Establishment of Reference Range for Serum Concentration of Vitamin A and Vitamin E in Southern Sichuan Area of China.

OBJECTIVE: To establish the reference range of serum concentration of vitamin A (VA) and vitamin E (VE) in Southern Sichuan area of China. METHODS: From August 1, 2021, to May 31, 2023, 9482 blood tablets were received for the screening of VA and VE. The information was divided into four different age groups: ≤1 year old, 1< to ≤6 years, 6< to ≤17 years, and 17< to ≤59 years. In each age group, the four seasons were further subdivided into spring, summer, autumn, and winter, as well as male and female genders. The serum concentration of VA and VE was detected by liquid chromatography-tandem mass spectrometry (HPLC-MS), and the reference range was established for verification. RESULTS: The concentration of VA and VE in 9482 cases showed skewed distribution. When comparing between different age groups, the serum concentration of VA and VE was statistically significant (p < 0.05). While comparing different seasons, the serum VA levels in different seasons were significantly different (p < 0.05) except in summer and autumn. There was statistical significance in VE level in different seasons (p < 0.05). And while comparing different genders, there was no statistical significance in VA concentration levels (p > 0.05). The VE concentration levels were statistically significant (p < 0.05). The established reference range was established and verified, and the results were in accordance with the standard. CONCLUSION: The reference range of VA and VE should be set according to different ages, different seasons, and different genders.

Genetic analysis of congenital unilateral renal agenesis in children based on next-generation sequencing.

BACKGROUND: Congenital unilateral renal agenesis (URA) is a kind of rare birth defect during fetal development with varies clinical phenotypes. The pathogenesis and the relationship between gene and phenotype are still unclear. METHODS: Ten URA fetuses were followed up after birth using postnatal renal ultrasound examination to confirm the diagnosis with nine children were URA and one was Renal Ectopy (RE). Trio- WES, CNV- seq were performed with the 10 children and their close relatives. RESULTS: There were 3 heterozygous variants of CHD7, PROKR2 and NRIP1 genes were identified in 3 children, respectively. CHD7 (c.2663T>C, p.M888T) is classified as likely pathogenic (LP), PROKR2 (c.685G>C, p.G229R) and NRIP1 (c.2705T>G, p.F902C) are classified as variants of uncertain significance (VUS). CHD7 (c.2663T>C, p.M888T) and PROKR2 (c.685G>C, p.G229R) as URA-related genes may be associated with idiopathic hypogonadotropic hypogonadism (IHH) or CHARGE syndrome (CS), and 3D-protein structure prediction revealed that the two variants may affect the stability in the CHD7 protein or PROKR2 protein, separately. The RE-related gene NRIP1 (c.2705T>G, p.F902C) may be causative of congenital anomalies of the kidneys and urinary tract (CAKUT). CONCLUSIONS: Identification of these variants can in exploring the etiology of URA or RE and improve the level of genetic counseling. IMPACTS: We performed trio-whole-exome sequencing (trio- WES) and copy number variation sequencing (CNV- seq) in 10 children, including 9 children with Unilateral Renal Agenesis and 1 with Renal Ectopy after birth. The possible pathogenic genes of URA can be screened using prenatal and postnatal diagnosis of URA fetuses and gene detection after birth. Future studies evaluating this association may lead to a better understanding of URA and elucidate exploring the etiology of URA or RE and improve the level of genetic counseling.

Prosthetic Metals: Release, Metabolism and Toxicity.

The development of metallic joint prostheses has been ongoing for more than a century alongside advancements in hip and knee arthroplasty. Among the materials utilized, the Cobalt-Chromium-Molybdenum (Co-Cr-Mo) and Titanium-Aluminum-Vanadium (Ti-Al-V) alloys are predominant in joint prosthesis construction, predominantly due to their commendable biocompatibility, mechanical strength, and corrosion resistance. Nonetheless, over time, the physical wear, electrochemical corrosion, and inflammation induced by these alloys that occur post-implantation can cause the release of various metallic components. The released metals can then flow and metabolize in vivo, subsequently causing potential local or systemic harm. This review first details joint prosthesis development and acknowledges the release of prosthetic metals. Second, we outline the metallic concentration, biodistribution, and elimination pathways of the released prosthetic metals. Lastly, we discuss the possible organ, cellular, critical biomolecules, and significant signaling pathway toxicities and adverse effects that arise from exposure to these metals.

NIR-activated electrospun nanodetonator dressing enhances infected diabetic wound healing with combined photothermal and nitric oxide-based gas therapy.

Diabetic wounds pose a challenge to healing due to increased bacterial susceptibility and poor vascularization. Effective healing requires simultaneous bacterial and biofilm elimination and angiogenesis stimulation. In this study, we incorporated polyaniline (PANI) and S-Nitrosoglutathione (GSNO) into a polyvinyl alcohol, chitosan, and hydroxypropyltrimethyl ammonium chloride chitosan (PVA/CS/HTCC) matrix, creating a versatile wound dressing membrane through electrospinning. The dressing combines the advantages of photothermal antibacterial therapy and nitric oxide gas therapy, exhibiting enduring and effective bactericidal activity and biofilm disruption against methicillin-sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and Escherichia coli. Furthermore, the membrane's PTT effect and NO release exhibit significant synergistic activation, enabling a nanodetonator-like burst release of NO through NIR irradiation to disintegrate biofilms. Importantly, the nanofiber sustained a uniform release of nitric oxide, thereby catalyzing angiogenesis and advancing cellular migration. Ultimately, the employment of this membrane dressing culminated in the efficacious amelioration of diabetic-infected wounds in Sprague-Dawley rats, achieving wound closure within a concise duration of 14 days. Upon applying NIR irradiation to the PVA-CS-HTCC-PANI-GSNO nanofiber membrane, it swiftly eradicates bacteria and biofilm within 5 min, enhancing its inherent antibacterial and anti-biofilm properties through the powerful synergistic action of PTT and NO therapy. It also promotes angiogenesis, exhibits excellent biocompatibility, and is easy to use, highlighting its potential in treating diabetic wounds.

Injectable thermo-responsive Poloxamer hydrogel/methacrylate gelatin microgels stimulates bone regeneration through biomimetic programmed release of SDF-1a and IGF-1.

Injectable hydrogels, offering adaptable drug delivery of growth factors (GFs), hold promise for treating bone defects. To optimize osteogenic efficacy, the release of GFs should mirror the natural bone healing. We developed an injectable thermo-responsive hydrogel/microgels platform for dual GF delivery for bone regeneration. Stromal cell-derived factor-1 alpha (SDF-1a) and the Methacrylate Gelatin (GelMA) microgels which encapsulated insulin-like growth factor-1 (IGF-1) loaded liposomes (Ls) were introduced into Poloxamer 407 (P407) hydrogel matrix. This system achieved the biomimetic release profile of SDF-1a and IGF-1, which covered the early stage from day 1 to 7 and the continuous stage from day 5 to 21, respectively. In vitro study confirmed the enhanced migration, osteogenic biomarker expression, and matrix mineralization of the bone marrow mesenchymal stem cells (BMSCs) co-cultivated with the dual GFs delivering hydrogel/microgels. Transcriptome sequencing revealed that the potential mechanism was associated with mitogen-activated protein kinase (MAPK) signaling activation and its downstream ribosomal protein S6 kinase 2 (RSK2) upregulation. In a critical-sized calvarial defect model in Sprague-Dawley (SD) rats, the injectable hydrogel/microgels system promoted significant bone regeneration. Collectively, our study suggested the current hydrogel/microgels system with the biomimetic release of SDF-1a and IGF-1 efficiently promoted bone regeneration, informing the future development of GF delivery systems intended for bone regeneration therapies.

Metal-Free Cyanation of gem-Difluoroalkenes via Azide-Mediated C-C Double Bond Fragmentation.

Activation and cleavage of C-C double bonds are long-standing challenges in synthetic chemistry. Herein, we report an unprecedented azide-mediated C-C double bond fragmentation of gem-difluoroalkenes under mild and metal-free conditions, enabling the efficient synthesis of structurally diverse aromatic nitriles in moderate to good yields. This protocol is also amenable to the cyanation of gem-dichloro and dibromo alkenes. This reaction features simple operation and good functional group compatibility and can be implemented at a gram scale.

Laparoscopic transabdominal-sacrococcygeal approach for resection of Altman type III sacrococcygeal teratoma in adult women: A case report.

INTRODUCTION: Adult sacrococcygeal teratoma (SCT) is a rare disease that is not easily detected or easily missed, and its treatment is based on surgery, including transabdominal, transsacral, or a combination of both, but there are no clear guidelines for diagnosis and treatment. We share a case of Altman type III SCT in order to provide more reference protocols for the diagnosis and treatment of adult SCT, and more importantly to increase our understanding of different types of SCT cases in adults. PATIENT CONCERNS: Our patient was a 31-year-old adult woman who underwent complete surgical resection of a cystic mature teratoma of the right ovary 8 years ago and is currently 13 months postpartum without menstruation, usually with a feeling of anal bulge, with symptoms such as constipation. DIAGNOSIS: We diagnosed SCT by vaginal ultrasonography, computed tomography and magnetic resonance imaging (MRI); benign tumors were considered in the results of serum tumor markers. INTERVENTIONS: We chose the surgical approach of laparoscopic transabdominal-sacrococcygeal approach to completely remove the patient SCT and coccyx. OUTCOMES: The location of SCT is concealed and the clinical symptoms are not obvious. Vaginal ultrasonography, CT and MRI can not only improve the diagnostic rate of SCT, but also understand the size and mass of SCT, providing an exact basis for clinicians to select the laparoscopic transabdominal-sacrococcygeal approach. CONCLUSION: Our sharing increases the reports of rare cases of teratoma with the same histological findings in different organ tissues of the same patient at different times, whether this occurs incidentally requires more case reports and further basic research; in addition, the laparoscopic transabdominal-sacrococcygeal approach is a safe and effective surgical approach for the treatment of Altman type III SCT in adults; finally, this case reminds us that SCT may not affect pregnancy and pregnancy outcomes and provides a reference for the selection of interventions for SCT with pregnancy.

Evaluation of the aroma and taste contributions of star anise (I. Verum hook. f.) in braised duck leg via flavor omics combined with multivariate statistics.

To promote the rationalized and standardized application of star anise in braised poultry products, the effects of different concentrations of star anise (0 %, 0.1 %, 0.2 %, 0.3 %, and 0.4 %) on the aroma and taste compounds intensities of braised duck legs from the perspective of flavor were evaluated by using flavor omics approach combined with multivariate statistics. The volatile flavor results showed that there were 17 key aroma compounds with odor activity values (OAVs) > 1, including aldehydes, alcohols, ketones, furans, hydrocarbons, and ethers. Most of the aroma compounds related to lipid oxidation were significantly inhibited when the concentration of star anise reached 0.2 %, especially inhibited the concentrations of the unpleasant off-odorants containing hexanal, heptanal, 1-octen-3-ol, and 2-pentyl-furan by 30.27 %, 15.08 %, 30.30 %, and 41.63 %, respectively. And the flavor intensities of these compounds were negatively correlated with the concentration of star anise. Additionally, star anise gave braised duck legs characteristic aroma such as floral and herbal notes. The taste results revealed that the maximum umami value (4.36 g MSG/100 g) of braised duck legs was observed when the concentration of star anise reached 0.2 %. Six flavor markers were obtained via PLS-DA model, and the flavors of braised duck legs with different concentrations of star anise were distinguished. This study provided a vital theoretical basis for the rational application and flavor control of star anise in braised poultry products.

Performance Evaluation of Noninvasive Prenatal Testing in Screening Chromosome Disorders: A Single-Center Observational Study of 15,304 Consecutive Cases in China.

Objective: This study was to evaluate the performance of noninvasive prenatal testing (NIPT) in detecting fetal chromosome disorders in pregnant women. Methods: From October 1st, 2017, to December 31th, 2022, a total of 15,304 plasma cell free DNA-NIPT samples were collected for fetal chromosome disorders screening. The results of NIPT were validated by confirmatory invasive testing or clinical outcome follow-up. Further, NIPT performance between low-risk and high-risk groups, as well as singleton pregnancy and twin pregnancy groups was compared. Besides, analysis of 111 false-positive cases was performed. Results: Totally, NIPT was performed on 15,086 eligible venous blood samples, of which 179 (1.19%) showed positive NIPT results and 68 were further validated to be true positive samples via confirmatory invasive testing or follow-up of clinical outcomes. For common chromosome aneuploidies, sex chromosome abnormalities (SCA) and other chromosomal aneuploidies, the detection sensitivities of NIPT were all 100%, the specificities were 99.87%, 99.70%, and 99.68% and the positive predictive values (PPVs) were 65.45%, 31.82%, and 10.91%, respectively. No statistically significant variance in detection performance was observed among 2987 high-risk and 12,099 low-risk subjects, as well as singleton and twin pregnancy subjects. The concentration of cell-free fetal DNA of 111 false-positive cases ranged from 5.5% to 33.7%, which was higher than the minimum requirement of NIPT. Conclusion: With stringent protocol, NIPT shows high sensitivity and specificity for detecting fetal chromosome disorders in a large-scale clinical service, helping improving overall pregnancy management.

Processed Polygonatum cyrtonema Hua attenuates postpartum depression in rat model by regulating monoamines and hormones.

Background: Polygonatum cyrtonema Hua is a traditional Chinese medicinal food herb which can regulate the liver and Qi, nourish the heart and blood, moisten the lungs and nourish the kidneys with the potential to treat emotional diseases. However, few studies have explored the effects of Polygonatum cyrtonema Hua on postpartum depression. Therefore, we investigated whether processed Polygonatum cyrtonema Hua could improve postpartum depression in rat models by regulating monoamines and hormones. Methods: Female Sprague-Dawley rats were randomized into normal control (0.9%Nacl), Sham operation (0.9%Nacl), postpartum depression model (0.9%Nacl), fluoxetine (2.5 mg/kg Fluoxetine), low, medium and high dose of processed Polygonatum cyrtonema Hua (2.5 g/kg, 5 g/kg, 10 g/kg) groups. Rats in these groups received drug intervention, and then subjected to Open-field test and Forced swimming test. Brain tissues and serum samples were collected and used to quantify levels of monoamines, hypothalamic-pituitary-adrenal axis and serum Estradiol. The status of neuronal cells in hippocampus 1 region was examined through hematoxylin-eosin staining, whereas expression of estrogen receptor α and ß was detected by immunohistochemistry. Results: Rats in the model group showed decreased mobility time, the disorder of neuronal cells in hippocampus 1 area, and decreased concentration of 5-hydroxytryptamine and dopamine in brain tissue, norepinephrine and estradiol in serum as well as estrogen receptor α and ß expression. They also exhibited increased adrenocorticotropic hormone, corticosterone and corticotropin releasing hormone in serum. However, the treatment with processed Polygonatum cyrtonem Hua or fluoxetine reversed the above abnormalities. Conclusion: The H group showed significant improvement in postpartum depression in rats, and processed Polygonatum cyrtonema Hua can be used as a developing drug for the prevention or treatment of depression.

New keratose sponges after the end-Permian extinction provide insights into biotic recoveries.

We challenge the prevailing view that the end-Permian extinction impeded the Triassic evolution of sponges. Here, we report a deep-water community dominated by abundant keratose sponges in the lowest Triassic strata from Southwest China. The sponge fossils occur as dark elliptical imprints in mudstone with distinct oscula on their tops. The structure of preserved fibers suggests closest affinity with the extant Dictyoceratida, an aspiculate demosponge. The exceptional preservation plays a crucial role in retaining their exquisite structures. Sedimentary, taphonomic, pyrite framboid, and trace elemental analyses indicate that the sponges proliferated in an oxygen-poor habitat, demonstrating the high tolerance of sponges to severe conditions. Sponge proliferation is a signal of environmental upheaval but they also stabilized the ecosystem, driving the first phase of biotic recovery after the end-Permian extinction.

Classification and description of the drainage state of manholes in urban drainage systems.

Manholes are important structures in urban storm drainage systems connecting roads and underground drainage networks, and they are also an important part of the research on improving urban resistance to storm flooding. Due to cost and space constraints, most of the existing experimental data on manholes come from scale model experiments obtained by scaling according to Froude's similarity criterion, and there is a lack of validation based on full-size experimental data. This also leads to inconsistencies in the form and parameter values of the manhole flow exchange equations derived from different experiments. To remedy this deficiency, a full-scale urban drainage engineering physics model was developed in this study with the aim of investigating the flow exchange of surface water as it flows through manholes into the sewer system. Experiments were conducted under steady flow conditions and compared with predictions from the existing models. The results show that the predictions of the existing model deviate significantly from the measured values when the flow is between free weir flow and submerged orifice flow. Therefore, we constructed a weighting equation based on weir and orifice flows and found that the weighting coefficients decayed exponentially during the transition from weir to orifice flow.

TEM Investigation on the Dislocation Loops in Zirconium Alloy by Neutron and Kr+ Ion Irradiation Tests.

Neutron irradiation (E ≥ 1 MeV) and 400 keV Kr+ ion irradiation tests were carried out and compared to study the formation and growth mechanism of dislocation loops in zirconium alloys. The results show that, as the irradiation reached 1.9 × 1025 n/m2 and 1.0 × 1020 Kr+/m2, a large number of -type dislocation loops and a small amount of large-sized -type dislocations hundreds of nanometers or even micrometers in size are observed in both samples. EDS results confirmed that the concentrations of Nb and Fe in the -type dislocation loops are higher than that in the matrix. With the increases of the dislocation loop size, part of the loop structure will decompose into the twisted, small-sized dislocation lines. Between two of the small-sized dislocation lines, a cubic structure was observed.

Converting peracetic acid activation by Fe3O4 from nonradical to radical pathway via the incorporation of L-cysteine.

Recently, peracetic acid (PAA) based Fenton (-like) processes have received much attention in water treatment. However, these processes are limited by the sluggish Fe(III)/Fe(II) redox circulation efficiency. In this study, L-cysteine (L-Cys), an environmentally friendly electron donor, was applied to enhance the Fe3O4/PAA process for the sulfamethoxazole (SMX) abatement. Surprisingly, the L-Cys incorporation was found not only to enhance the SMX degradation rate constant by 3.2 times but also to switch the Fe(IV) dominated nonradical pathway into the •OH dominated radical pathway. Experiment and theoretical calculation result elucidated -NH2, -SH, and -COOH of L-Cys can increase Fe solubilization by binding to the Fe sites of Fe3O4, while -SH of L-Cys can promote the reduction of bounded/dissolved Fe(III). Similar SMX conversion pathways driven by the Fe3O4/PAA process with or without L-Cys were revealed. Excessive L-Cys or PAA, high pH and the coexisting HCO3-/H2PO4- exhibit inhibitory effects on SMX degradation, while Cl- and humic acid barely affect the SMX removal. This work advances the knowledge of the enhanced mechanism insights of L-Cys toward heterogeneous Fenton (-like) processes and provides experimental data for the efficient treatment of sulfonamide antibiotics in the water treatment.

Identification of key phenolic compounds for alleviating gouty inflammation in edible chrysanthemums based on spectrum-effect relationship analyses.

Edible chrysanthemum is a common food resource for tea and functional foods with potential benefits for human health. Studies have indicated that chrysanthemum has the potential effect on inflammatory diseases, while the effects on gouty inflammation remain underexplored. The present study aimed to investigate the anti-gout activity and characterize the active ingredients of chrysanthemums by using metabolite profiles, in vitro experiments, and spectrum-effect analysis. Results showed that 'Boju' (BJ), 'Hangbaiju' (HBJ), and 'Huaiju' (HJ) exhibited regulatory effects on monosodium urate (MSU)-induced inflammation. At the dose of 50 µg/mL, the inhibitory rates of IL-1ß secretion were 24.53 %, 14.36 %, and 38.10 %, respectively. A total of 32 phenolic compounds were identified or preliminarily assigned in UPLC-Q/TOF-MS analysis. And seven phenolics related to anti-gout activity were identified by spectrum-effect relationships. According to ADME (absorption, distribution, metabolism, excretion) evaluation and experiments verification, luteolin, acacetin-7-O-glucoside, and apigenin-7-O-glucoside were critical constituents potentially associated with the reduction of inflammation in gout. Additionally, these phenolics might be suitable as quality control indicators. This study clarified the anti-gout properties of different cultivars of chrysanthemums and active compounds, providing a theoretical basis for its scientific utilization in functional foods.

[Correlation analysis between body mass index and clinical characteristics of rheumatoid arthritis].

OBJECTIVE: To analyze the clinical features of overweight and obese rheumatoid arthritis (RA)patients, and the relationship between body mass index (BMI) and disease characteristics. METHODS: The demographic data, extra-articular manifestations, comorbidities, and disease activity of RA patients admitted to the Rheumatology and Immunology Department of Peking University Third Hospital from January 2015 to December 2020 were collected, and the above characteristics of overweight and obese RA patients were retrospectively analyzed. According to the WHO, BMI≥30 kg/m2 referred to obese individuals, 25≤BMI < 30 kg/m2 referred to overweight individuals, 18.5≤BMI < 25 kg/m2 referred to normal individuals, BMI < 18.5 kg/m2 referred to reduced body mass individuals. t test was used for the quantitative data in accordance with normal distribution. Wilcoxon rank sum test was used for the quantitative data of non-normal distribution. The qualitative data were analyzed by chi square test. But while 1≤theoretical frequency < 5, Chi square test of corrected four grid table was used. And Fisher exact probability method was used when theoretical frequency < 1. Analyzing whether overweight or obesity was associated with comorbidities using Logistic regression adjusted confounding factors. RESULTS: A total of 481 RA patients were included in this study, with an average BMI value of (23.28±3.75) kg/m2.Of the patients, 31 cases (6.5%) were with BMI < 18.5 kg/m2, 309 cases (64.2%) with 18.5≤ BMI < 25 kg/m2, amounting to 340 cases (70.7%). There were 119 overweight individuals (25≤ BMI < 30 kg/m2, 24.7%) and 22 obese individuals (BMI≥30 kg/m2, 4.6%), totaling 141 (29.3%).The proportion of the overweight and obese RA patients suffering from hypertension (57.4% vs. 39.1%, P < 0.001), diabetes (25.5% vs. 15.0%, P=0.006), hyperlipidemia (22.7% vs. 10.9%, P=0.001), fatty liver (28.4% vs. 7.4%, P < 0.001), osteoarthritis (39.0% vs. 29.4%, P=0.040) was significantly higher, and the proportion of the patients with osteoporosis(59.6% vs. 70.9%, P=0.016) and anemia (36.2% vs. 55.6%, P < 0.001) was significantly lower. However, there was no difference between the two groups in coronary heart disease (5.7% vs. 7.6%, P=0.442), cerebrovascular disease (6.4% vs. 8.8%, P=0.372) and peripheral atherosclerosis (9.2% vs. 7.6%, P=0.565).The median C-reactive protein (CRP, 1.52 mg/dL vs. 2.35 mg/dL, P=0.008), median erythrocyte sedimentation rate (ESR, 34.0 mm/h vs. 50.0 mm/h, P=0.003), pain visual simulation score (VAS) (3.66±3.08 vs. 4.40±2.85, P=0.011), and 28 joint disease activity scores (DAS-28, 5.05±1.60 vs. 5.45±1.52, P=0.010) in the overweight and obese RA group were all lower than those in the normal and reduced weight groups. Multivariate regression analysis showed that overweight and obesity was an independent risk factor for hypertension, diabetes, hyperlipidemia and fatty liver, and had protective effects on osteoporosis and anemia. CONCLUSION: In RA patients, RA disease activity is lower in overweight and obesity patients. Overweight and obesity is associated with hypertension, diabetes and hyperlipidemia, but not with cardiovascular and cerebrovascular diseases.

[Correlation of anti-phosphatidylserine/prothrombin antibodies with unexplained recurrent miscarriages].

OBJECTIVE: To investigate whether anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes were correlated with unexplained recurrent miscarriages. METHODS: In our a single-center retrospective study, 283 patients with at least one unexplained miscarriage who visited the Third Hospital of Peking University between January 2021 and August 2023, aged between 18-40 years, and tested for anti-phosphatidylserine/prothrombin antibodies IgG or IgM subtypes, were included. The patients with either positive IgG or IgM anti-phosphatidylserine/prothrombin antibody were regarded as positive for anti-phosphatidylserine/prothrombin antibody. SPSS 26.0 software was used for statistical analysis. Chi-square test and Logistic regression analysis were used to study the correlation of anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes with unexplained recurrent miscarriages. And the diagnostic sensitivity, specificity, the positive predictive value, the negative predictive value of anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes in unexplained miscarriages was calculated with four-fold table. RESULTS: Chi-square analysis showed that anti-phosphatidylserine/prothrombin antibodies and its IgM subtypes were correlated with recurrent miscarriages (both P < 0.05), while the IgG subtype was not correlated with recurrent miscarriages (P>0.05). After adjusting with anticardiolipin antibodies, anti-ß2 glycoprotein antibodies, lupus anticoagulants, antinuclear antibodies, and age by Logistic regression analysis, anti-phosphatidylserine/prothrombin antibodies were correlated with unexplained recurrent miscarriages (OR=2.084, 95%CI 1.045-4.155, P < 0.05), and anti-phosphatidylserine/prothrombin antibody IgM subtypes were correlated with unexplained recurrent miscarriages (OR=2.368, 95%CI 1.187-4.722, P < 0.05).The sensitivity of anti-phosphatidylserine/prothrombin antibody in recurrent miscarriage was 65.43%, the specificity was 48.51%, the positive predictive value was 33.76%, and the negative predictive value was 77.78%. In the patients with recurrent miscarriages with negative classical antiphospholipid antibodies, the sensitivity of anti-phosphatidylserine/prothrombin antibody was 59.09%, the specificity was 63.23%, the positive predictive value was 40.63%, and the negative predictive value was 78.40%. The sensitivity of the anti-phosphatidylserine/prothrombin antibody IgM subtype for the diagnosis of recurrent miscarriage was 65.43%, the specificity was 50.99%, the positive predictive value was 34.87%, and the negative predictive value was 78.63%. CONCLUSION: Anti-phosphatidylserine/prothrombin antibody and IgM subtype antibody are correlated with unexplained recurrent miscarriages in patients with at least one unexplained miscarriage. Whether positive anti-phosphatidylserine/prothrombin antibody or IgM subtype could predict future unexplained recurrent miscarriages warrants a prospective study.

LOXL3 Inhibits Autophagy of Chondrocytes by Activating Rheb in Osteoarthritis.

OBJECTIVE: This study aimed to investigate the potential mechanisms by which lysyl oxidase like 3 (LOXL3) affects the autophagy in chondrocytes in osteoarthritis (OA), specifically through the activation of mammalian target of rapamycin complex 1 (mTORC1). METHODS: To establish an OA model, rats underwent anterior cruciate ligament transection (ACLT). Chondrocytes were isolated from cartilage tissues and cultured. Western blotting was performed to assess the expression of LOXL3, Rheb, phosphorylation of p70S6K (p-p70S6K, a downstream marker of mTORC1), and autophagy markers. The autophagy of chondrocytes was observed using an immunofluorescence assay. RESULTS: The expression levels of both LOXL3 and Rheb proteins were upregulated in chondrocytes isolated from the OA model cartilage, in comparison to those from the normal cartilage. The silencing of LOXL3 resulted in a decrease in the protein levels of Rheb and p-p70S6K, as well as an increase in the expression of autophagy-related proteins. Additionally, the effect of LOXL3 could be reversed through the silencing of Rheb. The results of the immunofluorescence assay confirmed the impact of LOXL3 and Rheb on chondrocyte autophagy. CONCLUSION: LOXL3 inhibits chondrocyte autophagy by activating the Rheb and mTORC1 signaling pathways.

Combined RNAi of CTTN and FGF2 Modulates Cell Migration, Invasion and G1/S Transition of Hepatocellular Carcinoma through Ras/ERK Signaling Pathway.

BACKGROUND: Most patients with hepatocellular carcinoma (HCC) die of rapid progression and distant metastasis. Gene therapy represents a promising choice for HCC treatment, but the effective targeted methods are still limited. OBJECTIVE: CTTN/cortactin plays a key role in actin polymerization and regulates cytoskeleton remodeling. However, the interaction network of CTTN in HCC is not well understood. METHODS: siRNA was designed for CTTN silencing and Affymetrix GeneChip sequencing was used to obtain the gene profile after CTTN knockdown in the HCC cell line SMMC-7721. Potential interacting genes of CTTN were identified using qRT-PCR. The inhibition on HCC by combined RNA interference (RNAi) of CTTN and fibroblast growth factor 2 (FGF2) was detected. RESULTS: A total of 1,717 significantly altered genes were screened out and 12 potential interacting genes of CTTN were identified. The interaction of CTTN and FGF2 was validated and combined RNAi of CTTN and FGF2 achieved a synergistic effect, leading to better inhibition of HCC cell migration, invasion and G1/S transition than single knockdown of CTTN or FGF2. Mechanistically, combined RNAi of CTTN and FGF2 modulated the Ras/ERK signaling pathway. In addition, the EMT epithelial marker E-cadherin was upregulated while the mesenchymal marker Vimentin and cell cycle protein Cyclin D1 were downregulated after combined RNAi of CTTN and FGF2. Additionally, qRT-PCR and immunohistochemical staining showed that both CTTN and FGF2 were highly expressed in metastatic HCC tissues. CONCLUSION: Combined RNAi of CTTN and FGF2 may be a novel and promising intervention strategy for HCC invasion and metastasis.

Articular Cartilage Regeneration via Induced Chondrocyte Autophagy by Sustained Release of Leptin Inhibitor from Thermo-Sensitive Hydrogel through STAT3/REDD1/mTORC1 Cascade.

The pathophysiology of osteoarthritis (OA) is closely linked to autophagy abnormalities in articular chondrocytes, the sole mature cell type in healthy cartilage. Nevertheless, the precise molecular mechanism remains uncertain. Previous research has demonstrated that leptin activates mTORC1 , thereby inhibiting chondrocyte autophagy during the progression of OA. In this study, it is demonstrated that the presence of leptin induces a substantial increase in the expression of STAT3, leading to a notable decrease in REDD1 expression and subsequent phosphorylation of p70S6K, a recognized downstream effector of mTORC1. Conversely, inhibition of leptin yields contrasting effects. Additionally, the potential advantages of utilizing a sustained intra-articular release of a leptin inhibitor (LI) via an injectable, thermosensitive poly(D,L-lactide)-poly(ethylene glycol)-poly(D,L-lactide) (PDLLA-PEG-PDLLA: PLEL) hydrogel delivery system for the purpose of investigating its impact on cartilage repair are explored. The study conducted on LI-loaded PLEL (PLEL@LI) demonstrates remarkable efficacy in inhibiting OA and displays encouraging therapeutic advantages in the restoration of subchondral bone and cartilage. These findings establish a solid foundation for the advancement of a pioneering treatment approach utilizing PLEL@LI for OA.