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Abstract Background Patients with type 2 diabetes often face early tubular injury, necessitating effective treatment strategies. This study aimed to evaluate the impact of the SGLT2 inhibitor empagliflozin on early tubular injury biomarkers in type 2 diabetes patients with normoalbuminuria. Methods A randomized controlled clinical study comprising 54 patients selected based on specific criteria was conducted. Patients were divided into an intervention group (empagliflozin, n = 27) and a control group (n = 27) and treated for 6 weeks. Tubular injury biomarkers KIM-1 and NGAL were assessed pre- and post-treatment. Results Both groups demonstrated comparable baseline characteristics. Post-treatment, fasting and postprandial blood glucose levels decreased similarly in both groups. The intervention group exhibited better improvements in total cholesterol, low-density lipoprotein, and blood uric acid levels. Renal function indicators, including UACR and eGFR, showed greater enhancements in the intervention group. Significant reductions in KIM-1 and NGAL were observed in the intervention group. Conclusion Treatment with empagliflozin in type 2 diabetes patients with normoalbuminuria led to a notable decrease in tubular injury biomarkers KIM-1 and NGAL. These findings highlight the potential of SGLT2 inhibitors in early tubular protection, offering a new therapeutic approach.

Abstract Background The influence of gestational diabetes mellitus (GDM) on postpartum cardiometabolic indicators is primarily restricted to glucose and lipid metabolism, however the indicators for liver and kidney function have been rarely explored, and the role of the third-trimester inflammatory factors in these associations has never been investigated. Methods Based on the Ma’anshan birth cohort (MABC), women with or without GDM history were selected and invited to participate in a 6-year postpartum follow-up. The fasting blood samples were collected to measure 16 comprehensive metabolic indicators during a 6-year postpartum follow-up: fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), triglycerides (TG), total cholesterol (TC), uric acid (UA), blood urea nitrogen (BUN), serum creatinine (SCR), etc. Seven inflammatory factors, including TNF-α, IFN-γ, IL-1β, IL-6, IL-10, IL-12p70, and IL-17 A, were measured with serum samples collected during the third trimester of pregnancy. Linear regression models were used to analyze the associations between GDM and 6-year postpartum metabolic indicators, GDM and third-trimester inflammatory factors, and the third-trimester inflammatory factors and 6-year postpartum metabolic indicators. Mediating and moderating effect analyses were further performed to explore if the third-trimester inflammatory factors mediate or modify the association between GDM and postpartum cardiometabolic indicators. Results From July 2021 to August 2022, 307 participants have been followed up, with 99 women with a prior GDM history. Compared with those without GDM, individuals with a prior history of GDM had significantly elevated levels of FPG (β = 0.40, 95% CI: 0.18 to 0.62, P FDR < 0.001), HbA1c (β = 0.22, 95% CI: 0.09 to 0.34, P FDR = 0.009), TyG (β = 0.22, 95% CI: 0.07 to 0.37, P FDR = 0.024) at 6 years postpartum, and the association between GDM and SCR (β = 2.43, 95% CI: 0.02 to 4.85, P FDR = 0.144) reached nominal significance level. GDM history was associated with a decreased level of third-trimester IL-17 A (β = -0.58, 95% CI: -0.99 to -0.18, P FDR = 0.035). No significant association between third-trimester inflammatory factors and 6-year postpartum metabolic indicators was observed. And no mediating or moderating effect of third-trimester inflammatory factors was observed in those associations. Conclusion A prior history of GDM was significantly associated with elevated FPG, HbA1c, and TyG in women at 6 years postpartum, whereas third-trimester inflammatory factors had no role in mediating or moderating these associations.

This study presents a comprehensive numerical investigation on the generation of a microwave frequency comb (MFC) using a semiconductor laser subjected to periodic-modulated optical injection. To enhance performance, optoelectronic feedback is incorporated through a dual-drive Mach–Zehnder modulator. The results show that the first optoelectronic feedback loop, with a delay time inversely proportional to the modulation frequency, can optimize MFC generation through a mode-locking effect and the second optoelectronic feedback loop with a multiple delay time of the first one can further enhance the performance of the MFC. The comb linewidth appears to decrease with the increase in the second-loop delay time in the power function. These results are consistent with experimental observations reported in the literature. We also explore the impact of the feedback index on comb contrast, the statistical characteristics of the central 128 lines within the MFC, and side peak suppression. The simulation results demonstrate the presence of an optimal feedback index. The study also reveals that linewidth reduction, through increasing the feedback index and delay time, comes at the cost of declining side peak suppression. These findings collectively contribute to a deeper understanding of the factors influencing MFC generation and pave the way for the design and optimization of high-performance MFC systems for various applications.

Introduction Perinatal anxiety (PNA) is a major public health concern.Methods A hybrid effectiveness-implementation trial was conducted in two antenatal clinics in Hefei, China, to assess the effectiveness and cost-effectiveness of application-based tiered care (Mom’s Good Mood, MGM) in treating PNA and to understand how well it fits into routine practices. Pregnant women who scored at least 5 points on the 7-Item Generalised Anxiety Disorder Scale (GAD-7) scale were successively assigned to the control group or the intervention group, which were given the usual care and MGM on usual care, respectively. At 6 months post partum, anxiety, depression and life satisfaction were assessed. Intention-to-treat analysis and the Reach, Effectiveness, Adoption, Implementation and Maintenance framework were adopted.Results A total of 214 women were assigned to the control group and 341 to the intervention group. The mean changes in GAD-7 scores (Least-squares means, LSM, −1.42, 95% CI −2.18 to −0.66) and the risk of anxiety (adjusted odds ratio, aOR 0.30, 95% CI 0.18 to 0.51) were decreased, and the anxiety remission rate (aOR 2.72, 95% CI 1.69 to 4.40) were improved in the intervention group. Similar findings were observed regarding the change in Edinburgh Postnatal Depression Scale scores (LS −1.92, 95% CI −2.85 to −0.99), depression remission rate (aOR 2.24, 95% CI 1.39 to 3.63) and the risk of depression (aOR 0.57, 95% CI 0.33 to 0.98). MGM only costs ¥1.88 (US$0.27) per pregnant woman to boost the postpartum anxiety remission rate by 1% and was revealed to have a high reach rate of 78.3%, an adoption rate of 51.3%–80.8%.Conclusion MGM is a cost-effective and accessible tool in coping with PNA.Trial registration number ChiCTR2100053419.

In this paper, 20Mn2SiCrMo bainitic crossing noses were repaired by depositing 420SS, Stellite 6, 17-4PH and 18Ni300 alloys on the rail surfaces to form functionally graded materials (FGM) using laser directed energy deposition (L-DED) technology. As a result, only 18Ni300 deposit achieves an excellent strength-toughness combination, which possesses a yield strength of ∼1120 MPa together with an impact energy of ∼85.05 J, better than those of substrates (∼1071 MPa, ∼71.34 J). Besides, the wear and rolling contact fatigue (RCF) resistance of 20Mn2SiCrMo/18Ni300 FGM is enhanced to 2.7 and 23.6 times as much as those of substrates. Massive ultrafine nanoprecipitates and a small amount of austenite make 18Ni300 deposit strong enough as well as a certain work-hardenability, ensuring good wear resistance therein; the significant RCF resistance originates from the improved shakedown limit. Therefore, all findings reveal that 18Ni300 is the most promising depositing material for repairing bainitic crossing noses by L-DED.

Introduction: Aging is an important process to improve the quality of cigar, but the effect of aging with media on cigar has not been reported.Therefore, this study aimed to prepare different aging media and clarify the influence of media on cigar quality.Methods: Effective media were first screened by sensory evaluation, then the effects of aging media on the chemical composition and microbial community of cigar were investigated.Results: The results showed that: 1) As aging media, coffee formula and cocoa formula could optimize the smoke and aroma characteristics of cigar, and 30 days was the appropriate period for cigar aging. 2) Aging with coffee or cocoa media could increase the content of amino acids, non-volatile organic acids, malic acid and aroma components. Particularly, the content of aroma components increased from 2.48 mg g−1 (W-30) to 3.21 mg g−1 (C-30) and 3.70 mg g−1 (K-30), respectively. 3) Aging with coffee can improve the diversity of bacteria and fungi on the cigar surface and change the succession rule of bacterial community. In contrast, aging with cocoa had no significant effect on microbial diversity of cigar.Discussion: In this study, the influence of aging media on cigar quality was analyzed multidimensionally for the first time, which provided a reference for the development of new aging media and technologies to improve cigar quality.

Abstract A high-sensitivity temperature sensor based on the harmonic Vernier effect is proposed and verified by experiments. The main component of the sensor is a Sagnac interferometer consisting of two sections of polarization maintaining fibers (PMFs) spliced with an intersection angle of 45° between their fast axes. The harmonic Vernier effect is achieved by setting the length of one of the PMFs an integral multiple (i-times) of the length of the other plus a detuning factor. Compared with the Sagnac interferometer based on the fundamental Vernier effect, the temperature sensitivity of the harmonic Vernier effect is higher, reaching i+1 times of that of the fundamental Vernier effect (i is the order of the harmonic).

Abstract Background Stressful life events (SLEs) and adverse childhood experiences (ACEs) have been reported to be associated with perinatal depression (PND) or perinatal anxiety (PNA) alone; however, in most cases, majority of PND and PNA coexist and could lead to more serious health consequences. The independent effect of recent SLEs and their joint effects with ACEs on perinatal comorbid anxiety and depression (CAD) remain inadequately explored. Methods Based on a longitudinal study, 1082 participants receiving prenatal care in Ma’anshan, China were included. Women were recruited in the first trimester (T1: ≤14+ 6 weeks) and followed up at 15 ~ 27 weeks (T2), 28 ~ 40 weeks (T3), and postpartum (T4). Depression and anxiety status were assessed at all time points, while recent SLEs and ACEs were measured at T1. Logistic regression was conducted to examine the associations of SLEs with the risks of CAD at different time points, as well as their joint effects with ACEs on CAD. Results Approximately 38.5% of women experienced at least one SLE, which was significantly associated with higher risks of CAD at all time points (p

Remote sensing technology applications for water quality inversion in large rivers are common. However, their application to medium/small-sized water bodies within rural areas is limited due to the low spatial resolution of remote sensing images. In this work, a typical small rural river was selected, and high-resolution unmanned aerial vehicle (UAV) multispectral images and ground monitoring data of the river were obtained. Then, a comparative analysis of three univariate regression models and nine machine learning models (Ridge Regression (RR), Support Vector Regression (SVR), Grid Search Support Vector Regression (GS-SVR), Random Forest (RF), Grid Search Random Forest (GS-RF), eXtreme Gradient Boosting (XGBoost), Deep Neural Networks (DNN), Convolutional Neural Networks (CNN), and Catboost Regression (CBR)) for their accuracy in the prediction of turbidity (TUB), total nitrogen (TN), and total phosphorus (TP) was performed. TUB can be achieved by simple statistical regression models. The CBR model exhibited the best performance for the three index inversions on the test set evaluation metrics: R2 (0.90~0.92), RMSE (7.57 × 10−3~1.59 mg/L), MAE (0.01~1.30 mg/L), RPD (3.21~3.56), and NSE (0.84~0.92). The water pollution of the study area was closely related to its land-use pattern, excessive and irrational fertilizer application, and distribution of pollutant outlets.

Abstract Lipoprotein lipase (LPL) hydrolyzes the triglyceride core of lipoproteins and also functions as a bridge, allowing for lipoprotein and cholesterol uptake. Transgenic mice expressing LPL in adipose tissue under the control of the adiponectin promoter (AdipoQ-LPL) have improved glucose metabolism when challenged with a high fat diet. Here, we studied the transcriptional response of the adipose tissue of these mice to acute high fat diet exposure. Gene set enrichment analysis (GSEA) provided mechanistic insight into the improved metabolic phenotype of AdipoQ-LPL mice. First, the cholesterol homeostasis pathway, which is controlled by the SREBP2 transcription factor, is repressed in gonadal adipose tissue AdipoQ-LPL mice. Furthermore, we identified SND1 as a link between SREBP2 and CCL19, an inflammatory chemokine that is reduced in AdipoQ-LPL mice. Second, GSEA identified a signature for pancreatic β-cells in adipose tissue of AdipoQ-LPL mice, an unexpected finding. We explored whether β-cell function is improved in AdipoQ-LPL mice and found that the first phase of insulin secretion is increased in mice challenged with high fat diet. In summary, we identify two different mechanisms for the improved metabolic phenotype of AdipoQ-LPL mice. One involves improved adipose tissue function and the other involves adipose tissue—pancreatic β-cell crosstalk.

In recent years, the increasing incidence of perinatal depression has become an important public health problem. In addition to the traditional social demographic factors, biological factors, obstetric factors, etc., the association between air pollution and perinatal depression (PND) has also attracted more and more attention. In this paper, studies on the association between air pollution and PND were reviewed, especially the associations of PND with ambient air pollutants such as PM2.5, PM10, NO2, and O3 as well as indoor air pollutants such as tobacco smoke, and the characteristics and possible biological mechanisms of the influence of different pollutants on PND were summarized. Based on the available studies, various outdoor air pollutants are associated with PND, and some pollutants may exhibit a dose-response relationship with it. As for indoor air pollution, studies only have focused on the impact of tobacco exposure on PND, and as yet, no study has explored the association between other indoor pollutants (e.g. cooking oil smoke and solid fuel) and PND. Current studies indicate that air pollution may act on PND through oxidative stress and neuroendocrine mechanisms, but the exact biological mechanism remains to be further studied. In the future, further studies should be encouraged on the epidemiological associations of other indoor air pollutants with PND and the interactions between other factors and air pollution on PND, and the underlying biological mechanisms, to provide new insights for the prevention of PND from the perspective of environmental health.

BackgroundObesity is a common and highly convincing risk factor for many cancers, including liver cancer. Sex disparities in the body composition and regulatory mechanisms involved in energy homeostasis may contribute to the difference in the incidence of cancer. However, evidence on the gender-specific association between body composition and liver cancer incidence is limited. We performed this study to investigate the linear and non-linear associations of body composition with liver cancer risk by gender.Materials and methodsThis prospective analysis included 4,75,659 participants free of cancer, based on the UK Biobank. We used Cox proportional hazard models to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) after adjusting for potential confounders. Restricted cubic spline was performed to investigate the potential non-linear associations.ResultsDuring a median follow-up, 275 cases (174 male patients and 101 female patients) of liver cancer were identified. Male patients in the highest body fat percentage group are more likely to develop liver cancer (HR = 1.89, 95% CI: 1.17–3.03) compared with those in the lowest group. The one-unit increase of whole-body fat mass, arm fat mass, and trunk fat mass was associated with 1.03-, 1.14-, and 1.05-fold increased risk of liver cancer in male subjects, respectively. U-shaped associations of body composition with liver cancer risk were observed in the female subjects. Both high and low levels of whole-body fat-free mass, particularly in the arm and trunk, were associated with an increased risk of liver cancer.ConclusionThis study found a gender-specific association between body composition and liver cancer risk and provided evidence for individualized weight management for the prevention of liver cancer.

Introduction The management of perinatal depression (PND) is challenging in China. The Thinking Healthy Programme (THP), developed under the core theory of cognitive–behavioural therapy, is an evidence-based approach that is recommended as a psychosocial intervention for managing PND in low/middle-income countries. Sparse evidence has been generated, however, to assess the effectiveness of THP and guide its implementation in China.Methods and analysis A hybrid type II effectiveness–implementation study is ongoing in four cities in Anhui Province, China. A comprehensive online platform, Mom’s Good Mood (MGM), has been developed. Perinatal women are screened using the WeChat screening tool (ie, Edinburgh Postnatal Depression Scale embedded as metrics) in clinics. Different intensities of the intervention are delivered through the mobile application for different degrees of depression, according to the stratified care model. The THP WHO treatment manual has been tailored to be the core component of intervention. Guided by the Reach, Effectiveness, Adoption, Implementation and Maintenance framework, process evaluations will be conducted to identify the facilitators and barriers to implementation and to modify the implementation strategy; summative evaluations will be carried out to examine the effectiveness of MGM in the management of PND within the primary healthcare system in China.Ethics and dissemination Ethics approval and consent for this programme were obtained from Institutional Review Boards in China: Anhui Medical University, Hefei, People’s Republic of China (20170358). Results will be submitted to relevant conferences and peer-reviewed journals.Trial registration number ChiCTR1800016844.

We propose higher-order adaptive energy-preserving methods for a charged particle system and a guiding center system. The higher-order energy-preserving methods are symmetric and are constructed by composing the second-order energy-preserving methods based on the averaged vector field. In order to overcome the energy drift problem that occurs in the energy-preserving methods based on the average vector field, we develop two adaptive algorithms for the higher-order energy-preserving methods. The two adaptive algorithms are developed based on using variable points of Gauss–Legendre’s quadrature rule and using two different stepsizes. The numerical results show that the two adaptive algorithms behave better in phase portrait and energy conservation than the Runge–Kutta methods. Moreover, it is shown that the energy errors obtained by the two adaptive algorithms can be bounded by the machine precision over long time and do not show energy drift.

Because the associations between different dietary protein sources and the risks of gestational diabetes mellitus (GDM) are inconsistent, and those of eating habits with GDM have rarely been explored, we aimed to investigate the independent and joint association of major dietary protein sources and eating habits with GDM in a case-control study including 353 GDM cases and 718 controls in China. Dietary protein intake and eating habits prior to GDM diagnosis were collected through questionnaires at 24~28 gestational weeks. Multivariate logistic regression was used to evaluate the independent and joint associations of dietary protein intake and eating habits with GDM. The Anderson model was used assess if there is an additive interaction between them. Animal protein, red meat protein and dairy products protein intake were significantly and positively associated with GDM. Among the eating habits, preferences for hot food, firm food and soft food were significantly associated with higher odds of GDM. Individuals with unhealthy eating habits and high dietary protein simultaneously had the highest odds of GDM, and the ORs were 2.06 (1.25, 3.41) for the total protein, 2.97 (1.78, 4.96) for animal meat, 3.98 (2.41, 6.57) for the red meat protein and 2.82 (1.81, 4.41) for the dairy protein; the p values for the trend were all significant (p < 0.001). However, no additive interaction was detected. In conclusion, our study found that dietary protein intake and eating habits prior to GDM diagnosis were both independently and jointly associated with the odds of GDM.

Abstract Background The association between gestational diabetes mellitus (GDM) and perinatal depression (PND) remains controversial. Our study aimed to comprehensively assess this association in a longitudinal cohort study with repeated measurements of depression. Methods Our cohort study was nested in a pilot study of an implementation study aiming to screen and manage perinatal depression within the primary health system in China. Women were recruited in the first trimester from May–September 2019 and followed four times up to 1 year postpartum. Data on sociodemographic characteristics and depression were collected using self-developed questionnaires incorporating the Edinburgh Postnatal Depression Scale (EPDS). Oral glucose tolerance test at 24 ~ 28 weeks and fasting plasma glucose (FPG) data were extracted from medical records. Depression throughout the whole period was divided into different trajectories. Associations of GDM with PND at different time periods and PND of different trajectories were determined by logistic regression. The path of association between blood glucose and depression over time was estimated with an autoregressive cross-lagged model. Results In total, 1043 women were included in this analysis and 313 (30.0%) were diagnosed with GDM. The prevalence of depression in the first, second, and third trimesters and postpartum period were 17.2, 6.9, 6.8 and 9.0%, respectively. GDM was neither significantly associated with PND at any time point nor with any specific trajectory of depression. Except for autoregressive paths, no cross-lagged path of FPG and scores of EPDS was significant. Conclusions Our study indicates no association between GDM/blood glucose and PND.

BackgroundReversible splenial lesion syndrome (RESLES) is a spectrum of disease radiologically characterized by reversible lesions caused by multiple factors, primarily involving the splenium of the corpus callosum (SCC). The most common causes of RESLES include infection, antiepileptic drug use and withdrawal, and severe metabolic disorders. Nevertheless, cases of autoimmune encephalitis (AE) are uncommon.Case presentationA 26-year-old female computer programming engineer with no previous medical or psychiatric history reported to the psychiatric hospital due to a 3-day episode of irritability, babbling, limb stiffness, sleepwalking, hallucinations, and paroxysmal mania. Brain MRI revealed abnormal signals of the SCC. Lumbar puncture was performed and further testing for auto-antibodies was conducted in both the CSF and serum. CSF of the patient was positive for anti-NMDAR (titer of 1:3.2) antibodies, and serum was also positive for anti-NMDAR (titer of 1:32) as well as mGluR5 (titer of 1:10) antibodies. Enhanced CT of the pelvis showed an enlarged pelvic mass; bilateral ovarian teratomas (mature teratoma and immature teratoma) were evaluated, which were pathologically confirmed after transabdominal left adnexal resection, right ovarian biopsy, and ovarian cystectomy. The patient considerably improved after intravenous administration of steroids, immunoglobulin, oral prednisone, surgical treatment, and chemotherapy. A follow-up MRI revealed completely resolved lesions. During a 3-month follow-up, the patient experienced complete resolution of symptoms without any sign of recurrence and tumors. The titer of the anti-NMDAR antibody decreased to 1:10 in serum.ConclusionHerein, we report a rare case of AE with overlapping auto-antibodies, along with RESLES and bilateral ovarian teratomas. The current case provides the possibility of the concurrence of mGluR5 antibodies in anti-NMDAR encephalitis. However, the underlying mechanism remains elusive. Furthermore, we provide additional evidence that overlapping antibodies-related pathology may be one of the many causes of RESLES. Nonetheless, caution should be observed in interpreting the observation, considering that this is a single-case study.

This work was designed to investigate the dynamic changes process of non-volatile organic compounds (n-VOCs) and volatile organic compounds (VOCs) in mulberries during different growth periods using UPLC-Q-Orbitrap-MS, HS-SPME-GC-MS, and HS-GC-IMS. A total of 166 compounds were identified, including 68 n-VOCs and 98 VOCs. Furthermore, principal component analysis (PCA), random forest analysis (RFA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to analyze differences in mulberries at different ripening stages. A total of 74 compounds appeared or disappeared at different ripening periods and 24 compounds were presented throughout the growth process. Quantitative analysis and antioxidant experiments revealed that as the mulberries continued to mature, flavonoids and phenolic acids continued to increase, and the best antioxidant activity occurred from stage IV. Conclusively, an effective strategy was established for analyzing the composition change process during different growth periods, which could assist in achieving dynamic change process analysis and quality control.

Abstract Acute cold induces beige adipocyte protein marker expression in human subcutaneous white adipose tissue (SC WAT) from both the cold treated and contralateral leg, and the immune system regulates SC WAT beiging in mice. Cold treatment significantly increased the gene expression of the macrophage markers CD68 and 86 in SC WAT. Therefore, we comprehensively investigated the involvement of macrophages in SC WAT beiging in lean and obese humans by immunohistochemistry. Cold treatment significantly increased CD163/CD68 macrophages in SC WAT from the cold treated and contralateral legs of lean and obese subjects, and had similar effects on CD206/CD68 macrophages, whereas the effects on CD86/CD68 macrophages were inconsistent between lean and obese. However, linear regression analysis did not find significant relationships between the change in macrophage numbers and the change in UCP1 protein abundance. A high percentage of CD163 macrophages in SC WAT expressed UCP1, and these UCP1 expressing CD163 macrophages were significantly increased by cold treatment in SC WAT of lean subjects. In conclusion, our results suggest that CD163 macrophages are involved in some aspect of the tissue remodeling that occurs during SC WAT beiging in humans after cold treatment, but they are likely not direct mediators of the beiging process.

In the present work, the laser-induction hybrid cladding technology with induction post-heating (post-LIHC) was utilized to deposit coatings on the full-scale rail surface, and the effects of different induction post-heating temperature on the morphology, microstructure and mechanical performance of the heat affected zone (HAZ) were first in-depth analyzed. Results indicate that with the increase of the average induction post-heating temperature (Ta) in post-LIHC, the microstructure of the HAZ first transforms from the fine acicular martensite structure to the composite structure of martensite and pearlite, then changes to the pure pearlite structure, and finally retransforms to the coarse martensite structure. Especially, the morphology of the “Martensite Zone” (MZ) in HAZ undergoes three remarkable change with Ta increasing: “flat-U-shaped” → “flat-W-shaped” → “vanished” → “flat-V-shaped”. Under the induction post-heating window of Ta = 508 °C ~ 565 °C, not only the MZ in HAZ can be inhibited absolutely, but also fine pearlite with much lower interlamellar spacing, smaller grain size and higher grain misorientation forms instead, making the strength and toughness are both enhanced significantly than the other three type HAZs and the rail substrate. In addition, increasing the induction post-heating temperature within the window of Ta = 508 °C ~ 565 °C can increase the interlamellar spacing and reduce the ferrite grain misorientation of the pearlite structure in HAZ, but has no obvious effect on the grain size therein.

This study focused on the non-covalent interaction between soybean protein isolate (SPI) and β-carotene (BC). The conformational changes of SPI with β-carotene in varying proportions (BC/SPI: 2%, 4%, 6%, 8%, and 10%) were investigated by multi-spectroscopy and molecular docking. Results showed that the quenching mode is static quenching and binding affinity increased with temperature. The stoichiometry was 1:1, indicating there was only one binding site in SPI. The binding was based on entropy and primarily driven by hydrophobic interactions and its binding constant was in the order of 104 L⋅mol–1. The addition of the β-carotene affected the secondary structure of SPI resulting in an increase in α-Helix and a decrease in random coil and β-turn content, indicating protein aggregated and hydrophobic interactions occurred. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) verified that no new larger molecular weight substance was formed and no covalent interaction existed. Molecular docking corroborated that electrostatic and hydrophobic interactions were both involved in the formation of complexes, where hydrophobic interaction was the dominant one. Moreover, β-carotene improved 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, foaming capacity, and emulsifying stability of SPI. These findings provide useful information about the interaction mechanism of SPI and β-carotene, which contributes to the further development and application of SPI products rich in β-carotene in the food industry.

The conformational changes and functional properties of SPI induced by quercetin was investigated via fourier transform infrared (FTIR) spectroscopy, fluorescence spectroscopy, circular dichroism (CD) spectroscopy and molecular docking. A decrease in the fluorescence intensity and a blue shift in the maximum wavelength were observed due to the binding process with fluorescent residues. The analysis of Stern-Volmer equation showed that the fluorescence quenching induced by quercetin took the form of static quenching, and the binding stoichiometry between SPI and quercetin was 1:1. The values of ΔH and ΔS were both positive illustrating that hydrophobic interaction was the primary binding force between quercetin and SPI. Results of FTIR and CD indicated that the binding with quercetin changed the secondary structure of SPI, resulting in a partially unfolded and more flexible structure. SDS-PAGE confirmed there was no covalent interaction between the two constituents. Molecular docking demonstrated that there were stable configurations and high matching degrees in both 11S and 7S proteins with quercetin via hydrogen bonds and hydrophobic interactions. Meanwhile, modification by quercetin enhanced the foaming and emulsifying capacities of SPI. These findings might provide theory reference for elucidation the mechanism of polyphenols-proteins interaction and development of related food additive products in future.

Objectives: Compared with other thyroid markers, fewer studies have explored the associations between triiodothyronine (T3), T3/free thyroxine (fT4) and glucose abnormality during pregnancy. Thus, we aimed to: (i) examine the associations of T3 and T3/fT4 with glucose metabolism indicators and (ii) evaluate, in the first trimester, the performance of the two markers as predictors of gestational diabetes mellitus (GDM) risk. Methods: Longitudinal data from 2723 individuals, consisting of three repeated measurements of T3 and fT4, from the Man’anshan birth cohort study (MABC), China, were analyzed using a time-specific generalized estimating equat ion (GEE). The receiver operating characteristic curve (ROC) – area under the curve (AUC) and Hosmer– Lemeshow goodness of fit test was used to assess the discriminat ion and calibration of prediction models. Results: T3 and T3/fT4 presented stable associations with the level of fasting glucose, glucose at 1h/2 h during pregnancy. T3 and T3/fT4 in both the fi rst and second trimesters were positively associated with the risk of GDM, with the larger magnitude of association observed in the second trimester (odds ratio (OR) = 2.50, 95% CI = 1.95, 3.21 for T3; OR = 1.09, 95% CI = 1.07, 1.12 for T3/fT4). T3 ((AUC) = 0.726, 95% CI = 0.698, 0.754) and T3/fT4 (AUC = 0.724, 95% CI = 0.696, 0.753) in the first trimester could improve the performance of the prediction model; however, the overall performance is not good. Conclusion: Significant and stable associations of T3, T3/fT4 and glucose me tabolism indicators were documented. Both T3 and T3/fT4 improve the performance of the GDM predictive model.

Myocardial infarction (MI) is a type of coronary heart disease, which refers to the ischemic necrosis of the heart muscle. A large number of studies have discussed the mechanism of MI from the perspective of competing endogenous RNA (ceRNA) network. However, the mechanisms underlying the function of lncRNAs in MI have still not been explained in an explicit manner. Therefore, we constructed a scale-free lncRNA-associated ceRNA network to identify some crucial lncRNAs in MI. Results showed that the given disease genes for MI were involved in the network, the degrees of which were significantly larger than the other nodes of the network. For measuring the network centrality, we then constructed a hub subnetwork. The miRNAs and mRNAs in the hub subnetwork have been validated to function in MI-related biological function. In addition, we identified 2 MI-related functional modules from the lncRNA-associated ceRNA network, which suggested that lncRNA exerted function in local network. Enrichment analysis showed that these functional modules corresponded to some similar and different pathways related to cardiovascular disease. More importantly, 3 MI-related crucial lncRNAs, CTD-3092A11.2, RP5-821D11.7 and CTC-523E23.1 were detected as potential biomarkers, which may be involved in MI-related biological progresses. Our study identified 20 functional lncRNAs based on ceRNA network analysis, which may provide novel diagnosis and therapeutic targets for MI from the ceRNA network perspective.

Background: In the past 5 years, China has quickly followed US’s steps to approve the new drug application of biologics for dermatological diseases. There is an increasing interest in the current biologic landscape and further potentials in China. Our study aims to analyze features of clinical trials on non-cancer dermatological biologics and synthesize recent achievements and impediments, in order to forecast the development trends in China.Methods: Three registers (the Chinese Clinical Trial Registry, Center for Drug Evaluation, and ClinicalTrials.gov) were searched for clinical trials of non-cancer dermatological biologics initiated between 2016 and 2020 in mainland China. Trial information (the first posted year, sponsor type, study phase and site, recruitment status, disease, drug target, and drug registration type) and certain study design (selection of the control group, primary efficacy outcome, and inclusion of patient-reported outcome for non–phase I or II trials only) information were extracted and analyzed.Results: A total of 60 trials were identified. The number of registered dermatological biologic trials significantly increased with an annual increase of 59% from 2016 to 2020, primarily driven by psoriasis (47/60, 78.3%) and atopic dermatitis (6/60, 10.0%) trials. The tumor necrosis factor (TNF)-α and interleukin (IL)-17 remained the hottest drug targets (17/60, 28.3% for TNF-α and 18/60, 30.0% for IL-17). In addition to TNF-α and IL-17, many new psoriasis drug targets came into place since 2018 (IL-12/23) and 2019 (IL-36 and glucagon-like peptide-1 (GLP-1)). Thirty percent (18/60) of the trials were conducted for biosimilar products, all of which were sponsored by local pharmaceutical companies and 88.9% of which were targeting on TNF-α. Targets of IL-36, IL-5, and IgE were only available in trials sponsored by global companies.Conclusion: There was great progress on the innovation of dermatological biologics in the past 5 years in China in terms of surged number of clinical trials, increased biosimilars and “me-too” drugs which greatly improved patient access to novel treatments, execution of parallel clinical trials, and improved hospital GCP office and regulatory environment. Further efforts for local pharmaceutical companies should include relocating resources to exploring novel drug targets and dermatological diseases other than psoriasis or atopic dermatitis.Systematic Review Registration: [website], identifier [registration number].

Abstract Emerging Xenes, mostly group IVA and VA elemental two‐dimensional (2D) materials, have small and tunable band gaps between graphene and transition metal dichalcogenides, giving versatile electrical properties. While their microelectronic or optoelectronic properties are being extensively explored, there remains a lack of study on Xenes' uniquely advantageous thermoelectric performance. This review highlights state‐of‐the‐art experimental and theoretical progress in the thermoelectric effect and devices of IVA and VA Xenes. Vertically displaced, a.k.a. “buckled” or “puckered,” atomic arrays result in exotic and tunable electrical or thermal transport behaviors. Different from chemical doping strategies usually employed in bulk thermoelectric materials, 2D Xenes can be tuned by physical means, such as atomic layer control and quantum confinement effects. A precise and compatible platform for 2D thermoelectric effect and devices study is available via the engagement between micro/nanofabrication of 2D Xene transistors and thermal property measurement techniques. This review also reveals potential thermoelectric applications of Xenes and their compounds (Bi2Te3, Bi2Se3, etc.), such as accurate stretchable temperature sensors, fast terahertz photodetectors, and so on.

Abstract Background Mental health in China is a significant issue, and perinatal depression has been recognized as a concern, as it may affect pregnancy outcomes. There are growing calls to address China’s mental health system capacity issues, especially among vulnerable groups such as pregnant women due to gaps in healthcare services and inadequate access to resources and support. In response to these demands, a perinatal depression screening and management (PDSM) program was proposed. This exploratory case study identified strategies for successful implementation of the proposed PDSM intervention, informed by the Consolidated Framework for Implementation Research (CFIR) framework, in Ma’anshan city, Anhui province. Methods This qualitative study included four focus group discussions and two in-depth individual interviews with participants using a semi-structured interview guide. Topics examined included acceptance, utility, and readiness for a PDSM program. Participants included perinatal women and their families, policymakers, and healthcare providers. Interviews were transcribed verbatim, coded, and analyzed for emergent themes. Results The analysis revealed several promising factors for the implementation of the PDSM program including: utilization of an internet-based platform, generation of perceived value among health leadership and decision-makers, and the simplification of the screening and intervention components. Acceptance of the pre-implementation plan was dependent on issues such as the timing and frequency of screening, ensuring high standards of quality of care, and consideration of cultural values in the intervention design. Potential challenges included perceived barriers to the implementation plan among stakeholders, a lack of trained human health resources, and poor integration between maternal and mental health services. In addition, participants expressed concern that perinatal women might not value the PDSM program due to stigma and limited understanding of maternal mental health issues. Conclusion Our analysis suggests several factors to support the successful implementation of a perinatal depression screening program, guidelines for successful uptake, and the potential use of internet-based cognitive behavioral therapy. PDSM is a complex process; however, it can be successfully navigated with evidence-informed approaches to the issues presented to ensure that the PDSM is feasible, effective, successful, and sustainable, and that it also improves maternal health and wellbeing, and that of their families.

Prostate apoptosis response-4 (Par-4) is a tumor suppressor that induces apoptosis in cancer cells. However, the physiological function of Par-4 remains unknown. Here we show that conventional Par-4 knockout (Par-4-/-) mice and adipocyte-specific Par-4 knockout (AKO) mice, but not hepatocyte-specific Par-4 knockout mice, are obese with standard chow diet. Par-4-/- and AKO mice exhibit increased absorption and storage of fat in adipocytes. Mechanistically, Par-4 loss is associated with mdm2 downregulation and activation of p53. We identified complement factor c3 as a p53-regulated gene linked to fat storage in adipocytes. Par-4 re-expression in adipocytes or c3 deletion reversed the obese mouse phenotype. Moreover, obese human subjects showed lower expression of Par-4 relative to lean subjects, and in longitudinal studies, low baseline Par-4 levels denoted an increased risk of developing obesity later in life. These findings indicate that Par-4 suppresses p53 and its target c3 to regulate obesity.

Linearly chirped microwave waveforms with high time-bandwidth products would have important applications but are difficult to achieve. Here the authors generate such a waveform in a photonic setting by implementing a micro-disk resonator as a tunable optical bandpass filter in a Fourier-domain mode-locked laser.

BACKGROUND Beige and brown adipose tissue (BAT) are associated with improved metabolic homeostasis. We recently reported that the β3-adrenergic receptor agonist mirabegron induced beige adipose tissue in obese insulin-resistant subjects, and this was accompanied by improved glucose metabolism. Here we evaluated pioglitazone treatment with a combination pioglitazone and mirabegron treatment and compared these with previously published data evaluating mirabegron treatment alone. Both drugs were used at FDA-approved dosages.METHODS We measured BAT by PET CT scans, measured beige adipose tissue by immunohistochemistry, and comprehensively characterized glucose and lipid homeostasis and insulin sensitivity by euglycemic clamp and oral glucose tolerance tests. Subcutaneous white adipose tissue, muscle fiber type composition and capillary density, lipotoxicity, and systemic inflammation were evaluated by immunohistochemistry, gene expression profiling, mass spectroscopy, and ELISAs.RESULTS Treatment with pioglitazone or the combination of pioglitazone and mirabegron increased beige adipose tissue protein marker expression and improved insulin sensitivity and glucose homeostasis, but neither treatment induced BAT in these obese subjects. When the magnitude of the responses to the treatments was evaluated, mirabegron was found to be the most effective at inducing beige adipose tissue. Although monotherapy with either mirabegron or pioglitazone induced adipose beiging, combination treatment resulted in less beiging than either alone. The 3 treatments also had different effects on muscle fiber type switching and capillary density.CONCLUSION The addition of pioglitazone to mirabegron treatment does not enhance beiging or increase BAT in obese insulin-resistant research participants.TRIAL REGISTRATION ClinicalTrials.gov NCT02919176.FUNDING NIH DK112282 and P20GM103527 and Clinical and Translational Science Awards grant UL1TR001998.

Pancreatic ductal adenocarcinoma is a lethal human cancer with a poor 5-year overall survival rate. Here the authors perform an exome-wide analysis in a cohort of PDAC patients to identify three novel missense variants in PKN1, DOK2, and APOB genes, that are associated with PDAC risk.

Objective. To investigate the potential therapeutic effect in a rheumatoid arthritis model of stable human CD8+ regulatory T cells (hCD8+Tregs) induced by TGF-β1 and rapamycin (RAPA) in vitro. Methods. Human CD8+T cells were isolated from human peripheral blood mononuclear cells and induced/expanded with TGF-β1 and RAPA along with anti-CD3/28 beads and IL-2 in vitro and harvested as hCD8+Tregs. The phenotypes, suppressive characteristics, and stability of the hCD8+Tregs in an inflammatory microenvironment were examined in vitro. Human CD8+Tregs were transfused into an acollagen-induced arthritis (CIA) mouse model, and their therapeutic effects and related mechanisms were investigated. Results. Human CD8+Tregs induced by TGF-β1/RAPA showed high expression of Foxp3 and CD103, exhibited vigorous suppression ability, and were stable in inflammatory microenvironments. In CIA mice, the clinical scores, levels of anti-collagen IgG antibody, and cartilage destruction were significantly reduced after adoptive transfusion with hCD8+Tregs. Moreover, hCD8+Treg treatment significantly reduced the number of Th17 cells, increased the number of CD4+IFN-γ+T cells, and produced self CD4+Foxp3+Tregs in vivo. In an in vitro cell coculture assay, hCD8+Tregs significantly inhibited mouse CD4+ effector T cell proliferation, induced mouse CD4+Foxp3+Treg and CD4+IFN-γ+Th1 cell production, reduced Th17 cell development, and downregulated CD80/86 expression on mature DCs (mDCs). Conclusion. TGF-β1/RAPA can induce hCD8+Tregs with stable suppressive characteristics, which could significantly alleviate the severity of CIA based on their stable suppressive ability in an inflammatory microenvironment and further influence the function of other downstream cell subtypes. Human CD8+Tregs might be a therapeutic strategy for rheumatoid arthritis.

Aim. This study investigated the associations among early pregnancy vitamin D concentrations, seasonality, and vitamin D metabolic gene variants and how these variables related alone and in interaction with the risk of gestational diabetes mellitus (GDM). Methods. Research participants were women from the Ma’anshan birth cohort study in China. The overall study included 3110 women to explore the association between early pregnancy vitamin D concentrations and the risk of GDM. In the current analysis, a nested case-control study of 274 GDM cases and 380 controls was conducted to investigate seven vitamin D metabolic gene variants and the risk of GDM. Vitamin D concentrations were measured by radioimmunoassay. Genotypes were determined by improved multiple ligase detection reaction. Interactions between genetic variants and vitamin D as predictors of the risk of GDM were evaluated by a pair-wise analysis under a multiplicative interaction model. Results. Vitamin D concentrations were not significantly associated with the risk of GDM (OR=0.79, 95% CI=0.55-1.13) after adjusting for seasonality. Fall-winter conceptions had a 37% decreased risk of GDM compared with spring-summer conceptions (OR=0.63, 95% CI=0.49-0.81), independent of vitamin D concentrations. Two VDR gene variants rs1544410 (OR=2.03, 95% CI=1.17-3.51 for CT versus CC) and rs731236 (OR=2.42, 95% CI=1.29-4.55 for GA versus AA) were significantly associated with the risk of GDM. No interactions among genetic variants and vitamin D concentrations were detected. Conclusion. Early pregnancy vitamin D insufficiency or deficiency was not significantly associated with the risk of GDM. The results of this study emphasize the importance of genetic variants in VDR and conception season as factors that affect the risk of GDM.

IntroductionMethadone maintenance treatment (MMT) programs have been rapidly scaled up nationwide in China in recent years, and psychosocial intervention measures, including counseling, were recommended for improving the outcomes of MMT. However, the effectiveness of counseling in MMT programs remains controversial. This study investigated the efficacy of educational and behavioral counseling (EBC) mode in an MMT program in China.MethodsA total of 125 eligible participants were randomized to EBC or a control group. Patients in the EBC group received weekly, manual-guided, group educational counseling for 8 weeks and individual behavioral counseling for the next 8 weeks. Patients in the control group received standard methadone maintenance treatment as usual (TAU).ResultsDuring the 16-week trial, the EBC group showed better treatment attendance (P = 0.022) and a greater increase in knowledge regarding heroin addiction (P = 0.001) and MMT (P = 0.005) than did the TAU group. Between the two groups, there were no significant differences regarding drug abstinence and reduction of risky behaviors.ConclusionEBC affiliated with MMT improved patients’ cognition and adherence to treatment, facilitating their successful recovery.Clinical Trial RegistrationChiCTR-IOR-15006673: http://www.chictr.org.cn.

ObjectiveIn a phase II clinical trial in nine obese, insulin-resistant humans, we observed that treatment with KDT501, a novel isohumulone drug, increased total and high-molecular weight (HMW) adiponectin in plasma. The objective was to determine whether KDT501 increased adiponectin secretion from subcutaneous white adipose tissue (SC WAT) and the underlying mechanism(s).MethodsNine obese participants with either prediabetes or with normal glucose tolerance plus three features of metabolic syndrome were part of the study. SC WAT biopsies were performed before and after 28 days of KDT501 treatment in a clinical research setting. In addition, a cold stimulus was used to induce thermogenic gene expression. Adiponectin secretion was measured, and gene expression of 130 genes involved in adipose tissue function was determined. The effect of KDT501 on adipocyte mitochondrial function was analyzed in vitro.ResultsSC WAT explants secreted more total and HMW adiponectin after KDT501 treatment (P

Lactate production is enhanced by adding calcium carbonate or sodium hydroxide during fermentation. However, Bacillus coagulans 2-6 can produce more than 180 g/L L-lactic acid when calcium lactate is accumulated, but less than 120 g/L L-lactic acid when sodium lactate is formed. The molecular mechanisms by which B. coagulans responds to calcium lactate and sodium lactate remain unclear. In this study, comparative transcriptomic methods based on high-throughput RNA sequencing were applied to study gene expression changes in B. coagulans 2-6 cultured in non-stress, sodium lactate stress and calcium lactate stress conditions. Gene expression profiling identified 712 and 1213 significantly regulated genes in response to calcium lactate stress and sodium lactate stress, respectively. Gene ontology assignments of the differentially expressed genes were performed. KEGG pathway enrichment analysis revealed that 'ATP-binding cassette transporters' were significantly affected by calcium lactate stress, and 'amino sugar and nucleotide sugar metabolism' was significantly affected by sodium lactate stress. It was also found that lactate fermentation was less affected by calcium lactate stress than by sodium lactate stress. Sodium lactate stress had negative effect on the expression of 'glycolysis/gluconeogenesis' genes but positive effect on the expression of 'citrate cycle (TCA cycle)' genes. However, calcium lactate stress had positive influence on the expression of 'glycolysis/gluconeogenesis' genes and had minor influence on 'citrate cycle (TCA cycle)' genes. Thus, our findings offer new insights into the responses of B. coagulans to different lactate stresses. Notably, our RNA-seq dataset constitute a robust database for investigating the functions of genes induced by lactate stress in the future and identify potential targets for genetic engineering to further improve L-lactic acid production by B. coagulans.

A new class of system of generalized parametric nonlinear quasivariational inequalities involving various classes of mappings is introduced and studied. With the properties of maximal monotone mappings, the equivalence between the class of system of generalized parametric nonlinear quasivariational inequalities and a class of fixed point problems is proved and an iterative algorithm with errors is constructed. A few existence and uniqueness results and sensitivity analysis of solutions are also established for the system of generalized nonlinear parametric quasivariational inequalities and some convergence results of iterative sequence generated by the algorithm with errors are proved.

ObjectivesRecent genome-wide association study found rs1801274, a functional single nucleotide polymorphism (SNP) in IgG receptor gene FCGR2A, was associated with increased risk of Kawasaki disease (KD). However, subsequent studies on the role of this SNP were limited and controversial.MethodsA case-control study was conducted in a Chinese Han population including 428 KD patients and 493 controls to examine the association between rs1801274 and KD susceptibility. A meta-analysis was performed in combination with the relevant published studies to further clarify such an association.ResultsOur case-control study found that rs1801274 was significantly associated with increased risk of KD in the Chinese Han population, with an odds ratio (OR) of 1.58 (95% CI = 0.96-2.62) for the GA genotype and 1.93 (95% CI = 1.16-3.19) for the AA genotype compared with the GG genotype. The result of meta-analysis further demonstrated that the A allele of rs1801274 was significantly correlated with KD risk under the allelic model (OR = 1.35, 95% CI = 1.27-1.44) without heterogeneity by fixed-effects model analysis (Q = 17.30, p = 0.139). Moreover, sensitivity analysis supported the robustness of this meta-analysis.ConclusionThese results further confirm that rs1801274 in the FCGR2A gene is significantly associated with increased risk of KD.

Epidemiological studies have investigated the potential anticancer effects of mushroom intake. This review aims to clarify the evidence on the association of dietary mushroom intake with breast cancer risk and to quantify its dose-response relationship. Relevant studies were identified by a search of PubMed, Web of Science and Google Scholar up to December 31, 2013. Observational studies with relative risks (RRs) or hazard ratios (HRs) or odd ratios (ORs) and 95% confidence intervals (CIs) of breast cancer for three or more categories of mushroom intake were eligible. The quality of included studies was assessed by using Newcastle-Ottawa Scale. A dose-response meta-analysis was performed by utilizing generalized least squares trend estimation. Eight case-control studies and two cohort studies with a total of 6890 cases were ultimately included. For dose-response analysis, there was no evidence of non-linear association between mushroom consumption and breast cancer risk (P = 0.337) and a 1 g/d increment in mushroom intake conferred an RR of 0.97 (95% CI: 0.96-0.98) for breast cancer risk, with moderate heterogeneity (I(2) = 56.3%, P = 0.015). Besides, available menopause data extracted from included studies were used to evaluate the influence of menopausal statues. The summary RRs of mushroom consumption on breast cancer were 0.96 (95% CI: 0.91-1.00) for premenopausal women and 0.94 (95% CI: 0.91-0.97) for postmenopausal women, respectively. Our findings demonstrated that mushroom intake may be inversely associated with risk of breast cancer, which need to be confirmed with large-scale prospective studies further.

The human forkhead box A1 (FOXA1) and A2 (FOXA2) transcription factors have been found to control estrogen and androgen signaling through co-regulating target genes with sex hormone receptors. Here we used an integrative strategy to examine the hypothesis that genetic variants at FOXA1/2 binding elements may be associated with sexual dimorphism of hepatocellular carcinoma (HCC) risk. Firstly we extracted chromatin immunoprecipitation-sequencing (ChIP-seq) data of FOXA1, FOXA2 and estrogen receptor 1(ERα) from ENCODE database to obtain dual target regions of FOXA/ERα, and further intersected these regions with genes' promoters. Then we used MATCH program to predict FOXA binding elements, in which genetic variants were retrieved by dbSNP database (NCBI, build 134). A total of 15 candidate variants were identified in this stage. Secondly we performed a case-control study with 1,081 HCC patients and 2,008 matched controls and found a significant association of SERPINA6-rs1998056 with female HCC risk under common genetic models (e.g. GG versus CC: OR = 2.03, 95% CI = 1.26-3.27, P = 0.004). Moreover, results from our real-time quantitative polymerase chain reaction (qPCR) using 72 normal liver tissues adjacent to the tumors showed that SERPINA6 expression was significantly different among different genotypes of this variant (GG versus CC: P = 0.032; Group test: P = 0.060). In summary, our study suggested that SERPINA6-rs1998056 regulated by FOXA/ERα might be associated with female HCC risk.

Adipose tissue in insulin resistant subjects contains inflammatory cells and extracellular matrix components. This study examined adipose pathology of insulin resistant subjects who were treated with pioglitazone or fish oil.Adipose biopsies were examined from nine insulin resistant subjects before/after treatment with pioglitazone 45 mg/day for 12 weeks and also from 19 subjects who were treated with fish oil (1,860 mg EPA, 1,500 mg DHA daily). These studies were performed in a clinical research center setting.Pioglitazone treatment increased the cross-sectional area of adipocytes by 18% (p = 0.01), and also increased capillary density without affecting larger vessels. Pioglitazone treatment decreased total adipose macrophage number by 26%, with a 56% decrease in M1 macrophages and an increase in M2 macrophages. Mast cells were more abundant in obese versus lean subjects, and were decreased from 24 to 13 cells/mm(2) (p = 0.02) in patients treated with pioglitazone, but not in subjects treated with FO. Although there were no changes in total collagen protein, pioglitazone increased the amount of elastin protein in adipose by 6-fold.The PPARγ agonist pioglitazone increased adipocyte size yet improved other features of adipose, increasing capillary number and reducing mast cells and inflammatory macrophages. The increase in elastin may better permit adipocyte expansion without triggering cell necrosis and an inflammatory reaction.

BACKGROUND: Congenital heart disease (CHD) is one of the most common birth defects and the leading cause of deaths among individuals with congenital structural abnormalities worldwide. Both Methionine synthase reductase (MTRR) and Methionine synthase (MTR) are key enzymes involved in the metabolic pathway of homocysteine, which are significant in the earlier period embryogenesis, particularly in the cardiac development. Evidence is mounting for the association between MTRR A66G (rs1801394)/MTR A2756G (rs1805087) and the CHD risk, but results are controversial. Therefore, we conducted a meta-analysis integrating case-control and transmitted disequilibrium test (TDT) studies to obtain more precise estimate of the associations of these two variants with the CHD risk. METHODS: To combine case-control and TDT studies, we used the Catmap package of R software to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 9 reports were included in the final meta-analysis. Eight of them comprised of 914 cases, 964 controls, and 441 families that were germane to MTRR A66G polymorphism; and 4 reports comprised of 250 cases, 205 controls, and 53 families that were relevant to MTR A2756G polymorphism. The pooled OR for the MTRR 66 G allele versus A allele was 1.35 (95% CI = 1.14-1.59, P

BACKGROUND: A common single nucleotide polymorphism (SNP), rs10795668, located at 10p14, was first identified to be significantly associated with risk of colorectal cancer (CRC) by a genome-wide association study (GWAS) in 2008; however, another GWAS and following replication studies yielded conflicting results. METHODS: We conducted a case-control study of 470 cases and 475 controls in a Chinese population and then performed a meta-analysis, integrating the current study and 9 publications to evaluate the association between rs10795668 and CRC risk. Heterogeneity among studies and publication bias were assessed by the χ²-based Q statistic test and Egger's test, respectively. RESULTS: In the case-control study, significant association between the SNP and CRC risk was observed, with per-A-allele OR of 0.71 (95%CI: 0.54-0.94, P = 0.017). The following meta-analysis further confirmed the significant association, with per-A-allele OR of 0.91 (95%CI: 0.89-0.93, P(heterogeneity) >0.05) in European population and 0.86 (95%CI: 0.78-0.96, P(heterogeneity)

BACKGROUND: Lung cancer is the most commonly diagnosed cancer and leading cause of cancer mortality in the world. A single nucleotide polymorphism (SNP), rs402710, located in 5p15.33, was firstly identified to be associated with the lung cancer risk in a genome-wide association study. However, some following replication studies yielded inconsistent results. METHODOLOGY AND FINDINGS: A case-control study of 611 cases and 1062 controls in a Chinese population was conducted, and then a meta-analysis integrating the current and previously published studies with a total 31811 cases and 36333 controls was performed to explore the real effect of rs402710 on lung cancer susceptibility. Significant associations between the SNP rs402710 and lung cancer risk were observed in both case-control study and meta-analysis, with ORs equal to 0.77 (95%CI = 0.63-0.95) and 0.83 (95%CI = 0.81-0.86) in dominant model, respectively. By stratified analysis of our case-control study, the associations were also observed in never smoker group and non-small cell lung cancer(NSCLC) group with ORs equal to 0.71 (95%CI = 0.53-0.95) and 0.69 (95%CI = 0.55-0.87), which was remarkable that larger effect of the minor allele T was seen in the two groups than that in overall lung cancer. Besides, the sensitive and cumulative analysis indicated the robust stability of the current results of meta-analysis. CONCLUSION: The results from our replication study and the meta-analysis provided firm evidence that rs402710 T allele significantly contributed to decreased lung cancer risk, and the case-control study implied that the variant may yield stronger effect on NSCLC and never smokers. However, the mechanism underlying the polymorphism conferring susceptibility to lung cancer is warranted to clarify in the follow-up studies.

NKX2-5 is a transcriptional factor, which plays an important role in heart formation and development. Two genetic variants in the coding region of NKX2-5, 63A>G (rs2277923) and 606G>C (rs3729753), have been investigated in the risk of congenital heart disease (CHD), although with inconsistent results. Thus, a meta-analysis was performed to clarify the associations between the two variants and CHD risk in the Chinese population.Relevant studies were identified by searching PubMed, ISI Web of Science and CNKI databases and by reviewing the reference lists of retrieved articles. Then, the data from eligible studies were combined in an allelic model. A total of 7 and 4 studies were ultimately included for 63A>G and 606G>C, respectively. The results of overall meta-analyses showed that significant association was detected for 63A>G (OR = 1.26, 95% CI = 1.02-1.56, P(heterogeneity )= 0.009, I (2) = 65.1%), but not for 606G>C (OR = 1.22, 95% CI = 0.75-1.96, P(heterogeneity )= 0.412, I (2) = 0.0%). Regarding 63A>G variant, positive results were also obtained in the subgroups of atrial septal defect and large-sample-size study. Besides, the sensitivity analysis indicated that significant association was still detected after deletion of the individual studies with positive result and striking heterogeneity.Our results revealed that the 63A>G variant in NKX2-5, but not the 606G>C, may contribute to CHD risk for Chinese.

BACKGROUND: To investigate the association between rs1820453 which located in the promoter region of yes-associated protein 1 (YAP1) gene and breast cancer (BC) risk. METHOD AND FINDINGS: We conducted a hospital-based case-control study including a total of 480 BC cases and 545 cancer-free controls in Chinese population. Then the expression quantitative trait locus (e-QTL) analysis was performed to explore the possible function of rs1820453 to the YAP1 gene expression. The association between rs1820453 and BC risk was significantly identified with the odds ratio (OR) was 1.27 (95 % confidence interval (CI) =1.03-1.57) under allelic model when adjusted by age and menopausal status. In addition, the correlation analysis of rs1820453 and YAP1 expression level found that this variant was significantly associated with the gene expression in Chinese population. When compared with level of mRNA expression of the AA genotype (6.011 ± 0.046), the mRNA expression level in CC genotype (5.903 ± 0.026) was statistically lower (P=0.024). CONCLUSION: The results from this study suggested that rs1820453 A>C change may affect the gene expression and contribute to the risk of developing BC in Chinese population though larger sample-size studies along with functional experiments were anticipated to warrant the results.

Supplementation with folic acid (FA) was proven to prevent neural tube defects (NTDs) and was recommended worldwide before and during early pregnancy. However, much less is known regarding the role of FA after the 12th gestational week (GW). This study aimed to investigate the related effects of continued FA supplementation after the first trimester of pregnancy on fetal growth. The study subjects came from the Ma’anshan-Anhui Birth Cohort Study (MABC) that recruited 3474 pregnant women from the city of Ma’anshan in Anhui Province in China during the period of May 2013 to September 2014. The information on use of vitamin and mineral supplements was recorded in different periods (the first/second/third trimester of pregnancy). Small-for-gestational-age (SGA) births were live-born infants that were