WSB1/2 target chromatin-bound lysine-methylated RelA for proteasomal degradation and NF-κB termination.

Proteasome-mediated degradation of chromatin-bound NF-κB is critical in terminating the transcription of pro-inflammatory genes and can be triggered by Set9-mediated lysine methylation of the RelA subunit. However, the E3 ligase targeting methylated RelA remains unknown. Here, we find that two structurally similar substrate-recognizing components of Cullin-RING E3 ligases, WSB1 and WSB2, can recognize chromatin-bound methylated RelA for polyubiquitination and proteasomal degradation. We showed that WSB1/2 negatively regulated a subset of NF-κB target genes via associating with chromatin where they targeted methylated RelA for ubiquitination, facilitating the termination of NF-κB-dependent transcription. WSB1/2 specifically interacted with methylated lysines (K) 314 and 315 of RelA via their N-terminal WD-40 repeat (WDR) domains, thereby promoting ubiquitination of RelA. Computational modeling further revealed that a conserved aspartic acid (D) at position 158 within the WDR domain of WSB2 coordinates K314/K315 of RelA, with a higher affinity when either of the lysines is methylated. Mutation of D158 abolished WSB2's ability to bind to and promote ubiquitination of methylated RelA. Together, our study identifies a novel function and the underlying mechanism for WSB1/2 in degrading chromatin-bound methylated RelA and preventing sustained NF-κB activation, providing potential new targets for therapeutic intervention of NF-κB-mediated inflammatory diseases.

PLK4 deubiquitination by Spata2-CYLD suppresses NEK7-mediated NLRP3 inflammasome activation at the centrosome.

The innate immune sensor NLRP3 assembles an inflammasome complex with NEK7 and ASC to activate caspase-1 and drive the maturation of proinflammatory cytokines IL-1ß and IL-18. NLRP3 inflammasome activity must be tightly controlled, as its over-activation is involved in the pathogenesis of inflammatory diseases. Here, we show that NLRP3 inflammasome activation is suppressed by a centrosomal protein Spata2. Spata2 deficiency enhances NLRP3 inflammasome activity both in the macrophages and in an animal model of peritonitis. Mechanistically, Spata2 recruits the deubiquitinase CYLD to the centrosome for deubiquitination of polo-like kinase 4 (PLK4), the master regulator of centrosome duplication. Deubiquitination of PLK4 facilitates its binding to and phosphorylation of NEK7 at Ser204. NEK7 phosphorylation in turn attenuates NEK7 and NLRP3 interaction, which is required for NLRP3 inflammasome activation. Pharmacological or shRNA-mediated inhibition of PLK4, or mutation of the NEK7 Ser204 phosphorylation site, augments NEK7 interaction with NLRP3 and causes increased NLRP3 inflammasome activation. Our study unravels a novel centrosomal regulatory pathway of inflammasome activation and may provide new therapeutic targets for the treatment of NLRP3-associated inflammatory diseases.

Long non-coding RNA NORAD regulates megakaryocyte differentiation and proplatelet formation via the DUSP6/ERK signaling pathway.

Megakaryopoiesis and platelet production is a complex process that is underpotential regulation at multiple stages. Many long non-coding RNAs (lncRNAs) are distributed in hematopoietic stem cells and platelets. lncRNAs may play important roles as key epigenetic regulators in megakaryocyte differentiation and proplatelet formation. lncRNA NORAD can affect cell ploidy by sequestering PUMILIO proteins, although its direct effect on megakaryocyte differentiation and thrombopoiesis is still unknown. In this study, we demonstrate NORAD RNA is highly expressed in the cytoplasm during megakaryocyte differentiation. Interestingly, we identified for the first time that NORAD has a strong inhibitory effect on megakaryocyte differentiation and proplatelet formation from cultured megakaryocytes. DUSP6/ERK1/2 pathway is activated in response to NORAD knockdown during megakaryocytopoiesis, which is achieved by sequestering PUM2 proteins. Finally, compared with the wild-type control mice, NORAD knockout mice show a faster platelet recovery after severe thrombocytopenia induced by 6 Gy total body irradiation. These findings demonstrate lncRNA NORAD has a key role in regulating megakaryocyte differentiation and thrombopoiesis, which provides a promising molecular target for the treatment of platelet-related diseases such as severe thrombocytopenia.

Isoalantolactone exerts anti-melanoma effects via inhibiting PI3K/AKT/mTOR and STAT3 signaling in cell and mouse models.

BACKGROUND AND AIM: Although the anti-cancer activity of isoalantolactone (IATL) has been extensively studied, the anti-melanoma effects of IATL are still unknown. Here, we have investigated the anti-melanoma effects and mechanism of action of IATL. MTT and crystal violet staining assays were performed to detect the inhibitory effect of IATL on melanoma cell viability. Apoptosis and cell cycle arrest induced by IATL were examined using flow cytometry. The molecular mechanism of IATL was explored by Western blotting, confocal microscope analysis, molecular docking, and cellular thermal shift assay (CETSA). A B16F10 allograft mouse model was constructed to determine the anti-melanoma effects of IATL in vivo. The results showed that IATL exerted anti-melanoma effects in vitro and in vivo. IATL induced cytoprotective autophagy in melanoma cells by inhibiting the PI3K/AKT/mTOR signaling. Moreover, IATL inhibited STAT3 activation both in melanoma cells and allograft tumors not only by binding to the SH2 domain of STAT3 but also by suppressing the activity of its upstream kinase Src. These findings demonstrate that IATL exerts anti-melanoma effects via inhibiting the STAT3 and PI3K/AKT/mTOR signaling pathways, and provides a pharmacological basis for developing IATL as a novel phytotherapeutic agent for treating melanoma clinically.

Constructing Interfacial Oxygen Vacancy and Ruthenium Lewis Acid-Base Pairs to Boost the Alkaline Hydrogen Evolution Reaction Kinetics.

Simultaneous optimization of the energy level of water dissociation, hydrogen and hydroxide desorption is the key to achieving fast kinetics for the alkaline hydrogen evolution reaction (HER). Herein, the well-dispersed Ru clusters on the surface of amorphous/crystalline CeO2-δ (Ru/ac-CeO2-δ ) is demonstrated to be an excellent electrocatalyst for significantly boosting the alkaline HER kinetics owing to the presence of unique oxygen vacancy (VO ) and Ru Lewis acid-base pairs (LABPs). The representative Ru/ac-CeO2-δ exhibits an outstanding mass activity of 7180 mA mgRu -1 that is approximately 9 times higher than that of commercial Pt/C at the potential of -0.1 V (V vs RHE) and an extremely low overpotential of 21.2 mV at a geometric current density of 10 mA cm-2 . Experimental and theoretical studies reveal that the VO as Lewis acid sites facilitate the adsorption of H2 O and cleavage of H-OH bonds, meanwhile, the weak Lewis basic Ru clusters favor for the hydrogen desorption. Importantly, the desorption of OH from VO sites is accelerated via a water-assisted proton exchange pathway, and thus boost the kinetics of alkaline HER. This study sheds new light on the design of high-efficiency electrocatalysts with LABPs for the enhanced alkaline HER.

Synthesis, Photophysics and Tunable Reverse Saturable Absorption of Bis-Tridentate Iridium(III) Complexes via Modification on Diimine Ligand.

Five novel bis-tridentate Ir(III) complexes (Ir-1−Ir-5) incorporating versatile N^N^C ligands and a N^C^N ligand (1,3-di(2-pyridyl)-4,6-dimethylbenzene) were synthesized. With the combination of experimental and theoretical methods, their steady and transient state characteristics were researched scientifically. The UV-visible absorption spectra show that the broadband charge transfer absorbance of those bis-tridentate Ir(III) complexes can reach 550 nm, all of these complexes reveal the long-lasting phosphorescent emission. Because the excited-state absorption is more powerful than the ground-state absorption, a sturdy reverse saturable absorption (RSA) process can ensue in the visible and near-infrared regions when the complexes are exposed to a 532 nm laser. Therefore, the optical power limiting (OPL) effect follows the trend: Ir-5 > Ir-4 ≈ Ir-3 > Ir-2 > Ir-1. Generally speaking, the expansion of π-conjugation and the introduction of electron donating/withdrawing groups on the N^N^C ligand could effectively elevate the OPL effect. Therefore, these octahedral bis-tridentate Ir(III) complexes might be exploited as potential OPL materials.

Cu Single-Atom Catalysts for High-Selectivity Electrocatalytic Acetylene Semihydrogenation.

The site isolation strategy has been employed in thermal catalytic acetylene semihydrogenation to inhibit overhydrogenation and C-C coupling. However, there is a dearth of analogous investigations in electrocatalytic systems. In this work, density functional theory (DFT) simulations demonstrate that isolated Cu metal sites have higher energy barriers on overhydrogenation and C-C coupling. Following this result, we develop Cu single-atom catalysts highly dispersed on nitrogen-doped carbon matrix, which exhibit high ethylene selectivity (>80 % Faradaic efficiency for ethylene, <1 % Faradaic efficiency for C4 , and no ethane) at high concentrations of acetylene. The superior performance observed in the electrocatalytic selective hydrogenation of acetylene can be attributed to the weak adsorption of ethylene intermediates and highly energy barriers on C-C coupling at isolated sites, as confirmed by both DFT calculations and experimental results. This study provides a comprehensive understanding of the isolated sites inhibiting the side reactions of electrocatalytic acetylene semihydrogenation.

Ligand Relay Catalysis Enables Asymmetric Migratory Reductive Acylation of Olefins or Alkyl Halides.

Design of ligands in transition-metal catalyzed reactions is challenging, especially in asymmetric transformations. With each step in the catalytic cycle promoted by its privileged ligand and different steps well-connected by dynamic ligand exchange, synergistic combination of multiple ligands could potentially enhance the catalytic efficiency and selectivity. Now, this concept has been applied to the NiH-catalyzed asymmetric remote hydroacylation of olefins and migratory acylation of alkyl halides with excellent regio- and enantioselectivity, utilizing two simple ligands, one for chain-walking and the other for asymmetric acylation. Starting from abundant alkenes/alkyl halides and carboxylic acids, a wide range of enantioenriched chiral α-aryl ketones can be efficiently accessed under mild conditions.

Vinexin ß deficiency exacerbates diet-induced obesity, hepatosteatosis, insulin resistance and endoplasmic reticulum stress in mice.

Vinexin ß is a member of an adaptor protein family. Previous research has elucidated its role in cell adhesion and growth factor signaling. Recently, several studies demonstrated its role in metabolic abnormality, such as obesity and atherosclerosis. In this study, we found that vinexin ß-knockout (KO) mice were more obese and gained more obvious visceral fat accumulation than their wildtype (WT) littermates fed with high fat diet (HFD). KO mice also showed more severe hepatosteatosis when compared with the WT control, which was in line with the significant increase of key serum lipids in KO mice. Furthermore, we confirmed the inhibited Akt signaling and exacerbated insulin resistance which resulted in high fasting blood glucose in KO mice. The endoplasmic reticulum stress response was found obviously activated which may mediate the metabolic changes in KO mice. Our studies indicated that vinexin ß deficiency promotes the diet-induced metabolic disorders.

Spata2L Suppresses TLR4 Signaling by Promoting CYLD-Mediated Deubiquitination of TRAF6 and TAK1.

Toll-like receptor 4 (TLR4) is a key pattern recognition receptor that can be activated by bacterial lipopolysaccharide to elicit inflammatory response. Proper activation of TLR4 is critical for the host defense against microbial infections. Since overactivation of TLR4 causes deleterious effects and inflammatory diseases, its activation needs to be tightly controlled by negative regulatory mechanisms, among which the most pivotal could be deubiquitination of key signaling molecules mediated by deubiquitinating enzymes (DUBs). CYLD is a member of the USP family of DUBs that acts as a critical negative regulator of TLR4-depedent inflammatory responses by deconjugating polyubiquitin chains from signaling molecules, such as TRAF6 and TAK1. Dysregulation of CYLD is implicated in inflammatory diseases. However, how the function of CYLD is regulated during inflammatory response remains largely unclear. Recently, we and other authors have shown that Spata2 functions as an important CYLD partner to regulate enzymatic activity of CYLD and substrate binding by this protein. Here, we show that a Spata2-like protein, Spata2L, can also form a complex with CYLD to inhibit the TLR4-dependent inflammatory response. We found that Spata2L constitutively interacts with CYLD and that the deficiency of Spata2L enhances the LPS-induced NF-κB activation and proinflammatory cytokine gene expression. Mechanistically, Spata2L potentiated CYLD-mediated deubiquitination of TRAF6 and TAK1 likely by promoting CYLD enzymatic activity. These findings identify Spata2L as a novel CYLD regulator, provide new insights into regulatory mechanisms underlying CYLD role in TLR4 signaling, and suggest potential targets for modulating TLR4-induced inflammation.

Evaluation and countermeasures of contracted services of Chinese family doctors from demanders' point of view - a case study of a city.

BACKGROUND: The "gatekeepers" for residents' health are their family doctors. The implementation of contracted services provided by family doctors is conducive to promoting hierarchical diagnosis and treatment and achieving the objective of providing residents comprehensive and full-cycle health services. Since its implementation in 2016, the contract service system for Chinese family doctors has yielded a number of results while also highlighting a number of issues that require further investigation. Consequently, the purpose of this study is to assess the impact of family doctors' contracted services in a Chinese city from the perspective of demanders (i.e., contracted residents), identify the weak links, and then propose optimization strategies. METHODS: In this study, a city in Shandong Province, China was selected as the sample city. In January 2020, 1098 contracted residents (including 40.5% men and 59.5% women) from 18 primary medical institutions (including township health centers and community health centers) were selected for on-site investigation. Take the PCAT-AS(Adult Short) scale revised in Chinese as the research tool to understand the medical experience of contracted residents in primary medical institutions, and interview some family doctors and residents to obtain more in-depth information. RESULTS: Among the four core dimensions of PCAT-AS, the score of Continuous was the highest (3.44 ± 0.58); The score of Coordinated was the lowest (3.08 ± 0.66); Among the three derived dimensions, the score of Family-centeredness was the highest (3.33 ± 0.65); The score of Culturally-competent was the lowest (2.93 ± 0.77). The types of contracting institutions, residents' age, marital status, occupation, and whether chronic diseases are confirmed are the influencing factors of PCAT scores. CONCLUSION: The family doctors' contracted services in the city has achieved certain results. At the same time, there are still some problems, such as difficult access to outpatient services during non-working hours, incomplete service items, an imperfect referral system, and inadequate utilization of traditional Chinese medicine services, it is recommended that the government continue to enhance and increase its investment in relevant policies and funds. Primary medical institutions should improve the compensation mechanism for family doctors and increase their work enthusiasm, improve and effectively implement the two-way referral system, gradually form an orderly hierarchical pattern of medical treatment, provide diversified health services in accordance with their own service capacity and the actual needs of residents, and improve the utilization rate of traditional Chinese medicine services in primary medical institutions.

Polyphyllin II Induces Protective Autophagy and Apoptosis via Inhibiting PI3K/AKT/mTOR and STAT3 Signaling in Colorectal Cancer Cells.

Polyphyllin II (PPII) is a natural steroidal saponin occurring in Rhizoma Paridis. It has been demonstrated to exhibit anti-cancer activity against a variety of cancer cells. However, the anti-colorectal cancer (CRC) effects and mechanism of action of PPII are rarely reported. In the present study, we showed that PPII inhibited the proliferation of HCT116 and SW620 cells. Moreover, PPII induced G2/M-phase cell cycle arrest and apoptosis, as well as protective autophagy, in CRC cells. We found that PPII-induced autophagy was associated with the inhibition of PI3K/AKT/mTOR signaling. Western blotting results further revealed that PPII lowered the protein levels of phospho-Src (Tyr416), phospho-JAK2 (Tyr1007/1008), phospho-STAT3 (Tyr705), and STAT3-targeted molecules in CRC cells. The overactivation of STAT3 attenuated the cytotoxicity of PPII against HCT116 cells, indicating the involvement of STAT3 inhibition in the anti-CRC effects of PPII. PPII (0.5 mg/kg or 1 mg/kg, i.p. once every 3 days) suppressed HCT116 tumor growth in nude mice. In alignment with the in vitro results, PPII inhibited proliferation, induced apoptosis, and lowered the protein levels of phospho-STAT3, phospho-AKT, and phospho-mTOR in xenografts. These data suggest that PPII could be a potent therapeutic agent for the treatment of CRC.

First-Principles-Based Optimized Design of Fluoride Electrolytes for Sodium-Ion Batteries.

Because of the abundance and low cost of sodium, sodium-ion batteries (SIBs) are next-generation energy storage mediums. Furthermore, SIBs have become an alternative option for large-scale energy storage systems. Because the electrolyte is a critical component of SIBs, fluorination is performed to improve the cycling performance of electrolytes. Based on the first-principles study, we investigated the effects of the type, quantity, and relative position relationships of three fluorinated units, namely -CF1, -CF2, and -CF3, on the cyclic ester molecule ethylene carbonate (EC) and the linear ether molecule 1,2-dimethoxylethane (DME). The optimal fluorination was proposed for EC and DME by studying the bond length, highest occupied molecular orbital, lowest unoccupied lowest orbital, and other relevant parameters. The results revealed that for EC, the optimal fluorination is 4 F fluorination based on four -CF1 units; for DME, CF3CF1CF1-, CF3CF2CF2-, CF3CF1CF2CF3, and CF3CF2CF2CF3, four combinations of three -CF1, -CF2, and -CF3 units are optimal. The designed fluorinated EC and DME exhibited a wide electrochemical stability window and high ionic solvation ability, which overcomes the drawback of conventional solvents and can improve SIB cycling performance.

LncRNA TONSL-AS1 participates in coronary artery disease by interacting with miR-197.

BACKGROUND: It has been reported that high expression levels of miR-197 can predict coronary artery disease (CAD). Our bioinformatics analysis showed that miR-197 may bind to long non-coding RNA (lncRNA) TONSL-AS1. This study aimed to investigate the role of TONSL-AS1 in CAD. METHODS: This study included 60 CAD patients and 60 healthy controls. Coronary angiography was performed to diagnose CAD. The interaction between TONSL-AS1 and miR-197 was predicted by IntaRNA2.0. Western-blot analysis was performed to illustrate the effect of MTONSL-AS1, miR-197 and BCL2 on human primary coronary artery endothelial cells (HCAECs). Cell migration assay was performed to explore the roles of MTONSL-AS1, miR-197 and BCL2 in regulating cell migration. Cell apoptosis assay was performed to investigate the role of MTONSL-AS1, miR-197 and BCL2 in regulating the apoptosis of HCAECs. RESULT: Significant differences in high-density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and gensini score were observed in patients with CAD. In addition, TONSL-AS1 was downregulated in CAD. Follow-up study revealed that low expression levels of TONSL-AS1 and high expression levels of miR-197 predicted poor survival of CAD patients. Overexpression experiments showed that TONSL-AS1 and miR-197 had no significant effect on the expression of each other. We speculated that MAFG-AS1 may sponge miR-145. Moreover, overexpression of TONSL-AS1 increased, while overexpression of miR-197 decreased the expression levels of BCL2. Furthermore, overexpression of TONSL-AS1 attenuated the effects of overexpression of miR-197 on migration and apoptosis of HCAECs. CONCLUSIONS: Therefore, the expression of TONSL-AS1 predicted the survival of CAD patients and it sponged miR-197 to inhibit the apoptosis of HCAECs.

Inactivation of cysteine 674 in the sarcoplasmic/endoplasmic reticulum calcium ATPase 2 causes retinopathy in the mouse.

Diabetic retinopathy is a multifactorial microvascular complication, and its pathogenesis hasn't been fully elucidated. The irreversible oxidation of cysteine 674 (C674) in the sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) was increased in the type 1 diabetic retinal vasculature. SERCA2 C674S knock-in (SKI) mouse line that half of C674 was replaced by serine 674 (S674) was used to study the effect of C674 inactivation on retinopathy. Compared with wild type (WT) mice, SKI mice had increased number of acellular capillaries and pericyte loss similar to those in type 1 diabetic WT mice. In the retina of SKI mice, pro-apoptotic proteins and intracellular Ca2+-dependent signaling pathways increased, while anti-apoptotic proteins and vessel density decreased. In endothelial cells, C674 inactivation increased the expression of pro-apoptotic proteins, damaged mitochondria, and induced cell apoptosis. These results suggest that a possible mechanism of retinopathy induced by type 1 diabetes is the interruption of calcium homeostasis in the retina by oxidation of C674. C674 is a key to maintain retinal health. Its inactivation can cause retinopathy similar to type 1 diabetes by promoting apoptosis. SERCA2 might be a potential target for the prevention and treatment of diabetic retinopathy.

Ultrasonographic study of fetal facial profile markers during the first trimester.

BACKGROUND: To establish reference ranges of fetal facial profile markers and study their correlations with crown-rump length (CRL) during the first trimester (11 ~ 13+ 6 weeks' gestation) in a Chinese population. METHODS: Ultrasonographic images of measuring fetal nuchal translucency (NT) were retrospectively selected randomly in normal fetuses whose parents were both Chinese. The facial markers included inferior facial angle (IFA), maxilla-nasion-mandible (MNM) angle, facial maxillary angle (FMA) and profile line (PL) distance. These markers were measured through ViewPoint 6 software by two experienced sonographers. RESULTS: Three hundred and eighty fetuses were selected. The ICCs (95 % CI) of intra-operator 1 reproducibility of IFA, MNM angle, FMA, PL distance were 0.944 (0.886 ~ 0.973), 0.804 (0.629 ~ 0.902), 0.834 (0.68 ~ 0.918) and 0.935 (0.868 ~ 0.969), respectively. The ICCs (95 % CI) of intra-operator 2 reproducibility of IFA, MNM angle, FMA, PL distance were 0.931 (0.857 ~ 0.967), 0.809 (0.637 ~ 0.904), 0.786 (0.600 ~ 0.892) and 0.906 (0.813 ~ 0.954), respectively. The ICCs (95 % CI) of inter-operator reproducibility of IFA, MNM angle, FMA, PL distance were 0.885 (0.663 ~ 0.953), 0.829 (0.672 ~ 0.915), 0.77 (0.511 ~ 0.891) and 0.844 (0.68 ~ 0.925), respectively. The average ± SD of IFA, MNM angle, FMA and PL distance were 80.2°±7.25°, 4.17°±1.19°, 75.36°±5.31°, 2.78 ± 0.54 mm, respectively. IFA and PL distance significantly decreased with CRL, while MNM angle and FMA significantly increased with CRL. CONCLUSIONS: It was feasible to measure fetal facial markers during the first trimester. In Chinese population, the reference ranges of IFA, MNM angle, FMA and PL distance were 80.2°±7.25°, 4.17°±1.19°, 75.36°±5.31°, 2.78 ± 0.54 mm, respectively, and the measurements were found to correlate with CRL.

Dauricine inhibits proliferation and promotes death of melanoma cells via inhibition of Src/STAT3 signaling.

Melanoma is the most common type of skin cancer. Signal transducer and activator of transcription 3 (STAT3) signaling has been demonstrated to be a therapeutic target for melanoma. Dauricine (Dau), an alkaloid compound isolated from the root of Menispermum dauricum DC., has shown tumor-suppressing effects in multiple human cancers, but its potential in melanoma remains unexplored. In this study, we demonstrated that Dau significantly inhibited the viability and proliferation of A375 and A2058 melanoma cells. Death of melanoma cells was also markedly promoted by Dau. Moreover, Dau inhibited phosphorylation-mediated activation of STAT3 and Src in a dose-dependent manner. Notably, constitutive activation of Src partially abolished the antiproliferative and cytotoxic activities of Dau on melanoma cells. Molecular docking showed that Dau could dock on the kinase domain of Src with a binding energy of -10.42 kcal/mol. Molecular dynamics simulations showed that Src-Dau binding was stable. Surface plasmon resonance imaging analysis also showed that Dau has a strong binding affinity to Src. In addition, Dau suppressed the growth of melanoma cells and downregulated the activation of Src/STAT3 in a xenograft model in vivo. These data demonstrated that Dau inhibits proliferation and promotes cell death in melanoma cells by inhibiting the Src/STAT3 pathways.

The application of three-dimensional ultrasound with reformatting technique in the diagnosis of fetal cleft lip/palate.

OBJECTIVE: To evaluate the clinical value of three-dimensional ultrasound (3D-US) with reformatting technique in the diagnosis of fetal cleft lip/palate (CL/P), especially those involving the secondary palate. METHODS: A total of 113 fetuses suspected with cleft lip (CL) on two-dimensional ultrasound (2D-US) were further evaluated by 2D-US and 3D-US with reformatting technique, in order to clarify the type of oral cleft. Lesions were classified as cleft lip (CL), cleft lip and alveolus (CLA), and cleft lip and palate (CLP) (including primary and secondary palate). All fetuses were followed until birth or termination of pregnancy. The diagnostic accuracies of 2D-US and 3D-US with reformatting technology were compared. RESULTS: Both 2D-US and 3D-US with reformatting successfully detected CLs in the final 103 participants. Among these, 29, 25, and 49 cases were confirmed to have CL, CLA, and CLP, respectively. CL, CLA, and CLP were diagnosed by 2D-US in 34, 66, and 3 cases, respectively, and by 3D-US with reformatting technology in 31, 27, and 45 cases, respectively. The sensitivities of 2D-US and 3D-US with reformatting technology in the diagnosis of CLA were 80% (20/25) and 92.0% (23/25), respectively, and the difference was not statistically significant. For CLP, however, the sensitivities were 6.1% (3/49) and 91.8% (45/49), respectively (P < .001). CONCLUSIONS: Both 2D-US and 3D-US with reformatting technique have high diagnostic accuracy for CL and CLA. However, 3D-US has a much higher diagnostic accuracy for CLP.

The Heterostructure of Ru2 P/WO3 /NPC Synergistically Promotes H2 O Dissociation for Improved Hydrogen Evolution.

Facilitating the dissociation of water and desorption of hydrogen are both crucial challenges for improving the hydrogen evolution reaction (HER) in alkaline media. Herein, we report the synthesis of heterostructure of Ru2 P/WO3 @NPC (N, P co-doped carbon) by a simple hydrothermal reaction using ruthenium and tungsten salts as precursors, followed by pyrolyzing under an Ar atmosphere. The Ru2 P/WO3 @NPC electrocatalyst exhibits an outstanding HER activity with an overpotential of 15 mV at a current density of 10 mA cm-2 and excellent durability in a 1.0 M KOH solution, outperforming state-of-the-art Pt/C and most reported electrocatalysts. Experimental results combined with density functional calculations reveal that the electron density redistribution in Ru2 P/WO3 @NPC is achieved by electron transfer from NPC to Ru2 P/WO3 and from Ru2 P to WO3 , which directly promotes the dissociation of water on W sites in WO3 and desorption of hydrogen on Ru sites in Ru2 P.

A familial cluster of coronavirus disease 2019 (COVID-19) caused by one family member during his asymptomatic incubation period.

An ongoing outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread in the world, whereas asymptomatic carriers may also play a critical role in the pandemic. We report a familial cluster of COVID-19 caused by one family member before his onset of illness, indicating that it seems to be potentially infectious during the incubation period, even earlier than we expected. Close contact, especially in a small enclosed space, might be the cause of familial transmission. The unsynchronized changes in the clinical symptoms and COVID-19 nucleic acid were found in this case, so consecutive nucleic acid detection of pretty suspected cases was recommended. Family members, especially of whom the confirmed cases contacted with since one incubation period before onset rather than 2 days before onset, should be regarded as close contact and centrally isolated in case of asymptomatic infection already existed in the family.