Search

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 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 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 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.

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 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.

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 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 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.

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.

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.

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.

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.

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.

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 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).

Soil nutrients are an important component of soil fertility, and having accurate and timely soil nutrients information is conducive to scientifically guided agricultural fertilization and improved crop yields. Traditional soil nutrient measurement methods are accurate but time-consuming and costly. Visible near-infrared (vis-NIR) and mid-infrared (MIR) as techniques of spectroscopy measurements are cheap, fast, and non-destructive, and, after training, have been used separately to predict soil nutrients. They can give complementary information, so using them separately may not be optimal. This study investigated whether the fusion of vis-NIR and MIR spectra would improve the prediction of six soil nutrients: total nitrogen (TN), total phosphorus (TP), total potassium (TK), alkali-hydrolyzable nitrogen (AN), available phosphorus (AP) and available potassium (AK). The sample set was 501 tillage (0 ∼ 20 cm) soil samples from Guizhou Province (China). Three different sensor fusion techniques were compared: (1) direct fusion of spectra (low-level fusion; SF1); (2) fusion of spectral features selected by the least absolute shrinkage and selection operator (LASSO) algorithm (middle-level fusion; SF2); and (3) fusion using the Granger-Ramanathan averaging (GRA) method of the separate vis-NIR and MIR results (high-level fusion; SF3). Prediction models were built using partial least squares regression (PLSR) and support vector machine (SVM), and evaluated using leave-one-out cross-validation (LOOCV), coefficient of determination (R2), and ratio of performance to interquartile (RPIQ), defined as Rcv2 and RPIQCV. All three sensor fusion methods were more accurate than single-sensor methods in predicting TN, TK and AN (0.60 ≤ Rcv2 ≤ 0.92, 1.86 ≤ RPIQCV ≤ 5.08), but were less accurate for TP, AP and AK (Rcv2 ≤ 0.34, RPIQCV ≤ 1.55). Compared to the best prediction using each single sensor model, low-level fusion improved the prediction of TN and AN; middle-level fusion improved the prediction of TN, TP, AN, AP and AK; and high-level fusion improved the prediction of all soil nutrients. Moreover, the SF2-PLSR model provided the best prediction for TN (Rcv2 = 0.83, RPIQCV = 3.18), the SF2-SVM model for AN (Rcv2 = 0.67, RPIQCV = 2.06), and the SF3-PLSR model for TK (Rcv2 = 0.92, RPIQCV = 5.08). The SF2 and SF3 methods are recommended to predict TN and AN, and MIR spectra are recommended to predict TK (Rcv2 = 0.92, RPIQCV = 5.02) since using only a single sensor is cost-effective. The SF2 and SF3 methods improved the prediction accuracy of AP and AK, but the prediction accuracy was still low. This study only covered one area with its set of soil landscapes, and only used well-established modelling methods. The results can motivate research on new spectra techniques and advanced modelling methods, as well as transferability to other soil landscapes.

Although para-aminosalicylic acid (PAS) has been used to treat tuberculosis agent for decades, its mechanisms of resistance are still not thoroughly understood. Previously, sporadic studies showed that certain mutations in the thyX-hsdS.1 region caused PAS resistance in M. tuberculosis, but a comprehensive analysis is lacking. Recently, we found a G–10A mutation in thyX-hsdS.1 in a PAS-resistant clinical isolate, but it did not cause PAS resistance. SNPs in thyX-hsdS.1 in 6550 clinical isolates were analyzed, and 153 SNPs were identified. C–16 T was the most common SNP identified (54.25%, 83/153), followed by C–4T (7.19%, 11/153) and G–9A (6.54%, 10/153). Subsequently, the effects of those SNPs on the promoter activity of thyX were tested, and the results showed that mutations C–1T, G–3A, C–4T, C–4G, G–7A, G–9A, C–16T, G–18C, and C–19G led to increased promoter activity compared with the wild-type sequence, but other mutations did not. Then, thyX and wild-type thyX-hsdS.1, or thyX-hsdS.1 containing specific SNPs, were overexpressed in M. tuberculosis H37Ra. The results showed that mutations resulting in increased promoter activity also caused PAS resistance. Moreover, the results of an electrophoretic mobility shift assay showed that thyX-hsdS.1 containing the C–16T mutation had a higher binding capacity to RNA polymerase than did the wild-type sequence. Taken together, our data demonstrated that among the SNPs identified in thyX-hsdS.1 of M. tuberculosis clinical isolates, only those able to increase the promoter activity of thyX caused PAS resistance and therefore can be considered as molecular markers for PAS resistance.

[C14H23N3S1], monoclinic, P21/c (no. 14), a = 15.1642(8) Å, b = 6.9215(3) Å, c = 15.2182(7) Å, β = 112.675(2)°, V = 1473.83(12) Å3, Z = 4, R gt(F) = 0.0453, wR ref(F 2) = 0.1240, T = 296(2) K.

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.

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 Metal regulatory transcription factor 1 (MTF1) has been reported to be correlated with several human diseases, especially like cancers. Exploring the underlying mechanisms and biological functions of MTF1 could provide novel strategies for clinical diagnosis and therapy of cancers. In this study, we conducted the comprehensive analysis to evaluate the profiles of MTF1 in pan-cancer. For example, TIMER2.0, TNMplot and GEPIA2.0 were employed to analyze the expression values of MTF1 in pan-cancer. The methylation levels of MTF1 were evaluated via UALCAN and DiseaseMeth version 2.0 databases. The mutation profiles of MTF1 in pan-cancers were analyzed using cBioPortal. GEPIA2.0, Kaplan–Meier plotter and cBioPortal were also used to explore the roles of MTF1 in cancer prognosis. We found that high MTF1 expression was related to poor prognosis of liver hepatocellular carcinoma (LIHC) and brain lower grade glioma (LGG). Also, high expression level of MTF1 was associated with good prognosis of kidney renal clear cell carcinoma (KIRC), lung cancer, ovarian cancer and breast cancer. We investigated the genetic alteration and methylation levels of MTF1 between the primary tumor and normal tissues. The relationship between MTF1 expression and several immune cells was analyzed, including T cell CD8 + and dendritic cells (DC). Mechanically, MTF1-interacted molecules might participate in the regulation of metabolism-related pathways, such as peptidyl-serine phosphorylation, negative regulation of cellular amide metabolic process and peptidyl-threonine phosphorylation. Single cell sequencing indicated that MTF1 was associated with angiogenesis, DNA repair and cell invasion. In addition, in vitro experiment indicated knockdown of MTF1 resulted in the suppressed cell proliferation, increased reactive oxygen species (ROS) and promoted cell death in LIHC cells HepG2 and Huh7. Taken together, this pan-cancer analysis of MTF1 has implicated that MTF1 could play an essential role in the progression of various human cancers.

Background: Early-life vitamin D is a potentially modifiable risk factor for the development of eczema, but there is a lack of data on longitudinal associations. Method: We measured 25(OH)D3 levels from neonatal dried blood spots in 223 high-allergy-risk children. Latent class analysis was used to define longitudinal eczema phenotype up to 25 years (4 subclasses). Skin prick tests (SPTs) to 6 allergens and eczema outcomes at 6 time points were used to define eczema/sensitization phenotypes. Associations between 25(OH)D3 and prevalent eczema and eczema phenotypes were assessed using logistic regression models. Results: Median 25(OH)D3 level was 32.5 nmol/L (P25-P75 = 23.1 nmol/L). Each 10 nmol/L increase in neonatal 25(OH)D3 was associated with a 26% reduced odds of early-onset persistent eczema (adjusted multinomial odds ratio (aMOR) = 0.74, 95% CI = 0.56–0.98) and 30% increased odds of early-onset-resolving eczema (aMOR = 1.30, 95% CI = 1.05–1.62) when compared to minimal/no eczema up to 12 years. Similar associations were seen for eczema phenotype up to 25 years. We did not see any strong evidence for the association between neonatal 25(OH)D3 and prevalent eczema or eczema/sensitization phenotype. Conclusions: Higher neonatal 25(OH)D3 levels, a reflection of maternal vitamin D levels in pregnancy, may reduce the risk of early-onset persistent eczema.

Diabetic wound healing is a significant clinical challenge because abnormal immune cells in the wound cause chronic inflammation and impair tissue regeneration. Therefore, regulating the behavior and function of macrophages may be conducive to improving treatment outcomes in diabetic wounds. Herein, sulfated chitosan (26SCS)-containing composite sponges (26SCS-SilMA/Col-330) with well-arranged layers and high porosity were constructed based on collagen and silk fibroin, aiming to induce an appropriate inflammatory response and promote angiogenesis. The results indicated that the ordered topological structure of composite sponges could trigger the pro-inflammatory response of Mφs in the early stage, and rapid release of 26SCS in the early and middle stages (within the concentration range of 1–3 mg/mL) induced a positive inflammatory response; initiated the pro-inflammatory reaction of Mφs within 3 days; shifted M1 Mφs to the M2 phenotype within 3–7 days; and significantly up-regulated the expression of two typical angiogenic growth factors, namely VEGF and PDGF-BB, on day 7, leading to rapid HUVEC migration and angiogenesis. In vivo data also demonstrated that on the 14th day after surgery, the 26SCS-SilMA/Col-330-implanted areas exhibited less inflammation, faster re-epithelialization, more abundant collagen deposition and a greater number of blood vessels in the skin tissue. The composite sponges with higher 26SCS contents (the (5.0) 26SCS-SilMA/Col-330 and the (7.5) 26SCS-SilMA/Col-330) could better orchestrate the phenotype and function of Mφs and facilitate wound healing. These findings highlight that the 26SCS-SilMA/Col-330 sponges developed in this work might have great potential as a novel dressing for the treatment of diabetic wounds.

Abstract Engineered nanosystems offer a promising strategy for macrophage-targeted therapies for various diseases, and their physicochemical parameters including surface-active ligands, size and shape are widely investigated for improving their therapeutic efficacy. However, little is known about the synergistic effect of elasticity and surface-active ligands. Here, two kinds of anti-inflammatory N-acetylcysteine (NAC)-loaded macrophage-targeting apoptotic-cell-inspired phosphatidylserine (PS)-containing nano-liposomes (PSLipos) were constructed, which had similar size and morphology but different Young’s modulus (E) (H, ~ 100 kPa > Emacrophage vs. L, ~ 2 kPa

Abstract During embryo development, DNA methylation is established by DNMT3A/3B and subsequently maintained by DNMT1. While much research has been done in this field, the functional significance of DNA methylation in embryogenesis remains unknown. Here, we establish a system of simultaneous inactivation of multiple endogenous genes in zygotes through screening for base editors that can efficiently introduce a stop codon. Embryos with mutations in Dnmts and/or Tets can be generated in one step with IMGZ. Dnmt-null embryos display gastrulation failure at E7.5. Interestingly, although DNA methylation is absent, gastrulation-related pathways are down-regulated in Dnmt-null embryos. Moreover, DNMT1, DNMT3A, and DNMT3B are critical for gastrulation, and their functions are independent of TET proteins. Hypermethylation can be sustained by either DNMT1 or DNMT3A/3B at some promoters, which are related to the suppression of miRNAs. The introduction of a single mutant allele of six miRNAs and paternal IG-DMR partially restores primitive streak elongation in Dnmt-null embryos. Thus, our results unveil an epigenetic correlation between promoter methylation and suppression of miRNA expression for gastrulation and demonstrate that IMGZ can accelerate deciphering the functions of multiple genes in vivo.

Abstract Objectives Rupture of intracranial aneurysm is very dangerous, often leading to death and disability. In this study, deep learning and radiomics techniques were used to automatically detect and differentiate ruptured and unruptured intracranial aneurysms. Materials and methods 363 ruptured aneurysms and 535 unruptured aneurysms from Hospital 1 were included in the training set. 63 ruptured aneurysms and 190 unruptured aneurysms from Hospital 2 were used for independent external testing. Aneurysm detection, segmentation and morphological features extraction were automatically performed with a 3-dimensional convolutional neural network (CNN). Radiomic features were additionally computed via pyradiomics package. After dimensionality reduction, three classification models including support vector machines (SVM), random forests (RF), and multi-layer perceptron (MLP) were established and evaluated via area under the curve (AUC) of receiver operating characteristics. Delong tests were used for the comparison of different models. Results The 3-dimensional CNN automatically detected, segmented aneurysms and calculated 21 morphological features for each aneurysm. The pyradiomics provided 14 radiomics features. After dimensionality reduction, 13 features were found associated with aneurysm rupture. The AUCs of SVM, RF and MLP on the training dataset and external testing dataset were 0.86, 0.85, 0.90 and 0.85, 0.88, 0.86, respectively, for the discrimination of ruptured and unruptured intracranial aneurysms. Delong tests showed that there was no significant difference among the three models. Conclusions In this study, three classification models were established to distinguish ruptured and unruptured aneurysms accurately. The aneurysms segmentation and morphological measurements were performed automatically, which greatly improved the clinical efficiency. Clinical relevance statement Our fully automatic models could rapidly process the CTA data and evaluate the status of aneurysms in one minute. Graphical Abstract

Dermal fibroblasts (dFBs) defend against deep bacterial skin infections by differentiating into preadipocytes (pAds) that produce the antimicrobial peptide cathelicidin; this differentiation is known as the dermal reactive adipogenesis response. However, the role of dFBs in fungal infection remains unknown. Here, we found that cathelicidin-producing pAds were present in high numbers in skin lesions from patients with cutaneous Candida granulomas. Second, we showed that dermal Candida albicans (C. albicans) infection in mice robustly triggered the dermal reactive adipogenesis response and induced cathelicidin expression, and inhibition of adipogenesis with pharmacological inhibitors of peroxisome proliferator-activated receptor γ (PPARγ) impaired skin resistance to C. albicans. In vitro, C. albicans products induced cathelicidin expression in pAds, and differentiating pAds markedly suppressed the growth of C. albicans by producing cathelicidin. Finally, we showed that C. albicans induced an antimicrobial response in pAds through the FGFR-MEK-ERK pathway. Together, our data reveal a previously unknown role of dFBs in the defense against skin infection caused by C. albicans.

Backgroundvon Willebrand factor (VWF) has been widely recognized as a biomarker for endothelial cell activation in trauma and inflammation. Traumatic brain injury (TBI) is characterized by cerebral vascular injury and subsequent inflammation. The objective of this study was to investigate the correlation between VWF levels and clinical severity, as well as imaging abnormalities, in TBI patients. Additionally, the predictive value of VWF for patient outcomes was assessed.MethodsWe conducted a prospective study to recruit acute TBI patients who were admitted to the emergency department within 24 h. Healthy individuals from the medical examination center were recruited as the control group. This study aimed to compare the accuracy of VWF in discriminating TBI severity and imaging abnormalities with the Glasgow Coma Scale (GCS) and Rotterdam computed tomography (CT) scores. We also analyzed the predictive value of these outcomes using the Glasgow Outcome Scale (GOS) and 6-month mortality.ResultsThe plasma concentration of VWF in TBI patients (84.7 ± 29.7 ng/ml) was significantly higher than in healthy individuals (40 ± 8.8 ng/ml). There was a negative correlation between VWF levels and GCS scores, as well as a positive correlation between VWF levels and Rotterdam CT scores. The area under the curve (AUC) for VWF in discriminating mild TBI was 0.76 (95% CI: 0.64, 0.88), and for predicting negative CT findings, it was 0.82 (95% CI: 0.72, 0.92). Meanwhile, the AUC of VWF in predicting mortality within 6 months was 0.70 (95% CI: 0.56, 0.84), and for a GOS score lower 4, it was 0.78 (95% CI: 0.67, 0.88). Combining VWF with either the GCS or Rotterdam CT score improved the prediction ability compared to using VWF alone.ConclusionVWF levels were significantly elevated in patients with TBI compared with healthy individuals. Furthermore, VWF levels demonstrated a negative correlation with GCS scores and a positive correlation with Rotterdam CT scores. In terms of predicting mortality, VWF alone was not sufficient, but its predictive power was enhanced when combined with either the Rotterdam CT score or GCS. These findings suggest that VWF may serve as a potential biomarker for assessing the severity and prognosis of TBI patients.

High-voltage cascaded energy storage systems have become a major technical direction for the development of large-scale energy storage systems due to the advantages of large unit capacity, high overall efficiency, satisfactory economy, reliable safety, and easy access to grid dispatching. The loss characteristics analysis is the design basis of the water-cooling system of a high-voltage cascaded energy storage system, and its accurate calculation can determine the system’s safe and reliable operation of the system. This paper first introduces the four-quadrant operation principles of a cascaded H-bridge energy storage system, and analyzes the calculation method of the loss of the Integrated Gate-Commutated Thyristor based power module; On this basis, it studies the loss characteristics of the cascaded energy storage system and analyzes the influence of different modulation strategies and third harmonic injection on the loss characteristics of the energy storage system; Finally, this paper has completed the loss test for the engineering prototype module and compared the test results with theoretical calculation results to verify the accuracy of the loss calculation method of the high-voltage cascaded energy storage system.

This article aimed to investigate the feasibility of using imaging spectroscopy (IS) to predict soil organic carbon density (SOCD) either directly or indirectly through soil organic carbon (SOC). Three methods, partial least square regression, support vector machine (SVM), and random forest, were utilized to calibrate the models and map the SOCD. The results showed that direct prediction was better than indirect prediction and the best model SVM had high R2 of 0.94 and 0.93 for calibration and validation, respectively. The measured SOCD was mainly concentrated in the surface soil layer from 0 to 40 cm, and the deeper layer tended to be gentle. The continuous depth variation trend of SOCD in the topsoil (0–40 cm) was relatively close to the measured values, while in the deeper layers (below 40 cm), it was much higher than the measured values. This article also found that the best fitting function of measured SOC stocks over time varied from linear to power and then to logarithmic with increasing depth, indicating less efficient accumulation of SOC in deep soil compared to topsoil, resulting in an overall decrease in SOC accumulation rate across soil depth. The best temporal functions for the predicted values differed from the measured values at each depth, but the changing trends of the three functions were basically consistent. It suggests that IS technology has the potential to quantitatively reveal the process of coastal soil evolution and offers a new insight for the rapid monitoring of soil property changes.

Objective: To observe the anti-anxiety effect of the water extracts of the mixture of Ziziphi Spinosae Semen (SZS) and Poria cocos (PC) with different ratios and to investigate the mechanism. Methods: Sixty-four SD rats were randomly divided into 8 groups, paroxetine group, SZS group, PC group, and the extracts with the different ratios of SZS to PC, which ranged from 1:1, 2:1 to 3:1. The anxiety model was established by chronic restraint and solitary which lasted for 28 days. During this period, the basic morphological features and body mass were observed. After 8 days of this treatment, paroxetine and different extracts were administrated. Elevated plus maze (EPM) and the open field test (OFT) were used to examine potential anxiolytic effects. It was determined by ELISA and quantitative real-time PCR for the total amount of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in serum, hippocampus, and amygdala tissues of rats, and the relative amount of mRNA expression. Results: Compared with the control group, the experimental groups that employed different proportions of SZS and PC could effectively improve the condition of morphological features, body mass, dysphoric behavior and regulate the level of inflammatory factors in serum and tissues (P

AIM: To explore the correlation between the integrity of the macular microstructures and the visual outcomes before and after idiopathic macular epiretinal membrane(IMEM)surgery.METHODS: A total of 43 patients(43 eyes)with IMEM who were treated in our hospital between January 2017 and December 2019 were selected. The best corrected visual acuity(BCVA)of each patient was examined preoperatively and at 3, 6, 9mo after surgery. Moreover, metamorphopsia(M-chart)examination was given, and spectral domain-optical coherence tomography(SD-OCT)was used to measure central foveal thickness(CFT), subfoveal choroidal thickness(SFCT), the thickness of ganglion cells-inner plexiform layer(GC-IPL)and the length of interdigitation zone(IZ)defect.RESULTS: The BCVA and the metamorphopsia were gradually improved at postoperative 3, 6 and 9 mo(all P0.05). The metamorphopsia assessment was positively correlated with the CFT at postoperative 3, 6, and 9mo(P0.05).CONCLUSIONS: The CFT and the length of IZ defect were significantly correlated with the BCVA after IMEM surgery, which can be used as indicators to predict the recovery of visual function after IMEM surgery.

Background: Myogenin is well known as a crucial transcription factor in skeletal muscle development, yet its other biological functions remain unexplored. Previous research showed that myogenin suppresses apoptosis induced by angiotensin II in human induced pluripotent stem cell-derived cardiomyocytes, and offered a new perspective on myogenin’s role in cardioprotection. However, the detailed mechanism of this cardioprotection, especially under oxidative stress, is still unclear. Methods: In this study, hydrogen peroxide (H2O2) was used to generate reactive oxygen species in myogenin-overexpressing cardiomyocytes. The apoptosis was examined by flow cytometry. Transcriptome sequencing (RNA-seq) was performed to identify genes regulated by myogenin. Western blotting was used to detect the protein level of DUSP13 and the phosphorylation level of p38 mitogen-activated protein kinase (MAPK). The dual-luciferase reporter assay and ChIP assay were used to confirm the binding of myogenin to the promoter region of DUSP13. DUSP13 overexpression and knockdown assays were performed to study its anti-apoptotic role. Results: Flow cytometry analysis of apoptosis showed that overexpressing myogenin for 24 and 48 hours decreased the apoptotic ratio by 47.9% and 63.5%, respectively, compared with untreated controls. Transcriptome sequencing performed on cardiomyocytes that expressed myogenin for different amounts of time (6, 12, 24, and 48 hours) identified DUSP13 as being up-regulated by myogenin. Western blotting showed that overexpression of myogenin increased the expression of DUSP13 and decreased the phosphorylation level of p38 MAPK. A dual-luciferase reporter assay proved that myogenin bound directly to the promoter region of DUSP13 and led to strong relative luciferase activity. Direct expression of DUSP13A and DUSP13B significantly reduced the rates of apoptosis and necrosis in cells treated with H2O2. Knockdown of DUSP13B significantly increased the rate of apoptosis in cells treated with H2O2. Conclusions: The present findings suggest that myogenin might attenuate apoptosis induced by reactive oxygen species by up-regulating DUSP13 and inactivating the p38 MAPK pathway.

BackgroundCurrently, the available evidence regarding the relationship between the lipid profile and Helicobacter pylori (H. pylori) infection is limited and conflicting. There is also a dearth of studies that have explored the possibility of sex-specific differences in the association between H. pylori infection and triglyceride levels.MethodsWe conducted a cross-sectional study involving 1,146 participants utilizing data from the National Health and Nutrition Examination Survey (NHANES) 1999-2000 conducted in the United States. A logistic regression model was employed to evaluate the association between H. pylori seropositivity and triglyceride levels. Subgroup analyses stratified by sex were conducted to explore sex-specific differences in this association.ResultsSerum triglyceride levels were significantly higher in H. pylori-seropositive participants than in H. pylori-seronegative participants. In the logistic regression analysis, there was a positive correlation between H. pylori seropositivity and triglyceride levels (OR=1.231; 95% CI, 1.016-1.491; P=0.033). In the subgroup analysis, the adjusted association between serum triglycerides and H. pylori seropositivity was significant in females (OR=1.732; 95% CI, 1.113-2.696; P=0.015) but not in males (OR=1.091; 95% CI, 0.698-1.705; P=0.704).ConclusionThe association between high triglyceride levels and H. pylori infection is specific to the female population.

Background: Previous studies have indicated that serum sex hormone-binding globulin (SHBG) levels increase with age; however, the causes remain unknown. The present study aimed to clarify whether the increase in SHBG levels is attributable to aging-related increases in SHBG synthesis. Methods: We examined and evaluated the association of serum SHBG levels with synthesis-related factors in men aged 18–80 years. Additionally, we examined the serum and liver levels of SHBG, hepatic nuclear factor 4α (HNF-4α), and peroxisome proliferator-activated receptor γ (PPAR-γ) in young, middle-aged, and old Sprague–Dawley rats. Results: The study included 209 men in the young group (median age, 33 ± 10 years), 174 men in the middle-aged group (median age, 53 ± 8 years), and 98 men in the elderly group (median age, 71 ± 8 years). Serum SHBG levels increased with age (P

Introduction: Zhixue Zhentong capsules (ZXZTCs) are a Tibetan medicine preparation solely composed of Lamiophlomis rotata (Benth.) Kudo. L. rotata is the only species of the genus Laniophlomis (family Lamiaceae) that has medicinal constituents derived from the grass or root and rhizome. L. rotata is one of the most extensively used folk medicines by Tibetan, Mongolian, Naxi, and other ethnic groups in China and has been listed as a first-class endangered Tibetan medicine. The biological effects of the plant include hemostasis, analgesia, and the removal of blood stasis and swelling.Purpose: This study aimed to profile the overall metabolites of ZXZTCs and those entering the blood. Moreover, the contents of six metabolites were measured and the hemostatic, analgesic, and anti-inflammatory effects of ZXZTCs were explored.Methods: Ultra-performance liquid chromatography–tandem quadrupole time-of-flight high-resolution mass spectrometry (UPLC-Q-TOF-MS) was employed for qualitative analysis of the metabolites of ZXZTCs and those entering the blood. Six metabolites of ZXZTCs were quantitatively determined via high-performance liquid chromatography The hemostatic, analgesic, and anti-inflammatory effects of ZXZTCs were evaluated in various animal models.Results: A total of 36 metabolites of ZXZTCs were identified, including 13 iridoid glycosides, 9 flavonoids, 9 phenylethanol glycosides, 4 phenylpropanoids, and 1 other metabolite. Overall, 11 metabolites of ZXZTCs entered the blood of normal rats. Quantitative analysis of the six main metabolites, shanzhiside methyl ester, chlorogenic acid, 8-O-acetyl shanzhiside methyl ester, forsythin B, luteoloside, and verbascoside, was extensively performed. ZXZTCs exerted hemostatic effects by reducing platelet aggregation and thrombosis and shortening bleeding time. Additionally, ZXZTCs clearly had an analgesic effect, as observed through the prolongation of the latency of writhing, reduction in writhing, and increase in the pain threshold of experimental rats. Furthermore, significant anti-inflammatory effects of ZXZTCs were observed, including a reduction in capillary permeability, the inhibition of foot swelling, and a reduction in the proliferation of granulation tissue.Conclusion: Speculative identification of the overall metabolites of ZXZTCs and those entering the blood can provide a foundation for determining its biologically active constituents. The established method is simple and reproducible and can help improve the quality control level of ZXZTCs as a medicinal product. Evaluating the hemostatic, analgesic, and anti-inflammatory activities of ZXZTCs can help reveal its mechanism.

Fumigation of soil using chloropicrin has been proven to significantly affect soil nutrient cycling, but the mechanism by which soil potassium conversion and plant uptake is promoted remains unclear. In this study, we conducted a fumigation experiment to investigate the effects of chloropicrin soil fumigation on the conversion of soil potassium post-fumigation (days 7–70), and its mechanisms, tomatos were planted in fumigated and non-fumigated soils to enable further comparisons. Results showed that the content of rapidly available potassium and available potassium decreased by 16–24% and 17–23% at day 28 respectively, when tomato was planted in chloropicrin-fumigated soils compared to the non-fumigated soils. The potassium content of tomato planted in fumigated soil was significantly higher than that planted in non-fumigated soil (30.3 vs. 21.9 mg g−1 dry weight). Chloropicrin fumigation resulted in a significant change in the soil bacterial and fungal community structures, and trigged a long-term (at least 70-day) decrease in microbial diversity. Network analysis showed that chloropicrin soil fumigation changed microbial co-occurrence patterns by decreasing bacterial total links, nodes, and average degree, and increasing fungal total links, nodes, and average degree. Chloropicrin fumigation caused significant changes in the relative abundance of Bacillus species, which are involved in potassium dissolution. Structural equation model (SEM) suggested that fumigation with chloropicrin enhanced the contribution of soil potassium to tomato growth and reduced the contribution of bacterial communities. Together, the results of our study help in understanding the crop yield enhancement mechanism of soil fumigation.

IntroductionVaricose veins are a common chronic disease that creates a significant economic burden on the healthcare system. Current treatment options, including pharmacological treatments, are not always effective, and there is a need for more targeted therapies. A Mendelian randomization (MR) method uses genetic variants as instrumental variables to estimate the causal effect of an exposure on an outcome, and it has been successful in identifying therapeutic targets in other diseases. However, few studies have used MR to explore potential protein drug targets for varicose veins.MethodsTo identify potential drug targets for varicose veins of lower extremities, we undertook a comprehensive screen of plasma protein with a two-sample MR method. We used recently reported cis-variants as genetic instruments of 2,004 plasma proteins, then applied MR to a recent meta-analysis of genome-wide association study on varicose veins (22,037 cases and 437,665 controls). Furthermore, pleiotropy detection, reverse causality testing, colocalization analysis, and external replication were utilized to strengthen the causal effects of prioritized proteins. Phenome-wide MR (PheW-MR) of the prioritized proteins for the risk of 525 diseases was conducted to screen potential side effects.ResultsWe identified eight plasma proteins that are significantly associated with the risk of varicose veins after Bonferroni correction (P

Abstract Background Personalized therapy has been at the forefront of cancer care, making cancer treatment more effective. Since cancer patients respond individually to drug therapy, predicting the sensitivity of each patient to specific drugs is very helpful to apply therapeutic agents. Traditional methods focus on node (molecular) information but ignore relevant interactions among different nodes, which has very limited application in complex situations, such as cancer drug responses in real clinical practice. Results Treatment evaluation with Quantified Network (TreeQNet) is a webserver which could predict sensitivity to drugs for patients through the innovative use of proteomic and phosphoproteomic network from tumor tissues. Conclusion TreeQNet service: http://bioinfo.ustc.edu.cn/ . TreeQNet source code: https://github.com/Really00/treeqnet-web-front/ .

Abstract Electro‐optic electric field sensors based on LiNbO3 are widely used for the measurement of electric fields or transient voltages. However, the working bias of the sensor is influenced by the temperature due to the thermo‐optic effect of LiNbO3. An athermal electro‐optic electric field sensor was demonstrated by coating a thin layer of TiO2 film which has a negative thermo‐optic coefficient, on the common‐path interferometer based sensor to compensate LiNbO3's positive thermo‐optic coefficient. Both calculation and experimental studies were conducted. The experimental results reasonably agree well with the calculated values, and the results show the sensor coated with a 640 nm thick TiO2 film has a much smaller temperature dependence of 0.011°/°C compared to the initial value of 0.1°/°C.

Negative emotion classification refers to the automatic classification of negative emotion of texts in social networks. Most existing methods are based on deep learning models, facing challenges such as complex structures and too many hyperparameters. To meet these challenges, in this paper, we propose a method for negative emotion classification utilizing a Robustly Optimized BERT Pretraining Approach (RoBERTa) and p-norm Broad Learning (p-BL). Specifically, there are mainly three contributions in this paper. Firstly, we fine-tune the RoBERTa to adapt it to the task of negative emotion classification. Then, we employ the fine-tuned RoBERTa to extract features of original texts and generate sentence vectors. Secondly, we adopt p-BL to construct a classifier and then predict negative emotions of texts using the classifier. Compared with deep learning models, p-BL has advantages such as a simple structure that is only 3-layer and fewer parameters to be trained. Moreover, it can suppress the adverse effects of more outliers and noise in data by flexibly changing the value of p. Thirdly, we conduct extensive experiments on the public datasets, and the experimental results show that our proposed method outperforms the baseline methods on the tested datasets.

Aim: This study aimed to investigate the effects and safety of metfo rmin in patients with concurrent diabetes mellitus (DM) and chronic obstructive pulmonary disease (COPD). Methods: PubMed, Embase, Web of Science, the China National Knowledge, and Cochrane Database were searched to find studies that examined th e effects and safety of metformin in patients with concurrent DM and COPD. We conducted a meta-analysis with a risk ratio (RR) and assessed the quality of included studies and pooled evidence. Results: Eight studies were involved. Metformin was associated with lower risk of COPD-related hospitalizations (RR: 0.72, 95% CI: 0.53–0.98; I2= 89%) and all-cause mortality (RR: 0.60, 95% CI: 0.36–1.01, I2= 69%) in patients with concurrent DM and COPD, but did not increase the risk of hyperlactatemia (RR: 1.14, 95% CI: 0.92–1.41, I2 = 8%). Conclusions: Metformin use is associated with lower risk of COPD-related hospitalizations and risk of all-cause mortality without increasing the risk of hyperlactatemia. Considerations should be given to conduct more high-quality randomized trials involving larger samples.