Facilely Fabricated Single-Site Ptδ+-O(OH)x- Species Associated with Alkali on Zirconia Exhibiting Superior Catalytic Oxidation Reactivity.

Fabrication of robust isolated atom catalysts has been a research hotspot in the environment catalysis field for the removal of various contaminants, but there are still challenges in improving the reactivity and stability. Herein, through facile doping alkali metals in Pt catalyst on zirconia (Pt-Na/ZrO2), the atomically dispersed Ptδ+-O(OH)x- associated with alkali metal via oxygen bridge was successfully fabricated. This novel catalyst presented remarkably higher CO and hydrocarbon (HCs: C3H8, C7H8, C3H6, and CH4) oxidation activity than its counterpart (Pt/ZrO2). Systematically direct and solid evidence from experiments and density functional theory calculations demonstrated that the fabricated electron-rich Ptδ+-O(OH)x- related to Na species rather than the original Ptδ+-O(OH)x-, serving as the catalytically active species, can readily react with CO adsorbed on Ptδ+ to produce CO2 with significantly decreasing energy barrier in the rate-determining step from 1.97 to 0.93 eV. Additionally, owing to the strongly adsorbed and activated water by Na species, those fabricated single-site Ptδ+-O(OH)x- linked by Na species could be easily regenerated during the oxidation reaction, thus considerably boosting its oxidation reactivity and durability. Such facile construction of the alkali ion-linked active hydroxyl group was also realized by Li and K modification which could guide to the design of efficient catalysts for the removal of CO and HCs from industrial exhaust.

[Nanocatalytic treatment of oral squamous cell carcinoma Cal 27 cells in vitro based on single-atom iron nanocatalysts].

PURPOSE: To prepare single-atom iron nanocatalysts(SAF NCs) and explore its efficacy on oral squamous cell carcinoma Cal 27 cells in vitro, and provide a new strategy for the treatment of oral squamous cell carcinoma. METHODS: SAF NCs were prepared with combination of isolation and pyrolysis, the microscopic characterization was observed by transmission electron microscopy, the morphology and chemical composition were analysed by X-ray diffractograms and elemental distribution energy spectroscopy. The catalytic properties were detected by TMB assay and electron spin resonance test, and finally the changes in the activity of Cal27 cells were observed by CCK-8, flow cytometry and confocal microscopy for in vitro treatment of oral squamous carcinoma, to investigate the therapeutic effect against Cal27 cells. Statistical analysis was performed with GraphPad Prism 9 software package. RESULTS: SAF NCs were successfully synthesized and characterized, which showed excellent catalytic properties at the solution level and good biocompatibility in in vitro cellular level. The viability of Cal27 cell was reduce to 32.08% after in vitro catalytic treatment under conditions mimicking the characteristics of the tumor microenvironment. CONCLUSIONS: Preliminary experiments demonstrated that SAF NCs with good biological properties could effectively inhibit the proliferation of Cal 27 cells in vitro, providing a new strategy for the treatment of oral squamous carcinoma.

Implementing a completely autotrophic nitrogen removal over nitrite process using a novel umbrella basalt fiber carrier.

The completely autotrophic nitrogen removal over nitrite (CANON) process is significantly hindered by prolonged start-up periods and unstable nitrogen removal efficiency. In this study, a novel umbrella basalt fiber (BF) carrier with good biological affinity and adsorption performance was used to initiate the CANON process. The CANON process was initiated on day 64 in a sequencing batch reactor equipped with umbrella BF carriers. During this period, the influent NH4+-N concentration gradually increased from 100 to 200 mg·L-1, and the dissolved oxygen was controlled below 0.8 mg L-1. Consequently, an average ammonia nitrogen removal efficiency (ARE) and total nitrogen removal efficiency (TNRE) of ∼90 and 80% were achieved, respectively. After 130 days, ARE and TNRE remained stable at 92 and 81.1%, respectively. This indicates a reliable method for achieving rapid start-up and stable operation of the CANON process. Moreover, Candidatus Kuenenia and Candidatus Brocadia were identified as dominant anammox genera on the carrier. Nitrosomonas was the predominant genus among ammonia-oxidizing bacteria. Spatial differences were observed in the microbial population of umbrella BF carriers. This arrangement facilitated autotrophic nitrogen removal in a single reactor. This study indicates that the novel umbrella BF carrier is a highly suitable biocarrier for the CANON process.

Targeting xCT with sulfasalazine suppresses triple-negative breast cancer growth via inducing autophagy and coordinating cell cycle and proliferation.

There is a substantial unmet need for effective treatment strategies in triple-negative breast cancer (TNBC). Recently, renewed attention has been directed towards targeting glutamine (Gln) metabolism to enhance the efficacy of cancer treatment. Nonetheless, a comprehensive exploration into the mechanistic implications of targeting Gln metabolism in TNBC is lacking. In this study, our objective was to probe the sensitivity of TNBC to alterations in Gln metabolism, using representative TNBC cell lines: MDA-MB-231, MDA-MB-468, and 4T1. Through an integration of bioinformatics, in-vitro, and in-vivo investigations, we demonstrated that sulfasalazine (SAS), like erastin (a known xCT inhibitor), effectively suppressed the expression and transport function of xCT, resulting in a depletion of glutathione levels in MDA-MB-231 and MDA-MB-468 cells. Furthermore, both xCT knockdown and SAS treatment demonstrated the promotion of cellular autophagy. We unveiled a positive correlation between xCT and the autophagy-related molecule p62, their co-expression indicating poor survival outcomes in breast cancer patients. In addition, our research revealed the influence of SAS and xCT on the expression of proteins regulating cell cycle and proliferation. Treatment with SAS or xCT knockdown led to the inhibition of MYC, CDK1, and CD44 expression. Significantly, the combined administration of SAS and rapamycin exhibited a synergistic inhibitory effect on the growth of transplanted breast tumor in mouse models constructed from murine-derived 4T1 cells. Taken together, our findings suggested the potential and clinical relevance of the SAS and rapamycin combination in the treatment of TNBC.

Fast and nondestructive discrimination of coal types based on spectral feature parameters.

Coal type identification is the basic work of coal quality inspection, which is of great significance to the normal operation of power generation, metallurgy, and other industries. The traditional coal-type identification method is complicated and requires comprehensive determination of various chemical parameters to obtain more accurate analysis results. Hyperspectral detection and analysis technology has the advantages of being simple, fast, nondestructive, and safe, and is widely used in a variety of fields. In this study, typical spectral feature parameters of coal samples were extracted based on hyperspectral data, and the parameters' sensitivity to coal types was explored using one-way ANOVA. The results showed that the coal spectral feature parameters of DI1-2µm and AD2.2µm significantly differed with coal species, indicating that the two parameters were class-sensitive features. When DI1-2µm and AD2.2µm were used to construct the Fisher discriminant model, the coal types could be discriminated with high accuracy. At the same time, the correlation between the extracted spectral feature parameters and the physicochemical parameters of bituminous coal and anthracite was analyzed. The results showed that there was a certain basis for using the extracted spectral feature parameters as the sensitive spectral characteristics of the model, and the application potential of the spectral characteristics of coal in the nondestructive prediction analysis of coal parameters was further discussed.

MiR-200b-3p elevates 5-FU sensitivity in cholangiocarcinoma cells via autophagy inhibition by targeting KLF4.

Cholangiocarcinoma is one of the most lethal human cancers, and chemotherapy failure is a major cause of recurrence and poor prognosis. We previously demonstrated that miR-200 family members are downregulated in clinical samples of cholangiocarcinoma and inhibit cholangiocarcinoma tumorigenesis and metastasis. However, the role of differentially expressed miR-200b-3p in 5-fluorouracil chemosensitivity remains unclear. Here, we examined how miR-200b-3p modulates 5-fluorouracil chemosensitivity in cholangiocarcinoma. We observed that miR-200b-3p was associated with 5-fluorouracil sensitivity in cholangiocarcinoma and increased 5-fluorouracil-induced mitochondrial apoptosis in cholangiocarcinoma cells. Mechanistically, miR-200b-3p suppressed autophagy in cholangiocarcinoma cells to mediate 5-fluorouracil sensitivity. Further, we identified KLF4 as an essential target of miR-200b-3p in cholangiocarcinoma. Notably, the miR-200b-3p/KLF4/autophagy pathway augmented the chemosensitivity of cholangiocarcinoma cells to 5-fluorouracil. Our findings underscore the key role of miR-200b-3p in chemosensitivity to 5-fluorouracil and highlight the miR-200b-3p/KLF4/autophagy axis as a potential therapeutic target for cholangiocarcinoma.

Development of a machine learning-based model to predict major adverse events after surgery for type A aortic dissection complicated by malnutrition.

Objective: This study aims to develop a predictive model for the risk of major adverse events (MAEs) in type A aortic dissection (AAAD) patients with malnutrition after surgery, utilizing machine learning (ML) algorithms. Methods: We retrospectively collected clinical data from AAAD patients with malnutrition who underwent surgical treatment at our center. Through least absolute shrinkage and selection operator (LASSO) regression analysis, we screened for preoperative and intraoperative characteristic variables. Based on the random forest (RF) algorithm, we constructed a ML predictive model, and further evaluated and interpreted this model. Results: Through LASSO regression analysis and univariate analysis, we ultimately selected seven feature variables for modeling. After comparing six different ML models, we confirmed that the RF model demonstrated the best predictive performance in this dataset. Subsequently, we constructed a model using the RF algorithm to predict the risk of postoperative MAEs in AAAD patients with malnutrition. The test set results indicated that this model has excellent predictive efficacy and clinical applicability. Finally, we employed the Shapley additive explanations (SHAP) method to further interpret the predictions of this model. Conclusion: We have successfully constructed a risk prediction model for postoperative MAEs in AAAD patients with malnutrition using the RF algorithm, and we have interpreted the model through the SHAP method. This model aids clinicians in early identification of high-risk patients for MAEs, thereby potentially mitigating adverse clinical outcomes associated with malnutrition.

Efficient recovery of gold from solution with a thiocyanate-modified Zr-MOF: adsorption properties and DFT calculations.

The design and development of new large-capacity and selective materials for extracting rare precious metals via electronic waste is practically essential. In this paper, a new efficient UiO-66-NCS has been obtained as a consequence of the modification of the classical Zr-MOF (UiO-66-NH2), and its ability to recover gold has been investigated. These batch results adequately illustrated that UiO-66-NCS exhibited good adsorption capacity (675.5 mg g-1) and exceptional selectivity. In addition, UiO-66-NCS achieved faster adsorption equilibrium times of about 120 min. Adsorption kinetics and isotherms demonstrated that the pseudo-second-order adsorption scheme and a Langmuir-type procedure were shown by the adsorption of Au(III) on UiO-66-NCS. Characterized by pH effect experiments, TEM, XRD, and XPS, the adsorption of UiO-66-NCS with Au(III) relies on coordination, which further results in reduction, and the generated Au(0) is uniformly dispersed in the MOF. The adsorbent has considerable advantages for cyclic regeneration. Finally, DFT fitting results showed that the adsorption binding energy of UiO-66-NCS with [AuCl4]- was -8.63 kcal mol-1 for the adsorption process. UiO-66-NCS is likely to be an ideal substance for gold recovery.

[TFEB activator 1 enhances autophagic degradation of oligomeric amyloid-ß in microglia].

The purpose of the study was to investigate the mechanism of TFEB activator 1 (TA1) improving the autophagic degradation of oligomeric amyloid-ß (oAß) in microglia, and to explore the therapeutic effect of TA1 on an in vitro model of microglia in Alzheimer's disease (AD). Primary microglia were exposed to 1 µmol/L oAß for 0, 3, 12, and 24 h respectively to construct the in vitro model of microglia in AD. In order to explore the therapeutic effect of TA1, primary microglia were co-treated with 1 µmol/L oAß and 1 µmol/L TA1 for 12 h. To determine the autophagy flux, the above cells were further treated with 100 nmol/L Bafilomycin A1 for 1 h before fixation. Fluorescent probes were used to detect the endocytosis or degradation of oAß1-42 by microglia. The autophagic flux was determined by infection of lentivirus mCherry-EGFP-LC3. The nuclear TFEB intensity, the autophagosomes number, and the colocalization ratio of oAß1-42 with lysosome-associated membrane protein 1 (LAMP1) or microtubule-associated protein light chain 3 (LC3), were detected by immunofluorescence assay. Expressions of autophagy-related-genes, including Lamp1, Atg5, and Map1lc3b, were detected by qRT-PCR. Results showed that prolonged oAß exposure inhibited the endocytosis and degradation of oAß by microglia. Meanwhile, the number of autophagosomes and autophagy flux in microglia decreased after 12 h of oAß treatment. We further found that the nuclear expression of autophagy regulator TFEB decreased after 12 h of oAß exposure, resulting in the decrease of autophagy genes, thus leading to the damage of autophagic degradation of oAß. Therefore, long-term oAß exposure was considered to construct the in vitro model of microglia in AD. After TA1 treatment, the nuclear expression of TFEB in cells was obviously upregulated. TA1 treatment upregulated the expressions of autophagy-related genes, leading to the recovery of autophagy flux. TA1 also recovered the endocytosis and degradation of oAß by microglia. In conclusion, TA1 could improve oAß clearance by microglia in AD by upregulating microglial TFEB-mediated autophagy, suggesting TA1 as a potential therapeutic drug for AD.

Fusobacterium nucleatum-infected periodontitis promotes renal interstitial fibrosis in rats through the TGF-ß/SMAD2/3 and ß-catenin signaling pathways.

OBJECTIVES: Periodontitis is associated with Fusobacterium nucleatum (F.n) infection. Although the colonization of renal tissue by F.n is well documented, its specific role in kidney disease has yet to be determined. This study aimed to investigate the potential association between F.n-induced periodontitis and renal interstitial fibrosis. METHODS: The rat gingival sulcus was injected with F.n suspension, while the control group (NC) was injected with PBS. The levels of total protein (TP), albumin (ALB), creatinine, and urea nitrogen (BUN) in rat serum and/or urine were quantified using the appropriate kits. Renal interstitial fibrosis and epithelial-mesenchymal transition (EMT) were evaluated in rats using Masson staining, Periodic Schiff-Methenamine (PASM) staining, and immunohistochemical staining. The levels of fibrosis- and EMT-related proteins and the TGF-ß/SMAD2/3 and ß-catenin signaling pathways were determined using Western blot analysis. F.n in the kidney tissues was quantitatively determined using bacterial 16S rRNA technology. RESULTS: Serum levels of TP, ALB, creatinine, and BUN were not significantly decreased in F.n-infected rats with periodontitis. The levels of creatinine and ALB in the urine were not statistically different between two groups. Masson and PASM staining showed that F.n-induced periodontitis could promote renal interstitial fibrosis in rats. The levels of collagen I, fibronectin (FN), vimentin, and α-SMA were upregulated in the kidney tissues of rats with F.n-induced periodontitis and in F.n-treated HK-2 cells. However, E-cadherin levels were reduced. F.n promoted renal interstitial and HK-2 cell fibrosis in rats by modulating the TGF-ß/SMAD2/3 and ß-catenin signaling pathways. F.n colonization increased renal interstitial fibrosis in rats. CONCLUSION: F.n-induced periodontitis promoted EMT by activating the TGF-ß/SMAD2/3 and ß-catenin signaling pathways, thus promoting renal interstitial fibrosis in rats.

A network meta-analysis of psychological interventions for children and adolescents after natural and man-made disasters.

INTRODUCTION: Children and adolescents, after natural and man-made disasters, often exhibit various psychological, emotional, and behavioral issues, showing a range of clinical symptoms related to post-traumatic stress disorder (PTSD) and depression. This review used a network meta-analysis (NMA) approach to compare and rank psychological interventions for PTSD and depression in children and adolescents after exposure to natural and man-made disasters. METHODS: Randomized studies of psychosocial interventions for PTSD and depression in children and adolescents exposed to natural and man-made disasters were identified. PTSD and depression symptoms at postintervention and 1-12 month follow-up are the outcomes. The standardized mean differences (SMDs) between pairs of interventions at postintervention and follow-up were pooled. Mean effect sizes with 95% credible intervals (CI) were calculated, and the ranking probabilities for all interventions were estimated using the surface under the cumulative ranking curve. Study quality was assessed with version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). RESULTS: In total, 26 studies with 4331 participants were included in this NMA. Eye movement desensitization and reprocessing therapy (EMDR) (SMD = - 0.67; 95% CI - 1.17 to - 0.17), exposure therapy (ET) (SMD = - 0.66; 95% CI - 1.11 to - 0.22), and cognitive behavioral therapy (CBT) (SMD = - 0.62; 95% CI - 0.90 to - 0.34) were significantly more effective for PTSD at postintervention than inactive intervention. EMDR (SMD = - 0.72; 95% CI - 1.11 to - 0.33) and ET (SMD = - 0.62; 95% CI - 0.97 to - 0.27) were associated with a higher reduction in PTSD symptoms at follow-up than inactive intervention. EMDR (SMD = - 0.40; 95% CI - 0.78 to - 0.03) and play therapy (PT) (SMD = - 0.37; 95% CI - 0.62 to - 0.12) were significantly more effective for depression at postintervention than inactive intervention. For all psychological interventions in reducing depression symptoms at follow-up compared with inactive intervention, the differences were not significant. CONCLUSION: EMDR appears to be most effective in reducing PTSD and depression in children and adolescents exposed to natural and man-made disasters. In addition, ET and CBT are potentially effective in reducing PTSD symptoms at postintervention, while PT is beneficial in managing depression symptoms at the treatment endpoint.

The G932C mutation of chitin synthase 1 gene (CHS1) mediates buprofezin resistance as confirmed by CRISPR/Cas9-mediated knock-in approach in the brown planthopper, Nilaparvata lugens.

The brown planthopper (Nilaparvata lugens) is a major destructive rice pest in Asia. High levels of insecticide resistance have been frequently reported, and the G932C mutation in the chitin synthase 1 (CHS1) gene has been found to mediate buprofezin resistance. However, there has been no direct evidence to confirm the functional significance of the single G932C substitution mutation leading to buprofezin resistance in N. lugens. Here, we successfully constructed a knock-in homozygous strain (Nl-G932C) of N. lugens using CRISPR/Cas9 coupled with homology-directed repair (HDR). Compared with the background strain susceptible to buprofezin (Nl-SS), the knock-in strain (Nl-G932C) showed a 94.9-fold resistance to buprofezin. Furthermore, resistant strains (Nl-932C) isolated from the field exhibited a 2078.8-fold resistance to buprofezin, indicating that there are other mechanisms contributing to buprofezin resistance in the field. Inheritance analysis showed that the resistance trait is incomplete dominance. In addition, the Nl-G932C strain had a relative fitness of 0.33 with a substantially decreased survival rate, emergence rate, and fecundity. This study provided in vivo functional evidence for the causality of G932C substitution mutation of CHS1 with buprofezin resistance and valuable information for facilitating the development of resistance management strategies in N. lugens. This is the first example of using CRISPR/Cas9 gene-editing technology in a hemipteran insect to directly confirm the role of a candidate target site mutation in insecticide resistance.

Predicted hot superconductivity in LaSc2H24 under pressure.

The recent theory-driven discovery of a class of clathrate hydrides (e.g., CaH6, YH6, YH9, and LaH10) with superconducting critical temperatures (Tc) well above 200 K has opened the prospects for "hot" superconductivity above room temperature under pressure. Recent efforts focus on the search for superconductors among ternary hydrides that accommodate more diverse material types and configurations compared to binary hydrides. Through extensive computational searches, we report the prediction of a unique class of thermodynamically stable clathrate hydrides structures consisting of two previously unreported H24 and H30 hydrogen clathrate cages at megabar pressures. Among these phases, LaSc2H24 shows potential hot superconductivity at the thermodynamically stable pressure range of 167 to 300 GPa, with calculated Tcs up to 331 K at 250 GPa and 316 K at 167 GPa when the important effects of anharmonicity are included. The very high critical temperatures are attributed to an unusually large hydrogen-derived density of states at the Fermi level arising from the newly reported peculiar H30 as well as H24 cages in the structure. Our predicted introduction of Sc in the La-H system is expected to facilitate future design and realization of hot superconductors in ternary clathrate superhydrides.

Microplastic-mediated environmental behavior of metal contaminants: mechanism and implication.

Microplastics (MPs) and metals are currently two of the most concerning environmental pollutants due to their persistent nature and potential threats to ecosystems and human health. This review examines the intricate interactions between MPs and metals in diverse environmental compartments, including aquatic, terrestrial, and atmospheric environments by focusing on the complex processes of adsorption and desorption and the mechanisms that govern these interactions. MPs act as carriers and concentrators of metals in aquatic and terrestrial environments, affecting the bioavailability and toxicity of these contaminants to aquatic and terrestrial organisms. This review highlights the existing challenges and constraints associated with current analytical methods, including microscopy, spectroscopy, and isotherm models in studying microplastic-heavy metal interactions. Moreover, we identified the knowledge gaps and future research directions that can enhance our understanding of the dynamic interplay between MPs and metals in various environmental settings.

S-ketamine Infusion on Chronic Postoperative Pain Following Breast Cancer Surgery: A Randomized Double-Blind Placebo-Controlled Trial.

BACKGROUND: Chronic postoperative surgical pain (CPSP) is a frequent complication following breast surgery and poses a challenge in terms of treatment. We hypothesized that the incidence of CPSP would be reduced at 3 months post-breast surgery with the administration of S-ketamine compared to a placebo. PATIENTS AND METHODS: Participants were recruited and randomly assigned to either the S-ketamine group (S) or the control group (C). In group S, S-ketamine was administered as a 1.5 mg kg-1 bolus followed by 2 mg kg-1h-1 infusion, while in group C, a placebo of 0.9% saline was administered in the same volume and rate as S-ketamine. The primary outcome was the incidence of CPSP, measured using a 0-10 numeric rating scale (NRS), at 3 months postsurgery. RESULTS: A total of 72 patients scheduled for mastectomy were enrolled (group S, n = 33; group C, n = 32). The incidence of CPSP at 3 months postsurgery was significantly lower in group S compared to group C (18.2% vs. 48.3%, P < .05). There was no statistical difference between the 2 groups in terms of the incidence of moderate to severe pain. NRS scores for postoperative pain at rest and during movement were significantly lower at 4 h and 24 h post-surgery (P < .05, respectively). Patients in Group S had lower Patient Health Questionnaire-9 (PHQ-9) scores at one week and 3 months post-surgery compared to Group C (P < .05, respectively). CONCLUSION: S-ketamine infusion reduces the incidence of CPSP 3 months after breast surgery.

Biotransformation of ginsenoside compound K using ß-glucosidase in deep eutectic solvents.

Ginsenoside compound K (CK) holds significant potential for application in the pharmaceutical industry, which exhibits numerous pharmacological activity such as cardioprotective and antidiabetic. However, the difficult separation technique and limited yield of CK hinder its widespread use. The study investigated the process of converting ginsenoside CK using ß-glucosidase. It aimed to determine the specific site where the enzyme binds and the most favorable arrangement of the enzyme. Molecular docking was also employed to determine the interaction between ß-glucosidase and ginsenosides, indicating a strong and spontaneous contact force between them. The effectiveness of the conversion process was further improved using a "green" deep eutectic solvent (DES). A univariate experimental design was used to determine the composition of DES and the optimal hydrolysis conditions for ß-glucosidase to convert ginsenoside Rb1 into ginsenoside CK. The employment of ß-glucosidase enzymatic hydrolysis in the synthesis of rare ginsenoside CK applying the environmentally friendly solvent DES is not only viable and effective but also appropriate for industrial use. The characterization methods confirmed that DES did not disrupt the structure and conformation of ß-glucosidase. In ChCl:EG = 2:1 (30%, v/v), pH 5.0 of DES buffer, reaction temperature 50 ℃, enzyme substrate mass ratio 1:1, after 36 h of reaction, the CK yield was 1.24 times that in acetate buffer, which can reach 86.2%. In this study, the process of using ß-glucosidase enzymatic hydrolysis and producing rare ginsenoside CK in green solvent DES is feasible, efficient and suitable for industrial production and application.

Effect of electroacupuncture on myocardial transient receptor potential channels in mice with myocardial hypertrophy. / ç”µé’ˆå¯¹å¿ƒè‚Œè‚¥åŽšå°é¼ å¿ƒè‚Œç»„ç»‡çž¬æ—¶å—ä½“ç”µä½é€šé“çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) at "Neiguan"(PC6) on cardiac function, cardiac morphology and transient receptor potential channel (TRPC) protein expressions in myocardial tissue of mice with myocardial hypertrophy, so as to explore its mechanisms underlying improvement of myocardial hypertrophy. METHODS: Forty-five male C57BL/6 mice were randomly divided into control, model and EA groups (15 mice/group). The myocardial hypertrophy model was established by subcutaneous injection of isoproterenol hydrochloride (15 mg·kg-1·d-1) for 14 days. The mice of the control group received subcutaneous injection of same amount of normal saline. The mice of the EA group received EA stimulation (frequency of 2 Hz, intensity of 1 mA) of bilateral PC6 for 20 min each time, once a day for 14 consecutive days. After the intervention, the body weight, tibia length and heart weight were measured. The left ventricular ejection fraction (EF), fractional shortening index (FS), left ventricular end-systolic volume (LVEV), left ventricular end-systolic internal diameter (LVID) and left ventricular posterior wall thickness (LVPW) were measured by using echocardiography for evaluating the cardiac function. The mean number and surface area of myocardial cells was detected by wheat germ agglutinin (WGA) staining, and changes of the cardiac morphology were observed under light microscopy after HE staining. The expression levels of TRPC1, TRPC3, TRPC4 and TRPC6 (TRPC1/3/4/6) in the myocardial tissue were detected by real-time quantitative PCR (qPCR) and Western blot, separately. RESULTS: Compared with the control group, the heart-body weight ratio(P<0.05) and heart-weight-to-tibia-length ratio (P<0.01), LVEV and LVID levels, the relative surface area, left ventricular area ratio, and the expression levels of cardiac TRPC1/3/4/6 were significantly increased (P<0.01, P<0.05), while the EF, FS, LVPW, number of cardiomyocytes, and the left ventricular posterior wall ratio were obviously decreased (P<0.01, P<0.05) in the model group. In comparison with the model group, the heart/body weight ratio, heart-weight-to-tibia-length ratio, LVEV and LVID levels, relative surface area, left ventricular area ratio, and the expression levels of cardiac TRPC1/3/4/6 were significantly decreased (P<0.01, P<0.05), while the EF, FS, LVPW, number of cardiomyocytes and left ventricular posterior wall ratio were significantly increased (P<0.01, P<0.05) in the EA group. H.E. staining showed disordered arrangement of cardiomyocytes and obvious myocardial interstitial inflammatory cell infiltration in the model group, and evident reduction of degree of cardiac fibrosis and interstitial edema in the EA group. CONCLUSIONS: EA of PC6 can improve the cardiac function and cardiac morphology in mice with myocardial hypertrophy, which may be related to its functions in down-regulating the expression of transient receptor potential channels.

Squaramide-catalyzed enantioselective Michael addition of nitromethane to 2-enoylazaarenes: synthesis of chiral azaarene-containing γ-nitroketones.

Bifunctional chiral squaramide-catalyzed highly enantioselective Michael addition of nitromethane to diverse 2-enoylazaarenes was successfully performed. This protocol provided a set of chiral azaarene-containing γ-nitroketones with up to 98% yield and 98% ee in a solvent-free catalytic system under mild conditions. Furthermore, gram-scale synthetic utility was also showcased.

Roles of combined femoral and acetabular anteversion in pathological changes of hip dysplasia and hip reconstructive surgery.

Combined femoral and acetabular anteversion is the sum of femoral and acetabular anteversion, representing their morphological relationship in the axial plane. Along with the increasing understanding of hip dysplasia in recent years, numerous scholars have confirmed the role of combined femoral and acetabular anteversion in the pathological changes of hip dysplasia. At present, the reconstructive surgery for hip dysplasia includes total hip replacement and redirectional hip preservation surgery. As an important surgery index, combined femoral and acetabular anteversion have a crucial role in these surgeries. Herein, we discuss the role of combined femoral and acetabular anteversion in pathological changes of hip dysplasia, total hip replacement, and redirectional hip preservation surgery.

Low GPR81 in ER+ breast cancer cells drives tamoxifen resistance through inducing PPARα-mediated fatty acid oxidation.

AIMS: The intricate molecular mechanisms underlying estrogen receptor-positive (ER+) breast carcinogenesis and resistance to endocrine therapy remain elusive. In this study, we elucidate the pivotal role of GPR81, a G protein-coupled receptor, in ER+ breast cancer (BC) by demonstrating low expression of GPR81 in tamoxifen (TAM)-resistant ER+ BC cell lines and tumor samples, along with the underlying molecular mechanisms. MAIN METHODS: Fatty acid oxidation (FAO) levels and lipid accumulation were explored using MDA and FAßO assay, BODIPY 493/503 staining, and Lipid TOX staining. Autophagy levels were assayed using CYTO-ID detection and Western blotting. The impact of GPR81 on TAM resistance in BC was investigated through CCK8 assay, colony formation assay and a xenograft mice model. RESULTS: Aberrantly low GPR81 expression in TAM-resistant BC cells disrupts the Rap1 pathway, leading to the upregulation of PPARα and CPT1. This elevation in PPARα/CPT1 enhances FAO, impedes lipid accumulation and lipid droplet (LD) formation, and subsequently inhibits cell autophagy, ultimately promoting TAM-resistant BC cell growth. Moreover, targeting GPR81 and FAO emerges as a promising therapeutic strategy, as the GPR81 agonist and the CPT1 inhibitor etomoxir effectively inhibit ER+ BC cell and tumor growth in vivo, re-sensitizing TAM-resistant ER+ cells to TAM treatment. CONCLUSION: Our data highlight the critical and functionally significant role of GPR81 in promoting ER+ breast tumorigenesis and resistance to endocrine therapy. GPR81 and FAO levels show potential as diagnostic biomarkers and therapeutic targets in clinical settings for TAM-resistant ER+ BC.