Mechanistic Insight into the Synthesis and Morphological Evolution of Superhydrophobic Silica Nanotubes.

Silica nanotubes have significant applications in various fields, including thermal insulation, self-cleaning, and catalysis. Currently, the synthesis methods of silica nanotubes are mostly limited to the template method. In this work, a template-free strategy and vapor-phase approach were used to prepare silica nanotubes. Poly(methylhydrosiloxane) (PMHS) was hydrolyzed and condensed in a high-temperature closed reactor by using ammonia as a catalyst. The resulting product was then subjected to template-free self-assembly to synthesize silica nanotubes incorporating methyl groups. The silica nanotubes were synthesized under varying conditions, resulting in lengths ranging from 50 nm to several micrometers, exterior diameters between 40 and 120 nm, and wall thicknesses varying from 7 to 30 nm. The synthesized products underwent morphology analysis using TEM and FESEM for morphology analysis, elemental composition analysis using XPS, and chemical structure identification using FTIR, and the possible formation mechanism of silica nanotubes formation was also speculated. Furthermore, the coatings formed by silica nanotubes exhibited remarkable superhydrophobic self-cleaning properties with a water contact angle of 162° and a rolling angle of less than 1°.

Delayed cutaneous hypersensitivity reactions following the use of infliximab or adalimumab in patients with coronavirus disease 2019.

Recent evidence has emerged concerning delayed cutaneous hypersensitivity reactions after infliximab or adalimumab applications in patients with coronavirus disease 2019 (COVID-19). A few real-world studies compared the events, clinical features, and prognosis of infliximab- or adalimumab-related delayed cutaneous hypersensitivity reactions in COVID-19 patients. Disproportionality analysis and Bayesian analysis were utilized to determine the suspected adverse events of delayed cutaneous hypersensitivity reactions after infliximab or adalimumab use based on the Food and Drug Administration's Adverse Event Reporting Systems (FAERS) from May 2020 to December 2021. Additionally, the times to onset and fatality rates of delayed cutaneous hypersensitivity reactions following infliximab or adalimumab were compared. In total, 475 reports of delayed cutaneous hypersensitivity reactions were associated with infliximab or adalimumab. Females were affected almost twice more than males. Among the two therapies, infliximab had the highest association with delayed cutaneous hypersensitivity reactions based on the highest reporting odds ratio (2.14, 95% two-sided confidence interval [CI] = 1.2-3.81), proportional reporting ratio (1.95, χ2 = 7.03), and empirical Bayesian geometric mean (1.94, 95% one-sided CI = 1.2). Infliximab-related delayed cutaneous hypersensitivity reactions had earlier onset (0 [interquartile range (IQR): 0-0] days vs. 166.5 (IQR: 18-889.5) days, p < 0.05), while adalimumab-related delayed cutaneous hypersensitivity reactions have higher fatality rate (0.44% vs. 0.00%). Based on the FAERS database, we profiled delayed cutaneous hypersensitivity reactions related to infliximab or adalimumab application in patients with COVID-19 with more points of occurrences, clinical characteristics, and prognosis.

Influence of Vitamin D supplementation on reproductive outcomes of infertile patients: a systematic review and meta-analysis.

BACKGROUND: Low vitamin D status has been associated with an increased risk for infertility. Recent evidence regarding the efficacy of vitamin D supplementation in improving reproductive outcomes is inconsistent. Therefore, this systematic review was conducted to investigate whether vitamin D supplementation could improve the reproductive outcomes of infertile patients and evaluate how the parameters of vitamin D supplementation affected the clinical pregnancy rate. METHODS: We searched seven electronic databases (CNKI, Cqvip, Wanfang, PubMed, Medline, Embase, and Cochrane Library) up to March 2022. Randomized and cohort studies were collected to assess the reproductive outcomes difference between the intervention (vitamin D) vs. the control (placebo or none). Mantel-Haenszel random effects models were used. Effects were reported as odds ratio (OR) and their 95% confidence interval (CI). PROSPERO database registration number: CRD42022304018. RESULTS: Twelve eligible studies (n = 2352) were included: 9 randomized controlled trials (RCTs, n = 1677) and 3 cohort studies (n = 675). Pooled results indicated that infertile women treated with vitamin D had a significantly increased clinical pregnancy rate compared with the control group (OR: 1.70, 95% CI: 1.24-2.34; I2 = 63%, P = 0.001). However, the implantation, biochemical pregnancy, miscarriage, and multiple pregnancy rates had no significant difference (OR: 1.86, 95% CI: 1.00-3.47; I2 = 85%, P = 0.05; OR: 1.49; 0.98-2.26; I2 = 63%, P = 0.06; OR: 0.98, 95% CI: 0.63-1.53; I2 = 0%, P = 0.94 and OR: 3.64, 95% CI: 0.58-11.98; I2 = 68%, P = 0.21). The improvement of clinical pregnancy rate in the intervention group was influenced by the vitamin D level of patients, drug type, the total vitamin D dosage, the duration, administration frequency, and daily dosage of vitamin D supplementation. The infertile women (vitamin D level < 30 ng/mL) treated with the multicomponent drugs including vitamin D (10,000-50,000 IU or 50,000-500,000 IU), or got vitamin D 1000-10,000 IU daily, lasting for 30-60 days could achieve better pregnancy outcome. CONCLUSION: To the best of our knowledge, this is the first meta-analysis systematically investigated that moderate daily dosing of vitamin D supplementation could improve the clinical pregnancy rate of infertile women and reported the effects of vitamin D supplementation parameters on pregnancy outcomes. A larger sample size and high-quality RCTs are necessary to optimize the parameters of vitamin D supplementation to help more infertile patients benefit from this therapy.

Synthesis and evaluation of sulfonamide derivatives targeting EGFR790M/L858R mutations and ALK rearrangement as anticancer agents.

Fourteen new compounds bearing sulfonamide groups that target EGFRT790M/L858R mutations and ALK rearrangement were synthesized and evaluated as dual-target tumor inhibitors. The study on the anti-proliferation activity on cancer cells showed that the sulfonamide derivative with pyrimidine nucleus had much better activities compared with those with quinazoline nucleus. Among them, compound 19e exhibited excellent activity against H1975 cancer cell lines (EGFRT790M/L858R high express) and H2228 cells (ALK rearrangement) with the IC50 values of 0.0215 µM and 0.011 µM, respectively. The ALK and EGFR kinase inhibition assays also provided similar results. Genotype selectivity of EGFR on kinase and cell level, cytotoxicity towards human normal cell lines and cell morphology assay implied that 19e had acceptable selectivity and low toxicity. In addition, the inhibitory activity of 19e on H1975 and H2228 cells cloning and its apoptosis-inducing effect on the two cell lines were studied, and its inhibitory effect on the invasion and migration of tumor cells were also investigated. All the results show that 19e is worthy of further study.

Few-layered boron nitride nanosheet as a non-metallic phosphatase nanozyme and its application in human urine phosphorus detection.

Human urine phosphorus (existing in the form of phosphate) is a biomarker for the diagnosis of several diseases such as kidney disease, hyperthyroidism, and rickets. Therefore, the selective detection of phosphate in urine samples is crucial in the field of clinical diagnosis. Herein, we reported the phosphatase-like catalytic activity of few-layered h-BNNS for the first time. As the phosphatase-like activity of few-layered h-BNNS could be effectively inhibited by phosphate, a selective fluorescent method for the detection of phosphate was proposed. The linear range for phosphate detection is 0.5-10 µM with a detection limit of 0.33 µM. The fluorescent method was then explored for the detection of human urine phosphorus in real samples. The results obtained by the proposed method were consistent with those of the traditional method, indicating that the present method has potential application for urine phosphorus detection in clinical disease diagnosis.

Engineering an Ag/Au bimetallic nanoparticle-based acetylcholinesterase SERS biosensor for in situ sensitive detection of organophosphorus pesticide residues in food.

Developing simple, efficient, and inexpensive method for trace amount organophosphorus pesticides' (OPs) detection with high sensitivity and specificity is of significant importance for guaranteeing food safety. Herein, an Ag/Au bimetallic nanoparticle-based acetylcholinesterase (AChE) surface-enhanced Raman scattering (SERS) biosensor was constructed for in situ simple and sensitive detection of pesticide residues in food. The principle of this biosensor exploited 4-mercaptophenylboronic acid (4-MPBA)-modified Ag/Au bimetallic nanoprobes as SERS signal probe to improve sensitivity and stability. The combination of AChE and choline oxidase (CHO) can hydrolyze acetylcholine (ATCh) to generate H2O2. The product of H2O2 selectively oxidizes the boronate ester of 4-MPBA, decreasing the Raman intensity of the B-O symmetric stretching. In the presence of OPs, it could inhibit the production of H2O2 by destroying the AChE activity, so the reduction of the SERS signal was also alleviated. Based on the principle, an Ag/Au bimetallic nanoparticle-based AChE SERS sensor was established without any complicated pretreatments. Benefiting from the synergistic effects of Ag/Au bimetallic hybrids, a linear detection range from 5×10-9 to 5×10-4 M was achieved with a limit of detection down to 1.7×10-9 M using parathion-methyl (PM) as the representative model of OPs. Moreover, the SERS biosensor uses readily available reagents and is simple to implement. Importantly, the proposed SERS biosensor was used to quantitatively analyze OP residues in apple peels. The levels of OPs detected in real samples by this method were consistent with those obtained using gas chromatography-mass spectrometry (GC-MS), suggesting the proposed assay has great potential applications for OPs in situ detection in food safety fields.

Polygonatum sibiricum Polysaccharide Inhibited Liver Cancer in a Simulated Tumor Microenvironment by Eliminating TLR4/STAT3 Pathway.

Liver cancer is one of the most aggressive tumors and one of the most common malignant tumors which seriously threatens human health. Traditional Chinese medicine (TCM) was reported to resist the proliferation and metastasis of liver cancer cells. In this study, we aimed to explore the potential anti-cancer effect of Polygonatum sibiricum polysaccharide (PSP) on the tumor immune microenvironment in liver cancer cells. HepG2 and Hep3B cells were pretreated in the absence or the presence of PSP (20, 50, 100 µg/mL) for a period of 24 h. Subsequently, dendritic cells (DCs) were co-cultured with HepG2 and Hep3B cell supernatant to investigate the effect of PSP on the tumor microenvironment. The results showed that PSP dose-dependently inhibited proliferation and promoted apoptosis of HepG2 and Hep3B cells. Meanwhile, PSP dose-dependently inhibited migration, invasion, and epithelial-to-mesenchymal transition (EMT) of liver cancer cells. In addition, PSP dose-dependently induced inflammatory response of DCs, characterized by increases of interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α in DCs. Mechanically, PSP dose-dependently reduced the activation of the Toll-like receptor 4 (TLR4)/Signal transducer and activator of transcription 3 (STAT3) and noncanonical nuclear factor-kappa B (NF-κB) signaling pathways. TLR4 agonist lipopolysaccharide (LPS) reversed the anti-oncogenic effects of PSP in liver cancer cells. Taken together, PSP inhibited liver cancer in a simulated tumor microenvironment by eliminating TLR4/STAT3 pathway. PSP promises an important and useful alternative to liver cancer treatment.

Serum kisspeptin levels in polycystic ovary syndrome: A meta-analysis.

AIM: To clarify the association of serum kisspeptin levels in women with polycystic ovary syndrome (PCOS) by meta-analysis. METHODS: Two English databases and two Chinese databases were searched for the relationship between kisspeptin and PCOS published from 2009. After the studies screening according to specific principles, we used STATA 12.0 for meta-analysis. Standardized mean difference (SMD) and its 95% confidence intervals (95% CIs) were used as the effect size and STATA 12.0 software was performed by this meta-analysis. RESULTS: Nine articles were included in the end, with a total of 1282 participants (699 patients and 583 controls). Heterogeneity between studies was statistically significant. Therefore, the random effects model was used to combine the effects. Meta-analysis showed statistically significant differences in serum kisspeptin levels between the PCOS patients and controls (SMD = 0.57, 95% CI [0.32, 0.82]), which indicated that there is a strong association between serum kisspeptin levels and PCOS. The source of high heterogeneity between the inclusion studies (I2  = 73.2%) might be due to the small sample size. The larger variation of kisspeptin concentration might be caused by different diagnosis criteria of PCOS and short half-time period of kisspeptin combined with nonstandard testing process. CONCLUSION: Serum kisspeptin levels in PCOS patients were higher than non-PCOS patients. It is a hint to indicate us that kisspeptin might be an independent biomarker of PCOS patients.

Distinct regulation of atonal in a visual organ of Drosophila: Organ-specific enhancer and lack of autoregulation in the larval eye.

Drosophila has three types of visual organs, the larval eyes or Bolwig's organs (BO), the ocelli (OC) and the compound eyes (CE). In all, the bHLH protein Atonal (Ato) functions as the proneural factor for photoreceptors and effects the transition from progenitor cells to differentiating neurons. In this work, we investigate the regulation of ato expression in the BO primordium (BOP). Surprisingly, we find that ato transcription in the BOP is entirely independent of the shared regulatory DNA for the developing CE and OC. The core enhancer for BOP expression, atoBO, lies ~6kb upstream of the ato gene, in contrast to the downstream location of CE and OC regulatory elements. Moreover, maintenance of ato expression in the neuronal precursors through autoregulation-a common and ancient feature of ato expression that is well-documented in eyes, ocelli and chordotonal organs-does not occur in the BO. We also show that the atoBO enhancer contains two binding sites for the transcription factor Sine oculis (So), a core component of the progenitor specification network in all three visual organs. These binding sites function in vivo and are specifically bound by So in vitro. Taken together, our findings reveal that the control of ato transcription in the evolutionarily derived BO has diverged considerably from ato regulation in the more ancestral compound eyes and ocelli, to the extent of acquiring what appears to be a distinct and evolutionarily novel cis-regulatory module.

[Progress of non-genomic action of estrogen and its impact on female reproduction].

Estrogen is one of the steroid hormones. Besides the genomic action mediated by its intracellular receptor on target cells, there is now increasing body of evidence indicating that estrogen also has non-genomic action. For the non-genomic action, estrogen binds to its receptor on cell membrane, subsequently rapidly activates various intracellular signaling pathways, such as PLC/Ca(2+), ERK/MAPK, cAMP-PKA, PI3K-AKT-NOS, and finally induces biological effects. The non-genomic effects of estrogen on physiologic and pathologic processes have been found in many tissues within the reproductive, nervous and cardiovascular systems and bone etc. In reproductive system, it has been demonstrated that estrogen plays important roles in follicle development, fertilization and embryo implantation, and it is involved in the genesis and development of genital tract tumors and breast cancer. In this review, we focus on the general characteristics of non-genomic action of estrogen, its main nonnuclear signaling pathways and physiological and pathological significance, especially its influences in female reproductive functions.

ato-Gal4 fly lines for gene function analysis: Eya is required in late progenitors for eye morphogenesis.

The Gal4/UAS system is one of the most powerful tools for the study of cellular and developmental processes in Drosophila. Gal4 drivers can be used to induce targeted expression of dominant-negative and dominant-active proteins, histological markers, activity sensors, gene-specific dsRNAs, modulators of cell survival or proliferation, and other reagents. Here, we describe novel atonal-Gal4 lines that contain regions of the regulatory DNA of atonal, the proneural gene for photoreceptors, stretch receptors, auditory organ, and some olfactory sensilla. During neurogenesis, the atonal gene is expressed at a critical juncture, a time of transition from progenitor cell to developing neuron. Thus, these lines are particularly well suited for the study of the transcription factors and signaling molecules orchestrating this critical transition. To demonstrate their usefulness, we focus on two visual organs, the eye and the Bolwig. We demonstrate the induction of predicted eye phenotypes when expressing the dominant-negative EGF receptor or a dsRNA against Notch in the developing eye disc. In another example, we show the deletion of the Bolwig's organ using the proapoptotic factor Hid. Finally, we investigate the function of the eye specification factor Eyes absent or Eya in late retinal progenitors, shortly before they begin morphogenesis. We show that Eya is still required in these late progenitors to promote eye formation, and show failure to induce the target gene atonal and consequent lack of neuron formation.

Relocalisation and activation of integrins induced rapidly by oestrogen via G-protein-coupled receptor 30 in mouse blastocysts.

Integrins are the dominant and final adhesion molecules in the attachment process between the blastocysts and endometrium. It is necessary for oestrogen to rapidly activate mouse blastocysts so that they attach to the endometrial epithelium. Our previous study suggested that oestrogen can rapidly induce an increase in intracellular calcium in mouse blastocysts via G-protein-coupled receptor 30 (GPR30). Thus, we deduced that integrins may be involved in GPR30 mediation of the fast effect of oestrogen on mouse blastocysts in implantation. To prove our hypothesis, we used immunofluorescence staining and in vitro coculture of mouse blastocysts and endometrial epithelial cell line (EECs), Ishikawa cells, in the present study. We found that αv and ß1 integrin clustered in mouse blastocysts, and that ß3 integrin was relocalised to the apical membrane of blastocyst cells when embryos were treated with 1 µM 17ß-estradiol (E2), 1 µM E2 conjugated to bovine serum albumin (E2-BSA) and 1 µM G-1, a specific GPR30 agonist, for 30 min respectively, whereas pretreatment with 1 µM G15, a specific GPR30 antagonist, and 5 µM 1,2-Bis(2-aminophenoxy)ethane-N,N,N'',N''-tetraacetic acid tetrakis (acetoxymethyl ester)(BAPTA/AM), a cellular Ca2+ chelator, blocked the localisation of integrins induced by oestrogen via GPR30 in mouse blastocyst cells. E2, E2-BSA and G-1 increased the fibronectin (FN)-binding activity of integrins in blastocysts, whereas G15 and BAPTA/AM blocked the activation of integrins induced by oestrogen via GPR30 in mouse blastocysts. Inhibition of integrins by Arg-Gly-Asp peptide in blastocysts resulted in their failure to adhere to EECs in vitro, even if oestrogen or G-1 was provided. Together, the results indicate the fast effect of oestrogen via the GPR30 membrane receptor further induces relocalisation and activation of integrins in mouse blastocysts, which play important roles in the adhesion of blastocysts to EECs.

[Estrogen induced rapid increase of intracellular calcium plays important role in the implantation of mouse blastocysts].

OBJECTIVE: To study the roles of the increased intracellular calcium induced rapidly by estrogen in the implantation of mouse blastocysts. METHODS: The mouse blastocysts were collected from the female mice on the pregnant day 4, divided into 3 groups: control, E2-BSA and BAPTA +E2-BSA. Immunofluorescence staining, confocal microscopy, embryo and endometrial epithenial cells co-culture and embryo transfer were used to investigate the effect of increased intracellular calcium induced by E2-BSA on the expression and localization of integrins in blastocysts and their adhesion to endometrial epithenial calls (EECs) and implantation into the endometrium. RESULTS: The increase of intracellular calcium induced rapidly by estrogen could cause the cluster and relocation of integrin av and beta3, and BAPTA might block this effect, the adhesion rate of blastocysts in contol group was 35.5%, BAPTA +E2-BSA group was 26.7% and significantly lower than 65.6% of E2-BSA group (P<0.05), and the implantation rate in BAPTA+E2-BSA group was 11.8%, which was significantly lower than 52.9% of E2-BSA group (P<0.05). CONCLUSION: The rapid increase of intracellular calcium induced by estrogen may cause the relocalization of integrin in blastocysts and their adhesion to ECCs, which is important in the process of implantation.

Spatial information extraction of fishing grounds for light purse seine vessels in the Northwest Pacific Ocean based on AIS data.

Ecological fishery management requires high-precision fishery information to support resource management and marine spatial planning. In this paper, the Automatic Identification System (AIS) was adopted to extract the spatial information on the fishing grounds of light purse seine vessels in the Northwest Pacific Ocean. The spatial distributions of fishing grounds mapped by the data mining, kernel density analysis and hotspot analysis methods were compared. The spatial similarity index was applied to determine the spatial consistency between the computed spatial information and fisheries resource information. Finally, the spatial information derived by the best method was used to investigate the characteristics of fishing activity. The results showed that: the speed of light purse seine vessels related to operations was lower than 1.6 knots. The spatial information extracted by the three methods was consistent with the catch data distribution, and the spatial similarity between the fishing effort and catch data was the highest. The spatial variation in fishing activity was similar to that in the chub mackerel migration route. AIS data could be used to provide high-resolution fishery information. Light purse seine fishing vessels typically operate and travel along the exclusive economic zone boundary, and increased attention must be given to fishing vessel operation supervision. A comprehensive supervision system can be employed to monitor the operations of fishing vessels more effectively. The results of this study can provide technical support for the management of fishing activities and conservation of marine resources in this region using AIS data.

Two new withanolides from Physalis minima L.

Two new withanolides named physaminilides L (1) and M (2), together with four known ones (3-6) were isolated from the Physalis minima L. The structures were established by analysis of the HR ESIMS, IR and NMR spectroscopic data. The absolute configurations were determined through NOESY and ECD spectra. For compounds 1-5 assayed at 20 µM and compound 6 at 10 µM, inhibition rates of hepatic fibrosis were 22.19%, 15.29%, 37.07%, 9.27%, 12.45%, and 37.03%, respectively.

Differences and Clinical Significance of Serum 25-Hydroxyvitamin D3 and Vasohibin-1 (VASH-1) Levels in Patients with Diabetic Nephropathy and Different Renal Injuries.

Objective: We investigate the relationship between the changes of serum 25-hydroxyvitamin D3 (25(OH)D3) and vasohibin-1 (VASH-1) and renal function injury in patients with type 2 diabetic nephropathy. Methods: In this study, 143 patients with diabetic nephropathy (DN) were selected as DN group, and 80 patients with type 2 diabetes mellitus were selected as T2DM group. The serum 25 (OH) D3, VASH-1, blood glucose index, inflammation index and renal function index were compared between the two groups. According to the urinary microalbumin/creatinine ratio (UACR), the DN group was divided into microalbuminuria group (UACR range≥30.0mg/g and <300.0mg/g) and macroalbuminuria group (UACR≥300.0mg/g) for stratified comparison. The correlation between 25-hydroxyvitamin D3, VASH-1 and inflammation index and renal function index was analyzed by simple linear correlation analysis. Results: The level of 25 (OH) D3 in DN group was significantly lower than that in T2DM group (P<0.05). The levels of VASH-1, CysC, BUN, Scr, 24h urine protein, serum CRP, TGF-ß1, TNF-α and IL-6 in DN group were higher than those in T2DM group (P<0.05). The level of 25 (OH) D3 in DN patients with massive proteinuria was significantly lower than that in DN patients with microalbuminuria. The level of VASH-1 in DN patients with massive proteinuria was higher than that in DN patients with microalbuminuria (P<0.05). There was a negative correlation between 25 (OH) D3 and CysC, BUN, Scr, 24h urine protein, CRP, TGF-ß1, TNF-α, IL-6 in patients with DN (P<0.05). VASH-1 was positively correlated with Scr, 24h urinary protein, CRP, TGF-ß1, TNF-α and IL-6 in patients with DN (P<0.05). Conclusion: The level of serum 25 (OH) D3 in DN patients was considerably decreased, and the level of VASH-1 was increased, which was related to the degree of renal function injury and inflammatory response.

Effect of SGLT2 Inhibitors on Improving Glucolipid Metabolism and Reproductive Hormone Status in Overweight/Obese Women with PCOS: A Systematic Review and Meta-Analysis.

BACKGROUND: Obesity, insulin resistance, and hyperandrogenemia are commonly seen in women with polycystic ovary syndrome (PCOS), and these three conditions form a vicious cycle leading to reproductive and metabolic abnormalities. Metformin improves the symptoms of PCOS by increasing insulin sensitivity but is not therapeutically optimal. Recent studies have reported that sodium-glucose co-transporter protein receptor inhibitors improve insulin resistance and reduce the weight of patients with PCOS. We performed a meta-analysis to assess the influence of sodium-glucose co-transporter protein-2 (SGLT2) inhibitors on anthropometric, glycolipid metabolism and reproductive outcomes after therapy of overweight/obese women with PCOS. METHODS: We searched the relevant literature published up to April 2023. Information on the effect of SGLT2 inhibitors on overweight/obese patients with PCOS was extracted independently by two reviewers. Review Manager 5.3 was used for meta-analysis. RESULTS: Five randomized controlled trials that met our criteria were retrieved. Our meta-analysis demonstrated that in overweight/obese patients with PCOS, SGLT2 inhibitors treatment was significantly superior to metformin treatment in terms of reducing body weight (P = 0.02, I2 = 36%), decreasing dehydroepiandrosterone sulfate concentrations [SMD = -0.42, 95% CI (-0.76, -0.07), I2 = 22%, P = 0.02], and reducing the incidence of nausea [RR = 0.35, 95% CI (0.21, 0.60), I2 = 71%, P = 0.0001]. CONCLUSIONS: SGLT2 inhibitors are a possible alternative therapy for treating overweight/obese women with PCOS who do not respond favorably to metformin treatment. However, further large randomized controlled trials and cost-effectiveness analyses are warranted to guide the implementation of SGLT2 inhibitors treatment in this population.

Identification of Bombyx atonal and functional comparison with the Drosophila atonal proneural factor in the developing fly eye.

The proneural genes are fundamental regulators of neuronal development in all metazoans. A critical role of the fly proneural factor Atonal (Ato(Dm)) is to induce photoreceptor neuron formation in Drosophila, whereas its murine homolog, Atonal7(Mm) (aka Ath5) is essential for the development of the ganglion cells of the vertebrate eye. Here, we identify the Bombyx mori ato homolog (ato(Bm) ). In a pattern strikingly reminiscent of ato(Dm), the ato(Bm) mRNA is expressed as a stripe in the silkworm eye disc. Its DNA-binding and protein-protein interaction domain is highly homologous to the Ato(Dm) bHLH. Targeted expression of Ato(Bm) in the endogenous ato(Dm) pattern rescues the eyeless phenotype of the fly ato(1) mutant and its ectopic expression induces similar gain-of-function phenotypes as Ato(Dm). Rescue experiments with chimeric proteins show that the non-bHLH portion of Ato(Bm) (N-region) can effectively substitute for the corresponding region of the fly transcription factor, even though no apparent conservation can be found at the amino acid level. On the contrary, the highly similar bHLH domain of Ato(Bm) cannot similarly substitute for the corresponding region of Ato(Dm). Thus, the bHLH(Bm) domain requires the Ato(Bm) N-region to function effectively, whereas the bHLH(Dm) domain can operate well with either N-region. These findings suggest a role for the non-bHLH portion of Ato proteins in modulating the function of the bHLH domain in eye neurogenesis and implicate specific aa residues of the bHLH in this process.

New pathogenetic characters of reticuloendotheliosis virus isolated from Chinese partridge in specific-pathogen-free chickens.

Avian reticuloendotheliosis virus (REV) infection can induce a runting syndrome, immunosuppression, acute reticulum cell neoplasia and lymphomas in a variety of domestic and wild birds. To evaluate the pathogenicity and oncogenicity of REV-JX0927 that isolated from Chinese partridge, experimental inoculated day-old specific-pathogen-free (SPF) White Leghorn chickens were examined at regular intervals. The examination procedures included hematology, serology and histopathology; also including immunohistochemistry and apoptosis assay. Body weight, relative immune organs weight and apoptosis assay results revealed that the immunosuppression of infected birds is associated with apoptosis of lymphocytes in lymphoid tissues, especially in thymus induced by REV-JX0927. Hematology and apoptosis assay results showed that the 7th week of post-infection is a critical time point for lymphocytes to be transformed into tumor cells. Histopathology evidences demonstrated that REV-JX0927 induced reticuloendotheliosis at early stage (1 week), and lymphosarcomas at middle stage (after 7 weeks). In addition, squamous-cell carcinoma, adenocarcinoma and aneurysm were found in infected birds. Arteritis was associated with concentration of serum protein and fat. REV antigen expression was observed in infected birds through the experimental period. REV has high tropism for proventriculus, kidney, liver, lymphoid tissues, pancreas, lymphosarcoma cells and blood vessels. Data from this study showed that several new pathogenitic characters caused by REV-JX0927 were observed. It indicated that REV-JX0927 is a multipotential oncogenic retrovirus.

Improving adaptive response to negative stimuli through non-emotional working memory training.

People with high working memory (WM) capacity tend to respond proactively and experience a decrease in undesired emotions, implying the potential influence of WM training on emotional responses. Although training emotional WM could enhance emotional control, the training also improves emotional response itself. Thus, the far-transfer effects of non-emotional WM training on emotional responses remain an open question. In the present study, two experiments were conducted to detect these effects. The Preliminary experiment matched the expectations of the gains of the training tasks between the experimental and active control groups (n = 33). In Experiments 1 and 2, participants performed 7-day and 15-day training procedures, respectively. Results indicated that after a 7-day training, non-emotional WM training (n = 17) marginally reduced individuals' emotional responses compared with the active control group (n = 18); importantly, this improvement became significant after a 15-day training (n (WM training) = 20, n (active control) = 18). A combination analysis for Experiments 1 and 2 showed that training gains on WM performance were significantly related to reduced emotional responses (r = -0.359), indicating a dosage effect. Therefore, non-emotional WM training provides a safe and effective way to enhance adaptive emotional responses.