Seasonal variation in non-volatile flavor substances of fresh tea leaves (Camellia sinensis) by integrated lipidomics and metabolomics using UHPLC-Q-Exactive mass spectrometry.

Harvest season exerts great influence on tea quality. Herein, the variations in non-volatile flavor substances in spring and summer fresh tea leaves of four varieties were comprehensively investigated by integrating UHPLC-Q-Exactive based lipidomics and metabolomics. A total of 327 lipids and 99 metabolites were detected, among which, 221 and 58 molecules were significantly differential. The molecular species of phospholipids, glycolipids and acylglycerolipids showed most prominent and structure-dependent seasonal changes, relating to polar head, unsaturation and total acyl length. Particularly, spring tea contained higher amount in aroma precursors of highly unsaturated glycolipids and phosphatidic acids. The contents of umami-enhancing amino acids and phenolic acids, e.g., theanine, theogallin and gallotannins, were increased in spring. Besides, catechins, theaflavins, theasinensins and flavone/flavonol glycosides showed diverse changes. These phytochemical differences covered key aroma precursors, tastants and colorants, and may confer superior flavor of black tea processed using spring leaves, which was verified by sensory evaluation.

Validity and Responsiveness of EQ-5D in Asthma: A Systematic Review and Meta-analysis.

OBJECTIVE: We aimed to synthesize the evidence on the construct validity and responsiveness of the EQ-5D and compare them with asthma-specific health-related quality-of-life scales, to guide further research and clinical applications in asthma. METHODS: We searched key databases from inception to 1 June, 2024 and used the COnsensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) method to appraise the evidence. The effect size estimates were aggregated using the inverse variance method to evaluate the relative efficiency of EQ-5D measures against the Asthma Quality of Life Questionnaire (AQLQ) and/or its corresponding preference-based index, Asthma Quality of Life-5 Dimensions (AQL-5D). RESULTS: There were 493 tests (construct validity: 428; responsiveness: 65) drawn from 37 selected articles (validation: 7; clinical: 30). Overall, 78.4% and 76.9% of the a priori hypotheses for assessing construct validity (convergent validity: 56.4%; known groups: 88.5%) and responsiveness, respectively, were satisfied. The methodological quality was "very good" or "adequate" in 78.2% of construct validity tests and 92.3% of responsiveness tests. The pooled correlation coefficient between EQ-5D index and AQLQ total scores was 0.52 (95% confidence interval 0.43-0.59), and between EQ visual analog scale and AQLQ total scores was 0.53 (95% confidence interval 0.34-0.69). The Cohen's d ratios for the index, level sum scores, and visual analog scale compared to AQLQ were 0.56 (n = 27), 1.16 (n = 16), and 0.75 (n = 37). The EQ-5D index's Cohen's d ratio compared to AQL-5D was 0.49 (n = 5). The standardized response mean ratios for the index and visual analog scale compared to AQLQ were 0.26 (n = 11) and 0.63 (n = 9). CONCLUSIONS: The EQ-5D demonstrated overall good validity and responsiveness in the adult asthma population. However, a comparison against disease-specific instruments suggested scope for improvement in its psychometric performance for this population.

Magnetic nanoparticles-immobilized phospholipase LM and phospholipase 3G: Preparation, characterization, and application on soybean crude oil degumming.

Immobilization of enzymes improves their stability and recoverability and is therefore crucial for scientific research and industrial applications. In this study, phospholipase LM (PLLM) and phospholipase 3G (PL3G) were immobilized using Fe3O4@SiO2@CS-COOH polycarboxylated magnetic nanoparticles (MNPs-COOH) as carriers and then used for degumming soybean crude oil. The immobilization rates and relative enzyme activities of these immobilized phospholipases were evaluated to determine the optimal immobilization parameters. The enzyme activities of PLLM-MNPs-COOH and PL3G-MNPs-COOH were 2830.87 and 1162.25 U/g, respectively. Enzymatic properties of the free and immobilized enzymes were compared. Both immobilized phospholipases exhibited higher condition tolerance and stability after immobilization. After 30-day storage at 4 °C, both immobilized phospholipases retained approximately 1.3 times the residual activity of the corresponding free phospholipases. When the degumming conditions were optimized, the residual phosphorus contents of the PLLM-MNPs-COOH- and PL3G-MNPs-COOH-degummed oils were 4.91 and 7.41 mg/kg, respectively, which were consistent with the safety standards for oil products. After 6 cycles, PLLM-MNPs-COOH and PL3G-MNPs-COOH continued to preserve 71.88 % and 70.00 % of their initial activities, respectively. The immobilized phospholipases are thus suitable for degumming soybean crude oil, and the mixed enzymes exhibited better degumming potential.

Insulin-like growth factor-binding protein7 exacerbates inflammatory response and lipid metabolism imbalance in alcohol-associated liver disease.

Alcohol-associated liver disease(ALD), caused by excessive alcohol consumption, are often associated with inflammatory outbreaks and lipid deposition in the liver. The role of Insulin-like growth factor-binding protein 7 (IGFBP7), an important metabolic regulator, in ALD, its underlying regulatory mechanism, and its potential implication in anti-ALD therapies remain unknown. We investigated the effects of IGFBP7 on hepatic inflammation and lipid metabolism disruption in a mouse model of ALD. Mice were fed by chronic ethanol feeding plus a single binge of ethanol feeding(chronic-plus-single-binge model). In addition, ethanol exposure modeling studies were performed on cultured hepatocytes to verify molecular correlations. The results showed that IGFBP7 expression was significantly elevated in the livers of mice and hepatocytes after chronic ethanol exposure. Subsequently, the results of a study by specific knockout of IGFBP7(IGFBP7-cKO) in mouse hepatocytes and lentiviral silencing of IGFBP7 in vivo suggested that IGFBP7 deletion could improve liver function levels in alcohol-fed mice; It also attenuated the outbreak of hepatitis factor and the disorder of lipid metabolism in mice.Using RNA-seq sequencing of mouse liver tissue, we found that IGFBP7 affects several downstream metabolic signaling pathways, including PPAR, MAPK, FoxO, etc. Then, we used the PPARα plasmid in hepatocytes and discovered that overexpressing PPARα reversed the impact of IGFBP7 on lipid metabolism disorders in hepatocytes. In conclusion, IGFBP7 deficiency in alcohol-associated liver disease alleviates the decline in liver function and the imbalance of lipid metabolism in mice, attenuates the inflammatory outbreak, and affects a variety of downstream lipid metabolism factors by regulating PPARα. Hence, IGFBP7 may be an effective therapeutic target in the treatment of ALD.

Insights into the soybean protein isolate hydrolysates: Performance characterization, emulsion construction and in vitro digestive behavior.

In this experiment, the co-constructed O/W emulsions of different soy protein hydrolysates (SPHs) and gum arabic (GA) were investigated. SPHs were prepared by hydrolyzing soy protein isolate (SPI) using different enzymes, and investigated the effects of enzyme types and hydrolysis time on the physicochemical properties of SPHs. Moreover, SPI/GA and SPHs/GA were prepared and used as hydrophilic emulsifiers to construct O/W emulsions. The results showed that the optimal hydrolysis times for bromelain, pepsin and trypsin were 2 h (BSPH2), 3 h (PSPH3) and 3 h (TSPH3), respectively. Compared with SPI/GA emulsions, SPHs/GA emulsions had smaller particle size, more negative charge, higher interfacial adsorbed protein, and more stable emulsion systems. During the digestion process, SPHs/GA emulsions were effective in realizing the release of bioactives. In conclusion, enzymatic hydrolysis can be an effective modification technique, and SPHs/GA can be used as an effective emulsifier for the emulsion system.

Targeted metabolomics reveals the contribution of degradation and oxidation of lipids and proteins mediated by pH to the formation of characteristic volatiles in preserved egg yolk during pickling.

Targeted metabolomics and flavouromics combined with relative odor activity value were performed to explore the effect of degradation and oxidation of matrix mediated by pH on the formation of characteristic volatiles in preserved egg yolk (PEY) during pickling. It was found that the oxidation of proteins and lipids in PEY induced by pH sequentially occurred in early and later periods, and degradation both mainly occurred in early stage. Moreover, 1-octen-3-one, heptanal, trimethylamine, etc., compounds and 5-HETrE, proline, etc., components were confirmed as up-regulated characteristic volatiles and differential metabolites in PEY during pickling. The formation of octanal-M/D and benzeneacetaldehyde-M was attributed to ß-oxidation of hydroxyeicosapentaenoic acid and L-isoleucine catalyzed by strong alkali at early period based on correlation network between them, respectively. Meanwhile, the generation of 1-octen-3-one-M/D mainly depended on L-serine and could be promoted by phosphatidylcholines oxidation. At later stage, the formation of heptanal-M/D was primarily attributed to phosphatidylethanolamines oxidation induced by alkali, and the enrichment of heptanal-M/D and nonanal were both enhanced by oxidized lipids. Lastly, trimethylamine was derived from L-lysine under alkaline conditions and promoted by protein oxidation during the whole process. This manuscript provided insight into the differential contribution of oxidation and degradation from matrix regulated by exogenous factors on the formation pathway for characteristic volatiles in foods.

Genome-centric metagenomic analysis reveals mechanisms of quorum sensing promoting anaerobic digestion under sulfide stress: Syntrophic metabolism and microbial self-adaptation.

Sulfide stress is a common inhibition factor in anaerobic digestion systems with sulfur-rich feedstocks. Quorum sensing (QS) signaling molecule N-acyl-homoserine lactones (AHLs) possess positive effect on promoting anaerobic digestion. However, the micro-biological mechanisms of AHLs affecting syntrophic metabolism and microbial self-adaptation have not yet been deciphered in anaerobic digestion under sulfide stress. In this study, the CH4 production increased by 21.34 % at 20 µM AHLs addition in anaerobic digestion under sulfide stress. AHLs contributed to establishing potential syntrophic relationship between acidifying bacteria (unclassified_o__Bacteroidales, Lentimicrobium, Acetoanaerobium, Longilinea, and Sphaerochaetaa) and Methanothrix. AHLs promoted syntrophic metabolism by boosting microbial metabolic activity and interspecies electron transfer (IET) process under sulfide stress. For microbial metabolic activity, AHLs promoted the key enzyme synthesis in acidogenesis and methanogenesis. For IET process, AHLs promoted the assembly and synthesis of conductive pili, and synthesis and secretion of riboflavin. Furthermore, AHLs promoted microbial self-adaptation including two component system, lipopolysaccharide biosynthesis, and DNA repair, which were important evidences that microbial resistance to sulfide stress was enhanced by AHLs. Microbial self-adaptation provided favorable foundation and safeguard for syntrophic metabolisms under sulfide stress. These findings deciphered the micro-biological mechanisms of AHLs enhancing anaerobic digestion under sulfide stress.

Effect of ultrasonic pretreatment on physicochemical, thermal, and rheological properties of chemically modified corn starch.

This study investigated the effects of ultrasonic and three chemical individual and dual modification treatments on corn starch's physicochemical, thermal, and rheological properties. Ultrasonication and the three chemical treatments disrupted the starch granules with a decrease in particle size and a significant increase in the ζ-potential. The hydrophilicity of ultrasonic-oxidized dual-modified starch (U-O-CS) was the highest, at 0.854 g/g. The lipophilicity of ultrasonic-esterified dual-modified starch (U-E-CS) was the highest, at 1.485 g/g. The gelatinization temperature of ultrasonic, oxidation, and cross-linking modified starches increased significantly, with cross-linking starches being the largest. Oxidative treatment significantly decreased the starch's G' and G" and weakened the textural properties. The rheological properties of U-O-CS were further weakened. The G' of the starch decreased after the esterification treatment, while the G" increased, and the textural properties were cut. The maximum rheological and textural properties were obtained for crosslinked modification, with a hardness value of 284.70 g.

Pyramid Textured Photonic Films with High-Refractive Index Fillers for Efficient Radiative Cooling.

Sub-ambient cooling technologies relying on passive radiation have garnered escalating research attention owing to the challenges posed by global warming and substantial energy consumption inherent in active cooling systems. However, achieving highly efficient radiative cooling devices capable of effective heat dissipation remains a challenge. Herein, by synergic optimization of the micro-pyramid surface structures and 2D hexagonal boron nitride nanoplates (h-BNNs) scattering fillers, pyramid textured photonic films with remarkable solar reflectivity of 98.5% and a mid-infrared (MIR) emittance of 97.2% are presented. The h-BNNs scattering filler with high thermal conductivity contributed to the enhanced through-plane thermal conductivity up to 0.496 W m-1 K-1 and the in-plane thermal conductivity of 3.175 W m-1 K-1. The photonic films exhibit an optimized effective radiative cooling power of 201.2 W m-2 at 40 °C under a solar irradiance of 900 W m-2 and a daily sub-ambient cooling effect up to 11 °C. Even with simultaneous internal heat generation by a 10 W ceramic heater and external solar irradiance of 500 W m-2, a sub-ambient cooling of 5 °C can be realized. The synergic matching strategy of high thermal conductivity scattering fillers and microstructured photonic surfaces holds promise for scalable sub-ambient radiative cooling technologies.

Expression patterns and clinical value of key m6A RNA modification regulators in smoking patients with coronary artery disease.

Even though N6-methyladenosine (m6A) RNA modifications are increasingly being implicated in human disease, their mechanisms are not fully understood in smokers with coronary artery disease (CAD). Thirty m6A-related regulators' expression (MRRE) in CAD individuals (smokers and non-smokers) were analyzed from GEO. Support Vector Machine, random forest, and nomogram models were constructed to assess its clinical value. Consensus clustering, principal component analysis, and ssGSEA were used to construct a full picture of m6A-related regulators in smokers with CAD. Oxygen-glucose deprivation (OGD) and qRT-PCR were used to validate hypoxia's effect on MRRE. A comparison between smokers with CAD and controls revealed lower expression levels of RBM15B, YTHDC2, and ZC3H13. Based on three key MRREs, all models showed good clinical value, and smokers with CAD were divided into two distinct molecular subgroups. The correlations were found between key MRRE and the degree of immune infiltration. Three key MRREs in HUVECs and FMC84 mouse cardiomyocytes were reduced in the OGD group. Through hypoxia, smoking might reduce the expression levels of RBM15B, YTHDC2, and ZC3H13 in smokers with CAD. Our findings provide an important theoretical basis for the treatment of smokers with CAD.

Immersive Virtual Reality Versus Video Distraction for the Management of Emergence Delirium in Children: A Randomized Controlled Study.

PURPOSE: Emergence delirium (ED) presents challenges for both parents and health care providers in pediatric surgical settings. This study aims to evaluate the effectiveness of immersive virtual reality (VR) distraction and video distraction combined with parental presence in reducing ED in preschool-aged children undergoing elective surgery. DESIGN: A prospective, randomized, controlled clinical trial was conducted with 90 children ages 4 to 7. Participants were randomly assigned to three groups: VR distraction (group V), tablet video distraction with parental presence (group T), and standard care (group C). The primary endpoints were the incidence of ED and Pediatric Anesthesia Emergence Delirium Scale scores, with secondary measures encompassing scores from the Parental Separation Anxiety Scale and the Faces, Legs, Activity, Cry, Consolability (FLACC) scale. METHODS: Participants were assigned to one of the three intervention groups, and relevant scales were used to assess ED, parental separation anxiety, and postoperative pain. The immersive VR distraction and video distraction with parental presence interventions were compared against standard care. FINDINGS: Immersive VR distraction significantly reduced the incidence of ED (6.67% in group V vs 40% in group T and 60% in group C), and the incidence of ED in group V was notably lower than in the other groups (P = .023 vs group T and P = .004 vs group C). Children in group V displayed significantly lower FLACC compared with the other groups as well (P < .05). However, no significant differences between the 3 groups were observed in perioperative anxiety as assessed by the Parental Separation Anxiety Scale scores (P = .27). CONCLUSIONS: This study underscores the potential of immersive VR distraction as an effective intervention for mitigating ED in pediatric surgical patients. The findings suggest that incorporating VR technology during the perioperative period can positively impact postoperative outcomes. Further research in diverse surgical contexts is recommended to validate these findings and explore the broader applicability of VR distraction in pediatric health care settings.

Promoting the healing of infected diabetic wound by nanozyme-containing hydrogel with anti-bacterial inflammation suppressing, ROS-scavenging and oxygen-generating properties.

Bacterial infections already pose a significant threat to skin wounds, especially in diabetic patients who have difficulty healing wounds. However, wound or bacterial infections are known to produce excess reactive oxygen species (ROS), and hypoxia may further hinder wound healing and the development of chronic wounds. In this study, a multifunctional hydrogel for ROS scavenging and bacterial inhibition was developed by cross-linking polyvinyl alcohol (PVA) and sodium alginate (SA) with graphene oxide (GO) loaded with silver-platinum hybrid nanoparticles (GO@Ag-Pt). The PVA/SA hydrogel loaded with GO@Ag-Pt exhibited the ability to scavenge different types of ROS, generate O2, and kill a broad spectrum of bacteria in vitro. The silver-platinum hybrid nanoparticles significantly increased the antibacterial ability against Escherichia coli and Staphylococcus aureus compared with silver nanoparticles (AgNps). GO@Ag-Pt loaded hydrogel was effective in treating infections caused by S.aureus, thereby significantly promoting wound healing during the inflammatory phase. Hydrogel therapy significantly reduced the level of ROS and alleviated inflammation levels. Notably, our ROS-scavenging, antibacterial hydrogels can be used to effectively treat various types of wounds, including difficult-to-heal diabetic wounds with bacterial infections. Thus, this study proposes an effective strategy for various chronic wound healing based on ROS clearance and bacteriostatic hydrogels.

Exploring the roles and therapeutic implications of melatonin-mediated KLF6 in the development of intracranial aneurysm.

BACKGROUND: Intracranial aneurysm (IA) is a cerebrovascular disease with a high mortality rate due to ruptured subarachnoid hemorrhage. While Krüppel-like factor 6 (KLF6) dysregulation has been implicated in cancer and cardiovascular diseases, its role in IA remains unclear. MATERIALS AND METHODS: The GSE122897 and GSE15629 datasets were downloaded from the Gene Expression Omnibus database. Immune cell infiltration and hypoxia analysis were performed to explore the effects of KLF6 on IA. Weighted gene co-expression network analysis was used to identify hub genes related to KLF6 expression for subsequent analyses. Hypoxia-related genes were identified. Drug prediction was performed for IA. Samples from healthy individuals and patients with IA were collected to detect the expression of endothelin-1 (ET-1), vascular hematoma factor (vWF), and KLF6. A model of H2O2-induced human brain vascular smooth muscle cells (HBVSMC) injury was constructed to explore the effects of KLF6 and melatonin to treat IA. RESULTS: T cells CD4 memory resting and monocytes were significantly different in the KLF6 high and low expression groups. Four hypoxia-related gene sets were significantly enriched in the KLF6 high-expression group. Six hypoxia-related hub genes were obtained, which were significantly associated with KLF6. Drug prediction showed that melatonin may be a potential drug for IA. The levels of ET-1, vWF, and KLF6 were significantly upregulated in patients with IA. KLF6 exacerbates H2O2-induced injury in HBVSMC, ameliorated by melatonin. CONCLUSION: KLF6 may be a potential target for IA treatment, with melatonin-mediated KLF6 effects playing a crucial role in the development of IA.

KLF6 was associated with infiltrated immune cells and hypoxia genes in intracranial aneurysm.KLF6 was significantly upregulated in patients with intracranial aneurysm.KLF6 exacerbates H₂O₂-induced injury in HBVSMC, ameliorated by melatonin.

An LF-NMR homogeneous sensor for highly sensitive and precise detection of E. coli based on target-triggered CuAAC click reaction.

In this study, a low field nuclear magnetic resonance (LF-NMR) homogeneous sensor was constructed for detection of Escherichia coli (E. coli) based on the copper metabolism of E. coli triggered click reaction. When live E. coli was present, a large amount of Cu2+ ions were transformed into Cu+ via copper metabolism, which then catalyzed a Cu+-catalyzed azide-alkyne cycloaddition (CuAAC) reaction between two materials, azide group modified gadolinium oxide nanorods (Gd2O3-Az) and PA-GO@Fe3O4 i.e., graphene oxide (GO) loaded with large amounts of alkynyl (PA) groups and Fe3O4 nanoparticles simultaneously. After magnetic separation, unbound Gd2O3-Az was dissolved by added hydrochloric acid (HCl) to generate homogeneous Gd3+ solution, enabling homogeneous detection of E. coli. Triple signal amplification was achieved through the CuAAC reaction induced by E. coli copper metabolism, functional nanomaterials, and HCl assisted homogeneous detection. Under the optimal experimental conditions, the linear range and limit of detection (LOD) for E. coli were 10-1.0 × 107 CFU/mL and 3.5 CFU/mL, respectively, and the relative standard deviations (RSDs) were all less than 2.8 %. In addition, the sensor has satisfactory selectivity, stability and practical sample application capability, providing a new approach for the LF-NMR detection of food-borne pathogenic bacteria.

Systematic review reveals that EQ-5D minimally important differences vary with treatment type and may decrease with increasing baseline score.

OBJECTIVES: To provide an updated summary of published anchor-based Minimally Important Difference (MID) estimates for the EQ-5D index and EQ visual analog scale (EQ VAS) scores and identify factors influencing those estimates. STUDY DESIGN AND SETTING: We systematically searched eight electronic databases from January 1990 to March 2023. We examined the association of baseline score, type of score change (improvement/worsening), data source, value set, disease/condition, treatment type (surgical/non-surgical), and type of anchor (clinical vs. self-rated) with MID estimates for the EQ-5D-3L and EQ-5D-5L indices, and EQ VAS. Significant variables were used to develop prediction formulas for MID by testing both linear and nonlinear regression models. RESULTS: Of 6786 records reviewed, 47 articles were included for analysis. MID ranges for improved scores were -0.13 to 0.68 (EQ-5D-3L), 0.01-0.41 (EQ-5D-5L), and 0.42-23.0 (EQ VAS). Surgical intervention and lower baseline scores were associated with higher MIDs for both the EQ indices but not for EQ VAS. The nonlinear polynomial model outperformed the linear model in predicting the MIDs. MIDs based on deteriorated scores were insufficient for quantitative synthesis (mean: -0.02 for EQ-5D-3L; -0.04 for EQ-5D-5L; and -6.5 for EQ VAS). CONCLUSION: This review revealed that the MID of EQ-5D index scores varies with baseline score and treatment type, indicating that use of a uniform MID may not be appropriate. We recommend using baseline score-adjusted and treatment type-specific EQ-5D MIDs, and call for more MID research, particularly in the context of assessing deterioration in health using this widely used generic health-status instrument.

High levels of mitochondrial dynamics, autophagy, and apoptosis contribute to stable testicular status in hibernating Daurian ground squirrels.

Daurian ground squirrels (Spermophilus dauricus) experience various stress states during winter hibernation, but the impact on testicular function remains unclear. This study focused on the effects of changes in testicular autophagy, apoptosis, and mitochondrial homeostasis signaling pathways at various stages on the testes of Daurian ground squirrels. Results indicated that: (1) During winter hibernation, there was a significant increase in seminiferous tubule diameter and seminiferous epithelium thickness compared to summer. Spermatogonia number and testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were higher during inter-bout arousal, suggesting that the testes remained stable during hibernation. (2) An increased number of mitochondria with intact morphology were observed during hibernation, indicating that mitochondrial homeostasis may contribute to testicular stability. (3) DNA fragmentation was evident in the testes during the hibernation and inter-bout arousal stages, with the highest level of caspase3 enzyme activity detected during inter-bout arousal, together with elevated levels of Bax/Bcl-2 and Lc3 II/Lc3 I, indicating an up-regulation of apoptosis and autophagy signaling pathways during hibernation. (4) The abundance of DRP1, MFF, OPA1, and MFN2 proteins was increased, suggesting an up-regulation of mitochondrial dynamics-related pathways. Overall, testicular autophagy, apoptosis, and mitochondrial homeostasis-related signaling pathways were notably active in the extreme winter environment. The well-maintained mitochondrial morphology may favor the production of reproductive hormones and support stable testicular morphology.

[Genetic study of a rare Chinese pedigree with a recombination occurring between the HLA-A/C loci in both parents].

OBJECTIVE: To analyze a Chinese pedigree with a recombination occurring between the HLA-A/C loci in both parents. METHODS: A patient who was planning to undergo hematopoietic stem cell transplantation due to "aplastic anemia" in February 2022 was selected as the study subject. Peripheral blood samples were collected from the patient, his parents and brother. HLA-A/C/B/DRB1/DQB1 high-resolution typing was carried out by using sequence-based typing and sequence-specific oligonucleotides. The recombination was identified by pedigree analysis. The HLA haplotype of each individual was identified by genealogical analysis. The parentage possibility was determined by short tandem repeat analysis. HLA-A/C/B/DRB1/DRB345/DQA1/DQB1/DPA1/DPB1 were determined with next-generation high-throughput sequence-based typing. The recombination sites were analyzed by family study. RESULTS: The high parentage possibilities of the family was confirmed by short tandem repeat analysis. Recombination was found between the HLA-A*24:02 A*33:03/C*14:03 in the paternally transmitted haplotype, whilst HLA-A*01:01 A*03:01/C*08:02 was found in the maternally transmitted haplotype, which had resulted in two novel HLA haplotypes in the proband. CONCLUSION: A rare case with simultaneous recombination of the paternal and maternal HLA-A/C loci has been discovered, which may facilitate further study of the mechanisms of the HLA recombination.

Cross-sectional associations of low body mass index and being underweight with joint damage in Chinese patients with rheumatoid arthritis.

Objective: To characterize BMI in Chinese patients with RA vs US patients and examine its association with joint damage in Chinese patients. Methods: Each of the 1318 patients from a real-world Chinese RA population was first stratified by gender and then individually age-matched with one American RA patient from the US National Health and Nutritional Examination Survey 1999-2018. Data on BMI, bilateral hand radiographs and risk factors at enrolment were collected but radiographs were unavailable for the American patients. Logistic regression was used to evaluate the association of BMI with radiographic joint damage (RJD) in Chinese patients. Results: Chinese patients had a significantly lower BMI [(weighted) median 21.8 vs 29.8 kg/m2; P < 0.001] and a higher prevalence of being underweight (15.2% vs 1.1%; P < 0.05) than their American counterparts. Underweight Chinese patients (BMI <18.5) had higher modified total Sharp scores (median 17 vs 10) and joint space narrowing (JSN) subscores (median 6 vs 2) (both P < 0.05) than normal-weight patients (BMI ≥18.5-<24). After controlling for confounding, continuous BMI was cross-sectionally negatively associated with RJD [adjusted prevalence odds ratio (OR) 0.90 (95% CI 0.85, 0.96)] and JSN [adjusted prevalence OR 0.92 (95% CI 0.87, 0.96)]; being underweight vs normal weight was associated with RJD [adjusted prevalence OR 2.14 (95% CI 1.37, 3.35)] and JSN [adjusted prevalence OR 1.77 (95% CI 1.10, 2.84)]. Conclusion: Low BMI and being underweight were cross-sectionally associated with joint damage in Chinese RA patients, especially JSN, suggesting the clinical importance of identifying underweight patients and focusing on weight gain to prevent joint damage.

Hepatic-derived BMP9 is involved in hepatic fibrosis-induced kidney injury through inhibition of renal VEGFA.

Clinical observations suggest that acute kidney injury (AKI) occurs in approximately 20-50% of hospitalized cirrhotic patients, suggesting a link between the liver and kidney. Bone morphogenetic protein 9 (BMP9) is a protein produced primarily by the liver and can act on other tissues at circulating systemic levels. Previous studies have demonstrated that controlling abnormally elevated BMP9 in acute liver injury attenuates liver injury; however, reports on whether BMP9 plays a role in liver injury-induced AKI are lacking. By testing we found that liver injury in mice after bile duct ligation (BDL) was accompanied by a significant upregulation of the kidney injury marker kidney injury molecule (KIM-1). Interestingly, all these impairments were alleviated in the kidneys of hepatic BMP9 knockout (BMP9-KO) mice. Peritubular capillary injury is a key process leading to the progression of AKI, and previous studies have demonstrated that vascular endothelial growth factor A (VEGFA) plays a key role in maintaining the renal microvascular system. In animal experiments, we found that high levels of circulating BMP9 had an inhibitory effect on VEGFA expression, while renal tubular epithelial cell injury was effectively attenuated by VEGFA supplementation in the hypoxia-enriched-oxygen (H/R) constructs of the AKI cell model in both humans and mice. Overall, we found that elevated BMP9 in hepatic fibrosis can affect renal homeostasis by regulating VEGFA expression. Therefore, we believe that targeting BMP9 therapy may be a potential means to address the problem of clinical liver fibrosis combined with AKI.

Circ_0000099/miR-223-3p/CTGF Regulates the Growth, Metastasis, and EMT Processes in TGF-ß2-Stimulated Human Lens Epithelial Cells.

PURPOSE: Posterior capsule opacification (PCO) is the major complication of visual impairment after cataract surgery. Circular RNAs (circRNAs) are involved in the development of many diseases. The purpose of this study was to explore the role and molecular mechanism of circ_0000099 in PCO. METHODS: SRA01/04 cells were treated with TGF-ß2 to establish a PCO cell model. The expression of circ_0000099, miR-223-3p, and connective tissue growth factor (CTGF) mRNA was determined by real-time quantitative polymerase chain reaction (qRT-PCR). Western blot assay was used to analyze the protein expression. Cell proliferation, migration, and invasion were analyzed by (4-5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), 5-ethynyl-2 '-Deoxyuridine (EdU), transwell, and wound healing tests. The circ_0000099/miR-223-3p/CTGF relationship was verified by dual luciferase reporter gene and RNA binding protein immunoprecipitation (RIP) assays. RESULTS: TGF-ß2 treatment promoted SRA01/04 cell proliferation invasion, migration, and EMT. Circ_0000099 expression was increased in POC patients and TGF-ß2-treated SRA01/04 cells.Knockdown of circ_0000099 suppressed TGF-ß2-induced proliferation, invasion, migration, and EMT in SRA01/04 cells. miR-223-3p was identified as the target of circ_0000099, and miR-223-3p inhibitor might partly abolish the repression of circ_0000099 silencing on TGF-ß2-triggered SRA01/04 cell disorders. MiR-223-3p directly targeted CTGF. Knockdown of CTGF suppressed TGF-ß2-induced SRA01/04 cell injury. Circ_0000099 can regulate CTGF expression by targeting miR-223-3p. CONCLUSIONS: Circ_0000099 silencing might relieve TGF-2-induced SRA01/04 cell injury by the miR-223-3p/CTGF axis, providing new avenues for the prevention and treatment of PCO.