Upregulating miR-181b promotes ferroptosis in osteoarthritic chondrocytes by inhibiting SLC7A11.

BACKGROUND: Osteoarthritis (OA) is a common disease with a complex pathology. This study aimed to investigate the correlation between the aberrant upregulation of miR-181b and ferroptosis in chondrocytes during the progression of OA. METHODS: An OA cell model was constructed with erastin. Ferrostatin-1 (Fer), bioinformatics, and dual-luciferase activity reports were used to investigate the effect of miR-181b on OA. Finally, a rat model of OA was induced by monosodium iodoacetate to verify that miR-181b inhibits SLC7A11 gene expression and increases ferroptosis. RESULTS: The results showed that Fer could effectively reverse the erastin-induced inhibition of human chondrocyte viability, increase the level of collagenous proteins in human chondrocytes, and inhibit oxidative stress and ferroptosis. MiR-181b is abnormally elevated in OA cell models. Transfection of a miR-181b inhibitor could increase the expression levels of the ferroptosis-related proteins solute carrier family 7 members 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), thereby inhibiting the occurrence of ferroptosis in chondrocytes. In addition, hsa-miR-181b-5p and SLC7A11 have a targeted regulatory effect. Transfection of SLC7A11 siRNA effectively abrogated the increase in chondrocyte viability induced by the miR-181 inhibitor and increased ferroptosis. Finally, miR-181b was shown to exacerbate OA disease progression by inhibiting SLC7A11 gene expression and increasing ferroptosis in a rat OA model. CONCLUSIONS: Elevating miR-181b may mediate chondrocyte ferroptosis by targeting SLC7A11 in OA.

[Research of progress of mitochondria in the pathogenesis of sepsis].

Sepsis is an organ dysfunction caused by dysregulation of the body's response to infection, with high morbidity and mortality. The pathogenesis of sepsis is still unclear, and there are no specific treatment drugs. As a cell energy supply unit, the dynamic changes of mitochondria are closely related to various diseases. Studies have shown that structure and function of mitochondria are changed in different organs during sepsis. The energy shortage, oxidative stress change, imbalance of fusion and fission, autophagy reduce, biological functions of mitochondria play important roles in sepsis progress, which can provide a research target for the treatment of sepsis.

ED90 of epidural esketamine with 0.075% ropivacaine for labor analgesia in nulliparous parturients: a prospective, randomized and dose-finding study.

Background: Because it has been reported that racemic ketamine had a local anesthetic-sparing effect when used for epidural analgesia this would suggest the likelihood of a potential advantage (less pruritus) over opioid drugs. Esketamine has greater analgesic efficacy than racemic ketamine, but the optimum dosage regimen for epidural use is undetermined. The aim of this study was to determine the ED90 of epidural esketamine when coadministered with 0.075% ropivacaine for labor analgesia. Methods: A total of 65 laboring nulliparous patients were enrolled in this study from 16 March 2022 to 15 October 2022. The patients were randomly assigned to receive 0, 0.25, 0.5, 0.75 or 1.0 mg/mL esketamine with 0.075% ropivacaine epidurally. An effective response to the epidural loading dose was defined as numerical rating scale pain score ≤3 at 30 min after the end of the epidural loading dose (10 mL of the ropivacaine 0.075% solution with the added esketamine). The ED90 of epidural esketamine coadministered with 0.075% ropivacaine with 95% confidence intervals for labor analgesia was determined using probit regression. Secondary outcomes and side effects were recorded. Results: The estimated value of ED90 with 95% CIs for epidural esketamine with 0.075% ropivacaine was 0.983 (0.704-2.468) mg/mL. The characteristics of sensory and motor block, consumption of ropivacaine per hour, duration of first or second stage, Apgar scores did not differ among the five groups. The incidence of mild dizziness in Group esketamine 1.0 mg/mL was significantly higher than that in other groups (p < 0.05). No statistical differences were found in other side effects among groups. Conclusion: The ED90 value of epidural esketamine coadministered with 0.075% ropivacaine for labor analgesia in nulliparous parturients was about 1.0 mg/mL. Furthermore, our results suggested that epidural esketamine would cause dose-dependent mild dizziness especially at doses up to 1.0 mg/mL. As a single epidural additive, esketamine may not be suitable for labor analgesia. Future studies may investigate the appropriate dosage of esketamine at slightly higher concentrations of local anesthetics or larger initial volume of analgesia, or explore other potential advantages of esketamine. Clinical Trial Registration: (https://www.chictr.org.cn/bin/project/edit?pid=159764), identifier (ChiCTR2200057662).

Transcatheter Treatment of Native Coarctation of the Aorta in a Child Using a Balloon-Expandable Endoprosthesis.

A 7-year-old child with native coarctation of the aorta was treated by transcatheter therapy using a 29-mm balloon-expandable stent. The procedure was successful and free of complications, and the patient was discharged home the same day. This stent has several features making it uniquely advantageous for treating this condition. (Level of Difficulty: Advanced.).

EoE behaves as a unique Th2 disease: a narrative review.

Background and Objective: To highlight and interpret two significant differences between eosinophilic esophagitis (EoE), a type 2 helper cell (Th2) disease, and three other representative Th2 diseases. EoE, asthma, atopic dermatitis (AD), chronic rhinosinusitis (CRS) and other Th2 diseases employ epithelial alarmins to recognize triggers, share a prototypical inflammatory cascade, and respond to glucocorticoids. However, EoE also has several distinguishing characteristics which may be explained by a distinct pathophysiologic mechanism. Methods: The following report consist of four related narrative reviews which combine comprehensive PubMed and Google searches. Two reviews were performed to identify and contrast all eligible studies describing serologic markers in EoE compared to asthma, AD, and CRS. Two additional reviews then compare the responses to parenteral biological therapies in EoE and in the same representative Th2 diseases. Key Content and Findings: Comprehensive literature searches definitively differentiate the absence of serologic markers in EoE compared to their identification in the other representative Th2 diseases. Similarly, a summary of therapeutic trials demonstrates that while EoE is unable to clinically respond to a variety of parenteral biological therapies, asthma, AD and CRS are very effectively treated with this same approach. A novel pathophysiology for EoE is proposed, and the emerging literature that support its existence is summarized. Conclusions: The fundamental properties described in this narrative regarding serologic signaling and response to parenteral therapy in EoE could be explained if EoE employs a unique application of the Th2 pathway. One potential mechanism consistent with these observations is that EoE employs exclusively esophageal mucosal constituents to initiate and generate the prototypical Th2 cascade and the fibrostenotic changes that follow.

Pediatric Eosinophilic Esophagitis: Searching for Serologic Markers.

OBJECTIVE: Eosinophilic esophagitis (EoE) is a Th2 disease that presently is diagnosed and followed by clinical symptoms in the presence of endoscopic biopsies documenting elevated esophageal eosinophilia. To simplify clinical care, multiple studies have attempted to identify a disease specific serologic marker. None have been successful. The goal of this study was to employ custom designed Luminex multiplex bead assays to identify a reliable serologic marker for EoE. METHODS: Luminex assays were employed to measure serum levels of 11 analytes associated with EoE (IL-5, lL13, periostin, eotaxin-3, thymic stromal lymphopoietin, and immunoglobulins) in a cohort of pediatric patients consisting of active EoE (n=30), EoE in remission (n=13), and controls (n=34). RESULTS: No analyte was found to be elevated or depressed in active EoE compared to the other groups. Additionally, among the cohort with active EoE, none of the 11 analytes correlated with peak esophageal eosinophilia, endoscopic features of EoE quantitatively defined by an EoE validated endoscopic reference score (EREFS), or esophageal thickness as determined by endosonography. CONCLUSION: This is the largest prospective survey of heterogeneous markers studied in a consecutive cohort to determine whether they could diagnose or follow EoE. Although none were identified in this cohort, Luminex provides a rapid, economical tool to simultaneously screen multiple sera for proteins that are increased or decreased in disease states.

Effect of Highland Barley on Rheological Properties, Textural Properties and Starch Digestibility of Chinese Steamed Bread.

Highland barley has a different composition and structure to other crops. It has higher contents of total polyphenol (TPC), total flavonoid (TFC) and ß-glucan, which can be supplemented to improve the nutrition of wheat-flour-based food. In this study, the flours of three different grain-colored highland barley varieties Beiqing 6 (BQ), Dulihuang (DLH), and Heilaoya (HLY), were added to Jimai60 (JM, a wheat variety with medium gluten) wheat flour at different substitution levels to investigate their effects on the unextractable polymeric protein (UPP) content, micro-structure, rheological properties and mixing properties of dough, and the color, texture, flavor, and in vitro digestion of Chinese steam bread (CSB). The results showed that the moderate substitution of highland barley (20%) increased the UPP%, optimized the micro-structure of gluten, and improved its rheological properties by increasing dough viscoelasticity. The CSBs made from the composite flours exhibited a similar specific volume, cohesiveness, springiness and resilience to wheat CSB, while the firmness of composite CSBs (particularly JM-HLY-20) was delayed during storage. Importantly, the addition of highland barley increased the contents of TPC, TFC and ß-glucan, but decreased the in vitro starch digestibility of CSBs. A sensory evaluation showed that JM-HLY CSB was the most preferable. Taken together, highland barley can be used as a fine supplement to food products, with health-promoting properties.

Deleterious Rare Mutations of GLI1 Dysregulate Sonic Hedgehog Signaling in Human Congenital Heart Disease.

The Glioma-associated oncogene (Gli) family members of zinc finger DNA-binding proteins are core effectors of Sonic hedgehog (SHH) signaling pathway. Studies in model organisms have identified that the Gli genes play critical roles during organ development, including the heart, brain, kidneys, etc. Deleterious mutations in GLI genes have previously been revealed in several human developmental disorders, but few in congenital heart disease (CHD). In this study, the mutations in GLI1-3 genes were captured by next generation sequencing in human cohorts composed of 412 individuals with CHD and 213 ethnically matched normal controls. A total of 20 patient-specific nonsynonymous rare mutations in coding regions of human GLI1-3 genes were identified. Functional analyses showed that GLI1 c.820G> T (p.G274C) is a gain-of-function mutation, while GLI1 c.878G>A (p.R293H) and c.1442T>A (p.L481X) are loss-of-function mutations. Our findings suggested that deleterious rare mutations in GLI1 gene broke the balance of the SHH signaling pathway regulation and may constitute a great contribution to human CHD, which shed new light on understanding genetic mechanism of embryo cardiogenesis regulated by SHH signaling.

Effect of Mineral Admixtures on the Performance of Ceramsite Shotcrete for High Geothermal Underground Engineering.

Ceramsite concrete is used in lining structures of underground engineering in the geothermal environment. This study, by means of mixing fly ash and silica fume, aims at diminishing the adverse effects on concrete performance caused by elevated temperature in high geothermal underground engineering. Under simulated geothermal conditions (20, 40, and 60 °C, RH ≥ 90%), it was first proposed that 15 and 5 wt % cement replacements by fly ash and silica fume, respectively, were most optimal. Then, the effect of mineral admixtures on ceramsite shotcrete performance was investigated. The results show that the mixing of fly ash and silica fume could improve ceramsite shotcrete adaptability in elevated curing temperature. Particularly for silica fume, at 40 °C curing temperature, the 28-day compressive strength and splitting tensile strength increased by 12.6 and 50.9%, respectively. The improvement effect of silica fume on permeability resistance and resistance to chloride ion permeability was higher than that of fly ash. Nevertheless, the mixing of fly ash was more effective than silica fume for reducing thermal conductivity.

Interaction of B-type starch with gluten skeleton improves wheat dough mixing properties by stabilizing gluten micro-structure.

Some recent studies have revealed individual and the combined interactions of gluten and starch affecting dough mixing properties. However, the combined influence of high-molecular-weight glutenin subunits (HMW-GS) and starch on dough mixing and rheological properties requires elucidation. Thus four recombinant inbred lines, SS 1, SS 2, ZZ 1 and ZZ 2, were selected based on their HMW-GSs compositions. Compared to ZZ 1 and ZZ 2, both SS 1 and SS 2 carried superior HMW-GS alleles, and exhibited extended dough development and stability time, indicating their significant dough mixing characteristics. The gluten skeleton of the wheat lines SS 2 and ZZ 2 with higher B-type starch proportions exhibited fewer breakages along with the rise of dough temperature during mixing. Higher content of B-type starch strengthens interaction between starch and gluten skeleton at the dough heating stage, suggesting a specific range of B-type starch proportion can improve dough mixing characteristics.

Presence and Absence of Barren Plateaus in Tensor-Network Based Machine Learning.

Tensor networks are efficient representations of high-dimensional tensors with widespread applications in quantum many-body physics. Recently, they have been adapted to the field of machine learning, giving rise to an emergent research frontier that has attracted considerable attention. Here, we study the trainability of tensor-network based machine learning models by exploring the landscapes of different loss functions, with a focus on the matrix product states (also called tensor trains) architecture. In particular, we rigorously prove that barren plateaus (i.e., exponentially vanishing gradients) prevail in the training process of the machine learning algorithms with global loss functions. Whereas, for local loss functions the gradients with respect to variational parameters near the local observables do not vanish as the system size increases. Therefore, the barren plateaus are absent in this case and the corresponding models could be efficiently trainable. Our results reveal a crucial aspect of tensor-network based machine learning in a rigorous fashion, which provide a valuable guide for both practical applications and theoretical studies in the future.

Effect of Hulless Barley Flours on Dough Rheological Properties, Baking Quality, and Starch Digestibility of Wheat Bread.

Hulless barley (Hordeum vulgare L.), also known as highland barley, contains nutritional compounds, such as ß-glucan and polyphenol, which can be added to wheat flour to improve the dough nutritional quality. In this study, different formulated dough samples were obtained by individually adding four hulless barley flours into flour of a wheat variety (Jimai 44, designated as JM) which has very strong gluten. The effects of hulless barley supplementation on gluten structure, dough rheological properties, bread-making properties, and starch digestibility were assessed. The results showed that compared with JM dough, substitution of hulless barley flour to wheat flour at levels ranging from 10 to 40% negatively affected gluten micro-structure and dough mixing behavior, because the cross-links of gluten network were partially broken and the dough development time and stability time were shortened. For the hulless barley-supplemented bread, specific volume was significantly (P < 0.05) increased while springiness was not greatly changed. Furthermore, the hydrolysed starch rate in hulless barley-supplemented bread was decreased, compared with that in JM bread. Importantly, the contents of ß-glucan, polyphenols and flavonoids in hulless barley-supplemented bread were 132.61-160.87%, 5.71-48.57%, and 25-293.75% higher than those in JM bread, respectively. Taken together, the hulless barley-supplemented bread has been fortified with enhanced nutritional components, more desirable bread-making quality, and improved starch hydrolytic properties, which shows a great potential to use hulless barley as a health supplement.

Integrated Analysis of miRNA-mRNA Regulatory Networks Associated with Osteonecrosis of the Femoral Head.

Osteonecrosis of the femoral head (ONFH) accounts for as many as 18% of total hip arthroplasties. Knowledge of genetic changes and molecular abnormalities could help identify individuals considered to be at a higher risk of developing ONFH. In this study, we sought to identify differentially expressed miRNAs (DEmiRs) and genes (DEGs) associated with ONFH by integrated bioinformatics analyses as well as to construct the miRNA-mRNA regulatory network involving in the pathogenesis of ONFH. We performed differential expression analysis using a gene expression profile GSE123568 and a miRNA expression profile GSE89587 deposited in the Gene Expression Omnibus and identified 47 DEmiRs (24 upregulated miRNAs and 23 downregulated miRNAs) and 529 DEGs (218 upregulated genes and 311 downregulated genes). Gene Ontology enrichment analyses of DEGs suggested that DEGs were significantly enriched in neutrophil activation, cytosol, and ubiquitin-protein transferase activity. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of DEGs revealed that DEGs were significantly enriched in transcriptional misregulation in cancer. DEGs-based miRNA-mRNA regulatory networks were obtained by searching miRNA-mRNA prediction databases, TargetScan, miTarBase, miRMap, miRDB, and miRanda databases. Then, overlapped miRNAs were selected between these putative miRNAs and DEmiRs between ONFH and non-ONFH, and pairs of the DEmiR-DEG regulatory network were finally depicted. There were 12 nodes and 64 interactions for upDEmiR-downDEG regulatory networks and 6 nodes and 16 interactions for downDEmiR-upDEG regulatory networks. Using the STRING database, we established a protein-protein interaction network based on the overlapped DEGs between ONFH and non-ONFH. C5AR1, CDC27, CDC34, KAT2B, CPPED1, TFDP1, and MX2 were identified as the hub genes. The present study characterizes the miRNA profile, gene profile, and miRNA-mRNA regulatory network in ONFH, which may contribute to the interpretation of the pathogenesis of ONFH and the identification of novel biomarkers and therapeutic targets for ONFH.

Control and Signal Acquisition System of Broad-Spectrum Micro-Near-Infrared Spectrometer Based on Dual Single Detector.

Based on the scanning grating mirror developed by us, this paper presents a method for precise control of the scanning grating mirror and high-speed spectrum data acquisition. In addition, a system circuit of the scanning grating mirror control and a spectrum signal acquisition system were designed and manufactured. The final results of the experiment show that the control system successfully allowed the precise control of the swing of the scanning grating mirror and the acquisition system successfully carried out the high-speed acquisition and transmission of the spectrum and angle data. The spectrum detection range of the NIR spectrometer was 80-2532 nm. The overall resolution of the spectrum was better than 12 nm.

Unsupervised Learning of Non-Hermitian Topological Phases.

Non-Hermitian topological phases bear a number of exotic properties, such as the non-Hermitian skin effect and the breakdown of conventional bulk-boundary correspondence. In this Letter, we introduce an unsupervised machine learning approach to classify non-Hermitian topological phases based on diffusion maps, which are widely used in manifold learning. We find that the non-Hermitian skin effect will pose a notable obstacle, rendering the straightforward extension of unsupervised learning approaches to topological phases for Hermitian systems ineffective in clustering non-Hermitian topological phases. Through theoretical analysis and numerical simulations of two prototypical models, we show that this difficulty can be circumvented by choosing the "on-site" elements of the projective matrix as the input data. Our results provide a valuable guidance for future studies on learning non-Hermitian topological phases in an unsupervised fashion, both in theory and experiment.

Addition of Aegilops geniculata 1Ug chromosome improves the dough rheological properties by changing the composition and micro-structure of gluten.

Aegilops geniculata, a relative of common wheat, has many useful traits for the improvements of wheat varieties. The wheat-Ae. geniculata disomic addition lines (DALs) carrying prior traits need to be characterized for wheat varieties improvement. We currently found that CS-1Ug (Chinese Spring-Ae. geniculata 1Ug DAL) possessed improved dough rheological properties than CS (Chinese Spring) did, and investigated the reasons of those rheological changes in dough. The results showed that CS-1Ug carries a novel high-molecular-weight glutenin subunit (HMW-GS), a substitute for Dx2 from CS, which led to the changes in the relative proportion of individual HMW-GS in total HMW-GSs. Changes in gluten composition improved the stability and elasticity of dough by promoting the accumulation of unextractable polymeric protein, and optimizing the micro-structure of the gluten. The current study provides basic information on CS-1Ug used as a potential resource for future wheat quality breeding.

Novel parameters characterizing size distribution of A and B starch granules in the gluten network: Effects on dough stability in bread wheat.

Our study on six wheat genotypes has revealed strong interaction between gluten and starch to affect dough stability. To establish gluten-starch interaction and its roles in dough stability, we randomly selected 16 wheat genotypes and investigated the physicochemical properties of gluten and starch. The manner in which the starch granules occupied available space in gluten network was quantitatively analyzed using gluten lacunarity and proportion of different sized A-type and B-type starch granules. Positive correlations were found between the morphological attributes (B/A/Lacunarity, B/Lacunarity) and dough stability. The correlation coefficient between B/A/Lacunarity and dough stability was highest, followed by the percentage of unextractable polymeric protein (UPP%), B/Lacunarity and dough stability. Dough mixing properties were strongly affected by gluten-starch interactions, as indicated by novel parameters. Whereas the effect of gluten on its own did not provide any evidence to suggest its concrete role in dough mixing properties because of the various genetic backgrounds.

The overexpression of high-molecular-weight glutenin subunit Bx7 improves the dough rheological properties by altering secondary and micro-structures of wheat gluten.

Bread wheat (Triticum aestivum L.) is one of the crucial cereals consumed by human beings and wheat gluten, the natural macromolecules, mainly determines the processing quality of wheat dough. The high-molecular-weight glutenin subunits (HMW-GSs) of gluten proteins are recognized as one of the main components regulating the rheological properties of dough. The overexpressed Bx7 subunit (Bx7OE) has been reported to improve wheat quality and rheological properties of dough, however its effect on secondary and micro- structures of gluten is still unclear. In this study, we evaluated the composition of main storage proteins in wheat grains of two near-isogenic lines and studied the effect of Bx7 subunit expression level on the secondary structures of gluten and micro-structure of gluten during dough mixing process. Results showed the protein content, HMW-GSs proportion in total glutenins and free sulfhydryl content increased in the flour of HMW-Bx7OE wheat line, and the accumulation of unextractable polymeric protein during grain filling stage accelerated. It was found that the content of ß-sheets in secondary structures of gluten increased and a more compact micro-structure of gluten network formed in the dough. Protein network analysis characterized and quantified the alterations in the gluten micro-structure. In the process of dough mixing, protein area, total protein length, number of junctions and branching rate reach the peak at dough development time, which was consistent with Chopin mixing profile. Interestingly, during dough mixing, the above-mentioned parameters of HMW-Bx7OE showed less changes than those of HMW-Bx7 wheat line, indicating Bx7OE improved the dough stability during mixing. To conclude, Bx7OE alters the secondary and micro- structures of gluten and thus improves the mixing and rheological properties of wheat dough.

Bilayer Designed Hydrocarbon Membranes for All-Climate Vanadium Flow Batteries To Shield Catholyte Degradation and Mitigate Electrolyte Crossover.

The use of low-cost hydrocarbon membranes in vanadium flow batteries (VFBs) still remains a great challenge because of the strong oxidation of VO2+ catholyte and rapid capacity fading. Here, we report a bilayer design strategy using an antioxidant and dense cross-linked sulfonated polyimide (cSPI) layer as a protective layer for a sulfonated poly(ether ether ketone) (SPEEK) membrane to shield catholyte degradation and mitigate electrolyte crossover. A scalable process is developed to fabricate an integrated bilayer SPEEK/cSPI membrane without delamination by spraying a SPEEK transition layer between the two polymers. The tightly bridged cSPI layer not only protects the SPEEK membrane from degradation but also enhances its mechanical strength, puncture resistance, and proton/vanadium-ion selectivity. When assembled in a VFB, the bilayer SPEEK/cSPI membrane demonstrates excellent rate performance under current densities of 40-200 mA cm-2, high adaptability at a wide temperature range of -15 to 60 °C, very slow capacity decay rate of 0.054% per cycle at 160 mA cm-2, and a maximum power density of 480 mW cm-2. These merits make the bilayer SPEEK/cSPI membrane a promising candidate for the next-generation VFB to achieve low-cost, high-rate, and all-climate energy storage.