Thyroid dysfunction caused by exposure to environmental endocrine disruptors and the underlying mechanism: A review.

Thyroid disease has been rapidly increasing, but its causes remain unclear. At present, many studies have focused on the relationship between environmental endocrine disruptors (EEDs) and the pathogenesis of thyroid disease. Herein, we summarize such studies exploring the effects of exposure to common EEDs on thyrotoxicosis, finding that EEDs appear to contribute to the pathogenesis of thyroid-related diseases such as thyroid cancer, goiter, thyroiditis, hyperthyroidism, and hypothyroidism. To explore this causative effect in detail, we have analyzed the following three aspects of how EEDs are believed to exert their impacts on the occurrence and development of thyroid disease: (1) damage to the thyroid tissue structure, including disrupted mitochondria and the stratification of thyroid follicular epithelial cells; (2) disruption of thyroid hormone signaling, including thyroid hormone synthesis and secretion disorders, destruction of normal function of the hypothalamus-pituitary-thyroid axis, disturbed estrogen signaling in the body, alterations to the level of thyroid-stimulating hormone, inhibition of the release of thyroglobulin from thyroid cells, and reductions in the levels of sodium iodide co-transporters, thyroid peroxidase, deiodinase, and transthyretin; and (3) molecular mechanisms underlying the disruption of thyroid function, including competitive binding to T3 and T4 receptors, disturbance of the hypothalamic-pituitary-thyroid axis, activation of the ERK and Akt pathways, oxidative stress, regulation of the expression of the proto-oncogene k-Ras, tumor suppressor gene PTEN, and thyroid TSHR gene, and induction of autophagy in thyroid cells. Overall, this article reviews how EEDs can affect the occurrence and development of thyroid disease via multiple routes, thus providing new ideas to intervene for the prevention, diagnosis, treatment, and prognosis of thyroid disease.

Role and mechanism of MiR-542-3p in regulating TLR4 in nonylphenol-induced neuronal cell pyroptosis.

BACKGROUND: This study aimed to investigate the spatial learning/memory and motor abilities of rats and the alteration of miR-542-3p and pyroptosis in the midbrain nigrostriatal area in vivo after nonylphenol (NP) gavage and to explore the mechanism of miR-542-3p regulation of Toll-like receptor 4 (TLR4) in NP-induced pyroptosis in BV2 microglia in vitro. METHODS: In vivo: Thirty-six specific-pathogen-free-grade Sprague-Dawley rats were divided into three equal groups: blank control group (treated with pure corn oil), NP group (treated with NP, 80 mg/kg body weight per day for 90 days), and positive control group [treated with lipopolysaccharide (LPS), 2 mg/kg body weight for 7 days]. In vitro: The first part of the experiment was divided into blank group (control, saline), LPS group [1 µg/ml + 1 mM adenosine triphosphate (ATP)], and NP group (40 µmol/L). The second part was divided into mimics NC (negative control) group, miR-542-3p mimics group, mimics NC + NP group, and miR-542-3p mimics + NP group. RESULTS: In vivo: Behaviorally, the spatial learning/memory and motor abilities of rats after NP exposure declined, as detected via Y-maze, open field, and rotarod tests. Some microglia in the substantia nigra of the NP-treated rats were activated. The downregulation of miR-542-3p was observed in rat brain tissue after NP exposure. The mRNA/protein expression of pyroptosis-related indicators (TLR4), NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), gasdermin-D (GSDMD), cysteinyl aspartate-specific proteinase-1 (caspase-1), and interleukin-1ß (IL-1ß) in the substantia nigra of the midbrain increased after NP exposure. In vitro: ASC fluorescence intensity increased in BV2 cells after NP exposure. The mRNA and/or protein expression of pyroptosis-related indicators (TLR4, NLRP3, GSDMD, caspase-1, and IL-1ß) in BV2 cells was upregulated after NP exposure. The transfection of miR-542-3p mimics inhibited NP-induced ASC expression in BV2 cells. The overexpression of miR-542-3p, followed by NP exposure, significantly reduced TLR4, NLRP3, ASC, caspase-1, and IL-1ß gene and/or protein expression. CONCLUSIONS: This study suggested that NP exposure caused a decline in spatial learning memory and whole-body motor ability in rats. Our study was novel in reporting that the upregulation of miR-542-3p targeting and regulating TLR4 could inhibit NLRP3 inflammatory activation and alleviate NP-induced microglia pyroptosis.

Fluorescent carbon dots synthesized by waste wind turbine blade for photocatalytic degradation.

Developing novel waste recycling strategies has become a feasible solution to overcome environmental pollution. In this work, a method of using waste wind turbine blade (WTB) as a carbon source to synthesize blue fluorescent carbon dots (B-CDs) by hydrothermal treatment is proposed. B-CDs are spherical and have an average particle size of 5.2 nm. The surface is rich in C-O, C=O, -CH3 , and N-H bond functional groups, containing five elements: C, O, N, Si, and Ca. The optimal emission wavelength of B-CDs is 463 nm, corresponding to an excitation wavelength of 380 nm. Notably, a relatively high quantum yield of 29.9% and a utilization rate of 40% were obtained. In addition, B-CDs can serve as a photocatalyst to degrade methylene blue dye, with a degradation efficiency of 64% under 40-min irradiation conditions. The presence of holes has a significant influence on the degradation process.

[Effects of Biochar and Soil Conditioner on Coastal Barren Saline-alkali Soil].

This study aimed to quantify the biological improvement and availability from a soil amendment substance for barren severe saline-alkali soils. A field experiment was conducted to apply biochar (B) and soil conditioner (C) rich in humic substances to pioneer crops and oil sunflower planted in the coastal barren severe saline-alkali area of the North China Low Plain. The six treatments included single or combined application of two-level biochar rates (0 and 1.25 kg·m-2) and three-level soil conditioner rates (0, 0.83, and 1.66 kg·m-2) at the start of the experiment. Soil samples were collected at 30 cm per layer and sampling from 0 to 90 cm after the oil was collected. The results revealed that the application of biochar increased the saline concentration of the 0-30 cm and 60-90 cm soil layers, whereas the soil conditioner significantly decreased the saline concentration of the 0-30 cm soil layers. Neither biochar nor conditioner showed a significant impact on soil pH. Biochar exhibited varying impacts on soil nutrients, that is, significantly inhibiting soil nitrification, which resulted in soil NO3--N decreasing while NH4+-N increased significantly, along with no significant impact on soil organic matter content (SOM) in the 0-90 cm soil profile. The application of soil conditioner exerted positive effects on improving SOM in the 0-30 cm layer and NO3--N in the 0-90 cm soil depth when the conditioner rate was at 1.66 kg·m-2. Either the sole application or the co-application of biomass and conditioner, along with their interaction, exhibited an increasing trend for the NH4+-N, available phosphorus (Olsen-P), and available potassium (Kex) contents, also seen in the 0-90 cm soil profile, although the increase effect for the three nutrients was primarily attributed to biochar. Soil conditioner was more effective in increasing SOM and reducing saline in the 0-30 cm soil layer. The application of a higher amount of conditioner accelerated soil nitrification, whereas biochar was applied essentially as a nitrification inhibitor. Therefore, the co-application of biochar with soil conditioner would be an effective practice for improving soil fertility, preventing soil nitrification, and deterring nitrate leaching, as well as reducing saline for topsoil, which would be a basis for developing soil amendments to control saline and a fertile soil environment for pioneer crops planted in coastal barren severe saline-alkali areas.

Co(II)-Based Metal-Organic Framework Derived CA-CoNiMn-CLDHs with Peroxidase-like Activity for Colorimetric Detection of Phenol.

Given the serious harm of toxic phenol to human health and the ecological environment, it is urgent to develop an efficient, low-cost and sensitive nanoenzyme-based method to monitor phenol. MOF-derived nanozyme has attracted wide interest due to its hollow polyhedra structure and porous micro-nano frameworks. However, it is still a great challenge to synthesize MOF-derived multimetal synergistic catalytic nanoenzymes in large quantities with low cost. Herein, we reported the synthetic strategy of porous hollow CA-CoNiMn-CLDHs with ZIF-67 as templates through a facile solvothermal reaction. The prepared trimetallic catalyst exhibits excellent peroxidase-like activity to trigger the oxidative coupling reaction of 4-AAP and phenol in the presence of H2O2. The visual detection platform for phenol based on CA-CoNiMn-CLDHs is constructed, and satisfactory results are obtained. The Km value for CA-CoNiMn-CLDHs (0.21 mM) is lower than that of HRP (0.43 mM) with TMB as the chromogenic substrate. Because of the synergistic effect of peroxidase-like activity and citric acid functionalization, the built colorimetric sensor displayed a good linear response to phenol from 1 to 100 µM with a detection limit of 0.163 µM (3σ/slope). Additionally, the CA-CoNiMn-CLDHs-based visual detection platform possesses high-chemical stability and excellent reusability, which can greatly improve economic benefits in practical applications.

Integrative analysis of metabolome and transcriptome reveals the different metabolite biosynthesis profiles related to palatability in winter and spring shoot in moso bamboo.

Moso bamboo winter shoot has good taste and rich nutritional value. To reveal the causes and regulatory mechanism of palatability deterioration from winter to spring shoot, a conjoint analysis of metabolome and transcriptome was conducted on winter and spring shoots of moso bamboo. Totally 909 metabolites were characterized for the first time. The significant increase of hydrolyzed tannin content intensified the bitterness of spring shoot, which was positively regulated by key metabolite (gallic acid) and genes (DAHPS, DHQS, DHQ, SDH) in the biosynthesis pathway of hydrolyzed tannin. The accumulation of lignified components enhanced the roughness of spring shoot, which was closely connected with the significant changes of important metabolites (cinnamic acid, ferulic acid, UDP-glucose and UDP-xylose) and up-regulation of most enzyme genes involved in the biosynthesis pathways of lignin, cellulose and hemicellulose. The present study provides theoretical support for understanding palatability transition and directional improvement of edible quality of moso bamboo shoots.

The relationship between perfluoroalkyl substances and hypertension: A systematic review and meta-analysis.

Hypertension is an important risk factor for cardiovascular diseases (CVDs) and a leading cause of premature death. Epidemiological studies have found that perfluoroalkyl substances (PFASs) are associated with hypertension. However, the correlation between PFASs and hypertension has not been systematically reported. Based on evidence from population epidemiological surveys, we conducted a meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to assess the correlation between PFASs exposure and hypertension. In this study, three databases of PubMed, Web of science, Embase were searched and 13 literatures with 81,096 participants were included. Literature heterogeneity was evaluated by I2 statistic, and the random effect model (I2 > 50%) and fixed effect model (I2 < 50%) were used to combine the studies in meta-analysis. The results showed that PFNA (OR = 1.11, 95% CI: 1.04-1.19), PFOA (OR = 1.12, 95% CI: 1.02-1.23), PFOS (OR = 1.19, 95% CI: 1.06-1.34) and PFHxS (OR = 1.03, 95% CI: 1.00-1.06) were significantly associated with hypertension, while other types of PFASs (∑PFAS, PFDA, PFUnDA) had no statistical significance. In addition, PFNA (OR = 1.12, 95% CI: 1.03-1.22), PFOA (OR = 1.12, 95% CI: 1.01-1.25) and PFOS (OR = 1.12, 95% CI: 1.00-1.25) exposure were positively correlated with the risk of hypertension in men, but not in women. Our study reveals that PFASs are risk factors for hypertension, with notable gender differences observed in PFASs-exposed populations. Specifically, males exposed to PFNA, PFOA, and PFOS exhibit a higher risk of hypertension compared to females. However, further investigations are needed to delve into the precise mechanism through which PFASs contribute to the development of hypertension.

Glass-Ceramic Coating on Silver Electrode Surface via 3D Printing.

Silver electrodes are commonly used as a conductive layer for electromagnetic devices. It has the advantages of good conductivity, easy processing, and good bonding with a ceramic matrix. However, the low melting point (961 °C) results in a decrease in electrical conductivity and migration of silver ions under an electric field when it works at high temperatures. Using a dense coating layer on the silver surface is a feasible way to effectively prevent the performance fluctuation or failure of the electrodes without sacrificing its wave-transmitting performance. Calcium-magnesium-silicon glass-ceramic (CaMgSi2O6) is a diopside material that has been widely used in electronic packaging materials. However, CaMgSi2O6 glass-ceramics (CMS) are facing tough challenges, such as high sintering temperature and insufficient density after sintering, which significantly confine its applications. In this study, CaO, MgO, B2O3, and SiO2 were used as raw materials to manufacture a uniform glass coating on the silver and Al2O3 ceramics surface via 3D printing technology followed by high-temperature sintering. The dielectric and thermal properties of the glass/ceramic layer prepared with various CaO-MgO-B2O3-SiO2 components were studied, and the protective effect of the glass-ceramic coating on the silver substrate at high temperatures were evaluated. It was found that the viscosity of the paste and the surface density of the coating increase with the increase of solid contents. The 3D-printed coating shows well-bonded interfaces between the Ag layer, the CMS coating, and the Al2O3 substrate. The diffusion depth was 2.5 µm, and no obvious pores and cracks can be detected. According to the high density and well-bonded glass coating, the silver was well protected from the corrosion environment. Increasing the sintering temperature and extending the sintering time is beneficial to form the crystallinity and the densification effect. This study provides an effective method to manufacture a corrosive-resistant coating on an electrically conductive substrate with outstanding dielectric performances.

Role of miR-219a-5p in regulating NMDAR in nonylphenol-induced synaptic plasticity damage.

Nonylphenol (NP) is a typical environmental endocrine disruptor with estrogenic effects. It serves as an emulsifier and as the main ingredient of detergents and has become an increasingly common pollutant in both fresh and salt water, vegetables, and fruits. This study aimed to clarify whether NP exposure could lead to cognitive dysfunction and synaptic plasticity impairment, and also explore the mechanism of microRNA (miR)- 219a-5p regulation of N-methyl-D-aspartate receptor (NMDAR) in NP-induced synaptic plasticity impairment in vivo and in vitro. In vivo, 30 male Sprague-Dawley rats were randomly divided into 2 groups: blank control group (pure corn oil) and NP-exposed group [NP 80 mg/(kg·d)], with 15 rats in each group. In vitro, the extracted hippocampal neurons were divided into 6 groups: blank control group, mimics NC group, miR-219 mimics group, NP group (70 µmol/L NP), NP + mimics NC group, and NP + miR-219 mimics group. In vivo, the content of NP in hippocampal tissues after 90 days of NP exposure was significantly higher in the NP-stained group than in the blank control group. NP exposure could lead to a decrease in the ability to learn and memory, ability to remember, and space spatial memory ability in rats. The dendrites in the NP-stained group were disordered, with few dendritic spines and significantly decreased dendritic spine density. The postsynaptic densities were loosely arranged, the thickness and length of the postsynaptic densities shortened, and the length and width of the synaptic gap increased. Glutamine (Glu) and γ-aminobutyric acid (GABA) contents in hippocampal tissues decreased in the NP-stained group. The expression of miR-219a-5p mRNA decreased in the NP-stained group after 3 months of NP exposure. The expression of NMDAR1, NMDAR2A, NMDAR2B, nerve growth-associated protein (GAP-43), and Ca/calmodulin-dependent kinase II (CaMKII) mRNA/proteins decreased in the NP-stained group. In vitro, NMDAR protein expression decreased, while GAP-43 and CaMKII protein expression increased in the miR-219 mimics group compared with the control group. The expression levels of NMDAR and GAP-43 and CaMKII proteins were higher in the NP + miR-219 mimics group compared with the NP group. The levels of neurotransmitters Glu and GABA decreased in the NP and NP + mimics NC groups compared with the blank group. Shortened synaptic active band length, decreased thickness of postsynaptic densities, and shortened length of postsynaptic densities were observed in the NP, NP + mimics NC, and NP + miR-219 mimics groups compared with the blank control group. In vivo, NP exposure reduced learning memory capacity and neurotransmitter content in rats and caused a decrease in dendritic spine density and synaptic number density and a decrease in miR-219a-5p expression. In vitro, high expression of miR-219a-5p inhibited the expression of NMDAR, thus reducing the effect of NP on synaptic plasticity impairment in hippocampal neurons. Our study provided a scientific basis for the prevention of cognitive impairment owing to NP exposure and the development of targeted drug treatment strategies.

Surface-Treated Recycling Fibers from Wind Turbine Blades as Reinforcement for Waste Phosphogypsum.

An attempt at the treatment of the waste fiber (WF) from the wind turbine blade (WTB) was made through the modifier of dopamine hydrochloride and the compound modifier of dopamine hydrochloride and 2,5-dihydroxy terephthalic acid or 3,4-dihydroxy cinnamic acid or 3,4-dihydroxy benzonitrile, corresponding to obtain four modified waste fibers (MWF1, MWF2, MWF3, and MWF4). The MWFs samples' microstructure properties were characterized using SEM, EDS, XPS, FTIR analyses, and water contact angle tests. The results revealed that all the MWF surfaces were wrapped by a distinct coating layer and had different elemental compositions and chemical groups, demonstrating the significant effect of the four modifications on the WF surfaces. The hydroxyl, amino, or nitrile groups were grafted onto the WF surfaces causing improvement of the hydrophilicity and reactivity. Furthermore, all the MWFs as the reinforced materials were incorporated into the industrial waste phosphogypsum (PG) to manufacture the phosphorous-building gypsum composites (PBGC). The effects on the micro-morphology and mechanical properties of the PBGC were evaluated. The results also show the improvement in flexural and compressive strength with the addition of MWFs into the PBGC, due to the enhancement of the compactness between the MWF and phosphogypsum matrix. In particular, the effects of three compound modifiers on the flexural and compressive strength are more significant. The highest flexural and compressive strength was contributed by the PBGC-MWF4 with 2% dosage using a compound modifier of dopamine hydrochloride and 3,4-dihydroxy benzonitrile, which were enhanced 61.04% and 25.97% compared with the PBG.

ZNF24 regulates the progression of KRAS mutant lung adenocarcinoma by promoting SLC7A5 translation.

Background: Clinical treatment of RAS mutant cancers is challenging because of the complexity of the Ras signaling pathway. SLC7A5 is a newly discovered downstream gene of the Ras signaling pathway, but the regulatory mechanism is unclear. We aimed to explore the molecular mechanism and role in KRAS mutant lung adenocarcinoma progression. Methods: Key gene that regulated SLC7A5 in KRAS mutant lung adenocarcinoma was screened by RNA sequencing and bioinformatics analysis. The effect of this gene on the expression of SLC7A5 was studied by RNAi. The regulatory mechanism between the two genes was investigated by immunofluorescence, CoIP, pulldown and yeast two-hybrid assays. The location of the two genes was determined by inhibiting Ras and the downstream pathways PI3K-AKT and MEK-ERK. By in vivo and in vitro experiments, the effects of the key gene on the biological functions of KRAS mutant lung adenocarcinoma were explored. Results: We found a novel gene, ZNF24, which upregulated SLC7A5 protein expression rather than mRNA expression in KRAS mutant lung adenocarcinoma. Endogenous protein interactions occurred between ZNF24 and SLC7A5. Ras inhibition reduced the expression of ZNF24 and SLC7A5. ZNF24 and SLC7A5 are located downstream of the MEK-ERK and PI3K-AKT pathways. In vivo and in vitro functional experiments confirmed that the ZNF24-SLC7A5 signaling axis promoted the proliferation, invasion and migration of KRAS mutant lung adenocarcinoma. Conclusions: ZNF24 promoted the growth of KRAS mutant lung adenocarcinoma by upregulating SLC7A5 protein expression, which suggested that ZNF24 is a new biomarker of KRAS mutant tumors and could be a new potential therapeutic target for Ras-driven tumors.

Environmental pathways affecting gene expression (E.PAGE) as an R package to predict gene-environment associations.

The purpose of this study is to manually and semi-automatically curate a database and develop an R package that will act as a comprehensive resource to understand how biological processes are dysregulated due to interactions with environmental factors. The initial database search run on the Gene Expression Omnibus and the Molecular Signature Database retrieved a total of 90,018 articles. After title and abstract screening against pre-set criteria, a total of 237 datasets were selected and 522 gene modules were manually annotated. We then curated a database containing four environmental factors, cigarette smoking, diet, infections and toxic chemicals, along with a total of 25,789 genes that had an association with one or more of gene modules. The database and statistical analysis package was then tested with the differentially expressed genes obtained from the published literature related to type 1 diabetes, rheumatoid arthritis, small cell lung cancer, COVID-19, cobalt exposure and smoking. On testing, we uncovered statistically enriched biological processes, which revealed pathways associated with environmental factors and the genes. The curated database and enrichment tool are available as R packages at https://github.com/AhmedMehdiLab/E.PATH and https://github.com/AhmedMehdiLab/E.PAGE respectively.

Nonylphenol induces anxiety-like behavior in rats by regulating BDNF/TrkB/CREB signal network.

This study aimed to verify whether chronic exposure to nonylphenol (NP) induces anxiety behavior in rats and explored NP's regulatory effect on the BDNF/TrkB/CREB signal network in vitro. Anxiety-like behavior was assessed by elevated plus-maze and light-dark box tests. The residence time in the closed arm increased with NP dose (4, 40 mg/kg) and exposure time (3 and 6 months) (P < 0.05). The hippocampal neurons in the medium dose (M-NP, 4 mg/kg) and high dose (H-NP, 40 mg/kg) groups showed disorderly arrangement, cell swelling, and nuclear pyknosis/necrosis. The protein/mRNA expressions of BDNF/TrkB/CREB in the H-NP group decreased, and the decrease was more significant at 6 months (P < 0.05). Both, NP exposure and BDNF knockdown, increase the number of apoptotic cells (P ＜0.001). NP downregulated the proteins/mRNA expressions of BDNF/TrkB/CREB, and the trend was consistent with the BDNF silence group. Chronic exposure to NP could induce anxiety-like behavior in rats and reduce the expression of key proteins/genes in the BDNF/TrkB/CREB signaling network.

BR2 cell penetrating peptide effectively delivers anti-p21Ras scFv to tumor cells with ganglioside expression for therapy of ras-driven tumor.

PURPOSE: Cell membrane penetrating peptide BR2 can bind with ganglioside and introduce foreign drugs into tumor cells. In this study, we employed BR2 to carry the broad-spectrum anti-p21Ras scFv prepared in our laboratory into ganglioside expressing tumor cells for therapy of ras-driven tumors. METHODS: BR2-p21Ras scFv gene was cloned to prokaryotic expression vector and expressed in E. coli BL21, then the fusion protein was purified with HisPur Ni-NTA. The immunoreactivity of the fusion protein with p21Ras was detected by ELISA and western blotting. The membrane-penetrating and immune co-localization with p21Ras of the fusion protein were determined by immunofluorescence. The antitumor activity was investigated using MTT, wound healing, colone formation, and apoptosis assays in vitro. RESULTS: BR2-p21Ras scFv fusion protein was successfully expressed and purified. We found that the fusion protein could specifically penetrate into human tumor cell lines which express ganglioside including human neuroblastoma cell line SK-N-SH, human colon cancer cell line HCT116 and human glioma cell line U251. After entering tumor cells the fusion protein bonded specifically with p21Ras. In vitro experiments revealed that it could significantly inhibit the proliferation, migration, and colone formation of HCT116, SK-N-SH, and U251 cells and promote the apoptosis of these tumor cells. CONCLUSIONS: BR2-p21Ras scFv can penetrate ganglioside expressing tumor cells and inhibit the growth of ras-driven tumor by binding with p21Ras, and producing an inhibitory effect. It is suggested that BR2-p21Ras scFv is a potential ras-driven tumor therapeutic antibody.

Total and Mitochondrial Transcriptomic and Proteomic Insights into Regulation of Bioenergetic Processes for Shoot Fast-Growth Initiation in Moso Bamboo.

As a fast-growing, woody grass plant, Moso bamboo (Phyllostachys edulis) can supply edible shoots, building materials, fibrous raw material, raw materials for crafts and furniture and so on within a relatively short time. Rapid growth of Moso bamboo occurs after the young bamboo shoots are covered with a shell and emerge from the ground. However, the molecular reactions of bioenergetic processes essential for fast growth remain undefined. Herein, total and mitochondrial transcriptomes and proteomes were compared between spring and winter shoots. Numerous key genes and proteins responsible for energy metabolism were significantly upregulated in spring shoots, including those involved in starch and sucrose catabolism, glycolysis, the pentose phosphate pathway, the tricarboxylic acid cycle and oxidative phosphorylation. Accordingly, significant decreases in starch and soluble sugar, higher ATP content and higher rates of respiration and glycolysis were identified in spring shoots. Further, the upregulated genes and proteins related to mitochondrial fission significantly increased the number of mitochondria, indirectly promoting intracellular energy metabolism. Moreover, enhanced alternate-oxidase and uncoupled-protein pathways in winter shoots showed that an efficient energy-dissipating system was important for winter shoots to adapt to the low-temperature environment. Heterologous expression of PeAOX1b in Arabidopsis significantly affected seedling growth and enhanced cold-stress tolerance. Overall, this study highlights the power of comparing total and mitochondrial omics and integrating physiochemical data to understand how bamboo initiates fast growth through modulating bioenergetic processes.

Development of a Novel Nomogram for Predicting Premature Rupture of Membrane in Pregnant Women With Vulvovaginal Candidiasis.

Objective: The aim of this study was to develop a nomogram to predict the risk of premature rupture of membrane (PROM) in pregnant women with vulvovaginal candidiasis (VVC). Patients and methods: We developed a prediction model based on a training dataset of 417 gravidas with VVC, the data were collected from January 2013 to December 2020. The least absolute shrinkage and selection operator regression model was used to optimize feature selection for the model. Multivariable logistic regression analysis was applied to build a prediction model incorporating the feature selected in the least absolute shrinkage and selection operator regression model. Discrimination, calibration, and clinical usefulness of the prediction model were assessed using the C-index, calibration plot, and decision curve analysis. Internal validation was assessed using bootstrapping validation. Results: Predictors contained in the prediction nomogram included age, regular perinatal visits, history of VVC before pregnancy, symptoms with VVC, cured of VVC during pregnancy, and bacterial vaginitis. The model displayed discrimination with a C-index of 0.684 (95% confidence interval: 0.631-0.737). Decision curve analysis showed that the PROM nomogram was clinically useful when intervention was decided at a PROM possibility threshold of 13%. Conclusion: This novel PROM nomogram incorporating age, regular perinatal visits, history of VVC before pregnancy, symptoms with VVC, cured of VVC during pregnancy, and bacterial vaginitis could be conveniently used to facilitate PROM risk prediction in gravidas.

RNA Demethylase FTO Mediated RNA m6A Modification Is Involved in Maintaining Maternal-Fetal Interface in Spontaneous Abortion.

The N6-methyladenosine (m6A) RNA modification regulates the expression of genes associated with various biological and pathological processes, including spontaneous abortion (SA). The aim of this study was to determine the role of the m6A demethylase fat mass and obesity (FTO)- associated protein in SA. The FTO,IGF2BP1 and IGF2BP2 mRNA levels were significantly lower in the chorionic villi obtained from spontaneously aborted pregnancies compared to that of normal pregnancies, while the expression levels of METTL3 and WTAP were significantly elevated. However, ALKBH5, YTHDF2, and IGF2BP3 were elevated with no statistical significance between groups. In addition, MDA was elevated and SOD levels were decreased in the villi tissues of the SA group compared to the normal group, which was indicative of placental oxidative stress in the former. Furthermore, the expression of FTO and HLA-G were significantly decreased in the trophoblasts of the SA patients compared to that of normal pregnant women, while that of m6A was markedly higher in the former. In addition, the HLA-G and VEGFR mRNA levels were downregulated in the SA versus the control group, and that of MMP2, MMP7, MMP9 and VEGFA were upregulated. Finally, The RIP assay showed significantly decreased levels of FTO-bound HLA-G, VEGFR and MMP9 RNA in SA patients (P < 0.05), which corresponded to an increase in transcripts enriched with the m6A antibody (P < 0.05). However, compared with normal pregnant women, the levels of HLA-G, VEGFA, VEGFR, and MMP2 mRNA bound by YTHDF2 were significantly decreased in SA patients. Compared to the normal pregnant women, both FTO- and m6A-bound MMP7 were significantly increased in SA patients (P < 0.05), but YTHDF2 almost unbound to MMP7 mRNA. In summary, the downregulation of FTO in the chorionic villi disrupts immune tolerance and angiogenesis at the maternal-fetal interface, resulting in aberrant methylation and oxidative stress that eventually leads to SA.

Inhibition of glioma by adenovirus KGHV500 encoding anti-p21Ras scFv and carried by cytokine-induced killer cells.

Ras gene mutation or overexpression can lead to tumorigenesis in multiple kinds of cancer, including glioma. However, no drugs targeting Ras or its expression products have been approved for clinical application thus far. Adenoviral gene therapy is a promising method for the treatment of glioma. In this study, the human glioma cell line U251 was co-cultured with recombinant adenovirus KGHV500, and the anti-tumor effects of KGHV500 were determined by MTT, scratch test, Transwell invasion, and apoptosis assays. Then, KGHV500 was delivered via the intravenous injection of CIK cells into glioma xenografts. Tumor volume, ki67 proliferation index, apoptosis levels, and anti-p21Ras scFv expression were tested to evaluate targeting ability, anti-tumor efficacy, and safety. We found that the KGHV500 exhibited anti-tumor activity in U251 cells and increased the intracellular expression of anti-p21Ras scFv compared with that in the control groups. CIK cells delivered KGHV500 to U251 glioma cell xenografts and enhanced anti-tumor activity against glioma xenografts compared to that produced by the control treatment. In conclusion, targeting Ras is a useful therapeutic strategy for gliomas and other Ras-driven cancers, and the delivery of anti-p21Ras scFv by recombinant adenovirus and CIK cells may play an essential role in the therapy of Ras-driven cancers.

Preparation of AgCl Particles with Different Superwettabilities by Particle Size Regulation.

In this work, a simple ammonia evaporation process to obtain AgCl powder with arbitrary superwettability, without introducing any low-surface-free-energy modifier, was investigated. By controlling the recrystallization parameters of the ammonia evaporation process, AgCl crystals precipitated from AgCl-ammonia solution show different wettabilities ranging from superhydrophilicity, via hydrophilicity and hydrophobicity, to superhydrophobicity, with the same chemical composition and structure. Characterization of the obtained AgCl samples with different wettabilities confirms the decisive effect of particle size although light irradiation also causes their wettability transformation.

Colla corii asini might upregulate ZNF471 and THOC5 by KRAB domain-containing zinc-finger protein pathway and THO complex subunit 5 pathway to improve anemia of pregnant women with ß-thalassemia.

Pregnant patients with ß-thalassemia are more likely to have progressive anemia which expose them to risk of adverse pregnancy outcomes, blood transfusion, and iron overload. Results from our previous study indicated that Colla corii asini (CCA, E'jiao), a natural ingredient of traditional Chinese medicine, could significantly increase hemoglobin level of pregnant women with ß- thalassemia, but the underlying molecular mechanism was unclear. Thus, we applied high-throughput transcriptome sequencing to study the transcriptomic change before and after the CCA treatment. Twenty eligible pregnant women were recruited and randomized to either the CCA treatment group or the blank control group in a 3:1 ratio. Patients in the treatment group orally received daily 15 g CCA powder for 4 weeks. We analyzed the therapeutic effect indexes and the transcriptomic change in subjects' peripheral blood before and after treatment. We found that ß CD 41-42(-TTCT)/ßA was the main genotype of the subjects. The regulatory impact of CCA treatment became more evident among the subjects of genotype ß CD 41-42(-TTCT)/ßA. Gene ontogenesis analysis revealed that the top five molecular functions of differentially expressed genes were involved in membrane functionality and cellular structure. We further identified two consistent upregulated genes ZNF471 and THOC5 in the effective treatment group, which were engaged in Kruppel-associated box (KRAB) domain-containing zinc-finger protein pathway and THOC5 pathway, respectively. Based on our current findings, we hypothesize that the anti-anemia effect of CCA on pregnant women with ß-thalassemia might be related to translation regulation of spectrin synthesis, membrane stability, and eventually prolonged the life span of erythrocytes.