[Postoperative effect analysis of different surgical techniques used in facial nerve reconstruction].

Objective:To investigate the factors and efficacy of different surgical techniques used in facial nerve（FN） reconstruction. Methods:A retrospective analysis was conducted on 24 patients who underwent facial nerve reconstruction surgery in our department from January 2016 to January 2021. The duration of total facial nerve paralysis was less than 18 months. The study included 5 surgical techniques, including 6 cases of FN anastomosis（Group A）, 5 cases of FN grafting（sural nerve or great auricular nerve）（Group B）, 5 cases of side-to-end facial-hypoglossal nerve anastomosis（Group C）, 4 cases of side-to-end FN grafting（sural nerve or great auricular nerve） hypoglossal nerve anastomosis（Group D）, and 4 cases of dual nerve reanimation（Group E）. The postoperative follow-up period was ≥1 year. Results:The HB-Ⅲ level of FN function at 1 year after surgery was 83.3%（5/6） in group A, 60.0%（3/5） in group B, 40.0%（2/5） in group C, 25.0%（1/4） in group D, and 50.0%（2/4） in group E. In patients without multiple FN repair, the incidence of synkinesis was 15.0%（3/20）, while no cases of synkinesis were observed in patients with dual nerve reanimation. The patients who underwent hypoglossal-facial side-to-end anastomosis showed no hypoglossal nerve dysfunction. Conclusion:Different FN repair techniques result in varying postoperative FN function recovery, as personalized repair should be managed. Among the various techniques, FN end-to-end anastomosis after FN transposition is recommended as to reduce the number of anastomotic stoma, while hypoglossal-facial side-to-end anastomosis is advocated as to prevent postoperative hypoglossal nerve dysfunction. Additionally, dual nerve repair can effectively improve smile symmetry and reduce synkinesis, which enhances patients' quality.

Effect of Chemical Composition on the Thermoplastic Formability and Nanoindentation of Ti-Based Bulk Metallic Glasses.

A series of Ti41Zr25Be34-xNix (x = 4, 6, 8, 10 at.%) and Ti41Zr25Be34-xCux (x = 4, 6, 8 at.%) bulk metallic glasses were investigated to examine the influence of Ni and Cu content on the viscosity, thermoplastic formability, and nanoindentation of Ti-based bulk metallic glasses. The results demonstrate that Ti41Zr25Be30Ni4 and Ti41Zr25Be26Cu8 amorphous alloys have superior thermoplastic formability among the Ti41Zr25Be34-xNix and Ti41Zr25Be34-xCux amorphous alloys due to their low viscosity in the supercooled liquid region and wider supercooled liquid region. The hardness and modulus exhibit obvious variations with increasing Ni and Cu content in Ti-based bulk metallic glasses, which can be attributed to alterations in atomic density. Optimal amounts of Ni and Cu in Ti-based bulk metallic glasses enhance thermoplastic formability and mechanical properties. The influence of Ni and Cu content on the hardness of Ti-based bulk metallic glasses is discussed from the perspective of the mean atomic distance.

Chimeric mutations in grapevine ENHANCED DISEASE RESISTANCE1 improve resistance to powdery mildew without growth penalty.

Grapevine (Vitis vinifera L.) incurs severequality degradation and yield loss from powdery mildew, a major fungal disease caused by Erysiphe necator. ENHANCED DISEASE RESISTANCE1 (EDR1), a Raf-like mitogen-activated protein kinase kinase kinase (MAPKKK), negatively regulates defense responses against powdery mildew in Arabidopsis (Arabidopsis thaliana). However, little is known about the role of the putatively orthologous EDR1 gene in grapevine. In this study, we obtained grapevine VviEDR1-edited lines using CRISPR/Cas9. Plantlets containing homozygous and bi-allelic indels in VviEDR1 developed leaf lesions shortly after transplanting into the soil and died at the seedling stage. Transgenic plants expressing wild-type VviEDR1 and mutant Vviedr1 alleles as chimera (designated as VviEDR1-chi) developed normally and displayed enhanced resistance to powdery mildew. Interestingly, VviEDR1-chi plants maintained a spatiotemporally distinctive pattern of VviEDR1 mutagenesis: while almost no mutations were detected from terminal buds, ensuring normal function of the apical meristem, mutations occurred in young leaves and increased as leaves matured, resulting in resistance to powdery mildew. Further analysis showed that the resistance observed in VviEDR1-chi plants was associated with callose deposition, increased production of salicylic acid (SA) and ethylene (ET), H2O2 production and accumulation, and host cell death. Surprisingly, no growth penalty was observed with VviEDR1-chi plants. Hence, this study demonstrated a role of VviEDR1 in the negative regulation of resistance to powdery mildew in grapevine and provided an avenue for engineering powdery mildew resistance in grapevine.

Novel metabolic biomarker for early detection and diagnosis to the patients with gastric cardia adenocarcinoma.

BACKGROUND: Gastric cardia adenocarcinoma (GCA) is classified as Siewert type II adenocarcinoma at the esophagogastric junction in Western countries. The majority of GCA patients do not exhibit early warning symptoms, leading to over 90% of diagnoses at an advanced stage, resulting in a grim prognosis, with less than a 20% 5-year survival rate. METHOD: Metabolic features of 276 GCA and 588 healthy controls were characterized through a widely-targeted metabolomics by UPLC-MS/MS analysis. This study encompasses a joint pathway analysis utilizing identified metabolites, survival analysis in both early and advanced stages, as well as high and negative and low expression of HER2 immunohistochemistry staining. Machine learning techniques and Cox regression models were employed to construct a diagnostic panel. RESULTS: A total of 25 differential metabolites were consistently identified in both discovery and validation sets based on criteria of p < 0.05, (VIP) ≥ 1, and FC ≥ 2 or FC ≤ 0.5. Early-stage GCA patients exhibited a more favorable prognosis compared to those in advanced stages. HER2 overexpression was associated with a more positive outcome compared to the negative and low expression groups. Metabolite panel demonstrated a robust diagnostic performance with AUC of 0.869 in discovery set and 0.900 in validation set. CONCLUSIONS: A total of 25 common and stable differential metabolites may hold promise as liquid non-invasive indicators for GCA diagnosis. HER2 may function as a tumor suppressor gene in GCA, as its overexpression is associated with improved survival. The downregulation of bile acid metabolism in GCA may offer valuable theoretical insights and innovative approaches for precision-targeted treatments in GCA patients.

Study on mechanism of removal of sudden Tetracycline by compound modified biological sand filtration process.

The removal of tetracycline from the sewage plant effluents through advanced treatment methods is key to controlling tetracycline levels in the water environment. In this study, modified quartz sands (QS) were used in a biological sand filter to remove tetracycline. The modified QS, with different surface characteristics, were prepared using glass etching technology combined with subsequent chemical modification methods, including hydroxylation treatment, metal ion modification, and amino modification. The adsorption efficiency of hydroxylated QS was higher than that of metal ion modified and amino modified QS, with adsorption efficiencies of 20.4331 mg/kg, 12.8736 mg/kg, and 10.1737 mg/kg, respectively. Results indicated that QS primarily reduce tetracycline through adsorption. Adsorption on ordinary QS fit the pseudo-first-order kinetic model, while adsorption on other modified QS and biofilm-coated QS fit the pseudo-second-order kinetics model. Biodegradation was identified as another mechanism for tetracycline reduction, which fit the zero-order kinetic model. Pseudomonas alcaligenes and unclassified Pseudomonas accounted for 96.6% of the total tetracycline-degrading bacteria. This study elucidates the effectiveness and mechanisms of five types of QS in treating tetracycline from sewage plant effluents. It provides a novel method for tetracycline reduction in real-world wastewater scenarios.

Modulation of starch synthesis in Arabidopsis via phytochrome B-mediated light signal transduction.

Starch is a major storage carbohydrate in plants and is critical in crop yield and quality. Starch synthesis is intricately regulated by internal metabolic processes and external environmental cues; however, the precise molecular mechanisms governing this process remain largely unknown. In this study, we revealed that high red to far-red (high R:FR) light significantly induces the synthesis of leaf starch and the expression of synthesis-related genes, whereas low R:FR light suppress these processes. Arabidopsis phytochrome B (phyB), the primary R and FR photoreceptor, was identified as a critical positive regulator in this process. Downstream of phyB, basic leucine zipper transcription factor ELONGATED HYPOCOTYL5 (HY5) was found to enhance starch synthesis, whereas the basic helix-loop-helix transcription factors PHYTOCHROME INTERACTING FACTORs (PIF3, PIF4, and PIF5) inhibit starch synthesis in Arabidopsis leaves. Notably, HY5 and PIFs directly compete for binding to a shared G-box cis-element in the promoter region of genes encoding starch synthases GBSS, SS3, and SS4, which leads to antagonistic regulation of their expression and, consequently, starch synthesis. Our findings highlight the vital role of phyB in enhancing starch synthesis by stabilizing HY5 and facilitating PIFs degradation under high R:FR light conditions. Conversely, under low R:FR light, PIFs predominantly inhibit starch synthesis. This study provides insight into the physiological and molecular functions of phyB and its downstream transcription factors HY5 and PIFs in starch synthesis regulation, shedding light on the regulatory mechanism by which plants synchronize dynamic light signals with metabolic cues to module starch synthesis.

Inhaled nanoparticles for treating idiopathic pulmonary fibrosis by inhibiting honeycomb cyst and alveoli interstitium remodeling.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with high mortality. The Food and Drug Administration-approved drugs, nintedanib and pirfenidone, could delay progressive fibrosis by inhibiting the overactivation of fibroblast, however, there was no significant improvement in patient survival due to low levels of drug accumulation and remodeling of honeycomb cyst and interstitium surrounding the alveoli. Herein, we constructed a dual drug (verteporfin and pirfenidone)-loaded nanoparticle (Lip@VP) with the function of inhibiting airway epithelium fluidization and fibroblast overactivation to prevent honeycomb cyst and interstitium remodeling. Specifically, Lip@VP extensively accumulated in lung tissues via atomized inhalation. Released verteporfin inhibited the fluidization of airway epithelium and the formation of honeycomb cyst, and pirfenidone inhibited fibroblast overactivation and reduced cytokine secretion that promoted the fluidization of airway epithelium. Our results indicated that Lip@VP successfully rescued lung function through inhibiting honeycomb cyst and interstitium remodeling. This study provided a promising strategy to improve the therapeutic efficacy for IPF.

Alternative splicing patterns of hnrnp genes in gill tissues of rainbow trout (Oncorhynchus mykiss) during salinity changes.

Alternative splicing (AS) plays an important role in various physiological processes in eukaryotes, such as the stress response. However, patterns of AS events remain largely unexplored during salinity acclimation in fishes. In this study, we conducted AS analysis using RNA-seq datasets to explore splicing patterns in the gill tissues of rainbow trout exposed to altered salinity environments, ranging from 0 ‰ (T0) to 30 ‰ (T30). The results revealed 1441, 351, 483, 1051 and 1049 differentially alternatively spliced (DAS) events in 5 pairwise comparisons, including T6 vs. T0, T12 vs. T0, T18 vs. T0, T24 vs. T0, and T30 vs. T0, respectively. These DAS events were derived from 1290, 328, 444, 963 and 948 genes. Enrichment analysis indicated that these DAS genes were related to RNA splicing and processing. Among these, 14 DAS genes were identified as members of the large heterogeneous nuclear RNP (hnRNP) gene family. Alternative 3' splice site (A3SS), exon skipping (SE) and intron retention (RI) events resulted in the fragmentation or even loss of the functional RNA recognition motif (RRM) domains in hnrnpa0, hnrnp1a, hnrnp1b and hnrnpc genes. The incomplete RRM domains would hinder the interactions between hnRNP genes and pre-mRNAs. It would in turn influence the splicing patterns and mRNA stability of downstream target genes in response to salinity changes. The study provides insights into salinity acclimation in gill tissues of rainbow trout and serves as a significant reference on the osmoregulation mechanisms at post-transcription regulation levels in fish.

An Autologous Macrophage-Based Phenotypic Transformation-Collagen Degradation System Treating Advanced Liver Fibrosis.

In advanced liver fibrosis (LF), macrophages maintain the inflammatory environment in the liver and accelerate LF deterioration by secreting proinflammatory cytokines. However, there is still no effective strategy to regulate macrophages because of the difficulty and complexity of macrophage inflammatory phenotypic modulation and the insufficient therapeutic efficacy caused by the extracellular matrix (ECM) barrier. Here, AC73 and siUSP1 dual drug-loaded lipid nanoparticle is designed to carry milk fat globule epidermal growth factor 8 (MFG-E8) (named MUA/Y) to effectively inhibit macrophage proinflammatory signals and degrade the ECM barrier. MFG-E8 is released in response to the high reactive oxygen species (ROS) environment in LF, transforming macrophages from a proinflammatory (M1) to an anti-inflammatory (M2) phenotype and inducing macrophages to phagocytose collagen. Collagen ablation increases AC73 and siUSP1 accumulation in hepatic stellate cells (HSCs) and inhibits HSCs overactivation. Interestingly, complete resolution of liver inflammation, significant collagen degradation, and HSCs deactivation are observed in methionine choline deficiency (MCD) and CCl4 models after tail vein injection of MUA/Y. Overall, this work reveals a macrophage-focused regulatory treatment strategy to eliminate LF progression at the source, providing a new perspective for the clinical treatment of advanced LF.

Highly efficient MoS2/MXene aerogel for interfacial solar steam generation and wastewater treatment.

Interfacial solar steam generation using aerogels holds great promise for seawater desalination and wastewater treatment. However, to achieve aerogels with both durable, high-efficiency evaporation performance and excellent salt resistance remains challenging. Here, a molybdenum disulphide (MoS2) and MXene composite aerogel with vertical pore channels is reported, which has outstanding advantages in mechanical properties, water transportation, photothermal conversion, and recycling stability. Benefiting from the plasmon resonance effect of MXene and the excellent photothermal conversion performance of MoS2, the aerogel exhibits excellent light absorption (96.58 %). The aerogel is resistant to deformation and able to rebound after water absorption, because of the support of an ordered vertical structure. Moreover, combined with the low water evaporation enthalpy, low thermal conductivity, and super hydrophilicity, the aerogel achieves an efficient and stable evaporation rate of about 2.75 kg m-2h-1 under one sun and exhibits excellent self-cleaning ability. Notably, the evaporator achieves removal rates of 99.9 % for heavy metal ions and 100 % for organic dyes, which has great potential in applications including seawater desalination and wastewater purification.

Quality assurance in a phase III, multicenter, randomized trial of POstmastectomy radioThErapy in Node posiTive breast cancer with or without Internal mAmmary nodaL irradiation (POTENTIAL): a planning benchmark case.

PURPOSE: To report the planning benchmark case results of the POTENTIAL trial-a multicenter, randomized, phase 3 trial-to evaluate the value of internal mammary nodal (IMN) irradiation for patients with high-risk breast cancer. METHODS: All participating institutions were provided the outlines of one benchmark case, and they generated radiation therapy plans per protocol. The plans were evaluated by a quality assurance team, after which the institutions resubmitted their revised plans. The information on beams arrangement, skin flash, inhomogeneity corrections, and protocol compliance was assessed in the first and final submission. RESULTS: The plans from 26 institutions were analyzed. Some major deviations were found in the first submission. The protocol compliance rates of dose coverage for the planning target volume of chest wall, supraclavicular fossa plus axilla, and IMN region (PTVim) were all significantly improved in the final submission, which were 96.2% vs. 69.2%, 100% vs. 76.9%, and 88.4% vs. 53.8%, respectively. For OARs, the compliance rates of heart Dmean, left anterior descending coronary artery V40Gy, ipsilateral lung V5Gy, and stomach V5Gy were significantly improved. In the first and final submission, the mean values of PTVim V100% were 79.9% vs. 92.7%; the mean values of heart Dmean were 11.5 Gy vs. 9.7 Gy for hypofractionated radiation therapy and 11.5 Gy vs. 11.0 Gy for conventional fractionated radiation therapy, respectively. CONCLUSION: The major deviations were corrected and protocol compliance was significantly improved after revision, which highlighted the importance of planning benchmark case to guarantee the planning quality for multicenter trials.

Enhancing stability of liposomes using high molecular weight chitosan to promote antioxidative stress effects and lipid-lowering activity of encapsulated lutein in vivo and in vitro.

Lutein is an antioxidant with multiple beneficial functions. However, its therapeutic potential is hampered by its low water solubility and bioavailability. The goal of this study is to compare the stability of lutein-loaded liposomes (Lu-lip) and low (LC)/high molecular weight (HC) chitosan-coated Lu-lip, along with their antioxidant capacity using H2O2-induced HepG2 cells and their lipid-lowering activity using high-fat diet mice. Both LC and HC reduced the lutein degradation rate by 17.5 % and 26.72 % in a challenging environment at pH 6 and T = 4 °C. Compared to LC, the HC coating improved the size- and zeta-potential-stability of Lu-lip at 5 < pH < 7, with the best performance at pH 6. The HC coating prolonged the lutein release profile, increased the cellular uptake of Lu-lip, and reduced the reactive oxygen species (ROS) levels and the H2O2-induced necrotic cell ratios by increasing the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Animal experiments have shown that oral administration of LC and HC coated Lu-lip can significantly reduce body weight levels, total triglycerides (TG), total cholesterol (TC), and non-high-density lipoprotein (n-HDL-C) in high-fat diet mice while significantly increasing the levels of CAT, SOD and GSH-Px in the liver of mice. LC and HC coated Lu-lip can reduce fat accumulation in the liver and epididymal adipose tissue.

Structure transformation from Sierpinski triangles to chains assisted by gas molecules.

Reversible transformations between fractals and periodic structures are of fundamental importance for understanding the formation mechanism of fractals. Currently, it is still a challenge to controllably achieve such a transformation. We investigate the effect of CO and CO2 molecules on Sierpinski triangles (STs) assembled from Fe atoms and 4,4″-dicyano-1,1':3',1″-terphenyl (C3PC) molecules on Au surfaces. Using scanning tunneling microscopy, we discover that the gas molecules induce a transition from STs into 1D chains. Based on density functional theory modeling, we propose that the atomistic mechanism involves the transformation of a stable 3-fold coordination Fe(C3PC)3 motif to Fe(C3PC)4 with an axially bonded CO molecule. CO2 causes the structural transformation through a molecular catassembly process.

Association Between Sleep Duration and Stroke in Different Status of Metabolic Syndrome: A Cross-Sectional Study in Shanghai Adult Residents.

Purpose: This study aimed to investigate the relationship between sleep duration (SD) and stroke, and examine the effects of SD on stroke with or without metabolic syndrome (Mets) and its components among the adult residents in Shanghai, China. Participants and Methods: A total of 20,245 participants (51.72% male, mean age 44.66 years) were included from Shanghai Chronic Disease and Risk Factors Surveillance (SCDRFS) in 2017. The weighted logistic regressions were performed to examine the associations between SD and stroke in different status of Mets and its components. Results: The mean SD was 7.51±0.03 h/d. After adjusting for all the potential factors, SD<6 h/d (OR=1.73, 95% CI: 1.35-2.20) or ≥10 h/d (OR=1.66, 95% CI: 1.08-2.57) was significantly positively associated with stoke in the total participants; moreover, in the non-Mets group, only SD<6 h/d (OR=1.77, 95% CI: 1.19, 2.64) significantly increased the risk of stroke; while, in the Mets group, SD<6 h/d (OR=1.80, 95% CI:1.17-2.76) and ≥10 h/d (OR=1.97, 95% CI: 1.00-3.88) both had a positive significantly association with stoke. In addition, the effects of SD<6 h/d on stroke were more pronounced among those with high WC (OR=2.24, 95% CI: 1.40-3.58) and high TG (OR=2.60, 95% CI: 1.86-3.62), and the effects of SD≥10 h/d on stroke were more evident among those with high TG (OR=2.28, 95% CI: 1.02-5.08) and high FBG (OR=2.58, 95% CI: 1.30-5.10). Conclusion: Both short and long SD were significantly positively associated with stroke in the total participants, and the associations were stronger in the Mets group; conversely, in the non-Mets group, only short SD was significantly positively associated with stroke, and no significant association was observed between long SD and stroke. Therefore, more precise sleep measures may be needed to prevent stroke according to the different status of Mets.

Differential outcomes of high-fat diet on age-related rescaling of cochlear frequency place coding.

Auditory frequency coding is place-specific, which depends on the mechanical coupling of the basilar membrane-outer hair cell (OHC)-tectorial membrane network. Prestin-based OHC electromotility improves cochlear frequency selectivity and sensitivity. Cochlear amplification determines the frequency coding wherein discrete sound frequencies find a 'best' place along the cochlear length. Loss of OHC is the leading cause of age-related hearing loss (ARHL) and is the most common cause of sensorineural hearing loss and compromised speech perception. Lipid interaction with Prestin impacts OHC function. It has been established that high-fat diet (HFD) is associated with ARHL. To determine whether genetic background and metabolism preserve cochlear frequency place coding, we examined the effect of HFD in C57BL/6J (B6) and CBA/CaJ (CBA) on ARHL.We found a significant rescuing effect on ARHL in aged B6 HFD cohort. Prestin levels and cell sizes were better maintained in the experimental B6-HFD group. We also found that distortion product otoacoustic emission (DPOAE) group delay measurement was preserved, which suggested stable frequency place coding. In contrast, the response to HFD in the CBA cohort was modest with no appreciable benefit to hearing threshold. Notably, group delay was shortened with age along with the control. In addition, the frequency dependent OHC nonlinear capacitance gradient was most pronounced at young age but decreased with age. Cochlear RNA-seq analysis revealed differential TRPV1 expression and lipid homeostasis. Activation of TRPV1 and downregulation of arachidonic acid led to downregulation of inflammatory response in B6 HFD, which protects the cochlea from ARHL. The genetic background and metabolic state-derived changes in OHC morphology and function collectively contribute to a redefined cochlear frequency place coding and improved age-related pitch perception.

Comparison of Cold-Sprayed Coatings of Copper-Based Composite Deposited on AZ31B Magnesium Alloy and 6061 T6 Aluminum Alloy Substrates.

Copper-coated graphite and copper mixture powders were deposited on AZ31B magnesium alloy and 6061 T6 aluminum alloy substrates under different process parameters by a solid-state cold spray technique. The microstructure of the copper-coated graphite and copper composite coatings was visually examined using photographs taken with an optical microscope and a scanning electron microscope. The surface roughness of the coatings was investigated with a 3D profilometer. The thickness of the coatings was determined through the analysis of the microstructure images, while the adhesion of the coatings was characterized using the scratch test method. The results indicate that the surface roughness of the coatings sprayed on the two different substrates gradually decreases as gas temperature and gas pressure increase. Additionally, the thickness and adhesion of the coatings deposited on the two different substrates both increase with an increase in gas temperature and gas pressure. Comparing the surface roughness, thickness, and adhesion of the coatings deposited on the two different substrates, the surface roughness and adhesion of the coatings on the soft substrate are greater than those of the coatings on the hard substrate, while the thickness of the coatings is not obviously affected by the hardness of the substrate. Furthermore, it is noteworthy that the surface roughness, thickness, and adhesion of the copper-coated graphite and copper composite coatings sprayed on the two different substrates exhibit a distinct linear relationship with particle velocity.

Transcriptomic Profiling of Shoot Apical Meristem Aberrations in the Multi-Main-Stem Mutant (ms) of Brassica napus L.

Rapeseed (Brassica napus L.) is a globally important oilseed crop with various uses, including the consumption of its succulent stems as a seasonal vegetable, but its uniaxial branching habit limits the stem yield. Therefore, developing a multi-stem rapeseed variety has become increasingly crucial. In this study, a natural mutant of the wild type (ZY511, Zhongyou511) with stable inheritance of the multi-stem trait (ms) was obtained, and it showed abnormal shoot apical meristem (SAM) development and an increased main stem number compared to the WT. Histological and scanning electron microscopy analyses revealed multiple SAMs in the ms mutant, whereas only a single SAM was found in the WT. Transcriptome analyses showed significant alterations in the expression of genes involved in cytokinin (CK) biosynthesis and metabolism pathways in the ms mutant. These findings provide insight into the mechanism of multi-main-stem formation in Brassica napus L. and lay a theoretical foundation for breeding multi-main-stem rapeseed vegetable varieties.

Erratum: [Corrigendum] Astragaloside IV alleviates heart failure by regulating SUMO­specific protease 1.

[This corrects the article DOI: 10.3892/etm.2021.10510.].

Molecular quantification for differentiation of fresh and dried Jinqian Baihua She.

Freshly-used crude drugs have unique functions and advantages in TCM practice of treating diseases. Jinlong Capsule is a patent traditional Chinese medicine product effective for treatment of hepatocarcinoma, and fresh Jinqian Baihua She (JBS, the body of juvenile Bungarus multicinctus) is one of its important ingredients. The emergence of counterfeit fresh JBS, often identified as dried JBS with almost identical appearance, poses a difficult problem in the quality control of the product. Herein we report a molecular quantification-based method for differentiation of fresh and dried JBS by determining the copy number of a specific DNA marker in the samples. Using species-specific primers and TaqMan probes, we established a real-time quantitative PCR system for amplification of a fragment in the 658-bp cytochrome oxidase subunit I (COI) region from JBS specimens. The amplicon copy number in the muscle tissues ranged from 1.14 × 107 to 4.83 × 107 copies/mg in fresh JBS samples, as compared with 1.13 × 105-8.91 × 106 copies/mg in dried JBS samples. Based upon Fisher discriminant analysis, we used 1.27 × 107 copies/mg as the cut-off value for differentiating fresh and dried JBS, which was validated in the single-blinded validation test of fresh and dried JBS samples. This qPCR system may provide an efficient means for accurate identification of fresh JBS to improve the quality control of the medicinal product.

Proteolytic rewiring of mitochondria by LONP1 directs cell identity switching of adipocytes.

Mitochondrial proteases are emerging as key regulators of mitochondrial plasticity and acting as both protein quality surveillance and regulatory enzymes by performing highly regulated proteolytic reactions. However, it remains unclear whether the regulated mitochondrial proteolysis is mechanistically linked to cell identity switching. Here we report that cold-responsive mitochondrial proteolysis is a prerequisite for white-to-beige adipocyte cell fate programming during adipocyte thermogenic remodelling. Thermogenic stimulation selectively promotes mitochondrial proteostasis in mature white adipocytes via the mitochondrial protease LONP1. Disruption of LONP1-dependent proteolysis substantially impairs cold- or ß3 adrenergic agonist-induced white-to-beige identity switching of mature adipocytes. Mechanistically, LONP1 selectively degrades succinate dehydrogenase complex iron sulfur subunit B and ensures adequate intracellular succinate levels. This alters the histone methylation status on thermogenic genes and thereby enables adipocyte cell fate programming. Finally, augmented LONP1 expression raises succinate levels and corrects ageing-related impairments in white-to-beige adipocyte conversion and adipocyte thermogenic capacity. Together, these findings reveal that LONP1 links proteolytic surveillance to mitochondrial metabolic rewiring and directs cell identity conversion during adipocyte thermogenic remodelling.