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The geodynamic mechanisms that controlled magmatic activity in South China during the late Mesozoic have been a cutting-edge focus of recent research. Southeastern Guangxi, which is located at the juncture between the Pacific and Neo-Tethyan tectonic domains, is a transitional zone characterized by the occurrence of widespread Jurassic–Cretaceous magmatic rocks. Investigation of this region can shed light on the late Mesozoic tectonic setting of South China. We conducted U–Pb geochronological and geochemical analyses of the Liuwang granodiorite and quartz porphyry, which are exposed in southeastern Guangxi. Zircon U–Pb dating yielded an age of 161.8 ± 1.2 Ma for the granodiorite and 97.89 ± 0.68 Ma for the quartz porphyry, indicating that they formed during the Late Jurassic and Late Cretaceous, respectively. The Liuwang granodiorites are weakly peraluminous high-K calc-alkaline rocks characterized by enrichment in large ion lithophile elements (including Rb) and high field strength elements (including Th, U, Pb, and Ta) and depletion in Ba, Nb, and Sr. The granodiorites also exhibit weak rare earth element (REE) fractionation and slightly negative Eu anomalies. Conversely, the Liuwang quartz porphyry is weakly peraluminous and belongs to the potassic syenite series, transitioning into the high-K calc-alkaline series. It is characterized by enrichment in Rb and high field strength elements (including Th, U, Pb, and Ta), with depletion in Ba, Nb, Sr, and Zr. It does not exhibit REE fractionation but does yield prominent negative Eu anomalies. The granodiorite and quartz porphyry yield εHf(t) values of −23.26 to −2.48 and −4.4 to +0.8, respectively, with tDM2 ages of 2642–1270 and 1411–1081 Ma, respectively. These data suggest that the Liuwang granodiorite formed under a background of Late Jurassic lithospheric extension–thinning and was derived from partial melting of Palaeoproterozoic–Mesoproterozoic metasedimentary sandstones with a minor contribution from mantle-derived melts. In contrast, the Liuwang quartz porphyry was derived from partial melting of Mesoproterozoic pelitic rocks and formed in a Late Cretaceous tectonic setting linked to the northward subduction of the Neo-Tethys Ocean beneath South China.

The implementation of the new ambient air quality standards (NAAQS) in 2012 is a milestone in China’s environmental information disclosure process. The fully automated collection and publication of pollution information provides a convenient way to measure the environmental protection process around the country. This paper investigates the association between NAAQS and green total factor energy efficiency (GTFEE) enhancement in Chinese resource-based cities, using the generalized multiperiod DID method and 2004–2019 panel data from 282 prefecture-level cities. We find that the implementation of this NAAQS significantly promotes GTFEE’s improvement in China’s resource-based cities. Furthermore, we discover that both the type of industrial base and the initial public monitoring motivation influence the improvement effect of the NAAQS on GTFEE. In further studies, NAAQS enhances GTFEE through industrial structure optimization, and the magnitude of the local NAAQS effect is influenced by the level of green innovation. Finally, we make recommendations including implementing targeted environmental regulations and enhancing environmental information regulation.

As the most prevalent type of birth malformation, congenital heart disease (CHD) gives rise to substantial mortality and morbidity as well as a socioeconomic burden. Although aggregating investigations highlight the genetic basis for CHD, the genetic determinants underpinning CHD remain largely obscure. In this research, a Chinese family suffering from autosomal dominant CHD (atrial septal defect) and arrhythmias was enrolled. A genome-wide genotyping with microsatellite markers followed by linkage assay as well as sequencing analysis was conducted. The functional effects of the discovered genetic mutation were characterized by dual patch-clamp electrophysiological recordings in N2A cells and propidium iodide uptake assays in HeLa cells. As a result, a novel genetic locus for CHD and arrhythmias was located on chromosome 17q21.31-q21.33, a 4.82-cM (5.12 Mb) region between two markers of D17S1861 and D17S1795. Sequencing assays of the genes at the mapped locus unveiled a novel heterozygous mutation in the GJC1 gene coding for connexin 45 (Cx45), NM_005497.4:c.550A>G;p.R184G, which was in co-segregation with the disease in the whole family and was not observed in 516 unrelated healthy individuals or gnomAD. Electrophysiological analyses revealed that the mutation significantly diminished the coupling conductance in homomeric cell pairs (R184G/R184G) and in cell pairs expressing either R184G/Cx45 or R184G/Cx43. Propidium iodide uptake experiments demonstrated that the Cx45 R184G mutation did not increase the Cx45 hemichannel function. This investigation locates a new genetic locus linked to CHD and arrhythmias on chromosome 17q21.31-q21.33 and indicates GJC1 as a novel gene predisposing to CHD and arrhythmias, implying clinical implications for prognostic risk assessment and personalized management of patients affected with CHD and arrhythmias.

Congenital heart disease (CHD) is the most frequent kind of birth deformity in human beings and the leading cause of neonatal mortality worldwide. Although genetic etiologies encompassing aneuploidy, copy number variations, and mutations in over 100 genes have been uncovered to be involved in the pathogenesis of CHD, the genetic components predisposing to CHD in most cases remain unclear. We recruited a family with CHD from the Chinese Han population in the present investigation. Through whole-exome sequencing analysis of selected family members, a new SOX18 variation, namely NM_018419.3:c.349A>T; p.(Lys117*), was identified and confirmed to co-segregate with the CHD phenotype in the entire family by Sanger sequencing analysis. The heterozygous variant was absent from the 384 healthy volunteers enlisted as control individuals. Functional exploration via luciferase reporter analysis in cultivated HeLa cells revealed that Lys117*-mutant SOX18 lost transactivation on its target genes NR2F2 and GATA4, two genes responsible for CHD. Moreover, the genetic variation terminated the synergistic activation between SOX18 and NKX2.5, another gene accountable for CHD. The findings strongly indicate SOX18 as a novel gene contributing to CHD, which helps address challenges in the clinical genetic diagnosis and prenatal prophylaxis of CHD.

Congenital heart disease (CHD), the most common type of birth defect, is still the leading non-infectious cause of infant morbidity and mortality in humans. Aggregating evidence demonstrates that genetic defects are involved in the pathogenesis of CHD. However, CHD is genetically heterogeneous and the genetic components underpinning CHD in an overwhelming majority of patients remain unclear. In the present study, the coding exons and flanking introns of the PITX2 gene, which encodes a paired-like homeodomain transcription factor 2essential for cardiovascular morphogenesis as well as maxillary facial development, was sequenced in 196 unrelated patients with CHD and subsequently in the mutation carrier's family members available. As a result, a novel heterozygous PITX2 mutation, p.Q102X for PITX2a, or p.Q148X for PITX2b, or p.Q155X for PITX2c, was identified in a family with endocardial cushion defect (ECD) and Axenfeld-Rieger syndrome (ARS). Genetic analysis of the pedigree showed that the nonsense mutation co-segregated with ECD and ARS transmitted in an autosomal dominant pattern with complete penetrance. The mutation was absent in 800 control chromosomes from an ethnically matched population. Functional analysis by using a dual-luciferase reporter assay system revealed that the mutant PITX2 had no transcriptional activity and that the mutation eliminated synergistic transcriptional activation between PITX2 and NKX2.5, another transcription factor pivotal for cardiogenesis. To our knowledge, this is the first report on the association of PITX2 loss-of-function mutation with increased susceptibility to ECD and ARS. The findings provide novel insight into the molecular mechanisms underpinning ECD and ARS, suggesting the potential implications for the antenatal prophylaxis and personalized treatment of CHD and ARS.

Tetraology of Fallot (TOF) is the most common form of cyanotic congenital heart disease and is a major cause of significant morbidity and mortality. Emerging evidence demonstrates that genetic risk factors are involved in the pathogenesis of TOF. However, TOF is genetically heterogeneous and the genetic defects responsible for TOF remain largely unclear. In the present study, the whole coding region of the GATA5 gene, which encodes a zinc-finger transcription factor essential for cardiogenesis, was sequenced in 130 unrelated patients with TOF. The relatives of the index patients harboring the identified mutations and 200 unrelated control individuals were subsequently genotyped. The functional characteristics of the mutations were analyzed using a luciferase reporter assay system. As a result, 2 novel heterozygous GATA5 mutations, p.R187G and p.H207R, were identified in 2 families with autosomal dominantly inherited TOF, respectively. The variations were absent in 400 control alleles and the altered amino acids were completely conserved evolutionarily. Functional analysis showed that the GATA5 mutants were associated with significantly decreased transcriptional activation compared with their wild-type counterpart. To our knowledge, this is the first report on the association of GATA5 loss-of-function mutations with TOF, suggesting potential implications for the early prophylaxis and allele-specific therapy of human TOF.

Congenital heart disease (CHD) is the most common form of birth defect in humans, and remains a leading non‑infectious cause of infant mortality worldwide. An increasing number of studies have demonstrated that genetic defects serve a pivotal role in the pathogenesis of CHD, and mutations in >60 genes have been causally associated with CHD. CHD is a heterogeneous disease and the genetic basis of CHD in the majority of patients remains poorly understood. In the present study, the coding exons and flanking introns of the mesoderm posterior 1 (MESP1) gene, which encodes a basic helix‑loop‑helix transcription factor required for normal cardiovascular development, were sequenced in 178 unrelated patients with CHD. The available relatives of the index patient carrying an identified mutation and 200 unrelated, ethnically‑matched healthy individuals, who were used as controls, were genotyped for MESP1. The functional characteristics of the MESP1 mutation were determined using a dual‑luciferase reporter assay system. As a result, a novel de novo heterozygous MESP1 mutation, p.Q118X, was identified in an index patient with double outlet right ventricle (DORV) and a ventricular septal defect. The nonsense mutation was absent in the 400 reference chromosomes and the altered amino acid was completely conserved evolutionarily across species. Functional assays indicated that the mutant MESP1 protein had no transcriptional activity when compared with its wild‑type counterpart. The present study firstly provided experimental evidence supporting the concept that a MESP1 loss‑of‑function mutation may contribute to the development of DORV in humans, which presents a significant insight into the molecular pathogenesis of CHD. The results highlight the potential implications for the genetic counseling and personalized treatment of patients with CHD. [ABSTRACT FROM AUTHOR]

ial septal defect (ASD) is a common cardiovascular malformation and an important contributor to substantial morbidity and mortality. Increasing evidence demonstrates that mutated NKX2-5, a gene encoding a homeobox transcription factor crucial to cardiogenesis, is a significant genetic determinant for congenital ASD. Nevertheless, the genetic basis for ASD in a majority of ASD patients remains largely unknown. In the current study, the entire coding region of NKX2-5 was sequenced initially for 58 unrelated probands with familial ASD. The relatives of the probands harboring identified mutations and 200 unrelated control individuals were subsequently genotyped. Three novel heterozygous NKX2-5 mutations (p.P43GfsX59, p.C46 W, and p.S179F) were identified respectively in three families with autosomal dominantly inherited ASD. These mutations, absent in 200 control individuals, cosegregated with ASD in the families that had complete penetrance. The findings expand the spectrum of mutations in NKX2-5 linked to ASD and contribute to genetic counseling, clinical interventions, and prenatal prevention of ASD for individuals with genetic susceptibility. [ABSTRACT FROM AUTHOR]

A voltammetric sensor for the determination of parathion has been developed based on the use of a poly(carmine) film electrode. The reduction of parathion at the poly(carmine) modified glassy carbon electrode (GCE) is studied by cyclic voltammetry (CV) and linear scan voltammetry (LSV). Parathion yields a well-defined reduction peak at a potential of −0.595 V on the poly(carmine) modified GCE in pH 6.0 phosphate buffer solution (PBS). Compared with that on a bare GCE, the reduction peak current of parathion is significantly enhanced. All the experimental parameters are optimized for the determination of parathion. The reduction peak current is linear with the parathion concentration in the range of 5.0 × 10−8 to 1.0 × 10−5 mol L−1, and the detection limit is 1.0 × 10−8 mol L−1. [ABSTRACT FROM AUTHOR]

Bicuspid aortic valve (BAV) is the most common form of congenital cardiovascular defect in humans and is associated with substantial morbidity and mortality. Emerging evidence demonstrates that genetic risk factors play an important role in the pathogenesis of BAV. However, BAV is a genetically heterogenous disorder, and the genetic defects underpinning BAV in most patients remain to be identified. In the present study, the coding exons and flanking introns of the NKX2.5 gene, which encodes a homeodomain-containing transcrip-tion factor essential for the normal development of the aortic valve, were sequenced in 142 unrelated patients with BAV. The available relatives of the mutation carrier and 200 unre-lated healthy subjects used as controls were also genotyped for NKX2.5. The functional characteristics of the mutation were delineated by using a dual-luciferase reporter assay system. As a result, a novel heterozygous NKX2.5 mutation, p.K192X, was identified in a family with BAV transmitted in an autosomal dominant pattern. The nonsense mutation was absent in 400 control chromosomes. Functional analyses revealed that the mutant NKX2.5 had no transcriptional activity compared with its wild-type counterpart. Furthermore, the mutation abolished the synergistic transcriptional activation between NKX2.5 and GATA5, another transcription factor crucial for the aortic valvular morphogenesis. In conclusion, this study is the first to link an NKX2.5 loss-of-function mutation to enhanced susceptibility to human BAV, providing novel insight into the molecular mechanism of BAV and suggesting potential implications for genetic counseling and clinical care of families presenting with BAV. [ABSTRACT FROM AUTHOR]