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Abstract Congenital long QT syndrome (LQTS) is a genetic heart disorder, which may lead to life-threatening arrhythmias, especially in children. Here, we reported two children who were initially misdiagnosed with epilepsy and experienced Torsades de Pointes (TdP) cardiac electrical storm (ES). Through whole exome sequencing (WES), we identified two Potassium voltage-gated channel subfamily H member 2 (KCHN2) mutations (c.1841 C > T and c.1838 C > T) respectively in a 6-year-old boy and a 13-year-old girl. Clinical data indicated that the QT interval was significantly prolonged, the T-wave pattern of chest V5-V6 leads and limb leads were inverted. Our study suggests that patients with epilepsy, especially those refractory epilepsy with atypical features, need comprehensive evaluation of cardiovascular function. KCNH2 mutation in pore region, QT interval prolongation and T wave inversion are high risk factors for ES. For LQT2 patients with ES, Nadolol and left cardiac sympathetic denervation are indicated, sometimes with an ICD.

To further enhance the corrosion protection capability of micro-arc oxidation (MAO) coatings on magnesium alloys， the effects of three different pH values of siloxane hydrolysis solutions on the surface structure and corrosion resistance of MAO/siloxane composite coatings on surface of AZ31B magnesium alloy were investigated.MAO coatings were prepared in a silicate electrolyte system using a constant pressure method.Subsequently， the pH values of the siloxane hydrolysis solutions were adjusted， and siloxane coatings were formed on the MAO coatings by immersion.The micro-morphology，porosity，thickness，roughness，hydrophobicity and corrosion resistance of the coatings were studied using scanning electron microscopy (SEM)， Image-J image analysis， thickness gauge， surface roughness tester， contact angle goniometer and electrochemical workstation.Results showed that compared to micro-arc oxidation coatings， the MAO/siloxane coatings significantly repaired the micropores and defects on the surface of the micro-arc oxidation coatings.The MAO/siloxane coatings also imparted hydrophobic properties， effectively preventing or slowing down the penetration of corrosive media and enhancing the corrosion resistance of the coatings.Among the three siloxanes compared， the composite coating prepared from KH-570 hydrolysate with a pH of 6 exhibited the lowest porosity， a water contact angle of (126.5±2.3)°， and a self-corrosion current density of 3.647×10-8 A/cm2， demonstrating the best corrosion resistance.

Abstract The otopetrin (OTOP) proteins were recently characterized as extracellular proton-activated proton channels. Several recent OTOP channel structures demonstrated that the channels form a dimer with each subunit adopting a double-barrel architecture. However, the structural mechanisms underlying some basic functional properties of the OTOP channels remain unresolved, including extracellular pH activation, proton conducting pathway, and rapid desensitization. In this study, we performed structural and functional characterization of the Caenorhabditis elegans OTOP8 (CeOTOP8) and mouse OTOP2 (mOTOP2) and illuminated a set of conformational changes related to the proton-conducting process in OTOP. The structures of CeOTOP8 reveal the conformational change at the N-terminal part of TM12 that renders the channel in a transiently proton-transferring state, elucidating an inter-barrel, Glu/His-bridged proton passage within each subunit. The structures of mOTOP2 reveal the conformational change at the N-terminal part of TM6 that exposes the central glutamate to the extracellular solution for protonation. In addition, the structural comparison between CeOTOP8 and mOTOP2, along with the structure-based mutagenesis, demonstrates that an inter-subunit movement at the OTOP channel dimer interface plays a central role in regulating channel activity. Combining the structural information from both channels, we propose a working model describing the multi-step conformational changes during the proton conducting process.

Abstract This study investigates how dynamic fluctuations in matrix stiffness affect the behavior of cardiac fibroblasts (CFs) within a three-dimensional (3D) hydrogel environment. Using hybrid hydrogels with tunable stiffness, we created an in vitro model to mimic the varying stiffness of the cardiac microenvironment. By manipulating hydrogel stiffness, we examined CF responses, particularly the expression of α-smooth muscle actin (α-SMA), a marker of myofibroblast differentiation. Our findings reveal that increased matrix stiffness promotes the differentiation of CFs into myofibroblasts, while matrix softening reverses this process. Additionally, we identified the role of focal adhesions and integrin β1 in mediating stiffness-induced phenotypic switching. This study provides significant insights into the mechanobiology of cardiac fibrosis and suggests that modulating matrix stiffness could be a potential therapeutic strategy for treating cardiovascular diseases.

Background Fibrinogen (FIB) is often elevated in children with Henoch Schonlein purpuric nephritis (HSPN), but the correlation between FIB and renal lesions has been less studied. Objective To explore the correlation between FIB in children with HSPN and the International Study Group on Pediatric Kidney Disease (ISKDC) pathology grading and micropathological changes in parts of renal units, and to clarify whether FIB can assess the severity of renal injury in children with HSPN. Methods In total, 922 children with HSPN who were hospitalized in the First Affiliated Hospital of Henan University of Chinese Medicine in the pediatric nephrology ward and underwent kidney biopsy at the same time from December 2017 to December 2022 were collected, and the clinical information, FIB and renal pathological information during renal biopsy were summarized, and based on the FIB level, the children were categorized into group A (low) 4.98 g/L. The correlation between FIB and ISKDC pathological grades, glomerular mesangial hyperplasia ratio, the crescentic bodies ratio and the nature of the glomerular lesions from acute to chronic was investigated by Spearman rank correlation analysis, and the prediction of FIB on the micropathological changes of renal units was analyzed by the subject's work characteristic (ROC) curve. Results Among 922 children with HSPN who had undergone renal biopsy, the FIB was (3.48±1.01) g/L. 113 cases in group A had a low FIB rate of 12.26%; 734 cases in group B had a standardized FIB rate of 79.61%; and 75 cases in group C had a high FIB rate of 8.13%. The ISKDC pathology classification was type Ⅱa in 173 cases (18.76%), type Ⅱb in 29 cases (3.15%), 466 cases (50.54%) of type Ⅲa, 232 cases (25.16%) of type Ⅲb, and 22 cases (2.39%) of type Ⅳ and above (including 2 cases of type Ⅳa, 18 cases of type Ⅳb, and 2 cases of type Ⅴ). The results of the Spearman's rank correlation analysis showed that the FIB and the grouping of the FIB of the children with HSPN were positively related to the renal pathology ISKDC grading (rs=0.146, P

The superhydrophobic coating can effectively prevent the intrusion, adhesion and condensation of water-containing corrosive media on the surface. However, the poor mechanical and chemical stability of traditional superhydrophobic coatings significantly limits their application in complex and harsh environments. In this study, a superhydrophobic PDMS-EP@SiO2-GO coating was formed on the surface of Q345 steel sheets by using a composite substrate of graphene oxide(GO) and nano silicon dioxide(SiO2) with polydimethylsiloxane(PDMS) and epoxy resin(EP), combined with spraying technology. The superhydrophobic, self-cleaning, anti-fouling, mechanical wear resistance, chemical corrosion resistance and anti-corrosion properties of the coating were studied. Results showed that the water contact angle of PDMS-EP@SiO2-GO was 166.57°, and the sliding angle was less than 3°. Due to the strengthening effect of GO on the coating substrate, the coating maintained a contact angle of more than 155° for liquids with water temperatures ranging from 20 ℃ to 100 ℃ and a contact angle of more than 160° for acidic/alkaline solutions. The sliding angle was less than 4° under the above conditions. After sandpaper friction(total friction length of 40 m) and 30 cycles of tape-peeling tests, the coating still exhibited good superhydrophobic ability, with the contact angle remaining above 152°. In addition, PDMS-EP@SiO2-GO, with excellent water resistance, demonstrated good anti-fouling and self-cleaning properties. In terms of corrosion protection, the lowest frequency impedance of PDMS-EP@SiO2-GO increased by an order of magnitude, and the charge transfer resistance increased by two orders of magnitude, showing excellent corrosion resistance. PDMS-EP@SiO2-GO addressed the problem of weak mechanical and chemical stability in traditional superhydrophobic coatings and enabled the persistent protection of the metal substrate. The as-prepared superhydrophobic coating, with good practicability, contributes to the safe and reliable service of mechanical equipment throughout its life cycle.

Abstract Excessive scar formation such as hypertrophic scars and keloids, resulting from trauma or surgical procedures, present a widespread concern for causing disfigurement, discomfort, and functional limitations. Macrophages play pivotal roles in maintaining tissue homeostasis, orchestrating tissue development, repair, and immune responses, and its transition of function and phenotype plays a critical role in regulating the balance between inflammation and tissue regeneration, which is central to cutaneous scar formation. Recent evidence suggests the involvement of Sonic Hedgehog (SHH) in the induction of anti-inflammatory M2-like macrophage phenotypes within tumor microenvironments. In our study, we observed increased SHH expression in human hypertrophic scars, prompting an investigation into its influence on macrophage polarization, efferocytosis, and cutaneous scar formation. Our findings reveal that SHH can enhance oxidative phosphorylation (OXPHOS) in macrophages, augment macrophage efferocytosis, and promote M2 polarization, finally contributing to the progression of cutaneous scar formation. Notably, targeting SHH signaling with vismodegib exhibited promising potential in mitigating scar formation by reversing the effects of enhanced OXPHOS and M2 polarization in macrophages. In conclusion, this study underscores the critical roles of macrophage metabolism, particularly OXPHOS, efferocytosis and SHH signaling in cutaneous scar formation. Understanding these mechanisms provides new avenues for potential interventions and scar prevention strategies.

Background The evidence for optical coherence tomography (OCT)–guided percutaneous coronary intervention (PCI) in improving the prognosis of individuals with in‐stent restenosis (ISR) is lacking. Methods and Results This retrospective study enrolled 588 consecutive individuals with drug‐eluting stent ISR undergoing PCI from March 2010 to March 2022. Two hundred seven (35.2%) underwent OCT guidance, and 381 (64.8%) underwent angiography guidance. Clinical outcomes were analyzed using survival curves. The primary clinical endpoint was 2‐year major adverse cardiovascular events (MACEs), a composite of all‐cause death, myocardial infarction, and target‐vessel revascularization. Compared with angiography guidance, OCT guidance demonstrated a higher frequency of drug‐coated balloon use and adjunctive therapeutic modalities, including predilation, postdilation, nonslip element balloons, and noncompliant balloons (P

Transient Receptor Potential Mucolipin 1 (TRPML1) is a lysosomal cation channel whose loss-of-function mutations directly cause the lysosomal storage disorder mucolipidosis type IV (MLIV). TRPML1 can be allosterically regulated by various ligands including natural lipids and small synthetic molecules and the channel undergoes a global movement propagated from ligand-induced local conformational changes upon activation. In this study, we identified a functionally critical residue, Tyr404, at the C-terminus of the S4 helix, whose mutations to tryptophan and alanine yield gain- and loss-of-function channels, respectively. These allosteric mutations mimic the ligand activation or inhibition of the TRPML1 channel without interfering with ligand binding and both mutant channels are susceptible to agonist or antagonist modulation, making them better targets for screening potent TRPML1 activators and inhibitors. We also determined the high-resolution structure of TRPML1 in complex with the PI(4,5)P2 inhibitor, revealing the structural basis underlying this lipid inhibition. In addition, an endogenous phospholipid likely from sphingomyelin is identified in the PI(4,5)P2-bound TRPML1 structure at the same hotspot for agonists and antagonists, providing a plausible structural explanation for the inhibitory effect of sphingomyelin on agonist activation.

BackgroundThe standardized extract of milk thistle seeds, known as silibinin, has been utilized in herbal medicine for over two centuries, with the aim of safeguarding the liver against the deleterious effects of various toxic substances. However, the role of silibinin in Particulate Matter (PM2.5)-induced intrahepatic triglyceride accumulation remains unclear. This study seeks to investigate the impact of silibinin on PM2.5-induced intrahepatic triglyceride accumulation and elucidate potential underlying mechanisms.MethodsA model of intrahepatic triglyceride accumulation was established in male C57BL/6J mice through intratracheal instillation of PM2.5, followed by assessment of liver weight, body weight, liver index, and measurements of intrahepatic triglycerides and cholesterol after treatment with silibinin capsules. Hep G2 cells were exposed to PM2.5 suspension to create an intracellular triglyceride accumulation model, and after treatment with silibinin, cell viability, intracellular triglycerides and cholesterol, fluorescence staining for Nile Red (lipid droplets), and DCFH-DA (Reactive Oxygen Species, ROS), as well as proteomics, real-time PCR, and mitochondrial function assays, were performed to investigate the mechanisms involved in reducing triglycerides.ResultsPM2.5 exposure leads to triglyceride accumulation, increased ROS production, elevated expression of inflammatory factors, decreased expression of antioxidant factors, and increased expression of downstream genes of aryl hydrocarbon receptor. Silibinin can partially or fully reverse these factors, thereby protecting cells and animal livers from PM2.5-induced damage. In vitro studies show that silibinin exerts its protective effects by preserving oxidative phosphorylation of mitochondrial complexes I and II, particularly significantly enhancing the function of mitochondrial complex II. Succinate dehydrogenase (mitochondrial complex II) is a direct target of silibinin, but silibinin A and B exhibit different affinities for different subunits of complex II.ConclusionSilibinin improved the accumulation of intrahepatic triglycerides induced by PM2.5, and this was, at least in part, explained by an enhancement of oxidative phosphorylation in mitochondrial Complexes I and II.

ObjectiveNanotechnology offers many advantages in various fields of cancer therapy. This study describes a new method of self-forming nanoparticles (self-nano) using ferric chloride (FeCl₃) and hydrogen peroxide (H2O2) to form the self-nanoparticles in an in vivo tumor. The treatment effect is evaluated.MethodA solution of 3% FeCl3 (0.5 mL) and 1.8% H2O2 (1.0 mL) was injected into the tumor. At various time points post-injection, tumors were collected, and sections were prepared for electron microscopy to evaluate the size of the self-nano particles. Single-cell RNA sequencing (scRNA-seq) was used to analyze the immune changes and their effect on tumor growth.ResultThe formation of self-nano in vitro was observed and confirmed, with particles averaging 421 nm in size for the FeCl3 + H2O2 solution. Over time points ranging from 1 to 14 days, the formed self-nano remained stable at a regular size of 421 ± 8 nm. The self-nano, primarily consisting of iron, induced ferroptosis under the influence of an external magnetic field, leading to tumor growth control through iron-induced cell death and immune reactions. These self-nanoparticles also showed stronger enrichment of pathways related to CD8+ T effect cells (Teff), T cell activation, and regulation of T cell proliferation.ConclusionThe FeCl3 + H2O2 solution can form Fe₂O₃-based self-nanoparticles within tumors through H2O2-incubated oxidation of FeCl3. The self-nano remains effective for over 14 days, inducing ferroptosis and upregulating immune cells under magnetic field treatment. This method offers a novel approach for cancer treatment that can be combined with other modalities.

Abstract Introduction This study aimed to analyze the risk factors associated with isoniazid-resistant and rifampicin-susceptible tuberculosis (Hr-TB) in adults. Method The clinical data of 1,844 adult inpatients diagnosed with culture-positive pulmonary tuberculosis (PTB) in Nanjing Second Hospital from January 2019 and December 2021 were collected. All culture positive strain from the patient specimens underwent drug susceptibility testing (DST). Among them, 166 patients with Hr-TB were categorized as the Hr-TB group, while the remaining 1,678 patients were classified as having drug-susceptible tuberculosis (DS-TB). Hierarchical logistic regression was employed for multivariate analysis to identify variables associated with Hr-TB. Results: Multivariate logistic regression analysis revealed that individuals with diabetes mellitus (DM) (OR 1.472, 95% CI 1.037–2.088, p = 0.030) and a history of previous tuberculosis treatment (OR 2.913, 95% CI 1.971–4.306, p = 0.000) were at higher risk of developing adult Hr-TB, with this risk being more pronounced in male patients. Within the cohort, 1,640 patients were newly treated, and among them, DM (OR 1.662, 95% CI 1.123–2.461, p = 0.011) was identified as risk factors for Hr-TB. Conclusions: Diabetes mellitus is a risk factor for Hr-TB in adults, and the contribution of diabetes as a risk factor was more pronounced in the newly treatment or male subgroup. And previous TB treatment history is also a risk factor for Hr-TB in adults.

For engineering structures with saline soil as a filling material, such as channel slope, road subgrade, etc., the rich soluble salt in the soil is an important potential factor affecting their safety performance. This study examines the Atterberg limits, shear strength, and compressibility of carbonate saline soil samples with different NaHCO3 contents in Northeast China. The mechanism underlying the influence of salt content on soil macroscopic properties was investigated based on a volumetric flask test, a mercury intrusion porosimetry (MIP) test, and a scanning electron microscopic (SEM) test. The results demonstrated that when NaHCO3 contents were lower than the threshold value of 1.5%, the bound water film adsorbed on the surface of clay particles thickened continuously, and correspondingly, the Atterberg limits and plasticity index increased rapidly as the increase of sodium ion content. Meanwhile, the bonding force between particles was weakened, the dispersion of large aggregates was enhanced, and the soil structure became looser. Macroscopically, the compressibility increased and the shear strength (mainly cohesion) decreased by 28.64%. However, when the NaHCO3 content exceeded the threshold value of 1.5%, the salt gradually approached solubility and filled the pores between particles in the form of crystals, resulting in a decrease in soil porosity. The cementation effect generated by salt crystals increased the bonding force between soil particles, leading to a decrease in plasticity index and an improvement in soil mechanical properties. Moreover, this work provides valuable suggestions and theoretical guidance for the scientific utilization of carbonate saline soil in backfill engineering projects.

Abstract Product assembly involves extensive production data that is characterized by high dimensionality, multiple samples, and data imbalance. The article proposes an edge computing-based framework for monitoring product assembly quality in industrial Internet of Things. Edge computing technology relieves the pressure of aggregating enormous amounts of data to cloud center for processing. To address the problem of data imbalance, we compared five sampling methods: Borderline SMOTE, Random Downsampling, Random Upsampling, SMOTE, and ADASYN. Finally, the quality monitoring model SMOTE-XGBoost is proposed, and the hyperparameters of the model are optimized by using the Grid Search method. The proposed framework and quality control methodology were applied to an assembly line of IGBT modules for the traction system, and the validity of the model was experimentally verified.

Abstract Objective This study aimed to compare the per OPU clinical outcomes for transfer of Day 3 double cleavage-stage embryos (DET) and Day 5 single blastocyst-stage (SBT) in patients with five or fewer good quality embryos on day 3 per occyte pick-up cycle (OPU) in antagonist cycles with consideration of blastocyst formation failure. Methods This was a retrospective, observational cohort study of 2,116 cases of OPU treated with antagonist protocol in the affiliated Chenggong Hospital of Xiamen University between January 2013 and December 2020. DET was performed in 1,811cycles and SBT was performed in 305 cycles. The DET group was matched to the SBT group by propensity score (PS) matching according to multiple maternal baseline covariates. After PS matching, there were 303 ET cycles in each group. The primary outcomes were the cumulative live birth rate (CLBR), cumulative multiple pregnancy rate(CMPR)per OPU and the number of ET to achieve live birth per OPU. Secondary outcomes were the percentage of clinical pregnancy(CPR), live birth rate(LBR), multiple pregnancy rate(MPR). Results Following PS mating, the CLBR was slightly higher (48.8% versus 40.3% ; P = 0.041) and the CMPR was significantly higher in the DET group compared to SBT group(44.2% versus 7.9%, P

The purpose of this paper was to introduce several $ b $-generalized contractive mappings in the framework of cone $ b $-metric spaces over Banach algebras. The obtained contractions generalized and extended the counterparts in metric spaces, cone metric spaces, and $ b $-metric spaces. Moreover, via weakening the completeness of the spaces, we gave some fixed point theorems for asymptotically regular mappings without considering the orbital continuity and $ k $-continuity of the mappings. Those who need a specification is our results do not rely on the continuity of $ b $-metric and the normality of cones. In addition, some nontrivial examples were presented to illustrate the superiority of our fixed point theorems.

Abstract. Background:. Due to the wide variety of morphology, size, and dynamics, selecting an optimal valve size and location poses great difficulty in percutaneous pulmonary valve implantation (PPVI). This study aimed to report our experience with in vitro bench testing using patient-specific three-dimensional (3D)-printed models for planning PPVI with the Venus P-valve. Methods:. Patient-specific 3D soft models were generated using PolyJet printing with a compliant synthetic material in 15 patients scheduled to undergo PPVI between July 2018 and July 2020 in Central China Fuwai Hospital of Zhengzhou University. Results:. 3D model bench testing altered treatment strategy in all patients (100%). One patient was referred for surgery because testing revealed that even the largest Venus P-valve would not anchor properly. In the remaining 14 patients, valve size and/or implantation location was altered to avoid valve migration and/or compression coronary artery. In four patients, it was decided to change the point anchoring because of inverted cone-shaped right ventricular outflow tract (RVOT) (n = 2) or risk of compression coronary artery (n = 2). Concerning sizing, we found that an oversize of 2–5 mm suffices. Anchoring of the valve was dictated by the flaring of the in- and outflow portion in the pulmonary artery. PPVI was successful in all 14 patients (absence of valve migration, no coronary compression, and none-to-mild residual pulmonary regurgitation [PR]). The diameter of the Venus P-valve in the 3D simulation group was significantly smaller than that of the conventional planning group (36 [2] vs. 32 [4], Z = -3.77, P

An experimental study on the recovery of phosphorus resource was carried out for the resource application of sludge residue. The effects of acid species and different leaching conditions on the leaching of phosphorus from sludge residue were systematically analyzed，and the effects of pH and n（Mg）∶n（N）∶n（P） on the synthesis of struvite from the solution containing phosphorus were investigated. The results showed that the leaching rate of phosphorus from sludge residue could reach 96.9% under the conditions of liquid/solid ratio of 20 mL/g，hydrochloric acid concentration of 0.4 mol/L and leaching time of 4 h. Moreover，the crystallization rate of the phosphorus purification solution purified by cation exchange resin could reach 98.1% at pH=10，n（Mg）∶n（N）∶n（P）=1.2∶1.2∶1，and the heavy metal content in the obtained struvite met the standard limit of Organic and Inorganic Compound Fertilizer （GB/T 18877-2020）. In summary，79% of phosphorus in sludge residue could be recovered after phosphorus extraction，purification and crystallization.

Antibody-drug conjugates (ADCs) are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells, thereby attracting considerable attention in precise oncology therapy. Cetuximab (Cet) is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma (cSCC); however, its anti-tumor activity is limited to a single use. Cisplatin (CisPt) shows good curative effects; however, its adverse effects and non-tumor-targeting ability are major drawbacks. In this study, we designed and developed a new ADC based on a new cytotoxic platinum (IV) prodrug (C8Pt(IV)) and Cet. The so-called antibody-platinum (IV) prodrugs conjugates, named Cet-C8Pt(IV), showed excellent tumor targeting in cSCC. Specifically, it accurately delivered C8Pt(IV) into tumor cells to exert the combined anti-tumor effect of Cet and CisPt. Herein, metabolomic analysis showed that Cet-C8Pt(IV) promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells, thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum (IV) prodrugs conjugates.