Solving the time-dependent protein distributions for autoregulated bursty gene expression using spectral decomposition.

In this study, we obtain an exact time-dependent solution of the chemical master equation (CME) of an extension of the two-state telegraph model describing bursty or non-bursty protein expression in the presence of positive or negative autoregulation. Using the method of spectral decomposition, we show that the eigenfunctions of the generating function solution of the CME are Heun functions, while the eigenvalues can be determined by solving a continued fraction equation. Our solution generalizes and corrects a previous time-dependent solution for the CME of a gene circuit describing non-bursty protein expression in the presence of negative autoregulation [Ramos et al., Phys. Rev. E 83, 062902 (2011)]. In particular, we clarify that the eigenvalues are generally not real as previously claimed. We also investigate the relationship between different types of dynamic behavior and the type of feedback, the protein burst size, and the gene switching rate.

Endometrial thickness is an independent risk factor of hypertensive disorders of pregnancy: a retrospective study of 13,458 patients in frozen-thawed embryo transfers.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are an important cause of maternal and fetal mortality, and its potential risk factors are still being explored. Endometrial thickness (EMT), as one of the important monitoring indicators of endometrial receptivity, has been confirmed to be related to the incidence of HDP in fresh embryo transfer. Our study was designed to investigate whether endometrial thickness is associated with the risk of hypertensive disorders of pregnancy in frozen-thawed embryo transfer (FET). METHODS: This respective cohort study enrolled 13,458 women who received vitrified embryo transfer and had a singleton delivery in the Reproductive Hospital affiliated to Shandong University from January 2015 to December 2019. We set strict screening criteria and obtained the information from the hospital electronic medical system. Statistical methods including logistic regression analysis, receiver operating characteristic curve and restricted cubic spline were used to evaluate the relationship between endometrial thickness and the incidence of pregnancy-induced hypertension. RESULTS: The incidences of HDP in a thin endometrial thickness group (< 0.8 cm) and a thick endometrial thickness group (> 1.2 cm) were significantly greater than in a reference group (0.8 cm-1.2 cm) (7.98 and 5.24% vs 4.59%, P <  0.001). A nonlinear relationship between endometrial thickness and risk of hypertensive disorders of pregnancy was examined by restricted cubic spline (P <  0.001). The thin endometrial thickness and thick endometrial thickness groups were significantly associated with the risk of HDP after adjusting for confounding variables by stepwise logistic regression analysis. Subsequently, subgroup logistic regression analysis based on endometrial preparation regimens showed that thin endometria were still significantly associated with a higher morbidity rate in the artificial cycle group, while in the natural cycle group, thick endometria were closely associated with increased morbidity. CONCLUSION: Our study manifested that both the thin and thick endometria were associated with an increased risk of hypertensive disorders of pregnancy in frozen embryo transfer cycles. Reproductive clinicians should focus on adjusting endometrial thickness in different preparation regimens; and obstetricians should be mindful of the risk of hypertension during pregnancy, when women with thin (< 0.8 cm) or excessively thicker (> 1.2 cm) endometrial thickness achieve pregnancy through frozen-thawed embryo transfer.

Generating Lifetime-Enhanced Microbubbles by Decorating Shells with Silicon Quantum Nano-Dots Using a 3-Series T-Junction Microfluidic Device.

Long-term stability of microbubbles is crucial to their effectiveness. Using a new microfluidic device connecting three T-junction channels of 100 µm in series, stable monodisperse SiQD-loaded bovine serum albumin (BSA) protein microbubbles down to 22.8 ± 1.4 µm in diameter were generated. Fluorescence microscopy confirmed the integration of SiQD on the microbubble surface, which retained the same morphology as those without SiQD. The microbubble diameter and stability in air were manipulated through appropriate selection of T-junction numbers, capillary diameter, liquid flow rate, and BSA and SiQD concentrations. A predictive computational model was developed from the experimental data, and the number of T-junctions was incorporated into this model as one of the variables. It was illustrated that the diameter of the monodisperse microbubbles generated can be tailored by combining up to three T-junctions in series, while the operating parameters were kept constant. Computational modeling of microbubble diameter and stability agreed with experimental data. The lifetime of microbubbles increased with increasing T-junction number and higher concentrations of BSA and SiQD. The present research sheds light on a potential new route employing SiQD and triple T-junctions to form stable, monodisperse, multi-layered, and well-characterized protein and quantum dot-loaded protein microbubbles with enhanced stability for the first time.

Safety of hydroxychloroquine in COVID-19 and other diseases: a systematic review and meta-analysis of 53 randomized trials.

INTRODUCTION: Many concerns still exist regarding the safety of hydroxychloroquine (HCQ) in the treatment of Coronavirus Disease 2019 (COVID-19). OBJECTIVES: The purpose of this study was to evaluate the safety of HCQ in the treatment of COVID-19 and other diseases by performing a systematic review and meta-analysis. METHODS: Randomized controlled trials (RCTs) reporting the safety of HCQ in PubMed, Embase, and Cochrane Library were retrieved starting from the establishment of the database till June 5, 2020. Literature screening, data extraction, and assessment of risk bias were performed independently by two reviewers. RESULTS: We identified 53 eligible studies involving 5496 patients. The meta-analysis indicated that the risk of adverse effects (AEs) in the HCQ group was significantly increased compared with that in the control group (RD 0.05, 95%CI, 0.02 to 0.07, P = 0.0002), and the difference was also statistically significant in the COVID-19 subgroup (RD 0.15, 95%CI, 0.07 to 0.23, P = 0.0002) as well as in the subgroup for other diseases (RD 0.03, 95%CI, 0.01 to 0.04, P = 0.003). CONCLUSIONS: HCQ is associated with a high total risk of AEs compared with the placebo or no intervention in the overall population. Given the small number of COVID-19 participants included, we should be cautious regarding the conclusion stating that HCQ is linked with an increase incidence of AEs in patients with COVID-19, which we hope to confirm in the future through well-designed and larger sample size studies.

Investigation on factors related to uterine fibroids in rural women of northern Anhui province.

AIM: Given the increasing prevalence of hysteromyoma among the Chinese rural women of childbearing age, it is imperative that more attention should be given to researching risk factors that predispose women to this condition so that early preventive measures may be taken. Our study investigates potential risk factors for uterine fibroids such as participants' demographic characteristics (age, ethnicity, education), physiological characteristics (age at menarche, primiparous age), and the occurrence of several different female reproductive diseases (vaginitis, pelvic inflammatory disease). METHODS: 2200 rural women of reproductive age were screened from a cross-sectional study carried out in the northern Anhui province. Data were collected by questionnaire surveys, gynecological and laboratory examinations and were subjected to univariate and multivariate analysis to evaluate the risk factors for uterine fibroids. RESULTS: Of the 2200 women, 440 had uterine fibroids. In general, women with endometriosis, ovarian cysts and early menarche were more likely to suffer from hysteromyoma. Factors including higher parity, late age of first childbirth, and a regular menstrual cycle were associated with the reduced risk of uterine fibroids. CONCLUSIONS: Our findings indicate that parameters such as earlier age of menarche, early primiparous age, lower parity and a variety of female reproductive diseases were associated with an increased risk of uterine fibroids. These findings may be used to guide the formulation of effective prevention and intervention protocols to improve the reproductive health of rural women.

Effectiveness of Oil-Layered Albumin Microbubbles Produced Using Microfluidic T-Junctions in Series for In Vitro Inhibition of Tumor Cells.

This work focuses on the synthesis of oil-layered microbubbles using two microfluidic T-junctions in series and evaluation of the effectiveness of these microbubbles loaded with doxorubicin and curcumin for cell invasion arrest from 3D spheroid models of triple negative breast cancer (TNBC), MDA-MB-231 cell line. Albumin microbubbles coated in the drug-laden oil layer were synthesized using a new method of connecting two microfluidic T-mixers in series. Double-layered microbubbles thus produced consist of an innermost core of nitrogen gas encapsulated in an aqueous layer of bovine serum albumin (BSA) which in turn, is coated with an outer layer of silicone oil. In order to identify the process conditions leading to the formation of double-layered microbubbles, a regime map was constructed based on capillary numbers for aqueous and oil phases. The microbubble formation regime transitions from double-layered to single layer microbubbles and then to formation of single oil droplets upon gradual change in flow rates of aqueous and oil phases. In vitro dissolution studies of double-layered microbubbles in an air-saturated environment indicated that a complete dissolution of such bubbles produces an oil droplet devoid of a gas bubble. Incorporation of doxorubicin and curcumin was found to produce a synergistic effect, which resulted in higher cell deaths in 2D monolayers of TNBC cells and inhibition of cell proliferation from 3D spheroid models of TNBC cells compared to the control.

Dorsoventral photosynthetic asymmetry of tobacco leaves in response to direct and diffuse light.

Plants can change leaf forms, adjusting light conditions on their adaxial and abaxial surfaces, to adapt to light environments and enhance their light use efficiencies. The difference between photosynthesis on the two leaf sides (dorsoventral asymmetry) is an important factor that affects light use efficiency. However, photosynthetic dorsoventral asymmetry is rarely compared under direct and diffuse light conditions. To estimate the impacts of recently reported alterations in direct and diffuse light in the sky radiation on plant carbon assimilation, variations in morphology between the two leaf sides in tobacco (Nicotiana tabacum L.) were investigated, and the dorsoventral responses of photosynthesis to illuminating directions were compared in direct and diffuse light. Dorsoventral asymmetry was reflected in stomatal densities, anatomic structures, and photochemical traits, which caused markedly different photosynthetic rates as well as stomatal conductances both in direct and diffuse light. However, the degree of photosynthetic asymmetry was weakened in diffuse light. The diffuse light caused a greater stomatal conductance on the abaxial side than direct light, which resulted in reduced photosynthetic asymmetry. In addition, the photosynthetic dorsoventral asymmetry could be affected by the photosynthetic photon flux density. These results contribute to understanding the dorsoventral regulation of photosynthesis in bifacial leaves, and provide a reference for breeding to cope with the increase in the proportion of diffuse light in the future.

Verticillium dahliae VdTHI20, Involved in Pyrimidine Biosynthesis, Is Required for DNA Repair Functions and Pathogenicity.

Verticillium dahliae (V. dahliae) infects roots and colonizes the vascular vessels of host plants, significantly reducing the economic yield of cotton and other crops. In this study, the protein VdTHI20, which is involved in the thiamine biosynthesis pathway, was characterized by knocking out the corresponding VdTHI20 gene in V. dahliae via Agrobacterium tumefaciens-mediated transformation (ATMT). The deletion of VdTHI20 resulted in several phenotypic defects in vegetative growth and conidiation and in impaired virulence in tobacco seedlings. We show that VdTHI20 increases the tolerance of V. dahliae to UV damage. The impaired vegetative growth of ΔVdTHI20 mutant strains was restored by complementation with a functional copy of the VdTHI20 gene or by supplementation with additional thiamine. Furthermore, the root infection and colonization of the ΔVdTHI20 mutant strains were suppressed, as indicated by green fluorescent protein (GFP)-labelling under microscope observation. When the RNAi constructs of VdTHI20 were used to transform Nicotiana benthamiana, the transgenic lines expressing dsVdTHI20 showed elevated resistance to V. dahliae. Together, these results suggest that VdTHI20 plays a significant role in the pathogenicity of V. dahliae. In addition, the pathogenesis-related gene VdTHI20 exhibits potential for controlling V. dahliae in important crops.

Formation Mechanism, Geometric Stability and Catalytic Activity of a Single Iron Atom Supported on N-Doped Graphene.

Based on density functional theory (DFT) calculations, the formation geometries, stability and catalytic properties of single-atom iron anchored on xN-doped graphene (xN-graphene-Fe, x=1, 2, 3) sheet are systemically investigated. It is found that the different kinds and numbers of gas reactants can effectively regulate the electronic structure and magnetic properties of the 3 N-graphene-Fe system. For NO and CO oxidation reactions, the coadsorption configurations of NO/O2 and CO/O2 molecules on a reactive substrate as the initial state are comparably analyzed. The NO oxidation reactions through the Langmuir-Hinshelwood (LH) and Eley-Rideal (ER) mechanisms have relatively smaller energy barriers than those of the CO oxidation processes. In comparison, the preadsorbed 2NO reacting with 2CO molecules (2NO+2CO→2CO2 +N2 ) through ER reactions (<0.4 eV) are energetically more favorable processes. These results can provide beneficial references for theoretical studies on NO and CO oxidation and designing graphene-based catalyst for toxic gas removal.

Association of bone metabolism markers with coronary atherosclerosis and coronary artery disease in postmenopausal women.

This study aimed to evaluate the association of bone metabolism markers with coronary atherosclerosis and coronary artery disease (CAD) in postmenopausal women. Based on the findings of coronary angiography, 111 women with CAD and 116 women without CAD were recruited. Serum calcium, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHD), osteocalcin, N-terminal propeptide of type I procollagen (P1NP) and C-terminal cross-linked telopeptide of type I collagen (CTX) were measured. The Gensini score was used to assess the severity of coronary atherosclerosis. Compared with women with serum calcium ≤2.29 mmol/L, women with serum calcium >2.29 mmol/L had a 2.63-fold increased risk of CAD after adjusting for multiple cardiovascular risks, PTH and 25OHD [odds ratio (OR) = 2.91, 95% confidence interval (CI) 1.35-6.28]. In the fully adjusted model plus PTH and 25OHD, the risk of CAD increased 1.87-fold with every 1-SD increment of serum calcium (OR = 1.87, 95% CI 1.21-2.88). To further analyze the potential strong confounding effect of albumin, the absolute levels of calcium were replaced by their albumin-corrected values in the regression model. Compared with women with albumin-corrected calcium ≤2.27 mmol/L, women with albumin-corrected calcium >2.27 mmol/L had a 2.36-fold increased risk of CAD in the fully adjusted model plus PTH and 25OHD (OR = 2.36, 95% CI 1.13-4.92). The risk of coronary atherosclerosis as defined by Gensini score >0 increased 1.73-fold with every 1-SD increment of serum calcium in the fully adjusted model plus PTH and 25OHD (OR = 1.73, 95% CI 1.09-2.73). However, albumin-corrected calcium was not associated with coronary atherosclerosis either as a categorical variable or as a continuous variable in all models. No significant association of PTH, 25OHD, osteocalcin, CTX and P1NP with CAD or coronary atherosclerosis was found in this study. Higher serum calcium levels were independently associated with CAD in postmenopausal women.

Two-dimensional MXene nanosheets on nano-scale fibrils in hierarchical porous structure to achieve ultra-high sensitivity.

The complex hybrid nanostructure combining a two-dimensional (2D) conductive material and a hierarchical nanoscale skeleton plays an important role to enhance its piezoresistive sensitivity. To construct such a novel hybrid nanostructure, a piezoresistive sensor was designed with the following strategy to take the full advantages of 2D MXene and nanoscale fibrils: ethylene oxide propylene oxide random copolymer (EOPO) was grafted to ethylene-vinyl alcohol (EVOH) molecular chains and was foamed by an environmentally-friendly supercritical CO2 (scCO2) foaming technology to fabricate abundant nanoscale EVOH fibrils surrounding micropores; MXene featured as a 2D structure of nanoscale size that strongly interacted with this hierarchical nanoscale skeleton, and MXene not only convolved on nanoscale fibrils to generate bumps but also MXene covered the end of broken fibrils to build spots, and furthermore, MXene adhered on the soft EOPO embedded EVOH fibrils to form wrinkles, in which these bumps, spots and wrinkles assembled by highly conductive 2D MXene offered sufficient contacts when the hierarchical nanoscale skeleton was compressed (these contacts would then destruct when the skeleton recovered). Such an elaborated hybrid nanostructural design exploits the full potential of 2D MXene and hence achieves an ultra-high sensitivity of 6895.0 kPa-1 for this fabricated MXene piezoresistive sensor.

Magnetic and injectable Fe-doped liquid metals for controlled movement and photothermal/electromagnetic therapy.

As a multifunctional material, gallium-based liquid metal (LM) mixtures with metal particles dispersed in the LM environment display many excellent and intriguing properties. In this study, biomaterials were prepared by mixing Fe particles with LM for easily manageable photothermal or electromagnetic therapy and evaluated. Clinically, the fabricated 5%Fe/LM sample was injectable and radiopaque, which allowed its smooth delivery through a syringe to the target tissues, where it could help achieve clear imaging under CT. Meanwhile, because of the loading of Fe particles, the 5%Fe/LM possessed a magnetic property, implying a high manipulation capability. According to the experiments, the capsule containing 5%Fe/LM when placed in an isolated pig large intestine could move as desired to the designated position through an external magnet. Further, the biosafety and low toxicity of the 5%Fe/LM were confirmed by cytotoxicity tests in vitro, and the temperature changes at the interface between the 5%Fe/LM and intestinal tissue after near-infrared (NIR) laser irradiation were determined through theoretical modeling and numerical simulation data analysis. Due to the excellent photothermal and magnetothermal effects of LM, the temperature of the 5%Fe/LM injected into the rabbit abdominal cavity could significantly increase under NIR laser or alternating magnetic field (AMF) administration. As a novel functional biomaterial, the 5%Fe/LM exhibited promising potential for designated position movement and photothermal or magnetothermal therapy in the near future.

Effect of Starch Type and Pre-Treatment on the Properties of Gelatin-Starch Foams Produced by Mechanical Foaming.

Incorporating biopolymers in packaging foams can contribute to a more circular packaging system, utilizing renewable and compostable materials. Gelatin, with its favorable physicochemical properties, allows for producing gelatin foams via mechanical foaming, a well-established and low-investment process. To improve foam properties, starch can be added to the gelatin formulation. However, the variability in the properties of starch powders can impact the polymer blend and, consequently, the properties of the dry foam. This study aimed to investigate the impact of different starch powders from different botanical origins (tapioca and corn) and treatments (native or pregelatinized) on the properties of gelatin-starch foams produced by mechanical foaming. The study successfully produced foams with densities of approximately 45-50 kg/m3 and compression properties comparable to EPS (expanded polystyrene) foams. The starch type and pre-treatment significantly influenced the properties of the foam. Pregelatinized starches exhibited slightly higher densities due to lower foamability caused by higher viscosity. Using starch exhibiting total loss of birefringence led to denser foams with greater compression properties than those with starch with a certain degree of crystallinity remaining. Therefore, selecting the appropriate starch type is crucial when developing starch-based materials to ensure optimal material and processing properties align with application requirements.

Comparison of the efficacy and safety of leflunomide versus placebo combined with basic prednisone therapy in patients with active disease phase of Takayasu arteritis: study protocol for a randomized, double-blinded controlled trial (Takayasu arteritis clinical trial in China: TACTIC).

Background: Takayasu arteritis (TAK) is an immune-induced granulomatous vasculitis that occurs primarily in young Asian women. Our previous cohort studies have indicated that leflunomide (LEF), which can lead to rapid induction and might be a promising alternative treatment for TAK. Objectives: To compare the efficacy and safety of LEF versus placebo combined with prednisone for active TAK in a Chinese population. Design: This will be a multicenter, randomized, double-blinded controlled trial aiming to recruit 116 TAK patients with active disease. This study will last 52 weeks. Methods and analysis: Participants will be assigned randomly to the LEF intervention arm or placebo control arm at a 1:1 ratio. Initially, LEF combined with prednisone will be given to the intervention arm and a placebo tablet combined with prednisone will be given to the placebo arm. At the end of week 24, subjects who achieved clinical remission or partial clinical remission will proceed to maintenance therapy with LEF to the end of week 52; those who did not achieve clinical remission or partial clinical remission in the LEF intervention arm will drop out from the study, and those in the placebo control arm will switch to LEF treatment to week 52. The primary endpoint will be the clinical remission rate of LEF versus placebo at the end of week 24. The secondary endpoints will be the time to clinical remission, mean dose of prednisone, disease recurrence, time to recurrence, adverse events, as well as clinical remission in subjects who switched from the placebo control arm to LEF therapy after week 24. Intention to treat will be the primary analysis. Discussion: This is the first randomized double-blinded placebo-controlled trial to clarify the efficacy and safety of LEF in treating active TAK. The results will provide more evidence for TAK management. Registration: ClinicalTrials.gov identifier: NCT02981979.

Genome-Wide Identification and Evolutionary Analysis of Gossypium YTH Domain-Containing RNA-Binding Protein Family and the Role of GhYTH8 in Response to Drought Stress.

YTH domain-containing proteins are one kind of RNA-binding protein involved in post-transcriptional regulation and play multiple roles in regulating the growth, development, and abiotic stress responses of plants. However, the YTH domain-containing RNA-binding protein family has not been previously studied in cotton. In this study, a total of 10, 11, 22, and 21 YTH genes were identified in Gossypium arboreum, Gossypium raimondii, Gossypium barbadense, and Gossypium hirsutum, respectively. These Gossypium YTH genes were categorized into three subgroups by phylogenetic analysis. The chromosomal distribution, synteny analysis, structures of Gossypium YTH genes, and the motifs of YTH proteins were analyzed. Furthermore, the cis-element of GhYTH genes promoter, miRNA targets of GhYTH genes, and subcellular localization of GhYTH8 and GhYTH16 were characterized. Expression patterns of GhYTH genes in different tissues, organs, and in response to different stresses were also analyzed. Moreover, functional verifications revealed that silencing GhYTH8 attenuated the drought tolerance in the upland cotton TM-1 line. These findings provide useful clues for the functional and evolutionary analysis of YTH genes in cotton.

Trajectories of Blood Lipids Profile in Midlife Women: Does Menopause Matter?

Background It remains controversial whether changes of lipids over menopause transition (MT) are more age-related or more menopause-related. We aimed to classify women into different trajectory groups based on pattern and level of total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B (ApoB), high-density lipoprotein cholesterol (HDL-C), triglyceride, and apolipoprotein A-I over the MT, as well as examine the effect of MT-related factors on lipid trajectory groups and levels. Methods and Results The cohort included 2582 subjects from the Study of Women's Health Across the Nation. Different trajectory patterns of lipids during the MT were determined using the latent class growth mixture model. The predictors of distinct blood lipids trajectory groups were determined by multiple linear regression models and multinomial logistic regression models. Women were categorized into either inverse U-shape or progressing trajectory group in each blood lipids measurement. The inverse U-shape total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, high-density lipoprotein cholesterol, log(TG), and apolipoprotein A-I trajectories showed an increasing trend before menopause but a decreasing trend after menopause. The U-shape total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B trajectories started to rise 5 years before menopause. Age at menopause, follicle-stimulating hormone, vasomotor symptoms, and estradiol predicted the shape and level of the women's lipids over the MT. Conclusions Distinct lipid trajectories were identified during the MT, and the existence of at least 1 trajectory in each lipid parameters suggested a contribution of menopause. Our study highlights the need for earlier and continuous surveillance of lipids during the MT.

"Double Frozen Transfer" Could Influence the Perinatal and Children's Growth: A Nested Case-Control Study of 6705 Live Birth Cycles.

Objective: This study aims to evaluate neonatal and children growth outcomes of cryotransfer of embryos developed from frozen gametes [double frozen transfer (DFT)]. Methods: This nested case-control study included 6,705 women who had a singleton live birth after embryo transfer at the Center for Reproductive Medicine, Shandong University, from 2008 to 2020. Of these, 745 women underwent frozen embryo transfer (FET) using embryos developed from frozen gametes (DFT). Propensity score methodology was used to balance the two groups by maternal age and body mass index (BMI) before evaluating outcomes. After age and BMI were matched using the propensity score methodology in a ratio of 1:4, the control groups enrolled 2,980 women who underwent fresh embryo transfer (ET) and 2,980 women underwent FET from fresh gametes. The children born were followed to at least 5 years of age, and some were followed up to 10 years. Neonatal outcomes and childhood growth measurements were compared among the three groups. Results: The average birth weight of the DFT group (3,462 g) was significantly higher than the FET group (3,458 g) and ET group (3,412 g). The rate of large for gestational age (LGA) babies in the DFT and FET group was higher than that for the ET group (30.9% vs. 24.8%; 29.4% vs. 24.8%, respectively). After adjusting for different confounder combinations in the three models, the birth weight and risk of LGA in the DFT and FET groups were still higher than in the ET group, and the values group of P for trend in the models were significant. In multiple linear regression analysis of the children's development, the height Z-score of children born from the DFT and FET group was higher than that for children from the ET group (ß = 0.21, 95% CI 0.07-0.35; b = 0.17, 95% CI 0.05-0.28, respectively). However, childhood growth measurements including body weight Z-score and BMI Z-score were not significantly different among the three groups. In addition, the proportion of male children born from DET was higher than that from ET. Conclusions: There is an increased risk of LGA babies associated with pregnancies conceived from DFT. Children are inclined to be taller in the future in this group than after FET. The related etiology and pathophysiology mechanisms still need to be revealed. In the future, well-designed, observational studies with in-depth collection of patients' characteristics may shed more light on this issue.

Genome-Wide Identification of Cotton (Gossypium spp.) Trehalose-6-Phosphate Phosphatase (TPP) Gene Family Members and the Role of GhTPP22 in the Response to Drought Stress.

Trehalose-6-phosphate phosphatase (TPP) is a key enzyme involved in trehalose synthesis in higher plants. Previous studies have shown that TPP family genes increase yields without affecting plant growth under drought conditions, but their functions in cotton have not been reported. In this study, 17, 12, 26 and 24 TPP family genes were identified in Gossypium arboreum, Gossypium raimondii, Gossypium barbadense and Gossypium hirsutum, respectively. The 79 TPP family genes were divided into three subgroups by phylogenetic analysis. Virus-induced gene silencing (VIGS) of GhTPP22 produced TRV::GhTPP22 plants that were more sensitive to drought stress than the control plants, and the relative expression of GhTPP22 was decreased, as shown by qRT-PCR. Moreover, we analysed the gene structure, targeted small RNAs, and gene expression patterns of TPP family members and the physicochemical properties of their encoded proteins. Overall, members of the TPP gene family in cotton were systematically identified, and the function of GhTPP22 under drought stress conditions was preliminarily verified. These findings provide new information for improving drought resistance for cotton breeding in the future.

Genome-Wide Identification of Cotton (Gossypium spp.) Glycerol-3-Phosphate Dehydrogenase (GPDH) Family Members and the Role of GhGPDH5 in Response to Drought Stress.

Glycerol-3-phosphate dehydrogenase (GPDH) is a key enzyme in plant glycerol synthesis and metabolism, and plays an important role in plant resistance to abiotic stress. Here, we identified 6, 7, 14 and 14 GPDH genes derived from Gossypium arboreum, Gossypium raimondii, Gossypium barbadense and Gossypium hirsutum, respectively. Phylogenetic analysis assigned these genes into three classes, and most of the genes within the family were expanded by whole-genome duplication (WGD) and segmental duplications. Moreover, determination of the nonsynonymous substitution rate/synonymous substitution rate (Ka/Ks) ratio showed that the GPDH had an evolutionary preference for purifying selection. Transcriptome data revealed that GPDH genes were more active in the early stages of fiber development. Additionally, numerous stress-related cis-elements were identified in the potential promoter region. Then, a protein-protein-interaction (PPI) network of GPDH5 in G. hirsutum was constructed. In addition, we predicted 30 underlying miRNAs in G. hirsutum. Functional validation results indicated that silencing GhGPDH5 diminished drought tolerance in the upland cotton TM-1 line. In summary, this study provides a fundamental understanding of the GPDH gene family in cotton, GhGPDH5 exerts a positive effect during drought stress and is potentially involved in stomatal closure movements.

Association between long-term ambient air pollution exposure and the risk of breast cancer: a systematic review and meta-analysis.

Breast cancer is a complex and multifactorial disease which stems significantly from both environmental and genetic factors. A growing number of epidemiological studies have suggested that ambient air pollution (AAP) exposure may play an important role in breast cancer development. However, no consistency has been reached concerning whether high levels of air pollutant exposure were related to increased breast cancer risk among the current evidence. To further clarify such association of long-term AAP exposure with risk of breast cancer, a systematic review and meta-analysis of available evidence was performed. An extensive literature search in 3 academic databases was conducted before March 10, 2020. The risk of bias (RoB) for each individual study was evaluated with a domain-based assessment tool, developed by the National Toxicology Program/Office of Health Assessment and Translation (NTP/OHAT). Meta-estimates for air pollutant-breast cancer combinations were calculated for a standardized increment in exposure by random-effect models. The confidence level in the body of evidence and the certainty of evidence was also assessed for each air pollutant-breast cancer combination. The initial search identified 5446 studies, and 18 of them were eligible. The pooled analysis found an increased risk of breast cancer was associated with an increase in each 10 µg/m3 in nitrogen dioxide (NO2) exposure (hazard ratio (HR) = 1.02, 95% confidence interval (CI) = 1.01, 1.04), while particulate matter with aerodynamic diameters ≤ 2.5 µm and 10 µm (PM2.5, PM10) revealed no statistically significant associations with breast cancer risk. Our evaluation on the certainty of evidence indicates that there was a "moderate level of evidence" in the body of evidence for an association of NO2 exposure with an increased breast cancer risk and an "inadequate level of evidence" in the body of evidence for an association of PM2.5 and PM10 exposure with an increased breast cancer risk. Our study suggests long-term exposure to NO2 is related to an increased risk of breast cancer. However, in consideration of the limitations, further studies, especially performed in developing countries, with improvements in exposure assessment, outcome ascertainment, and confounder adjustment, are needed to draw a definite evidence of a causal relationship.