Hybrid plasmonic aerogel with tunable hierarchical pores for size-selective multiplexed detection of VOCs with ultrahigh sensitivity.

Sensitive and rapid identification of volatile organic compounds (VOCs) at ppm level with complex composition is vital in various fields ranging from respiratory diagnosis to environmental safety. Herein, we demonstrate a SERS gas sensor with size-selective and multiplexed identification capabilities for VOCs by executing the pre-enrichment strategy. In particular, the macro-mesoporous structure of graphene aerogel and micropores of metal-organic frameworks (MOFs) significantly improved the enrichment capacity (1.68 mmol/g for toluene) of various VOCs near the plasmonic hotspots. On the other hand, molecular MOFs-based filters with different pore sizes could be realized by adjusting the ligands to exclude undesired interfering molecules in various detection environments. Combining these merits, graphene/AuNPs@ZIF-8 aerogel gas sensor exhibited outstanding label-free sensitivity (up to 0.1 ppm toluene) and high stability (RSD=14.8%, after 45 days storage at room temperature for 10 cycles) and allowed simultaneous identification of multiple VOCs in a single SERS measurement with high accuracy (error < 7.2%). We visualize that this work will tackle the dilemma between sensitivity and detection efficiency of gas sensors and will inspire the design of next-generation SERS technology for selective and multiplexed detection of VOCs.

Social vulnerability assessment under different extreme precipitation scenarios: A case study in Henan Province, China.

Extreme precipitation usually cause grievous losses&casualties, which varies greatly under different scenarios. This paper took Henan province as an example, it innovatively constructed three different extreme precipitation scenarios and built indicators system of social vulnerability from exposure, sensitivity and resilience based on MOVE framework. Social Vulnerability Indexs(SoVI) were then calculated by mathematical models under three different reoccurrence intervals. The results show that SoVI was low in the west and high in the north. High SoVI areas expanded to the middle and south as recurrence intervals increased. SoVI in each area of Henan province increased along with the recurrence intervals at different growth rates. The larger the recurrence interval was, the faster the SoVI increased. The results indicate SoVI is greatly affected by disaster levels, which need to be incorporated into social vulnerability. This study provides not only a new thought for social vulnerability assessment, but also a reference for the policymakers to formulate related risk management policies.

Social support systems involved in suicide prevention and intervention among adolescents: A Delphi study in Shanghai.

The rotes of attempted and completed suicide among adolescents are increasing globally. Social support can help decrease the risk of adolescent suicide, but this aspect has been rarely studied in China. The present study aimed to use the Delphi methodology to establish a set of guidelines for the development of social support resources, with the goal of collectively reducing suicide risks among adolescents in Shanghai. We commenced the study in April 2021, established a research team, searched the keywords using Web of Science from 2016 to 2021 and ultimately designed a pre-evaluation index. Next, following Donabedian's Structure-Process-Outcome model, the research developed a questionnaire comprising 3 level-1, 12 level-2, and 73 level-3 indicators. Ten experts were enlisted to conduct three rounds of e-mail inquiries in order to finalize the indicator system, resulting in 2 level-1, 11 level-2, and 52 level-3 indicators, as well as expert consensus. Our findings indicate that the social support systems should include parents, schools, psychiatric hospitals, social organizations, and government departments, with the government sector being the most important ((M = 9.4). Furthermore, our study revealed that school counselors and psychologists play similar roles to psychiatrists within the interdisciplinary team (M ± S = 9.2 ± 1.1). As per the expert consensus, social support systems should strengthen government-led and interdisciplinary collaboration, prioritize suicide prevention in schools and encourage greater involvement from social organizations.

Wearable Plasmonic Sensors Engineered via Active-Site Maximization of TiVC MXene for Universal Physiological Monitoring at the Molecular Level.

Two-dimensional transition metal carbon/nitrides (MXenes) are promising candidates to revolutionize next-generation wearable sensors as high-performance surface-enhanced Raman scattering (SERS) substrates. However, low sensitivity of pure MXene nanosheets and weak binding force or uncontrolled in situ growth of plasmonic nanoparticles on hybrid MXene composites limit their progress toward universal and reliable sensors. Herein, we designed and manufactured a highly sensitive, structurally stable wearable SERS sensor by in situ fabrication of plasmonic nanostructures on the flexible TiVC membranes via the maximization of chemically reducing sites using alkaline treatment. DFT calculations and experimental characterization demonstrated that the hydroxyl functional groups on the surface of MXenes can facilitate the reduction of metal precursors and the nucleation of gold nanoparticles (AuNPs) and can be covalently attached to AuNPs. Thus, the fabricated flexible TiVC-OH-Au sensor satisfied the rigorous mechanical requirements for wearable sensors. In addition, combining the electromagnetic (EM) enhancement from dense AuNPs formed by the activation of nucleation sites and charge transfer (CT) between target molecule and substrate induced by the abundant DOS near the Fermi level of TiVC, the fabricated sensor exhibits ultrasensitivity, long-term stability, good signal repeatability, and excellent mechanical durability. Moreover, the proof-of-concept application of the wearable SERS sensor in sweat sensing was demonstrated to monitor the content of nicotine, methotrexate, nikethamide, and 6-acetylmorphine in sweat at the molecular level, which was an important step toward the universality and practicality of the wearable sensing technology.

Genetic Intratumor Heterogeneity Remodels the Immune Microenvironment and Induces Immune Evasion in Brain Metastasis of Lung Cancer.

INTRODUCTION: Brain metastasis, with the highest incidence in patients with lung cancer, significantly worsens prognosis and poses challenges to clinical management. To date, how brain metastasis evades immune elimination remains unknown. METHODS: Whole-exome sequencing and RNA sequencing were performed on 30 matched brain metastasis, primary lung adenocarcinoma, and normal tissues. Data from The Cancer Genome Atlas primary lung adenocarcinoma cohort, including multiplex immunofluorescence, were used to support the findings of bioinformatics analysis. RESULTS: Our study highlights the key role of intratumor heterogeneity of genomic alterations in the metastasis process, mainly caused by homologous recombination deficiency or other somatic copy number alteration-associated mutation mechanisms, leading to increased genomic instability and genomic complexity. We further proposed a selection model of brain metastatic evolution in which intratumor heterogeneity drives immune remodeling, leading to immune escape through different mechanisms under local immune pressure. CONCLUSIONS: Our findings provide novel insights into the metastatic process and immune escape mechanisms of brain metastasis and pave the way for precise immunotherapeutic strategies for patients with lung cancer with brain metastasis.

Triple-enhanced Raman scattering sensors from flexible MXene/Au nanocubes platform via attenuating the coffee ring effect.

Developing substrates that combine sensitivity and signal stability is a major challenge in surface enhanced Raman scattering (SERS) research. Herein, we present a flexible triple-enhanced Raman Scattering MXene/Au nanocubes (AuNCs) sensor fabricated by selective filtration of Ti3C2Tx MXene/AuNCs hybrid on the Ti3C2Tx MXene membrane and subsequent treatment with 1H,1H,2H,2H-perfluoro-octyltriethoxysilane (FOTS). The resultant superhydrophobic MXene/AuNCs-FOTS membrane not only provides the SERS substrate with environmental stability, but also imparts analyte enrichment to enhance the sensitivity (LOD = 1 × 10-14 M) and reliability (RSD = 6.41%) for Rhodamine 6G (R6G) molecules owing to the attenuation of the coffee ring effect. Moreover, the triple enhancement mechanism of combining plasmonic coupling enhancement from plasmonic coupling (EM) of nearby AuNCs at lateral and longitudinal direction of MXene/AuNCs-FOTS membrane, charge transfer (CT) from Ti3C2Tx MXene and target molecules and analyte enrichment function provides the substrate with excellent SERS performance (EF = 3.19 × 109), and allows efficient quantification of biomarkers in urine. This work could provide new insights into MXenes as building blocks for high-performance substrates and fill existing gaps in SERS techniques.

Li-Mg-Si bioceramics provide a dynamic immuno-modulatory and repair-supportive microenvironment for peripheral nerve regeneration.

Biomaterials can modulate the local immune and repair-supportive microenvironments to promote peripheral nerve regeneration. Inorganic bioceramics have been widely used for regulating tissue regeneration and local immune response. However, little is known on whether inorganic bioceramics can have potential for enhancing peripheral nerve regeneration and what are the mechanisms underlying their actions. Here, the inorganic lithium-magnesium-silicon (Li-Mg-Si, LMS) bioceramics containing scaffolds are fabricated and characterized. The LMS-containing scaffolds had no cytotoxicity against rat Schwann cells (SCs), but promoted their migration and differentiation towards a remyelination state by up-regulating the expression of neurotrophic factors in a ß-catenin-dependent manner. Furthermore, using single cell-sequencing, we showed that LMS-containing scaffolds promoted macrophage polarization towards the pro-regenerative M2-like cells, which subsequently facilitated the migration and differentiation of SCs. Moreover, implantation with the LMS-containing nerve guidance conduits (NGCs) increased the frequency of M2-like macrophage infiltration and enhanced nerve regeneration and motor functional recovery in a rat model of sciatic nerve injury. Collectively, these findings indicated that the inorganic LMS bioceramics offered a potential strategy for enhancing peripheral nerve regeneration by modulating the immune microenvironment and promoting SCs remyelination.

Respiratory Movements at Different Ages.

Background and Objectives: The current study aimed to better understand the changes in respiration that occur with aging in men and women to provide accurate recommendations for breathing exercises to improve health. Materials and Methods: A total of 610 healthy subjects, aged 20 to 59, participated in the study. They performed quiet breathing while wearing two respiration belts (Vernier, Beaverton, OR, USA) at the height of the navel and at the xiphoid process to record abdominal motion (AM) and thoracic motion (TM), respectively. Vital capacity, representing maximal inhalation movement, was measured using a spirometer (Xindonghuateng, Beijing, China). After exclusion, 565 subjects (164 men, aged 41 ± 11; 401 women, aged 42 ± 9) were included for statistical analysis using the Kruskal-Wallis U test and stepwise multiple linear regression. Results: Abdominal motion and its contribution to spontaneous breathing were significantly larger for older men, while the contribution of thoracic motion was smaller for older men. There was no significant difference in thoracic motion between the younger and older men. The differences in women's respiratory movements among various ages were mild and negligible. The contribution of thoracic motion to spontaneous breathing in women was larger than in men for those of older ages (40-59 years), but not for those of younger ages (20-39 years). Additionally, men's and women's vital capacities were less in those of older ages, and the men's were larger than the women's. Conclusions: The findings indicate that men's abdominal contribution to spontaneous breathing increased from 20 to 59 years of age due to increased abdominal motion. Women's respiratory movements did not change much with aging. The maximal inhalation movement became smaller with aging for men and women. Healthcare professionals should focus on improving thoracic mobility when addressing health concerns about aging.

High-efficient adsorption for versatile adsorbates by elastic reduced graphene oxide/Fe3O4 magnetic aerogels mediated by carbon nanotubes.

Fabrication of highly elastic three-dimensional aerogel adsorbents with outstanding adsorption capacities is a long pursuit for the treatment of industrial contaminated water. In this work, a magnetic reduced graphene oxide (rGO)/Fe3O4/carbon nanotubes (CNTs) aerogel material was constructed by the electrostatic attraction between the negatively charged GO and positively charged CNTs following a one-pot water bath treatment. The as-synthesized aerogel demonstrated high compressive stress (28.4 kPa) and lower density (24.11 mg/cm3) with exceptional adsorption capacities for versatile adsorbates which are attributed to CNTs and magnetic Fe3O4 nanoparticles. The effect of pH, initial concentration of adsorbates (dyes, Cd (ІІ) ions, organic solvents, and pump oil), content of CNTs and cyclic times on the adsorption capacities of the aerogel were investigated in detail. Furthermore, from simulation, the adsorption kinetics, and thermodynamics of the aerogel for adsorbates were more satisfied by endothermic quasi-second-order kinetic model with characteristic physical adsorption. Thus, the optimized rGO/Fe3O4/CNTs-10 aerogel adsorbent can be used as a powerful and versatile tool to deal with contaminated industrial or domestic wastewater.

Sales of antibiotics without a prescription in pharmacies, 2017 and 2021, China.

Objective: To measure sales of antibiotics without a prescription in pharmacies in China in 2017 and 2021, before and during the coronavirus disease 2019 (COVID-19) pandemic, and determine the factors associated with such sales. Methods: We conducted cross-sectional surveys using the simulated patient method in retail pharmacies in 13 provinces in eastern, central and western China in 2017 and 2021. At the pharmacies, the simulated patients (trained medical students) reported that they had mild respiratory tract symptoms and asked for treatment, using a three-stage process: (i) request some treatment; (ii) request antibiotics; (iii) request specific antibiotics. We used multivariable logistic regression analysis to determine factors associated with sale of antibiotics without a prescription. Findings: Of the pharmacies visited in 2017, 83.6% (925/1106) sold antibiotics without a prescription; this figure was 78.3% (853/1090) in 2021 (P-value: 0.002). After excluding pharmacies prohibited from selling antibiotics because of COVID-19, this difference was not significant (83.6% versus 80.9%; 853/1054; P-value: 0.11). Factors significantly associated with selling antibiotics without a prescription in both 2017 and 2019 were: location in central and western China compared with eastern China; being in a township or village compared with in a city; and presence of a counter where antibiotics were dispensed. Conclusion: Although laws became stricter between 2017 and 2021, antibiotic sales without a prescription were still common in pharmacies across China. Existing regulations need to be more strictly enforced, and pharmacy staff and the public should be made more aware of the risks of antibiotic misuse and dangers of antimicrobial resistance.

Plasmonic Coupling of Au Nanoclusters on a Flexible MXene/Graphene Oxide Fiber for Ultrasensitive SERS Sensing.

High sensitivity, good signal repeatability, and facile fabrication of flexible surface enhanced Raman scattering (SERS) substrates are common pursuits of researchers for the detection of probe molecules in a complex environment. However, fragile adhesion between the noble-metal nanoparticles and substrate material, low selectivity, and complex fabrication process on a large scale limit SERS technology for wide-ranging applications. Herein, we propose a scalable and cost-effective strategy to a fabricate sensitive and mechanically stable flexible Ti3C2Tx MXene@graphene oxide/Au nanoclusters (MG/AuNCs) fiber SERS substrate from wet spinning and subsequent in situ reduction processes. The use of MG fiber provides good flexibility (114 MPa) and charge transfer enhancement (chemical mechanism, CM) for a SERS sensor and allows further in situ growth of AuNCs on its surface to build highly sensitive hot spots (electromagnetic mechanism, EM), promoting the durability and SERS performance of the substrate in complex environments. Therefore, the formed flexible MG/AuNCs-1 fiber exhibits a low detection limit of 1 × 10-11 M with a 2.01 × 109 enhancement factor (EFexp), signal repeatability (RSD = 9.80%), and time retention (remains 75% after 90 days of storage) for R6G molecules. Furthermore, the l-cysteine-modified MG/AuNCs-1 fiber realized the trace and selective detection of trinitrotoluene (TNT) molecules (0.1 µM) via Meisenheimer complex formation, even by sampling the TNT molecules at a fingerprint or sample bag. These findings fill the gap in the large-scale fabrication of high-performance 2D materials/precious-metal particle composite SERS substrates, with the expectation of pushing flexible SERS sensors toward wider applications.

Cancer cells co-opt nociceptive nerves to thrive in nutrient-poor environments and upon nutrient-starvation therapies.

Although nutrient-starvation therapies can elicit strong anti-tumor effects in multiple carcinomas, it has been convincingly demonstrated that cancer cells exploit the tumor microenvironment to thrive in nutrient-poor environments. Here, we reveal that cancer cells can co-opt nociceptive nerves to thrive in nutrient-poor environments. Initially examining the low-glucose environment of oral mucosa carcinomas, we discovered that cancer cells employ ROS-triggered activation of c-Jun to secrete nerve growth factor (NGF), which conditions nociceptive nerves for calcitonin gene-related peptide (CGRP) production. The neurogenic CGRP subsequently induces cytoprotective autophagy in cancer cells through Rap1-mediated disruption of the mTOR-Raptor interaction. Both anti-glycolysis and anti-angiogenesis-based nutrient-starvation therapies aggravate the vicious cycle of cancer cells and nociceptive nerves and therapeutically benefit from blocking neurogenic CGRP with an FDA-approved antimigraine drug. Our study sheds light on the role of the nociceptive nerve as a microenvironmental accomplice of cancer progression in nutrient-poor environments and upon nutrient-starvation therapies.

Unveiling the Noncanonical Autophagy-Independent Role of ATG7 and ATG9B in Head and Neck Squamous Cell Carcinoma (HNSCC).

The role of autophagy in cancer remains elusive, and nontargeted autophagy inhibitors have limited therapeutic effects in HNSCC. Here, we systematically analyzed the correlation of autophagy-related genes in HNSCC through TCGA and single-cell sequencing data (GSE103322). ATG9B and ATG7 were found to have noncanonical autophagy-independent functions in HNSCC. Specifically, ATG9B was a protective factor in HNSCC patients through downregulating cancer cell EMT, and ATG7 was correlated with the immunosuppressive environment in HNSCC. Mechanistically, single-cell analysis revealed that ATG9B increased the epithelial phenotype of cancer cells but did not influence EMT signaling pathways. ATG7 was strongly correlated with elevated immunosuppressive checkpoints like PD-1, PD-L1, and CTLA4 in HNSCC. Further single-cell analysis and multiple immunofluorescence colocalization analyses indicated that ATG7 contributed to the high expression of PD-L1 in myeloid cells but not cancer cells. Collectively, our results revealed noncanonical autophagy-independent functions of autophagy-related genes. These results increase understanding of the intricacies of autophagy and may contribute to precision treatment using autophagy-targeted therapies.

Transcriptomic analysis provides a new insight: Oleuropein reverses high glucose-induced osteogenic inhibition in bone marrow mesenchymal stem cells via Wnt10b activation.

Adverse events of diabetes mellitus (DM) include bone damages, such as the increased incidence of osteoporosis and bone fractures, which are known as diabetic osteopathy. The pathogenic mechanism of diabetic osteopathy is complex, and hyperglycemia is a vital cause involved in it. Bone marrow mesenchymal stem cells (BMSCs) exert a significant effect on bone formation. Therefore, in this paper, transcriptomic changes of BMSCs cultured in high glucose (35 mM) for 30 days are mainly investigated. In addition, 794 up-regulated genes and 1,162 down-regulated genes were identified. Then, biological functions of the differentially expressed genes in the high glucose microenvironment were investigated by two kinds of functional analyses. Gene Set Enrichment Analysis was also applied to focus on the significant gene sets and it is found that Wnt10b expression witnessed a remarkable decrease in BMSCs under the high glucose microenvironment. At last, in vitro experiments revealed that oleuropein effectively reversed high glucose-induced osteogenic inhibition via activating Wnt10b in BMSCs.

Blockade of STAT3/IL-4 overcomes EGFR T790M-cis-L792F-induced resistance to osimertinib via suppressing M2 macrophages polarization.

BACKGROUND: The mechanism of missense alteration at EGFR L792F in patients with non-small cell lung cancer resistant to osimertinib has not been sufficiently clarified. We aimed to explore the critical molecular events and coping strategies in osimertinib resistance due to acquired L792F mutation. METHODS: Circulating tumor DNA-based sequencing data of 1153 patients with osimertinib resistance were collected to illustrate the prevalence of EGFR L792F mutation. Sensitivity to osimertinib was tested with constructed EGFR 19Del/T790M-cis-L792F cell lines in vitro and in vivo. The correlation and linked pathways between M2 macrophage polarization and EGFR L792Fcis-induced osimertinib resistance were investigated. Possible interventions to suppress osimertinib resistance by targeting IL-4 or STAT3 were explored. FINDINGS: The concomitant EGFR L792F was identified as an independent mutation following the acquisition of T790M after osimertinib resistance, in that 5 of the 946 patients with osimertinib resistance harbored EGFR T790M-cis-L792F mutation. Transfected EGFR 19Del/T790M-cis-L792F in cell lines had decreased sensitivity to osimertinib and enhanced infiltrating macrophage with M2 polarization. Silico analyses confirmed the role of M2 polarization in osimertinib resistance induced by EGFR T790M-cis-L792F mutation. EGFR T790M-cis-L792F mutation upregulated phosphorylation of STAT3 Tyr705 and promoted its specific binding to IL4 promoter, enhancing IL-4 expression and secretion and inducing macrophage M2 polarization. Furthermore, blockade of STAT3/IL-4 (SH-4-54 or dupilumab) suppressed macrophage M2 polarization and regressed tumor sensitivity to osimertinib. INTERPRETATION: Our results proved that targeting EGFR T790M-cis-L792F/STAT3 Tyr705/IL-4 pathway could be a potential strategy to suppress osimertinib resistance in NSCLC. FUNDING: This work was supported by the National Natural Science Foundation of China (81871889, 82072586, 81902910), Beijing Natural Science Foundation (7212084, 7214249), the China National Natural Science Foundation Key Program (81630071), the National Key Research and Development Project (2019YFC1315704), CAMS Innovation Fund for Medical Sciences (CIFMS 2021-1-I2M-012), Aiyou Foundation (KY201701) and CAMS Key Laboratory of translational research on lung cancer (2018PT31035).

PD-1 inhibitors plus oxaliplatin or cisplatin-based chemotherapy in first-line treatments for advanced gastric cancer: A network meta-analysis.

Background: Currently, there has been no direct comparison between programmed cell death protein 1 (PD-1) inhibitors plus different chemotherapy regimens in first-line treatments for advanced gastric cancer (AGC). This study performed a network meta-analysis (NMA) to evaluate the efficacy and safety of PD-1 inhibitors plus oxaliplatin- or cisplatin-based chemotherapy. Methods: PubMed, Embase, and the Cochrane Central Register were used to seek a series of phase III randomized controlled trials (RCTs) studying on first-line PD-1 inhibitors plus chemotherapy and phase III RCTs comparing first-line oxaliplatin and cisplatin-based chemotherapy for AGC to perform NMA. The main outcome was overall survival (OS) and other outcomes included progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAEs). Results: Eight eligible RCTs involving 5723 patients were included. Compared with PD-1 inhibitors plus cisplatin-based chemotherapy, PD-1 inhibitors plus oxaliplatin-based chemotherapy could prolong the OS without statistical significance (hazard ratio [HR]: 0.82, 95% credible interval [CI]: 0.63-1.06). However, for patients with combined positive score (CPS) ≥ 1, PD-1 inhibitors plus oxaliplatin-based chemotherapy significantly prolonged the OS (HR: 0.75, 95% CI: 0.57-0.99). PFS in PD-1 inhibitors plus oxaliplatin-based chemotherapy was significantly longer than that in PD-1 inhibitors plus cisplatin-based chemotherapy (HR: 0.72, 95% CI: 0.53-0.99). Regarding safety, the incidence of ≥ 3 TRAEs was similar between PD-1 inhibitors plus oxaliplatin-based chemotherapy and PD-1 inhibitors plus cisplatin-based chemotherapy (RR: 0.86, 95% CI: 0.66-1.12). The surface under the cumulative ranking area curve (SUCRA) indicated that PD-1 inhibitors plus oxaliplatin-based chemotherapy ranked first for OS (97.7%), PFS (99.3%), and ORR (89.0%). For oxaliplatin-based regimens, there was no significant difference between nivolumab plus oxaliplatin-based chemotherapy and sintilimab plus oxaliplatin-based chemotherapy in terms of OS, PFS, ORR, and ≥3 TRAEs. Conclusion: Compared with PD-1 inhibitors plus cisplatin-based chemotherapy, PD-1 inhibitors plus oxaliplatin-based chemotherapy significantly prolonged PFS. Considering both efficacy and safety, PD-1 inhibitors plus oxaliplatin-based chemotherapy might be a better option in the first-line treatment for AGC.

The Effects of Charged Amino Acid Side-Chain Length on Diagonal Cross-Strand Interactions between Carboxylate- and Ammonium-Containing Residues in a ß-Hairpin.

The ß-sheet is one of the common protein secondary structures, and the aberrant aggregation of ß-sheets is implicated in various neurodegenerative diseases. Cross-strand interactions are an important determinant of ß-sheet stability. Accordingly, both diagonal and lateral cross-strand interactions have been studied. Surprisingly, diagonal cross-strand ion-pairing interactions have yet to be investigated. Herein, we present a systematic study on the effects of charged amino acid side-chain length on a diagonal ion-pairing interaction between carboxylate- and ammonium-containing residues in a ß-hairpin. To this end, 2D-NMR was used to investigate the conformation of the peptides. The fraction folded population and the folding free energy were derived from the chemical shift data. The fraction folded population for these peptides with potential diagonal ion pairs was mostly lower compared to the corresponding peptide with a potential lateral ion pair. The diagonal ion-pairing interaction energy was derived using double mutant cycle analysis. The Asp2-Dab9 (Asp: one methylene; Dab: two methylenes) interaction was the most stabilizing (-0.79 ± 0.14 kcal/mol), most likely representing an optimal balance between the entropic penalty to enable the ion-pairing interaction and the number of side-chain conformations that can accommodate the interaction. These results should be useful for designing ß-sheet containing molecular entities for various applications.

Structure of the dengue virus RNA promoter.

Dengue virus, a single-stranded positive sense RNA virus, is the most prevalent mosquito-borne pathogen in the world. Like all RNA viruses, it uses conserved structural elements within its genome to control essential replicative steps. A 70 nt stem-loop RNA structure (called SLA), found at the 5'-end of the genome of all flaviviruses, functions as the promoter for viral replication. This highly conserved structure interacts with the viral polymerase NS5 to initiate RNA synthesis. Here, we report the NMR structure of a monomeric SLA from dengue virus serotype 1, assembled to high-resolution from independently folded structural elements. The DENV1 SLA has an L-shaped structure, where the top and side helices are coaxially stacked, and the bottom helix is roughly perpendicular to them. Because the sequence is highly conserved among different flavivirus genomes, it is very likely that the three-dimensional fold and local structure of SLA are also conserved among flaviviruses and required for efficient replication. This work provides structural insight into the dengue promoter and provides the foundation for the discovery of new antiviral drugs that target this essential replicative step.

The Effects of Sesamin Supplementation on Obesity, Blood Pressure, and Lipid Profile: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Aims: Sesamin, the main lignin constituent of sesame, plays a pivotal role in regulating physical state. Some studies have evidenced that the supplementation of sesamin may decrease cardiovascular disease risk. The goal of this systematic review was to summarize evidence of the effects of sesamin supplementation on obesity, blood pressure, and lipid profile in humans by performing a meta-analysis of randomized controlled trials. Data Synthesis: Five databases (PubMed, Cochrane Library, EMBASE, Web of Science, and Scopus) were searched electronically from inception to July 2021 to identify randomized controlled trials that assessed the impact of sesamin on obesity, blood pressure, and lipid profile. Weighted mean difference (WMD) and standard deviation (SD) were used to present the major outcomes. Conclusions: Seven trials (n = 212 participants) were included in the overall analysis. Results showed that sesamin supplementation caused a great reduction in TC (WMD: -10.893 mg/dl, 95% CI: -19.745 to -2.041, p = 0.016), LDL-c (WMD: -8.429 mg/dl, 95% CI: -16.086 to -0.771, p = 0.031), and SBP (WMD: -3.662 mmHg, 95% CI: -6.220 to -1.105, p = 0.005), whereas it had no effect on HDL-c, TG, DBP, or weight. Subgroup analysis showed that duration, parallel design, and unhealthy status can affect TC, LDL-c, and SBP evidently. We did not discover a strong link between indicators' changes and duration of supplementation. Sesamin can be used as an obtainable dietary supplement to improve blood pressure and blood lipids, and further as a health product to prevent cardiovascular diseases.