Search

Li metal is recognized as one of the most promising anode candidates for next‐generation high specific energy batteries. However, the fragile solid electrolyte interface (SEI) and heterogeneous Li plating/stripping in carbonate electrolyte severely encumber its practical application. Here, the heptafluorobutyramide (HFT) and lithium nitrate (LiNO3) are proposed to synergistically construct a robust SEI layer with excellent Li+ transport kinetics. The HFT can promote the dissolution of LiNO3 in carbonate electrolyte due to the strong cooperation. The results of theoretical calculations, in situ Raman and X‐ray photoelectron spectroscopy with deep Ar‐ion etching demonstrate that HFT and NO3− will be preferentially reduced to a Li3N/LiF‐rich composite structure on the surface of Li metal. Particularly, after the addition of additives, the first solvent shell is converted from solvent‐dominated to anion‐dominated structure, and thus a significantly lower Li‐ion desolvation barrier is presented. Consequently, the Coulombic efficiency (CE) of Li||Cu half cells using the designed carbonate electrolyte can reach 97.1%. The full cells matched with LiFePO4 and LiNi0.8Co0.1Mn0.1O2 (NCM 811) can deliver high‐capacity retention over 100% at −20°C. This work provides an effective strategy for the regulation of solvation structure and the construction of high‐performance Li metal batteries. [ABSTRACT FROM AUTHOR]

Alleviating the decomposition of the electrolyte is of great significance to improving the cycle stability of cathodes, especially for LiCoO2 (LCO), its volumetric energy density can be effectively promoted by increasing the charge cutoff voltage to 4.6 V, thereby supporting the large‐scale application of clean energy. However, the rapid decomposition of the electrolyte under 4.6 V conditions not only loses the transport carrier for lithium ion, but also produces HF and insulators that destroy the interface of LCO and increase impedance. In this work, the decomposition of electrolyte is effectively suppressed by changing the adsorption force between LCO interface and EC. Density functional theory illustrates the LCO coated with lower electronegativity elements has a weaker adsorption force with the electrolyte, the adsorption energy between LCO@Mg and EC (0.49 eV) is weaker than that of LCO@Ti (0.73 eV). Meanwhile, based on the results of time of flight secondary ion mass spectrometry, conductivity‐atomic force microscopy, in situ differential electrochemical mass spectrometry, soft X‐ray absorption spectroscopy, and nuclear magnetic resonance, as the adsorption force increases, the electrolyte decomposes more seriously. This work provides a new perspective on the interaction between electrolyte and the interface of cathode and further improves the understanding of electrolyte decomposition. [ABSTRACT FROM AUTHOR]

Clonal integration is an important ecological advantage of clonal plants. To ask whether clonal integration can help invasive plants escape space limitations, we tested the hypothesis that it can promote the growth of apical ramets when their connected basal ramets grow in limited space. We conducted a greenhouse experiment on the common perennial herb Hydrocotyle vulgaris. Clonal fragments consisting of pairs of connected ramets grew with basal ramets in three different sizes of pots (small, medium, and large) and apical ramets in large pots, and the connection between ramets was either severed or left intact. Pot size significantly affected the growth of basal ramets such that the biomass, number of leaves and flowers, and stolon length were in general greater in medium pots than in large and small pots when stolons were intact and were greater in medium and large pots than in small pots when stolons were severed. Furthermore, pot size interacted with severance to affect the performance of H. vulgaris. When the basal ramets grew in small pots, the intact stolon resulted in a significant promotion of apical ramet growth, but such positive effect was not found when the basal ramets grew in medium and large pots. Our results suggest that H. vulgaris is able to promote the growth of apical ramets to occupy the surrounding areas through clonal integration when the space where basal ramets grow is limited. [ABSTRACT FROM AUTHOR]

Summary: High‐quality genome of rosemary (Salvia rosmarinus) represents a valuable resource and tool for understanding genome evolution and environmental adaptation as well as its genetic improvement. However, the existing rosemary genome did not provide insights into the relationship between antioxidant components and environmental adaptability. In this study, by employing Nanopore sequencing and Hi‐C technologies, a total of 1.17 Gb (97.96%) genome sequences were mapped to 12 chromosomes with 46 121 protein‐coding genes and 1265 non‐coding RNA genes. Comparative genome analysis reveals that rosemary had a closely genetic relationship with Salvia splendens and Salvia miltiorrhiza, and it diverged from them approximately 33.7 million years ago (MYA), and one whole‐genome duplication occurred around 28.3 MYA in rosemary genome. Among all identified rosemary genes, 1918 gene families were expanded, 35 of which are involved in the biosynthesis of antioxidant components. These expanded gene families enhance the ability of rosemary adaptation to adverse environments. Multi‐omics (integrated transcriptome and metabolome) analysis showed the tissue‐specific distribution of antioxidant components related to environmental adaptation. During the drought, heat and salt stress treatments, 36 genes in the biosynthesis pathways of carnosic acid, rosmarinic acid and flavonoids were up‐regulated, illustrating the important role of these antioxidant components in responding to abiotic stresses by adjusting ROS homeostasis. Moreover, cooperating with the photosynthesis, substance and energy metabolism, protein and ion balance, the collaborative system maintained cell stability and improved the ability of rosemary against harsh environment. This study provides a genomic data platform for gene discovery and precision breeding in rosemary. Our results also provide new insights into the adaptive evolution of rosemary and the contribution of antioxidant components in resistance to harsh environments. [ABSTRACT FROM AUTHOR]

SUMMARY: As a plant‐specific transcription factor, lateral organ boundaries domain (LBD) protein was reported to regulate plant growth and stress response, but the functional research of subfamily II genes is limited. SlMYC2, a master regulator of Jasmonic acid response, has been found to exhibit high expression levels in fruit and has been implicated in the regulation of fruit ripening and resistance to Botrytis. However, its role in fruit expansion remains unknown. In this study, we present evidence that a subfamily II member of LBD, namely SlLBD40, collaborates with SlMYC2 in the regulation of fruit expansion. Overexpression of SlLBD40 significantly promoted fruit growth by promoting mesocarp cell expansion, while knockout of SlLBD40 showed the opposite result. Similarly, SlMYC2 knockout resulted in a significant decrease in cell expansion within the fruit. Genetic analysis indicated that SlLBD40‐mediated cell expansion depends on the expression of SlMYC2. SlLBD40 bound to the promoter of SlEXPA5, an expansin gene, but did not activate its expression directly. While, the co‐expression of SlMYC2 and SlLBD40 significantly stimulated the activation of SlEXPA5, leading to an increase in fruit size. SlLBD40 interacted with SlMYC2 and enhanced the stability and abundance of SlMYC2. Furthermore, SlMYC2 directly targeted and activated the expression of SlLBD40, which is essential for SlLBD40‐mediated fruit expansion. In summary, our research elucidates the role of the interaction between SlLBD40 and SlMYC2 in promoting cell expansion in tomato fruits, thus providing novel insights into the molecular genetics underlying fruit growth. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) presents a formidable global health challenge, and conventional therapies face efficacy limitations. Ubiquitin‐specific protease 7 (USP7) plays pivotal roles in GC development, immune response, and chemo‐resistance, making it a promising target. Various USP7 inhibitors have shown selectivity and efficacy in preclinical studies. However, the mechanistic role of USP7 has not been fully elucidated, and currently, no USP7 inhibitors have been approved for clinical use. In this study, DHPO is identified as a potent USP7 inhibitor for GC treatment through in silico screening. DHPO demonstrates significant anti‐tumor activity in vitro, inhibiting cell viability and clonogenic ability, and preventing tumor migration and invasion. In vivo studies using orthotopic gastric tumor mouse models validate DHPO's efficacy in suppressing tumor growth and metastasis without significant toxicity. Mechanistically, DHPO inhibition triggers ferroptosis, evidenced by mitochondrial alterations, lipid Reactive Oxygen Species (ROS), Malondialdehyde (MDA) accumulation, and iron overload. Further investigations unveil USP7's regulation of Stearoyl‐CoA Desaturase (SCD) through deubiquitination, linking USP7 inhibition to SCD degradation and ferroptosis induction. Overall, this study identifies USP7 as a key player in ferroptosis of GC, elucidates DHPO's inhibitory mechanisms, and highlights its potential for GC treatment by inducing ferroptosis through SCD regulation. [ABSTRACT FROM AUTHOR]

The research on fracture mechanisms of brittle materials is extremely difficult such as the determination of the energy absorption modes and the geometric characteristics of debris. In this paper, a dynamic experimental fragment recovery device was developed to study the facture characteristics of A99 ceramics (the mass of Al2O3 accounts for 99%) based on the Split‐Hopkinson pressure bar (SHPB) experiments, in which the energy absorption mechanism was revealed. A three‐view characterization method was developed to obtain the geometric characterization formula under various strain rate; therefore, the geometric parameters of the fragments can be quickly characterized. The failure mode was investigated in correlation between strain rate and micro‐cracks. It was found that the shape of the strain rate controlled the proportion of dissipated energy. At a lower strain rate the fragment was prone to needle shape, while at a higher strain rate (above 2001 s−1) the proportion of dissipated energy increased to 72% and the fragment shape tended to be nearly spherical. A formula based on strain rate was proposed to characterize the geometric parameters of the fragments without the need of geometry dimensions; therefore, the fragment rate can be quickly obtained, which could provide guidance for the design of ceramics parts. [ABSTRACT FROM AUTHOR]

The adsorption properties of five gases on metal oxides (CuO, Ag2O) modified Ti3C2O2 are studied by the first‐principles density functional theory. The gas sensitivity of nitric oxide, ammonia, nitrogen dioxide, methane, and formaldehyde on metal oxides (CuO, Ag2O) modified Ti3C2O2 is systematically discussed on the aspects of adsorption energy, the density of state, electronic localization function, and desorption time. The results prove that metal oxides (CuO, Ag2O) modification can enhance the adsorption abilities of Ti3C2O2. The adsorption capacity of CuO‐modified Ti3C2O2 is NH3 > NO > NO2 > CH2O > CH4, and the adsorption capacity of Ag2O‐modified Ti3C2O2 is NO > NO2 > CH2O >NH3 > CH4. The NO2 adsorption capacity of Ag2O‐modified Ti3C2O2 is 11.24 times that of pure Ti3C2O2. By comparison, CuO‐modified Ti3C2O2 is more suitable for capturing NO gas than Ag2O‐modified Ti3C2O2, and the former exhibits chemically adsorbed. Considering the results, CuO‐ and Ag2O‐modified Ti3C2O2 can be used as oxynitride gas sensors. [ABSTRACT FROM AUTHOR]

Objective: Obesity can affect periodontal tissues and exacerbate periodontitis. Pyroptosis, a newly identified type of inflammatory cell death, is involved in the development of periodontal inflammation. The saturated fatty acid palmitic acid (PA) is elevated in obese patients. The effect of PA on pyroptosis in periodontal ligament cells (PDLCs) and its underlying mechanisms remain unknown. Materials and Methods: Human PDLCs were isolated from healthy individuals and cultured for experiments. The effects of PA on PDLC pyroptosis and the underlying mechanisms were examined by transmission electron microscopy, quantitative real‐time PCR and western blotting. Results: The morphology of PDLCs in the PA group indicated pyroptotic characteristics, including swollen cells, plasma membrane rupture and changes in subcellular organelles. PA induced inflammatory responses in PDLCs, as indicated by an increase in IL‐1β in the cell culture supernatant. Furthermore, we found that the pyroptosis‐related proteins caspase‐1, caspase‐4 and GSDMD were involved in PA‐induced cell death. GSDMD and caspase‐4 inhibitors alleviated pyroptotic death of PDLCs. Moreover, PA promoted NF‐κB P65 phosphorylation. A NF‐κB inhibitor decreased IL‐1β expression and partly rescued cell death induced by PA. Conclusion: PA activated the NF‐κB pathway and induced the inflammatory response in PDLCs. Caspase‐4/GSDMD mediated PDLC pyroptosis induced by PA. [ABSTRACT FROM AUTHOR]

Background: A variety of viruses can cause acute respiratory infections (ARIs), resulting in a high disease burden worldwide. To explore the dominant viruses and their prevalence characteristics in children with ARIs, comprehensive surveillance was carried out in the Pudong New Area of Shanghai. Methods: Between January 2013 and December 2022, the basic and clinical information, and respiratory tract specimens of 0–14 years old children with ARIs were collected in five sentinel hospitals in Shanghai Pudong. Each specimen was tested for eight respiratory viruses, and the positive rates of different age groups, case types (inpatient or outpatient) were analyzed. Results: In our study, 30.67% (1294/4219) children with ARIs were positive for at least one virus. Influenza virus (IFV) was the most commonly detected respiratory virus (349/4219, 8.27%), followed by respiratory syncytial virus (RSV) (217/4219, 5.14%), para‐influenza virus (PIV) (215/4219, 5.10%), and human coronavirus (HCoV, including 229E, OC43, NL63, and HKU1) (184/4219, 4.36%). IFV was the leading respiratory virus in outpatients aged 5–14 years (201/1673, 12.01%); RSV was the most prevalent respiratory virus in both inpatients (61/238, 25.63%) and outpatients (4/50, 8.00%) for ARI patients aged <6 months old. For PIV, HMPV, HCoV, and HRV, the risk of infection usually was higher among young children. Co‐infection with more than two viruses was seen in 3.25% (137/4219). Conclusions: IFV and RSV played important roles in ARIs among children, but the risk populations were different. There are needs for targeted diagnosis and treatment and necessary immunization and non‐pharmaceutical interventions. [ABSTRACT FROM AUTHOR]

Domino reaction of benzo[d]thiazole‐2‐methylamine (S1) has been developed in the presence of MnCl2 ⋅ 4H2O, leading to tetrasubstituted pyrrole coordinated dinuclear Mn(II) complex 1 ([MnClP]2, P−=2,3,4,5‐tetrakis(benzo[d]thiazol‐2‐yl)pyrrol‐1‐ide). The reaction process has been studied by assigning a series of intermediates based on time‐dependent mass spectrometry, control experiments, crystallography, and density functional theory (DFT) theoretical calculation. A plausible mechanism involving an unprecedented divergent‐convergent domino sequence has been proposed. Compound S1 could be activated by MnCl2 ⋅ 4H2O via coordination, which divergently produces two intermediates imine II (1‐(benzo[d]thiazol‐2‐yl)‐N‐(benzo[d]thiazol‐2‐ylmethyl)methanimine) and alkene C (1,2‐bis(benzo[d]thiazol‐2‐yl)ethene) through oxidative self‐condensation and free radical coupling followed by elimination, respectively. They could then react with each other convergently via formal [3+2] cycloaddition to give deprotonated tetrasubstituted pyrrole coordinated intermediate [MnClP] after aromatization. Dimerization of [MnClP] produces the final product 1. Three C−C bonds and one C−N bond are formed through this six‐step domino sequence. The corresponding organic skeleton (HP: 2,2′,2′′,2′′′‐(1H‐pyrrole‐2,3,4,5‐tetrayl)tetrakis(benzo[d]thiazole)) has been obtained from 1 and shows a higher fluorescent quantum yield (52 %) than the reported 3,4‐diphenyl substituted analogue 2,2′‐(3,4‐diphenyl‐1H‐pyrrole‐2,5‐diyl)bis(benzo[d]thiazole) (DPB) (42 %). [ABSTRACT FROM AUTHOR]

Aim: We investigated the relationship between the group 2 innate lymphoid cells (ILC2s)‐myeloid‐derived suppressor cells (MDSCs) axis and obesity‐related breast cancer. Methods: Fifty‐eight patients with breast cancer who had first relapse and metastasis between January 2019 and August 2021 were enrolled. The proportions of ILC2s and MDSCs in blood and the levels of cytokines in serum were detected with flow cytometry. Correlation analysis among clinical characteristics (such as body mass index [BMI]), cytokines, ILC2s, and MDSCs was conducted. Results: There was a significant difference in the proportions of ILC2s and MDSCs between the high BMI group and the normal BMI group (p <.05). In the triple‐negative breast cancer (TNBC) patients, the proportions of ILC2s and MDSCs in the obese group were significantly higher than those in the nonobese group (p <.05). In all breast cancer patients, there was a positive correlation between BMI and the ILC2s‐MDSCs axis (p <.05). However, there was no correlation observed between the number of metastases, progression‐free survival, and the ILC2s‐MDSCs axis (p >.05). Additionally, ILC2s showed positive correlations with MDSCs, interleukin‐5 (IL‐5), IL‐10, IL‐17A, (PD‐L1), programmed cell death 2 ligand 2 (PD‐L2), and molecular typing (p <.05). Similarly, MDSCs exhibited positive correlations with IL‐5, IL‐8, IL‐9, IL‐17A, PD‐L1, and PD‐L2 (p <.05). In patients with TNBC, there was a positive correlation between BMI and IL‐5 (p <.05). Conclusion: Conclusively, obesity may enhance the immunosuppressive effect of the ILC2‐MDSC axis in advanced breast cancer. IL‐5 may play a vital role in the ILC2‐MDSC axis and obesity in TNBC. [ABSTRACT FROM AUTHOR]

Aims: This study was designed to evaluate the magnetic resonance imaging (MRI) patterns of the lower limb muscles in dermatomyositis (DM) with anti‐transcriptional intermediate factor 1‐γ (anti‐TIF1‐γ) antibody. Methods: This retrospective, observational, cross‐sectional study enrolled 12 adult DM patients with anti‐TIF1‐γ antibody. Muscles were assessed for fascial edema, subcutaneous‐tissue edema, muscle edema, and fatty replacement. These features were analyzed in relation to clinical characteristics. Results: All 12 patients underwent hip and thigh MRI, and 8 completed calf MRI. All patients showed myofascial edema, muscle edema, and fatty replacement, and 8 out of 12 further exhibited subcutaneous‐tissue edema. Specifically, myofascial edema of the gastrocnemius was observed in all patients (8/8). The vastus intermedialis and vastus lateralis muscles showed the most severe muscle edema, whereas the caput breve of the biceps femoris, semitendinosus, and soleus muscles exhibited the most severe fatty replacement. Although only 1 patient exhibited asymmetric muscle weakness, 9 showed asymmetric muscle edema, and 10 showed asymmetric fatty replacement. Changes in muscle edema positively correlated with creatine kinase (CK) levels. Conclusions: Myofascial edema of gastrocnemius was a prominent characteristic of anti‐TIF1‐γ‐positive DM. Early detection of muscle edema, as well as CK levels, may be helpful for monitoring disease activity. [ABSTRACT FROM AUTHOR]

Dichloro‐diphenyl‐trichloroethane (DDT) analogs, classified as environmental endocrine disrupting compounds (EDCs), have been extensively employed as potent insecticides that can cause endocrine system disruption. However, the precise dynamic structural characteristics and interactions between human estrogen‐related receptor gamma (hERRγ) and DDT analogs are not yet fully understood. In this study, we comprehensively investigate the impact of these EDCs (DDT, dichloro‐diphenyl‐dichloroethane (DDD), 2,2‐bis(4‐chlorophenyl)ethanol (DDOH), O,P′‐DDT (2,4′‐DDT), 4,4′‐dichlorobenzophenone (DCBP), and 4‐hydrotamoxifen (4‐OHT) on the structural changes of hERRγ and their interaction mechanisms by employing multiple molecular dynamics (MD) simulations coupled with MM‐PBSA and SIE approaches. The consequence manifested that overall structures of these six complexes did not transform markedly, but these compounds can affect the local hERRγ structure, leading to essential changes in interactions with pivotal residues nearby L268, V313, L309, Y326, and F435. And van der Waals interactions are the key to how these EDCs interact with hERRγ. These outcomes contribute to our comprehension the risks of DDT analogues to human health. [ABSTRACT FROM AUTHOR]

Introduction: Intimate partner violence (IPV) is associated with multiple adverse health consequences. Nurses (including midwives) are well positioned to identify patients subjected to IPV, and provide care, support, and referrals. However, studies about nursing response to IPV are limited especially in low‐ and middle‐income countries (LMICs). The study aimed to examine nurses' perceived preparedness and opinions toward IPV and to identify barriers and facilitators in responding to IPV. Design: An explanatory sequential mixed‐methods study was conducted by collecting quantitative data first and explaining the quantitative findings with qualitative data. Methods: The study was conducted in two tertiary general hospitals in northeastern (Shenyang city) and southwestern (Chengdu city) China with 1500 and 1800 beds, respectively. A total of 1071 survey respondents (1039 female [97.0%]) and 43 interview participants (34 female [79.1%]) were included in the study. An online survey was administered from September 3 to 23, 2020, using two validated scales from the Physician Readiness to Manage Intimate Partner Violence Survey. In‐depth, semistructured interviews were conducted from September 15 to December 23, 2020, guided by the Consolidated Framework for Implementation Research. Results: The survey respondents largely agreed with feeling prepared to manage IPV, e.g., respond to discourses (544 [50.8%] of 1071) and report to police (704 [65.7%] of 1071). The findings of surveyed opinions (i.e., Response competencies; Routine practice; Actual activities; Professionals; Victims; Alcohol/drugs) were mixed and intertwined with social desirability bias. The quantitative and qualitative data were consistent, contradicted, and supplemented. Key qualitative findings were revealed that may explain the quantitative results, including lack of actual preparedness, absence of IPV‐related education, training, or practice, and socially desirable responses (especially those pertaining to China's Anti‐domestic Violence Law). Commonly reported barriers (e.g., patients' reluctance to disclose; time constraints) and facilitators (e.g., patients' strong need for help; female nurses' gender advantage), as well as previously unreported barriers (e.g., IPV may become a workplace taboo if there are healthcare professionals known as victims/perpetrators of IPV) and facilitators (e.g., nurses' responses can largely meet the first‐line support requirements even without formal education or training on IPV) were identified. Conclusions: Nurses may play a unique and important role in responding to IPV in LMICs where recognition is limited, education and training are absent, policies are lacking, and resources are scarce. Our findings support World Health Organization recommendations for selective screening. Clinical Relevance: The study highlights the great potential of nurses for IPV prevention and intervention especially in LMICs. The identified barriers and facilitators are important evidence for developing multifaceted interventions to address IPV in the health sector. [ABSTRACT FROM AUTHOR]

Lithium‐rich manganese‐based layered oxides (LMLOs) are considered to be one type of the most promising materials for next‐generation cathodes of lithium batteries due to their distinctive anionic redox processes contributing ultrahigh capacity and energy density. Unfortunately, their practical applications are still plagued by several challenges such as undesirable interfacial reactions and structural evolution, as well as voltage hysteresis/recession, in which irreversible anionic redox behavior bears the brunt as the primacy factor. Undoubtedly, a deep understanding of anionic redox reaction mechanisms and irreversible behavior of oxygen species is crucial in order to provide essential guidance for modification strategies for LMLOs. In this paper, the fundamental understanding of intricate anionic redox reaction mechanisms from thermodynamics models to kinetic anionic redox reaction pathways is comprehensively reviewed, and the existing challenges of LMLOs related with irreversible oxygen reaction behavior are analyzed. Furthermore, numerous representative modification strategies for overcoming these challenges, coupled with their underlying mechanisms for regulating anionic redox reversibility are summarized. In addition, the aspects of multi‐scale structural modifications, integration of interdisciplinary technologies, and application in quasi‐/all‐solid‐state battery systems are given some emphasis in terms of further improvement of LMLOs‐based cathode materials for advanced lithium batteries‐based energy storage systems. [ABSTRACT FROM AUTHOR]

With orotic acid (H3OA) as building ligand, one one‐dimensional (1D) Zn(II) coordination polymer, [Zn2(HOA)(μ2‐OH)(μ3‐OH)(H2O)]n (1), and one tetra‐nuclear Cd(II) cluster, [Cd4(HOA)4(μ2‐OH2)2(H2O)10] (2), have been synthesized at 90 °C and room temperature, respectively. Single‐crystal X‐ray diffraction analyses reveal that complex 1 has an 1D stair‐stepping structure consisting of co‐edge bi‐rhomboid [Zn6] structural motif and μ3‐HOA2− linker, and 2 owns a quasi‐linear tetra‐nuclear [Cd4] cluster structure fastened by μ2‐OH2 and HOA2− fixators. The solid‐state photophysical properties were investigated and 1 and 2 display a distinct emission centered at 374 and 393 nm, respectively. [ABSTRACT FROM AUTHOR]

A recent study conducted in China examined the impact of pre-existing lung diseases on the outcomes of COVID-19 in cancer patients who had received immune checkpoint inhibitors (ICIs). The study found that lung diseases, specifically interstitial lung disease (ILD) and atelectasis, were associated with worse clinical outcomes, severe symptoms, and increased respiratory support in these patients. However, lung cancer, pneumonia, and chronic bronchitis/COPD were not found to be associated with COVID-19 outcomes. The study emphasizes the importance of considering pre-existing lung diseases in the prevention and treatment of COVID-19, particularly in high-risk patients with poor prognoses. Further research is needed to better understand the underlying mechanisms. [Extracted from the article]

Endowing room‐temperature polymorphs with both long‐term stability and easy interconvertibility is a big challenge due to the complexity of intermolecular interactions. Herein, we present a chiral hexagonal perovskite (R‐3‐hydroxy‐1‐methylpiperidinium)[CdCl3] having two room‐temperature crystalline forms featuring obviously distinct second‐harmonic‐generation (SHG) signals with a high switching contrast of ~18 times. The two room‐temperature forms could be long‐term stable yet easily interconvertible through an irreversible thermal‐induced phase transition and a pressure‐driven backward transition, by switching hydrogen bonds via collective reorientation of ordered homochiral cations. Based on the essential role of homochiral organic cations in inducing switchable hydrogen bond linkages, this present instance provides good evidence that relatively irregular organic cations could induce more obvious inorganic chain deformations, thus endowing polymorphs with significantly different SHG signals at room temperature. [ABSTRACT FROM AUTHOR]

Background: Genitourinary and/or brain malformation syndrome (GUBS) is a recently discovered syndrome involving abnormalities of the neurological or urogenital system. PPP1R12A may be the pathological gene causing this syndrome. Currently, to our knowledge, there is only one study related to GUBS in the world. Here, we report a clinical case of a Chinese newborn with congenital micropenis caused by a non‐coding sequence pathogenic variant of PPP1R12A, providing additional evidence on genetic causes of genital malformation. Methods: The genetic cause of the patient's malformation was detected using trio‐whole exome sequencing and Sanger sequencing, and reverse transcription‐PCR analysis was performed by constructing the minigene mutant plasmid in vitro. Results: Genetic testing revealed a novel heterozygous variant, c.2666+3A>G, of the PPP1R12A gene of the patient. The parents at this site were wild‐type, indicating that this might be a de novo variant. The minigene experiment showed that the c.2666+3A>G plasmid led to the deletion of 17 bp in exon 20, and a new mRNA product c.2650_2666del (p.Thr884IleTer2) with skipping of exon 20 was produced. This may lead to PPP1R12A haploinsufficiency and cause biological harm. Conclusions: To our knowledge, this is the first clinical study on a rare variant of PPP1R12A in the Chinese population. The c.2666+3A>G may lead to external genitalia malformation, such as congenital micropenis in male neonates. The results of this study further verified the correlation between GUBS and PPP1R12A haploinsufficiency and revealed the important role of a non‐coding sequence variant in the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

A water‐soluble C‐shaped receptors based on glycoluril and naphthalene building blocks is reported. The complexation formed in water was confirmed by 1H NMR spectroscopy and NOESY technique and DOSY technique. 1H NMR spectroscopy, fluorescence spectroscopy and DLS measurements provide strong evidence that compound 2 undergoes self‐recognition that naphthalene moiety can bind into the bisnaphthalene cleft and head‐to‐tail host–guest complexation to form new supramolecular assemblies in water. SEM and AFM visualized that the complexation formed the cyclic structure. This kind of highly designable monomer structure has great possibility to construct novel supramolecular polymer materials. [ABSTRACT FROM AUTHOR]

Multicellular organisms such as plants contain various cell types with specialized functions. Analyzing the characteristics of each cell type reveals specific cell functions and enhances our understanding of organization and function at the organismal level. Guard cells (GCs) are specialized epidermal cells that regulate the movement of the stomata and gaseous exchange, and provide a model genetic system for analyzing cell fate, signaling, and function. Several proteomics analyses of GC are available, but these are limited in depth. Here we used enzymatic isolation and flow cytometry to enrich GC and mesophyll cell protoplasts and perform in‐depth proteomics in these two major cell types in Arabidopsis leaves. We identified approximately 3,000 proteins not previously found in the GC proteome and more than 600 proteins that may be specific to GC. The depth of our proteomics enabled us to uncover a guard cell‐specific kinase cascade whereby Raf15 and Snf1‐related kinase2.6 (SnRK2.6)/OST1(open stomata 1) mediate abscisic acid (ABA)‐induced stomatal closure. RAF15 directly phosphorylated SnRK2.6/OST1 at the conserved Ser175 residue in its activation loop and was sufficient to reactivate the inactive form of SnRK2.6/OST1. ABA‐triggered SnRK2.6/OST1 activation and stomatal closure was impaired in raf15 mutants. We also showed enrichment of enzymes and flavone metabolism in GC, and consistent, dramatic accumulation of flavone metabolites. Our study answers the long‐standing question of how ABA activates SnRK2.6/OST1 in GCs and represents a resource potentially providing further insights into the molecular basis of GC and mesophyll cell development, metabolism, structure, and function. [ABSTRACT FROM AUTHOR]

LiCoO2 plays a key role in energy storage devices due to its high energy density. And the volumetric energy density of LiCoO2 cathode can be significantly improved by increasing the charging cut‐off voltage to 4.6 V. However, the increase in resistance at the LiCoO2 interface, and the damage to the LiCoO2 from the outside to the inside by the HF generated that caused by the decomposition of the organic electrolyte and LiPF6 under 4.6 V conditions are not conducive to structural stability during cycling. Here, it is shown that the decomposition of electrolyte and LiPF6 is effectively mitigated by inhibiting the interfacial catalytic activity of LiCoO2 using an atomically thin layer of MXenes as a interlayer. Density functional theory results suggest that the decomposition energy of LiPF6 is 1.13 and 3.21 eV at the interface of LiCoO2 and MXenes, respectively. Time of Flight Secondary Ion Mass Spectrometry results further indicate that the decomposition products of the organic electrolyte and LiPF6 have a thinner thickness at the interface of MXenes (5 nm) than LiCoO2 (10 nm). This study provides a new and universal strategy for stabilizing the cathode interface to support the development of high energy density lithium‐ion batteries. [ABSTRACT FROM AUTHOR]

In the ultra‐deep reservoir or other deep‐buried subsurface engineering, the in situ stress is high enough to make the rock transition from the brittle to the plastic. In such situation, the fracturing process always goes with the plastic deformation together. Therefore, to develop an elastoplastic constitutive model which can simultaneously account for both fracture and plastic deformation is critically important. In this paper, an elastoplastic augmented virtual internal bond (EP‐AVIB) model is developed. In EP‐AVIB, a hyperelastic AVIB is developed to characterize the elastic deformation of rock, in which the micro bond is linear elastic in compression whereas is hyperelastic in tension. The Drucker‐Prager yield criterion is employed to characterize the plastic deformation. Thus, the EP‐AVIB can combine the fracture and plastic deformation together. The simulation examples show that the EP‐AVIB can simulate the elastoplastic mechanical behaviors and the fracturing process of rock subjected to compression. It provides a simple approach to the elastoplastic failure simulation of rock. Its perspective in deep reservoir and deep‐buried subsurface engineering simulation should be inspiring. [ABSTRACT FROM AUTHOR]

The frequent outbreaks of the AIDS (Acquired Immune Deficiency Syndrome) pandemic and the limited availability of anti‐Human Immunodeficiency Virus (HIV) drugs highlight the urgent need to develop new antiviral drugs. A detailed understanding of the interactions between TAR‐Binding Proteins (TBP) and RNA will facilitate the discovery of new anti‐AIDS drugs. In order to characterize and explore the key interactions between RNA and TBP, we focused on the wild type (WT) and three mutant TBPs (TBP6.9, TBP6.7, and TBP6.3) with RNA, multiple molecular dynamics simulation and energy computation were performed. The results showed that 12 key residues played a major role in the interaction between TBP and RNA. The mutated residues of TBP changed the interaction between their surrounding residues and RNA, thus affecting the binding of TBP to RNA. In addition, structural and energy analyses showed that in contrast with WT TBP‐RNA complex, the mutated residues had little effect on the backbone structure of TBP, but changes in the van der Waals interactions and electrostatic interaction associated with the side chains are responsible for the altered the binding between three mutant TBPs and RNA complexes. The discovery of TBP‐RNA recognition mechanism in our work provides some useful insights and new opportunities for the development of anti‐aids drugs. [ABSTRACT FROM AUTHOR]

Cistanche deserticola has recently been included in the category of food. In this study, the physical and chemical attributes and antioxidant capacity of six kinds of C. deserticola powders prepared by jet milling were discussed. With the decrease of particle size, the specific surface areas of C. deserticol powders had increased significantly (from 0.040 ± 0.0060 to 0.86 ± 0.030 m2·g−1). The repose angles and slide angles (from 18.43 ± 1.15° to 34.21 ± 1.72° and 27.38 ± 1.72° to 35.80 ± 1.49°, respectively), water and oil holding capacities (from 2.40 ± 0.11 to 1.23 ± 0.12 g/g, 0.73 ± 0.12 to 1.39 ± 0.11 g/g, respectively) of superfine C. deserticola powders were compared with coarse powders. Superfine grinding promoted the dissolution of active substances, such as the dissolution of phenylethanol glycoside increased from 0.15% to 2.11%. The ultrafine powders of C. deserticola show great potential in food industry, such as health foods and dietary foods, extending the application of C. deserticola. Practical Applications: Cistanche deserticola have recently been included into food catalogue and the ultrafine particles of C. deserticola would be widely used in food industry. Therefore, to understand the physico‐chemical and antioxidant properties are very necessary, which could be conducive to improve their application. The study showed that the ultrafine powders of C. deserticola have better physico‐chemical and antioxidant properties than coarse powders. [ABSTRACT FROM AUTHOR]

Antibacterial fabric with high thermal stability and mechanical strength is important for personalized protection, especially under the background of coronavirus pandemic (COVID‐19). This paper presents a facile approach toward high‐efficient antibacterial polypropylene spunbonded nonwoven fabrics (SNFs), which are decorated by a composite of graphene oxide embedded with silver nanoparticles (AgNPs/GO) through dip‐coating and in situ reduction effect of pre‐introduced amino‐terminated hyperbranched polymer (HBP‐NH2). Typically, HBP‐NH2 was grafted onto the GO nanosheets, then silver ions were trapped and self‐reduced by the HBP‐NH2 to generate silver nanoparticles decorated GO. The produced AgNPs are uniformly dispersed on the GO with a size of 13 nm. As an antibacterial coating, the Ag/GO composite could tightly wrap the SNFs fibers through the dip‐padding method, capable of enhancing the thermal stability and mechanical property of SNFs. The treated SNFs exhibited excellent antibacterial activities (~99.9%) against both Echerisia coli and Staphylococcus aureus, promising important potential for biomedical and personal protection applications. [ABSTRACT FROM AUTHOR]

Background: Myocardial injury is a major complication of sepsis and a key factor affecting prognosis. Therefore, early and accurate diagnosis and timely management of sepsis‐induced cardiomyopathy (SICM) are of great significance for the prevention and treatment of sepsis. The gut microbiota has been shown to be closely associated with sepsis or myocardial injury, but the association between the gut microbiota and SICM is not fully understood. This study aimed to explore the link between gut microbiota composition and SICM. Methods: A case‒control and single‐center study of clinical features and gut microbiota profiles by Metagenome and Virome was conducted in SICM patients (n = 15) and sepsis‐uninduced cardiomyopathy patients (SNICM, n = 16). Results: Compared with SNICM patients, SICM patients showed significant myocardial injury and higher 28‐day mortality, SOFA scores, lactate levels, and infection levels on admission. Meanwhile, differences in the composition of gut bacteria, archaea, fungi, and viruses were analyzed between the two groups. Differential gut bacteria or viruses were found to have a good predictive effect on SICM. Furthermore, gut bacteria and viruses that differed between the two groups were strongly related. The abundance of Cronobacter and Cronobacter phage was higher in the SICM group than in the SNICM group, and the receiver operating characteristic curve showed that Cronobacter and Cronobacter phage both had a good predictive effect on SICM. Conclusions: SICM patients may have specific gut microbiota signatures, and Cronobacter and Cronobacter phages have a good ability to identify and diagnose SICM. [ABSTRACT FROM AUTHOR]

Summary: The aim of this study was to investigate the effect of the combination of citrus fibre (CF) and soy protein isolate (SPI) on pork myofibrillar protein (MP) gel properties under low‐sodium salt conditions during the heating process. The composite (with CF and SPI) and single (with 1% and 2% NaCl) MP gels properties were evaluated by colour, water holding capacity (WHC), gel strength, rheological properties, microstructure, secondary structure, and water state. The addition of 0.45% CF and 1.5% SPI significantly improved WHC and gel strength, as well as increased the values of G′ and G′′ (P < 0.05). The microstructure indicated that the CF/SPI could decrease the water channels and form a denser structure through filling effects, which was also proved by the fast T21 relaxation time. However, the addition of 0.9% CF and 3.0% SPI could inhibit the protein aggregation and disrupt the stable and homogeneous structure. The analysis of the secondary structure showed that the CF/SPI resulted in a lower α‐helix content and a higher β‐sheet content compared with MP gels. This study may provide some guidance for the use of CF/SPI to improve MP gel properties in low‐salt meat products. [ABSTRACT FROM AUTHOR]

Background and Purpose: Cancer cachexia and cancer‐associated thrombosis are potentially fatal outcomes of advanced cancer. Nevertheless, thrombin expression in non‐small cell lung cancer (NSCLC) primary tumour tissues and the association between prognosis of NSCLC patients remain largely unknown. Experimental Approach Clinical pathological analysis was performed to determine the relationship between thrombin and tumour progression. Effects of r‐hirudin and direct thrombin inhibitor peptide (DTIP) on cancer progression were evaluated. Western blotting, immunohistochemistry, and immunofluorescence were used to explore the inhibition mechanism of r‐hirudin and DTIP. The therapeutic effect of the combination of DTIP and chemotherapy was determined. Key Results: Thrombin expression in NSCLC tissues was closely related to clinicopathological features and the prognosis of patients. Thrombin deficiency inhibited tumour progression. The novel thrombin inhibitors, r‐hirudin and DTIP, inhibited cell invasion and metastasis in vitro. They inhibited tumour growth and metastasis in orthotopic lung cancer model, inhibited cell invasion, and prolonged survival after injection of tumour cells via the tail vein. They also inhibited angiogenesis and spontaneous metastases from subcutaneously inoculated tumours. The promotion by thrombin of invasion and metastasis was abolished in PAR‐1‐deficient NSCLC cells. r‐hirudin and DTIP inhibited tumour progression through the thrombin‐PAR‐1‐mediated RhoA and NF‐κB signalling cascades via inhibiting MMP9 and IL6 expression. DTIP potentiated chemotherapy‐induced growth and metastatic inhibition and inhibited chemotherapy‐induced resistance in mice. Conclusions and Implications: Thrombin makes a substantial contribution, together with PAR‐1, to NSCLC malignancy. The anti‐coagulants, r‐hirudin and DTIP, could be used in anti‐tumour therapy and a combination of DTIP and chemotherapy might improve therapeutic effects. [ABSTRACT FROM AUTHOR]

NFAT5, an activated T‐cell factor, plays a regulatory role in a variety of autoimmune processes through specific recognition with DNA. However, the details of the interaction of NFAT5 with DNA are unclear. Focused on the complexes of wild type (WT) and mutant NFAT5 with DNA complexes, respectively, we have conducted research on the conformational and dynamics effects caused by residue mutations through molecular dynamics (MD) simulations combined with MM‐PBSA prediction. According to the results of MM‐PBSA, non‐polar interactions are the main driving force in the interaction between NFAT5 and DNA. At the same time, 26 residues play a key role in the interaction with DNA. The energy decomposition results suggest that extensive interactions between the nitrogenous bases of DNA and NFAT5 are responsible for the specific recognition of DNA by NFAT5. By superimposing the structures of mutants and WT complexes, it was found that mutations not only affect the mutated residues, but also change the binding contribution of other amino acids, hydrogen bonding interactions and the stability of the complexes. These results provide a strong rationale and new ideas for NFAT5 as a new target for the treatment of autoimmune diseases. [ABSTRACT FROM AUTHOR]

In this paper, a novel approach is proposed to determine target reliability index based on modeling performance degradation of concrete structures as a stochastic process. First, the Wiener process with drift is used to simulate the degradation process of relative dynamic elastic modulus of concrete, and the drift coefficient and diffusion coefficient of Wiener process are estimated according to the experimental data of degradation of relative dynamic elastic modulus. Then, based on the relations between concrete compressive strength, dynamic elastic modulus, and relative dynamic elastic modulus, the relationship between compressive strength and the amount of degradation of relative dynamic elastic modulus are deduced, and then, the statistical parameters of concrete compressive strength under different service time can be calculated. Finally, based on the established limit state equation of flexural capacity of the weak section and the statistical parameters of compressive strength at different times, the reliability index of a structure under different service life is calculated. On the other hand, according to the drift Wiener process model of relative dynamic elastic modulus degradation of concrete, the time‐varying failure probability of structural durability degradation is calculated based on the first‐passage failure probability formula of drift Wiener process. Taking a concrete plant structure as an example, the time‐varying reliability index calculated based on the limit state equation and the time‐varying failure probability obtained based on the first‐passage failure probability analysis of drift Wiener process are compared, and then the recommended values of target reliability index of structural bearing capacity are comprehensively determined. [ABSTRACT FROM AUTHOR]

In order to accelerate the popularization of high‐strength (HS) steel, the fracture property of Chinese Q690 HS steel was investigated through experiments, numerical simulation, and model establishment in this paper. A three‐dimensional fracture dataset of Q690 steel based on "stress triaxiality‐Lode angle parameter‐fracture strain" was obtained by a hybrid method of experiment and simulation, illustrating that the ductility of Q690 steel under plane strain is lower than that under axisymmetric tension. Eight existing uncoupled fracture models were calibrated, and the Xue‐W model shows reasonable applicability on Q690 steel. To improve the accuracy of fracture prediction, a stress triaxiality and Lode angle parameter dependent uncoupled ductile fracture model was newly proposed, and a simplified version that can be conveniently calibrated without specially designed specimen was provided for engineering application. The proposed model and the simplified version were verified, respectively, and both can achieve satisfactory prediction on the fracture behavior of Q690 HS steel. Highlights: A 3‐D fracture dataset of Q690 steel was obtained by experiment and numerical simulation.Xue‐W model shows reasonable applicability on Q690 steel among 8 existing fracture models.A high‐accuracy uncoupled fracture model was proposed based on complex stress states.A simplified model that can be conveniently calibrated was established for engineering. [ABSTRACT FROM AUTHOR]

Exploring the advanced techniques for protein detection facilitates cell fate investigation. However, it remains challenging to quantify and visualize the protein with one single probe. Here, a luminescent approach to detect hepatic cell fate marker albumin in vitro and living cell labeling with upconversion nanoparticles (UCNPs), which are conjugated with antibody (Ab) and rose bengal hexanoic acid (RBHA) is reported. To guarantee the detection quality and accuracy, an "OFF–ON" strategy is adopted: in the presence of albumin, the luminescence of nanoparticles remains suppressed owing to energy transfer to the quencher. Upon albumin binding to the antibody, the luminescence is recovered under near‐infrared light. In various bio‐samples, the UCNPs‐Ab‐RBHA (UCAR) nanoprobe can sense albumin with a broad detection range (5–315 ng mL−1). When applied to liver ductal organoid culture medium, the UCAR can monitor hepatocyte differentiation in real time by sensing the secreted albumin. Further, UCAR enables live imaging of cellular albumin in cells, organoids, and tissues. In a CCl4‐induced liver injury model, UCAR detects reduced albumin in liver tissue and serum. Thus, a biocompatible nanoprobe for both quantification and imaging of protein in complex biological environment with superior stability and high sensitivity is provided. [ABSTRACT FROM AUTHOR]

Summary: Salicylic acid (SA) is a key phytohormone regulating plant immunity. Although the transcriptional regulation of SA biosynthesis has been well‐studied, its post‐translational regulation is largely unknown.We report that a Kelch repeats‐containing F‐box (KFB) protein, SMALL AND GLOSSY LEAVES 1 (SAGL1), negatively influences SA biosynthesis in Arabidopsis thaliana by mediating the proteolytic turnover of SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1 (SARD1), a master transcription factor that directly drives SA biosynthesis during immunity.Loss of SAGL1 resulted in characteristic growth inhibition. Combining metabolomic, transcriptional and phenotypic analyses, we found that SAGL1 represses SA biosynthesis and SA‐mediated immune activation. Genetic crosses to mutants that are deficient in SA biosynthesis blocked the SA overaccumulation in sagl1 and rescued its growth. Biochemical and proteomic analysis identified that SAGL1 interacts with SARD1 and promotes the degradation of SARD1 in a proteasome‐dependent manner.These results unravelled a critical role of KFB protein SAGL1 in maintaining SA homeostasis via controlling SARD1 stability. [ABSTRACT FROM AUTHOR]

Ethanol is a principal ingredient of alcoholic beverages with potential neurotoxicity and genotoxicity, and the ethanol‐associated oxidative DNA damage in the central nervous system is well documented. Natural product may offer new options to protect the brain against ethanol‐induced neurotoxicity. The male flower of Eucommia ulmoides (EUF) Oliver has been extensively utilized as the tea, the healthy hot drink on the market. In this study, 19 constituents in the effective fraction of EUF were identified by ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS). In the single‐cell gel electrophoresis assay, EUF was observed to ameliorate DNA damage in mouse cerebellum and cerebral cortex caused by acute ethanol administration, which was further confirmed by the morphological observation. The protective effects of EUF were associated with increasing total superoxide dismutase (T‐SOD) and glutathione peroxidase (GSH‐PX) activities, and a decrease in nitric oxide (NO), malondialdehyde (MDA), 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG), and kelch‐like ECH‐associated protein‐1 (Keap1) levels. Molecular docking results demonstrated that compounds 4, 7, 9, and 16 from EUF have a strong affinity to the Keap1 Kelch domain to hinder the interaction of nuclear factor‐erythroid 2‐related factor 2 (Nrf2) with Keap1. These findings suggest that EUF is a potent inhibitor of ethanol‐induced brain injury possibly via the inhibition of oxidative stress. [ABSTRACT FROM AUTHOR]

Black phosphorus (BP), a new member of 2D materials, is an ideal selection to construct spin‐based devices due to its tunable direct bandgap and high carrier mobility. Assembling van der Waals heterostructures is the most popular method to create spintronic devices for 2D materials, especially for the easily oxidized BP. However, it is too complicated to be realized for fabricating large‐scale integrated circuits in practical applications. To overcome this flaw, an oxide layer on BP simultaneously serving as the protection layer and barrier to fabricate a Co/MgO/BP‐based non‐local spin valve is employed. The non‐local spin signals demonstrate the diffusion of pure spin current in the BP channel, which is the direct evidence of the spin injection from Co into BP. Combining the Hanle precession measurements with the Bloch equation fitting, the spin transport parameters of the few‐layer BP can be extracted. The spin diffusion length λs and spin relaxation time τs are 6.15 µm and 241.7 ps, respectively. Therefore, the MgO layer in the non‐local spin valve can simplify the fabrication of 2D material‐based spintronic devices and accelerate their applications. [ABSTRACT FROM AUTHOR]

Objective: In recent years, there are several systematic reviews published on animal experiments of Traditional Chinese medicine (TCM). PRISMA (preferred reporting items for systematic reviews and meta‐analysis) guidelines provide a guarantee for significantly improving the reporting quality of systematic reviews (SRs) and meta‐analysis (MAs) to a certain extent; however, there are still certain defects found in the quality of SRs/MAs of animal experiments of TCM. It has been found that especially, the descriptions of the rationale and animal characteristics of TCM interventions are inadequate. As a result, we have developed a novel reporting guideline for SRs/MAs of animal experimental in the field of TCM (PRISMA‐ATCM) to overcome these problems. Methods: PRISMA‐ATCM reporting guidelines were formed by analyzing both the status and quality of published SRs/MAs of animal experiments and consulting experts in the related fields, and then by Delphi consultation, consensus meeting and revision. Results: Among the 27 items on the PRISMA checklist, Title (1), Structured summary (2), Rationale (3), Objectives (4), Protocol and registration (5), Eligibility criteria (6), Data items (11), Planned methods of analysis (14), Study characteristics (18), Summary of evidence (24), Limitations (25), and Funding (27) have been extensively revised and expanded, to specifically include the details about TCM intervention and animal characteristics. In addition, illustrative examples and explanations have been provided for each item. Conclusion: PRISMA‐ATCM could markedly improve the quality SRs/MAs of animal experiments in the field of TCM. [ABSTRACT FROM AUTHOR]

A novel naphthalimides‐based fluorescent probe (NPHD) selectively detected Cu2+ and PPi through "strong yellow‐weak green‐strong yellow" photonic response in a sequential manner. The formation of NPHD‐Cu2+ resulted in obvious fluorescence decreased and wavelength shift from 595 nm to 525 nm by adding Cu2+ to NPHD solution. The mechanism could be attributed to d→π* electron transfer (ET) from Cu2+ to NPHD. Furthermore, the NPHD‐Cu2+ complex exhibited high selectivity toward PPi through via emission recovery of chemosensor NPHD. The detection limits of NPHD to Cu2+ and NPHD‐Cu2+ to PPi were estimated to be 5.72×108M and 2.39×108M. In addition, NPHD could be employed to detect exogenous Cu2+ and PPi in Hep G2 cells. [ABSTRACT FROM AUTHOR]

Rationale: A large number of studies have shown that the production of aberrant and deleterious copper zinc superoxide dismutase (SOD1) species is closely related to amyotrophic lateral sclerosis (ALS). Therefore, it is of great significance to screen effective inhibitors of misfolding and aggregation of SOD1 for treating ALS disease. Methods: The interaction between flavanone compounds with apo‐SOD1was investigated using native electrospray ion mobility mass spectrometry (native ESI‐IM‐MS). Binding affinities of ligands were compared using native MS, ESI‐MS/MS, collision‐induced unfolding, and competitive experiments. The effect of ligands on apo‐SOD1 aggregation was investigated using the fluorescence spectroscopy method. Results: The results of MS showed that the binding affinity of liquiritin apioside was the strongest, better than the corresponding monosaccharide and aglycone, indicating that the presence and the number of glycosyl group are beneficial to enhance ligand affinity to protein. The results of fluorescence spectroscopy for inhibiting protein aggregation in vitro were consistent with the binding affinity. In addition, the results of the collision‐induced unfolding indicated that liquiritin apioside can slow down the unfolding of the protein. Meanwhile, the results of competition experiment suggested that liquiritin apiosides share different binding sites with naringin and 5‐fluorouridine, which are significant for the structural stability of SOD1. Conclusions: This study revealed that the binding of liquiritin apioside can stabilize apo‐SOD1 dimer and inhibit the aggregation of apo‐SOD1, and illustrated that native ESI‐IM‐MS is a powerful tool for providing insight into investigating the structure–activity relationship between small molecules and protein, and screening protein conformation stabilizers. [ABSTRACT FROM AUTHOR]

Euthyroidism is of profound importance for lifetime health. However, the early diagnosis or therapeutics of thyroid developmental defects has not been established, mainly due to limited understanding of human thyroid development and a lack of recapitulating research model. Herein, the authors elaborate the cell atlas and potential regulatory signaling of the evolution of heterogeneous thyrocyte population from 12 to 16 gestational weeks. Moreover, they establish a long‐term culture of human fetal thyroid organoids (hFTOs) system, which retains the fetal thyroid lineages and molecular signatures, as well as the ability to generate functional human thyroid follicles post mice renal transplantation. Notably, cAMP signaling activation in hFTOs by forskolin boosts the maturation of follicle and thus thyroid hormone T4 secretion, which recapitulates the key developmental events of fetal thyroid. Employing this ex vivo system, it is found that enhanced chromatin accessibility at thyroid maturation genes (such as TPO and TG) loci permits the transcription for hormone production. This study provides the cell atlas of and an organoid model for human thyroid development, which will facilitate thyroid research and prospective medicine. [ABSTRACT FROM AUTHOR]