced by C. acnes biofilm in human primary keratinocytes. Results: Our investigations showed that the expression of hsa_circ_0102678 was significantly decreased in acne tissues, and hsa_circ_0102678 was a type of circRNAs, which was mainly localized in the cytoplasm of primary human keratinocytes. Moreover, hsa_circ_0102678 remarkably affected the expression of IL-8, IL-6, and TNF-α, which induced by C. acnes biofilm. Importantly, mechanistic studies indicated that the YTHDC1 could bind directly to hsa_circ_0102678 and promote the export of N6-methyladenosine-modified hsa_circ_0102678 to the cytoplasm. Besides, hsa_circ_0102678 could bind to miR-146a and sponge miR-146a to promote the expression of IRAK1 and TRAF6. Conclusion: Our findings revealed a previously unknown process by which hsa_circ_0102678 promoted keratinocyte inflammation induced by C. acnes biofilm via regulating miR-146a/TRAF6 and IRAK1 axis.

Abstract Multi‐terminal flexible DC power grid plays an important role in large‐scale new energy integration, which usually requires the installation of multi‐terminal DC circuit breaker (MTCB) at the intersection of multiple DC lines. At present, the research on multi‐terminal DC circuit breaker is mostly limited to theoretical simulation calculation, and there are few experimental studies and engineering applications. In this paper, a four‐terminal DC circuit breaker based on commutating path multiplexing is proposed, which combines with the compact natural commutation scheme of hybrid gap, greatly reducing the cost and volume of the circuit breaker. The commutation characteristics of the four‐terminal hybrid DC circuit breaker equivalent prototype at 10‐kV voltage level were tested. On this basis, the equivalent prototype of the circuit breaker test results shows that under 10‐kV voltage level, the four‐terminal circuit breaker topology can achieve breaking of 11 kA in 2.8 ms by the natural commutation method.

IntroductionThis study emphasizes the importance of agricultural efficiency for food security and income generation, especially among smallholder rice farmers in southern China. Limited access to essential agricultural services hinders productivity in this region. The study highlights the significant potential of agricultural socialized services (ASS) in improving the technical efficiency of smallholder rice production.MethodsTo analyze the impact of ASS on technical efficiency in rice production, we focused on tillage, transplanting, crop protection, and harvest operations. We employed stochastic frontier analysis and collected data from smallholder farmers in Hunan, Jiangxi, and Zhejiang provinces. By estimating the technical efficiency of rice production, we aimed to assess the relationship between ASS and smallholder farmers’ technical efficiency.Results and discussionThe results of our analysis revealed that ASS significantly enhance the technical efficiency of rice production among smallholder farmers by supporting agricultural practices such as transplanting, crop protection, and harvest operations. However, we found that the impact of ASS on tillage operations was not statistically significant. Participation in ASS enhances smallholders’ access to modern production techniques, resources, and knowledge, leading to improved technical efficiency. These services also empower smallholder rice producers to adopt sustainable farming practices, access credit, financing, and market information, and promote collective action and cooperation, ultimately influencing technical efficiency.ConclusionThis study emphasizes the potential of ASS in improving the technical efficiency of smallholder rice production in southern China. Policymakers and agricultural organizations can use these insights to design interventions that promote efficient practices, enhance productivity, support livelihoods, and ensure food security in the region.

Background: The treatment of acne vulgaris is often challenging due to the antibiotic resistance frequently observed in Cutibacterium acnes (C.acnes), a prevalent bacterium linked to this condition. Objective: The objective of this research was to examine the impact of curcumin photodynamic therapy (PDT) on the survival of C.acnes and activity of biofilms produced by this microorganism. Methods: Following the Clinical and Laboratory Standards Institute (CLSI) guidelines, we assessed the drug sensitivity of 25 clinical C.acnes strains to five antibiotics (erythromycin, clindamycin, tetracycline, doxycycline, minocycline) and curcumin by implementing the broth microdilution technique. In addition, we established C.acnes biofilms in a laboratory setting and subjected them to curcumin-PDT(curcumin combined with blue light of 180 J/cm2). Afterwards, we evaluated their viability using the XTT assay and observed them using confocal laser scanning microscopy. Results: The result revealed varying resistance rates among the tested antibiotics and curcumin, with erythromycin, clindamycin, tetracycline, doxycycline, minocycline, and curcumin exhibiting resistance rates of 72 %, 44 %, 36 %, 28 %, 0 %, and 100 %, respectively. In the curcumin-PDT inhibition tests against four representative antibiotic-resistant strains, it was found that the survival rate of all strains of planktonic C. acnes was reduced, and the higher the concentration of curcumin, the lower the survival rate. Furthermore, in the biofilm inhibition tests, the vitality and three-dimensional structure of the biofilms were disrupted, and the inhibitory effect became more significant with higher concentrations of curcumin. Conclusion: The results emphasize the possibility of using curcumin PDT as an alternative approach for the treatment of C.acnes, especially in instances of antibiotic-resistant variations and infections related to biofilms.

Abstract Alveolar epithelial barrier is a potential therapeutic target for acute respiratory distress syndrome (ARDS). However, an effective intervention against alveolar epithelial barrier has not been developed. Here, based on single-cell RNA and mRNA sequencing results, death receptor 3 (DR3) and its only known ligand tumor necrosis factor ligand-associated molecule 1A (TL1A) were significantly reduced in epithelium from an ARDS mice and cell models. The apparent reduction in the TL1A/DR3 axis in lungs from septic-ARDS patients was correlated with the severity of the disease. The examination of knockout (KO) and alveolar epithelium conditional KO (CKO) mice showed that TL1A deficiency exacerbated alveolar inflammation and permeability in lipopolysaccharide (LPS)-induced ARDS. Mechanistically, TL1A deficiency decreased glycocalyx syndecan-1 and tight junction-associated zonula occludens 3 by increasing cathepsin E level for strengthening cell-to-cell permeability. Additionally, DR3 deletion aggravated barrier dysfunction and pulmonary edema in LPS-induced ARDS through the above mechanisms based on the analyses of DR3 CKO mice and DR3 overexpression cells. Therefore, the TL1A/DR3 axis has a potential value as a key therapeutic signaling for the protection of alveolar epithelial barrier.

Abstract Background Few studies have investigated the efficacy of comprehensive therapies, including immunotherapy, for gastric cancer with synchronous liver metastases (GCLM). We retrospectively compared the effect of immunochemotherapy and chemotherapy alone as conversion therapies on the oncological outcomes of patients with GCLM. Methods The clinicopathological data of 100 patients with GCLM from February 2017 to October 2021 at our institution were retrospectively analyzed. Patients were divided into immunochemotherapy (n = 33) and chemotherapy‐alone (n = 67) groups. Results Baseline clinicopathological data did not differ significantly between the two groups. The immunochemotherapy group had a higher overall response rate (59.4% vs. 44.0%, p = 0.029) and disease control rate (71.9% vs. 49.2%, p = 0.036) than the chemotherapy group. The immunochemotherapy group showed better tumor regression in the gastric mass, metastatic lymph nodes, and liver lesions than the chemotherapy group. Ten (30.3%) patients in the immunochemotherapy group and 13 (19.4%) patients in the chemotherapy group underwent surgery after conversion therapy. However, the difference was not statistically significant. The overall survival (OS) and progression‐free survival (PFS) rates were better in the immunochemotherapy group than in the chemotherapy group. Treatment‐related adverse events occurred in 24 (72.7%) and 47 (70.1%) patients in the immunochemotherapy and chemotherapy groups, respectively. Conclusions As a conversion therapy for GCLM, immunotherapy yielded better primary and metastatic tumor regression and survival benefits, with no increase in adverse events compared to chemotherapy.