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Abstract The aim of this study was to develop a three-dimensional (3D) cell model in order to evaluate the effectiveness of a traditional Chinese medicine decoction in the treatment of arthritis. Chondrocytes (ATDC5) and osteoblasts (MC3T3-E1) were 3D printed separately using methacryloyl gelatin (GelMA) hydrogel bioinks to mimic the natural 3D cell environment. Both cell types showed good biocompatibility in GelMA. Lipopolysaccharide (LPS) was added to the cell models to create inflammation models, which resulted in increased expression of inflammatory factors IL-1β, TNF-α, iNOS, and IL-6, and decreased expression of cell functional genes such as Collagen II (COLII), transcription factor SOX-9 (Sox9), Aggrecan, alkaline phosphatase (ALP), RUNX family transcription factor 2 (Runx2), Collagen I (COLI), Osteopontin (OPN), and bone morphogenetic protein-2 (BMP-2). The created inflammation model was then used to evaluate the effectiveness of Dangguiniantongtang (DGNT) decoctions. The results showed that DGNT reduced the expression of inflammatory factors and increased the expression of functional genes in the cell model. In summary, this study established a 3D cell model to assess the effectiveness of traditional Chinese medicine (TCM) decoctions, characterized the gene expression profile of the inflammatory state model, and provided a practical reference for future research on TCM efficacy evaluation for arthritis treatment.

Abstract Background Early menarche is an established risk factor for breast cancer but its molecular contribution to tumor biology and prognosis remains unclear. Methods We profiled transcriptome-wide gene expression in breast tumors (N = 846) and tumor-adjacent normal tissues (N = 666) from women in the Nurses’ Health Studies (NHS) to investigate whether early menarche (age

Abstract We aimed to investigate the effects of Bacillus cereus YB1 on the growth, intestinal digestive enzyme activity, liver antioxidant enzyme activity, and intestinal tissue structure of juvenile black rockfish (Sebastes schlegelii). A 50‐day feeding experiment was conducted. Feeding was conducted in four diet groups: control group with no YB1 supplement in diet and three treatment groups E‐L, E‐M, and E‐H containing 105, 106, and 107 CFU/g YB1, respectively. The results revealed that the weight gain and specific growth rate of juvenile fish significantly increased, while the feed coefficient was reduced in all three diet treatment groups. This indicated that the growth of black rockfish was significantly and positively affected by YB1 feeding. Enzyme activity in the intestinal tract was not significantly affected by YB1. However, the activity of protease, amylase, and lipase increased because of YB1 treatment, except for the proteases in the E‐M diet group. Meanwhile, no significant differences were recorded in the activities of the antioxidant enzymes in liver, but the level of catalase, superoxide dismutase, and malondialdehyde activities in treatments shows a better performance compared with the control in overall perspective. Furthermore, the structural features of the intestine (i.e., number of intestinal villi, length of gut villi, and thickness of muscularis) was significantly elevated with the inclusion of B. cereus YB1 in the diet. These results reveal that dietary supplementation of B. cereus YB1 is beneficial to the boosting of enzymatic activities and structure of intestinal tissue as well as the antioxidative ability of liver tissue. Such findings suggest that fish growth would be improved under YB1 feeding conditions.

Abstract Background Circulating tumor DNA (ctDNA) has emerged as a potential novel biomarker to predict molecular residual disease (MRD) in lung cancer after definitive treatment. Herein, we investigated the value of ctDNA in prognosing risk of relapse and monitoring the effect of adjuvant therapy in surgical non‐small cell lung cancer (NSCLC). Methods We enrolled 58 NSCLC patients in a real‐world setting, and 58 tumor tissues and 325 plasma samples were analyzed. Tumor tissues and plasma samples were subjected to targeted next‐generation sequencing (NGS) of 1021 cancer‐related and ultra‐deep targeted NGS covering 338 genes, respectively. Results ctDNA was detected in 31.0% of cases at the first postoperative time, which was associated with advanced tumor stage, T stage and KEAP1 or GRIN2A mutations in tissues. ctDNA positivity at landmark and longitudinal indicated the shorter disease‐free survival. For patients with ctDNA positivity at the first postoperative time, regardless of adjuvant therapy, all patients who were persistently ctDNA positive during postoperative surveillance had disease recurrence. Among the patients who were ctDNA negative, only two patients (15.4%, 2/13) receiving adjuvant therapy relapsed, while one patient (50.0%, 1/2) without adjuvant therapy relapsed. For the first postoperative ctDNA negative patients, the recurrence rate of patients with adjuvant therapy was and higher than without adjuvant therapy (22.6% [7/31] vs. 11.1% [1/9]). The patients who became ctDNA positive may also benefit from intervention therapy. Conclusion Postoperative ctDNA is a prognostic marker, and ctDNA‐detection may facilitate personalized adjuvant therapy, and applying adjuvant therapy to the patients with detectable ctDNA could bring clinical benefits for them.

As a response of the coastal oceans to more severe anthropogenic disturbance, increasing coastal primary production has been more frequently observed in recent years. This raises the question of how this progressive change reshapes the long-term carbon sequestration in the coastal oceans. With this question in mind, we investigated the sediment organic matter (OM) preserved on the shelf of the northern South China Sea (NSCS) where high primary production has been observed. Across this sediment core, relatively low total organic carbon content of around 0.60% was observed. Fatty acids with less carbon numbers exhibit exponential decreases downward with degradation rate constants ranging from 0.10 to 0.17 y-1, no matter they were from single sources (14:0 presumably from marine OM and ai-15:0, i-15:0, 15:0 from bacterial OM) or mixed sources (16:0). Meanwhile fatty acids with more carbon numbers, either 18:0 and 24:0 from mixed sources, or 26:0 and 28:0 presumably from terrestrial input, were less varied in concentrations with depth. This demonstrates a preferential decomposition of labile fatty acids during the early diagenesis of coastal sediment organic matter. A decrease of labile fatty acids δ13C values was observed with the decomposition, from which kinetic isotope fractionations were predicted ranging from 0.7 to 1.5‰. This provides an isotopic constraint of the mixing model to quantify labile organic matter from terrestrial input and local phytoplankton production, from which declined contribution of local phytoplankton production to labile fatty acids was identified in more recent sediment. This finding together with the low organic carbon content and rapid removal of fatty acids in the top sediment, demonstrates the poor preservation of labile organic matter on the shelf of NSCS, implying that the increasing primary production has not enhanced the coastal carbon sequestration yet, but rather leads to more intensified respiration with a potential risk to increase the CO2 outgassing from the coastal oceans.

Sebastes schlegelii is a cold temperate ovoviviparous fish found near the seabed layer and is widely distributed in the Yellow Sea and Bohai Sea of China, as well as in the coasts of South Korea and Japan. It is characterized by its tender meat, delicious taste, rich nutrition, and high medicinal value, thus it is an economically important marine fish species in the northern coastal areas of China. In recent years, deep-water cage cultures have rapidly developed in China. Among the economically important fish species suitable for cage culture in northern China, S. schlegelii is the most important local breed with excellent quality and characteristics. However, with the expansion of the scale of the aquaculture industry, aquaculture diseases including those caused by Vibrio harveyi, Vibrio anguillarum, and Photobacterium damselae subsp. damselae, occur frequently. The authors isolated and identified a dominant pathogenic bacterium, the P5W of V. harveyi, from the lesions of diseased S. schlegelii and studied the response of S. schlegelii to V. harveyi infection. Multitissue transcriptome analysis screened the immune differential gene protein kinase B. Protein kinase B, also known as Akt protein, is a serine or threonine protein kinase, which mainly conducts signal transduction by phosphorylating other proteins. It plays an important role in various biological processes such as cell metabolism, transcriptional regulation, cell cycle regulation, immune defense, and embryonic development. Many studies have shown that during viral infection of cells, the Akt pathway is activated, thereby inhibiting viral proliferation. To clarify the sequence information, evolutionary characteristics, and biological functions of the Akt gene in S. schlegelii and to understand the immune response mechanism of S. schlegelii to bacterial invasion, the full-length cDNA of the SsAkt gene was obtained using molecular biology, and the sequence characteristics, tissue expression rules of the gene, and the response rules to Micrococcus luteus and V. anguillarum were studied. The results showed that the length of the open reading frame was 1 440 bp. The predicted relative molecular mass of the SsAkt protein was 55.80 kDa and the isoelectric point was 5.64. Sequence analysis revealed that the SsAkt protein contains three conserved domains: the PH domain (residues 6–109), serine/threonine protein kinase catalytic (S_TKc) domain (residues 148–405), and serine/threonine protein kinase (S_TK_X) domain (residues 406–475). The conserved amino acid site appears in the center of the S_TKc domain and at the end of the S_TK_ X domain: Thr305 and Ser472. Homologous alignment showed that the amino acid sequence of this gene was highly conserved among different species. Phylogenetic tree analysis showed that SsAkt is closely related to Akt in vertebrates, such as Sebastes umbrosus, Lates calcarifer, Larimichthys crocea, and Cyprinus carpio. The relative expression of SsAkt in different tissues of S. schlegelii was detected by real-time fluorescence quantitative PCR. The results showed that SsAkt was expressed in all tested healthy tissues of S. schlegelii, which indicated the relative expression of the SsAkt gene in S. schlegelii. This expression has distinct tissue specificity. The expression of SsAkt in the kidney is the highest, and in the blood and brain, it is also higher than that in other tissues. Therefore, it is speculated that higher expression of SsAkt in the kidney and brain is closely related to immune defense, neurodevelopment, and other processes. To study the role of SsAkt in the immune response of S. schlegelii, we designed a bacterial challenge experiment. The results showed that the transcription level of SsAkt changed significantly, and the relative expression of SsAkt in the three tissues increased after stimulation with M. luteus and V. anguillarum compared with the control group (PBS). After infection with M. luteus, its expression only increased sharply in the kidney, whereas its expression increased slowly in the blood and liver. In the experimental group infected with V. anguillarum, the expression increased significantly in the liver and kidney, and the two relative expression peaks in the kidney occurred at 12 h and 72 h after infection, respectively. The results revealed that the SsAkt gene may play an important role in the immune defense of S. schlegelii, which can further enrich the sequence information and evolutionary data of the Akt gene in marine fish and provide reference materials for an in-depth study of the biological function of this gene. In follow-up experiments, we will explore the specific mechanism of SsAkt in the innate immune defense of S. schlegelii to provide theoretical guidance for the study of the immune signaling pathway of S. schlegelii and to lay a theoretical foundation for revealing the role of SsAkt in other important biological functions in growth and development.

Abstract Background The pathogenic mechanisms shared between kidney stones and diabetes at the transcriptional level remain elusive, and the molecular mechanisms by which resveratrol exerts its protective effects against these conditions require further investigation. Methods To address these gaps in knowledge, we conducted a comprehensive analysis of microarray and RNA-seq datasets to elucidate shared biomarkers and biological pathways involved in the pathogenesis of kidney stones and diabetes. An assortment of bioinformatic approaches was employed to illuminate the common molecular markers and associated pathways, thereby contributing to the identification of innovative therapeutic targets. Further investigation into the molecular mechanisms of resveratrol in preventing these conditions was conducted using molecular docking simulation and first-principles calculations. Results The study identified 11 potential target genes associated with kidney stones and diabetes through the intersection of genes from weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) screening. Among these, Interleukin 11 (IL11) emerged as a pivotal hub gene and a potential diagnostic biomarker for both conditions, particularly in males. Expression analysis of IL11 demonstrated elevated levels in kidney stones and diabetes groups compared to controls. Additionally, IL11 exhibited correlations with specific cell types and differential expression in normal and pathological conditions. Gene set enrichment analysis (GSEA) highlighted significant disparities in biological processes, pathways, and immune signatures associated with IL11. Moreover, molecular docking simulation of resveratrol towards IL11 and a first-principles investigation of Ca adsorption on the resveratrol surface provided structural evidence for the development of resveratrol-based drugs for these conditions. Conclusions Overall, this investigation illuminates the discovery of common molecular mechanisms underlying kidney stones and diabetes, unveils potential diagnostic biomarkers, and elucidates the significance of IL11 in these conditions. It also provides insights into IL11 as a promising therapeutic target and highlights the role of resveratrol. Nonetheless, further research is warranted to enhance our understanding of IL11 targeting mechanisms and address any limitations in the study.

Marine fish are rich in minerals (calcium and iron), vitamins (riboflavin and niacin), nutrients that are beneficial for brain (fatty acids), docosahexaenoic acid that prevent cardiovascular and cerebrovascular diseases, and are an important source of protein for humans. In recent years, the nexus between the increased demand of high-quality protein and the decrease in marine fishery resources resulted in the intensification of marine farming. However, this high-density farming has led to various bacterial diseases frequently due to lack of disease control methods, which has caused economic losses in the farming industry and impeded the healthy development of the industry. Therefore, it is particularly important to reduce the rates of bacterial diseases and improve the survival rate of cultured fish. It is of particular concern on how to maintain intestinal health of cultured fish under this farming method. Probiotics, a kind of living microorganisms, are beneficial to the health of the host. In the 1980s, probiotics have been viewed as an environmentally friendly and effective product in aquaculture; they improve the host health by influencing intestinal microbiota and nonspecific immunity to increase disease resistance ability. Moreover, they can be used as an ideal substitute for antibiotics in aquaculture production. Probiotics from Bacillus, lactic acid bacteria, saccharomyces, and nitrobacteria are diverse, and the function of each varies widely. As the typical representative of probiotics, lactic acid bacteria, may inhibit the growth of pathogens by the production of its metabolites, such as lactic acid, acetic acid, peroxide hydrogen, and bacteriocin. Lactic acid bacteria are also able to balance intestinal microecological imbalance and maintain intestinal microbiota balance when the intestinal microbiota contains pathogenic bacteria or the host is treated with antibiotics. Bacillus is an aerobic or facultative anaerobic gram-positive bacteria, which is stable, possesses strong stress resistance and high resurrection rate, and can produce various macromolecules, such as proteases and amylases and thus can improve the digestive function of the host by promoting the absorption of nutrients. Furthermore, as a non-specific immune antigen, Bacillus can improve the immune resistance of the host by stimulation of the components of cells or cell walls. The application of lactic acid bacteria and Bacillus has demonstrated favorable results, but this has been limited in marine fish culture because the non-fish origin of some strains and the different specificity of strains for different fish species or the same growth stage make their application difficult. Thus, it is essential to develop marine fish-derived probiotics, analyze their characteristics, define growth conditions, verify safety effects, and determine dosage and methods for their administer in marine fish culture. In this study, probiotics from marine fish were screened for the development of microbial ecological agents; 80 strains of culturable bacteria were obtained by separating bacteria from the mucosa samples of the digestive tract of wild Sebastes schlegelii and Hexagrammos otakii. The enzyme-producing ability of the strains was determined using a selective culture medium. The common pathogenic bacteria infecting marine fish were selected as indicator bacteria to determine the antibacterial activity of the isolated strains. Two potential probiotics, strains TS2 and TH8, were screened, and their physiological and biochemical identification, 16S rDNA sequence, growth characteristics, and host safety were determined. The results showed that TS2 had the strongest ability to hydrolyze starch, protein, and fat, and its sterile culture products could significantly inhibit the growth of Vibrio anguillarum, V. parahaemolyticus, V. Harvey, and Pseudoalteromonas nigrifaciens. TH8 has the strongest ability to hydrolyze protein and fat, and its sterile culture products could significantly inhibit the growth of V. anguillarum, V. alginolyticus, V. parahaemolyticus, P. nigrifaciens, Aeromonas hydrophila, Staphyloccocus aureus, and Escherichia coli. According to the analysis of the physiological and biochemical characteristics of the bacteria and 16S rDNA sequence alignment analysis, strain TS2 was identified as Bacillus subtilis and strain TH8 as Vagococcus fluvialis. Strain TS2 showed significant growth at 15–40 ℃, sodium chloride concentration of 0–0.08 g/L, and pH of 5–9; it entered the logarithmic phase after 6 h and the stable phase after 26 h. TH8 grew rapidly at 20–40 ℃, sodium chloride concentration of 0–0.08 g/L, and pH of 5–12; it entered the logarithmic phase after 2 h and the stable phase after 14 h. The safety of strains TS2 and TH8 was analyzed on a homologous host, and it was found that the strains were relatively safe for the homologous host at the concentration of 108 CFU/mL. The screened B. subtilis TS2 and V. fluvialis TH8 strains have a strong enzyme production ability and inhibit the growth of various pathogens by their metabolites; they have the following advantages: Wide temperature and salt tolerance, acid and alkali resistance, and fast growth speed. Thus, they could be considered as potential probiotic candidates for the development of microbial pharmaceuticals and can be used in more applications in marine aquaculture.

Rheumatoid arthritis poses a significant threat to the well-being of individuals as an autoimmune disorder. Calycosin is a flavonoid isolated from the root of Astragalus that may be beneficial in treating rheumatoid arthritis. The anti-inflammatory role and mechanism of calycosin were validated in this study through the utilization of collagen-induced arthritis mice models and lipopolysaccharide/interferon gamma stimulated bone marrow-derived macrophages. By applying RNA sequencing technology and the network pharmacological method, it is demonstrated in the findings that the treatment with calycosin leads to a significant alleviation of arthritis symptoms, mitigation of synovial proliferation, impediment of bone and cartilage devastation, and suppression of activated synovial macrophages in collagen-induced arthritis. Mechanistically, activation of JNK and NF-κB pathways is inhibited by calycosin in lipopolysaccharide/interferon gamma stimulated bone marrow-derived macrophages. These results confirm the potential of calycosin, a natural compound, for attenuating rheumatoid arthritis by acting as an anti-inflammatory agent through multiple pathways.

Abstract Background Osteoporosis is a metabolic disease, and osteoporotic fracture (OPF) is one of its most serious complications. It is often ignored that the influence of the muscles surrounding the fracture on the healing of OPF. We aimed to clarify the role of skeletal muscle satellite cells (SMSCs) in promoting OPF healing by β‐catenin, to improve our understanding of SMSCs, and let us explore its potential as a therapeutic target. Methods Skeletal muscles were obtained from control non‐OPF or OPF patients for primary SMSCs culture (n = 3, 33% females, mean age 60 ± 15.52). Expression of SMSCs was measured. In vivo, 3‐month‐old female C57BL/6 mice underwent OVX surgery. Three months later, the left tibia fracture model was again performed. The control and the treatment group (n = 24, per group, female). The treatment group was treated with an agonist (osthole). Detection of SMSCs in muscles and fracture healing at 7, 14, and 28 three time points (n = 8, 8, 8, female). To further clarify the scientific hypothesis, we innovatively used Pax7‐CreERT2/+;β‐cateninfx/fx transgenic mice (n = 12, per group, male). Knock out β‐catenin in SMSC to observe the proliferation and osteogenic differentiation of SMSCs, and OPF healing. In vitro primary cells of SMSCs from 3‐month‐old litter‐negative β‐cateninfx/fx transgenic mice. After adenovirus‐CRE transfection, the myogenic and osteogenic differentiation of SMSC was observed. Results We find that human SMSCs reduced proliferation and osteogenic differentiation in patients with OPF (−38.63%, P

Maturases can specifically bind to intron-containing pre-RNAs, folding them into catalytic structures that facilitate intron splicing in vivo. Plants possess four nuclear-encoded maturase-related factors (nMAT1-nMAT4) and some maturases have been shown to involve in the splicing of different mitochondrial group II introns; however, the specific biological functions of maturases in maize are largely uncharacterized. In this study, we identified a maize ZmnMAT1 gene, which encodes a mitochondrion-localized type I maturase with an RT domain at N-terminus and an X domain at C-terminus. Loss-of-function mutation in ZmnMAT1 significantly reduced the splicing efficiencies of Nad1 intron 1 and Nad4 intron 2, and showed arrested embryogenesis and endosperm development, which may be related to impaired mitochondrial ultrastructure and function due to the destruction of the assembly and activity of complex I. Direct physical interaction was undetectable between ZmnMAT1 and the proteins associated with the splicing of Nad1 intron 1 and/or Nad4 intron 2 by yeast two-hybrid assays, suggesting the complexity of group II intron splicing in plants.

Introduction Pulsed radiofrequency (PRF) ablation is commonly used for the treatment of neuropathic pain (NP). However, it is unclear whether increasing the output voltage of PRF can safely improve its efficacy. This study aims to compare the efficacy and safety of high-voltage PRF ablation and standard-voltage PRF ablation for the treatment of patients with NP.Methods and analysis We will search PubMed/MEDLINE, EMBASE, Web of Science, the Cochrane Library, conference proceedings for relevant abstracts, clinical trials registers (ClinicalTrials.gov) and the WHO’s International Clinical Trial Registry Platform (from the date of inception until 15 March 2022). Only randomised controlled trials will be included. Two reviewers (YJ and GF) will independently perform study screening and selection, data extraction, risk-of-bias assessment and quality-of-evidence assessment. The primary outcome of this meta-analysis will be the efficiency rate in patients with NP. The secondary outcomes will include numeric rating scale score, visual analogue scale score, time to take effect, rescue drug dosage, quality of life using the health questionnaire (SF-36) and the incidence of adverse events. Meta-analyses will be conducted using standard meta-analysis software (RevMan V.5.3, The Nordic Cochrane Center, The Cochrane Collaboration, Copenhagen, Denmark).Ethics and dissemination The requirement for ethical approval was waived as our systematic review will be based on the published literature. The results of this study will be submitted to a peer-reviewed journal.PROSPERO registration number CRD42022297804.

An adaptive backstepping fuzzy neural network (FNN) controller using a fuzzy sliding mode controller is designed to suppress the harmonics and improve the performance of a shunt active power filter (APF). A backstepping method transforms the APF system into a series of subsystems and uses the virtual control to simplify the controller design. A FNN controller is utilized to approach the nonlinear APF system. An adaptive fuzzy system is employed to adjust the sliding gain to compensate the approximation error of neural network and diminish the chattering. The weights of the fuzzy neural network and fuzzy system parameters are adjusted in real-time to guarantee the asymptotic stability of the designed control system. Simulation and experiemental studies indicate the validitiy of the proposed control method, demonstrating the good compensation performance and strong robustness.

Digital pathology can efficiently assess immunohistochemistry (IHC) data on tissue microarrays (TMAs). Yet, it remains important to evaluate the comparability of the data acquired by different software applications and validate it against pathologist manual interpretation. In this study, we compared the IHC quantification of 5 clinical breast cancer biomarkers—estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), and cytokeratin 5/6 (CK5/6)—across 3 software applications (Definiens Tissue Studio, inForm, and QuPath) and benchmarked the results to pathologist manual scores.IHC expression for each marker was evaluated across 4 TMAs consisting of 935 breast tumor tissue cores from 367 women within the Nurses’ Health Studies; each women contributing three 0.6-mm cores. The correlation and agreement between manual and software-derived results were primarily assessed using Spearman’s ρ, percentage agreement, and area under the curve (AUC).At the TMA core-level, the correlations between manual and software-derived scores were the highest for HER2 (ρ ranging from 0.75 to 0.79), followed by ER (0.69–0.71), PR (0.67–0.72), CK5/6 (0.43–0.47), and EGFR (0.38–0.45). At the case-level, there were good correlations between manual and software-derived scores for all 5 markers (ρ ranging from 0.43 to 0.82), where QuPath had the highest correlations. Software-derived scores were highly comparable to each other (ρ ranging from 0.80 to 0.99). The average percentage agreements between manual and software-derived scores were excellent for ER (90.8%–94.5%) and PR (78.2%–85.2%), moderate for HER2 (65.4%–77.0%), highly variable for EGFR (48.2%–82.8%), and poor for CK5/6 (22.4%–45.0%). All AUCs across markers and software applications were ≥0.83.The 3 software applications were highly comparable to each other and to manual scores in quantifying these 5 markers. QuPath consistently produced the best performance, indicating this open-source software is an excellent alternative for future use.

Noninvasive drug delivery is a promising treatment strategy for ocular posterior segment diseases. Many physiological and anatomical barriers of the eye considerably restrict effective diffusion of therapeutics to the target site. To overcome this problem, a novel cyclic arginine-glycine-aspartate (RGD) hexapeptide and penetratin (PEN) co-modified PEGylation polyamidoamine (PAMAM) was designed as a nanocarriers (NCs), and its penetrating and targeting abilities were evaluated. In this study, we show that PAMAM-PEG (reaction molar ratio 1:32) has a relatively high grafting efficiency and low cytotoxicity. The particle size was within the range of 15–20 nm after modification with RGD and PEN. Cellular uptake of RGD-modified NCs involved significant affinity toward integrin αvβ3, which validated the targeting of neovasculature. An in vitro permeation study indicated that modification with PEN significantly improved penetration of the NCs (1.5 times higher). In vivo ocular distribution studies showed that, the NCs (modified with PEN or co-modified with RGD and PEN) were highly distributed in the cornea and retina (p

Objective This study aimed to present our experience of concomitant management of renal calculi and recurrent ureteropelvic junction obstruction (UPJO) with percutaneous nephrolithotomy (PCNL) and antegrade balloon dilation. Methods We retrospectively reviewed 31 patients who underwent PCNL and antegrade balloon dilation for treatment of renal calculi and recurrent UPJO. The inclusion criterion was the presence of UPJO after failed pyeloplasty with ipsilateral renal calculi. Success was defined as achievement of both symptomatic and radiographic resolution of any stones and obstruction. Results All operations were successful without grade III or higher postoperative complications. A stone-free status was observed in all patients and the overall success rate of the procedure was 87.1% (27/31). The success rate of the procedure was significantly higher in patients with mild or moderate preoperative hydronephrosis (96%) than in those with high-grade preoperative hydronephrosis (50%). Moreover, the success rate of the procedure was lower in patients with poor preoperative renal function (0%) than in those with good or moderate renal function (93.1%). Conclusion Combined PCNL and antegrade balloon dilation management represents a safe and effective approach for patients with renal calculi and recurrent UPJO after failed pyeloplasty.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that is primarily characterized by synovial inflammation. In this study, we found that a traditional Chinese decoction, Juanbi-Tang (JBT), JBT attenuated the symptoms of collagen-induced arthritis (CIA) mice and in tumor necrosis factor transgenic (TNF-Tg) mice by attenuating the arthritis index and hind paw thickness. According to histopathological staining of ankle sections, JBT significantly decreased the area of inflammation and reduced bone destruction of ankle joints in both these two types of mice. Moreover, decreased tartaric acid phosphatase-positive osteoclasts were observed in the JBT group compared with those found in the control group. We also revealed that JBT suppressed monocytes and T cells as well as the production of CCL2, CCR6, and CXCR3 ligands. We next used high-performance liquid chromatography to investigate the components and pharmacological properties of this classical herbal medicine in traditional Chinese medicine. Based on network pharmacology, we performed computational prediction simulation of the potential targets of JBT, which indicated the NF-kappa B pathway as its target, which was confirmed in vitro. JBT suppressed the production of pro-inflammatory cytokines including interleukin-6 (IL-6) and IL-8, and inhibited the expression of matrix metalloproteinase 1 in fibroblast-like synoviocytes derived from RA patients (MH7A cells). Furthermore, JBT also suppressed the phosphorylation of p38, JNK, and p65 in TNF-α-treated MH7A cells. In summary, this study proved that JBT could inhibit synovial inflammation and bone destruction, possibly by blocking the phosphorylation of NF-kappa B pathway-mediated production of proinflammatory effectors.

Lung cancer is a leading cause of cancer mortality worldwide. As the incidence of lung cancer increases in recent years, the number of patients diagnosed with synchronous multiple primary lung cancers (SMPLC) is also rising. SMPLC diagnosis is often made based on the clinical course, imaging findings, and histologic and molecular features. Standard lobectomy is the main therapeutic modality for SMPLC. Because maximum retention of lung function is essential, sublobectomy is also a commonly used surgical strategy when appropriate. The question is how to optimize the sequence of lobectomy and sublobectomy for patients with SMPLC. Thoracoscope lobectomy for the primary lesion plus sublobectomy for the secondary lesions is the most commonly used approach. Here we present a case of SMPLC with sublobectomy followed by lobectomy.

Astragalin, as a bioactive flavonoid with anti-inflammatory, antioxidant, and protective properties, provides a potential agent for rheumatoid arthritis (RA). In this study, its therapeutic efficacy and the underlying mechanisms were explored using DBA/1J mice with collagen-induced arthritis (CIA). It was demonstrated that astragalin could significantly attenuate inflammation of CIA mice. The effects were associated with decreased severity of arthritis (based on the arthritis index), joint swelling and reduced bone erosion and destruction. Furthermore, astragalin treatment suppressed the production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-8), and inhibited the expression of matrix metalloproteinases (MMP-1, MMP-3, and MMP-13) in chondrocytes and synovial cells of CIA mice. Fibroblast-like synoviocytes derived from RA patients (MH7A cells) were applied to verify these effects. In vitro, astragalin inhibited the expression of matrix metalloproteinases (MMP-1, MMP-3, and MMP-13) dose-dependently in TNF-α-induced MH7A cells, with no apparent cytotoxicity. Furthermore, astragalin suppressed the phosphorylation of p38, JNK, and the activation of c-Jun/AP-1 in TNF-α-induced MH7A cells. In conclusion, it has proven that astragalin could attenuate synovial inflammation and joint destruction in RA at least partially by restraining the phosphorylation of MAPKs and the activating of c-Jun/AP-1. Therefore, astragalin can be a potential therapeutic agent for RA.

Graphene’s outstanding properties make it a potential material for reinforced cementitious composites. However, its shortcomings, such as easy agglomeration and poor dispersion, severely restrict its application in cementitious materials. In this paper, a highly dispersible graphene (TiO2-RGO) with better dispersibility compared with graphene oxide (GO) is obtained through improvement of the graphene preparation method. In this study, both GO and TiO2-RGO can improve the pore size distribution of cement mortars. According to the results of the mercury intrusion porosity (MIP) test, the porosity of cement mortar mixed with GO and TiO2-RGO was reduced by 26% and 40%, respectively, relative to ordinary cement mortar specimens. However, the TiO2-RGO cement mortars showed better pore size distribution and porosity than GO cement mortars. Comparative tests on the strength and durability of ordinary cement mortars, GO cement mortars, and TiO2-RGO cement mortars were conducted, and it was found that with the same amount of TiO2-RGO and GO, the TiO2-RGO cement mortars have nearly twice the strength of GO cement mortars. In addition, it has far higher durability, such as impermeability and chloride ion penetration resistance, than GO cement mortars. These results indicate that TiO2-RGO prepared by titanium dioxide (TiO2) intercalation can better improve the strength and durability performance of cement mortars compared to GO.

A novel adaptive radial basis function neural network H-infinity control strategy with robust feedback compensator using linear matrix inequality (LMI) approach is proposed for micro electro mechanical systems vibratory gyroscopes involving parametric uncertainties and external disturbances. The proposed system is comprised of a neural network controller, which is designed to mimic an equivalent control law aimed at relaxing the requirement of exact mathematical model and a robust feedback controller, which is derived to eliminate the effect of modeling error and external disturbances. Based on the Lyapunov stability theorem, it is shown that H-infinity tracking performance of the gyroscope system can be achieved, all variables of the closed-loop system are bounded, and the effect due to external disturbances on the tracking error can be attenuated effectively. Numerical simulations are investigated to demonstrate that the satisfactory tracking performance and strong robustness against external disturbances can be obtained using the proposed adaptive neural H-infinity control strategy with robust feedback compensator by LMI technique.

This paper proposes an adaptive radial basis function (RBF) neural network (NN) fuzzy control scheme to enhance the performance of shunt active power filter (APF).The RBF NN is utilized on the approximation of nonlinear function in the APF dynamic model and the weights of the RBF NN are adjusted online according to adaptive law from the Lyapunov stability analysis to ensure the state hitting the sliding surface and sliding along it. In order to compensate the network approximation error and eliminate the existing chattering, the sliding mode control term is adjusted by adaptive fuzzy systems, which can enhance the robust performance of the system. The simulation results of APF using the proposed method confirm the effectiveness of the proposed controller, demonstrating the outstanding compensation performance and strong robustness.

A novel adaptive method for the micro-electro mechanical systems (MEMSs) gyroscope based on a dynamic surface control and combined with the approach of adaptive fuzzy and sliding mode control (SMC) was shown in this paper. The first-order filter was introduced to the conventional adaptive backstepping technique in the dynamic surface control, which not only maintains the advantage of original backstepping technique, but also reduces the number of parameters and avoids the problem of parameter expansion. The adaptive fuzzy logic system is employed to approximate the dynamic characteristics of the gyroscope; the SMC is a kind of compensation for the error of the fuzzy approximation, which reduced the chattering phenomenon in adaptive control significantly. The proposed control scheme has improved the dynamic characteristics of the gyroscope, reducing the chattering of inputs and improving the timeliness and effectiveness of tracking. Simulation results indicate that the proposed control scheme has superior performance compared with conventional SMC.