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Obesity and insulin resistance (IR) are common features of polycystic ovary syndrome (PCOS). Metformin (MET) increases insulin sensitivity, but it is associated with unsatisfactory weight loss. The glucagon-like peptide-1 receptor agonist exenatide has been shown to reduce weight and IR in patients with diabetes. This study aimed to explore the therapeutic effects of exenatide once-weekly (QW) combined with MET on body weight, as well as metabolic and endocrinological parameters in overweight/obese women with PCOS. Fifty overweight/obese women with PCOS diagnosed via the Rotterdam criteria were randomized to one of two treatment groups: MET (500 mg three times a day [TID]) or combination treatment (COM) (MET 500 mg TID, exenatide 2 mg QW) for 12 weeks. The primary outcomes were anthropometric changes associated with obesity, and the secondary outcomes included changes in reproductive hormone levels, glucose and lipid metabolism, and C-reactive protein. Forty (80%) patients completed the study. COM therapy was superior to MET monotherapy in reducing weight (P = 0.045), body mass index (BMI) (P = 0.041), and waist circumference (P = 0.023). Patients in the COM group on an average lost 3.8 ± 2.4 kg compared with 2.1 ± 3.0 kg in the MET group. In the COM group, BMI and waist circumference decreased by 1.4 ± 0.87 kg/m2 and 4.63 ± 4.42 cm compared with 0.77 ± 1.17 kg/m2 and 1.72 ± 3.07 cm in the MET group, respectively. Moreover, levels of fasting glucose, oral glucose tolerance test (OGTT) 2-h glucose, and OGTT 2-h insulin were significantly lower with COM therapy than with MET (P < 0.050). Mild and moderate gastrointestinal reactions were the most common adverse events in both groups. COM therapy was more effective than MET alone in reducing body weight, BMI, and waist circumference, and improving insulin sensitivity in overweight/obese women with PCOS, with acceptable short-term side effects. ClinicalTrials.gov, NCT04029272. https://clinicaltrials.gov/ct2/show/NCT04029272.

Ibrutinib resistance remains a major obstacle in the treatment of diffuse large B‐cell lymphoma (DLBCL). Fat mass and obesity‐associated protein (FTO) has been implicated in drug resistance through its regulation of N6‐methyladenosine (m6A) modifications; however, whether FTO mediates ibrutinib resistance in DLBCL remains unclear. In this study, we found that FTO expression was significantly upregulated in patient samples and DLBCL cell lines. Functional assays showed that FTO knockout or knockdown suppressed cell proliferation and colony formation, whereas FTO overexpression promoted tumor growth and increased ibrutinib half‐maximal inhibitory concentration. Mechanistically, FTO directly bound to myelocytomatosis oncogene (Myc) mRNA and removed m6A modifications, stabilizing Myc transcripts and enhancing Myc protein expression. Methylated RNA immunoprecipitation–quantitative polymerase chain reaction confirmed that FTO knockout increased m6A enrichment on Myc mRNA, leading to decreased Myc stability. Rescue experiments showed that reintroducing Myc partially restored the proliferative and drug‐resistant phenotype of FTO‐deficient cells. Consistently, in xenograft models, FTO promoted tumor growth and ibrutinib resistance in a manner partly dependent on Myc. Overall, FTO promotes DLBCL progression and ibrutinib resistance by demethylating Myc mRNA and stabilizing its expression. These findings highlight the FTO‐m6A‐Myc axis as a potential therapeutic target for overcoming drug resistance in DLBCL.

Developing chiral receptors with an endo-functionalized cavity for chiral recognition is of great significance in the field of molecular recognition. This study presents two pairs of chiral naphthotubes containing a bis-thiourea endo-functionalized cavity. Each chiral naphthotube has two homochiral centers which were fixed adjacent to the thiourea groups, causing the skeleton and thiourea groups to twist enantiomerically through chiral transfer. These chiral naphthotubes are highly effective at enantiomerically recognizing various neutral chiral molecules with an enantioselectivity up to 17.0. Furthermore, the mechanism of the chiral recognition has been revealed to be originated from differences in multiple non-covalent interactions. Various factors, such as the shape of cavities, substituents of guests, flexibility of host and binding modes are demonstrated to contribute to creating differences in the non-covalent interactions. Additionally, the driving force behind enantioselectivity is mainly attributed to enthalpic differences, and enthalpy -entropy compensation has also been observed to influence enantioselectivity. Chiral receptors with an endo-functionalized cavity for chiral recognition are of interest in the field of molecular recognition. Here, the authors develop chiral naphthotubes containing a bis-thiourea endo-functionalized cavity to effectively recognize neutral chiral molecules with high enantioselectivity.

To meet the requirements of the biopharmaceutical industry, improving the yield of recombination therapeutic protein (RTP) from Chinese hamster ovary (CHO) cells is necessary. The human cytomegalovirus (CMV) promoter is widely used for RTP expression in CHO cells. To further improve RTP production, we truncated the human CMV intron and further evaluated the effect of four synthetic introns, including ctEF-1α first, EF-1α first, chimeric, and β-globin introns combined with the CMV promoter on recombinant expression levels in transient and stably recombinant CHO cells. The results showed that the truncated, EF-1α first, chimeric, and β-globin introns can significantly improve stable transgene expression in CHO cells. The qPCR results indicated that the mRNA level of transgene increased through optimizing intron sequences combined with the CMV promoter. Transcriptomics analysis was performed and found that differential expression of genes involved in mRNA processing, RNA export from nucleus, cytoplasmic translation, transcriptional activation and cell cycle regulation. In conclusion, optimization of the intron sequences combined with the CMV promoter can achieve a higher yield of recombinant proteins in CHO cells. This will be valuable for generating CHO cell lines with high productivity for industrial applications.

Background： Menopausal hormone therapy （MHT） has been proven to have beneficial effects on several components of metabolic syndrome. However, the effects vary according to different regimens, dosages, and duration of MHT. The aim of the study was to evaluate the effect of standard-dose 0.625 mg conjugated equine estrogen （CEE） and half-dose 0.3 mg CEE daily with different progestogens in a continuous sequential regimen on postmenopausal metabolic parameters in generally healthy postmenopausal women. Methods： A prospective, open-label, randomized controlled clinical trial was conducted between February 2014 and December 2015. Totally 123 Chinese postmenopausal women with climacteric symptoms were included in this study and were randomly assigned to three groups： Group A received CEE 0.3 mg/micronized progesterone （MP） 100 mg daily; Group B received CEE 0.625 mg/MP 100 mg daily; and Group C received CEE 0.625 mg/dydrogesterone 10 mg daily. Drugs were given in a continuous sequential pattern. The duration of treatment was 12 months. Clinical, anthropometrical, and metabolic variables were measured. Data were analyzed according to intention-to-treat analysis, using Student＇s t-test and analysis of variance. Results： A total of 107 participants completed the 12-month follow-up and were included in the data analysis. At 12 months of treatment, high-density lipoprotein cholesterol and apolipoprotein A significantly increased, and low-density lipoprotein cholesterol, fasting glucose, and glycosylated hemoglobin significantly decreased in Groups B and C, compared with baseline （all P 〈 0.05）. Among the three groups, only Group C showed significantly increased triglycerides compared with baseline （ 1.61 ± 0.80 mmol/L vs. 1.21 ± 0.52 mmol/L, P 0.026）. Each group showed a neutral effect on total cholesterol, lipoprotein A, apolipoprotein B, and fasting insulin levels. No cardiovascular and venous thromboembolic events occurred in the three groups. Conclusions： Among Chinese postmenopausal women, half-dose CEE was not sufficient to induce a favorable lipid and carbohydrate profile compared with standard-dose CEE. Adding natural MP may counterbalance the TG-increasing effect of CEE.

Penicillium marneffei is a dimorphic fungus endemic in Southeast Asia. It can cause fatal penicilliosis in humans, particularly in HIV-infected people. Diagnosis of this infection is difficult because its clinical manifestations are not distinctive. Specialized laboratory tests are necessary to establish a definitive diagnosis for successful management. We have demonstrated previously that a cell wall mannoprotein Mp1p, abundant in P. marneffei, is a potential biomarker for diagnosis of P. marneffei infections. In the present study, we describe immunoassays based on Mp1p derived from the yeast Pichia pastoris expression system. We generated monoclonal antibodies (MAbs) and rabbit polyclonal antibodies (PAbs) against Mp1p expressed in P. pastoris. Subsequently, we developed two Mp1p antigen capture ELISAs which employed MAbs for both the capture and detecting antibodies (MAb-MAb pair) or PAbs and MAbs as the capture and detecting antibodies (PAbs-MAb pair) respectively. The two Mp1p antigen ELISAs detected Mp1p specifically in cultures of P. marneffei yeast phase at 37-40°C and had no cross-reaction with other tested pathogenic fungi. The sensitivities and specificities of the two antigen assays were found to be 55% (11/20) and 99.6% (538/540) for MAb-MAb Mp1p ELISA, and 75% (15/20) and 99.4% (537/540) for PAbs-MAb Mp1p ELISA performed using 20 sera with culture-confirmed penicilliosis, and 540 control sera from 15 other mycosis patients and 525 healthy donors. Meanwhile, we also developed an anti-Mp1p IgG antibody ELISA with an evaluated sensitivity of 30% (6/20) and a specificity of 98.5% (532/540) using the same sera. Furthermore, combining the results of Mp1p antigen and antibody detection improved the sensitivity of diagnosis to 100% (20/20). Simultaneous detection of antigen and antibody using the immunoassays based on Mp1p derived from P. pastoris greatly improves detection sensitivity. The procedures should be useful for the routine diagnosis of penicilliosis.

Background Evidence-based practice (EBP) education or training are considered fundamental to building and strengthening an EBP culture, as well as to encouraging evidence-based academic and clinical practice in the nursing community. However, few valid and reliable instruments are available for the assessment of EBP teaching and learning in clinical nurses in China. Translation, reliability, and validity testing of the English Evidence-Based Practice Profile Questionnaire (EBP 2 Q), which has strong psychometric properties, may encourage evaluation and promote the implementation of EBP in Mainland China. Methods Based on established guidelines for the development of questionnaires, the English EBP 2 Q was translated and cross-culturally adapted. The Chinese version of the EBP 2 Q (EBP 2 Q-C) was validated using a sample of 543 nurses. Structural validity was evaluated through exploratory factor analysis and confirmatory factor analysis, and the questionnaire was tested for convergent and criterion validity. The internal consistency and test-retest reliability were also evaluated. Results The content validity index demonstrated good content validity (≥0.98). An eight-factor structure was obtained in the exploratory factor analysis, and verified by a three-order factor model from the confirmatory factor analysis ( χ 2 /df  = 2.001; RMSEA = 0.065; SRMR = 0.077; and CFI = 0.884). The Spearman’s rank correlation analysis of the EBP 2 Q-C with the Evidence-Based Practice Questionnaire showed moderate correlations for Practice (0.58) and Confidence (0.68) and a low correlation for Sympathy (0.32). Criterion validity was demonstrated by significant differences in terms of nurses’ highest education, present position, EBP training, involvement in research programs, and level of understanding of English. Both the overall Cronbach’s α and the Cronbach’s α for the domains exceeded 0.70. The intraclass correlation coefficients for the domains ranged between 0.75 and 0.96, indicating satisfactory repeatability. Conclusions Except for the convergent validity of the Sympathy domain, the EBP 2 Q-C provided evidence of validity and reliability. Therefore, it can be applied in EBP education or training assessment in Mainland China.

The isotopic fractionation factor and element partition coefficient can be calculated only after the geometric optimization of the molecular clusters is completed. Optimization directly affects the accuracy of some parameters, such as the average bond length, molecular volume, harmonic vibrational frequency, and other thermodynamic parameters. Here, we used the improved volume variable cluster model (VVCM) method to optimize the molecular clusters of a typical oxide, quartz. We documented the average bond length and relative volume change. Finally, we extracted the harmonic vibrational frequencies and calculated the equilibrium fractionation factor of the silicon and oxygen isotopes. Given its performance in geometrical optimization and isotope fractionation factor calculation, we further applied the improved VVCM method to calculate isotope equilibrium fractionation factors of Cd and Zn between the hydroxide (Zn–Al layered double hydroxide), carbonate (cadmium-containing calcite) and their aqueous solutions under superficial conditions. We summarized a detailed procedure and used it to re-evaluate published theoretical results for cadmium-containing hydroxyapatite, emphasizing the relative volume change for all clusters and confirming the optimal point charge arrangement (PCA). The results showed that the average bond length and isotope fractionation factor are consistent with those published in previous studies, and the relative volume changes are considerably lower than the results calculated using the periodic boundary method. Specifically, the average Si–O bond length of quartz was 1.63 Å, and the relative volume change of quartz centered on silicon atoms was − 0.39%. The average Zn–O bond length in the Zn–Al-layered double hydroxide was 2.10 Å, with a relative volume change of 1.96%. Cadmium-containing calcite had an average Cd–O bond length of 2.28 Å, with a relative volume change of 0.45%. At 298 K, the equilibrium fractionation factors between quartz, Zn–Al-layered double hydroxide, cadmium-containing calcite, and their corresponding aqueous solutions were Δ30/28SiQtz-H4SiO4=2.20‰, Δ18/16OQtz-(H2O)n=36.05‰, Δ66/64ZnZn-Al LDH-Zn(H2O)n2+=1.12‰ and Δ114/110Cd(Cd--Cal)-Cd(H2O)n2+=-0.26‰ respectively. These results strongly support the reliability of the improved VVCM method for geometric optimization of molecular clusters.

Hi‐C can obtain three‐dimensional chromatin structure information and is widely used for genome assembly. We constructed the GutHi‐C technology. As shown in the graphical , it is a highly efficient and quick‐to‐operate method and can be widely used for human, livestock, and poultry gut microorganisms. It provides a reference for the Hi‐C methodology of the microbial metagenome. DPBS, Dulbecco's phosphate‐buffered saline; Hi‐C, high‐through chromatin conformation capture; LB, Luria‐Bertani; NGS, next‐generation sequencing; PCR, polymerase chain reaction; QC, quality control.

In the present work, we described the preparation of polyaniline-graphene oxide composite film (PANI/GO) by the stirring electropolymerization method and then it was characterized. A graphite rod electrode (GE) modified with the composite film showed enhanced electrochemical sensing capability for formaldehyde solution. Cyclic voltammetry showed an increase in the formaldehyde oxidation peak current at the GE modified with PANI/GO (GO/PANI/GE). The sensitivity in the linear segment was 502.42 μA mM−1 cm−2. The oxidation peak current increased linearly with increasing formaldehyde concentration from 0.1 to 20 μM. The detection limit was 0.0185 µM (S/N = 3). In addition, the sensor displays an acceptable repeatability and reproducibility along with appreciable storage and excellent operational stabilities.