Salicylic Acid Spray Delays Sand Pear Fruit Senescence during Room Temperature Shelf Life by Regulating Antioxidant Capacity and Senescence-Related Genes.

'Whangkeumbae' (Pyrus pyrifolia) is a variety of sand pear fruit well-known for its smooth surface and good taste. However, the fruit quality is adversely affected by postharvest ethylene production. Therefore, improving postharvest shelf life by regulating fruit senescence is critical to promoting the 'Whangkeumbae' fruit industry. Here, we investigated the effect of salicylic acid (SA) spray on fruit senescence in sand pears during room temperature shelf life. Exogenous SA reduced polyphenol oxidase (PPO) activity and malondialdehyde (MDA) content during room temperature shelf life. Additionally, SA effectively maintained the fruit skin coloration and increased the activity of antioxidant enzymes, such as superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX). SA treatment inhibited PpPPO1 expression and upregulated PpSOD1, PpAPX6, and PpGST2 expression. Furthermore, SA application downregulated the expression of PpACO2, PpEIN3a, PpNCED1, and PpAOC2, while upregulating PpNPR-1, PpTAR2, and PpCOMT1 during room temperature shelf life. SA treatment also influenced cell wall metabolism and modification genes by inhibiting PpPG1, PpPME2, and PpCEL3 and inducing PpPGIP1 expression. Additionally, SA treatment affected sugar and acid metabolism genes and increased the expression of PpSPS1, PpSUS1, PpSOT1, PpTMT4, PpSWEET15, and PpcyNAD-MDH, but suppressed the expression of PpcyNADP-ME. The Pearson correlation analysis indicated that PPO activity and MDA content were positively correlated with the expression of PpPPO1, PpACO2, PpEIN3a, PpNCED1, PpAOC2, PpPG1, PpPME2, PpCEL3, and PpcyNDA-MDH. Conversely, these factors were negatively associated with the activities of SOD, POD, CAT, and APX, as well as the expression levels of PpSOD1, PpPOD1, PpCAT1, PpAPX6, PpGST2, PpNPR-1, PpTAR2, PpCOMT1, PpPGIP1, PpSPS1, PpSUS1, PpSOT1, PpTMT4, PpSWEET15, and PpcyNAD-MDH. Our results reveal that exogenous SA could delay fruit senescence in sand pear fruit by regulating various biochemical and molecular mechanisms and can be used to effectively extend fruit shelf life during room temperature storage. However, further research is necessary to determine whether the fruits sprayed with SA are suitable for direct human consumption.

The in vivo study on antioxidant activity of wendan decoction in treating hyperlipidemia: a pharmacokinetic-pharmacodynamic (PK-PD) model.

Background: Wendan Decoction (WDD) is a six-herb Chinese medicine recipe that was first mentioned in about 652 AD. It is frequently used to treat hyperlipidemic patients' clinical complaints. According to reports, oxidative stress has a significant role in hyperlipidemia. Purpose: There has not yet been a thorough pharmacokinetic-pharmacodynamic (PK-PD) examination of the clinical efficacy of WDD in the context of hyperlipemia-related oxidative stress. Therefore, the goal of this research is to explore the antioxidant essence of WDD by developing a PK-PD model, ordering to assure its implication in treating hyperlipidemia in medical practice. Methods: The model rats of foodborne hyperlipidemia were established by feeding with high-fat feed, and the lipid-lowering effect of WDD was explored. The plasma drug concentration of rats at different doses were measured by UPL-MS/MS technology, and PK parameters were calculated using Phoenix WinNonlin 8.1 software. The level of lipid peroxide (LPO) in plasma at different time points was measured by enzyme labeling instrument. Finally, the PK-PD model was established by using Phoenix WinNonlin 8.1 software, to explore the lipid-lowering effect of WDD and the relation between the dynamic changes of chemical components and antioxidant effect. Results: The findings suggested that, WDD can reduce the levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) in plasma, and high-density lipoprotein cholesterol (HDL-C) was related to the dosage. Between the peak drug levels and the WDD's maximal therapeutic response, there existed a hysteresis. WDD's effect-concentration curves displayed a counterclockwise delaying loop. Alternatively, among the ten components of WDD, hesperetin, quercetin, naringenin and tangeretin might exert more significant effects in regulating the LPO levels in hyperlipidemic rats. Conclusion: This study can be helpful for other investigators to study the lipid-lowering effect of WDD.

Anisotropic microtopography surface of chitosan scaffold regulating skin precursor-derived Schwann cells towards repair phenotype promotes neural regeneration.

For repairing peripheral nerve and spinal cord defects, biomaterial scaffold-based cell-therapy was emerged as an effective strategy, requiring the positive response of seed cells to biomaterial substrate and environment signals. Previous work highlighted that the imposed surface properties of scaffold could provide important guidance cues to adhered cells for polarization. However, the insufficiency of native Schwann cells and unclear cellular response mechanisms remained to be addressed. Given that, this study aimed to illuminate the micropatterned chitosan-film action on the rat skin precursor-derived Schwann cells (SKP-SCs). Chitosan-film with different ridge/groove size was fabricated and applied for the SKP-SCs induction. Results indicated that SKP-SCs cultured on 30 µm size microgroove surface showed better oriented alignment phenotype. Induced SKP-SCs presented similar genic phenotype as repair Schwann cells, increasing expression of c-Jun, neural cell adhesion molecule, and neurotrophic receptor p75. Moreover, SKP-SC-secretome was subjected to cytokine array GS67 assay, data indicated the regulation of paracrine phenotype, a panel of cytokines was verified up-regulated at secreted level and gene expression level in induced SKP-SCs. These up-regulated cytokines exhibit a series of promotive neural regeneration functions, including cell survival, cell migration, cell proliferation, angiogenesis, axon growth, and cellular organization etc. through bioinformatics analysis. Furthermore, the effectively polarized SKP-SCs-sourced secretome, promoted the proliferation and migration capacity of the primarily cultured native rat Schwann cells, and augmented neurites growth of the cultured motoneurons, as well as boosted axonal regrowth of the axotomy-injured motoneurons. Taken together, SKP-SCs obtained pro-neuroregeneration phenotype in adaptive response to the anisotropic topography surface of chitosan-film, displayed the oriented parallel growth, the transition towards repair Schwann cell genic phenotype, and the enhanced paracrine effect on neural regeneration. This study provided novel insights into the potency of anisotropic microtopography surface to Schwann-like cells phenotype regulation, that facilitating to provide promising engineered cell-scaffold in neural injury therapies.

Li13YGe4O16: A Mid-infrared Rare-Earth Germanate Nonlinear Optical Crystal Featuring a Broad Transmission Range and an Enlarged Band Gap.

Germanate is garnering increasing attention in the field of optoelectronics owing to its competitive optical transparency and robust stability. Herein, a novel lithium-rich rare-earth germanate, Li13YGe4O16, was fabricated for the first time using a high-temperature solution approach. This compound adopts the asymmetric space group Cmc21 (no. 36), characterized by isolated [YO6] and [GeO4] structural motifs with Li+ cations located in the channel. Notably, Li13YGe4O16 presents a short ultraviolet cutoff edge at 240 nm, indicative of an enlarged band gap of 4.96 eV and showcases a wide mid-infrared transmission region exceeding 6.0 µm. Moreover, Li13YGe4O16 features exceptional thermal stability and moderate second harmonic generation (SHG) intensity. Additionally, a theoretical analysis suggests that the distorted [YO6] octahedra. [GeO4] and [LiO4] tetrahedra play a significant role in the optical activities of Li13YGe4O16. These attributes endow Li13YGe4O16 with the potential to serve as a new mid-IR nonlinear optical (NLO) crystal and enrich the structural chemistry of germanates.

Population pharmacokinetics of lenalidomide in Chinese patients with influence of genetic polymorphisms of ABCB1.

Affected by differences in the pharmacokinetics (PK) of lenalidomide, the toxicity of lenalidomide varies among different patients, with serious toxicity leading to dose reduction or discontinuation. The differences in the PK of lenalidomide may be related to factors such as patients' physiological characteristics, pathological characteristics and gene polymorphisms etc., which may also affect its toxicity. The aim of this study is to establish a population pharmacokinetic (PPK) model of lenalidomide and explore factors associated with the adverse events (AEs) of lenalidomide from a PK perspective. Blood samples were collected by opportunistic blood collection. Drug concentrations were determined by using HPLC/MS and genotype of ABCB1 3435 C > T (rs1045642), ABCB1 1236 A > G (rs1128503) and ABCB1 2677 A > C/T (rs2032582) was tested by the first-generation DNA sequencing technology. NONMEM software and SPSS 26.0 software were used respectively to establish PPK model of lenalidomide and explore the correlation between PK parameters and the incidence of serious AEs of lenalidomide. 51 patients were enrolled in the PPK study, and one-compartment model with first-order absorption and elimination agreed well with the observed data. The significant covariate affecting lenalidomide apparent volume of distribution (V/F) were the gene polymorphism of ABCB1 3435 C > T and diet. Safety studies could be conducted in 39 patients. The V/F value in patients suffering from serious AEs was significantly higher than that in others ( median = 67.04 L vs 37.17 L, P = 0.033). According to the covariates screened, the incidence of serious AEs was higher in patients with genotype CT or TT at ABCB1 3435 C > T locus than that in patients with genotype CC (P = 0.039). Additionally, V/F value was the highest in patients carrying genotype TT with postprandial medication, in whom the incidence of serious AEs was higher than others (P = 0.037). In conclusion, the genotype of ABCB1 3435 C > T locus and diet had pharmacokinetically relevant impact on lenalidomide, which may also be related to the incidence of serious AEs. Patients with gene variants of CT or TT at ABCB1 3435 C > T locus may be more susceptible to serious AEs, and monitoring of adverse reactions should be particularly strengthened in patients who carried genotype TT with postprandial medication.

Effects of aerobic exercise or Tai Chi Chuan interventions on problematic mobile phone use and the potential role of intestinal flora: A multi-arm randomized controlled trial.

BACKGROUND: Problematic use of mobile phones (PMPU) has been described as a serious public health issue. METHODS: This study was a parallel three-arm randomized controlled trial and has completed registration (ClinicalTrials.gov Identifier: NCT05843591). Ninety college students with PMPU were randomly assigned to the aerobic exercise group (AE group, n = 30), the Tai Chi Chuan group (TCC group, n = 30), or the wait-list control group (WLC group, n = 30). At the end of the intervention, stool samples from the study participants were collected for biological analysis based on 16 S rDNA amplicon sequencing technology. The primary outcome was addiction symptoms assessed by the Smartphone Addiction Scale-Short Version (SAS-SV). The secondary outcomes are emotional symptoms, physical symptoms, and flora species. RESULTS: Compared with the WLC group, the AE and TCC groups showed reductions in PMPU levels, physical and mental fatigue, but there was no difference between the two groups. Moreover, the effect of increasing self-esteem embodied in the TCC group was not present in the AE group. Compared to the WLC group, the relative abundance of Bacteroidaceae and Bacteroides were lower in the AE group, while the relative abundance of Erysipelotrichaceae and Alistipes were lower in the TCC group. And the relative abundance of Bacteroidaceae, Bacteroides, and Alistipes were significantly and negatively correlated with the decline in PMPU scores. CONCLUSION: AE or TCC is an effective, safe and efficient intervention for college students with PMPU, providing some physiological and psychological benefits and having some impact on their intestinal flora.

Characteristics and correlation of body fat distribution and brachial-ankle pulse wave velocity in adults aged 20-59 years: a cross-sectional study.

BACKGROUND: Fat distribution is closely related to vascular stiffness. This study aimed to investigate age and sex differences in fat distribution and brachial-ankle pulse wave velocity (baPWV), and the association between fat parameters and baPWV. METHODS: A total of 10,811 participants aged 20-59 years were recruited. Measures included waist and hip circumference, waist-to-hip ratio (WHR), body mass index (BMI), percentage body fat (PBF), subcutaneous fat area (SFA), visceral fat area (VFA), and baPWV. RESULTS: The results confirm that fat accumulates with age and that men tend to carry more abdominal fat than women in the same age group. The findings also indicate that baPWV increases with age and is significantly higher in men than in women in the same age group. In addition, WHR, VFA, and baPWV were more strongly correlated than baPWV and BMI, SFA, and PBF. Finally, the effects of age, PBF, WHR, and VFA on baPWV were greater for the higher quantiles. CONCLUSIONS: There are age and sex differences in fat distribution and baPWV. Abdominal obesity is more closely linked to arterial stiffness than overall obesity, and people with higher baPWV are more affected by obesity parameters.

Correlation between preoperative systemic immune inflammation index, nutritional risk index, and prognosis of radical resection of liver cancer.

BACKGROUND: Radical surgery is the most commonly used treatment for hepatocellular carcinoma (HCC). However, the surgical effect remains not ideal, and prognostic evaluation is insufficient. Furthermore, clinical intervention is rife with uncertainty and not conducive to prolonging patient survival. AIM: To explore correlations between the systemic immune inflammatory index (SII) and geriatric nutritional risk index (GNRI) and HCC operation prognosis. METHODS: This retrospective study included and collected follow up data from 100 HCC. Kaplan-Meier survival curves were used to analyze the correlation between SII and GNRI scores and survival. SII and GNRI were calculated as follows: SII = neutrophil count × platelet count/lymphocyte count; GNRI = [1.489 × albumin (g/L) + 41.7 × actual weight/ideal weight]. We analyzed the predictive efficacy of the SII and GNRI in HCC patients using receiver operating characteristic (ROC) curves, and the relationships between the SII, GNRI, and survival rate using Kaplan-Meier survival curves. Cox regression analysis was utilized to analyze independent risk factors influencing prognosis. RESULTS: After 1 year of follow-up, 24 patients died and 76 survived. The area under the curve (AUC), sensitivity, specificity, and the optimal cutoff value of SII were 0.728 (95% confidence interval: 0.600-0.856), 79.2%, 63.2%, and 309.14, respectively. According to ROC curve analysis results for predicting postoperative death in HCC patients, the AUC of SII and GNRI combination was higher than that of SII or GNRI alone, and SII was higher than that of GNRI (P < 0.05). The proportion of advanced differentiated tumors, tumor maximum diameter (5-10 cm, > 10 cm), lymph node metastasis, and TNM stage III-IV in patients with SII > 309.14 was higher than that in patients with SII ≤ 309.14 (P < 0.05). The proportion of patients aged > 70 years was higher in patients with GNRI ≤ 98 than that in patients with GNRI > 98 (P < 0.05). The 1-year survival rate of the SII > 309.14 group (compared with the SII ≤ 309.14 group) and GNRI ≤ 98 group (compared with the GNRI > 98 group) was lower (P < 0.05). CONCLUSION: The prognosis after radical resection of HCC is related to the SII and GNRI and poor in high SII or low GNRI patients.

Screening for a Fenpropidin Enantiomer with High Activity and Low Toxicity.

Fenpropidin has been extensively used for managing fungal diseases in different crops. There is a lack of literature on the enantioselective bioactivity and toxicity of fenpropidin. This study aims to explore the enantioselective bioactivity and toxicity of fenpropidin. R-Fenpropidin exhibited more potent bioactivity against seven plant pathogens than S-fenpropidin. R-Fenpropidin was more effective than S-fenpropidin in inhibiting sclerotial production, affecting mycelial growth and morphology, increasing cell membrane permeability, and decreasing the ergosterol content of Rhizoctonia solani. R-Fenpropidin exhibited a tighter binding affinity and formed hydrogen bonds with two target proteins. Fenpropidin also has enantioselective toxicity to Selenastrum capricornutum, with the toxicity of S-fenpropidin being seven times that of R-fenpropidin. S-Fenpropidin significantly reduced the content of the photosynthetic pigments. The results showed that R-fenpropidin was a highly active enantiomer with low toxicity. This study can provide a basis for the development of enantiomers with high activity and low toxicity.

The impact of aerobic exercise on health-related quality of life among patients undergoing maintenance hemodialysis.

To investigate the effect of exercise on cardiopulmonary function and the life quality of maintenance hemodialysis patients. Eighty-four patients who underwent maintenance hemodialysis treatment for more than 3 months were randomly divided into experimental group and control group. The general data and nutritional indexes, including hemoglobin and plasma albumin, before and after the experiment. The differences in lung function, cardiac ultrasound, cardiopulmonary function, exercise endurance between the 2 groups before and after intervention were compared. The short form 36-item health survey (SF-36) and self-rating depression scale (SDS) were assessed. In our study, the experimental group had better Force vital capacity (FVC) and peak expiratory flow (PEF) after the intervention compared to the control group (P < .05). Anaerobic threshold and 6-minute walk test (6MWT) improved significantly in the experimental group (P < .05), and SF-36 showed better physical functioning, social functioning, general health, and vitality scores in the experimental group compared to the control group (P < .05). In addition, following 24 weeks of exercise, the Depression score of the exercise group showed a statistically significant improvement when compared to the control group (P < .05). After the intervention, hemoglobin improved significantly in the experimental group (P < .05). Intradialytic exercise can improve hemoglobin, Alb, pulmonary function, aerobic capacity, and exercise endurance in maintenance hemodialysis patients, so as to improve the quality of life, which is worthy of further promotion.

Pre-Exposure Prophylaxis Care Continuum for HIV Risk Populations: An Umbrella Review of Systematic Reviews and Meta-Analyses.

Pre-exposure prophylaxis (PrEP) is an effective biomedical strategy for HIV prevention. This umbrella review is aimed at providing a comprehensive summary of the current status of each stage of the PrEP care cascade. A systematic literature search was conducted in PubMed, Embase, and Cochrane. Additionally, a Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2) tool and Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) checklist were used to evaluate their methodological and reporting quality, respectively. A total of 30 systematic reviews met the inclusion criteria. According to the results of methodological quality assessment, 3 reviews were rated as low, while 27 as critically low. Furthermore, the results of the reporting quality evaluation revealed a mean score of 23.03 for the included reviews. Across all the reviews, awareness of PrEP was generally moderate in all populations, and the acceptability was even higher compared with awareness. Unfortunately, the PrEP uptake among different groups was even less optimal, although the adherence was almost above moderate, and several barriers that hindered the utilization of PrEP were identified, and the most common are as follows: cost, stigma, lack of knowledge, mistrust, low risk perception, and more. Although PrEP has proven to be an effective prevention method to date, the promotion of PrEP failed to achieve the anticipated outcome. To reinforce the generalization of and use of PrEP, and effectively control HIV transmission, it is urgent to identify the underlying causes of low uptake rates so that efficient interventions can be implemented.

miR-30c-2-3p suppresses the proliferation of human renal cell carcinoma cells by targeting TOP2A.

Background: The ambiguity of renal cell carcinoma (RCC) symptoms hinders early diagnosis, thereby contributing to high mortality rates. By attaching to the 3'-untranslated region (UTR) of the target gene, microRNAs (miRNAs) exert significant control over the expression of genes. Objectives: To investigate the influence of miR-30c-2-3p and DNA topoisomerase II alpha (TOP2A) on RCC growth and the mechanisms underlying the regulation of its expression. Methods: The expression of miRNA-30c-2-3p and TOP2A in RCC cells was examined using quantitative real-time polymerase chain reaction (qRT-PCR). MiR-30c-2-3p mimics, its inhibitors, and controls, as well as TOP2A short hairpin RNA (shRNA) and controls, were used to transfect the human RCC cell lines 786-O, Caki-1, and ACHN. Additionally, the roles of miRNA-30c-2-3p and TOP2A in the growth of RCC were evaluated using the cell counting kit (CCK)-8 test, colony formation assay, apoptosis analysis, and Western blotting. Meanwhile, binding of miRNA-30c-2-3p and TOP2A was verified using dual-luciferase reporter assays and Western blotting. Results: miR-30c-2-p is underexpressed in RCC cells. Overexpression of miR-30c-2-p promotes apoptosis and inhibits proliferation of ACHN, Caki-1, and 786-O cells. miR-30c-2-3p targets TOP2A, which is elevated in RCC tissues and cells, whereas TOP2A silencing inhibits the proliferation ability of RCC cells. The miRNA-30c-2-3p inhibitor compromises TOP2A shRNA-induced apoptosis of RCC. RCC cells cotransfected with miRNA-30c-2-3p inhibitors and TOP2A shRNAs have a higher proliferation rate than those transfected with only TOP2A shRNAs. Conclusions: Collectively, our results verify that miRNA-30c-2-3p has a tumor suppressor property. miRNA-30c-2-3p inhibits the proliferation of RCC through regulation of TOP2A. The data provide a viable therapeutic target for RCC.

Meropenem Clearance in a Child With End-stage Renal Disease Undergoing Prolonged Intermittent Renal Replacement Therapy: A Case Report and Literature Review.

BACKGROUND: Meropenem is frequently used to treat severe infections in critically ill children. However, pharmacokinetic data on meropenem in children with end-stage renal disease (ESRD) undergoing prolonged intermittent renal replacement therapy (PIRRT) is limited. Our objectives were to evaluate meropenem clearance in a child with ESRD with and without PIRRT, compare the results to previous continuous renal replacement therapy studies in children, toddlers and neonates, and assess whether the currently used dose of meropenem is sufficient. CASE DESCRIPTION: A 5-year-old girl with an estimated glomerular filtration rate of 12.8 mL/min/1.73 m 2 was diagnosed with pulmonary infection and treated with 300 mg meropenem once a day. PIRRT was performed for 8 hours every 2 days. We used WinNonlin to evaluate meropenem clearance with and without PIRRT. RESULTS: Our case showed that PIRRT increased the clearance of meropenem from 1.39 (1.3) to 2.42 L/h (2.3 mL/kg/min) and caught up 42.6% of the total clearance. This result is in accordance with previous studies in children but slightly less than seen in toddlers and neonates under continuous renal replacement therapy. The current dose of 300 mg once a day is not sufficient to reach the therapeutic target. CONCLUSIONS: Predicting meropenem clearance in children with ESRD undergoing PIRRT is difficult as clearance will be affected by renal function, PIRRT settings and other factors. Further studies are needed to explore the individual variability of meropenem clearance and optimize the dosing regimen.

Enantioselective uptake, translocation, and biotransformation of pydiflumetofen in wheat (Triticum aestivum L.): Insights from chiral profiling and molecular simulation.

Pydiflumetofen (PYD), a highly effective and broad-spectrum fungicide, is commonly employed for the control of fungal diseases. In this study, the uptake, translocation, and biotransformation of PYD by wheat (Triticum aestivum L.) were firstly investigated at a chiral level. The findings revealed that the residue concentration of R-PYD in wheat was higher than that of S-PYD, because of its higher uptake rate (k1 = 0.0421 h-1) and lower elimination rate (k2 = 0.0459 h-1). Additionally, R-PYD exhibited higher root bioconcentration factors and translocation factors compared with S-enantiomer, indicating R-PYD was more easily accumulating in roots and translocating to shoots. Furthermore, a total of 9 metabolites, including hydroxylated, demethylated, demethoxylated, dechlorinated, hydrolyzed, and glycosylated-conjugated products, were detected qualitatively in wheat roots or shoots. Symplastic pathway-mediated uptake, which predominantly relied on aquaporins and anion channels, was confirmed by root adsorption and inhibition experiments, without displaying any enantioselective effect. Molecular simulations demonstrated that R-PYD exhibited stronger binding affinity with TaLTP 1.1 with a lower grid score (-6.79 kcal/mol), whereas weaker interaction with the metabolic enzyme (CYP71C6v1) compared to the S-enantiomer. These findings highlight the significance of plant biomacromolecules in the enantioselective bioaccumulation and biotransformation processes. Importantly, a combination of experimental and theoretical evidence provide a comprehensive understanding of the fate of chiral pesticides in plants from an enantioselective perspective.

Synergistic effect of chlorhexidine and azoles on candida biofilm on titanium surface.

BACKGROUND: Candida infections of orthopedic implants are one of the most detrimental orthopedic implant-related complications with unsuccessful treatment and a poor prognosis. Most orthopedic Candida infections form biofilms and have resistance to the commonly used antifungal agents. This study aimed to develop a novel combination of normally prescribed drugs against Candida biofilm on orthopedic implants. METHODS: We cultured 26 clinical isolates of Candida strains to form biofilm without titanium sheets or on titanium sheets, which are the most commonly used materials for permanent or orthopedic implants. The checkerboard method was used to evaluate the synergistic effects of chlorhexidine (CHL) and azoles on these Candida biofilms. For the evaluation of synergistic effects, we constructed the cell viability assay by fluorescence staining and CFU reduction hot map of Candida. RESULTS: Twenty-six clinical isolates of Candida strains formed biofilm in 96-well plates without titanium sheets, and we selected 9 of them to form biofilm on titanium sheets in 24-well plates. In Candida biofilm formed in 96-wells, the synergistic rates of CHL with fluconazole, itraconazole, and voriconazole were 61% (16/26), 65% (17/26), and 23% (6/26), respectively. When compared to the blank control group, CHL monotherapy significantly inhibited biofilm formation on titanium sheets (P < 0.05). We demonstrated 100% synergistic rates of the CHL and fluconazole combination against Candida biofilm formation on titanium sheets, and the minimum inhibitory concentration of CHL and FLU decreased four- to eight-fold. CONCLUSIONS: We concluded that CHL combined with azoles inhibited the Candida biofilm formation 96-wells or on titanium sheets and has the potential to control the infections of orthopedic implants.

Relationship between Uric Acid to High Density Lipoprotein Cholesterol Ratio and Nonalcoholic Fatty Liver Disease in Nonoverweight/Obese Patients with Type 2 Diabetes.

Aims: To investigate the relationship between uric acid to high-density lipoprotein cholesterol ratio (UHR) levels and nonalcoholic fatty liver disease (NAFLD) in nonoverweight/obese patients with type 2 diabetes. Methods: A retrospective study was designed including a total of 343 inpatients with type 2 diabetes whose BMI<24 kg/m2. The population was divided into three groups as the UHR tertiles. Logistic regression analysis was performed to estimate odds ratios (ORs) of UHR for NAFLD. ROC curve analysis was used to estimate the diagnostic value of UHR for NAFLD. Results: The prevalence rat of NAFLD enhanced progressively from the tertile 1 to tertile 3 of UHR (30.70% vs. 56.52% vs. 73.68%). Logistic regression analysis showed that participants in the higher UHR groups, compared with those in the first tertile group, had higher occurrence risks for NAFLD. The positive association between UHR and NAFLD was independent of age, BMI, blood pressure, hepatic enzymes, and other components of metabolic disorders. ROC curve analysis showed that the area under curve (AUC), sensitivity, and specificity for UHR were 0.697, 0.761, and 0.553, respectively. Conclusions: In type 2 diabetic patients without overweight or obesity, UHR is significantly associated with NAFLD and can be used as a novel and useful predictor for NAFLD onset.

Ultra-compact and ultra-broadband arbitrary-order silicon photonic multi-mode converter designed by an intelligent algorithm.

Multi-mode converters, which can achieve spatial mode conversion in multimode waveguide, play a key role in multi-mode photonics and mode-division multiplexing (MDM). However, rapid design of high-performance mode converters with ultra-compact footprint and ultra-broadband operation bandwidth is still a challenge. In this work, through combining adaptive genetic algorithm (AGA) and finite element simulations, we present an intelligent inverse design algorithm and successfully designed a set of arbitrary-order mode converters with low excess losses (ELs) and low crosstalk (CT). At the communication wavelength of 1550 nm, the footprint of designed TE0-n (n = 1, 2, 3, 4) and TE2-n (n = 0, 1, 3, 4) mode converters are only 1.8 × 2.2 µm2. The maximum and minimum conversion efficiency (CE) is 94.5% and 64.2%, and the maximum and minimum ELs/CT are 1.92/-10.9 dB and 0.24/-20 dB, respectively. Theoretically, the smallest bandwidth for simultaneously achieving ELs ≤ 3 dB and CT ≤ -10 dB exceeds 70 nm, which can be as large as 400 nm for the case of low-order mode conversion. Moreover, the mode converter in conjunction with a waveguide bend allows for mode-conversion in ultra-sharp waveguide bends, significantly increasing the density of on-chip photonic integration. This work provides a general platform for the realization of mode converters and has good prospect in application of multimode silicon photonics and MDM.

ADAMDEC1 induces EMT and promotes colorectal cancer cells metastasis by enhancing Wnt/ß-catenin signaling via negative modulation of GSK-3ß.

Colorectal cancer (CRC) is a highly invasive malignant tumor with pronounced proliferation capacity and is prone to epithelial-mesenchymal transition (EMT) and subsequent metastasis. A disintegrin and metalloproteinase domain-like decysin 1 (ADAMDEC1) is a proteolytically active metzincin metalloprotease that is involved in extracellular matrix remodeling, cell adhesion, invasion, and migration. However, the effects of ADAMDEC1 on CRC are unclear. This study was conducted to investigate the expression and biological role of ADAMDEC1 in CRC. We found that ADAMDEC1 was differentially expressed in CRC. Further, ADAMDEC1 was found to enhance CRC proliferation, migration, and invasion while inhibiting apoptosis. Exogenous ADAMDEC1 overexpression elicited EMT in CRC cells, as evidenced by alterations in E-cadherin, N-cadherin, and vimentin expression. In ADAMDEC1 knockdown or ADAMDEC1 overexpressed CRC cells, the western blotting analysis revealed that Wnt/ß-catenin signaling pathway-related proteins were down-regulated or up-regulated. Furthermore, an inhibitor of the Wnt/ß-catenin pathway (FH535) partially negated the effect of ADAMDEC1 overexpression on EMT and CRC cell proliferation. Further mechanistic research suggested that ADAMDEC1 knockdown may upregulate GSK-3ß and inactivate the Wnt/ß-catenin pathway, accompanied by suppressing the expression of ß-catenin. Additionally, the blocker of GSK-3ß (CHIR-99021) markedly abolished the inhibitory effect of ADAMDEC1 knockdown on Wnt/ß-catenin signaling. Our results indicate that ADAMDEC1 promotes CRC metastasis by negatively regulating GSK-3ß, activating the Wnt/ß-catenin signaling pathway, and inducing EMT, presenting its potential as a therapeutic target for the treatment of metastatic CRC.