Nonylphenol (NP) is a known endocrine-disrupting chemical (EDC) that has been shown to affect bone development in mammals. However, the detrimental impacts of NP on the skeletal growth and ...development of aquatic species, especially bony fish, remain poorly understood. Bone morphogenic proteins (BMPs), essential for bone formation and osteoblast differentiation, act through the BMP-Smad signaling pathway. In this study, two BMP genes, BMP2 and BMP4, were cloned and characterized in the red crucian carp (Carassius auratus red var.). The full-length cDNAs of BMP2 and BMP4 were 2029 bp and 2095 bp, respectively, encoding polypeptides of 411 and 433 amino acids, and share a typical TGF-β domain with other BMPs. The tissue expression patterns of both genes were identified, showing ubiquitous expression across all studied tissues. Additionally, the exposure of embryos or adult fish to NP stress resulted in a downregulation of BMP2, BMP4, and other genes associated with the BMP-Smad signaling pathway. Moreover, the combined treatment of adult fish with NP and the specific BMP receptor inhibitor significantly reduced these genes’ expression. These findings elucidate the mechanism of NP stress on BMP2 and BMP4, suggesting a role for the BMP-Smad signaling pathway in the response to endocrine-disrupting chemicals in fish.
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•The δ44/40Ca values of polyhalite in the world were reported for the first time.•The two forms of polyhalite include long columnar and fibrous radial.•Primary sedimentary polyhalite ...was evaporated from original seawater.•Late metasomatic polyhalite involving the interaction of external brines.•Combining Ca-S isotope can deciphering the source and processes of polyhalite.
Polyhalite is a special potash fertilizer resource, which is widely distributed in the Triassic evaporite strata in the Sichuan Basin, but its genetic mechanism has always been controversial. This contribution presents new petrological, geochemistry, electron probe analyses, and Ca-S isotope systematics on Triassic polyhalite minerals for the first time from the Sichuan Basin aiming to better understand their origin. We present petrological observations of long columnar and granular polyhalites co-existing with halites (rock salt) and anhydrites that are not metasomatic in origin. Metasomatic polyhalites have also been studied, which have a fibrous and radial habit interwoven with anhydrite. The primary (sedimentary) polyhalite is solely formed from the evaporation of seawater, and the formation of metasomatic polyhalite involved impure meteoric water. The Ca and S isotopic values show that the sulphur and calcium in diamond-drillholes ZK001 and ZK601 are derived from seawater, whereas the sulphur and calcium in Well YS01 are derived from meteoric water. The sulphur and calcium in Well ZK02 are derived weathered terrigenous gypsum. This study demonstrates that the combined sulphur (δ34S) and calcium (δ44/40Ca) isotopes can be used to reveal the genesis of polyhalite.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Aim
Neuroblastoma amplified sequence (NBAS)‐associated disease has a wide phenotypic spectrum, including infantile liver failure syndrome type 2 (ILFS2, OMIM #616483), short stature with optic nerve ...atrophy and Pelger–Huët anomaly (SOPH) syndrome (OMIM #614800), and a combined phenotype overlapping ILFS2 and SOPH syndrome. The mutation spectra of NBAS and its genotype–phenotype correlation among Chinese were not clear.
Methods
Clinical and genetic data were retrospectively collected from the medical charts of patients with biallelic NBAS mutations, as well as from Chinese patients in previously published reports.
Results
Fourteen new patients were identified, including 10 novel mutations: c.648‐1G>A, c.2563_c.2577+5del/p.His855_Gln859del, c.3115C>T/p.Gln1039Ter, c.3284G>A/p.Trp1095Ter, c.2570C>T/p.Ala857Val, c.6859G>T/p.Asp2287Tyr, c.1028G>A/p.Ser343Asn, c.1177_1182delinsAGATAGA/p.Val393ArgfsTer2, c.3432_3435dupCAGT/p.Ala1146GlnfsTer14, and c.680_690dupACTGTTTCAGC/p.Phe231ThrfsTer35. All 14 patients presented as fever‐triggered liver injury, including nine patients that satisfied the criteria of acute liver failure (ALF) in whom c.3596G>A/p.Cys1199Tyr occurred five times. Nine patients had extrahepatic manifestations including short stature, skeletal abnormalities, intellectual disability, ophthalmic abnormalities, low levels of serum immunoglobulins, facial dysmorphism, and cardiac abnormalities. Ten other Chinese patients were collected through a review of published works. Genotype–phenotype analysis in 24 Chinese patients revealed that the percentage of ALF patients with variants in the Sec39 domain was significantly higher than that in the C‐terminal (100% vs. 12.5%, P = 0.000), and the percentage of multi‐organ/system involvement in patients with variants in the Sec39 domain was significantly lower than that in the C‐terminal (40% vs. 100%, P = 0.0128).
Conclusions
We reported 14 new patients, 10 novel mutations, and a unique recurrent mutation. Correlation analysis indicated that the domain of missense and non‐frameshift insertion/deletion mutations in NBAS protein is related to phenotype among Chinese patients.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Familial glucocorticoid deficiency type 1 (FGD1) is an autosomal recessive disorder caused by mutations in the melanocortin 2 receptor (
) gene, characterized by a low or undetectable serum cortisol ...level and a high adrenocorticotropic hormone (ACTH) level. Clinical manifestations include hypoglycemia, seizure, skin hyperpigmentation, hyperbilirubinemia, cholestasis, and a tall stature. Some dysmorphic features such as, a prominent forehead, hypertelorism, a broad nasal bridge, and small tapering fingers, have been reported. Children with FGD1 may have other isolated endocrine abnormalities. To date, no patient with FGD1 has been reported in mainland China. Here we report on a Chinese patient with FGD1 having a novel MC2R gene variant, a mild transverse palm crease, hypertelorism, and subtle/transient endocrine abnormalities relating to all three zones of the adrenal cortex and thyroid gland. We also reviewed cases with dysmorphic features or additional endocrine abnormalities.
There are growing evidence demonstrating that coronavirus disease 2019 (COVID-19) is companied by acute myocardial injury. However, the associations of SARS-CoV-2-induced myocardial injury with the ...risk of death and prognosis after discharge in COVID-19 patients are unclear.
This prospective cohort study analyzed 355 COVID-19 patients from two hospitals in different regions. Clinical and demographic information were collected and prognosis was followed up.
Of 355 hospitalized patients with COVID-19, 213 were mild, 90 severe, and 52 critically ill patients. On admission, 59 (16.7%) patients were with myocardial injury. Myocardial injury was more popular in critically ill patients. Univariate and multivariate logistic regression revealed that male, older age and comorbidity with hypertension were three crucial independent risk factors predicting myocardial injury of COVID-19 patients. Among 59 COVID-19 patients with myocardial injury, 25 (42.4%) died on average 10.9 days after hospitalization. Mortality was increased among COVID-19 patients with myocardial injury (42.4 vs. 3.38%,
= 12.542,
< 0.001). Follow-up study observed that 4.67% COVID-19 patients with myocardial injury were not fully recovered in 14 days after discharge.
Myocardial injury at early stage elevates mortality of COVID-19 patients. Male elderly patients with hypertension are more vulnerable to myocardial injury. SARS-CoV-2-induced myocardial injury has not completely recovered in 14 days after discharge.
Bradykinin (BK) and its biologically active metabolite des-Arg9 bradykinin (DABK) play a pivotal role in inflammation. Since chorioamnionitis is the leading cause of preterm birth and prostaglandin ...E2 (PGE2) derived from the amnion is key to labor initiation, we investigated if bradykinin peptides are part of the regulatory network of PGE2 synthesis in human amnion at parturition.
Human amnion tissue was obtained from term and preterm birth for the study of the changes of the bradykinin system at parturition. Cultured primary human amnion fibroblasts, the major source of PGE2, were used to study the effects of bradykinin peptides on PTGS2 expression and PGE2 production as well as the effects of infection mediators on bradykinin receptors.
Bradykinin peptides and their receptors BDKRB1 and BDKRB2 were present in human amnion, and their abundance increased in term and preterm labor. However, transcripts of the genes encoding the bradykinin precursor and its proteolytic cleavage enzymes were hardly detectable in human amnion despite the increased abundance of bradykinin peptides in term and preterm labor, suggesting that there is an alternative source of bradykinin peptides for human amnion and their actions are enhanced in human amnion at parturition.
studies in cultured human amnion fibroblasts showed that both BK and DABK increased the expression of prostaglandin-endoperoxide synthase 2 (PTGS2), the rate-limiting enzyme in prostaglandin synthesis, and subsequent PGE2 production. These effects of BK and DABK were mediated through BDKRB2 and BDKRB1 receptors, respectively, with subsequent activation of the p38 and ERK1/2 pathways. Moreover, lipopolysaccharide (LPS) and serum amyloid A1 (SAA1), the important mediators of infectious inflammation, induced the expression of both BDKRB1 and BDKRB2 through toll-like receptor 4 (TLR4). Induction of BDKRB1 and BDKRB2 expression by LPS and SAA1 enhanced BK- or DABK-induced PTGS2 expression and PGE2 production in human amnion fibroblasts.
This study demonstrated for the first time that the human amnion is a target tissue of bradykinin peptides and the bradykinin system may be part of the regulatory network of PTGS2 expression and PGE2 production in human amnion fibroblasts at both term and preterm birth, which may be enhanced by infection.
Background and aims
Although low-density lipoprotein cholesterol (LDL-C) has been considered as a risk factor of atherosclerotic cardiovascular disease, limited studies can be available to evaluate ...the association of LDL-C with risk of mortality in the general population. This study aimed to examine the association of LDL-C level with risk of mortality using a propensity-score weighting method in a Chinese population, based on the health examination data.
Methods
We performed a retrospective cohort study with 65,517 participants aged 40 years or older in Ningbo city, Zhejiang. LDL-C levels were categorized as five groups according to the Chinese dyslipidemia guidelines in adults. To minimize potential biases resulting from a complex array of covariates, we implemented a generalized boosted model to generate propensity-score weights on covariates. Then, we used Cox proportional hazard regression models with all-cause and cause-specific mortality as the dependent variables to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs).
Results
During the 439,186.5 person years of follow-up, 2403 deaths occurred. Compared with the median LDL-C group (100–130 mg/dL), subjects with extremely low LDL-C levels (group 1) had a higher risk of deaths from all-cause (HR = 2.53, 95% CI:1.80–3.53), CVD (HR = 1.84, 95% CI: 1.28–2.61), ischemic stroke (HR = 2.29, 95% CI:1.32–3.94), hemorrhagic stroke (HR = 3.49, 95% CI: 1.57–7.85), and cancer (HR = 2.12, 95% CI: 1.04–4.31) while the corresponding HRs in LDL-C group 2 were relatively lower than that in group 1.
Conclusions
Low LDL-C levels were associated with an increased risk of all-cause, CVD, ischemic stroke, hemorrhagic stroke, and cancer mortality in the Chinese population.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Hyalectan cleavage may play an important role in extracellular matrix remodeling. However, the proteolytic enzyme responsible for hyalectan degradation for fetal membrane rupture at parturition ...remains unknown. Here, we reveal that versican (VCAN) is the major hyalectan in the amnion, where its cleavage increases at parturition with spontaneous rupture of membrane. We further reveal that ADAMTS4 is a crucial proteolytic enzyme for VCAN cleavage in the amnion. Inflammatory factors may enhance VCAN cleavage by inducing ADAMTS4 expression and inhibiting ADAMTS4 endocytosis in amnion fibroblasts. In turn, versikine, the VCAN cleavage product, induces inflammatory factors in amnion fibroblasts, thereby forming a feedforward loop between inflammation and VCAN degradation. Mouse studies show that intra-amniotic injection of ADAMTS4 induces preterm birth along with increased VCAN degradation and proinflammatory factors abundance in the fetal membranes. Conclusively, there is enhanced VCAN cleavage by ADAMTS4 in the amnion at parturition, which can be reenforced by inflammation.
The plant-specific lateral organ boundaries (LOB) domain (LBD) proteins, a family of transcription factors, play important roles in plant growth and development, as well as in responses to various ...stresses. However, little is known about the functions of
genes in soybean (
). In this study, we investigated the evolution and classification of the LBD family in soybean by a phylogenetic tree of the
gene family from 16 species. Phylogenetic analysis categorized these proteins into two classes (Class I and Class II) with seven subgroups. Moreover, we found that all the 18
ancestors in angiosperm were kept in soybean, common bean genomes, and genome-wide duplication, suggesting the main force for the expansion of LBD from common bean to soybean. Analysis of gene expression profiling data indicated that 16
genes were significantly induced at different time points after inoculation of soybean plants (cv. Huachun 6) with
(
). We further assessed the role of four highly upregulated genes,
,
,
, and
, in plant defense in soybean hairy roots using the transient overexpression and knockdown assays. The results showed that
and
negatively regulate plant immunity against
, whereas
and
positively manipulate plant immunity against
. Collectively, our findings expand our knowledge of the origin and evolution of the
gene family in soybean and promote the potential application of these genes in soybean genetic improvement.
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