Search

Objectives: To explore the associations of parental smoking and alcohol consumption during the periconceptional period and their interactions with risk of congenital heart disease (CHD) in offspring., Methods: The parents of children with simple CHD aged 0 to 1 year ( n =683) were recruited as the case group, while the parents of healthy children aged 0 to 1 year ( n =740) served as the control group. A case-control study was conducted, and a questionnaire was used to collect information on perinatal exposures. After controlling for relevant confounding factors using multivariate logistic regression analysis and propensity score matching, the associations of parental smoking and alcohol consumption during the periconceptional period and their interactions with CHD were examined, as well as the cumulative effects of smoking and drinking on CHD risk., Results: Maternal active smoking ( OR =2.91, 95% CI : 1.60-5.30), passive smoking ( OR =1.94, 95% CI : 1.56-2.42), and alcohol consumption ( OR =2.59, 95% CI : 1.89-3.54), as well as paternal smoking ( OR =1.52; 95% CI : 1.22-1.90) and drinking ( OR =1.48, 95% CI : 1.19-1.84), were associated with an increased risk of CHD in offspring. There was no interaction between parental smoking and drinking behaviors during the periconceptional period concerning the risk of CHD in offspring ( P >0.05). The more parents' smoking and drinking behaviors during the perinatal pregnancy, the higher the risk of CHD in their offspring ( OR =1.50, 95% CI : 1.36-1.65)., Conclusions: Parental smoking and alcohol consumption during the periconceptional period are associated with the occurrence of CHD in offspring, and there is a cumulative effect on CHD risk, suggesting that reducing tobacco and alcohol exposure during the periconceptional period may lower the incidence of CHD.

Objectives: To investigate how maternal MTR gene polymorphisms and their interactions with periconceptional folic acid supplementation are associated with the incidence of ventricular septal defects (VSD) in offspring., Methods: A case-control study was conducted, recruiting 426 mothers of infants with VSD under one year old and 740 mothers of age-matched healthy infants. A questionnaire survey collected data on maternal exposures, and blood samples were analyzed for genetic polymorphisms. Multivariable logistic regression analysis and inverse probability of treatment weighting were used to analyze the associations between genetic loci and VSD. Crossover analysis and logistic regression were utilized to examine the additive and multiplicative interactions between the loci and folic acid intake., Results: The CT and TT genotypes of the maternal MTR gene at rs6668344 increased the susceptibility of offspring to VSD ( P <0.05). The GC and CC genotypes at rs3768139, AG and GG at rs1050993, AT and TT at rs4659743, GG at rs3768142, and GT and TT at rs3820571 were associated with a decreased risk of VSD ( P <0.05). The variations at rs6668344 demonstrated an antagonistic multiplicative interaction with folic acid supplementation in relation to VSD ( P <0.05)., Conclusions: Maternal MTR gene polymorphisms significantly correlate with the incidence of VSD in offspring. Mothers with variations at rs6668344 can decrease the susceptibility to VSD in their offspring by supplementing with folic acid during the periconceptional period, suggesting the importance of periconceptional folic acid supplementation in genetically at-risk populations to prevent VSD in offspring.

Converting CO 2 into value-added products containing B-C bonds is a great challenge, especially for multiple B-C bonds, which are versatile building blocks for organoborane chemistry. In the condensed phase, the B-C bond is typically formed through transition metal-catalyzed direct borylation of hydrocarbons via C-H bond activation or transition metal-catalyzed insertion of carbenes into B-H bonds. However, excessive amounts of powerful boryl reagents are required, and products containing B-C bonds are complex. Herein, a novel method to construct multiple B-C bonds at room temperature is proposed by the gas-phase reactions of CO 2 with LaB m O n - ( m = 1-4, n = 1 or 2). Mass spectrometry and density functional theory calculations are applied to investigate these reactions, and a series of new compounds, CB 2 O 2 - , CB 3 O 3 - , and CB 3 O 2 - , which possess B-C bonds, are generated in the reactions of LaB 3,4 O 2 - with CO 2 . When the number of B atoms in the clusters is reduced to 2 or 1, there is only CO-releasing channel, and no CB x O y - compounds are released. Two major factors are responsible for this quite intriguing reactivity: (1) Synergy of electron transfer and boron-boron Lewis acid-base pair mechanisms facilitates the rupture of C═O double bond in CO 2 . (2) The boron sites in the clusters can efficiently capture the newly formed CO units in the course of reactions, favoring the formation of B-C bonds. This finding may provide fundamental insights into the CO 2 transformation driven by clusters containing lanthanide atoms and how to efficiently build B-C bonds under room temperature.

Several observational studies have found that exposure to sunlight reduces the risk of colorectal cancer (CRC). However, sun exposure remains ambiguous in its relationship to CRC. We carried out a Mendelian randomization (MR) study to explore the potential associations between them. We examined the exposure to sunlight summary statistics of the UK Biobank Consortium using a 2-sample MR analysis. Using data from the FinnGen consortium, we derived summary statistics for CRC. We conducted our analysis with various methods, incorporating inverse variance weighted (IVW) along with 4 other approaches. A Cochran Q statistic was used to measure the heterogeneity of instrumental variables (IVs). We screened 133 single nucleotide polymorphisms (SNPs) (time spent outdoors in summer), 41 SNPs (time spent outdoors in winter), and 35 SNPs (frequency of solarium/sunlamp use) representing sunlight exposure for MR analysis. All selected SNPs had an F-statistic >20, indicating that IVs did not weakly bias the results. The summer outdoor activity trait exhibited significant heterogeneity (Cochran Q statistic = 183.795, P = .002 < 0.05), but we found no horizontal polymorphisms or significant heterogeneity for the other exposure traits. According to IVW estimates, no causal association exists between time spent outdoors in summer and CRC (Odds Ratio, OR = 0.735, 95% confidence interval, CI = 0.494-1.017, P = .128 > 0.017). No causal relationship existed between time spent outdoors in winter and CRC, as indicated by Bonferroni-corrected adjusted p-values. The OR was 0.877 with a 95% CI of 0.334-2.299, and the P value was .789, more significant than the significance threshold of 0.017. The solarium/sunlamp use frequency was not associated with CRC (OR = 1.567, 95%CI = 0.243-10.119, P = .637 > .017). Also, an IVW with random effects was applied to determine the causal relationship between summer outdoor time and CRC. No causal association between summer outdoor time and CRC was found (OR = 0.735, 95% CI = 0.494-1.017, P = .128 > .017). Additionally, 4 additional analyses yielded similar results. The findings of our study suggest that exposure to sunlight may reduce CRC risk, but the causal relationship remains unsolved. There is no evidence to suggest that exposure to sunlight prevents CRC. Randomized, controlled trials are needed to determine whether sunlight exposure protects against CRC., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Studying the cleavage of the C═O bond during CO 2 activation at room temperature is highly significant for comprehending the CO 2 conversion processes. Herein, mass spectrometry experiments and density functional theory calculations indicate that the niobium carbide anions Nb 3 C 4 - can continuously convert five CO 2 molecules to CO under thermal collision conditions, while the other clusters with less carbon ligands Nb 3 C 1-3 - reduce fewer CO 2 molecules. Size-dependent reactivity of Nb 3 C 1-4 - cluster anions toward CO 2 is observed. Interestingly, the carbon atoms in Nb 3 C 4 - not only act as highly active adsorption sites for CO 2 but also serve as electron donors to reduce CO 2 . The stored electrons are released through a carbon-carbon coupling process. Our findings on the role of carbon ligands in enhancing transition metal carbide reactivity can offer new insights for designing active sites on catalysts with both high activity and selectivity.

In 2022, American Urological Association updated the guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). A significant change has been made in treatment recommendations. The updated guideline no longer divided treatments into first-line through sixth-line tiers. Instead, treatment is categorized into behavioral/non-pharmacologic, oral medicines, bladder instillations, procedures, and major surgery. This change emphasizes the heterogeneity of IC/BPS patients and the importance of individualized treatment, overturns traditional unreasonable ideas about hierarchical and progressive treatment, and encourages patients and physicians to make treatment decisions together. At the same time, the panel emphasized the importance of early implementation of cystoscopy in patients suspected of Hunner lesions and warned against the possibility of pentosan polysulfate causing a unique retinal pigmentary maculopathy. Urinary reconstruction surgery was considered to only be used as a last resort for the treatment of IC/BPS, and there is uncertainty about the overall balance between benefits and risks/burdens. The updated guideline provides a new understanding and decision-making basis for the diagnosis and treatment of IC/BPS. However, it should be noted that the clinical characteristics of Chinese patients should be considered in practice and the application of the guideline should be localized.

Three new diterpenoids, named nematocynine A-C (1-3), together with twelve known compounds (4-15) were isolated from the aerial part of Euphorbia nematocypha Hand.-Mazz (Hereinafter referred to E. nematocypha ). Their structures were elucidated by detailed spectroscopic analysis and comparison with literature data. In addition, all the compounds were tested for their anti- candida albicans activities used alone or in combination with fluconazole against sensitive strain and resistant strain in vitro . Wherein only compound 11 shows weak activity against candida albicans resistant strain (MIC 50 = 128.15 μg/mL) when used alone. Compounds 1 , 4 , 7 , 8 , 9 , 10 , 12 , 13 and 15 in combination with fluconazole showed potent anti-fungal activities (MIC 50  = 15 ± 5 μg/mL, FICI = 0.05 ± 0.04) against the Candida albicans resistant strain SC5314-FR. The synergistic effects were weaker against the Candida albicans resistant strain SC5314-FR when the compounds 2, 3, 5 and 14 were combined with fluconazole (FICI = 0.16 ± 0.06).

N 2 adsorption is a prerequisite for activation and transformation. Time-of-flight mass spectrometry experiments show that the Nb 2 C 6 H 4 + cation, resulting from the gas-phase reaction of Nb 2 + with C 6 H 6 , is more favorable for N 2 adsorption than Nb + and Nb 2 + cations. Density functional theory calculations reveal the effect of the ortho -C 6 H 4 ligand on N 2 adsorption. In Nb 2 C 6 H 4 + , interactions between the Nb-4d and C-2p orbitals enable the Nb 2 + cation to form coordination bonds with the ortho -C 6 H 4 ligand. Although the ortho -C 6 H 4 ligand in Nb 2 C 6 H 4 + is not directly involved in the reaction, its presence increases the polarity of the cluster and brings the highest occupied molecular orbital (HOMO) closer to the lowest occupied molecular orbital (LUMO) of N 2 , thereby increasing the N 2 adsorption energy, which effectively facilitates N 2 adsorption and activation. This study provides fundamental insights into the mechanisms of N 2 adsorption in "transition metal-organic ligand" systems.

Traditional medicines are becoming more popular as people become more aware of the dangers of synthetic pharmaceuticals. Tribulus terrestris L., (Gokharu) an annual herbaceous plant, has been extensively utilized by herbalists for numerous medicinal purposes. T. terrestris has been studied for its multiple therapeutic effects, including immunomodulatory, aphrodisiac, anti-urolithic, absorption enhancer, cardioprotective, antidiabetic, anti-inflammatory, hypolipidemic, neuro-protective, anticancer, and analgesic properties. Saponins and flavonoids are two examples of beneficial substances that have recently been found in T. terrestris . These chemicals are very important for a variety of therapeutic effects. Numerous studies have shown that T. terrestris products and various parts may have antioxidant, anti-inflammatory, anti-cancer, anti-diabetic, testosterone-boosting, and liver protective effects. According to the published evidence, T. terrestris boosts testosterone secretion, regulates blood pressure, and protects the human body against injuries. The cardiovascular, reproductive, and urinary systems are all severely impacted. Due to its potent bioactive compounds, the literature evaluated from a wide range of sources including books, reports, PubMed, ScienceDirect, Wiley, Springer, and other databases demonstrated the extraordinary potential to treat numerous human and animal ailments. Our review is different from other published articles because we explored its importance for humans and especially in veterinary like poultry health. It could also be used as an aphrodisiac to treat different fertility-related disorders in human and animal science. More research into the pharmacodynamics of herbs like T. terrestris is needed so that it can be used in a wider variety of nutraceutical products for humans and poultry., Competing Interests: The author declared that they have no conflict of interest., (© 2024 Published by Elsevier Ltd.)

The cleavage of inert C-H bonds in methane at room temperature and the subsequent conversion into value-added products are quite challenging. Herein, the reactivity of boron-doped cobalt oxide cluster cations CoBO 2 + toward methane under thermal collision conditions was studied by mass spectrometry experiments and quantum-chemical calculations. In this reaction, one H atom and the CH 3 unit of methane were transformed separately to generate the product metaboric acid (HBO 2 ) and one CoCH 3 + ion, respectively. Theoretical calculations strongly suggest that a catalytic cycle can be completed by the recovery of CoBO 2 + through the reaction of CoCH 3 + with sodium perborate (NaBO 3 ), and this reaction generates sodium methoxide (CH 3 ONa) as the other value-added product. This study shows that boron-doped cobalt oxide species are highly reactive to facilitate thermal methane transformation and may open a way to develop more effective approaches for methane (CH 4 ) activation and conversion under mild conditions.

Nitrogen (N 2 ) activation at room temperature has long been a great challenge. Therefore, the rational design of reactive species to adsorb N 2 , which is a prerequisite for cleavage of the strong N≡N triple bond in industrial and biological processes, is highly desirable and meaningful. Herein, the N 2 adsorption process is controlled by regulating the types and numbers of organic ligands, and the organic ligands are produced through the reactions of Ir + with methane and ethane. CH 4 molecules dissociate on the Ir + cations to form Ir(CH 2 ) 1,2 + . The reaction of Ir + with C 2 H 6 can generate HIrC 2 H 3 + , which is different from the structure of Ir(CH 2 ) 2 + obtained from Ir + /CH 4 . The reactivity order of N 2 adsorption is Ir(CH 2 ) 2 + > HIrC 2 H 3 + ≫ HIrCH + ≈ Ir + (almost inert under similar reaction conditions), indicating that different organic ligand structures affect reactivity dramatically. The main reason for this interesting reactivity difference is that the lowest unoccupied molecular orbital (LUMO) level of Ir(CH 2 ) 2 + is much closer to the highest occupied molecular orbital (HOMO) level of N 2 than those of the other three systems. This study provides new insights into the adsorption of N 2 on metal-organic ligand species, in which the organic ligand dominates the reactivity, and it discovers new clues in designing effective transition metal carbine species for N 2 activation.

Purpose: This study aimed to investigate the efficacy and safety of ultrasound-guided percutaneous radiofrequency ablation (RFA) for the treatment of synovial hyperplasia in the knee joints of antigen-induced arthritis (AIA) model rabbits., Methods: Forty Japanese large-eared white rabbits were divided into AIA and control groups. After successful induction of the AIA model, the knee joints were randomly assigned to RFA and non-RFA groups. The RFA group underwent ultrasound-guided RFA to treat synovial hyperplasia in the knee joint. Dynamic observation of various detection indices was conducted to evaluate the safety and effectiveness of the RFA procedure., Results: Successful synovial ablation was achieved in the RFA group, with no intraoperative or perioperative mortality. Postoperative the circumference of the knee joint reached a peak before decreasing in the third week after surgery. The incidence and diameter of postoperative skin ulcers were not significantly different compared to the non-RFA group ( p  > .05). Anatomical examination revealed an intact intermuscular fascia around the ablated area in the RFA group. The ablated synovial tissue initially presented as a white mass, which subsequently liquefied into a milky white viscous fluid. Gross articular cartilage was observed, along with liquefied necrosis of the synovium on pathological histology and infiltration of inflammatory cells in the surrounding soft tissue., Conclusion: The experimental results demonstrated that ultrasound-guided RFA of the knee in the treatment of synovial hyperplasia in AIA model animals was both effective and safe.

Dinitrogen (N 2 ) activation and its chemical transformations are some of the most challenging topics in chemistry. Herein, we report that heteronuclear metal anions AuNbBO - can mediate the direct coupling of N 2 and O 2 to generate NO molecules. N 2 first forms the nondissociative adsorption product AuNbBON 2 - on AuNbBO - . In the following reactions with two O 2 molecules, two NO molecules are gradually released, with the formation of AuNbBO 2 N - and AuNbBO 3 - . In the reaction with the first O 2 , the generated nitrene radical (N ••- ) originating from the dissociated N 2 , induces the activation of O 2 . Subsequently, the second O 2 is anchored and forms a superoxide radical (O 2 •- ); this radical attacks the other N atom to form an N-O bond, releasing the second NO. The N ••- and O 2 •- radicals play key roles in the reactions. The mechanism adopted in this direct oxidation of N 2 by O 2 to NO can be labeled as a Zeldovich-like mechanism.

Fourteen undescribed seco-type diterpenoids, named nudifloids A-N, together with ten known analogs, were isolated from the leaves of Callicarpa nudiflora. Nudifloids A-N had a characteristic 3,4-seco-labdane-type diterpenoid skeleton, whereas nudifloids A-C and K-N were 3,4-seco-norditerpenoids. Nudifloid A was the first example of a 3,4-seco-12,13,14,15,16-quartnor-labdane diterpenoid, with a seven-membered lactone ring formed through esterification between C-3 and C-11. Nudifloids B and C were a pair of highly modified 3,4-seco-labdane nor-diterpenoid epimers, of which C-2 and C-18 were cyclized together to form a cyclohexene fragment. The structures of these undescribed diterpenoids were established by spectroscopic analysis and reference data. The anti-inflammatory activity of diterpenoids in rich yield was evaluated by analyzing the inhibition of lipopolysaccharide plus nigericin-induced pyroptosis in J774A.1 cells. Nudifloids D and E exhibited prominent anti-NLRP3 inflammasome activity, with IC 50 values of 1.80 and 1.59 μM, respectively. Cell permeability assays revealed that nudifloid D inhibited pyroptosis, which could ameliorate inflammation by blocking the activation of the NLRP3 inflammasome., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The direct coupling of dinitrogen (N 2 ) and oxygen (O 2 ) to produce value-added chemicals such as nitric acid (HNO 3 ) at room temperature is fascinating but quite challenging because of the inertness of N 2 molecules. Herein, an interesting reaction pathway is proposed for a direct conversion of N 2 and O 2 mediated by all-metal Y 3 + cations. This reaction pattern begins with the N≡N triple bond cleavage by Y 3 + to generate a dinitride cation Y 2 N 2 + , and the electrons that lead to N 2 activation in this process mainly originate from Y atoms. In the following consecutive reactions with two O 2 molecules, the electrons stored in the N atoms are gradually released to reduce O 2 through re-formation and re-fracture of the N-N bonds, with concomitant release of two NO molecules. Therefore, the reversible N-N bond switching acts as an efficient electron reservoir to drive the oxidation of the reduced N atoms, leading to the formation of NO molecules. This method of producing NO by direct coupling N 2 and O 2 molecules, which is the reversible N-N bond switching, may provide a new strategy for the direct synthesis of HNO 3 , etc.

Compared with transition metals, nonmetallic elements have always been considered to have low reactivity toward carbon dioxide. However, in recent years, main-group compounds such as boron-based species have gradually attracted increasing attention due to their prospective applications in different kinds of reactions. Herein, we report that metal-free anions B 2 O 2 - can promote two CO 2 reductions, producing the oxygen-rich product B 2 O 4 - . In most of the reported CO 2 reduction reactions mediated by transition-metal-containing clusters, transition metals usually provide electrons for the activation of CO 2 ; one oxygen atom in CO 2 is transferred to metal atoms, and CO is released from the metal atoms. In sharp contrast, B atoms are electron donors in the current systems and the formed CO is liberated directly from the activated CO 2 unit. The synthesis of novel-metal-free gas-phase clusters and investigation of their reactivity toward carbon dioxide as well as reaction mechanisms can provide a fundamental basis in practice for the rational design of active sites on metal-free catalysts.

A pair of new oxindole alkaloids, named macrophyllines C ( 1 ) and D ( 2 ), together with two known oxindole alkaloids isorhynchophylline ( 3 ) and corynoxine ( 4 ) were isolated from Uncaria macrophylla . Their structures were elucidated based on detailed spectroscopic analysis and by comparison with literature data. In addition, all the isolates were tested for their anti-HIV activities and cytotoxicities in C8166 cells and compounds 2-4 showed weak anti-HIV activities with EC 50 values of 11.31 ± 3.29 μM, 18.77 ± 6.14 μM and 30.02 ± 3.73 μM, respectively.

The conversion of dinitrogen to more useful and reactive molecules has been the focus of intense research by chemists. In contrast to reductive N 2 fixation, direct oxidation of N 2 by O 2 to nitric oxide under mild conditions via a thermochemical process is extremely challenging. Herein, we report the first example of N 2 and O 2 activation and coupling under thermochemical conditions through the remarkable ability of Y 2 BO + to react with one N 2 and two O 2 molecules. Detailed mechanistic studies using mass spectrometry and quantum chemical calculations revealed that the N 2 activation by Y 2 BO + is facilitated by the double aromatic character of the Y 2 BON 2 + intermediate. Subsequent oxidation with O 2 releases NO in a dearomatization process driven by the formation of stronger Y-O bonds over the Y-N bonds. Our findings represent the first example of N 2 and O 2 activation and coupling under thermochemical conditions at room temperature, providing a novel strategy for small-molecule activation.

Transition-metal catalyzed coupling to form C-N bonds is significant in chemical science. However, the inert nature of N 2 and CO 2 renders their coupling quite challenging. Herein, we report the activation of dinitrogen in the mild plasma atmosphere by the gas-phase monometallic YB 1-4 - anions and further coupling of CO 2 to form C-N bonds by using mass spectrometry and theoretical calculation. The observed product anions are NCNBO - and N(BO) 2 - , accompanied by the formation of neutral products YO and YB 0-2 NC, respectively. We can tune the reactivity and the type of products by manipulating the number of B atoms. The B atoms in YB 1-4 N 2 - act as electron donors in CO 2 reduction reactions, and the carbon atom originating from CO 2 serves as an electron reservoir. This is the first example of gas-phase monometallic anions, which are capable to realize the functionalization of N 2 with CO 2 through C-N bond formation and N-N and C-O bond cleavage., (© 2022 Wiley-VCH GmbH.)

To simulate the ADME process such as absorption, distribution, metabolism, and excretion in the human body after drug administration and to confirm the applicability of the mass production process, a microfluidic chip injection molded with polycarbonate (injection-molded chip (I-M chip)) was fabricated. Polycarbonate materials were selected to minimize drug absorption. As a first step to evaluate the I-M chip, RPTEC (Human Renal Proximal Tubule Epithelial Cells) and HUVEC (Human Umbilical Vein Endothelial Cells) were co-cultured, and live and dead staining, TEER (trans-epithelial electrical resistance), glucose reabsorption, and permeability were compared using different membrane pore sizes of 0.4 μm and 3 μm. Drug excretion was confirmed through a pharmacokinetic test with metformin and cimetidine, and the gene expression of drug transporters was confirmed. As a result, it was confirmed that the cell viability was higher in the 3 μm pore size than in the 0.4 μm, the cell culture performed better, and the drug secretion was enhanced when the pore size was large. The injection-molded polycarbonate microfluidic chip is anticipated to be commercially viable for drug screening devices, particularly ADME tests.

DNA damage repair (DDR) is essential for maintaining genome integrity and modulating cancer risk, progression, and therapeutic response. DDR defects are common among non-small lung cancer (NSCLC), resulting in new challenge and promise for NSCLC treatment. Thus, a thorough understanding of the molecular characteristics of DDR in NSCLC is helpful for NSCLC treatment and management. Here, we systematically analyzed the relationship between DDR alterations and NSCLC prognosis, and successfully established and validated a six-DDR gene prognostic model via LASSO Cox regression analysis based on the expression of prognostic related DDR genes, CDC25C , NEIL3 , H2AFX , NBN , XRCC5 , RAD1 . According to this model, NSCLC patients were classified into high-risk subtype and low-risk subtype, each of which has significant differences between the two subtypes in clinical features, molecular features, immune cell components, gene mutations, DDR pathway activation status and clinical outcomes. The high-risk patients was characterized with worse prognosis, lower proportion and number of DDR mutations, unique immune profile and responsive to immunetherapy. And the low-risk patients tend to have superior survival, while being less responsive to immunotherapy and more sensitive to treatment with DNA-damaging chemotherapy drugs. Overall, this molecular classification based on DDR expression profile enables hierarchical management of patients and personalized clinical treatment, and provides potential therapeutic targets for NSCLC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Zou, Zhao, Liang, She, Zhou, Lin, Tian, Luo and He.)

Ten new prenylated flavonoids, named denticulains A-J (1-10), together with seven known prenylated flavonoids (11-17) were isolated from Macaranga denticulata. Their structures were elucidated on the basis of detailed spectroscopic analysis and by comparison with literature data. In addition, compounds 1 and 14 inhibited the proliferation of SW620 and HCT-116 cell lines with an IC 50 value of 46.08 μM and 56.83 μM, respectively., Competing Interests: Declaration of Competing Interest The authors have declared that there is no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

Since ancient times, the Cucurbitaceae family is used as a therapeutic option in human medicine. This family has around 130 genera and 800 species. Researchers have studied the various plants of this family including Lagenaria siceraria due to their medicinal potential. Various properties are beneficial for human health, that have been attributed to L. siceraria like antioxidant, hypolipidemic, diuretic, laxative, hepatoprotective, analgesic, antihypertensive, cardioprotective, central nervous system stimulant, anthelmintic, free radical scavenging, immunosuppressive, and adaptogenic. The fruit of this plant is commonly used as a vegetable that has a low-calorie value. The species possess a diverse set of biological compounds like flavonoids, sterols, saponins, and terpenoids. Vitamins, choline, flavonoids, minerals, proteins, terpenoids, and other phytochemicals are also found in the edible parts of this plant. Besides 17 different amino acids, many minerals are reported to be present in the seeds of L. siceraria . According to the USDA nutritional database per 100 g of L. siceraria contains 14 Kcal energy, 3.39 g carbohydrates, 0.62 g protein, 0.2 g fat, and 0.5 g fiber. L. siceraria performs a wide range of pharmacological and physiological actions. The literature reviewed from various sources including PubMed, Science Direct, Google scholar, etc. shows the remarkable potential to treat various human and animal illnesses due to its' potent bioactive chemicals. The key objective of this thorough analysis is to present a summary of the data about the beneficial and harmful effects of L. siceraria intake on human health, as well as in veterinary fields., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Saeed, Khan, Amir, Bi, Asif, Madni, Kamboh, Manzoor, Younas and Chao.)

Objectives: To study the association of maternal methylenetetrahydrofolate dehydrogenase 1 ( MTHFD1 ) and methylenetetrahydrofolate dehydrogenase 2 ( MTHFD2 ) gene polymorphisms with congenital heart disease (CHD) in offspring., Methods: A hospital-based case-control study was conducted. The mothers of 683 children with CHD alone who attended Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group, and the mothers of 740 healthy children who attended the same hospital during the same period and did not have any deformity were enrolled as the control group. A questionnaire survey was performed to collect related exposure data, and then venous blood samples (5 mL) were collected from the mothers to detect MTHFD1 and MTHFD2 gene polymorphisms. A multivariate logistic regression analysis was used to evaluate the association of MTHFD1 and MTHFD2 gene polymorphisms with CHD. The four-gamete test in Haploview 4.2 software was used to construct haplotypes and evaluate the association between haplotypes and CHD. The generalized multifactor dimensionality reduction method and logistic regression analysis were used to examine gene-gene interaction and its association with CHD., Results: The multivariate logistic regression analysis showed that maternal MTHFD1 gene polymorphisms at rs11849530 (GA vs AA: OR =1.49; GG vs AA: OR =2.04) andat rs1256142 (GA vs GG: OR =2.34; AA vs GG: OR =3.25) significantly increased the risk of CHD in offspring ( P <0.05), while maternal MTHFD1 gene polymorphisms at rs1950902 (AA vs GG: OR =0.57) and MTHFD2 gene polymorphisms at rs1095966 (CA vs CC: OR =0.68) significantly reduced the risk of CHD in offspring ( P <0.05). The haplotypes of G-G-G ( OR =1.86) and G-A-G ( OR =1.35) in mothers significantly increased the risk of CHD in offspring ( P <0.05). The gene-gene interaction analyses showed that the first-order interaction between MTHFD1 rs1950902 and MTHFD1 rs2236222 and the second-order interaction involving MTHFD1 rs1950902, MTHFD1 rs1256142, and MTHFD2 rs1095966 might be associated with risk of CHD ( P <0.05)., Conclusions: Maternal MTHFD1 and MTHFD2 gene polymorphisms and their haplotypes, as well as the interaction between MTHFD1 rs1950902 and MTHFD1 rs2236222 and between MTHFD1 rs1950902, MTHFD1 rs1256142, and MTHFD2 rs1095966, are associated with the risk of CHD in offspring.

The adsorption of atmospheric dinitrogen (N 2 ) on transition metal sites is an important topic in chemistry, which is regarded as the prerequisite for the activation of robust N≡N bonds in biological and industrial fields. Metal hydride bonds play an important part in the adsorption of N 2 , while the role of hydrogen has not been comprehensively studied. Herein, we report the N 2 adsorption on the well-defined Y 2 C 4 H 0,1 - cluster anions under mild conditions by using mass spectrometry and density functional theory calculations. The mass spectrometry results reveal that the reactivity of N 2 adsorption on Y 2 C 4 H - is 50 times higher than that on Y 2 C 4 - clusters. Further analysis reveals the important role of the H atom: (1) the presence of the H atom modifies the charge distribution of the Y 2 C 4 H - anion; (2) the approach of N 2 to Y 2 C 4 H - is more favorable kinetically compared to that to Y 2 C 4 - ; and (3) a natural charge analysis shows that two Y atoms and one Y atom are the major electron donors in the Y 2 C 4 - and Y 2 C 4 H - anion clusters, respectively. This work provides new clues to the rational design of TM-based catalysts by efficiently doping hydrogen atoms to modulate the reactivity towards N 2 .

The activation and functionalization of dinitrogen with carbon dioxide into useful chemicals containing C-N bonds are significant research projects but highly challenging. Herein, we report that N 2 molecules are dissociated by heterobimetallic CuNb - anions assisted by surface plasma radiation, leading to the formation of CuNbN 2 - anions; the CuNbN 2 - anions can further react with CO 2 to generate products NCO - with one C-N bond and NbO 2 NCN - with two C-N bonds under thermal collision conditions. For the activation of dinitrogen, the plasma atmosphere is conducive to the dissociation of the NN bond, which renders the coupling reactions of N 2 and CO 2 molecules easier to proceed. This is the first report of coupling of N 2 and CO 2 to generate C-N bonds by making good use of the plasma effect to assist in the activation of N 2 molecules. This new strategy with the assistance of plasma provides a practicable route to construct C-N bonds by directly using N 2 and CO 2 at room temperature.

Nitrogen fixation and hydrogenation are important issues in chemistry and industry. Herein, we used mass spectrometry and quantum chemical calculations to identify the quaternary AuNbBO - anions that can efficiently activate N 2 and H 2 to form imido (or amido) units in the products AuNbBON 2 H 2 - under thermal collision conditions. In these reactions, Nb and B atoms work in synergy to dissociate N 2 and the Au atom acts as a reducing agent, which facilitates the removal of one activated N atom for the following hydrogenation process; generation of three-centered, two-electron bonds facilitates N 2 activation and N transformation. This study shows that the noble metal-assisted early transition metal boronyl cluster is highly reactive to facilitate thermal N-N and H-H bond cleavage, and NH (or NH 2 ) and NBO units, which are important intermediates in N 2 hydrogenation reactions, are formed. These findings may provide insight into the design of new catalysts for the synthesis of NH 3 from N 2 and H 2 .

Alkali atoms are usually used as promoters to significantly increase the catalytic activity of transition-metal catalysts in a wide range of reactions such as dinitrogen conversion reactions. However, the role of alkali metal atoms remains controversial. Herein, a series of quaternary cluster anions containing lithium atoms Nb 2 LiNO 1-4 - have been synthesized and reacted with N 2 at room temperature. The detailed experimental and theoretical investigations indicate that Nb 2 LiNO - is capable to cleave the N≡N bond and the Li atoms in Nb 2 LiNO 1,2 - act as electron donors in the N 2 reduction reaction. With the increase in the number of oxygen atoms, the reactivity toward N 2 is reduced from adsorption via a side-on end-on mode in Nb 2 LiNO 2 - to the inertness of Nb 2 LiNO 4 - . In Nb 2 LiNO 3,4 - anions, the Li atoms are bonded with oxygen atoms, acting as structural units to stabilize structures. Therefore, the roles of alkali atoms are able to change with different chemical environments of active sites. For the first time, we reveal how the number of ligands (oxygen atoms herein) can be used to finely regulate the reactivity toward N 2 .

Coupling conversion of CO 2 and N 2 molecules under mild conditions to form useful N-C bond-containing products has attracted significant attention. However, the activation and direct coupling of such very inert molecules are quite challenging. Herein, we determined that this coupling reaction can be realized by AuNbBO - quaternary anions at room temperature. The well-defined AuNbBO - anions can cleave the N≡N bond in N 2 and two C═O bonds in CO 2 to form a novel product NCNBO - . To the best of our knowledge, the NCNBO - anion has been experimentally synthesized for the first time by coupling N 2 and CO 2 . Comparative studies with Nb 2 BO - /N 2 and NbBO - /N 2 systems further indicate that the presence of a Au atom in AuNbBO - is indispensable for this N 2 and CO 2 coupling reaction, because the Au atom can decrease the active orbital energies of AuNbBO - anions to facilitate the π-back-donating interaction between AuNbBO - and N 2 .

Objective: This study aimed to assess the associations between maternal drug use, cytochrome P450 ( CYP450 ) genetic polymorphisms, and their interactions with the risk of congenital heart defects (CHDs) in offspring., Methods: A case-control study involving 569 mothers of CHD cases and 652 controls was conducted from November 2017 to January 2020., Results: After adjusting for potential confounding factors, the results show that mothers who used ovulatory drugs (adjusted odds ratio [a OR ] = 2.12; 95% confidence interval [ CI ]: 1.08-4.16), antidepressants (a OR = 2.56; 95% CI : 1.36-4.82), antiabortifacients (a OR = 1.55; 95% CI : 1.00-2.40), or traditional Chinese drugs (a OR = 1.97; 95% CI : 1.26-3.09) during pregnancy were at a significantly higher risk of CHDs in offspring. Maternal CYP450 genetic polymorphisms at rs1065852 (A/T vs . A/A: OR = 1.53, 95% CI : 1.10-2.14; T/T vs. A/A: OR = 1.57, 95% CI : 1.07-2.31) and rs16947 (G/G vs. C/C: OR = 3.41, 95% CI : 1.82-6.39) were also significantly associated with the risk of CHDs in offspring. Additionally, significant interactions were observed between the CYP450 genetic variants and drug use on the development of CHDs., Conclusions: In those of Chinese descent, ovulatory drugs, antidepressants, antiabortifacients, and traditional Chinese medicines may be associated with the risk of CHDs in offspring. Maternal CYP450 genes may regulate the effects of maternal drug exposure on fetal heart development., (Copyright © 2022 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Objectives: To investigate the incidence of preterm birth and risk factors for preterm birth., Methods: A prospective cohort study was performed for the pregnant women in early pregnancy and their spouses, who underwent prenatal examination for the first time in Hunan Provincial Maternal and Child Health Care Hospital from May 2014 to December 2016 and decided to be hospitalized for delivery. A questionnaire survey was performed to collect exposure information possibly related to preterm birth. The hospital's medical record system was used for information verification and to record the pregnancy outcome. A multivariate logistic regression analysis was used to investigate the risk factors for preterm birth., Results: A total of 6 764 pregnant women with complete data were included, and the incidence rate of preterm birth was 17.09%. The multivariate logistic regression analysis showed that a history of adverse pregnancy outcomes, eating areca nut before pregnancy, a history of pregnancy complications, a history of hepatitis, no folate supplementation during pregnancy, medication during pregnancy, active smoking and passive smoking during pregnancy, drinking during pregnancy, unbalanced diet during pregnancy, high-intensity physical activity during pregnancy, and natural conception after treatment of infertility or assisted conception as the way of conception were risk factors for preterm birth ( P <0.05). Additionally, the pregnant women whose spouses were older, had a higher body mass index or smoked had an increased risk for preterm birth ( P <0.05). A higher level of education of pregnant women or their spouses and lower gravidity were protective factors against preterm birth ( P <0.05)., Conclusions: There are many risk factors for preterm birth. Special attention should be paid to the life behaviors of pregnant women during pregnancy, and health education should be strengthened for pregnant women and their spouses to develop good living habits and reduce the incidence of preterm births.

Objectives: To investigate the epidemic situation of hand-foot-mouth disease (HFMD) in Hunan Province, China, from 2008 to 2019, as well as its spatial autocorrelation characteristics and spatial-temporal clustering, and to provide a reference for the prevention and control of HFMD in Hunan Province., Methods: Spatial autocorrelation and spatial-temporal clustering analyses were used to analyze the monitoring data of HFMD in Hunan Province from 2008 to 2019., Results: The epidemic situation of HFMD in Hunan Province from 2008 to 2019 showed obvious seasonal distribution, with a low incidence rate in January to March and a high incidence rate in April to July. As for population distribution, children aged 0-5 years had the highest number of HFMD cases and accounted for 95.89% (1 460 391/1 522 910) of all cases, with a mean annual incidence rate of 2 197.784/100 000, and scattered children had the highest number of cases and accounted for 82.59% (1 257 739/1 522 910) of all cases. The global spatial autocorrelation analysis showed that the onset of HFMD in Hunan Province showed a significant clustering distribution, and the local spatial autocorrelation analysis showed that the high clustering areas of HFMD were mainly the districts and counties of Changsha, Zhuzhou, and Yueyang cities. Time-space scanning showed that clustering time was mainly April to July; the cases were clustered in the northeast of Hunan Province from 2008 to 2010 and in the central part of Hunan Province from 2011 to 2019., Conclusions: The high incidence rate of HFMD is observed in April to July in Hunan Province. Children under 5 years of age are at a high risk of this disease. Spatial-temporal clustering is observed for the epidemic of HFMD, mainly clustered in the northeastern and central areas of Hunan Province. It is suggested that the results may be used as guidance to determine the key areas for HFMD prevention and control in Hunan Province and optimize the allocation of health resources.

The activation of carbon dioxide (CO 2 ) mediated by NbBN 2 - cluster anions under the conditions of thermal collision has been investigated by time-of-flight mass spectrometry combined with density functional theory calculations. Two CO double bonds in the CO 2 molecule are completely broken and two C-N bonds are further generated to form the novel molecule NCNBO - . To the best of our knowledge, this new molecule is synthesized and reported for the first time. In addition, one oxygen atom transfer channel produces another product, NbBN 2 O - . Both of the Nb and B atoms in NbBN 2 - donate electrons to reduce CO 2 , and the carbon atom originating from CO 2 serves as an electron reservoir. The reaction of NbB - with N 2 was also investigated theoretically, and the formation of NbBN 2 - from this reaction is thermodynamically and kinetically quite favorable, indicating that NCNBO - might be produced from the coupling of N 2 and CO 2 mediated by NbB - anions.

Aim: Atrial fibrillation (AF) is a common clinical arrhythmia and can cause a variety of complications. To study the therapeutic effect of H 2 S in atrial fibrosis and explore the important role of miR-133a, in vitro experiments in human atrial fibroblasts (HAFs) were conducted., Methods: The fibrosis in HAFs was induced by Ang II. The expression levels of miR-133a and CTGF in HAFs were examined by qRT-PCR. The proliferation and migration of HAFs were detected by CCK-8 and cell scratch assays. The protein expressions of CTGF, collagen I, collagen III and α-SMA were detected by western blotting. The dual-luciferase reporter gene was used to detect the interaction between miR-133a and CTGF., Results: The proliferation and migration of HAFs stimulated by Ang II were enhanced, the expression of miR-133a was reduced, and the levels of CTGF and fibrosis markers (collagen I, collagen III and α-SMA) were increased. Furthermore, H 2 S reduced fibrosis, proliferation and migration of HAFs induced by Ang II. Accordingly, overexpression of miR-133a inhibited the proliferation and migration ability on Ang II-induced HAFs, and decreased the protein expressions of related fibrosis markers and CTGF. Meanwhile, miR-133a inhibitor could reverse the inhibition effect of H 2 S on proliferation and migration in HAFs by Ang II-induced. By targeting CTGF, miR-133a inhibited the expression of CTGF., Conclusion: H 2 S improved myocardial cell fibrosis by significantly increasing the expression of miR-133a, and CTGF might be a potential target for miR-133a to play an important role in myocardial fibrosis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Dinitrogen activation and transformation at room temperature is a goal that has been long sought after. Despite that, it remains underdeveloped due to being a challenging research area and the need for a better mechanistic understanding. Herein, we report that well-defined NbB 3 O 2 - gas-phase clusters can activate one N 2 molecule and generate the products B 3 N 2 O - and B 3 N 2 O 2 - , as applying mass spectrometry and theoretical calculations. This unusual N 2 activation reaction results from the different functions of the Nb and B 3 O 2 moieties in NbB 3 O 2 - . Theoretical calculations suggest that a catalytic cycle can be completed by the recovery of NbB 3 O 2 - , which is achieved through the reactions of Nb and NbO with B 3 O 2 - and B 3 O - , respectively. This is the first example of N 2 efficient transformation at a monometallic cluster, and this method for generating dual active sites by designing proper ligands may open the way toward the development of more effective N 2 fixation and functionalization methodologies.

Cleavage of all C-H bonds in two methane molecules by gas-phase cluster ions at room temperature is a challenging task. Herein, mass spectrometry and quantum chemical calculations have been used to identify one single metal boride cluster anions NbB4- that can activate eight C-H bonds in two methane molecules and release one H2 molecule each time under thermal collision conditions. In these consecutive reactions, the loaded Nb atoms and the support B4 units play different roles but act synergistically to activate CH4, which is responsible for the interesting reactivity of NbB4-. Moreover, there are some mechanistic differences in these two reactions, including the mechanisms for the first C-H bond activation steps, dihydrogen desorption sites, and major electron donors. This study shows that non-noble metal boride species are reactive enough to facilitate thermal C-H bond cleavages, and boron-based materials may be one kind of potential support material facilitating surface hydrogen transport.

Objective: To study the association between maternal reduced folate carrier ( RFC ) gene polymorphisms and congenital heart disease (CHD) in offspring., Methods: A hospital-based case-control study was conducted. The mothers of 683 infants with CHD who attended the Department of Cardiothoracic Surgery, Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group. The mothers of 740 healthy infants without any deformity who attended the hospital during the same period of time were enrolled as the control group. A questionnaire survey was performed to collect the exposure data of subjects. Venous blood samples of 5 mL were collected from the mothers for genetic polymorphism detection. A multivariate logistic regression analysis was used to evaluate the association of RFC gene polymorphisms and their haplotypes with CHD. A generalized multifactor dimensionality reduction method was used to analyze gene-gene interactions., Results: After control for confounding factors, the multivariate logistic regression analysis showed that maternal RFC gene polymorphisms at rs2236484 (AG vs AA: OR =1.91, 95% CI :1.45-2.51; GG vs AA: OR =1.96, 95% CI :1.40-2.75) and rs2330183 (CT vs CC: OR =1.39, 95% CI :1.06-1.83) were significantly associated with the risk of CHD in offspring. The haplotypes of G-G ( OR =1.21, 95% CI :1.03-1.41) and T-G ( OR =1.25, 95% CI :1.07-1.46) in mothers significantly increased the risk of CHD in offspring. The interaction analysis showed significant gene-gene interactions between different SNPs of the RFC gene in CHD ( P < 0.05)., Conclusions: Maternal RFC gene polymorphisms and interactions between different SNPs are significantly associated with the risk of CHD in offspring.

In light of the current energy requirements, the conversion of CO 2 and N 2 into useful C-N bond-containing products under mild conditions has become an area of intense research. However, the inert nature of N 2 and CO 2 renders their coupling extremely challenging. Herein, nitrogen and carbon atoms originating from N 2 and CO 2 , respectively, are fixed sequentially by NbH 2 - anions in the gas phase at room temperature. Isocyanate and NbO 2 CN - anions were formed under thermal collision conditions, thus achieving the formation of new C-N bonds directly from simple N 2 and CO 2 . The anion structures and reaction details were studied by mass spectrometry, photoelectron spectroscopy, and quantum chemical calculations. A novel N 2 activation mode (metal-ligand activation, MLA) and a related mechanism for constructing C-N bonds mediated by a single non-noble metal atom are proposed. In this MLA mode, the C atom originating from CO 2 serves as an electron reservoir to accept and donate electrons.

The activation and hydrogenation of nitrogen are central in industry and in nature. Through a combination of mass spectrometry and quantum chemical calculations, this work reports an interesting result that scandium nitride cations Sc 3 N + can activate sequentially H 2 and N 2 , and an amido unit (NH 2 ) is formed based on density functional theory calculations, which is one of the inevitable intermediates in the N 2 reduction reactions. If the activation step is reversed, i.e., sequential activation of first N 2 and then H 2 , the reactivity decreases dramatically. An association mechanism, prevalent in some homogeneous catalysis and enzymatic mechanisms, is adopted in these gas-phase H 2 and N 2 activation reactions mediated by Sc 3 N + cations. The mechanistic insights are important to understand the mechanism of the conversion of H 2 and N 2 to NH 3 synthesis under ambient conditions.

The heterogeneous oxidation of isoprene (C5H8) by metal-oxide particles, such as the typical mineral aerosols TiO2, plays an important role in the isoprene atmospheric chemistry. However, the underlying mechanism of C5H8 oxidation remains elusive owing to the complexities of aerosol surfaces and reaction channels. Herein, we report the gas-phase reactions of TixOy+ (x = 1-7, y = 1-14) cations with isoprene by using mass spectrometry and density functional theory (DFT) calculations. Five types of reaction channels were observed: association, hydrogen atom transfer (HAT), C-C bond cleavage, combined oxygen atom transfer (OAT) and HAT and combined OAT and C-C bond cleavage. It is noteworthy that formaldehyde is known as the major oxidation product of isoprene/hydroxyl radicals in the atmosphere. In addition, CO has not been observed in the reactions of isoprene with gas-phase ions. Therefore, the reaction mechanisms of CH2O and CO generation observed in Ti2O5+/C5H8 and Ti4O8+/C5H8 systems were further investigated by DFT calculations, and the calculated results are in agreement with the experimental observations. In these two reactions, both Ti and O atoms can be the adsorption sites for C5H8. The reaction channels and mechanistic information gained in these gas-phase model reactions may offer fundamental insights relevant to the corresponding oxidation processes over titanium oxide aerosols in the atmosphere.

The thermal gas-phase reactions of Nb2BN2- cluster anions with carbon dioxide have been explored by using the art of time-of-flight mass spectrometry and density functional theory calculations. Four CO2 molecules can be consecutively reduced by Nb2BN2-, resulting in the formation of Nb2BN2O1-4- anions and the release of one CO molecule each time. To illustrate the role of ligands in Nb2BN2-, the reactivities of Nb2N2- and Nb2B- toward CO2 were also investigated; two and three CO2 molecules are activated, respectively, and the rate constants are slower than that of Nb2BN2-/CO2 systems. This comparison indicates that metal-metal multiple bonds and appropriate ligands, such as B, are important factors for CO2 reduction. The synergy between a transition metal atom (Nb) and a main-group atom (B) in CO2 reduction mediated by gas-phase clusters is revealed for the first time. To the best of our knowledge, Nb2BN2- anions are gas-phase clusters that reduce the largest number of CO2 molecules. A fundamental understanding of the efficient reduction of carbon dioxide molecules may shed light on the rational design of active sites on supported transition metal/boron nitride catalysts.

Objective: To study the association of maternal diabetes mellitus (DM), uncoupling protein 2 (UCP2) gene polymorphisms, and their interaction with the risk of congenital heart disease (CHD) in offspring., Methods: A hospital-based case-control study was conducted. A total of 464 mothers of children with CHD alone who were diagnosed in Hunan Children's Hospital from March 2018 to August 2019 were enrolled as the case group. A total of 504 mothers of healthy children who were hospitalized during the same period and did not have any deformity were enrolled as the control group. A questionnaire survey was performed to collect the information on exposure. Venous blood samples (5 mL) were collected from the mothers to detect UCP2 gene polymorphisms. A multivariate logistic regression analysis was used to investigate the association of maternal DM, UCP2 gene polymorphisms, and their interaction with CHD in offspring., Results: After control for confounding factors, the multivariate logistic regression analysis showed that mothers with gestational DM (OR=2.96, 95%CI: 1.57-5.59), a history of gestational DM (OR=3.16, 95%CI: 1.59-6.28), and pregestational DM (OR=4.52, 95%CI: 2.41-8.50) significantly increased the risk of CHD in offspring (P<0.05). The polymorphisms of the UCP2 gene at rs659366 (T/C vs C/C: OR=1.49, 95%CI: 1.02-2.16; T/T vs C/C: OR=2.77, 95%CI: 1.67-4.62) and rs660339 (A/A vs G/G: OR=2.19, 95%CI: 1.34-3.58) were significantly associated with risk of CHD in offspring (P<0.05). The interaction analysis showed an interaction between the polymorphisms of the UCP2 gene at rs659366 and rs660339 and maternal DM in the development of CHD (P<0.05)., Conclusions: Maternal DM, UCP2 gene polymorphisms, and their interaction are associated with the development of CHD in offspring.

Background: Postoperative acute kidney injury (AKI) is a complex pathological process involved intrarenal and systemic inflammation caused by renal hypoperfusion, nephrotoxic drugs and urinary obstruction. Neutrophil-to-lymphocyte ratio (NLR) is a marker of inflammation reflecting the progress of many diseases. However, whether NLR at admission can predict the occurrence of AKI after surgery in the intensive care unit (ICU) remains unknown., Aim: To clarify the relationship between NLR and the occurrence of AKI in patients with gastrointestinal and hepatobiliary surgery in the ICU., Methods: A retrospective analysis of 282 patients receiving surgical ICU care after gastrointestinal and hepatobiliary surgery in our hospital from December 2014 to December 2018 was performed., Results: Postoperative AKI occurred in 84 patients (29.79%) in this cohort. NLR by the multivariate analysis was an independent risk factor for occurrence of postoperative AKI in patients with gastrointestinal and hepatobiliary surgery in the ICU. In this cohort, receiver operating characteristic curves of AKI occurrence showed that the optimal cut-off value of NLR was 8.380. NLR was found to be significantly correlated with the white blood cell count, neutrophil count, lymphocyte count, arterial lactate and dialysis ( P < 0.05). Additionally, NLR value at admission was higher in AKI patients compared with the non-AKI patients and increased with the severity of AKI. Patients with NLR ≥ 8.380 exhibited significantly higher incidences of postoperative AKI and severe AKI than patients with NLR < 8.380 (AKI: 38.12% vs 14.85%, P < 0.001; severe AKI: 14.36% vs 1.98%, P = 0.001)., Conclusion: NLR at admission is a predictor of AKI occurrence in patients with gastrointestinal and hepatobiliary surgery in ICU. NLR should be included in the routine assessment of AKI occurrence., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Platelet-derived growth receptor α (PDGFRα) is a key factor in many pathophysiological processes. The expression level of PDGFRα is significantly elevated in the early stage of liver development and maintained at a lower level in adult normal livers. In this study, we constructed a liver-specific PDGFRαD842 mutant transgenic (TG) mice model to explore the effect of continuous activation of PDGFRα on liver regeneration and hepatocarcinogenesis. 14-day-old TG and wild-type (WT) mice were intraperitoneally injected with diethylnitrosamine (DEN) at a dose of 25 μg/g body weight. Two-month-old male TG and WT mice were subjected to partial hepatectomy (PH). The liver tissues were collected for further analysis at different time points. Overexpression of PDGFRα D842V and its target genes, Akt, c-myc and cyclin D1 in hepatocytes with no overt phenotype versus WT mice were compared. Unexpectedly, a dramatic decrease in hepatocyte proliferation was noted after PH in TG versus WT mice, possibly due to the downregulation of hepatocyte growth factor receptor (MET) and epidermal growth factor receptor (EGFR). No TG mice developed HCC spontaneously after 14 months follow-up. However, TG mice were more resistant to DEN-induced hapatocarcinogenesis at 6, 10, and 12 months of age, showing delayed hepatocyte proliferation and apoptosis, lower tumor incidence, smaller size and fewer number, compared with age-matched WTs, partially through downregulation of MET and EGFR. In conclusion, continuous activation of PDGFRα signaling by expression of PDGFRα D842V does not promote, but inhibit hepatic regeneration and hepatocarcinogenesis, possibly through compensatory downregulation of MET and EGFR., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)