Unraveling the spatial organization and development of human thymocytes through integration of spatial transcriptomics and single-cell multi-omics profiling.

The structural components of the thymus are essential for guiding T cell development, but a thorough spatial view is still absent. Here we develop the TSO-his tool, designed to integrate multimodal data from single-cell and spatial transcriptomics to decipher the intricate structure of human thymus. Specifically, we characterize dynamic changes in cell types and critical markers, identifying ELOVL4 as a mediator of CD4+ T cell positive selection in the cortex. Utilizing the mapping function of TSO-his, we reconstruct thymic spatial architecture at single-cell resolution and recapitulates classical cell types and their essential co-localization for T cell development; additionally, previously unknown co-localization relationships such as that of CD8αα with memory B cells and monocytes are identified. Incorporating VDJ sequencing data, we also delineate distinct intermediate thymocyte states during αß T cell development. Overall, these insights enhance our understanding of thymic biology and may inform therapeutic interventions targeting T cell-mediated immune responses.

Exogenous gibberellin suppressed taproot secondary thickening by inhibiting the formation and maintenance of vascular cambium in radish (Raphanus sativus L.).

Introduction: The thickening of radish taproots is primarily determined by secondary growth driven by the vascular cambium and is a highly intricate process regulated by plant hormones, transcription factors, and many metabolic pathways. Gibberellin (GA), a plant hormone associated with cell elongation, is essential in secondary growth. However, the mechanism through which exogenous GA3 regulates secondary taproot growth in radishes remains unclear. Methods: Integrated morphological, anatomical, hormonal, and transcriptomic analyses of taproots in radishes treated with GA3 and its biosynthesis inhibitor paclobutrazol (PBZ) were performed to explore their effects on taproot secondary growth and key regulatory pathways. Results: GA3 significantly hindered taproot thickening by inhibiting the formation and maintenance of the vascular cambium, and PBZ promoted root development by increasing root length rather than root diameter. Transcriptome analysis revealed 2,014, 948, and 1,831 differentially expressed genes identified from the control vs. GA3, control vs. PBZ, and GA3 vs. PBZ comparisons, respectively. Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis revealed that differentially expressed genes were primarily involved in the biosyntheses of secondary metabolites and metabolic pathways. GA3 significantly increased the levels of endogenous indole-acetic acid and the expression of auxin synthesis and signal transduction genes. Discussion: Exogenous GA3 significantly inhibited the expression of genes involved in the maintenance and differentiation of vascular cambium, including WOX14, ER/ERL1, and XCP2. Exogenous GA3 affects root thickening in radishes primarily by regulating hormone signal transduction pathways, vascular cambium activity, and substance and energy metabolisms. Our findings provide insights into the mechanisms underlying taproot thickening in radishes and provide a valuable gene database for future studies.

Ni Cluster-Decorated Single-Atom Catalysts Achieve Near-Unity CO2-to-CO Conversion with an Ultrawide Potential Window of ≈1.7 V.

Developing efficient electrocatalysts for CO2 reduction to CO within a broad potential range is meaningful for cascade application integration. In this work, hydrogen spillover is created and utilized to cultivate a proton-rich environment via the simple thermolysis of a Ni-doped Zn coordination polymer (Zn CPs (Ni)) to create asymmetric Ni single atoms co-located with adjacent Ni nanoclusters on nitrogen-doped carbon, termed as NiNC&SA/N-C, which expedites the hydrogenation of adsorbed CO2. Therefore, the sample demonstrates near-unity CO2-to-CO conversion efficiency under pH-universal conditions in ultra-wide potential windows: -0.39 to -2.05 V versus RHE with the current densities ranging from 0.1 to 1.0 A cm-2 in alkaline conditions, -0.83 to -2.40 V versus RHE from 0.1 to 0.9 A cm-2 in neutral environments, and -0.98 to -2.25 V versus RHE across 0.1 to 0.8 A cm-2 in acid conditions. Corresponding in situ measurements and density functional theory (DFT) calculations suggest that the enhanced H2O dissociation and more efficient hydrogen spillover on NiNC&SA/N-C (compared to NiSA/N-C) accelerate the protonation of adsorbed CO2 to form *COOH intermediates. This work emphasizes the significant role of proton spillover in CO2RR, opening novel avenues for designing high-performance catalysts applicable to various electrocatalytic processes.

Studying the effects of Saposhnikoviae Radix on the pharmacokinetic profiles of 10 bioactive compounds originating from Astragali Radix in rat plasma by UHPLC-QTRAP-MS/MS.

ETHNOPHARMACOLOGICAL RELEVANCE: Astragali Radix-Saposhnikoviae Radix (AR-SR) is a well-known and effective herb pair. Although the compatibility of these two herbs has been widely applied in many traditional Chinese medicine formulas, its potential mechanism still needs to be investigated. AIM OF STUDY: To evaluate the pharmacokinetic profiles of 10 bioactive compounds derived from AR when administrated alone and in combination with SR to rats, aiming to further reveal the impact of SR on AR. MATERIALS AND METHODS: Two groups of male Sprague-Dawley rats received oral administration of AR and AR-SR freeze-dried powder solutions, respectively. UHPLC-QTRAP-MS/MS technology was utilized to perform the pharmacokinetic studies of 10 compounds derived from AR in rat plasma samples. RESULTS: A reliable UHPLC-QTRAP-MS/MS method was established to simultaneously determine the rat plasma concentrations of eight isoflavonoids, referring to calycosin (CAL), calycosin-7-O-ß-D-glucoside (CAL-G), formononetin (FOR), formononetin-7-O-ß-D-glucoside (FOR-G), astrapterocarpan (APC), astrapterocarpan-3-O-ß-D-glucoside (APC-G), astraisoflavan-7-O-ß-D-glucoside (AIF-G) and formononetin-7-O-ß-D-glucuronide (FOR-GN), and two saponins, including astragaloside IV (AS IV) and cycloastragenol (CAG), originating from AR. Following the oral administration of AR, seven isoflavonoids were quickly absorbed but exhibited low plasma concentrations under 17.88 ng/mL except FOR-GN. The latter maintained higher plasma concentration level more than 15 ng/mL for at least 10 h. Besides, for the first time, AS IV was observed with an obvious double-peak phenomenon after administering AR extract, whereas the concentration of CAG was lower than LLOQ before 6 h. When AR and SR were administrated together, the double-peak phenomena of CAL, FOR, APC, AIF-G and FOR-GN were enhanced and there was a significant increase in their values of area under the concentration-time curve (AUC) and mean residence time (MRT) (P < 0.05) while the pharmacokinetic profiles of CAL-G, FOR-G, APC-G, AS IV and CAG stayed almost unchanged (P > 0.05). Moreover, the elimination half-time (t1/2) values of CAL, FOR and APC were significantly elevated, and the clearance rate/bioavailability (CLz/F) for CAL and FOR was reduced (P < 0.05). CONCLUSIONS: SR has the potential to modulate the ADME process of five out of the eight isoflavonoids (CAL, FOR, APC, AIF-G and FOR-GN, except CAL-G, FOR-G and APC-G) originating from AR. This interaction is especially likely to affect the hepatic and intestinal drug disposition of these isoflavonoids, thereby extending the duration of their pharmacological effects, which may subsequently impact the therapeutic efficacy of AR.

Analysis of the microbial community diversity in various regions of the healthy oral cavity.

BACKGROUND: Microbiomics offers new methods for conducting epidemiological surveys of oral microbiota in large populations. Compared to curette sampling, swab sampling is more convenient and less technically sensitive, making it more suitable for such surveys. To verify the feasibility of using swabs for buccal mucosa sampling in large-scale studies, we collected samples from the buccal mucosa and tooth surfaces of healthy individuals using both swabs and curettes. Microbiomics was employed to analyze and compare microbial abundance and diversity between these two methods. METHODS: Four sites were assessed: the buccal mucosa on both sides and the buccal surfaces of the left and right mandibular first molars. Two sampling methods, swab and curette, were used to collect bacterial communities from healthy individuals. Specifically, buccal mucosa samples (n = 10) and tooth surface samples (n = 20) were analyzed using 16 S rDNA gene sequencing. Bacterial signals were detected through fluorescence in situ hybridization (FISH), targeting the bacterial 16 S rDNA gene. Metastats analysis and Wilcoxon test were used. RESULTS: A total of 383 OTUs were detected in the 30 samples, which belonged to 1 kingdom (bacteria), 11 phyla, 23 classes, 40 orders, 75 families, 143 genus, and 312 species. Among them, 223 OTUs were found on both the buccal mucosa and tooth surfaces. The statistics suggest that although there were no significant differences in colony composition, there were differences in the abundance and distribution of colonies on the dental and buccal mucosal surfaces. When detecting oral disease-causing pathogens such as Enterococcus faecalis and Porphyromonas gingivalis, the efficiency of detection is higher when using curette sampling. Compared to right tooth sampling with a curette, the swab sampling group had higher levels of Firmicutes, while Fusobacteria and Bacteroidetes were more prevalent in the curette tissues. CONCLUSIONS: In oral health individuals, there is no difference in the bacterial composition of the oral buccal mucosa and the dental surface, differing only in abundance. Thus, the buccal mucosa can act as a substitute for the teeth in epidemiological investigations exploring the bacterial composition of the oral cavity.

Constructing Pd and Cu Crowding Single Atoms by Protein Confinement to Promote Sonogashira Reaction.

For multicenter-catalyzed reactions, it is important to accurately construct heterogeneous catalysts containing multiple active centers with high activity and low cost, which is more challenging compared to homogeneous catalysts because of the low activity and spatial confinement of active centers in the loaded state. Herein, a convenient protein confinement strategy is reported to locate Pd and Cu single atoms in crowding state on carbon coated alumina for promoting Sonogashira reaction, the most powerful method for constructing the acetylenic moiety in molecules. The single-atomic Pd and Cu centers take advantage in not only the maximized atomic utilization for low cost, but also the much-enhanced performance by facilitating the activation of aryl halides and alkynes. Their locally crowded dispersion brings them closer to each other, which facilitates the transmetallation process of acetylide intermediates between them. Thus, the Sonogashira reaction is drove smoothly by the obtained catalyst with a turnover frequency value of 313 h-1, much more efficiently than that by commercial Pd/C and CuI catalyst, conventional Pd and Cu nanocatalysts, and mixed Pd and Cu single-atom catalyst. The obtained catalyst also exhibits the outstanding durability in the recycling test.

Phosphorus-doped Ti3C2Tx MXene nanosheets enabling ambient NH3 synthesis with high current densities.

Herein, we show that P-doped Ti3C2Tx MXene nanosheets can effectively catalyze the NO3RR-to-NH3 conversion with a high faradaic efficiency of 95% and a yield rate of 5.39 mg h-1 mgcat.-1. Moreover, the catalyst achieves an impressive high current density of -1200 mA cm-2 at a low potential of -1.51 V, accompanied by an NH3 productivity of 123.5 mg h-1 mgcat.-1. Theoretical calculations further reveal that phosphorous dopants facilitate the adsorption and activation of reactants/intermediates and thus lower the energy barrier.

Side-Opened Hollow Fiber-Based SPR Sensor for High Refractive Index Detection.

To facilitate the sensor fabrication and sensing operation in microstructured optical fiber-based surface plasmon resonance (SPR) sensors for high refractive index (RI) detection, we propose a special hollow fiber-based SPR sensor that comprises an opening on its body side and a thin gold layer coated on its outer surface. The analyte is able to flow into the hollow core through the side-opening to form new fiber core, with the Gaussian-like mode propagating in it. We investigate the sensing performance of the proposed sensor in a higher RI range of 1.48 to 1.54 at two feasible schemes: one is to only fill the fiber core with analyte (Scheme A), and the other is to directly immerse the sensor in the analyte (Scheme B). The results demonstrate that our sensor exhibits higher wavelength sensitivity at Scheme A with a maximum wavelength sensitivity of 12,320 nm/RIU, while a greater amplitude sensitivity was found at Scheme B with a maximum amplitude sensitivity of 1146 RIU-1. Our proposed sensor features the advantages of simple fabrication, flexible operation, easy analyte filling and replacing, enhanced real-time detection capabilities, high RI detection, and very high wavelength sensitivity and amplitude sensitivity, which makes it more competitive in SPR sensing applications.

Effect of depression and the antidepressant fluoxetine on osseointegration-A pre-clinical in vivo experimental study.

OBJECTIVE: The aim of this study was to explore the effect of depression and selective serotonin reuptake inhibitors on implant osseointegration and bone healing. METHODS: Forty-eight 6- to 8-week-old SPF Sprague-Dawley male rats were randomly divided into four groups: the Control group, the Fluoxetine group, the Depression group and the De&Flu group. The rats in the Depression group and the De&Flu group were subjected to a depression modelling process, and the rats in the Control group and the Fluoxetine group were raised normally. Then, a titanium implant was placed in the right tibia of each rat. In the Fluoxetine group and De&Flu group, fluoxetine was injected subcutaneously daily, while subcutaneously injecting physiological saline in the Control group and Depression group. Collecting serum from the rats used for ELISA. The surgical area was cut for microcomputed tomography and histology observation. RESULTS: After 12 weeks, bone mineral density was lower in the De&Flu group than in the Control group, Depression group and Fluoxetine group. Bone mineral density was also lower in the Depression group and the Fluoxetine group than in the Control group. The percentage of bone-implant contact (BIC%) in De&Flu rats was lower than in the Control, Depression and Fluoxetine groups. The BIC% in the Depression group and the Fluoxetine group was lower than in the Control group. CONCLUSIONS: Depression and fluoxetine negatively affect bone density and implant osseointegration independently, and this damaging effect is exacerbated when both factors are present. The mechanism may be related to the dysregulation of the hypothalamic-pituitary-adrenal axis and inflammation in the body.

Serum immunoglobulin concentrations and risk of type 2 diabetes mellitus in adults: a prospective cohort study from the TCLSIH study.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia resulting from defects in insulin secretion and/or insulin action. Increasing evidence suggests that inflammation played an important role in the pathogenesis of T2DM. Prospective studies on the link between immunoglobulins concentrations and the risk of T2DM in adults are limited. We developed a cohort study including 7,093 adults without T2DM history. The incidence of T2DM was 16.45 per 1,000 person-years. Compared with the lowest quartiles, the hazard ratios (95% confidence intervals) of T2DM for the highest quartiles of IgG, IgE, IgM and IgA were 0.64 (0.48-0.85), 0.94 (0.72-1.23), 0.68 (0.50-0.92) and 1.62 (1.24-2.11) (P for trend was < 0.01, 0.84, 0.02 and < 0.0001), respectively, suggesting that serum IgG and IgM concentrations were inversely associated with the incidence of T2DM, and IgA levels were positively associated with the risk of T2DM in a general adult population.

Establishment and application of quadruple fluorescence quantitative RT-PCR method for the identification of waterfowl astrovirus.

Avian astrovirus can infect a variety of poultry species and cause viral diarrhea, with a wide epidemic range strong pathogenicity and a high incidence. Among them, Duck astrovirus 3(DAstV-3), Duck astrovirus 4(DAstV-4), Goose astrovirus 1(GoAstV-1) and Goose astrovirus 2(GoAstV-2) are four types of astroviruses newly discovered in waterfowl in recent years. In order to realize the rapid detection of these four kinds of waterfowl stellate viruses, specific primers and probes were engineered to target a highly conserved region of ORF1b gene of DAstV-3, GoAstV-1 and GoAstV-2 and the ORF2 gene of DAstV-4, and a quadruple fluorescence quantitative RT-PCR method was developed. The results indicate that the method established in this study has good specificity and no cross reactivity with other pathogens. This method can detect viruses with a minimum concentration of 1 × 101 copies/µL for DAstV-4, GoAstV-1 and GoAstV-2, respectively, while the minimum concentration for DAstV-3 is 1 × 102 copies/µL. Compared with the routinely used RT-PCR method, the limit of detection by the multiplex RT-PCR lower. Both intra- and inter-assay variability tests revealed excellent reproducibility. This method was then used to analyze 269 field samples, and the results were verified by genome sequencing. In conclusion, this study presents a sensitive, accurate, and specific method for detecting DAstV-3, DAstV-4, GoAstV-1, and GoAstV-2 in a single reaction, enabling the monitoring and differential diagnosis of these four types of waterfowl astroviruses.

Ultrafast Unidirectional On-Chip Heat Transfer.

Effective and rapid heat transfer is critical to improving electronic components' performance and operational stability, particularly for highly integrated and miniaturized devices in complex scenarios. However, current thermal manipulation approaches, including the recent advancement in thermal metamaterials, cannot realize fast and unidirectional heat flow control. In addition, any defects in thermal conductive materials cause a significant decrease in thermal conductivity, severely degrading heat transfer performance. Here, the utilization of silicon-based valley photonic crystals (VPCs) is proposed and numerically demonstrated to facilitate ultrafast, unidirectional heat transfer through thermal radiation on a microscale. Utilizing the infrared wavelength region, the approach achieves a significant thermal rectification effect, ensuring continuous heat flow along designed paths with high transmission efficiency. Remarkably, the process is unaffected by temperature gradients due to the unidirectional property, maintaining transmission directionality. Furthermore, the VPCs' inherent robustness affords defect-immune heat transfer, overcoming the limitations of traditional conduction methods that inevitably cause device heating, performance degradation, and energy waste. The design is fully CMOS compatible, thus will find broad applications, particularly for integrated optoelectronic devices.

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Soil matrix infiltration is an important pathway for plantations to obtain water, which affects ecological benefits and water conservation function of plantations. The changes of soil matrix infiltration and its influencing factors in different growth stages of Chinese fir plantations remain unclear. We measured soil matrix infiltration process using a tension infiltrometer in Chinese fir plantations (5, 8, 11, and 15 years old) of Beijiang River Forest Farm in Rongshui, Guangxi, and analyzed soil basic physicochemical properties to identify the dominant factors influencing soil matrix infiltration. The results showed that initial infiltration rate, stable infiltration rate, and cumulative infiltration increased with stand ages. The ranges of different stand ages were 141-180 mm·h-1, 109-150 mm·h-1, and 188-251 mm, respectively. The initial infiltration rate, stable infiltration rate, and cumulative infiltration were significantly positively correlated with soil capillary porosity, soil organic matter, soil water stable macroaggregate, sand content, and clay content, while negatively correlated with soil bulk density and silt content. Early thinning had a positive effect on soil matrix infiltration, but thinning measures after 11 years did not enhance soil matrix infiltration further. Philip model was optimal for describing soil matrix infiltration process in this region. In conclusion, soil matrix infiltration capacity of Chinese fir plantations gradually increased from young to middle-aged stands, but matrix infiltration capacity tended to stabilize after 11 years old. Silt content and water stable macroaggregate were the dominant factors influencing matrix infiltration.

Conservative Interventions for Urinary Incontinence on Postpartum Women: A Systematic Review and Meta-Analysis.

INTRODUCTION: Urinary incontinence (UI) is common in postpartum women and can lead to a reduced quality of life and withdrawal from fitness and exercise activities. Conservative management interventions such as pelvic floor muscle training (PFMT), use of vaginal cones, and biofeedback have been recommended as first-line treatment. We aimed to explore the effects of conservative interventions on UI rate, severity, and incontinence-specific quality of life in postpartum women with UI. METHODS: Nine databases were searched from inception to August 2022: PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, CINAHL, Wanfang, China National Knowledge Infrastructure, China Biological Medicine, and VIP Journal Integration Platform. Randomized controlled trials examining the effects of conservative interventions on postpartum UI were included. RESULTS: Initial searches produced 1839 results, of which 17 studies were eligible. All included studies had a low to moderate risk of bias. Supervised PFMT and use of a vaginal cone were more effective than individual PFMT in decreasing rates of UI (odds ratio, 0.29; 95% CI, 0.14-0.61). Individual PFMT combined with acupuncture (mean difference, -1.91; 95% CI, -2.46 to -1.37) or electroacupuncture and supervised PFMT combined with moxibustion were more effective than individual supervised PFMT alone in improving the severity of symptoms. Furthermore, electrical stimulation and biofeedback combined with acupoint stimulation or core training were more effective than electrical stimulation and biofeedback alone. For improving the incontinence-specific quality of life, supervised PFMT was more efficacious than individual PFMT; electrical stimulation and biofeedback plus core training were more beneficial than electrical stimulation and biofeedback alone. DISCUSSION: Supervised PFMT and use of a vaginal cone were more beneficial in decreasing rates of UI compared with individual PFMT. Superior effects in decreasing UI severity may be achieved by combining PFMT or electrical simulation and biofeedback with other therapies. Electrical stimulation and biofeedback plus core training, as well as supervised PFMT, are most effective in improving incontinence-specific quality of life. Further research is required to provide more evidence on the efficacy of these therapies.

Structure-Based Design of Novel Thiazolone[3,2-a]pyrimidine Derivatives as Potent RNase H Inhibitors for HIV Therapy.

Ribonuclease H (RNase H) was identified as an important target for HIV therapy. Currently, no RNase H inhibitors have reached clinical status. Herein, a series of novel thiazolone[3,2-a]pyrimidine-containing RNase H inhibitors were developed, based on the hit compound 10i, identified from screening our in-house compound library. Some of these derivatives exhibited low micromolar inhibitory activity. Among them, compound 12b was identified as the most potent inhibitor of RNase H (IC50 = 2.98 µM). The experiment of magnesium ion coordination was performed to verify that this ligand could coordinate with magnesium ions, indicating its binding ability to the catalytic site of RNase H. Docking studies revealed the main interactions of this ligand with RNase H. A quantitative structure activity relationship (QSAR) was also conducted to disclose several predictive mathematic models. A molecular dynamics simulation was also conducted to determine the stability of the complex. Taken together, thiazolone[3,2-a]pyrimidine can be regarded as a potential scaffold for the further development of RNase H inhibitors.

A scale for measuring nursing digital application skills: a development and psychometric testing study.

BACKGROUND: The adoption of digitization has emerged as a new trend in the advancement of healthcare systems. To ensure high-quality care, nurses should possess sufficient skills to assist in the digital transformation of healthcare practices. Suitable tools have seldom been developed to assess nurses' skills in digital applications. This study aimed to develop the Nursing Digital Application Skill Scale (NDASS) and test its psychometric properties. METHODS: The Nursing Digital Application Skill Scale was developed in three phases. In Phase 1, an item pool was developed based on previous literature and the actual situation of nursing work. Phase 2 included 14 experts' assessment of content validity and a focus group interview with 30 nurses to pretest the scale. In phase 3, 429 registered nurses were selected from March to June 2023, and item analysis, exploratory factor analysis, and confirmatory factor analysis were used to refine the number of items and explore the factor structure of the scale. Additionally, reliability was determined by internal consistency and test-retest reliability. RESULTS: The final version of the NDASS consisted of 12 items. The content validity index of NDASS reached 0.975 at an acceptable level. The convergent validity test showed that the average variance extracted value was 0.694 (> 0.5) and the composite reliability value was 0.964 (> 0.7), both of which met the requirements. The principal component analysis resulted in a single-factor structure explaining 74.794% of the total variance. All the fitting indices satisfied the standard based upon confirmatory factor analyses, indicating that the single-factor structure contributed to an ideal model fit. The internal consistency appeared high for the NDASS, reaching a Cronbach's alpha value of 0.968. The test-retest reliability was 0.740, and the split-half coefficient was 0.935. CONCLUSION: The final version of the NDASS, which possesses adequate psychometric properties, is a reliable and effective instrument for nurses to self-assess digital skills in nursing work and for nursing managers in designing nursing digital skill training.

Association of added sugar intake and its forms and sources with handgrip strength decline among middle-aged and older adults: A prospective cohort study.

PURPOSE: The consumption of added sugar has increased rapidly in recent years. Limited knowledge exists regarding the association between added sugar intake and muscle strength, although the latter is a predictor of physical disability in older adults. This study aimed to investigate the association between added sugar intake and longitudinal changes in handgrip strength among middle-aged and elderly Chinese adults. METHODS: This prospective cohort study included 5298 adults aged 40 years and older (62.6% men) from the TCLSIH (Tianjin Chronic Low-grade Systemic Inflammation and Health) cohort study. Added sugar intake was obtained through a frequency questionnaire containing 100 items of food. Handgrip strength is measured annually using a handheld digital dynamometer. Multivariate linear regression models were used to examine the association between added sugars intake and the annual changes in handgrip strength and weight-adjusted handgrip strength. RESULTS: In the fully adjusted model, the annual change in handgrip strength for one unit increase in total added sugar, solid added sugar, and liquid added sugar intake was -0.0353 kg, (95% confidence intervals (CI) -0.000148, -0.0000164; P = 0.01), -0.0348 kg (95% CI: -0.000227, -0.0000269; P = 0.01) and -0.0189 kg (95% CI -0.000187, 0.0000338; P = 0.17), respectively. Added sugar from bread and biscuits sources were remarkably associated with a decline in handgrip strength (ß = -0.0498; 95%CI -0.00281, -0.000787) and (ß = -0.0459; 95%CI 0.00158, 0.00733) (P < 0.01). CONCLUSIONS: Our data suggest that the higher the intake of solid added sugars, but not liquid sugars, were associated with the declined handgrip strength in the Chinese middle-aged and elderly population. In addition, the consumption of added sugars from bread and biscuits sources was also associated with a decline in grip strength.

Design, synthesis and biological evaluation of Thiazolo[3, 2-a]Pyrimidine derivatives as novel RNase H inhibitors.

Targeting Ribonuclease H (RNase H) has been considered a viable strategy for HIV therapy. In this study, a series of novel thiazolo[3, 2-a]pyrimidine derivatives were firstly designed and synthesized as potential inhibitors of HIV-1 RNase H. Among these compounds, A28 exhibited the most potent inhibition against HIV-1 RNase H with an IC50 value of 4.14 µM, which was about 5-fold increase in potency than the hit compound A1 (IC50 = 21.49 µM). To gain deeper insights into the structure-activity relationship (SAR), a CoMFA model was constructed to yield reasonable statistical results (q2 = 0.658 and R2 = 0.969). Results from magnesium ion chelation experiments and molecular docking studies revealed that these thiazolopyrimidine inhibitors may exert their inhibitory activity by binding to an allosteric site on RNase H at the interface between subunits p51 and p66. Furthermore, this analog demonstrated favorable physicochemical properties. Our findings provide valuable groundwork for further development of allosteric inhibitors targeting HIV-1 RNase H.

Non-negligible Toxicity to Fish in the Early Life Stages Triggered by Aqueous Leachate of Takeaway Plastic Containers.

Ordering takeout is a growing social phenomenon and may raise public health concerns. However, the associated health risk of compounds leaching from plastic packaging is unknown due to the lack of chemical and toxicity data. In this study, 20 chemical candidates were tentatively identified in the environmentally relevant leachate from plastic containers through the nontargeted chemical analysis. Three main components with high responses and/or predicted toxicity were further verified and quantified, namely, 3,5-di-tert-butyl-4-hydroxycinnamic acid (BHC), 2,4-di-tert-butylphenol (2,4-DTBP), and 9-octadecenamide (oleamide). The toxicity to zebrafish larvae of BHC, a degradation product of a widely used antioxidant Irganox 1010, was quite similar to that of the whole plastic leachate. In the same manner, RNA-seq-based ingenuity analysis showed that the affected canonical pathways of zebrafish larvae were quite comparable between BHC and the whole plastic leachate, i.e., highly relevant to neurological disease, metabolic disease, and even behavioral disorder. Longer-term exposure (35 days) did not cause any effect on adult zebrafish but led to decreased hatching rate and obvious neurotoxicity in zebrafish offspring. Collectively, this study strongly suggests that plastic containers can leach out a suite of compounds causing non-negligible impacts on the early stages of fish via direct or parental exposure.

Electron Deficient Ir-O Bonds Promote Heterogeneous Ir-Catalyzed Anti-Markovnikov Hydroboration of Alkenes under Mild Neat Conditions.

Tuning electronic characteristics of metal-ligand bonds based on reaction pathways to achieve efficient catalytic processes has been widely studied and proven to be feasible in homogeneous catalysis, but it is scarcely investigated in heterogeneous catalysis. Herein, we demonstrate the regulation of the electronic configuration of Ir-O bonds in an Ir single-atom catalyst according to the borane activation mechanism. Ir-O bonds in Ir1/Ni(OH)x are found to be more electron-poor than those in Ir1/NiOx. Despite the mild solvent-free conditions and ambient temperature, Ir1/Ni(OH)x exhibits outstanding performance for the hydroboration of alkenes, furnishing the desired alkylboronic esters with a turnover frequency value of ≤3060 h-1 and 99% anti-Markovnikov selectivity, which is significantly better than that of Ir1/NiOx (42 h-1). It is further proven that the more electron-poor Ir-O bonds as active centers are more oxidative and so benefit the activation of the H-B bond in the reductive pinacolborane.