Enantioselective Nickel-Electrocatalyzed Reductive Propargylic Carboxylation with CO2.

The exploitation of carbon dioxide (CO2) as a sustainable, plentiful, and harmless C1 source for the catalytic synthesis of enantioenriched carboxylic acids has long been acknowledged as a pivotal task in synthetic chemistry. Herein, we present a current-driven nickel-catalyzed reductive carboxylation reaction with CO2 fixation, facilitating the formation of C(sp3)-C(sp2) bonds by circumventing the handling of moisture-sensitive organometallic reagents. This electroreductive protocol serves as a practical platform, paving the way for the synthesis of enantioenriched propargylic carboxylic acids (up to 98% enantiomeric excess) from racemic propargylic carbonates and CO2. The efficacy of this transformation is exemplified by its successful utilization in the asymmetric total synthesis of (S)-arundic acid, (R)-PIA, (S)-chizhine D, (S)-cochlearin G, and (S,S)-alexidine, thereby underscoring the potential of asymmetric electrosynthesis to achieve complex molecular architectures sustainably.

Association between two novel anthropometric measures and type 2 diabetes in a Chinese population.

AIMS: To investigate the associations of conicity index (C-index) and relative fat mass (RFM) with incident type 2 diabetes mellitus (T2DM) among adults in China. MATERIALS AND METHODS: A total of 10 813 participants aged over 18 years in Shenzhen Longhua district were enrolled in a follow-up study conducted from 2018 to 2022. The participants were categorized based on quartiles (Q) of C-index and RFM. The Cox proportional hazards model was performed to examine the relationships between C-index, RFM and the risk of T2DM. RESULTS: After adjusting for potential confounding factors, including age, sex, occupation, marital status, education level, smoking status, alcohol consumption, physical exercise, hypertension status, fasting blood glucose (FBG) and total cholesterol (TC), both C-index and RFM showed positive and independent associations with risk of T2DM. The multivariable-adjusted hazard ratios (95% confidence intervals) for T2DM risk in participants in C-index Q3 and Q4 compared with those in C-index Q1 were 1.50 (1.12, 2.02) and 1.73 (1.29, 2.30), and 1.94 (1.44, 2.63), 3.18 (1.79, 5.64), 4.91 (2.68, 9.00) for participants in RFM Q2, Q3 and Q4 compared with RFM Q1. These differences were statistically significant (all p < 0.05). CONCLUSION: C-index and RFM are strongly associated with new-onset T2DM and could be used to identify the risk of diabetes in large-scale epidemiological studies.

Long-term air pollutants exposure and respiratory mortality: A large prospective cohort study.

Ambient air pollution is a major global health concern. Yet, no study has thoroughly assessed its link to respiratory mortality. Our research evaluated the combined and individual effects of air pollutants on respiratory mortality risks based on the UK Biobank. A total of 366,478 participants were studied. A Cox proportional hazards model was used to estimate the respiratory mortality risk from combined long-term exposure to five pollutants, summarized as a weighted air pollution score. During a median of 13.6 years of follow-up, 6113 deaths due to respiratory diseases were recorded. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) of respiratory diseases were 2.64 (2.05-3.39), 1.62 (1.23-2.12), 2.06 (1.73-2.45), 1.20 (1.16-1.25), and 1.07 (1.05-1.08) per 10 µg/m3 increase in PM2.5, PM2.5-10, PM10, NO2, and NOx, respectively. The air pollution score showed a dose-response association with an elevated respiratory mortality risk. The highest versus lowest quartile air pollution score was linked to a 44% increase in respiratory mortality risk (HR 1.44, 95% CI: 1.33-1.57), with consistent findings in subgroup and sensitivity analyses. Long-term individual and joint air-pollutant exposure showed a dose-response association with an increased respiratory mortality risk, highlighting the importance of a comprehensive air-pollutant assessment to protect public health.

Effect of Novel Processing Techniques on the Carotenoid Release during the Production of Red Guava Juice.

Red guava, distinguished by its elevated lycopene content, emerges as a promising natural source of carotenoids. This study systematically evaluates the impact of diverse processing techniques on the efficient release of carotenoids. The primary objective is to facilitate the transfer of carotenoids into the juice fraction, yielding carotenoid-enriched juice seamlessly integrable into aqueous-based food matrices. The untreated guava puree exhibited a modest release of carotenoids, with only 66.26% of ß-carotene and 57.08% of lycopene reaching the juice. Contrastly, both high-pressure homogenization (HPH) at 25 MPa and enzyme (EM) treatment significantly enhanced carotenoid release efficiency (p < 0.05), while high hydrostatic pressure (HHP) at 400 MPa and pulsed electric field (PEF) of 4 kV/cm did not (p > 0.05). Notably, HPH demonstrated the most substantial release effect, with ß-carotene and lycopene reaching 90.78% and 73.85%, respectively. However, the stability of EM-treated samples was relatively poor, evident in a zeta-potential value of -6.51 mV observed in the juice. Correlation analysis highlighted the interactions between pectin and carotenoids likely a key factor influencing the stable dissolution or dispersion of carotenoids in the aqueous phase. The findings underscore HPH as a potent tool for obtaining carotenoid-enriched guava juice, positioning it as a desirable ingredient for clean-label foods.

Dual-Catalyzed Stereodivergent Electrooxidative Homocoupling of Benzoxazolyl Acetate.

The development of a reliable strategy for stereodivergent radical reactions that allows convenient access to all stereoisomers of homocoupling adducts with multiple stereogenic centers remains an unmet goal in organic synthesis. Herein, we describe a dual-catalyzed electrooxidative C(sp3)-H/C(sp3)-H homocoupling with complete absolute and relative stereocontrol for the synthesis of molecules with contiguous quaternary stereocenters in a general and predictable manner. The stereodivergent electrooxidative homocoupling reaction is achieved by synergistically utilizing two distinct chiral catalysts that convert identical racemic substrates into inherently distinctive reactive chiral intermediates, dictate enantioselective radical addition, and allow access to the full complement of stereoisomeric products via simple catalyst permutation. The successful execution of the dual-electrocatalytic strategy programmed via electrooxidative activation provides a significant conceptual advantage and will serve as a useful foundation for further research into cooperative stereocontrolled radical transformations and diversity-oriented synthesis.

Encoding fluorescence intensity with tetrahedron DNA nanostructure based FRET effect for bio-detection.

Biocoding technology constructed by readable tags with distinct signatures is a brand-new bioanalysis method to realize multiplexed identification and bio-information decoding. In this study, a novel fluorescence intensity coding technology termed Tetra-FICT was reported based on tetrahedron DNA nanostructure (TDN) carrier and Forster Resonance Energy Transfer (FRET) effect. By modulating numbers and distances of Cy3 and Cy5 at four vertexes of TDN, different fluorescence intensities of twenty-six samples were produced at ∼565.0 nm (FICy3) and ∼665.0 nm (FICy5) by detecting fluorescence spectra. By developing an error correction mechanism, eleven codes were established based on divided intensity ranges of the final FICy3 together with FICy5 (Final-FICy3&FICy5). These resulting codes were used to construct barcode probes, with three miRNA biomarkers (miRNA-210, miRNA-199a and miRNA-21) as cases for multiplexed bio-assay. The high specificity and sensitivity were also demonstrated for the detection of miRNA-210. Overall, the proposed Tetra-FICT enriched the toolbox of fluorescence coding, which could be applied to multiplexing biomarkers detection.

Association of changes in waist circumference, waist-to-height ratio and weight-adjusted-waist index with multimorbidity among older Chinese adults: results from the Chinese longitudinal healthy longevity survey (CLHLS).

BACKGROUND: The association of changes in waist circumference (WC), waist-to-height ratio (WHtR) and weight-adjusted-waist index (WWI) with subsequent risk of multimorbidity remains unclear among older Chinese adults. Therefore, we aimed to assess this association by utilizing data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). METHODS: Our study was based on the 2011/2012 wave of the CLHLS whose follow-up surveys were conducted in 2014 and 2017/2018. A total of 2900 participants aged 65 and above at baseline were enrolled. WC, WHtR, and WWI were calculated from measured height, weight, and waist circumference. Multimorbidity refers to the coexistence of two or more of 18 chronic diseases. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs) to evaluate the effect of three-year changes in WC, WHtR, and WWI on the risk of multimorbidity. RESULTS: During a mean follow-up time of 4.2 (2.0) years, 906 multimorbidity cases were identified. Compared to participants in the persistently low WC group, those in the WC gain group and the persistently high WC group had a higher multimorbidity risk with adjusted HRs (95%CI) of 1.23 (1.01-1.50) and 1.34(1.14-1.58), respectively. Participants in the WHtR gain group and the persistently high WHtR group also had higher risks of multimorbidity with HRs (95%CI) of 1.35 (1.08-1.67) and 1.27 (1.05-1.53), respectively, relative to the persistently low WHtR group. Compared to the persistently low WWI group, those in the WWI loss group had a lower risk of multimorbidity with HRs (95%CI) of 0.80 (0.66-0.98). For every standard deviation increase in WC, WHtR, and WWI over three years, the risk of multimorbidity was higher by 12% (95%CI: 1.05-1.19), 13% (95%CI: 1.06-1.20), and 12% (95%CI: 1.05-1.20), respectively. CONCLUSIONS: Associations of changes in WC, WHtR and WWI with multimorbidity are significant among older Chinese adults. The findings highlight the importance of evaluating changes in WC, WHtR, and WWI in screening and prevention of multimorbidity in older adults.

Endometrial Glucose Metabolism During Early Pregnancy.

Approximately 50% of human pregnancies humans fail, most before or during implantation. One factor contributing to pregnancy loss is abnormal glucose metabolism in the endometrium. Glucose contributes to preimplantation embryo development, uterine receptivity, and attachment of the embryo. Across multiple species, the epithelium stores glucose as the macromolecule glycogen at estrus. This reserve is mobilized during the preimplantation period. Glucose from circulation or glycogenolysis can be secreted into the uterine lumen for use by the embryo or metabolized via glycolysis, producing ATP for the cell. The resulting pyruvate could be converted to lactate, another important nutrient for the embryo. Fructose is an important nutrient for early embryos, and the epithelium and placenta can convert glucose to fructose via the polyol pathway. The epithelium also uses glucose to glycosylate proteins, which regulates embryo attachment. In some species, decidualization of the stroma is critical to successful implantation. Formation of the decidua requires increased glucose metabolism via the pentose phosphate pathway and glycolysis. After decidualization, the cells switch to aerobic glycolysis to produce ATP. Paradoxically, the decidua also stores large amounts of glucose as glycogen. Too little glucose or an inability to take up glucose impairs embryo development and decidualization. Conversely, too much glucose inhibits these same processes. This likely contributes to the reduced pregnancy rates associated with conditions like obesity and diabetes. Collectively, precise control of glucose metabolism is important for several endometrial processes required to establish a successful pregnancy. The factors regulating these metabolic processes remain poorly understood.

Associations Between Specific Diets, Dietary Diversity, and Cognitive Frailty in Older Adults - China, 2002-2018.

What is already known about this topic?: The relationship between specific dietary patterns and dietary diversity with cognitive frailty continues to be a subject of ambiguity. What is added by this report?: This research revealed that regular consumption of fruit, meat, bean products, garlic, and tea was connected to a decreased risk of cognitive frailty. Compared to participants with dietary diversity score (DDS) ≤6 points, those with DDS of 9-10, 11-12, and ≥12 had a lower risk of cognitive frailty. What are the implications for public health practice?: The results of the study corroborate the relationship between the augmented consumption frequency of meat, fruit, bean products, garlic, and tea, in conjunction with an elevated DDS, and an increased risk of developing cognitive frailty.

Dietary Diversity Changes and Cognitive Frailty in Chinese Older Adults: A Prospective Community-Based Cohort Study.

Evidence for the effects of dietary diversity changes and cognitive frailty (CF) in the older adults is not clear. This study aimed to investigate the relationship between dietary diversity changes and CF in older adults Chinese. A total of 14,382 participants (mean age: 82.3 years) were enrolled. Dietary diversity scores (DDSs) were collected and calculated using a food frequency questionnaire. DDS changes between baseline and first follow-up were categorized into nine patterns. The associations between DDS changes and the incidence of CF were estimated using Cox proportional hazards models. During an 80,860 person-year follow-up, 3023 CF cases were identified. Groups with a decrease in DDS had increased CF risk compared with the high-to-high DDS group, with adjusted hazard ratios (HRs; 95% confidence intervals (Cis)) of 1.30 (1.06, 1.59), 2.04 (1.51, 2.74), and 1.81 (1.47, 2.22) for high-to-medium, high-to-low, and medium-to-low groups, respectively. Lower overall DDS groups were associated with greater CF risks, with HRs (95% CIs) of 1.49 (1.19, 1.86) for the low-to-medium group and 1.96 (1.53, 2.52) for the low-to-low group. Compared with the high-to-high group, significant associations with CF were found in other DDS change groups; HRs ranged from 1.38 to 3.12 for the plant-based DDS group and from 1.24 to 1.32 for the animal-based DDS group. Additionally, extreme and moderate declines in overall DDS increased CF risk compared with stable DDS, with HRs (95% CIs) of 1.67 (1.50, 1.86) and 1.13 (1.03, 1.24), respectively. In conclusion, among older adults, a declining or persistently low DDS and a moderately or extremely declining DDS were linked to higher incident CF. Plant-based DDS changes correlated more strongly with CF than animal-based DDS changes.

Long-term air pollution exposure, habitual physical activity, and incident chronic kidney disease.

Both air pollution and physical inactivity contribute to the increased risk of incident chronic kidney disease (CKD). However, the detrimental effects of air pollution exposure could be augmented by an elevated intake of air pollutants during exercise. In the present study, we analyzed 367,978 participants who were CKD-free at baseline (2006-2010) based on the UK Biobank. Air pollutants included fine particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOX). Physical activity (PA) was obtained by the self-reported questionnaire. Using Cox proportional hazards models, hazard ratios (HRs) for incident CKD related to air pollution, PA, and incident CKD were evaluated. During a median of 12.4 years of follow-up, 14,191 incident CKD events were documented. High PM2.5, PM10, NO2, and NOX increased CKD risks by 11 %, 15 %, 14 %, and 12 %, respectively, while moderate and high PA reduced CKD risks by 18 % and 22 %, respectively. Participants with high PA and low air pollution exposure had 29 %, 31 %, 30 %, and 30 % risks of incident CKD than those with low PA and high air pollution exposure for the four air pollutants, with multivariable-adjusted HRs of 0.71 (95 % confidence intervals [CI]: 0.65-0.76) for PM2.5, 0.69 (95 % CI: 0.64-0.75) for PM10, 0.70 (95 % CI: 0.64-0.75) for NO2, and 0.70 (95 % CI: 0.64-0.75) for NOX. No clear interactions were observed between each air pollutant exposure and PA (all P for interaction > 0.05). The findings that reducing air pollution exposure and increasing PA were both independently correlated with a diminished risk of incident CKD suggest that PA could be targeted to prevent CKD generally regardless of air pollution levels. Further research is needed in areas polluted moderately and severely to examine our findings.

Discrete RNA-DNA hybrid cleavage by the EXD2 exonuclease pinpoints two rate-limiting steps.

EXD2 is a recently identified exonuclease that cleaves RNA and DNA in double-stranded (ds) forms. It thus serves as a model system for investigating the similarities and discrepancies between exoribonuclease and exodeoxyribonuclease activities and for understanding the nucleic acid (NA) unwinding-degradation coordination of an exonuclease. Here, using a single-molecule fluorescence resonance energy transfer (smFRET) approach, we show that despite stable binding to both substrates, EXD2 barely cleaves dsDNA and yet displays both exoribonuclease and exodeoxyribonuclease activities toward RNA-DNA hybrids with a cleavage preference for RNA. Unexpectedly, EXD2-mediated hybrid cleavage proceeds in a discrete stepwise pattern, wherein a sudden 4-bp duplex unwinding increment and the subsequent dwell constitute a complete hydrolysis cycle. The relatively weak exodeoxyribonuclease activity of EXD2 partially originates from frequent hybrid rewinding. Importantly, kinetic analysis and comparison of the dwell times under varied conditions reveal two rate-limiting steps of hybrid unwinding and nucleotide excision. Overall, our findings help better understand the cellular functions of EXD2, and the cyclic coupling between duplex unwinding and exonucleolytic degradation may be generalizable to other exonucleases.

Effects of lotus seedpod oligomeric procyanidins on the inhibition of AGEs formation and sensory quality of tough biscuits.

The advanced glycation end products (AGEs) are formed in baked products through the Maillard reaction (MR), which are thought to be a contributing factor to chronic diseases such as heart diseases and diabetes. Lotus seedpod oligomeric procyanidins (LSOPC) are natural antioxidants that have been added to tough biscuit to create functional foods that may lower the risk of chronic diseases. The effect of LSOPC on AGEs formation and the sensory quality of tough biscuit were examined in this study. With the addition of LSOPC, the AGEs scavenging rate and antioxidant capacity of LSOPC-added tough biscuits were dramatically improved. The chromatic aberration (ΔE) value of tough biscuits containing LSOPC increased significantly. Higher addition of LSOPC, on the other hand, could effectively substantially reduced the moisture content, water activity, and pH of LSOPC toughen biscuits. These findings imply that using LSOPC as additive not only lowers the generation of AGEs, but also improves sensory quality of tough biscuit.

Habitual fish oil supplementation and incident chronic obstructive pulmonary disease: Data from a prospective cohort study.

BACKGROUND: Fish oil is one of the most popular supplements in the UK and other developed countries. However, the relationship between fish oil use and chronic obstructive pulmonary disease (COPD) is unclear. OBJECTIVE: To prospectively examine the association of habitual fish oil supplementation with incident COPD risk and to evaluate potential effect modification by genetic predisposition. METHODS: This study included 484,414 participants (mean and standard deviation [SD] age: 56.5 [8.1] years) from the UK Biobank who completed a touchscreen questionnaire on habitual fish oil supplement use between 2006 and 2010 and were followed up through 2018. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) with adjustment for sociodemographic and lifestyle behaviours, health conditions, and other potential confounding factors. A weighted genetic risk score (GRS) for COPD was derived from 112 validated single nucleotide polymorphisms. RESULTS: During a median follow-up of 9.0 years, 8860 incident COPD events were recorded. A total of 31.4% (152,230) of the study participants reported habitual fish oil supplementation at baseline. Habitual fish oil supplementation was significantly associated with a lower risk of incident COPD (adjusted HR: 0.88; 95% CI: 0.84-0.93). The association with COPD did not differ by GRS strata (P for interaction = 0.880). The results from subgroup and sensitivity analyses supported the robustness of our findings. CONCLUSIONS: Our findings suggest that habitual fish oil supplementation is associated with a lower risk of incident COPD, irrespective of genetic predisposition.

Endometrial glycogen metabolism during early pregnancy in mice.

Glucose is critical during early pregnancy. The uterus can store glucose as glycogen but uterine glycogen metabolism is poorly understood. This study analyzed glycogen storage and localization of glycogen metabolizing enzymes from proestrus until implantation in the murine uterus. Quantification of diastase-labile periodic acid-Schiff (PAS) staining showed glycogen in the glandular epithelium decreased 71.4% at 1.5 days postcoitum (DPC) and 62.13% at DPC 3.5 compared to proestrus. In the luminal epithelium, glycogen was the highest at proestrus, decreased 46.2% at DPC 1.5 and 63.2% at DPC 3.5. Immunostaining showed that before implantation, glycogen metabolizing enzymes were primarily localized to the glandular and luminal epithelium. Stromal glycogen was low from proestrus to DPC 3.5. However, at the DPC 5.5 implantation sites, stromal glycogen levels increased sevenfold. Similarly, artificial decidualization resulted in a fivefold increase in glycogen levels. In both models, decidualization increased expression of glycogen synthase as determine by immunohistochemistry and western blot. In conclusion, glycogen levels decreased in the uterine epithelium before implantation, indicating that it could be used to support preimplantation embryos. Decidualization resulted in a dramatic increase in stromal glycogen levels, suggesting it may have an important, but yet undefined, role in pregnancy.

Inhibitory effect of LSOPC on AGEs formation and sensory quality in cookies.

At the conclusion of the Maillard reaction (MR), free amino groups of proteins, amino acids, or lipids with the carboxyl groups of reducing sugars to form stable molecules known as advanced glycation end products (AGEs), which hasten aging and may potentially be the root cause of a number of chronic degenerative diseases. According to researches, lotus seedpod oligomeric procyanidins (LSOPC), a premium natural antioxidant produced from lotus waste, can be included in cookies to improve flavor and lower the risk of illnesses linked to AGEs. In this work, we used cookies without LSOPC as a control to examine the effects of adding various concentrations of LSOPC (0, 0.05, 0.1, 0.2, and 0.4%) on the AGEs formation and the sensory quality in cookies. The amounts of AGEs and N-ε-carboxymethyl lysine (CML) decreased with the increase of LSOPC concentration, indicating that the concentration of LSOPC was positively correlated with the ability to inhibit AGEs formation. It was also demonstrated that the amount of antioxidant capacity of the cookies increased significantly with the increase of LSOPC concentration. On the other hand, the chromaticity, texture, electronic nose, and other aspects of the cookies' sensory attributes were also evaluated. The color of the cookies deepened and the flavor varied as LSOPC added content increased. The sensory quality of the cookies was examined, and the findings indicated that LSOPC would somewhat improve that quality. These findings implied that AGEs formation could be decreased in cookies while also enhancing their sensory quality by adding LSOPC.

Efficient DNA interrogation of SpCas9 governed by its electrostatic interaction with DNA beyond the PAM and protospacer.

Streptococcus pyogenes Cas9 (SpCas9), a programmable RNA-guided DNA endonuclease, has been widely repurposed for biological and medical applications. Critical interactions between SpCas9 and DNA confer the high specificity of the enzyme in genome engineering. Here, we unveil that an essential SpCas9-DNA interaction located beyond the protospacer adjacent motif (PAM) is realized through electrostatic forces between four positively charged lysines among SpCas9 residues 1151-1156 and the negatively charged DNA backbone. Modulating this interaction by substituting lysines with amino acids that have distinct charges revealed a strong dependence of DNA target binding and cleavage activities of SpCas9 on the charge. Moreover, the SpCas9 mutants show markedly distinguishable DNA interaction sites beyond the PAM compared with wild-type SpCas9. Functionally, this interaction governs DNA sampling and participates in protospacer DNA unwinding during DNA interrogation. Overall, a mechanistic and functional understanding of this vital interaction explains how SpCas9 carries out efficient DNA interrogation.

Proximal Single-Stranded RNA Destabilizes Human Telomerase RNA G-Quadruplex and Induces Its Distinct Conformers.

Single-stranded guanine-rich RNA sequences have a propensity to fold into compact G-quadruplexes (RG4s). The conformational transitions of these molecules provide an important way to regulate their biological functions. Here, we examined the stability and conformation of an RG4-forming sequence identified near the end of human telomerase RNA. We found that a proximal single-stranded (ss) RNA significantly impairs RG4 stability at physiological K+ concentrations, resulting in a reduced RG4 rupture force of ∼ 24.4 pN and easier accessibility of the G-rich sequence. The destabilizing effect requires a minimum of six nucleotides of ssRNA and is effective at either end of RG4. Remarkably, this RG4-forming sequence, under the influence of such a proximal ssRNA, exhibits interconversions between at least three less stable RG4 conformers that might represent potential intermediates along its folding/unfolding pathway. This work provides insights into the stability and folding dynamics of RG4 that are essential for understanding its biological functions.