Highly Efficient and Stable Mo-CoP3 @FeOOH Electrocatalysts for Alkaline Seawater Splitting.

The introduction of high-valence state elements and highly active species is promisingly desired to design superior electrocatalysts for water electrolysis. Exploring scalable synthetic strategies is necessary for an in-depth understanding of the mechanism of improving electrocatalytic performance. But it remains challenging. Herein, several electrocatalysts through element doping are prepared. The obtained Mo-CoP3 -2@FeOOH samples show the overpotentials (OER) of 232 mV (alkaline seawater) and 262 mV (KOH electrolyte). As HER catalyst, it also presents an excellent electrocatalytic performance. The above electrocatalysts are utilized as anode/cathode to assemble devices for alkaline seawater/water electrolysis, which delivers a cell voltage of 1.58 V and durability of 350 h. Density functional theory calculations reveal that Mo ion doping and FeOOH significantly enhance the density states of the Fermi level and tune the position of the d-band center. It expedites the charge transfer and decreases the adsorption energy of intermediates. It demonstrates that transition-metal phosphides coated with highly active FeOOH offer an effective route to fabricate high-performance and durable catalysts for seawater/water electrolysis.

Copper catalyzed Shono-type oxidation of proline residues in peptide.

Since the initial report in 1975, the Shono oxidation has become a powerful tool to functionalize the α position of amines, including proline derivatives, by electrochemical oxidation. However, the application of electrochemical Shono oxidations is restricted to the preparation of simple building blocks and homogeneous Shono-type oxidation of proline derivatives remains challenging. The late-stage functionalization at proline residues embedded within peptides is highly important as substitutions about the proline ring are known to affect biological and pharmacological activities. Here, we show that homogenous copper-catalyzed oxidation conditions complement the Shono oxidation and this general protocol can be applied to a series of formal C-C coupling reactions with a variety of nucleophiles using a one-pot procedure. This protocol shows good tolerance toward 19 proteinogenic amino acids and was used to functionalize several representative bioactive peptides, including captopril, enalapril, Smac, and endomorphin-2. Last, peptide cyclization can also be achieved by using an appropriately positioned side-chain hydroxyl moiety.

The Effect of Intramolecular Hydrogen Bonds on the Rotational Barriers of the Biaryl C-C Axis.

Axially chiral compounds are attracting more attention recently. Although hydrogen bonds are reported as a vital weak force that influences the properties of compounds, the effect of intramolecular hydrogen bonds on the atropisomerization of the Caryl -Caryl single bonds has not yet been well quantitatively investigated. Here, a series of axially chiral biaryl compounds were synthesized to study the effect of hydrogen bonds on the rotational barriers of the biaryl C-C axis. Experimental studies demonstrated that the rotational barrier of hydrogen bonding biaryl 9 was significantly lower (46.7 kJ mol-1 ) than biaryl 10 without hydrogen bonds. Furthermore, theoretical studies revealed that the intramolecular hydrogen bond stabilized the transition state (TS) of tri-ortho-substituted biaryl 9, relieving the steric repulsion in the TS. We believe that this study will provide chemists with a deeper understanding of the atropisomerization process of axially chiral biaryl compounds.

Ssc-mir-221-3p regulates melanin production in Xiang pigs melanocytes by targeting the TYRP1 gene.

BACKGROUND: MicroRNAs (miRNAs) are small endogenous non-coding RNAs that regulate gene expression by down-regulating it. Several studies have suggested that miRNAs plays a crucial role in mammalian skin color production. The TYRP1 gene, a member of the tyrosine family, is an important candidate gene that affects melanogenesis. This study aimed to identify genes and miRNAs that affect melanin production in Xiang pigs by transcriptome sequencing, and to validate their targeted regulatory relationships. RESULTS: 17 miRNAs and 1,230 genes were significantly differentially expressed (P < 0.05) in the black and white skin tissues of Jianbai Xiang pigs. miRNA-221-3p was identified as a candidate miRNA for melanin formation and its target gene, TYRP1, was selected. The TYRP1 gene is a member of the TYR gene family, which evolved from the TYR gene through chromosome segmental duplication. The function of the gene was highly conserved throughout the evolutionary process. overexpression of TYRP1 gene significantly increased the expression of TYR, TYRP1, and DCT genes P < 0.01, which led to an increase in the relative content of melanin. Silencing of TYRP1 through the use of TYRP1-siRNA significantly reduced the expression of TYR, TYRP1, and DCT genes in Jianbai Xiang pig melanocytes P < 0.01, which in turn decreased the relative melanin content. The targeted binding relationship between ssc-miR-221-3p and TYRP1 gene was validated. After transfection of porcine melanocytes with ssc-miR-221-3p mimic, the expression of ssc-miR-221-3p was significantly up-regulated (P < 0.01). Furthermore, the mRNA and protein levels of TYR, TYRP1, and DCT genes were significantly down-regulated (P < 0.01), and melanin content in cells was significantly reduced (P < 0.01). CONCLUSION: The TYRP1 gene affects melanogenesis in melanocytes of Jianbai Xiang pigs, and ssc-miR-221-3p targets the TYRP1 gene to regulate melanogenesis in melanocytes of Jianbai Xiang pigs.

Determinants of low birth weight among newborns delivered in China: a prospective nested case-control study in a mother and infant cohort.

This nested case-control study aimed to investigate the determinants of low birth weight among newborn babies delivered in Shenzhen, Guangdong, China. We recorded socio-demographic data, health status before pregnancy, pregnancy outcomes and complications in a Shenzhen mother and infant cohort. Among 8951 cases, 401 (4.48%) had low birth weight and 1.65% were full-term with LBW. Maternal body mass index, family income, history of pregnancy, hypertension before pregnancy, vaginal bleeding in 1st trimester, pregnancy-related diabetes, hypertension, placenta previa, placental abruption, premature rupture of membrane, oligohydramnios, and placental types were significantly associated with low birth weight (P < 0.05). In this study, high-risk and mainly preventable factors were linked to low birth weight. Adequate antenatal care, proper maternal nutrition and implementation of proven strategies to prevent high-risk factors may be effective ways to reduce the incidence of low birth weight.

What is already known on this subject? Low birth weight (LBW) is associated with adverse perinatal outcomes and neonatal disease and death. The aim of this study was to investigate the factors affecting low birth weight infants in a developed region in China.What the results of this study add? According to this study, the incidence of LBW in Shenzhen of China was 4.48%. Maternal body mass index, family income, history of pregnancy, hypertension before pregnancy, vaginal bleeding in 1st trimester, pregnancy-related diabetes, hypertension, placenta previa, placental abruption, premature rupture of membrane, oligohydramnios, and placental types were significantly associated with LBW.What the implications are of these findings for clinical practice and/or further research? This study suggests that good prenatal care, maternal nutrition and implementation of proven strategies to manage high-risk factors are needed to prevent and reduce the incidence of LBW. Health care providers could use our findings to identify good antenatal care and provide individualised interventions targeting women with risk factors.

Late-stage functionalization of 5-nitrofurans derivatives and their antibacterial activities.

Structure modification of drugs is a reliable way to optimize lead compounds, among which the most striking and direct method is late-stage functionalization (LSF). Here, we employed the Cu-catalyzed C-H LSF to modify 5-nitrofuran drugs. A series of modifications have been carried out including hydroxylation, methylation, azidination, cyanation, arylation, etc. Antibacterial activities of all compounds in vitro were measured. The results showed that compound 1 and compound 18 were the most active among all compounds. Meanwhile, the cell cytotoxicity assays of potent compounds 1, 3, 4, 5 & 18 and the parent drug FZD were conducted.

Comparison of pregnancy outcome after fresh embryo transfer between GnRH antagonist and GnRH agonist regimens in patients with thin endometrium.

Objective: To compare the pregnancy outcome after fresh embryo transfer between GnRH antagonist and GnRH agonist regimens in patients with thin endometrium. Methods: This retrospective study included all fresh embryo transfers following GnRH agonist or GnRH antagonist protocols in patients with thin endometrium from 2016 to 2021. The thin endometrium was defined as an endometrial thickness of 7.5 mm or less on the triggering day. Multivariant regression analysis was applied to assess the association of GnRH agonist or GnRH antagonist regimen with live birth following fresh embryo transfer in patients with thin endometrium. Results: A total of 69 and 192 cases were, respectively, included in the GnRH antagonist or GnRH agonist group. The stimulation duration was significantly longer by the GnRH agonist protocol than the GnRH antagonist protocol (11.2 ± 2.1 vs. 9.1 ± 1.9 days, P = 0.002). The rates of clinical pregnancy or live birth were significantly lower in the GnRH antagonist group compared to the GnRH agonist group (26.1 vs. 47.9%, P = 0.027; 17.4 vs. 40.1%, P = 0.01, respectively). Multivariable regression analysis demonstrated that GnRH agonist regimen was related to higher live birth rate compared with GnRH agonist protocol [adjusted OR: 2.6, 95% confidence intervals (CI): 1.3-5.3]. No significant difference in miscarriage rate and the neonatal outcome was present between the two protocols. Conclusion: Our findings suggest that GnRH agonist protocol results in a higher rate of live birth after fresh embryo transfer than GnRH antagonist protocol in patients with thin endometrium.

The single-cell expression profile of transposable elements and transcription factors in human early biparental and uniparental embryonic development.

Transposable elements (TEs) and transcription factors (TFs) are involved in the precise regulation of gene expression during the preimplantation stage. Activation of TEs is a key event for mammalian embryonic genome activation and preimplantation early embryonic development. TFs are involved in the regulation of drastic changes in gene expression patterns, but an inventory of the interplay between TEs and TFs during normal/abnormal human embryonic development is still lacking. Here we used single-cell RNA sequencing data generated from biparental and uniparental embryos to perform an integrative analysis of TE and TF expression. Our results showed that endogenous retroviruses (ERVs) are mainly expressed during the minor embryonic genome activation (EGA) process of early embryos, while Alu is gradually expressed in the middle and later stages. Some important ERVs (e.g., LTR5_Hs, MLT2A1) and Alu TEs are expressed at significantly lower levels in androgenic embryos. Integrative analysis revealed that the expression of the transcription factors CTCF and POU5F1 is correlated with the differential expression of ERV TEs. Comparative coexpression network analysis further showed distinct expression levels of important TFs (e.g., LEUTX and ZSCAN5A) in dizygotic embryos vs. parthenogenetic and androgenic embryos. This systematic investigation of TE and TF expression in human early embryonic development by single-cell RNA sequencing provides valuable insights into mammalian embryonic development.

Circular RNA hsa-circ-0005238 enhances trophoblast migration, invasion and suppresses apoptosis via the miR-370-3p/CDC25B axis.

Background: Fetal growth restriction (FGR) is attributed to various maternal, fetal, and placental factors. Trophoblasts participate in the establishment and maintenance of pregnancy from implantation and placentation to providing nutrition to fetus. Studies have reported that impaired trophoblast invasion and proliferation are among factors driving development of FGR. Circular RNAs (circRNAs) can regulate trophoblast function. We assessed the significance of circRNAs underlying FGR development. Materials and methods: Next generation sequencing (NGS) was carried out to quantify levels of circRNAs in placenta tissues with and without FGR. In vitro experiments including transfection, (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium) (MTS) assays, flow cytometry analyses, Transwell assays, wound healing assays, western blotting, qRT-PCR, dual-luciferase assays, immunofluorescence staining, and RIP assay were performed. Results: There were 18 differentially expressed circRNAs between FGR placentas and uncomplicated pregnancies, while levels of hsa-circ-0005238 were markedly low in FGR placentas. Our in vitro experiments further revealed that hsa-circ-0005238 suppressed apoptosis and enhanced proliferation, migration, invasion of trophoblast cell lines. The hsa-miR-370-3p was identified as a direct target of hsa-circ-0005238. Mechanistically, hsa-miR-370-3p prevents invasion as well as migration of trophoblast cells by downregulating CDC25B. Conclusion: The hsa-circ-0005238 modulates FGR pathogenesis by inhibiting trophoblast cell invasion and migration through sponging hsa-miR-370-3p. Hence, targeting this circRNA may be an attractive strategy for FGR treatment.

Intrinsically unidirectional chemically fuelled rotary molecular motors.

Biological systems mainly utilize chemical energy to fuel autonomous molecular motors, enabling the system to be driven out of equilibrium1. Taking inspiration from rotary motors such as the bacterial flagellar motor2 and adenosine triphosphate synthase3, and building on the success of light-powered unidirectional rotary molecular motors4-6, scientists have pursued the design of synthetic molecular motors solely driven by chemical energy7-13. However, designing artificial rotary molecular motors operating autonomously using a chemical fuel and simultaneously featuring the intrinsic structural design elements to allow full 360° unidirectional rotary motion like adenosine triphosphate synthase remains challenging. Here we show that a homochiral biaryl Motor-3, with three distinct stereochemical elements, is a rotary motor that undergoes repetitive and unidirectional 360° rotation of the two aryl groups around a single-bond axle driven by a chemical fuel. It undergoes sequential ester cyclization, helix inversion and ring opening, and up to 99% unidirectionality is realized over the autonomous rotary cycle. The molecular rotary motor can be operated in two modes: synchronized motion with pulses of a chemical fuel and acid-base oscillations; and autonomous motion in the presence of a chemical fuel under slightly basic aqueous conditions. This rotary motor design with intrinsic control over the direction of rotation, simple chemical fuelling for autonomous motion and near-perfect unidirectionality illustrates the potential for future generations of multicomponent machines to perform mechanical functions.

para-Selective Radical Trifluoromethylation of Benzamide Derivatives via Iminium Intermediates.

The direct C-H trifluoromethylation of arenes via a radical pathway has attracted considerable attention recently. However, a major challenge of C-H trifluoromethylation is the lack of site-selectivity on the phenyl ring especially para-selectivity. Herein we show a new strategy for para-selective C-H trifluoromethylation of benzamide derivatives using iminium activation. The reaction undergoes a radical-type nucleophilic substitution instead of a radical-type electrophilic substitution owing to iminium activation as a result of lowering the LUMO (lowest unoccupied molecular orbital). A wide range of substrates are compatible with this method giving almost exclusive para-trifluoromethylated products.

Hierarchical Co3O4@Ni3S2 electrode materials for energy storage and conversion.

Transition metal oxides are considered to be one of the most potential electrode materials. However, poor conductivity and insufficient active sites limit their actual applications. Rationally designed electrode materials with unique structural features can be ascribed to the efficient route for enhancing electrochemical performance. Here, we report hybrid Co3O4@Ni3S2 nanostructures obtained via a hydrothermal strategy and subsequent electrodeposition process. The obtained products can be used as electrodes for a hybrid supercapacitor with a specific capacity of 1071 C g-1 at 1 A g-1 and excellent rate capability. The as-assembled device delivers an energy density of 77.92 W h kg-1 at 2880 W kg-1. As an electrocatalyst, the above electrode possesses an overpotential of 237.6 mV at 50 mA cm-2 for oxygen evolution reaction.

Constructing High Efficiency CoZnx Mn2-x O4 Electrocatalyst by Regulating the Electronic Structure and Surface Reconstruction.

It is an effective strategy to develop novel electrocatalysts with controllable defects to enhance their electrocatalytic activity and stability. However, how to precisely design these catalysts on the atom scale remains very difficult. Herein, several vacancy-dependent CoZnx Mn2-x O4 catalysts are prepared through tailoring the concentration of Zn ions. The in situ activation of the obtained products accelerates the surface reconstruction. The superior electrocatalytic performance can be ascribed to the formations of MOOH (Mn, Co) active species and abundant oxygen vacancies, which are comparable to noble IrO2 and Pt/C catalysts. Zn-CoMn2 O4 -1.5 catalyst delivers a cell voltage of 1.63 V and long durability. Density functional theory calculations demonstrate that the appropriate Zn ion doping can improve the density states of p electron on the surface of catalysts significantly and benefit the d-band center closing to Fermi level, suggesting their high charge carrier density and low adsorption energy.

The novel indomethacin derivative CZ-212-3 exerts antitumor effects on castration-resistant prostate cancer by degrading androgen receptor and its variants.

Androgen receptor (AR) serves as a main therapeutic target for prostate cancer (PCa). However, resistance to anti-androgen therapy (SAT) inevitably occurs. Indomethacin is a nonsteroidal anti-inflammatory drug that exhibits activity against prostate cancer. Recently, we designed and synthesized a series of new indomethacin derivatives (CZ compounds) via Pd (II)-catalyzed synthesis of substituted N-benzoylindole. In this study, we evaluated the antitumor effect of these novel indomethacin derivatives in castration-resistant prostate cancer (CRPC). Upon employing CCK-8 cell viability assays and colony formation assays, we found that these derivatives had high efficacy against CRPC tumor growth in vitro. Among these derivatives, CZ-212-3 exhibited the most potent efficacy against CRPC cell survival and on apoptosis induction. Mechanistically, CZ-212-3 significantly suppressed the expression of AR target gene networks by degrading AR and its variants. Consistently, CZ-212-3 significantly inhibited tumor growth in CRPC cell line-based xenograft and PDX models in vivo. Taken together, the data show that the indomethacin derivative CZ-212-3 significantly inhibited CRPC tumor growth by degrading AR and its variants and could be a promising agent for CRPC therapy.

The Dynamic Changes of Transcription Factors During the Development Processes of Human Biparental and Uniparental Embryos.

Previous studies have revealed that transcription factors (TFs) play important roles in biparental (BI) early human embryogenesis. However, the contribution of TFs during early uniparental embryo development is still largely unknown. Here we systematically studied the expression profiles of transcription factors in early embryonic development and revealed the dynamic changes of TFs in human biparental and uniparental embryogenesis by single-cell RNA sequencing (scRNA-seq). In general, the TF expression model of uniparental embryos showed a high degree of conformity with biparental embryos. The detailed network analysis of three different types of embryos identified that 10 out of 17 hub TFs were shared or specifically owned, such as ZNF480, ZNF581, PHB, and POU5F1, were four shared TFs, ZFN534, GTF3A, ZNF771, TEAD4, and LIN28A, were androgenic (AG) specific TFs, and ZFP42 was the only one parthenogenetic (PG) specific TF. All the four shared TFs were validated using human embryonic stem cell (hESC) differentiation experiments; most of their target genes are responsible for stem cell maintenance and differentiation. We also found that Zf-C2H2, HMG, and MYB were three dominant transcription factor families that appeared in early embryogenesis. Altogether, our work provides a comprehensive regulatory framework and better understanding of TF function in human biparental and uniparental embryogenesis.

Platelet Count Might Be Associated With the Closure of Hemodynamically Significant Patent Ductus Arteriosus.

Background: Platelet-rich thrombosis leads to the occlusion of arteries. Whether the association between platelet count and closure of hemodynamically significant patent ductus arteriosus (hsPDA) exists remains inconclusive. Given that neonatal platelet count is significantly affected by infection, this study aims to evaluate the association of platelet parameters before ibuprofen treatment with the closure of hsPDA in very low birth weight (VLBW) infants without concurrent infection. Methods: A retrospective study was conducted at the NICU of Shenzhen Maternity and Child Healthcare Hospital from January 2016 to August 2020. VLBW infants diagnosed with hsPDA, treated with oral ibuprofen and without concurrent infection were included in this study. The platelet parameters were retrieved from the whole-blood test routinely performed within 24 h before starting treatment of oral ibuprofen. A multiple regression model was built to evaluate the association between platelet parameters before ibuprofen treatment and successful closure of hsPDA. Results: A total of 129 premature infants with hsPDA were analyzed in this study. After oral ibuprofen treatment, successful closure of hsPDA was achieved in 70 (54.3%) infants. The gestational age at birth and birth weight in infants with successful or failed closure of hsPDA after ibuprofen treatment were 28.3 vs. 27.6 weeks (p = 0.016) and 1,120 vs. 960 g (p = 0.043), respectively. The rate of mechanical ventilation in infants with successful closure of hsPDA was significantly lower compared to those with failed closure of hsPDA, 31.4 vs. 54.2%, p = 0.014. The platelet count in infants with successful closure of hsPDA after ibuprofen treatment was significantly higher compared to those with failed closure of hsPDA, 212 vs. 183 (in a unit of 109/L), respectively (p = 0.024). Multivariate logistic regression analysis showed that a higher platelet count (≥181 × 109/L) before ibuprofen treatment was independently associated with successful closure of hsPDA [odds ratio 2.556, 95% confidence interval (1.101-5.932), p = 0.029]. Conclusion: The findings in this study suggest that a higher platelet count before oral ibuprofen treatment may predict the probability of successful closure of hsPDA in VLBW infants.

Copper catalyzed late-stage C(sp3)-H functionalization of nitrogen heterocycles.

Nitrogen heterocycle represents a ubiquitous skeleton in natural products and drugs. Late-stage C(sp3)-H bond functionalization of N-heterocycles with broad substrate scope remains a challenge and of particular significance to modern chemical synthesis and pharmaceutical chemistry. Here, we demonstrate copper-catalysed late-stage C(sp3)-H functionalizaion of N-heterocycles using commercially available catalysts under mild reaction conditions. We have investigated 8 types of N-heterocycles which are usually found as medicinally important skeletons. The scope and utility of this approach are demonstrated by late-stage C(sp3)-H modification of these heterocycles including a number of pharmaceuticals with a broad range of nucleophiles, e.g. methylation, arylation, azidination, mono-deuteration and glycoconjugation etc. Preliminary mechanistic studies reveal that the reaction undergoes a C-H fluorination process which is followed by a nucleophilic substitution.

The Role of Elastase in Corneal Epithelial Barrier Dysfunction Caused by Pseudomonas aeruginosa Exoproteins.

Purpose: To investigate the role of elastase in corneal epithelial barrier dysfunction caused by the exoproteins secreted by Pseudomonas aeruginosa. Methods: Exoproteins obtained from Pseudomonas aeruginosa culture supernatant were analyzed by shotgun proteomics approach. In vitro multilayered rabbit corneal epithelial barrier model prepared by air-liquid interface technique (CECs-ALI) were treated with 2 µg/ml exoproteins and/or 8 mM elastase inhibitor. Then the epithelial barrier function was evaluated by transepithelial electrical resistance (TEER) assay and tight junction proteins immunofluorescence. Cell viability and the apoptosis rate were examined by CCK8 assay and flow cytometry. TNF-α, IL-6, IL-8, and IL-1ß levels were measured by ELISA. Mice cornea treated with exoproteins and/or elastase inhibitor were evaluated in vivo and in vitro. Results: Elastase (24.2%) is one of the major components of exoproteins. After 2 µg/ml exoproteins were applied to CECs-ALI for two hours, TEER decreased from 323.2 ± 2.7 to 104 ± 6.8 Ω/cm2 (P < 0.001). The immunofluorescence results showed a distinct separation in tight junction and significant degradation of ZO-1 and occludin (P < 0.05). Elastase inhibitor (8 mM) alleviated the decrease in TEER value (234 ± 6.8 Ω cm2) induced by exoproteins. Inhibition of elastase decreased the apoptosis rate of CECs treated with exoproteins from 30.2 ± 3.8% to 7.26 ± 1.3% and the levels of inflammatory factors (P < 0.05). Mice corneal epithelium defect could be induced by exoproteins and protected by elastase inhibitor. Conclusions: Elastase plays a critical role in corneal epithelial barrier dysfunction caused by Pseudomonas aeruginosa exoproteins via damaging tight junctions. The inhibition of elastase could protect the corneal epithelial barrier via reducing virulence and inflammation.

Pulmonary ACE2 expression in neonatal and adult rats.

Children show a distinct presentation of COVID-19, characterized by a lower incidence and mild phenotype, but the reason for this is still unknown. The angiotensin-converting enzyme 2 (ACE2) functions as the primary cell entry receptor for Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is thought to cause distinct clinical features between children and old people. The primary purpose of this study was to determine whether differences exist in the level of expression and distribution of ACE2 between neonatal and adult rat lungs. The lung tissues from rats of various ages were used to investigate the expression patterns of ACE2. Western blot, immunohistochemistry, and immunofluorescence were used to quantify or identify the localization of ACE2 in rat lungs. ACE2 was homogenously expressed in fewer alveolar type II (AT2) cells in the neonatal lung, with no polarization to the alveolar space and additional expression in pulmonary endothelium when compared to adult rat lungs. These findings suggest that the patterns of ACE2 distribution and cellular localization in rat lungs change with age.