Enantioselective Construction of Quaternary Stereocenters via Cooperative Photoredox/Fe/Chiral Primary Amine Triple Catalysis.

The catalytic and enantioselective construction of quaternary (all-carbon substituents) stereocenters poses a formidable challenge in organic synthesis due to the hindrance caused by steric factors. One conceptually viable and potentially versatile approach is the coupling of a C-C bond through an outer-sphere mechanism, accompanied by the realization of enantiocontrol through cooperative catalysis; however, examples of such processes are yet to be identified. Herein, we present such a method for creating different compounds with quaternary stereocenters by photoredox/Fe/chiral primary amine triple catalysis. This approach facilitates the connection of an unactivated alkyl source with a tertiary alkyl moiety, which is also rare. The scalable process exhibits mild conditions, does not necessitate the use of a base, and possesses a good functional-group tolerance. Preliminary investigations into the underlying mechanisms have provided valuable insights into the reaction pathway.

Association between the triglyceride glucose-body mass index and future cardiovascular disease risk in a population with Cardiovascular-Kidney-Metabolic syndrome stage 0-3: a nationwide prospective cohort study.

BACKGROUND: The American Heart Association (AHA) has recently introduced the concept of Cardiovascular-Kidney-Metabolic (CKM) syndrome, which is the result of an increasing emphasis on the interplay of metabolic, renal and cardiovascular diseases (CVD). Furthermore, there is substantial evidence of a correlation between the triglyceride glucose-body mass index (TyG-BMI ) and CVD as an assessment of insulin resistance (IR). However, it remains unknown whether this correlation exists in population with CKM syndrome. METHODS: All data for this study were obtained from the China Health and Retirement Longitudinal Study (CHARLS). The exposure was the participants' TyG-BMI at baseline, which was calculated using a combination of triglycerides (TG), fasting blood glucose (FBG) and body mass index (BMI). The primary outcome was CVD, which were determined by the use of a standardised questionnaire during follow-up. To examine the relationship between TyG-BMI and CVD incidence in population with CKM syndrome, both Cox regression analyses and restricted cubic spline (RCS) regression analyses were performed. RESULTS: A total of 7376 participants were included in the final analysis. Of these, 1139, 1515, 1839, and 2883 were in CKM syndrome stages 0, 1, 2, and 3, respectively, at baseline. The gender distribution was 52.62% female, and the mean age was 59.17 ± 9.28 (years). The results of the fully adjusted COX regression analyses indicated that there was a 6.5% increase in the risk of developing CVD for each 10-unit increase in TyG-BMI,95% confidence interval (CI):1.041-1.090. The RCS regression analyses demonstrated a positive linear association between TyG-BMI and the incidence of CVD in the CKM syndrome population (P for overall < 0.001, P for nonlinear = 0.355). CONCLUSIONS: This cohort study demonstrated a positive linear association between TyG-BMI index and increased CVD incidence in a population with CKM syndrome stage 0-3. This finding suggests that enhanced assessment of TyG-BMI index may provide a more convenient and effective tool for individuals at risk for CVD in CKM syndrome stage 0-3.

Phosphine-Catalyzed 1,2-cis-Diboration of 1,3-Butadiynes.

Trialkyl phosphines PMe3 and PEt3 catalyze the 1,2-cis-diboration of 1,3-butadiynes to give 1,2-diboryl enynes. The products were utilized to synthesize 1,1,2,4-tetraaryl enynes using a Suzuki-Miyaura protocol and can readily undergo proto-deborylation.

Quality of life, household income, and dietary habits are associated with the risk of sarcopenia among the Chinese elderly.

BACKGROUND: Health-related quality of life (HRQoL), which can be influenced by various aspects, especially socioeconomic status and lifestyle, has been identified as an important predictor of the prognosis of older adults. Dietary habit, a major part of lifestyle, can affect the nutritional status, which is closely correlated with the development of geriatric syndromes in the elderly. AIMS: The aim of the study was to examine the association of HRQoL, socioeconomic status, and lifestyle with the risk and severity of sarcopenia, a geriatric syndrome characterized by progressive loss of skeletal muscle mass, strength and function. METHODS: A cross-sectional retrospective study with 2877 participants aged ≥65 years was performed. HRQoL was assessed using EuroQoL Five Dimensions questionnaire. Socioeconomic status was assessed by the educational attainment, occupation, and household income. Lifestyle was assessed using 12 items closely related to Chinese living habits. The information of daily dietary habits including tea, alcohol, type of diet, and volume of drinking water were collected. The associations of HRQoL, socioeconomic status, and lifestyle with the risk of sarcopenia were examined by multivariate regression logistical analysis. The potential causal role of age, body mass index, and waist circumference in the effect of HRQoL on sarcopenia risk was analyzed by causal mediation analysis. RESULTS: High HRQoL [adjusted odds ratio (OR) =0.85, 95% confidence interval (CI) =0.69-0.95, P=0.034] and household income levels (adjusted OR =0.74, 95% CI =0.57-0.95, P=0.019) were inversely associated with the risk of sarcopenia. Meanwhile, more consumption of spicy food (adjusted OR =1.34, 95% CI =1.09-1.81, P =0.037) and occasionally drinking (adjusted OR =1.46, 95% CI =1.07-2.00, P =0.016, as compared to those never drinking) were associated with higher risk of sarcopenia, while skipping breakfast occasionally (adjusted OR =0.37, 95% CI =0.21-0.64, P <0.001, as compared to those eating breakfast every day) and less consumption of salt (adjusted OR =0.71, 95% CI =0.52-0.96, P =0.026, as compared to those consuming high amount of salt) were associated with lower risk of sarcopenia. Further causal mediation analysis aimed to explore how much age, body mass index, and waist circumference might explain the effect of HRQoL on the risk of sarcopenia showed that the estimated proportion that mediated the effect of HRQoL on the risk of sarcopenia by age was 28.0%. CONCLUSIONS: In summary, our findings demonstrate that low levels of HRQoL and household income, more intake of salt and spicy food, and occasional intake of alcohol are correlated with higher risk of sarcopenia, while skipping breakfast occasionally is associated with lower risk of sarcopenia in a Chinese population of older adults.

Nickel-Catalyzed Highly Selective Radical C-C Coupling from Carboxylic Acids with Photoredox Catalysis.

Controlling the cross-coupling reaction between two different radicals is a long-standing challenge due to the process occurring statistically, which would lead to three products, including two homocoupling products and one cross-coupling product. Generally, the cross-coupling selectivity is achieved by the persistent radical effect (PRE) that requires the presence of a persistent radical and a transient radical, thus resulting in limited radical precursors. In this paper, a highly selective cross-coupling of alkyl radicals with acyl radicals to construct C(sp2)-C(sp3) bonds, or with alkyl radicals to construct C(sp3)-C(sp3) bonds have been achieved with the readily available carboxylic acids and their derivatives (NHPI ester) as coupling partners. The success originates from the use of tridentate ligand (2,2' : 6',2''-terpyridine) to enable radical cross-coupling process to Ni-mediated organometallic mechanism. This protocol offers a facile and flexible access to structurally diverse ketones (up to 90 % yield), and also a new solution for the challenging double decarboxylative C(sp3)-C(sp3) coupling. The broad utility and functional group tolerance are further illustrated by the late-stage functionalization of natural-occurring carboxylic acids and drugs.

Spatial-temporal pattern of change in production-living-ecological space of Nanchong City from 2000 to 2020 and underlying factors.

This study analyzed the spatial-temporal change pattern and underlying factors in production-living-ecological space (PLES) of Nanchong City, China, over the past 20 years using historical land use data (2000, 2010, 2020). A land use transfer matrix was calculated from the historical land use maps, and spatial analysis was conducted to analyze changes in the land use dynamics degree, standard deviation ellipse, and center of gravity. The results showed that there was a rapid spatial evolution of the PLES in Nanchong from 2000 to 2010, followed by a stabilization in the second decade. The transfer of ecological-production space occurred mainly in the Jialing and Yilong River basins, while the reduction of production space and the increase of living space were most prominent in the intersection of three districts (Shunqing, Jialing, and Gaoping districts). The return of production-ecological space was observed in the south and northeast of Yingshan, and there was little notable transfer of other types. The distribution of production space in Nanchong evolved in a north-south to east-west trend, with the center of gravity moving from Yilong to Peng'an County. The living space and production space expanded in a north-south direction, and the center of gravity position was in Nanbu, indicating a more balanced growth or decrease in the last 20 years. The changes in the spatial-temporal pattern of PLES in Nanchong were attributed to the intertwined factors of national policies, economic development, population growth, and the natural environment. This study introduced a novel approach towards rational planning of land resources in Nanchong, which may facilitate more sustainable urban planning and development.

The 3'UTR Polymorphisms in the NLRP3 Gene Associated with the Risk of COPD and Their Putative Effects on the microRNA Mechanism.

Aims: Evaluating the association between a single nucleotide polymorphism in the 3' untranslated region (3'UTR) of the miRNA binding site of the NLRP3 gene and the occurrence and development of chronic obstructive pulmonary disease (COPD) and providing information to aid in the early detection and treatment of COPD. Materials and Methods: The regulatory single nuclear polymorphisms (SNPs) located in NLRP3 3'UTR were searched by using the dbSNP database and miRNA binding site prediction database. Meanwhile, samples from COPD patients and healthy controls in the same period were used for verification. The clinical baseline information of all subjects was collected, and the transcription level and protein expression level of NLRP3 and the expression level of inflammatory factors downstream of NLRP3 were detected. The effects of SNPs' single nucleotide changes on the transcription and expression of inflammatory factors were analyzed. Results: The study included 418 participants (249 in the COPD group and 169 in the control group). NLRP3 SNPs with miRNA binding sites include rs10754558 (G > C), rs1664774076 (ATAT > del), and rs1664775106 (C > G). Furthermore, two genotypes, GCG and GCA, were discovered to have a linkage mutation at 3'UTR 459-461. COPD susceptibility is tightly associated with the expression of the rs1664774076 del/del genotype, and the risk of COPD increased by 2.770 times (p = 0.003). Type 459-461 GCA was substantially related to the likelihood of developing COPD at various stages (p < 0.05). Except for rs10754558, all homozygous mutants increased NLRP3 mRNA and protein levels. NLRP3 had the greatest area under the receiver operating characteristic (ROC) curve for predicting the development and diagnosis of COPD when compared with its downstream inflammatory variables (AUC = 0.9291). Conclusions: The NLRP3 rs1664774076 del/del genotype is a COPD susceptibility gene, and the GCA genotype at 459-461 can be used as an early predictor of COPD exacerbation. The NLRP3 3'UTR polymorphism may alter the loss of miRNA binding sites, leading to an increase in NLRP3 expression. In the development of COPD, NLRP3 has a better diagnostic value than traditional inflammatory factors. The Clinical Trials Registration number Z: protocol KY01-2020-11-06.

Development and validation of a machine learning model to improve precision prediction for irrational prescriptions in orthopedic perioperative patients.

OBJECTIVE: Our objective was to develop a machine learning model capable of predicting irrational medical prescriptions precisely within orthopedic perioperative patients. METHODS: A dataset comprising 3047 instances of suspected irrational medication prescriptions was collected from a sample of 1318 orthopedic perioperative patients from April 2019 to March 2022. Four machine learning models were employed to forecast irrational prescriptions, following which, the performance of each model was meticulously assessed. Subsequently, a thorough variable importance analysis was conducted on the model that performed the best predictive capabilities. Thereafter, the efficacy of integrating this optimal model into the existing audit prescription process was rigorously evaluated. RESULTS: Of the models utilized in this study, the RF model yielded the highest AUC of 92%, whereas the NB model presented the lowest AUC of 68%. Also, the RF model boasted the most robust performance in terms of PPV, reaching 82.4%, and NPV, reaching 86.6%. The ANN and the XGBoost model were neck and neck, with the ANN slightly edging out with a higher PPV of 95.9%, while the XGBoost model boasted an impressive NPV of 98.2%. The RF model singled out the following five factors as the most influential in predicting irrational prescriptions: the type of drug, the type of surgery, the number of comorbidities, the date of surgery after hospitalization, as well as the associated hospital and drug costs. CONCLUSION: The RF model showcased significantly high level of proficiency in predicting irrational prescriptions among orthopedic perioperative patients, outperforming other models by a considerable margin. It effectively enhanced the efficiency of pharmacist interventions, displaying outstanding performance in assisting pharmacists to intervene with irrational prescriptions.

Catalytic Nanoparticles in Biomedical Applications: Exploiting Advanced Nanozymes for Therapeutics and Diagnostics.

Catalytic nanoparticles (CNPs) as heterogeneous catalyst reveals superior activity due to their physio-chemical features, such as high surface-to-volume ratio and unique optical, electric, and magnetic properties. The CNPs, based on their physio-chemical nature, can either increase the reactive oxygen species (ROS) level for tumor and antibacterial therapy or eliminate the ROS for cytoprotection, anti-inflammation, and anti-aging. In addition, the catalytic activity of nanozymes can specifically trigger a specific reaction accompanied by the optical feature change, presenting the feasibility of biosensor and bioimaging applications. Undoubtedly, CNPs play a pivotal role in pushing the evolution of technologies in medical and clinical fields, and advanced strategies and nanomaterials rely on the input of chemical experts to develop. Herein, a systematic and comprehensive review of the challenges and recent development of CNPs for biomedical applications is presented from the viewpoint of advanced nanomaterial with unique catalytic activity and additional functions. Furthermore, the biosafety issue of applying biodegradable and non-biodegradable nanozymes and future perspectives are critically discussed to guide a promising direction in developing span-new nanozymes and more intelligent strategies for overcoming the current clinical limitations.

Dinuclear gold-catalyzed divergent dechlorinative radical borylation of gem-dichloroalkanes.

The enormous and widespread use of organoboronic acids has prompted the development of innovative synthetic methodologies to meet the demands on structural diversity and functional group tolerance. The existing photoinduced defunctionalization radical borylation, typically focused on the conversion of one C-X bond (X= Br, I, or other leaving group) into only one C-B bond. Herein, we disclose a divergent radical dechloroborylation reaction enabled by dinuclear gold catalysis with visible light irradiation. A wide range of structurally diverse alkyl boronic, α-chloroboronic, and gem-diboronic esters can be synthesized in moderate to good yields (up to 92%). Its synthetic robustness is further demonstrated on a preparative scale and applied to late-stage diversification of complex molecules. The process hinges on a C-Cl bond relay activation in readily available gem-dichloroalkanes through inner-sphere electron transfer, overcoming the redox potential limits of unreactive alkyl chlorides.

Stereoselective benzylic C(sp3)-H alkenylation enabled by metallaphotoredox catalysis.

Selective activation of the benzylic C(sp3)-H bond is pivotal for the construction of complex organic frameworks. Achieving precise selectivity among C-H bonds with comparable energetic and steric profiles remains a profound synthetic challenge. Herein, we unveil a site- and stereoselective benzylic C(sp3)-H alkenylation utilizing metallaphotoredox catalysis. Various linear and cyclic (Z)-all-carbon tri- and tetrasubstituted olefins can be smoothly obtained. This strategy can be applied to complex substrates with multiple benzylic sites, previously deemed unsuitable due to the uncontrollable site-selectivity. In addition, sensitive functional groups such as terminal alkenyl and TMS groups are compatible under the mild conditions. The exceptional site-selectivity and broad substrate compatibility are attributed to the visible-light catalyzed relay electron transfer-proton transfer process. More importantly, we have extended this methodology to achieve enantioselective benzylic C(sp3)-H alkenylation, producing highly enantioenriched products. The applicability and scalability of our protocol are further validated through late-stage functionalization of complex structures and gram-scale operations, underscoring its practicality and robustness.

Device for Measuring Contact Reaction Forces during Animal Adhesion Landing/Takeoff from Leaf-like Compliant Substrates.

A precise measurement of animal behavior and reaction forces from their surroundings can help elucidate the fundamental principle of animal locomotion, such as landing and takeoff. Compared with stiff substrates, compliant substrates, like leaves, readily yield to loads, presenting grand challenges in measuring the reaction forces on the substrates involving compliance. To gain insight into the kinematic mechanisms and structural-functional evolution associated with arboreal animal locomotion, this study introduces an innovative device that facilitates the quantification of the reaction forces on compliant substrates, like leaves. By utilizing the stiffness-damping characteristics of servomotors and the adjustable length of a cantilever structure, the substrate compliance of the device can be accurately controlled. The substrate was further connected to a force sensor and an acceleration sensor. With the cooperation of these sensors, the measured interaction force between the animal and the compliant substrate prevented the effects of inertial force coupling. The device was calibrated under preset conditions, and its force measurement accuracy was validated, with the error between the actual measured and theoretical values being no greater than 10%. Force curves were measured, and frictional adhesion coefficients were calculated from comparative experiments on the landing/takeoff of adherent animals (tree frogs and geckos) on this device. Analysis revealed that the adhesion force limits were significantly lower than previously reported values (0.2~0.4 times those estimated in previous research). This apparatus provides mechanical evidence for elucidating structural-functional relationships exhibited by animals during locomotion and can serve as an experimental platform for optimizing the locomotion of bioinspired robots on compliant substrates.

Frontiers and hotspots in comorbid epilepsy and depression: a bibliometric analysis from 2003 to 2023.

Background: Epilepsy ranks among the most common neurological disorders worldwide, frequently accompanied by depression as a prominent comorbidity. This study employs bibliometric analysis to reveal the research of comorbid epilepsy and depression over the past two decades, aiming to explore trends and contribute insights to ongoing investigations. Methods: We conducted a comprehensive search on the Web of Science Core Collection database and downloaded relevant publications on comorbid epilepsy and depression published from 2003 to 2023. VOSviewer and CiteSpace were mainly used to analyze the authors, institutions, countries, publishing journals, reference co-citation patterns, keyword co-occurrence, keyword clustering, and other aspects to construct a knowledge atlas. Results: A total of 5,586 publications related to comorbid epilepsy and depression were retrieved, with a general upward trend despite slight fluctuations in annual publications. Publications originated from 121 countries and 636 institutions, with a predominant focus on clinical research. The United States led in productivity (1,529 articles), while Melbourne University emerged as the most productive institution (135 articles). EPILEPSY & BEHAVIOR was the journal with the highest publication output (1,189 articles) and citation count. Keyword analysis highlighted emerging trends, including "recognitive impairment" and "mental health," indicating potential future research hotspots and trends. Conclusion: This study is one of the first to perform a bibliometric analysis of the 20-year scientific output of comorbid epilepsy and depression. While research has trended upwards, ambiguity in pathogenesis and the absence of standardized diagnostic guidelines remain concerning. Our analysis offers valuable guidance for researchers, informing that this might be a strong area for future collaborations.

The value of dual time-point fluorine-18 fluorodeoxyglucose PET/computed tomography imaging in predicting lymph node metastasis in non-small cell lung cancer patients.

OBJECTIVE: The purpose of this study was to analyze the correlation between specified dual time-point fluorine-18 fluorodeoxyglucose ( 18 F-FDG) PET/computed tomography (CT) imaging parameters and pathological characteristics in non-small cell lung cancer (NSCLC) patients. METHODS: This study retrospectively analyzed 47 patients with NSCLC. All patients underwent dual time-point 18 F-FDG PET/CT imaging. We obtained the metabolic parameters, standardized uptake value (SUV) maximum, SUV mean , delayed standardized uptake value (DSUV) maximum, DSUV mean , delay index standardized uptake value (DISUV) maximum, and DISUV mean , of the primary tumor. The tumor size was measured by CT. All lymph nodes had a definite pathological diagnosis. We next evaluated the status of the lymph node metastases (LNM) and the correlations between metabolic parameters and clinical characteristics. Receiver operating characteristic curves were drawn for the prediction of LNM. RESULTS: We found that the DSUV max , DISUV max , DSUV mean , and tumor size were significantly related to LNM ( P  = 0.036, 0.009, and 0.049, respectively). Multivariate analysis revealed that tumor size and DISUV max were independent risk factors for LNM in lung cancer patients. According to the receiver operating characteristic curve analysis, the optimal cutoff values for DISUV max and tumor size were 0.33 and 2.8 cm, respectively. When these two parameters were combined, the area under the curve for predicting LNM in NSCLC was 0.768, and the sensitivity was 95.7% for predicting LNM in lung cancer patients. We further allocated the patients to three groups: the high-risk group (tumor size ≥ 2.8 cm, DISUV max  ≥ 0.33), the moderate-risk group (tumor size ≥ 2.8 cm, DISUV max  < 0.33, or tumor size < 2.8 cm, DISUV max  ≥ 0.33), and the low-risk group (tumor size < 2.8 cm, DISUV max  < 0.33). The rates of LNM were 70, 50, and 0%, respectively. CONCLUSION: Tumor size and DISUV max are risk factors for predicting LNM, and they are more useful in combination. Compared with standard PET/CT imaging, dual time-point PET/CT imaging has added value in predicting LNM in NSCLC patients.

Photo-Responsive Ascorbic Acid-Modified Ag2S-ZnS Heteronanostructure Dropping pH to Trigger Synergistic Antibacterial and Bohr Effects for Accelerating Infected Wound Healing.

Nonantibiotic approaches must be developed to kill pathogenic bacteria and ensure that clinicians have a means to treat wounds that are infected by multidrug-resistant bacteria. This study prepared matchstick-like Ag2S-ZnS heteronanostructures (HNSs). Their hydrophobic surfactants were then replaced with hydrophilic poly(ethylene glycol) (PEG) and thioglycolic acid (TGA) through the ligand exchange method, and this was followed by ascorbic acid (AA) conjugation with TGA through esterification, yielding well-dispersed PEGylated Ag2S-ZnS@TGA-AA HNSs. The ZnS component of the HNSs has innate semiconductivity, enabling the generation of electron-hole pairs upon irradiation with a light of wavelength 320 nm. These separate charges can react with oxygen and water around the HNSs to produce reactive oxygen species. Moreover, some holes can oxidize the surface-grafted AA to produce protons, decreasing the local pH and resulting in the corrosion of Ag2S, which releases silver ions. In evaluation tests, the PEGylated Ag2S-ZnS@TGA-AA had synergistic antibacterial ability and inhibited Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus (MRSA). Additionally, MRSA-infected wounds treated with a single dose of PEGylated Ag2S-ZnS@TGA-AA HNSs under light exposure healed significantly more quickly than those not treated, a result attributable to the HNSs' excellent antibacterial and Bohr effects.

Boosting Upconversion Efficiency in Optically Inert Shelled Structures with Electroactive Membrane through Electron Donation.

This study innovatively addresses challenges in enhancing upconversion efficiency in lanthanide-based nanoparticles (UCNPs) by exploiting Shewanella oneidensis MR-1, a microorganism capable of extracellular electron transfer. Electroactive membranes, rich in c-type cytochromes, are extracted from bacteria and integrated into membrane-integrated liposomes (MILs), encapsulating core-shelled UCNPs with an optically inactive shell, forming UCNP@MIL constructs. The electroactive membrane, tailored to donate electrons through the inert shell, independently boosts upconversion emission under near-infrared excitation (980 or 1550 nm), bypassing ligand-sensitized UCNPs. The optically inactive shell restricts energy migration, emphasizing electroactive membrane electron donation. Density functional theory calculations elucidate efficient electron transfer due to the electroactive membrane hemes' highest occupied molecular orbital being higher than the valence band maximum of the optically inactive shell, crucial for enhancing energy transfer to emitter ions. The introduction of a SiO2 insulator coating diminishes light enhancement, underscoring the importance of unimpeded electron transfer. Luminescence enhancement remains resilient to variations in emitter or sensitizing ions, highlighting the robustness of the electron transfer-induced phenomenon. However, altering the inert shell material diminishes enhancement, emphasizing the role of electron transfer. This methodology holds significant promise for diverse biological applications. UCNP@MIL offers an advantage in cellular uptake, which proves beneficial for cell imaging.