Characterization the prognosis role and effects of snoRNAs in melanoma patients.

Melanoma is a melanocyte-derived malignant cancer and is known for its early metastasis and high mortality rates. It is a highly cutaneous tumour disease that could be related to the abnormal immune microenvironment, and the identification of reliable diagnostic and prognostic markers is crucial for improving patient outcomes. In the search for biomarkers, various types of RNAs have been discovered and recognized as reliable prognostic markers. Among these, small nucleolar RNAs (snoRNAs) have emerged as a promising avenue for studying early diagnosis and prognostic markers in tumours due to their widespread presence in tissues, tumour specificity and stability. In our study, we analysed snoRNAs data from melanoma samples in the TCGA-SKCM cohort and developed a prognostic model comprising 12 snoRNAs (SNORD9, SNORA31, SNORD14E, SNORA14A, SNORA5A, SNORD83A, SNORA75, AL096855, AC007684, SNORD14A, SNORA65 and AC004839). This model exhibited unique prognostic accuracy and demonstrated a significant correlation with the immune infiltration tumour microenvironment. Additionally, analysis of the GSE213145 dataset, which explored the sensitivity and resistance of immune checkpoint inhibitors, further supported the potential of snoRNAs as prognostic markers for immunotherapy. Overall, our study contributes reliable prognostic and immune-related biomarkers for melanoma patients. These findings can offer valuable insights for the future discovery of novel melanoma treatment strategies and hold promise for improving clinical outcomes in melanoma patients.

Photocatalyzed Defluorinative Dichloromethylation of α-CF3 Alkenes Using CHCl3 as the Radical Source.

A visible-light-induced defluorinative dichloromethylation of α-CF3 alkenes was developed with cheap and readily accessible chloroform simultaneously as a dichloromethylation reagent and reaction medium, leading to the facile preparation of new polyhalogenated scaffolds. Notably, the change from CHCl3 to CDCl3 offers a straightforward pathway for accessing the deuterated analogues with excellent degrees of D incorporation. Mechanistic studies suggested the reaction underwent a radical addition of the dichloromethyl radical with alkenes, followed by sequential single-electron transfer and defluorination. This protocol features mild conditions, easy operation, facile scalability, and high efficiency, allowing convenient access to dichloronated gem-difluoroalkenes.

Association between the cut-off value of the first trimester fasting plasma glucose level and gestational diabetes mellitus: a retrospective study from southern China.

PURPOSE: Our previous studies have suggested that the first trimester fasting plasma glucose (FPG) level is associated with gestational diabetes mellitus (GDM) and is a predictor of GDM. The aim of the present study was to provide valuable insights into the accuracy of the first trimester FPG level in the screening and diagnosis of GDM in southern China. METHODS: This retrospective study included pregnant women who had their first trimester FPG level recorded at 9-13+6 weeks and underwent screening for GDM using the 2-h 75 g oral glucose tolerance test (OGTT) between the 24th and 28th gestational weeks. Differences between the GDM and non-GDM groups were assessed by Student's t test and the chi-squared test according to the nature of the variables. A restricted cubic spine was used to explore the relationship between the first trimester FPG level and the odds ratio (OR) of GDM in pregnant women. Cut-off values of first trimester FPG were determined using receiver operating characteristic (ROC) curves and the area under the curve (AUC), and 95% confidence intervals (CIs), the positive predictive value (PPV) and the negative predictive value (NPV) were calculated. RESULTS: The medical records of 28,030 pregnant women were analysed, and 4,669 (16.66%) of them were diagnosed with GDM. The average first trimester FPG level was 4.62 ± 0.37 mmol/L. The OR of GDM increased with increasing first trimester FPG levels and with a value of first trimester FPG of approximately 4.6 mmol/L, which was equal to 1 (Chi-Square = 665.79, P < 0.001), and then started to increase rapidly afterwards. The ROC curve for fasting plasma glucose in the first trimester (4.735 mmol/L) for predicting gestational diabetes mellitus in pregnant women was 0.608 (95% CI: 0.598-0.617), with a sensitivity of 0.490 and a specificity of 0.676. CONCLUSION: Based on the research, we recommend that all pregnant women undergo FPG testing in the first trimester, particularly at the first antenatal visit. Furthermore, we suggest that the risks of GDM should be given increased attention and management as soon as the first trimester FPG value is more than 4.7 mmol/L. First trimester FPG levels should be considered a screening marker when diagnosing GDM in pregnant women but this needs to be confirmed by more prospective studies. These factors may have a significant impact on the clinical treatment of pregnant women.

Ultra-low switching reverse mode liquid crystal gels.

This research investigates the electro-optical properties of reverse mode liquid crystal gel (LC-gel) scattering films. The LC-gel has been fabricated through the fibrous self-assembly of the gelator 12-hydroxydodecanoic acid (G12) and mesogen monomer (RM257) in nematic LC HTW106700-100 (HTW). Adding RM257 monomer improves the transparency in the OFF state and enhances scattering effects in the ON state. Moreover, an extremely low switching voltage (∼ 1 V) is demonstrated.

The Protective Effect of Cordycepin On Alcohol-Induced Osteonecrosis of the Femoral Head.

BACKGROUND: Alcohol abuse is known to be a leading risk factor for atraumatic osteonecrosis of the femoral head (ONFH), in which the suppression of osteogenesis plays a critical role. Cordycepin benefits bone metabolism; however, there has been no study to determine its effect on osteonecrosis. METHODS: Human bone mesenchymal stem cells (hBMSCs) were identified by multi-lineage differentiation. Alkaline phosphatase (ALP) activity, RT-PCR, western blots, immunofluorescent assay and Alizarin red staining of BMSCs were evaluated. A rat model of alcohol-induced ONFH was established to investigate the protective role of cordycepin against ethanol. Hematoxylin & eosin (H&E) staining and micro-computerized tomography (micro-CT) were performed to observe ONFH. Apoptosis was assessed by TdT-mediated dUTP nick end labeling (TUNEL). Immunohistochemical staining was carried out to detect OCN and COL1. RESULTS: Ethanol significantly suppressed ALP activity, decreased gene expression of OCN and BMP2, lowered levels of RUNX2 protein, and reduced immunofluorescence staining of OCN and COL1 and calcium formation of hBMSCs. However, these inhibitory effects were attenuated by cordycepin co-treatment at concentrations of 1 and 10 µg/mL Moreover, it was revealed that the osteo-protective effect of cordycepin was associated with modulation of the Wnt/ß-catenin pathway. In vivo, by micro-CT, TUNEL and immunohistochemical staining of OCN and COL1, we found that cordycepin administration prevented alcohol-induced ONFH. CONCLUSION: Cordycepin treatment to enhance osteogenesis may be considered a potential therapeutic approach to prevent the development of alcohol-induced ONFH.

Low switching voltage ZnO quantum dots doped polymer-dispersed liquid crystal film.

This paper investigates the effects of ZnO nanoparticles (NPs) on the switching voltages of polymer dispersed liquid crystal (PDLC) films. The threshold and driving electric fields of PDLC film doped with 2.44 wt% ZnO NPs were 0.13 and 0.31 V/µm, respectively, with a contrast ratio of 26. The results of field emission scanning electron microscopy show that the size of the droplets in doped PDLC films increases with the doping concentration. The development of ZnO-doped PDLC films with low driving voltages greatly broadens the applicability of these devices.

Lei's formula attenuates osteoarthritis mediated by suppression of chondrocyte senescence via the mTOR axis: in vitro and in vivo experiments.

Lei's formula (LSF), a traditional Chinese herbal remedy, is recognized for its remarkable clinical effectiveness in treating osteoarthritis (OA). Despite its therapeutic potential, the exact molecular mechanisms underlying LSF's action in OA have remained enigmatic. Existing research has shed light on the role of the mTOR signaling pathway in promoting chondrocyte senescence, a central factor in OA-related cartilage degeneration. Consequently, targeting mTOR to mitigate chondrocyte senescence presents a promising avenue for OA treatment. The primary objective of this study is to establish LSF's chondroprotective potential and confirm its anti-osteoarthritic efficacy through mTOR inhibition. In vivo assessments using an OA mouse model reveal substantial articular cartilage degeneration. However, LSF serves as an effective guardian of articular cartilage, evidenced by reduced subchondral osteosclerosis, increased cartilage thickness, improved surface smoothness, decreased OARSI scores, elevated expression of cartilage anabolic markers (Col2 and Aggrecan), reduced expression of catabolic markers (Adamts5 and MMP13), increased expression of the chondrocyte hypertrophy marker (Col10), and decreased expression of chondrocyte senescence markers (P16 and P21). In vitro findings demonstrate that LSF shields chondrocytes from H2O2-induced apoptosis, inhibits senescence, enhances chondrocyte differentiation, promotes the synthesis of type II collagen and proteoglycans, and reduces cartilage degradation. Mechanistically, LSF suppresses chondrocyte senescence through the mTOR axis, orchestrating the equilibrium between chondrocyte anabolism and catabolism, ultimately leading to reduced apoptosis and decelerated OA cartilage degradation. LSF holds significant promise as a therapeutic approach for OA treatment, offering new insights into potential treatments for this prevalent age-related condition.

Inhibition of acid sensing ion channels by eugenol in rat trigeminal ganglion neurons.

Eugenol is widely used as an analgesic in the dental treatment. The underlying mechanisms may involve its modulation of various ion channels. Acid-sensing ion channels (ASICs) are pH sensors and expressed in trigeminal ganglion (TG) neurons. In the present study, we found that eugenol concentration-dependently inhibited ASIC currents in TG neurons with an IC50 of 98.8 ± 7.4 µM. Eugenol decreased the maximum response to acidic pH and did not alter pH0.5 in the concentration-response curve of acidic pH, suggesting a noncompetitive inhibition of ASICs by eugenol. G-proteins were not involved in eugenol-induced inhibition, since pre-application of eugenol also decreased ASIC currents in the presence of the G-protein blocker GDP-ß-S. In addition, eugenol also partly inhibited ASIC3 currents in Chinese hamster ovary cells transfected with ASIC3. In conclusion, eugenol partly inhibited ASIC currents in TG neurons in a concentration-dependent, non-competitive and G-protein independent manner. These results suggested that the ASICs could be a molecular target for eugenol in TG neurons, which contributed to its analgesic effect.

Down-regulation of histone deacetylase 7 reduces biological activities of retinal microvascular endothelial cells under high glucose condition and related mechanism.

AIM: To investigate the expression and effect of histone deacetylase 7 (HDAC7) in human retinal microvascular endothelial cells (HRMECs) under high glucose condition and related mechanism, and the expression of HDAC7 in the retinal tissue in diabetic rats. METHODS: The expression of HDAC7 in HRMECs under high glucose and the retinal tissue from normal or diabetic rats were detected with immunohistochemistry and Western blot. LV-shHDAC7 HRMECs were used to study the effect of HDAC7 on cell activities. Cell count kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, scratch test, Transwell test and tube formation assay were used to examine the ability of cell proliferation, migration, and angiogenesis. Finally, a preliminary exploration of its mechanism was performed by Western blot. RESULTS: The expression of HDAC7 was both up-regulated in retinal tissues of diabetic rats and high glucose-treated HRMECs. Down-regulation of HDAC7 expression significantly reduced the ability of proliferation, migration, and tube formation, and reversed the high glucose-induced high expression of CDK1/Cyclin B1 and vascular endothelial growth factor in high glucose-treated HRMECs. CONCLUSION: High glucose can up-regulate the expression of HDAC7 in HRMECs. Down-regulation of HDAC7 can inhibit HRMECs activities. HDAC7 is proposed to be involved in pathogenesis of diabetic retinopathy and a therapeutic target.

Visible-light-driven oxidation of organosilanes by a charge-transfer complex.

Direct oxidation of organosilanes is one of the most straightforward ways to access silanols. Herein, we describe a novel photo-induced strategy for oxidation of organosilanes to access silanols, promoted by a photoactive charge-transfer complex (CTC) between sodium benzenesulfinate and molecular O2. A streamlined sequence transformation of organosilanes to silyl ethers was also readily achieved. This developed protocol represents the first example of CTC-based oxidation of organosilanes, offering a facile approach to access a series of silanol and silyl ether products.

Reference values of gait parameters in healthy Chinese university students: A cross-sectional observational study.

BACKGROUND: Gait is influenced by race, age, and diseases type. Reference values for gait are closely related to numerous health outcomes. To gain a comprehensive understanding of gait patterns, particularly in relation to race-related pathologies and disorders, it is crucial to establish reference values for gait in daily life considering sex and age. Therefore, our objective was to present sex and age-based reference values for gait in daily life, providing a valuable foundation for further research and clinical applications. AIM: To establish reference values for lower extremity joint kinematics and kinetics during gait in asymptomatic adult women and men. METHODS: Spatiotemporal, kinematics and kinetics parameters were measured in 171 healthy adults (70 males and 101 females) using the computer-aided soft tissue foot model. Full curve statistical parametric mapping was performed using independent and paired-samples t-tests. RESULTS: Compared with females, males required more time (cycle time, double-limb support time, stance time, swing time, and stride time), and the differences were statistically significant. In addition, the step and stride lengths of males were longer. Compared to males, female cadence was faster, and statures-per-second and stride-per-minute were higher. There were no statistical differences in speed and stride width between the two groups. After adjusting for height, it was observed that women walked significantly faster than men, and they also had a higher cadence. However, in terms of step length, stride length, and stride width, both genders exhibited similarities. CONCLUSION: We established reference values for gait speed and spatiotemporal gait parameters in Chinese university students. This contributes to a valuable database for gait assessment and evaluation of preventive or rehabilitative programs.

Alcohol-induced inhibition of bone formation and neovascularization contributes to the failure of fracture healing via the miR-19a-3p/FOXF2 axis.

AIMS: Alcoholism is a well-known detrimental factor in fracture healing. However, the underlying mechanism of alcohol-inhibited fracture healing remains poorly understood. METHODS: MicroRNA (miR) sequencing was performed on bone mesenchymal stem cells (BMSCs). The effects of alcohol and miR-19a-3p on vascularization and osteogenic differentiation were analyzed in vitro using BMSCs and human umbilical vein endothelial cells (HUVECs). An in vivo alcohol-fed mouse model of femur fracture healing was also established, and radiological and histomorphometric analyses were used to evaluate the role of miR-19a-3p. The binding of miR-19a-3p to forkhead box F2 (FOXF2) was analyzed using a luciferase reporter assay. RESULTS: miR-19a-3p was identified as one of the key regulators in the osteogenic differentiation of BMSCs, and was found to be downregulated in the alcohol-fed mouse model of fracture healing. In vitro, miR-19a-3p expression was downregulated after ethanol administration in both BMSCs and HUVECs. Vascularization and osteogenic differentiation were independently suppressed by ethanol and reversed by miR-19a-3p. In addition, the luciferase reporter assay showed that FOXF2 is the direct binding target of miR-19a-3p. In vivo, miR-19a-3p agomir stimulated callus transformation and improved the alcohol-impaired fracture healing. CONCLUSION: This study is the first to demonstrate that the miR-19a-3p/FOXF2 axis has a pivotal role in alcohol-impaired fracture healing, and may be a potential therapeutic target. Cite this article: Bone Joint Res 2022;11(6):386-397.

Pregestational diabetes mediates the association between maternal obesity and the risk of congenital heart defects.

AIMS/INTRODUCTION: We aimed to explore whether the association between obesity and congenital heart defects (CHDs) can be mediated by maternal pregestational diabetes (PGDM). MATERIALS AND METHODS: We included 53,708 mother-infant pairs with deliveries between 2017 and 2019 from the Birth Cohort in Shenzhen. Mothers were categorized into four groups: the underweight group (body mass index [BMI] <18.5), normal weight group (18.5 ≤ BMI < 24), overweight group (24 ≤ BMI < 28) and obesity group (BMI ≥28). Multivariable logistic regression models were used to evaluate the association between BMI and CHDs. Mediation analysis was used to confirm the effect of PGDM on the association between maternal obesity and CHDs. RESULTS: The proportion of obese individuals in the Birth Cohort in Shenzhen was 2.11%. Overall, 372 (0.69%) infants were diagnosed with CHDs. Maternal obesity was associated with an increased risk of CHDs (odds ratio 1.97, 95% confidence interval 1.14-3.41). The mediation effect of PGDM on the association between maternal obesity and CHDs was significant (odds ratio 1.18, 95% confidence interval 1.06-1.32). The estimated mediation proportion was 24.83%. CONCLUSIONS: Maternal obesity was associated with increased risk for CHDs, and PGDM partially mediated the association between maternal obesity and CHDs.

Photoredox-Catalyzed C-H Trideuteromethylation of Quinoxalin-2(1H)-ones with CDCl3 as the "CD3" source.

Herein, readily available and inexpensive CDCl3 was first identified as a new trideuteromethylation reagent under photoredox-catalyzed conditions. Thus, a facile photocatalytic protocol for the C-H trideuteromethylation of quinoxalin-2(1H)-one was achieved. This operationally straightforward transformation displays a broad scope and provides a new route to introduce the trideuteromethyl group (CD3) with excellent levels of deuterium content.

Photochemical Organocatalytic Aerobic Cleavage of C═C Bonds Enabled by Charge-Transfer Complex Formation.

A novel visible-light-driven organocatalytic protocol to access aerobic oxidative cleavage of olefins, promoted by sodium benzene sulfinate, is described herein. An array of alkenes smoothly delivered the corresponding aldehydes and ketones under transition-metal-free conditions. Notably, α-halo-substituted styrenes proceeded with photoinduced oxidation to finally afford α-halo-acetophenones with halogen migration. Crucial to this oxidation was the formation of charge-transfer complexes between sodium benzene sulfinate with molecular O2 to ultimately deliver the carbonyl products.

Visible-Light-Induced, Palladium-Catalyzed 1,4-Difunctionalization of 1,3-Dienes with Bromodifluoroacetamides.

A highly modular 1,4-difunctionalization of 1,3-dienes with bromodifluoroacetamides and sulfinates/amines through a photoinduced palladium-catalyzed radical relay process is described herein. This developed protocol offers a facile and general route to access a variety of value-added CF2-incorporated alkenes in moderate to good yields. The versatility and flexibility of this approach have been well illustrated by readily accessible starting materials, synthetic convenience, and wide functional group compatibility.

Fasting plasma glucose in the first trimester is related to gestational diabetes mellitus and adverse pregnancy outcomes.

PURPOSE: To investigate and identify first-trimester fasting plasma glucose (FPG) is related to gestational diabetes mellitus (GDM) and other adverse pregnancy outcomes in Shenzhen population. METHODS: We used data of 48,444 pregnant women that had been retrospectively collected between 2017 and 2019. Logistic regression analysis was used to evaluated the associations between first-trimester FPG and GDM and adverse pregnancy outcomes, and used to construct a nomogram model for predicting the risk of GDM. The performance of the nomogram was evaluated by using ROC and calibration curves. Decision curve analysis (DCA) was used to determine the clinical usefulness of the first-trimester FPG by quantifying the net benefits at different threshold probabilities. RESULTS: The mean first-trimester FPG was 4.62 ± 0.42 mmol/L. A total of 6998 (14.4%) pregnancies developed GDM.489(1.01%) pregnancies developed polyhydramnios, the prevalence rates of gestational hypertensive disorder (GHD), cesarean section, primary cesarean section, preterm delivery before 37 weeks (PD) and dystocia was 1130 (2.33%), 20,426 (42.16%), 7237 (14.94%), 2386 (4.93%), and 1865 (3.85%), respectively. 4233 (8.74%) of the newborns were LGA, and the number of macrosomia was 2272 (4.69%), LBW was 1701 (3.51%) and 5084 (10.49%) newborns had admission to the ICU, which all showed significances between GDM and non-GDM groups (all P < 0.05). The univariate analysis showed that first-trimester FPG was strongly associated with risks of outcomes including GDM, cesarean section, macrosomia, GHD, primary cesarean section, and LGA (all OR > 1, all P < 0.05), furthermore, the risks of GDM, primary cesarean section, and LGA was increasing with first-trimester FPG as early as it was at 4.19-4.63 mmol/L. The multivariable analysis showed that the risks of GDM (ORs for FPG 4.19-4.63, 4.63-5.11 and 5.11-7.0 mmol/L were 1.137, 1.592, and 4.031, respectively, all P < 0.05) increased as early as first-trimester FPG was at 4.19-4.63 mmol/L, and first-trimester FPG which was also associated with the risks of cesarean section, macrosomia and LGA (OR for FPG 5.11-7.0 mmol/L of cesarean section: 1.128; OR for FPG 5.11-7.0 mmol/L of macrosomia: 1.561; OR for FPG 4.63-5.11 and 5.11-7.0 mmol/L of LGA: 1.149 and 1.426, respectively, all P < 0.05) and with its increasing, the risks of LGA increased. Furthermore, the nomogram had a C-indices 0.771(95% CI: 0.763~0.779) and 0.770(95% CI:0.758~0.781) in training and testing validation respectively, which showed an acceptable consistency between the observed, validation and nomogram-predicted probabilities, the DAC curve analysis indicated that the nomogram had important clinical application value for GDM risk prediction. CONCLUSIONS: FPG in the first trimester was an independent risk factor for GDM which can be used as a screening test for identifying pregnancies at risk of GDM and adverse pregnancy outcomes.

Visible-Light-Driven Sulfonation of α-Trifluoromethylstyrenes: Access to Densely Functionalized CF3-Substituted Tertiary Alcohol.

Reported herein is a visible-light-induced sulfonation of α-trifluoromethylstyrenes with sodium sulfinates, which provides a series of α-trifluoromethyl-ß-sulfonyl tertiary alcohols. This new synthetic protocol is enabled by a charge-transfer complex between oxygen and sulfinates, featuring broad substrate scope and scalability. Excellent functional group compatibility and chemoselectivity render this method suitable for sulfonation of pharmaceutically relevant molecules. In the presence of D2O, deuteriotrifluorinated products were also obtained, further demonstrating the flexibility and synthetic potentials of this strategy.

Elaboration of Charged Poly(Lactic-co-Glycolic Acid) Microparticles for Effective Release of Tranexamic Acid.

In this study, tranexamic acid (TA) was used as a model compound to study the charge effect on the physicochemical properties of poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs). Charged PLGA MPs were elaborated by the incorporation of a quaternary ammonium, cetyltrimethylammonium bromide (CTAB), during the double emulsion solvent evaporation process. Three TA-CTAB-carrying modes of PLGA MPs were designed in the CTAB-free (TA-MP), adsorption (TA-CTABAD), or encapsulation (TA-CTABEN) form. The obtained MPs were characterized by morphology and TA-MP affinity. The experiment revealed that the three prepared MPs were spherical and smooth, with pores on their surfaces. TA-CTABAD had a relatively narrow size distribution, compared with that of TA-MP and TA-CTABEN. The particle sizes of TA-MP, TA-CTABEN, TA-CTABAD were measured as 59 ± 17, 54 ± 20, and 19 ± 8 µm, respectively. The zeta potential of the three MPs was found to be in the order: TA-CTABAD > TA-CTABEN > TA-MP. Differential scanning calorimetry (DSC) indicated that the manufacturing process had no influence on the glass transition temperature of the MPs, which was close to 48 °C. Thermogravimetric analysis illustrated that the presence of CTAB slightly changed the thermal stability of PLGA MPs. In vitro release showed that TA-CTABAD exhibited faster TA release than TA-MP and TA-CTABEN in a basic environment (pH of 13), probably because of electrostatic attraction. At pH = 1, the release of TA from TA-CTABEN was faster than those from TA-MP and TA-CTABAD, probably because of electrostatic repulsion. However, the effect of electrostatic interaction was not significant at pH = 7.4.