Biallelic variants in SLC26A2 cause multiple epiphyseal dysplasia-4 by disturbing chondrocyte homeostasis.

BACKGROUND: Multiple epiphyseal dysplasia-4 (MED-4, MIM 226900) is a rare autosomal recessive disease characterized by disproportionate height and early onset osteoarthritis of the lower limbs. MED-4 is caused by homozygous or compound heterozygous pathogenic variants in the SLC26A2 gene. However, the underlying pathogenic mechanisms in chondrocytes remains unknown. This study aimed to identify the pathogenic variants within a MED-4 family and explore the molecular etiology of this condition in human primary chondrocyte cells. METHODS: Clinical data were recorded and peripheral blood samples were collected for analysis. Whole exome sequencing (WES) and bioinformatic analyses were performed to determine causative variants. Wild-type SLC26A2 and corresponding mutant expression plasmids were constructed and transfected into human primary chondrocytes. The expression and subcellular distribution of SLC26A2 protein in chondrocytes were detected by immunoblotting and immunofluorescence. Effects of these variants on chondrocytes viability and apoptosis were measured by Cell Counting Kit-8 (CCK-8) assay. Expression of genes related to cartilage homeostasis was subsequently analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: We identified two compound heterozygous variants c.1020_1022delTGT(p.Val341del) and c.1262 T > C(p.Ile421Thr) in the SLC26A2 gene in the patients. Mutant SLC26A2Val341del and SLC26A2Ile421Thr proteins were distributed in relatively few cells and were observed only within the nucleus. The viability of chondrocytes with the SLC26A2 variant group was similar to the wild-type (WT) group. However, the protein expressions of SLC26A2Val341del and SLC26A2Ile421Thr were decreased compared with SLC26A2WT. Expression levels of matrix metallopeptidase 13 (MMP13), α-1 chain of type X collagen (COL10A1), and Runt-related transcription factor 2 (RUNX2) were significantly decreased in the variant group. However, aggrecan (ACAN) expression was higher in the variant group than the WT group. CONCLUSIONS: Overall, our data demonstrate that the variants p.Val341del and p.Ile421Thr in SLC26A2 cause MED-4 and that these two variants promote chondrocyte proliferation while inhibiting chondrocyte differentiation.

Enhancing osteoporosis treatment using a targeted, sustained-release drug delivery system based on macrocyclic amphiphile.

Osteoporosis, a prevalent systemic bone metabolic disorder, primarily affects postmenopausal women and is characterized by increased bone fragility and a heightened risk of fractures. The efficacy of current osteoporosis treatments is often limited by non-specific drug targeting and undesirable off-target skeletal side effects. To address this challenge, we have developed a novel hydroxyapatite-responsive drug delivery system. This system utilizes a self-assembled p-phosphonatocalix[4]arene tetradodecyl ether (PC4A12C), engineered to specifically target and sustain the release of osteoporosis medication at sites of bone remodeling. Our focus centers on icariin (ICA), a drug known for its potent osteogenic properties and minimal adverse effects. In vitro, ICA-loaded PC4A12C (ICA@PC4A12C) demonstrated enhanced proliferation, differentiation, and mineralization in bone marrow mesenchymal stem cells (BMSCs). In vivo, ICA@PC4A12C exhibited superior efficacy in specifically targeting bone tissue, ensuring a controlled and slow release of icariin directly within the bone environment. In an osteoporosis mouse model, treatment with ICA@PC4A12C showed notable enhancement in osteogenic activity and a significant increase in bone density compared to ICA alone. These results demonstrate the potential of PC4A12C as an effective drug carrier in the development of advanced antiosteoporotic drug delivery systems.

Synergic effects and possible mechanism of emodin and stilbene glycosides on colorectal cancer.

BACKGROUND: Polygonum multiflorum (PM) is a core herb that enhances immunity. It can also detoxify, reduce swelling, and intercept malaria. Its main components, emodin (EMD) and 2,3,5,4'-Tetrahydroxy stilbene-2-O-ß-D-glucoside (stilbene glycoside, TSG), have good anti-cancer potential. PURPOSE: The study aims to investigate synergic effects of EMD and TSG on CRC and its possible mechanism. METHODS: Network pharmacology and bioinformatics were used to identify targets. HPLC was used to analyze the effective ingredients in PM and to determine the content of the main ingredients. HT-29 cells were used for in vitro experiments. Cell Counting Kit-8 (CCK8) and scratch test were used to detect the effects of various chemical components of PM on the proliferation and migration of HT-29 cells, and Western Bolt (WB) test was used to evaluate the effects of EMD and TSG on P53 pathway. In vivo experiments, the effects of EMD and TSG were evaluated by measuring tumor weight and tumor volume in CRC mice model and histological analysis were carried out with HE staining. The expressions of HSP90, P53, COX2, and ROS were detected by quantitative reverse transcription polymerase chain reaction (PCR), and IL-1ß, IL-4, IL-6, IL-10, TGF-ß and IFN-γ were detected by enzyme linked immunosorbent assay (ELISA). WB and Immunohistochemistry (IHC) were used to detect the expression of P53 related proteins. RESULTS: Network pharmacology showed PM closely related to colorectal cancer pathway and the core targets included STAT3 and P53; bioinformatics indicated P53 played an important role in the development and prognosis of CRC; chemical analysis showed identified and quantified gallic acid (GA), cis-TSG, trans-TSG, Emodin glucoside(EMDG), physcion glucoside (PHYG), EMD in PM; EMD induced apoptosis and TSG inhibited migration of HT-29 cells; EMD and TSG could coordinately shrink tumor size of CRC mice, elevate expressions of F4/80, decrease the content of IL-6 and TGF-ß, promote tumor oxidized and reduce expression of P53 and STAT3 in the tumor. CONCLUSIONS: In vitro experiments showed that TSG inhibited cancer cell migration and EMD induced apoptosis. EMD and TSG had synergic effects on CRC, whose possible mechanism might be to regulate the expression of cytokines and inhibit P53 pathway.

[Dental treatment under general anesthesia among pediatric patients in 120 consecutive cases: a retrospective study].

PURPOSE： To investigate the clinical features of children who received treatment under dental general anesthesia (DGA). METHODS: The clinical records of dental patients below 18 years old who were treated under DGA at the Department of Pediatric Dentistry, Affiliated Dental Hospital of Kunming Medical University during June 2017 to November 2019 were obtained, including the baseline information, causes for DGA, anesthesia methods, intubation methods, treatment items, treatment time and follow-up visits. SPSS 26.0 software package was used to analyze the data. RESULTS: A total of 120 patients were included, 58.3% were males, and children aged 3 to 6 years showed the highest demand for DGA (85.0%). Fear of dental treatment, ineffective non-drug behavior management was the main causes for DGA in young children, while the most common causes for children over 6 years old to choose DGA were mental retardation (38.9%) and patients' needs(38.9%). The average number of teeth treated was (15.16±3.42) for each child, and the average time for treating one tooth was 12.26 min. Restoration, root canal treatment and primary teeth pre-forming crown(including anterior preformed resin transparent crown and posterior preformed metal crown) were the main treatment items. At 1-week follow-up visits, 98.3% of children had no discomfort. During 2017 to 2019, there was an increasing tendency in the number of patients who chose DGA in the authors' institute. CONCLUSIONS： The dental issues of children with fear of dental treatment, ineffectiveor non-drug behavior management or mental retardation can be treated under DGA conveniently, safely and efficiently. The acceptance rate of DGA among pediatric patients is on the rise. DGA training programs and related support projects are needed to meet the treatment demands among patients in less developed areas.

Implementing a completely autotrophic nitrogen removal over nitrite process using a novel umbrella basalt fiber carrier.

The completely autotrophic nitrogen removal over nitrite (CANON) process is significantly hindered by prolonged start-up periods and unstable nitrogen removal efficiency. In this study, a novel umbrella basalt fiber (BF) carrier with good biological affinity and adsorption performance was used to initiate the CANON process. The CANON process was initiated on day 64 in a sequencing batch reactor equipped with umbrella BF carriers. During this period, the influent NH4+-N concentration gradually increased from 100 to 200 mg·L-1, and the dissolved oxygen was controlled below 0.8 mg L-1. Consequently, an average ammonia nitrogen removal efficiency (ARE) and total nitrogen removal efficiency (TNRE) of ∼90 and 80% were achieved, respectively. After 130 days, ARE and TNRE remained stable at 92 and 81.1%, respectively. This indicates a reliable method for achieving rapid start-up and stable operation of the CANON process. Moreover, Candidatus Kuenenia and Candidatus Brocadia were identified as dominant anammox genera on the carrier. Nitrosomonas was the predominant genus among ammonia-oxidizing bacteria. Spatial differences were observed in the microbial population of umbrella BF carriers. This arrangement facilitated autotrophic nitrogen removal in a single reactor. This study indicates that the novel umbrella BF carrier is a highly suitable biocarrier for the CANON process.

The role of anti-citrullinated protein antibody in pathogenesis of RA.

Rheumatoid arthritis (RA) is a common autoimmune rheumatic disease that causes chronic synovitis, bone erosion, and joint destruction. The autoantigens in RA include a wide array of posttranslational modified proteins, such as citrullinated proteins catalyzed by peptidyl arginine deiminase4a. Pathogenic anti-citrullinated protein antibodies (ACPAs) directed against a variety of citrullinated epitopes are abundant both in plasma and synovial fluid of RA patients. ACPAs play an important role in the onset and progression of RA. Intensive and extensive studies are being conducted to unveil the mechanisms of RA pathogenesis and evaluate the efficacy of some investigative drugs. In this review, we focus on the formation and pathogenic function of ACPAs.

[Protective effects of 2-methoxyestradiol against hypoxic pulmonary hypertension in neonatal rats]. / 2-ç”²æ°§åŸºé›ŒäºŒé†‡å¯¹æ–°ç”Ÿå¤§é¼ ç¼ºæ°§æ€§è‚ºåŠ¨è„‰é«˜åŽ‹çš„ä¿æŠ¤ä½œç”¨.

OBJECTIVES: To investigate the protective effects of 2-methoxyestradiol (2ME) against hypoxic pulmonary hypertension (HPH) in neonatal rats. METHODS: Ninety-six Wistar neonatal rats were randomly divided into a normoxia group, a hypoxia group, and a hypoxia + 2ME group, with each group further subdivided into 3-day, 7-day, 14-day, and 21-day subgroups, containing eight rats each. The hypoxia and hypoxia + 2ME groups received daily subcutaneous injections of saline and 2ME (240 µg/kg), respectively, while the normoxia group was raised in a normoxic environment with daily saline injections. Right ventricular systolic pressure (RVSP) was measured using the direct pressure method. Pulmonary vascular morphology was assessed using hematoxylin and eosin staining, with metrics including the percentage of medial thickness of small pulmonary arteries relative to the external diameter (MT%) and the cross-sectional area of the media of small pulmonary arteries relative to the total cross-sectional area (MA%). Immunohistochemistry was used to detect the expression levels of hypoxia-inducible factor-1α (HIF-1α) and proliferating cell nuclear antigen (PCNA) proteins, while real-time quantitative PCR was used to to assess HIF-1α and PCNA mRNA levels. RESULTS: Compared to the normoxia group, the hypoxia and hypoxia + 2ME groups showed increased RVSP and upregulated HIF-1α and PCNA protein and mRNA expression levels at 3, 7, 14, and 21 days after hypoxia (P<0.05). Furthermore, at 7, 14, and 21 days after hypoxia, the hypoxia group showed increased MT% and MA% (P<0.05). In comparison to the hypoxia group, the hypoxia + 2ME group exhibited reduced RVSP and downregulated HIF-1α and PCNA protein and mRNA expression levels, along with decreased MT% and MA% at 7, 14, and 21 days after hypoxia (P<0.05). CONCLUSIONS: 2ME may protect against HPH in neonatal rats by inhibiting the expression of HIF-1α and PCNA and reducing pulmonary vascular remodeling. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 757-764.

MaMYBR30, a Novel 1R-MYB, Plays Important Roles in Plant Development and Abiotic Stress Resistance.

The V-myb myeloblastosis viral oncogene homolog (MYB) family participate in various bioprocesses including development and abiotic stress responses. In the present study, we first report a 1R SHAQKYF-class MYB, MaMYBR30, in mulberry. Subcellular localization and sequence analysis indicated MaMYBR30 is located in the nucleus and belongs to a CCA-like subgroup with a conserved SHAQKYF motif. Expression profile analysis showed that MaMYBR30 is expressed in leaves and can be induced by drought and salt stress. The down-regulation of MaMYBR30 using virus-induced gene silence (VIGS) in mulberry and the overexpression of MaMYBR30 in Arabidopsis were induced to explore the function of MaMYBR30. The functional characterization of MaMYBR30 in vivo indicated that MaMYBR30 can positively regulate the resistance of mulberry to drought while negatively regulating the resistance of mulberry to salt stress. In addition, MaMYBR30 also affects flower development and reproductive growth, especially after exposure to salt stress. Weighted gene co-expression network analysis (WGCNA) primarily revealed the possible genes and signal pathways that are regulated by MaMYBR30. Our results also imply that complex molecular mechanisms mediated by MaMYBR30, including crosstalk of ion toxicity, phytohormone signal transduction, flowering development, and epigenetic modification, need to be further explored in the future.

Extracorporeal membrane oxygenation states basilar artery thrombectomy and left posterior cerebral artery stent thrombectomy: A case report.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a new type of extracorporeal respiratory and circulatory assistance device. It can drain venous blood out of the body and inject it into veins or arteries after being oxygenated by an oxygenator (membrane lung) to replace lung and heart functions in a short time. ECMO can provide tissue blood perfusion and gas exchange almost equivalent to cardiac output and extend the effective treatment time window for patients with acute circulatory failure to restore cardiopulmonary function. CASE SUMMARY: We report a case of an 81-year-old woman who underwent whole cerebral angiography, basilar artery thrombectomy and stent thrombectomy in the posterior artery of the left brain after implantation of ECMO. The patient was admitted to the hospital due to myocardial infarction. Considering that the cause of the patient's disturbance of consciousness was unknown and cerebrovascular accident could not be ruled out after the implantation of ECMO, the department of Radioactive Intervention performed cerebral angiography. And the result of the angiography indicated vascular occlusion. After the basilar artery thrombectomy and stent thrombectomy in the posterior artery of the left brain, the patency of the occlusive vessel was achieved. CONCLUSION: Although the patient eventually died of circulatory failure, the result of this case verifies the feasibility of cerebral angiography and thrombectomy in patients with implanted ECMO in the intubated state.

REDD1 knockdown ameliorates endothelial cell senescence through repressing TXNIP-mediated oxidative stress.

Endothelial cell senescence characterized by reactive oxygen species (ROS) accumulation and chronic inflammation is widely recognized as a key contributor to atherosclerosis (AS). Regulated in development and DNA damage response 1 (REDD1), a conserved stress-response protein that regulates ROS production, is involved in the pathogenesis of various age-related diseases. However, the role of REDD1 in endothelial cell senescence is still unclear. Here, we screened REDD1 as a differentially expressed senescence-related gene in the AS progression using bioinformatics methods, and validated the upregulation of REDD1 expression in AS plaques, senescent endothelial cells, and aging aorta by constructing AS mice, D-galactose (DG)-induced senescent endothelial cells and DG-induced accelerated aging mice, respectively. siRNA against REDD1 could improve DG-induced premature senescence of endothelial cells and inhibit ROS accumulation, similar to antioxidant N-Acetylcysteine (NAC) treatment. Meanwhile, NAC reduced the upregulation of REDD1 induced by DG, supporting the positive feedback loop between REDD1 and ROS contributes to endothelial cell senescence. Mechanistically, the regulatory effect of REDD1 on ROS might be related to the TXNIP-REDD1 interaction in DG-induced endothelial cell senescence. Collectively, experiments above provide evidence that REDD1 participates in endothelial cell senescence through repressing TXNIP-mediated oxidative stress, which may be involved in the progression of atherosclerosis.

GB and gH/gL fusion machinery: a promising target for vaccines to prevent Epstein-Barr virus infection.

Epstein‒Barr virus (EBV) is a double-stranded DNA virus belonging to the family Orthoherpesviridae that is associated with the development of various tumors, such as lymphoma, nasopharyngeal carcinoma, and gastric cancer. There are no uniformly effective treatments for human EBV infection, and vaccines and immunotherapies are currently the main research directions. The glycoproteins gB and gH/gL are surface glycoproteins that are common to all herpesviruses, with subtle differences in structure and function between different viruses. The core membrane fusion machinery constituted by EBV gB and gH/gL is an important target of neutralizing antibodies in epithelial EBV infection due to its essential role in the fusion of viral and target cell membranes. In this article, we review the main modes of EBV infection, the structure and function of the core fusion machinery gB and gH/gL, and the development of neutralizing antibodies and prophylactic vaccines based on this target.

Screening of ent-copalyl diphosphate synthase and metabolic engineering to achieve de novo biosynthesis of ent-copalol in Saccharomyces cerevisiae.

The diterpene ent-copalol is an important precursor to the synthesis of andrographolide and is found only in green chiretta (Andrographis paniculata). De novo biosynthesis of ent-copalol has not been reported, because the catalytic activity of ent-copalyl diphosphate synthase (CPS) is very low in microorganisms. In order to achieve the biosynthesis of ent-copalol, Saccharomyces cerevisiae was selected as the chassis strain, because its endogenous mevalonate pathway and dephosphorylases could provide natural promotion for the synthesis of ent-copalol. The strain capable of synthesizing diterpene geranylgeranyl pyrophosphate was constructed by strengthening the mevalonate pathway genes and weakening the competing pathway. Five full-length ApCPSs were screened by transcriptome sequencing of A. paniculata and ApCPS2 had the best activity and produced ent-CPP exclusively. The peak area of ent-copalol was increased after the ApCPS2 saturation mutation and its configuration was determined by NMR and ESI-MS detection. By appropriately optimizing acetyl-CoA supply and fusion-expressing key enzymes, 35.6 mg/L ent-copalol was generated. In this study, de novo biosynthesis and identification of ent-copalol were achieved and the highest titer ever reported. It provides a platform strain for the further pathway analysis of andrographolide and derivatives and provides a reference for the synthesis of other pharmaceutical intermediates.

Comprehensive biochemical analysis and nutritional evaluation of fatty acid and amino acid profiles in eight seahorse species (Hippocampus spp.).

Seahorses are increasingly recognized for their nutritional potential, which underscores the necessity for comprehensive biochemical analyses. This study aims to investigate the fatty acid and amino acid compositions of eight seahorse species, including both genders of Hippocampus trimaculatus, Hippocampus kelloggi, Hippocampus abdominalis, and Hippocampus erectus, to evaluate their nutritional value. We employed Gas Chromatography-Mass Spectrometry (GC-MS) and High-Performance Liquid Chromatography (HPLC) to analyze the fatty acid and amino acid profiles of the seahorse species. GC-MS was used to detect 34 fatty acid methyl esters, while HPLC provided detailed amino acid profiles. GC-MS analysis demonstrated high precision with relative standard deviations (RSDs) generally below 2.53 %, satisfactory repeatability (RSDs from 6.55 % to 8.73 %), and stability (RSDs below 2.82 %). Recovery rates for major fatty acids ranged from 98.73 % to 109.12 %. HPLC analysis showed strong separation of amino acid profiles with theoretical plate numbers exceeding 5000. Precision tests yielded RSDs below 1.23 %, with reproducibility and stability tests showing RSDs below 2.73 % and 2.86 %, respectively. Amino acid recovery rates ranged from 97.58 % to 104.66 %. Nutritional analysis revealed significant variations in fatty acid content among the species. Female H. erectus showed higher levels of hexadecanoic acid and saturated fatty acids, while male H. abdominalis had lower concentrations of n-3 full cis 4,7,10,13,16,19-docosahexaenoic acid (DHA). Total lipid yields varied from 3.2491 % to 12.3175 %, with major fatty acids constituting 17.9717 %-74.6962 % of total lipids. In conclusion, this study provides essential insights into the fatty acid and amino acid composition of seahorses, supporting their potential as valuable dietary supplements. The differences between genders in specific fatty acids suggest a nuanced nutritional profile that could be exploited for targeted dietary applications. Further research is needed to explore the seasonal and environmental variations affecting seahorse biochemical composition.

Determining the Minimal Clinically Important Difference (MCID) and Responsiveness of the Chinese Version of Zurich Chronic Middle Ear Inventory (ZCMEI-21-Chn): A Prospective Multicenter Study.

OBJECTIVES: This study aimed to establish the minimal clinically important difference (MCID) and assess the responsiveness of the Chinese version of Zurich Chronic Middle Ear Inventory (ZCMEI-21-Chn). STUDY DESIGN: Prospective multicenter study. SETTING: Four Chinese tertiary referral centers admitting patients nationwide. PATIENTS: 230 adult patients with chronic otitis media (COM) undergoing tympanoplasty. INTERVENTION: Patients were required to complete the ZCMEI-21-Chn to measure health-related quality of life both preoperatively and postoperatively. An anchor-based method was used to determine the MCID of the derivative cohort by including the Global Rating of Change Questionnaire as an anchor. The generalizability and consistency with functional outcomes of the MCID estimates were externally examined in a validation cohort using a receiver operating characteristic curve analysis. RESULTS: A total of 161 and 69 patients were included in the derivative and validation cohort. The mean preoperative and postoperative ZCMEI-21-Chn total scores were 28.4 (standard deviation [SD] 14.5) and 17.5 (SD 12.6). The mean change in ZCMEI-21-Chn score was 10.9 (SD 14.3, p < 0.001). The MCIDs of the ZCMEI-21-Chn for improvement and deterioration were estimated at 13 (SD 13.0) and -7 (SD 12.9), accordingly. For patients who have reported an improved health-related quality of life, a cutoff value of 15.6 dB HL for elevation of the air-conducted hearing threshold was noticed. However, change of clinical importance judged according to MCID and Japan Otological Society criteria disagreed with each other, notably with a Cohen's kappa ( κ ) of 0.14 ( p = 0.21) in the validation cohort. CONCLUSION: This study is the first to establish the MCID of a COM-specific questionnaire in Chinese. For the COM population undergoing surgical intervention, MCID values of 13 for improvement and -7 for deterioration are recommended. The results were externally validated to be generalizable to nationwide usage, yet distinguishable from the audiological criteria. The availability of the MCID greatly adds to the clinical utility of the ZCMEI-21-Chn by enabling a clinically meaningful interpretation of its score changes.

Navß2 Intracellular Fragments Contribute to Aß1-42-Induced Cognitive Impairment and Synaptic Deficit Through Transcriptional Suppression of BDNF.

A pathological hallmark of Alzheimer's disease (AD) is the region-specific accumulation of the amyloid-beta protein (Aß), which triggers aberrant neuronal excitability, synaptic impairment, and progressive cognitive decline. Previous works have demonstrated that Aß pathology induced aberrant elevation in the levels and excessive enzymatic hydrolysis of voltage-gated sodium channel type 2 beta subunit (Navß2) in the brain of AD models, accompanied by alteration in excitability of hippocampal neurons, synaptic deficits, and subsequently, cognitive dysfunction. However, the mechanism is unclear. In this research, by employing cell models treated with toxic Aß1-42 and AD mice, the possible effects and potential mechanisms induced by Navß2. The results reveal that Aß1-42 induces remarkable increases in Navß2 intracellular domain (Navß2-ICD) and decreases in both BDNF exons and protein levels, as well as phosphorylated tropomyosin-related kinase B (pTrkB) expression in cells and mice, coupled with cognitive impairments, synaptic deficits, and aberrant neuronal excitability. Administration with exogenous Navß2-ICD further enhances these effects induced by Aß1-42, while interfering the generation of Navß2-ICD and/or complementing BDNF neutralize the Navß2-ICD-conducted effects. Luciferase reporter assay verifies that Navß2-ICD regulates BDNF transcription and expression by targeting its promoter. Collectively, our findings partially elucidate that abnormal enzymatic hydrolysis of Navß2 induced by Aß1-42-associated AD pathology leads to intracellular Navß2-ICD overload, which may responsible to abnormal neuronal excitability, synaptic deficit, and cognition dysfunction, through its transcriptional suppression on BDNF. Therefore, this work supplies novel evidences that Navß2 plays crucial roles in the occurrence and progression of cognitive impairment of AD by transcriptional regulatory activity of its cleaved ICD.

[Analysis of genetic variants and molecular pathogenesis in a Chinese pedigree affected with Multiple epiphyseal dysplasia].

OBJECTIVE: To analyze the genetic variant and molecular pathogenesis in a Chinese pedigree affected with Multiple epiphyseal dysplasia (MED). METHODS: A MED pedigree which had presented at the Beijing Jishuitan Hospital Affiliated to Capital Medical University on September 13, 2020 was selected as the study subject. Clinical data of the pedigree were collected. Peripheral blood samples were drawn from pedigree members for the extraction of genomic DNA. Whole exome sequencing (WES) was carried out for the pedigree. Candidate variant was verified by Sanger sequencing. Wild type and mutant SLC26A2 expression plasmids were constructed and transfected into human primary chondrocytes. The effect of the variants on the protein localization and cell proliferation was determined by immunofluorescence and CCK8 assays. RESULTS: WES and Sanger sequencing revealed that the proband has harbored compound heterozygous variants of the SLC26A2 gene, including a paternally derived c.484G>T (p.Val162Leu) missense variant and a maternally derived c.485_486delTG (p.Val162Glyfs*12) frameshifting variant. The SLC26A2WT and its mutant SLC26A2Val162Leu and SLC26A2Val162Glyfs*12 expression plasmids were distributed in the nuclei and cytoplasm of human primary chondrocytes. Compared with SLC26A2WT, the expressions of SLC26A2Val162Leu and SLC26A2Val162Glyfs*12 were decreased, along with reduced proliferation of human primary chondrocytes. CONCLUSION: The c.484G>T and c.485_486delTG compound heterozygous variants of the SLC26A2 gene may affect the proliferation of human primary chondrocytes and underlay the pathogenesis of MED in this pedigree.

Ripening and rot: How ripening processes influence disease susceptibility in fleshy fruits.

Fleshy fruits become more susceptible to pathogen infection when they ripen; for example, changes in cell wall properties related to softening make it easier for pathogens to infect fruits. The need for high-quality fruit has driven extensive research on improving pathogen resistance in important fruit crops such as tomato (Solanum lycopersicum). In this review, we summarize current progress in understanding how changes in fruit properties during ripening affect infection by pathogens. These changes affect physical barriers that limit pathogen entry, such as the fruit epidermis and its cuticle, along with other defenses that limit pathogen growth, such as preformed and induced defense compounds. The plant immune system also protects ripening fruit by recognizing pathogens and initiating defense responses involving reactive oxygen species production, mitogen-activated protein kinase signaling cascades, and jasmonic acid, salicylic acid, ethylene, and abscisic acid signaling. These phytohormones regulate an intricate web of transcription factors (TFs) that activate resistance mechanisms, including the expression of pathogenesis-related genes. In tomato, ripening regulators, such as RIPENING INHIBITOR and NON_RIPENING, not only regulate ripening but also influence fruit defenses against pathogens. Moreover, members of the ETHYLENE RESPONSE FACTOR (ERF) family play pivotal and distinct roles in ripening and defense, with different members being regulated by different phytohormones. We also discuss the interaction of ripening-related and defense-related TFs with the Mediator transcription complex. As the ripening processes in climacteric and non-climacteric fruits share many similarities, these processes have broad applications across fruiting crops. Further research on the individual contributions of ERFs and other TFs will inform efforts to diminish disease susceptibility in ripe fruit, satisfy the growing demand for high-quality fruit and decrease food waste and related economic losses.

When quantum dots meet blue phase liquid crystal elastomers: visualized full-color and mechanically-switchable circularly polarized luminescence.

Polymer-based circularly polarized luminescence (CPL) materials with the advantage of diversified structure, easy fabrication, high thermal stability, and tunable properties have garnered considerable attention. However, adequate and precise tuning over CPL in polymer-based materials remains challenging due to the difficulty in regulating chiral structures. Herein, visualized full-color CPL is achieved by doping red, green, and blue quantum dots (QDs) into reconfigurable blue phase liquid crystal elastomers (BPLCEs). In contrast to the CPL signal observed in cholesteric liquid crystal elastomers (CLCEs), the chiral 3D cubic superstructure of BPLCEs induces an opposite CPL signal. Notably, this effect is entirely independent of photonic bandgaps (PBGs) and results in a high glum value, even without matching between PBGs and the emission bands of QDs. Meanwhile, the lattice structure of the BPLCEs can be reversibly switched via mechanical stretching force, inducing on-off switching of the CPL signals, and these variations can be further fixed using dynamic disulfide bonds in the BPLCEs. Moreover, the smart polymer-based CPL systems using the BPLCEs for anti-counterfeiting and information encryption have been demonstrated, suggesting the great potential of the BPLCEs-based CPL active materials.

Interfacial behaviour of short-chain fluorocarbon surfactants at the n-hexane/water interface: a molecular dynamics study.

The utilization of long-chain fluorocarbon surfactants is restricted due to environmental regulations, prompting a shift in the focus of research towards short-chain fluorocarbon surfactants. The present study employs molecular dynamics techniques to model the behaviour of potassium perfluorobutylsulfonate (PFBS) at the n-hexane/water interface, aiming to investigate the efficacy of short-chain fluorocarbon surfactants in enhancing oil recovery. The findings suggest that ionized PFBS- has the ability to autonomously migrate to the oil/water interface, forming a layered thin film, with the sulfonic acid group being submerged in water, while the fluorocarbon chain is oriented towards the oil phase. This phenomenon aligns with the fundamental concept of surfactants in reducing interfacial tension between oil and water. The spontaneous dispersion process is supported by changes in the number of water molecules surrounding each PFBS- anion, as is well indicated by the number density distribution within the simulation box. Based on the analysis conducted by IGMH (Independent Gradient Model based on Hirshfeld partition), it was determined that sulfonic acid molecules are capable of forming hydrogen bonds with water molecules, whereas the interaction between fluorocarbon chains and the oil phase is predominantly characterized by weak van der Waals interactions.