Variations in the alveolar bone morphology in maxillary molar area: a retrospective CBCT study.

BACKGROUND: This study quantitatively analyzed the anatomic structure of the alveolar bone in the maxillary molar region at three potential locations for Temporary Anchorage Device (TAD) placement. Additionally, the study compared the variability in this region across different age groups, sagittal skeletal patterns, vertical facial types, and sexes. METHODS: In this retrospective cone-beam computed tomography study, the buccal alveolar bone was analyzed in the posterior molar area of 200 patients, the measurement items include buccal alveolar bone height, alveolar bone thickness, interradicular distance, and maxillary retromolar space. RESULTS: Buccal alveolar height was greatest in the U56 region. The interradicular space was largest in the U56 region and increased from the alveolar crest to the sinus floor. Buccal alveolar bone thickness was highest in the U67 region and generally increased from the alveolar crest to the sinus floor. The maxillary retromolar space gradually increased from the alveolar crest to the root apex. CONCLUSIONS: TADs are safest when placed in the buccal area between the maxillary second premolar and the first molar, particularly at the 9 mm plane. The U67 region is the optimal safe zone for TAD placement for maxillary dentition distalization. TADs placement in adolescents can be challenging. Maxillary third molar extraction can be considered for maxillary dentition distalization.

Adult outpatients with long COVID infected with SARS-CoV-2 Omicron variant. Part 1: Oral microbiota alterations.

BACKGROUND: Many individuals experience long COVID after SARS-CoV-2 infection. As microbiota can influence health, it may change with COVID-19. This study investigated differences in oral microbiota between COVID-19 patients with and without long COVID. METHODS: Based on a prospective follow-up investigation, this nested case-control study evaluated the differences in oral microbiota in individuals with and without long COVID (Symptomatic and Asymptomatic groups), which were assessed by 16S rRNA sequencing on tongue coating samples. A predictive model was established using machine learning based on specific differential microbial communities. RESULTS: One-hundred-and-eight patients were included (n=54 Symptomatic group). The Symptomatic group had higher Alpha diversity indices (observed_otus, Chao1, Shannon, and Simpson indices), differences in microbial composition (Beta diversity), and microbial dysbiosis with increased diversity and relative abundance of pathogenic bacteria. Marker bacteria (c__Campylobacterota, o__Coriobacteriales, o__Pseudomonadales, and o__Campylobacterales) were associated with long COVID by linear discriminant analysis effect size and receiver operating characteristic curves (AUC 0.821). CONCLUSION: There were distinct variations in oral microbiota between COVID-19 patients with and without long COVID. Changes in oral microbiota may indicate long COVID.

Erratum to 'B4GALNT1 promotes hepatocellular carcinoma stemness and progression via integrin α2ß1-mediated FAK and AKT activation' (JHEP Reports 5 [2023] 100903).

[This corrects the article DOI: 10.1016/j.jhepr.2023.100903.].

The impact of evidence-based nursing leadership in healthcare settings: a mixed methods systematic review.

BACKGROUND: The central component in impactful healthcare decisions is evidence. Understanding how nurse leaders use evidence in their own managerial decision making is still limited. This mixed methods systematic review aimed to examine how evidence is used to solve leadership problems and to describe the measured and perceived effects of evidence-based leadership on nurse leaders and their performance, organizational, and clinical outcomes. METHODS: We included articles using any type of research design. We referred nurses, nurse managers or other nursing staff working in a healthcare context when they attempt to influence the behavior of individuals or a group in an organization using an evidence-based approach. Seven databases were searched until 11 November 2021. JBI Critical Appraisal Checklist for Quasi-experimental studies, JBI Critical Appraisal Checklist for Case Series, Mixed Methods Appraisal Tool were used to evaluate the Risk of bias in quasi-experimental studies, case series, mixed methods studies, respectively. The JBI approach to mixed methods systematic reviews was followed, and a parallel-results convergent approach to synthesis and integration was adopted. RESULTS: Thirty-one publications were eligible for the analysis: case series (n = 27), mixed methods studies (n = 3) and quasi-experimental studies (n = 1). All studies were included regardless of methodological quality. Leadership problems were related to the implementation of knowledge into practice, the quality of nursing care and the resource availability. Organizational data was used in 27 studies to understand leadership problems, scientific evidence from literature was sought in 26 studies, and stakeholders' views were explored in 24 studies. Perceived and measured effects of evidence-based leadership focused on nurses' performance, organizational outcomes, and clinical outcomes. Economic data were not available. CONCLUSIONS: This is the first systematic review to examine how evidence is used to solve leadership problems and to describe its measured and perceived effects from different sites. Although a variety of perceptions and effects were identified on nurses' performance as well as on organizational and clinical outcomes, available knowledge concerning evidence-based leadership is currently insufficient. Therefore, more high-quality research and clinical trial designs are still needed. TRAIL REGISTRATION: The study was registered (PROSPERO CRD42021259624).

Enhanced anaerobic digestion of waste-activated sludge by thermal-alkali pretreatment: a pilot-scale study.

The composition of waste-activated sludge (WAS) is complex, containing a large amount of harmful substances, which pose a threat to the environment and human health. The reduction and resource utilization of sludge has become a development demand in sludge treatment and disposal. Based on the technical bottlenecks in the practical application of direct anaerobic digestion technology, this study adopted two different thermal and thermal-alkali hydrolysis technologies to pretreat sludge. A pilot-scale experiment was conducted to investigate the experimental conditions, parameters, and effects of two hydrolysis technologies. This study showed that the optimal hydrolysis temperature was 70 °C, the hydrolysis effect and pH can reach equilibrium with the hydrolysis retention time was 4-8 h, and the optimal alkali concentration range was 0.0125-0.015 kg NaOH/kg dry-sludge. Thermal-alkali combination treatment greatly improved the performance of methane production, the addition of NaOH increased methane yield by 31.2% than that of 70 °C thermal hydrolysis. The average energy consumption is 75 kWh/m3 80% water-content sludge during the experiment. This study provides a better pretreatment strategy for exploring efficient anaerobic digestion treatment technologies suitable for southern characteristic sewage sludge.

Advances in the Differentiation of hiPSCs into Cerebellar Neuronal Cells.

The cerebellum has historically been primarily associated with the regulation of precise motor functions. However, recent findings suggest that it also plays a pivotal role in the development of advanced cognitive functions, including learning, memory, and emotion regulation. Pathological changes in the cerebellum, whether congenital hereditary or acquired degenerative, can result in a diverse spectrum of disorders, ranging from genetic spinocerebellar ataxias to psychiatric conditions such as autism, and schizophrenia. While studies in animal models have significantly contributed to our understanding of the genetic networks governing cerebellar development, it is important to note that the human cerebellum follows a protracted developmental timeline compared to the neocortex. Consequently, employing animal models to uncover human-specific molecular events in cerebellar development presents significant challenges. The emergence of human induced pluripotent stem cells (hiPSCs) has provided an invaluable tool for creating human-based culture systems, enabling the modeling and analysis of cerebellar physiology and pathology. hiPSCs and their differentiated progenies can be derived from patients with specific disorders or carrying distinct genetic variants. Importantly, they preserve the unique genetic signatures of the individuals from whom they originate, allowing for the elucidation of human-specific molecular and cellular processes involved in cerebellar development and related disorders. This review focuses on the technical advancements in the utilization of hiPSCs for the generation of both 2D cerebellar neuronal cells and 3D cerebellar organoids.

ER-GUARD: an evolutionarily conserved antioxidant defense system at ER membranes.

Oxidative protein folding in the endoplasmic reticulum (ER) is essential for all eukaryotic cells yet generates hydrogen peroxide (H2O2), a reactive oxygen species (ROS). The ER-transmembrane protein that provides reducing equivalents to ER and guards the cytosol for antioxidant defense remains unidentified. Here we combine AlphaFold2-based and functional reporter screens in C. elegans to identify a previously uncharacterized and evolutionarily conserved protein ERGU-1 that fulfills these roles. Deleting C. elegans ERGU-1 causes excessive H2O2 and transcriptional gene up-regulation through SKN-1, homolog of mammalian antioxidant master regulator NRF2. ERGU-1 deficiency also impairs organismal reproduction and behaviors. Both C. elegans and human ERGU-1 proteins localize to ER membranes and form network reticulum structures. We name this system ER-GUARD, Endoplasmic Reticulum Guardian Aegis of Redox Defense. Human and Drosophila homologs of ERGU-1 can rescue C. elegans mutant phenotypes, demonstrating evolutionarily ancient and conserved functions. Together, our results reveal an ER-membrane-specific protein machinery and defense-net system ER-GUARD for peroxide detoxification and suggest a previously unknown but conserved pathway for antioxidant defense in animal cells.

Metal-Free Cascade Formation of C-C and C-N Bond for the Construction of 3-Cyano-2-Pyridones with Insecticidal Properties.

A straightforward and efficient methodology has been developed for the synthesis of 3-cyano-2-pyridones via the C-C and C-N bond formation processes. A total of 51 diverse 3-cyano-2-pyridone derivatives were obtained in moderate to excellent yields. This reaction featured advantages such as a metal-free process, wide functional group tolerance, simple operation, and mild conditions. A plausible mechanism for the reaction was proposed. 3-cyano-2-pyridones as ricinine analogues for insecticidal properties were evaluated, and the compound 3ci (LC50 = 2.206 mg/mL) showed the best insecticidal property.

Maize Autophagy-Related Protein ZmATG3 Confers Tolerance to Multiple Abiotic Stresses.

Abiotic stresses pose a major increasing problem for the cultivation of maize. Autophagy plays a vital role in recycling and re-utilizing nutrients and adapting to stress. However, the role of autophagy in the response to abiotic stress in maize has not yet been investigated. Here, ZmATG3, which is essential for ATG8-PE conjugation, was isolated from the maize inbred line B73. The ATG3 sequence was conserved, including the C-terminal domains with HPC and FLKF motifs and the catalytic domain in different species. The promoter of the ZmATG3 gene contained a number of elements involved in responses to environmental stresses or hormones. Heterologous expression of ZmATG3 in yeast promoted the growth of strain under salt, mannitol, and low-nitrogen stress. The expression of ZmATG3 could be altered by various types of abiotic stress (200 mM NaCl, 200 mM mannitol, low N) and exogenous hormones (500 µM ABA). GUS staining analysis of ZmATG3-GUS transgenic Arabidopsis revealed that GUS gene activity increased after abiotic treatment. ZmATG3-overexpressing Arabidopsis plants had higher osmotic and salinity stress tolerance than wild-type plants. Overexpression of ZmATG3 up-regulated the expression of other AtATGs (AtATG3, AtATG5, and AtATG8b) under NaCl, mannitol and LN stress. These findings demonstrate that overexpression of ZmATG3 can improve tolerance to multiple abiotic stresses.

Alginate nanogel-embedded liposomal drug carriers facilitate drug delivery efficiency in arthritis treatment.

Despite numerous advantages of liposomes in treating rheumatoid arthritis (RA), the in vivo stability remains a critical issue. Current strategies for improving liposomal stability often compromise their original properties. Herein, we designed an alginate nanogel-embedded liposome aiming at retaining those inherent advantages while enhancing their in vivo stability. The introduction of alginate network within the liposome core can provide mechanical support and controlled drug release without affecting the surface properties. Results showed the cross-linking of alginate network within the inner core of liposomes elevated the particle rigidity to 3 times, allowing for improved stability and decreased drug leakage. Moreover, this nanogel-embedded liposome with optimized elasticity obviously facilitated cellular uptake in inflammatory macrophages. When entering blood circulation, increased rigidity altered the composition of protein corona on the particle surface, resulting in 2-fold increase in circulation time and improved drug accumulation in arthritic joints. When anti-inflammatory chlorogenic acid (CA) was encapsulated into the nanogel network, this CA-loaded nanogel-embedded liposome significantly inhibited ROS production and inflammatory response, ultimately achieved superior therapeutic outcome in arthritic rats. Results demonstrated that this nanogel-embedded liposomes can essentially retain the inherent advantages and overcome the drawbacks of liposomes, thereby improving the drug delivery efficiency.

Development and evaluation of a family-child reading picture book on reducing autism spectrum disorder caregivers' psychological stress: a mixed method study.

Introduction: The rapid increasing prevalence of ASD has become a significant global health issue. Caregivers of children with ASD are experiencing higher level of psychological stress and mental disorders. However, interventions to improve the psychological health of caregivers of children with ASD have largely been neglected. Methods: Based on the ADDIE (Analysis, Design, Development, Implementation, and Evaluation) model, we initially did in-depth interviews with 8 caregivers, and conducted field observation in two rehabilitation centers to analyze the daily lives, the empowered components, the emotional moments of the children with autism and their caregivers. Then we designed the outline of the picture book, and developed it by a multi-disciplinary team by 4 rounds. After that, this picture book was sent out to 54 caregivers of children with ASD for family-child reading in one month. A quantitative questionnaire was administered before and after their reading to evaluate the efficacy of reducing their stress and affiliate stigma, and improving self-efficacy, resilience, empowerment capacity; and exit interviews were conducted after their initial reading to assess the acceptability, content appropriateness, perceived benefits and generalizability of this picture book. Quantitative data were analyzed by descriptive analysis and paired t-tests using IBM SPSS 26.0. Qualitative data were analyzed using template analysis. Results: In total, 54 caregivers read the picture book with their child, with the total of 149 (an average of 2.76 per family) times reading in one month. Among them, 39 caregivers returned the following-up questionnaires. Although most of the outcome measures did not showed significant changes except the stress level decreased statistically significant (13.38 ± 3.864 to 11.79 ± 3.238, P=0.001), caregivers reported that the picture book echoed their daily lives and gave them a sense of warmth, inspiration, and hope, as well as some insight on family relationships and attitudes towards the disorder. They also expressed a willingness to disseminate the book to other families with children suffering ASD and the public. Conclusion: This specially designed picture book has been proven to be an acceptable, content-appropriate, and effective family-centered psychological intervention, which could be easily scaled up.

Genetic analysis of congenital unilateral renal agenesis in children based on next-generation sequencing.

BACKGROUND: Congenital unilateral renal agenesis (URA) is a kind of rare birth defect during fetal development with varies clinical phenotypes. The pathogenesis and the relationship between gene and phenotype are still unclear. METHODS: Ten URA fetuses were followed up after birth using postnatal renal ultrasound examination to confirm the diagnosis with nine children were URA and one was Renal Ectopy (RE). Trio- WES, CNV- seq were performed with the 10 children and their close relatives. RESULTS: There were 3 heterozygous variants of CHD7, PROKR2 and NRIP1 genes were identified in 3 children, respectively. CHD7 (c.2663T>C, p.M888T) is classified as likely pathogenic (LP), PROKR2 (c.685G>C, p.G229R) and NRIP1 (c.2705T>G, p.F902C) are classified as variants of uncertain significance (VUS). CHD7 (c.2663T>C, p.M888T) and PROKR2 (c.685G>C, p.G229R) as URA-related genes may be associated with idiopathic hypogonadotropic hypogonadism (IHH) or CHARGE syndrome (CS), and 3D-protein structure prediction revealed that the two variants may affect the stability in the CHD7 protein or PROKR2 protein, separately. The RE-related gene NRIP1 (c.2705T>G, p.F902C) may be causative of congenital anomalies of the kidneys and urinary tract (CAKUT). CONCLUSIONS: Identification of these variants can in exploring the etiology of URA or RE and improve the level of genetic counseling. IMPACTS: We performed trio-whole-exome sequencing (trio- WES) and copy number variation sequencing (CNV- seq) in 10 children, including 9 children with Unilateral Renal Agenesis and 1 with Renal Ectopy after birth. The possible pathogenic genes of URA can be screened using prenatal and postnatal diagnosis of URA fetuses and gene detection after birth. Future studies evaluating this association may lead to a better understanding of URA and elucidate exploring the etiology of URA or RE and improve the level of genetic counseling.

Prognostic prediction of patients having classical papillary thyroid carcinoma with a 4 mRNA-based risk model.

The dysregulation of protein-coding genes involved in various biological functions is closely associated with the progression of thyroid cancer. This study aimed to investigate the effects of dysregulated gene expressions on the prognosis of classical papillary thyroid carcinoma (cPTC). Using expression profiling datasets from the Cancer Genome Atlas (TCGA) database, we performed differential expression analysis to identify differentially expressed genes (DEGs). Cox regression and Kaplan-Meier analysis were used to identify DEGs, which were used to construct a risk model to predict the prognosis of cPTC patients. Functional enrichment analysis unveiled the potential significance of co-expressed protein-encoding genes in tumors. We identified 4 DEGs (SALL3, PPBP, MYH1, and SYNDIG1), which were used to construct a risk model to predict the prognosis of cPTC patients. These 4 genes were independent of clinical parameters and could be functional in cPTC carcinogenesis. Furthermore, PPBP exhibited a strong correlation with poorer overall survival (OS) in the advanced stage of the disease. This study suggests that the 4-gene signature could be an independent prognostic biomarker to improve prognosis prediction in cPTC patients older than 46.

DNA methylation plays important roles in lifestyle transition of Arthrobotrys oligospora.

Trap formation is the key indicator of carnivorous lifestyle transition of nematode-trapping fungi (NTF). Here, the DNA methylation profile was explored during trap induction of Arthrobotrys oligospora, a typical NTF that captures nematodes by developing adhesive networks. Whole-genome bisulfite sequencing identified 871 methylation sites and 1979 differentially methylated regions (DMRs). This first-of-its-kind investigation unveiled the widespread presence of methylation systems in NTF, and suggested potential regulation of ribosomal RNAs through DNA methylation. Functional analysis indicated DNA methylation's involvement in complex gene regulations during trap induction, impacting multiple biological processes like response to stimulus, transporter activity, cell reproduction and molecular function regulator. These findings provide a glimpse into the important roles of DNA methylation in trap induction and offer new insights for understanding the molecular mechanisms driving carnivorous lifestyle transition of NTF.

A high internal heat flux and large core in a warm Neptune exoplanet.

Interactions between exoplanetary atmospheres and internal properties have long been proposed to be drivers of the inflation mechanisms of gaseous planets and apparent atmospheric chemical disequilibrium conditions1. However, transmission spectra of exoplanets have been limited in their ability to observationally confirm these theories owing to the limited wavelength coverage of the Hubble Space Telescope (HST) and inferences of single molecules, mostly H2O (ref. 2). In this work, we present the panchromatic transmission spectrum of the approximately 750 K, low-density, Neptune-sized exoplanet WASP-107b using a combination of HST Wide Field Camera 3 (WFC3) and JWST Near-Infrared Camera (NIRCam) and Mid-Infrared Instrument (MIRI). From this spectrum, we detect spectroscopic features resulting from H2O (21σ), CH4 (5σ), CO (7σ), CO2 (29σ), SO2 (9σ) and NH3 (6σ). The presence of these molecules enables constraints on the atmospheric metal enrichment (M/H is 10-18× solar3), vertical mixing strength (log10Kzz = 8.4-9.0 cm2 s-1) and internal temperature (>345 K). The high internal temperature is suggestive of tidally driven inflation4 acting on a Neptune-like internal structure, which can naturally explain the large radius and low density of the planet. These findings suggest that eccentricity-driven tidal heating is a critical process governing atmospheric chemistry and interior-structure inferences for most of the cool (<1,000 K) super-Earth-to-Saturn-mass exoplanet population.

The dual-configured hydrogen bonds induced by polymerized deep eutectic solvents-modified magnetic biochar enhanced the selectivity for 3,4-methylenedioxymethamphetamine.

The accurate discovering and monitoring of 3,4-methylenedioxymethamphetamine (MDMA) are especially important because of its substantial toxicity and potential harm to human and the ecological systems. Three types of polymerized deep eutectic solvents functionalized magnetic biochar (MBC@poly (AA/AAC/AAm-ChCl)) were successfully synthesized to adsorb MDMA. The isotherm and kinetic data confirmed that MBC@poly (AAm-ChCl) had the strongest adsorption capacity, and the order of adsorption capacity is as follow: MBC@poly(AAm-ChCl) > MBC@poly(AA-ChCl) > MBC@poly(MAA-ChCl), which also revealed that the adsorption was heterogeneous multi-layer chemisorption. The findings of the characterizations manifested that MBC@poly(AAm-ChCl) was the optimal adsorbent owning to its higher nitrogen content, resulting in the formation of a greater number of hydrogen bonds. Due to the strong hydrogen bonding effect of CO and -NH2 functional groups, MBC@poly(AAm-ChCl) exhibited the high selectivity towards MDMA under the coexistence of multiple chemical substances, and excellent adsorption performance over the pH range of 4-11. Urea as a hydrogen bond inhibitor further confirmed MBC@poly(AAm-ChCl) had high-density active hydrogen bonding sites. Furthermore, utilizing density functional theory (DFT) for simulating adsorption both before and after the process verified that the high selectivity of MBC@poly(AAm-ChCl) attributed to the formation of the dual-configured hydrogen bonds. This study provides support for the production of highly selective biochar for use in pretreatment during drug detection.

AMPK regulates immature boar Sertoli cell proliferation through affecting CDK4/Cyclin D3 pathway and mitochondrial function.

Sertoli cell (SC) proliferation plays an important role in sperm production and quality; however, the regulatory mechanism of SC proliferation is not well understood. This study investigated the role of adenosine monophosphate-activated protein kinase (AMPK) in the regulation of immature boar SC activity. Cell counting kit-8, Seahorse XFe96, mitochondrial respiratory enzyme-related assay kits, and transmission electron microscopy were used to detect SC proliferative viability, oxygen consumption rate (OCR), mitochondrial respiratory enzyme activity, and the ultrastructure of primary cultured SCs in vitro from the testes of 21-day-old boars. A dual luciferase reporter assay was performed to determine the miRNA-mRNA target interaction. Western blotting was used to analyze cell proliferation-related protein expression of p38, p21, proliferating cell nuclear antigen (PCNA), Cyclin-dependent kinase 4 (CDK4), Cyclin D3, and phosphorylated retinoblastoma protein (Rb). Each experiment had a completely randomized design, with three replicates in each experiment. The results showed that the AMPK inhibitor (Compound C, 20 µM-24 h) increased cell proliferation viability, ATP production, and maximal respiration of SCs by 0.64-, 0.12-, and 0.08-fold (p < 0.05), respectively; increased the SC protein expression of PCNA, CDK4, Cyclin D3, and p-Rb by 0.13-, 0.09-, 0.88-, and 0.12-fold (p < 0.05), respectively; and decreased the SC protein expression of p38 and p21 by 0.36- and 0.27-fold (p < 0.05), respectively. The AMPK agonist AICAR (2 mM-6 h) significantly inhibited SC ultrastructure, OCR, mitochondrial respiratory enzyme activity, and cell proliferation-related protein levels. AMPK was validated to be a target gene of miR-1285 based on the result in which the miR-1285 mimic inhibited the luciferase activity of wild-type AMPK by 0.54-fold (p < 0.001). MiR-1285 mimic promoted the OCR of SCs, with 0.45-, 0.15-, 0.21-, and 0.30-fold (p < 0.01) increases in ATP production, basal and maximal respiration, and spare capacity, respectively. MiR-1285 mimic increased the mitochondrial respiratory enzyme activity of SCs, with 0.63-, 0.70-, and 0.97-fold (p < 0.01) increases in NADH-Q oxidoreductase, cytochrome c oxidase, and ATP synthase, respectively. Moreover, the miR-1285 mimic increased the protein expression of PCNA, CDK4, Cyclin D3, and p-Rb by 0.24-, 0.30-, 0.22-, and 0.13-fold (p < 0.05), respectively, and reduced the protein expression of p38 and p21 by 0.58- and 0.66-fold (p < 0.001). MiR-1285 inhibitor showed opposite effects on the above indicators and induced numerous autophagosomes and large lipid droplets in SCs. A high dose of estradiol (10 µM-6 h, showed a promotion of AMPK activation in a previous study) significantly inhibited SC ultrastructure, mitochondrial function, and proliferation-related pathways, while these adverse effects were weakened by Compound C treatment or miR-1285 mimic transfection. Our findings suggest that the activation and inhibition of AMPK induced by specific drugs or synthesized targeted miRNA fragments could regulate immature boar SC proliferative activity by influencing the CDK4/Cyclin D3 pathway and mitochondrial function; this helps to provide a basis for the prevention and treatment of male sterility in clinical practice.

Establishment of an induced pluripotent stem cell (iPSC) line (INNDSUi004-A) from a patient with Congenital Nemaline Myopathy.

We used a non-integrated reprogramming approach to establish a human induced pluripotent stem cell (hiPSC) line (INNDSUi004-A) from the skin fibroblasts of a 13-year-old female individual with Congenital Nemaline Myopath. The cells obtained have typical characteristics of embryonic stem cells, show expression of specific pluripotency markers, and can differentiate into three germ layers in vitro. This iPSC cell line has the genetic information of the patient and is a good model for studying disease mechanisms and developing novel therapies.

Overcoming strength-ductility tradeoff with high pressure thermal treatment.

Conventional material processing approaches often achieve strengthening of materials at the cost of reduced ductility. Here, we show that high-pressure and high-temperature (HPHT) treatment can help overcome the strength-ductility trade-off in structural materials. We report an initially strong-yet-brittle eutectic high entropy alloy simultaneously doubling its strength to 1150 MPa and its tensile ductility to 36% after the HPHT treatment. Such strength-ductility synergy is attributed to the HPHT-induced formation of a hierarchically patterned microstructure with coherent interfaces, which promotes multiple deformation mechanisms, including dislocations, stacking faults, microbands and deformation twins, at multiple length scales. More importantly, the HPHT-induced microstructure helps relieve stress concentration at the interfaces, thereby arresting interfacial cracking commonly observed in traditional eutectic high entropy alloys. These findings suggest a new direction of research in employing HPHT techniques to help develop next generation structural materials.

C(sp)-C(sp) Lever-Based Targets of Orientational Chirality: Design and Asymmetric Synthesis.

In this study, the design and asymmetric synthesis of a series of chiral targets of orientational chirality were conducted by taking advantage of N-sulfinylimine-assisted nucleophilic addition and modified Sonogashira catalytic coupling systems. Orientational isomers were controlled completely using alkynyl/alkynyl levers [C(sp)-C(sp) axis] with absolute configuration assignment determined by X-ray structural analysis. The key structural element of the resulting orientational chirality is uniquely characterized by remote through-space blocking. Forty examples of multi-step synthesis were performed, with modest to good yields and excellent orientational selectivity. Several chiral orientational amino targets are attached with scaffolds of natural and medicinal products, showing potential pharmaceutical and medical applications in the future.