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Background: Cornelia de Lange syndrome (CdLS) is an uncommon congenital developmental disorder distinguished by intellectual disorder and distinctive facial characteristics, with a minority of cases attributed to RAD21 variants. Methods: A patient was admitted to the endocrinology department at Peking Union Medical College Hospital, where 2 mL of peripheral venous blood was collected from the patient and his parents. DNA was extracted for whole‐exome sequencing (WES) analysis, and the genetic variation of the parents was confirmed through Sanger sequencing. Results: A 13.3‐year‐old male patient with a height of 136.5 cm (−3.5 SDS) and a weight of 28.4 kg (−3.1 SDS) was found to have typical craniofacial features. WES revealed a pathogenic variant c.1143G>A (p.Trp381*) in the RAD21 gene. He was diagnosed with CdLS type 4 (OMIM #614701). We reviewed 36 patients with CdLS related to RAD21 gene variants reported worldwide from May 2012 to March 2024. Patient's variant status, clinical characteristics, and rhGH treatment response were summarized. Frameshift variants constituted the predominant variant type, representing 36% (13/36) of cases. Clinical features included verbal developmental delay and intellectual disorder observed in 94% of patients. Conclusion: This study reported the third case of CdLS type 4 in China caused by a RAD21 gene variant, enriching the genetic mutational spectrum. [ABSTRACT FROM AUTHOR]

This article was the first to prepare CeZrNiOx ternary solid solution using CeZrNi BDC MOFs as a template, and investigate its effect on improving the dispersion stability of Pd components in three‐way catalysts and the catalytic performance of natural gas exhaust purification. The experimental results indicated that CeZrNiOx derived from CeZrNi‐BDC MOFs had a stable solid solution uniform structure and relatively good thermal stability of the porous structure. Therefore, the thermal stability of Pd/CZN−M derived from CeZrNi BDC MOFs was significantly better than that of Pd/CZN−C prepared by citric acid complexation method. The PdO particle size of Pd/CZN−M before and after thermal aging was only about 2.0 and 4.5 nm, respectively. At GHSV50000 ml/(g⋅h), the T90 of aged Pd/CeZrNiOx for CH4, NO, and CO reached 410, 370, and 175 °C, respectively, showing better three‐way catalytic (TWC) activity than reported in existing literature. In addition, CeZeNiOx carriers derived from MOFs also enhanced the co‐activation ability of NO and CH4, and exhibited certain activity in the low‐temperature self‐decomposition reaction of NO, thus showing significant advantages in the TWC catalytic activity of NGVs. This work would provide a new method for preparing NGVs exhaust TWC catalysts with high dispersion stability. [ABSTRACT FROM AUTHOR]

In this paper, the bimetallic metal–organic frameworks (MOFs) of FeNi-BDC and FeNi-BDC-NH2 (BDC, 1,4-benzenedicarboxylate) with similar Fe/Ni molar ratio, crystal structure, porosity and thermal stability were synthesized by a solvothermal method. The results of adsorption experiments at ambient conditions showed that the adsorptive uptake of NO, CO2, O2 and N2 on FeNi-BDC were all very small under different adsorption partial pressures, with FeNi-BDC displaying a weak adsorption property because of its lack of unsaturated adsorption sites. On the contrary, at 100 kPa, the adsorption of NO by FeNi-BDC-NH2 was considerably higher than that by FeNi-BDC, indicating that the incorporation of NH2 on the ligand could effectively enhance the adsorption of NO. The adsorption capacity of FeNi-BDC-NH2 for NO reached 142.17 cm3 g−1, which was considerably higher than its capacity for CO2, O2 and N2 under the same conditions. Ideal Adsorption Solution Theory simulations calculated the adsorption selectivity for NO/CO2 and NO/O2 under a mixed atmosphere to reach 1325 and 13,346 respectively, demonstrating high adsorption selectivity. Through in situ infrared experiments and calculations of the enthalpy of adsorption, it was demonstrated that FeNi-BDC-NH2 adsorbed NO because NO can combine with NH2 in the material to form a NONOate structure. A preliminarily exploration of the mechanism of NO adsorption and the influence of NH2 functional groups on the adsorption and separation of NO revealed that the selectivity of adsorption was closely related to the variability of the enthalpy of adsorption. This also provided a new strategy for the adsorption and separation of NO in the flue gas environment. The bimetallic metal–organic frameworks of FeNi-BDC and FeNi-BDC-NH2 (BDC, 1,4-benzenedicarboxylate) with similar Fe/Ni molar ratio, crystal structure, porosity and thermal stability were synthesized by a solvothermal method. FeNi-BDC-NH2 demonstrated superior NO adsorption performance and high adsorption selectivity, indicating that the introduction of NH2 on the ligand can improve the adsorption capacity and selectivity of the material for NO, which also provides a new strategy for adsorption and separation of NO in a flue gas environment. (Image credit: Li Hao.) [ABSTRACT FROM AUTHOR]

In this work, the effect of amine groups of MOFs materials on the NO separation selectivity under the simulated mixed atmosphere had been first investigated by comparison of NO adsorptive separation selectivity of Fe‐BDC, Al‐BDC, FeAl‐BDC and Fe‐BDC‐NH2, Al‐BDC‐NH2, FeAl‐BDC‐NH2 synthesized by solvothermal method. The experimental results showed that the adsorption capacity of NO by Fe‐BDC‐NH2, Al‐BDC‐NH2, and FeAl‐BDC‐NH2 was significantly larger than Fe‐BDC, Al‐BDC, and FeAl‐BDC at 100 kPa, which indicated ‐NH2 promotes the adsorption of NO and was much higher than the adsorption capacity of CO2, O2, and N2 under the same conditions. The NO adsorption capacity and selectivity of bimetallic FeAl‐BDC‐NH2 were significantly better than that of monometallic Fe‐BDC‐NH2 and Al‐BDC‐NH2. The NO adsorption capacity of FeAl‐BDC‐NH2 can reach 216.42 cc g−1, which exceeded lots of MOFs materials reported, and the adsorption selectivities of NO/CO2 and NO/O2 by IAST under the simulated mixed atmosphere reached 1,350 and 15,962. It also proved that the material adsorbed NO because NO forms NONOate with ‐NH2 by the in situ IR and enthalpy calculation of adsorption, and the adsorption mechanism of NO was preliminarily investigated. The results provided a new direction for the application of adsorption and separation of NO in flue gas. [ABSTRACT FROM AUTHOR]

Purpose: Polycystic ovary syndrome (PCOS) is one of the leading causes of infertility in women of childbearing age, and many patients with PCOS have obesity and insulin resistance (IR). Although obesity is related to an increased risk of IR, in clinical practice, PCOS patients exhibit different effects on improving insulin sensitivity after weight loss. Therefore, in the present study, we aimed to examine the moderating effect of polymorphisms of mtDNA in the D-loop region on the associations of body mass index (BMI) with the homeostasis model assessment of insulin resistance index (HOMA-IR) and pancreatic β cell function index (HOMA-β) among women with PCOS. Methods: Based on a cross-sectional study, women with PCOS were recruited from the Reproductive Center of the First Affiliated Hospital of Anhui Medical University from 2015 to 2018. A total of 520 women who were diagnosed with PCOS based on the revised 2003 Rotterdam criteria were included in the study. Peripheral blood was collected from these patients, followed by DNA extraction, PCR amplification, and sequencing at baseline. HOMA-IR and HOMA-β were calculated according to blood glucose-related indices. Moderating effect models were performed with BMI as an independent variable, polymorphisms of mtDNA in the D-loop region as moderators, and ln (HOMA-IR) and ln (HOMA-β) as dependent variables. To verify the stability of moderating effect, sensitivity analysis was performed with the quantitative insulin sensitivity check index (QUICKI), fasting plasma glucose/fasting insulin (G/I), and fasting insulin as dependent variables. Results: BMI was positively associated with ln (HOMA-IR) and ln (HOMA-β) (β = 0.090, p < 0.001; β = 0.059, p < 0.001, respectively), and the relationship between BMI and ln (HOMA-IR) or ln (HOMA-β) was moderated by the polymorphisms of mtDNA in the D-loop region. Compared with the respective wild-type, the variant -type of m.16217 T > C enhanced the association between BMI and HOMA-IR, while the variant-type of m.16316 A > G weakened the association. On the other hand, the variant-type of m.16316 A > G and m.16203 A > G weakened the association between BMI and HOMA-β, respectively. The results of QUICKI and fasting insulin as dependent variables were generally consistent with HOMA-IR, and the results of G/I as dependent variables were generally consistent with HOMA-β. Conclusion: Polymorphisms of mtDNA in the D-loop region moderate the associations of BMI with HOMA-IR and HOMA-β among women with PCOS. [ABSTRACT FROM AUTHOR]

SARS-CoV Spike (S) protein shares considerable homology with SARS-CoV-2 S, especially in the conserved S2 subunit (S2). S protein mediates coronavirus receptor binding and membrane fusion, and the latter activity can greatly influence coronavirus infection. We observed that SARS-CoV S is less effective in inducing membrane fusion compared with SARS-CoV-2 S. We identify that S813T mutation is sufficient in S2 interfering with the cleavage of SARS-CoV-2 S by TMPRSS2, reducing spike fusogenicity and pseudoparticle entry. Conversely, the mutation of T813S in SARS-CoV S increased fusion ability and viral replication. Our data suggested that residue 813 in the S was critical for the proteolytic activation, and the change from threonine to Serine at 813 position might be an evolutionary feature adopted by SARS-2-related viruses. This finding deepened the understanding of Spike fusogenicity and could provide a new perspective for exploring Sarbecovirus' evolution. Author summary: The Spike of SARS-CoV-2 has accumulated many mutations during its time in circulation, most of which have occurred in the S1 region, and more specifically in the RBD, in an effort to either improve the virus's affinity for the receptor ACE2 or to enhance its ability to evade the immune system. Mutations in the Spike S2 region have more far-reaching effects than those in the S1 region because it is more conserved across Sarbecoviruses. By comparing SARS-CoV and SARS-CoV-2, we found that an important substitution at amino acid position 813 in the S2 region (T813S) disrupts the utilization of TMPRSS2 and can significantly influence viral entry into cells. This discovery deepens our knowledge of S proteins and provides new prospects for tracing the evolution of Sarbecoviruses. [ABSTRACT FROM AUTHOR]

Idiopathic oligoastenoteratozoospermia (iOAT) affects 30% of infertile men of reproductive age. However, the associations between Cr, Fe, Cu, Se or Co levels and iOAT risk have not been determined. This research aimed to assess the associations between Cr, Fe, Cu, Se and Co levels as well as their mixtures in seminal plasma and the risk of iOAT and severe iOAT. Therefore, a case‒control study including 823 participants (416 iOAT patients and 407 controls) recruited from October 2021 to August 2022 at the reproductive medicine center of the First Affiliated Hospital of Anhui Medical University was conducted in Anhui, China. The concentrations of Cr, Fe, Cu, Se and Co in seminal plasma were detected via inductively coupled plasma‒mass spectrometry. Binary logistic regression models were used to assess the associations between the levels of Cr, Fe, Cu, Se and Co and the risk of iOAT and severe iOAT; additionally, Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regressions were performed to evaluate the joint effect of seminal plasma levels of Cr, Fe, Cu, Se and Co on the risk of iOAT and explore which elements contributed most to the relationship. We found significant associations between the concentrations of Fe, Cu and Se in seminal plasma and iOAT risk after adjusting for covariates (Fe, lowest tertile vs. second tertile: aOR = 1.86, 95% CI = 1.31, 2.64; Cu, lowest tertile vs. second tertile: aOR = 1.95, 95% CI = 1.37, 2.76; Se, lowest tertile vs. second tertile: aOR = 1.65, 95% CI = 1.17, 2.35). A lower Se concentration in seminal plasma (lowest tertile vs. second tertile: aOR = 1.84, 95% CI = 1.10, 3.10) was positively associated with the risk of severe iOAT. Additionally, we also observed an association between the concentration of Cr in seminal plasma and the risk of iOAT before adjusting for covariates (Cr, third tertile vs. lowest tertile: OR=1.44, 95% CI: 1.03, 2.02). According to the BKMR analyses, the risk of iOAT increased when the overall concentrations were less than the 25th percentile. The results from the WQS regression indicated that a negative WQS index was significantly associated with the iOAT risk, while a positive WQS index was not. Se and Fe had significant weights in the negative direction. In conclusion, lower Cu, Fe and Se levels in seminal plasma were positively associated with iOAT risk, while higher Cr levels in seminal plasma were positively associated with iOAT risk according to the single element model, and lower levels of Se were related to a greater risk of severe iOAT; when comprehensively considering all the results from BKMR and WQS regression, Fe, Se and Cr levels contributed most to this relationship. [Display omitted] • Lower Cr, Fe, Cu, Se and Co increased risk of iOAT. • Se and Fe plays a dominant role in modulating the risk of iOAT. • Lower Se was associated with risk of iOAT severity. • Lower Cu, Fe and Se were individually associated with increased iOAT risk. • Higher Cr was associated with increased iOAT risk. [ABSTRACT FROM AUTHOR]

The melanocortin 4 receptor (MC4R) plays a critical role in the long-term regulation of energy homeostasis, and mutations in the MC4R are the most common cause of monogenic obesity. However, the precise molecular and cellular mechanisms underlying the maintenance of energy balance within MC4R-expressing neurons are unknown. We recently reported that the MC4R localizes to the primary cilium, a cellular organelle that allows for partitioning of incoming cellular signals, raising the question of whether the MC4R functions in this organelle. Here, using mouse genetic approaches, we found that cilia were required specifically on MC4R-expressing neurons for the control of energy homeostasis. Moreover, these cilia were critical for pharmacological activators of the MC4R to exert an anorexigenic effect. The MC4R is expressed in multiple brain regions. Using targeted deletion of primary cilia, we found that cilia in the paraventricular nucleus of the hypothalamus (PVN) were essential to restrict food intake. MC4R activation increased adenylyl cyclase (AC) activity. As with the removal of cilia, inhibition of AC activity in the cilia of MC4R-expressing neurons of the PVN caused hyperphagia and obesity. Thus, the MC4R signaled via PVN neuron cilia to control food intake and body weight. We propose that defects in ciliary localization of the MC4R cause obesity in human inherited obesity syndromes and ciliopathies. [ABSTRACT FROM AUTHOR]