Cs2CO3 Promoted [4 + 2] Cycloaddition of 1,6-Enynes: An Approach to Tetrahydro-1H-benzo-f-isoindole Isomers.

A Cs2CO3-promoted [4 + 2] cycloaddition of 1,6-enynes under mild reaction conditions has been developed. This protocol provides a facile approach to a series of tetrahydro-1H-benzo[f]isoindole isomerized products promoted by Cs2CO3 with moderate to high yields. By simply switching the reaction solvent and controlling the reaction time, two isomerization products could be obtained, both with good selectivity.

ALKBH5-mediated m6A demethylation ameliorates extracellular matrix deposition in cutaneous pathological fibrosis.

BACKGROUND: Elevated extracellular matrix (ECM) accumulation is a major contributing factor to the pathogenesis of fibrotic diseases. Recent studies have indicated that N6-methyladenosine (m6A) RNA modification plays a pivotal role in modulating RNA stability and contribute to the initiation of various pathological conditions. Howbeit, the precise mechanism by which m6A influences ECM deposition remains unclear. METHODS: In this study, we used hypertrophic scars (HTSs) as a paradigm to investigate ECM-related diseases. We focused on the role of ALKBH5-mediated m6A demethylation within the pathological progression of HTSs and examined its correlation with clinical stages. The effects of ALKBH5 ablation on ECM components were studied both in vivo and in vitro. Downstream targets of ALKBH5, along with their underlying mechanisms, were identified using integrated high-throughput analysis, RNA-binding protein immunoprecipitation and RNA pull-down assays. Furthermore, the therapeutic potential of exogenous ALKBH5 overexpression was evaluated in fibrotic scar models. RESULTS: ALKBH5 was decreased in fibroblasts derived from HTS lesions and was negatively correlated with their clinical stages. Importantly, ablation of ALKBH5 promoted the expression of COL3A1, COL1A1, and ELN, leading to pathological deposition and reconstruction of the ECM both in vivo and in vitro. From a therapeutic perspective, the exogenous overexpression of ALKBH5 significantly inhibited abnormal collagen deposition in fibrotic scar models. As determined by integrated high-throughput analysis, key ECM components including COL3A1, COL1A1, and ELN are direct downstream targets of ALKBH5. By means of its mechanism, ALKBH5 inhibits the expression of COL3A1, COL1A1, and ELN by removing m6A from mRNAs, thereby decreasing their stability in a YTHDF1-dependent manner. CONCLUSIONS: Our study identified ALKBH5 as an endogenous suppressor of pathological ECM deposition, contributing to the development of a reprogrammed m6A-targeted therapy for HTSs.

The effect of family physician team processes on chronic disease management performance from a structural network perspective.

OBJECTIVE: The family physician team has become the core carrier for delivery primary health care in China. This study aimed to measure the effect of the network structural characteristics of family physician team processes on health performance. Strategic recommendations for optimizing the family physician team processes with a view to improving performance were presented. METHODS: A cross-sectional survey was conducted from October to December 2021 in Qianjiang in Hubei Province and Changsha in Hunan Province. Task performance, contextual performance, social networks, and sociodemographic characteristics were collected. Social network analysis was conducted to calculate density and centralization, then hierarchical linear regression analysis was employed to explore the relationship between the network structural characteristics of family physician team processes and performance. RESULTS: In total, 88 family physician teams attended in this investigation. The transition processes of family physician team showed a distinctive low density (0.272 ± 0.112), high centralization (0.866 ± 0.197) network structure. For family physician team, the density of action processes significantly and positively affected task performance (B = 0.600, P < 0.05); the centralization of action processes positively affected task performance (B = 0.604, P < 0.01); the density of action processes positively affected contextual performance (B = 0.545, P < 0.01); the density of interpersonal processes significantly and positively affected contextual performance (B = 0.326, P < 0.05). CONCLUSION: The network density and centralization of family physician team processes have positive effects on chronic disease management performance. The results from this study help to enhance our conceptual understanding of social network and its implications for team-dynamics. Optimizing family physician team processes is an effective way to strengthen the construction of family physician team and promote the quality and efficiency of family physician-contracted service. It is recommended to strengthen the management of team processes, enhance the internal collaboration mechanism, and optimize the centralized network structure of family physician team.

Sublethal Imidacloprid Administration to Honey Bee Workers is More Lethal to the Queen Larvae.

Imidacloprid and other neonicotinoid insecticides severely impact the performance and survival of honey bees and other pollinators. In the present study, we focused on the gene expression profile of newly emerged Apis mellifera queen bees after sublethal imidacloprid treatment during the larval stage. Royal jelly containing 1 ppb imidacloprid was provided to larvae for 3 consecutive days (2-4 days postemergence). Queen larvae treated with imidacloprid showed lower capping and emergence rates (35.5% and 24.22%, respectively) than did control larvae (61.68% and 52.95%, respectively), indicating a high failure rate of queen rearing associated with imidacloprid exposure during the larval stage. The molecular response to imidacloprid treatment was examined next. By comparing the gene expression profiles of imidacloprid-treated queen larvae and those of control queen larvae using DESeq2, we identified 215 differentially expressed genes, with 105 and 111 up- and downregulated genes, respectively. Gene Ontology results indicated that chitin binding- and calcium ion binding-related genes were upregulated, while phototransduction- and visual perception-related genes were downregulated. The high mortality rate and altered gene expression profiles suggest that treatment with even 1 ppb imidacloprid can severely impact queen bee survival. Environ Toxicol Chem 2024;00:1-11. © 2024 SETAC.

Bimetal loaded graphitic carbon nitride with synergistic enhanced peroxidase-like activity for colorimetric detection of p-phenylenediamine.

In recent years, great progress has been made on the study of nanozymes with enzyme-like properties. Here, bimetallic Fe and Ni nanoclusters were anchored on the nanosheets of nitrogen-rich layered graphitic carbon nitride by one-step pyrolysis at high temperature (Fe/Ni-CN). The loading content of Fe and Ni on Fe/Ni-CN is as high as 8.0%, and Fe/Ni-CN has a high specific surface area of 121.86 m2 g-1. The Fe/Ni-CN can effectively oxidize 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2, and exhibits efficient peroxidase-like activity, leading to a 17.2-fold increase compared to pure graphitic carbon nitride (CN). Similar to the natural horseradish peroxidase (HRP), the Fe/Ni-CN nanozyme follows catalytic kinetics. The Michaelis-Menten constant (Km) value of the Fe/Ni-CN nanozyme for TMB is about 8.3-fold lower than that for HRP, which means that the Fe/Ni-CN nanozyme has better affinity for TMB. In addition, the catalytic mechanism was investigated by combination of free radical quenching experiments and density-functional theory (DFT) calculations. The results show that the high peroxidase-like activity is due to the easy adsorption of H2O2 after bimetal loading, which is conducive to the production of hydroxyl radicals. Based on the extraordinary peroxidase-like activity, the colorimetric detection of p-phenylenediamine (PPD) was constructed with a wide linear range of 0.2-30 µM and a low detection limit of 0.02 µM. The sensor system has been successfully applied to the detection of residual PPD in real dyed hair samples. The results show that the colorimetric method is sensitive, highly selective and accurate. This study provides a new idea for the efficient enhancement of nanozyme activity and effective detection of PPD by a bimetallic synergistic strategy.

[Mechanism of Mailuo Shutong Pills on posterior limb muscle swelling caused by femoral fracture in rats based on network pharmacology and experimental verification].

This study aims to investigate the mechanism of Mailuo Shutong Pills(MLST) on posterior limb muscle swelling caused by femoral fracture(SCFF) through network pharmacology and animal experiments. The plasma components of MLST were analyzed by LC-MS, and the target and signal pathway of SCFF were predicted by network pharmacology and verified by molecular docking. SCFF model rats were established through animal experiments, and different doses of MLST were administered to detect the degree of limb swelling. Hematoxylin-eosin(HE) staining was used to observe pathological changes in muscle tissue, and interleukin-6(IL-6), interleukin-1ß(interleukin-1ß), and tumor necrosis factor-α(TNF-α) in peripheral blood were determined by enzyme-linked immunosorbent assay(ELISA). The expression of relevant signaling pathways was measured by Western blot. Network pharmacological results showed that MLST and SCFF had a total of 153 disease targets, and the key targets were IL-6, TNF, etc., involving mitogen-activated protein kinase(MAPK) signaling pathway, phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) signaling pathway, etc. The binding energies of the main components and key targets were lower than-7.0 kcal·mol~(-1), indicating that the network analysis results were reliable. The results of animal experiments showed that MLST could reduce the swelling degree and pathological damage of the posterior limb muscles of SCFF rats compared with the model group. ELISA results showed that MLST could reduce the levels of IL-6, IL-1ß, and TNF-α in the serum of SCFF rats. Western blot results showed that MLST can reduce the expression of p-AKT, p-PI3K, p-NF-κB, p-p38 MAPK, and p-ERK in SCFF rats. MLST may reduce the content of inflammatory factors in serum by regulating the expression of PI3K/AKT and MAPK-related signaling pathway protein and improving posterior limb muscle SCFF in rats.

The Oncolytic Avian Reovirus p17 Protein Inhibits Invadopodia Formation in Murine Melanoma Cancer Cells by Suppressing the FAK/Src Pathway and the Formation of theTKs5/NCK1 Complex.

To explore whether the p17 protein of oncolytic avian reovirus (ARV) mediates cell migration and invadopodia formation, we applied several molecular biological approaches for studying the involved cellular factors and signal pathways. We found that ARV p17 activates the p53/phosphatase and tensin homolog (PTEN) pathway to suppress the focal adhesion kinase (FAK)/Src signaling and downstream signal molecules, thus inhibiting cell migration and the formation of invadopodia in murine melanoma cancer cell line (B16-F10). Importantly, p17-induced formation of invadopodia could be reversed in cells transfected with the mutant PTENC124A. p17 protein was found to significantly reduce the expression levels of tyrosine kinase substrate 5 (TKs5), Rab40b, non-catalytic region of tyrosine kinase adaptor protein 1 (NCK1), and matrix metalloproteinases (MMP9), suggesting that TKs5 and Rab40b were transcriptionally downregulated by p17. Furthermore, we found that p17 suppresses the formation of the TKs5/NCK1 complex. Coexpression of TKs5 and Rab40b in B16-F10 cancer cells reversed p17-modulated suppression of the formation of invadopodia. This work provides new insights into p17-modulated suppression of invadopodia formation by activating the p53/PTEN pathway, suppressing the FAK/Src pathway, and inhibiting the formation of the TKs5/NCK1 complex.

Ligand-Enabled ortho-Selective C-H Olefination of Tertiary Aniline Derivatives.

A highly ortho-selective CAr-H olefination of tertiary anilines without a directing group was developed. This reaction tolerated various substituted arenes and olefin coupling partners, affording ortho-olefination products in moderate to good yields. Preliminary mechanistic studies showed that N-Ac-d-Ala, Ag2CO3, and BQ were the key factors for tuning the regioselectivity from para to ortho. Density functional theory was used to achieve a theoretical understanding of the ortho selectivity.

Cobalt(II) Single-Ion Magnet Coordinated by Double Deprotonation of 2,2'-Bipyridine-6,6'-diol Ligands.

In this study, we synthesized a new Co(II) complex, [NMe4]2[Co(bpyO2)2] (1), using deprotonated 2,2'-bipyridine-6,6'-diol ligands (bpyO2 2-). This compound exhibits a significant zero-field splitting (D) value. The far-infrared magneto spectroscopy and high-frequency and field electron paramagnetic resonance (HFEPR) measurements indicated that compound 1 possesses D = -54.8 cm-1 and E ∼ 0 cm-1. These findings were subsequently confirmed by other experimental data, including DC magnetic susceptibilities and variable temperature and variable magnetic field reduced magnetizations. Additionally, we conducted a series of AC magnetic susceptibility measurements to investigate the kinetics of magnetization relaxation. Below 6.6 K and under zero external magnetic field, fast quantum tunneling of magnetization (QTM) dominates (∼570 Hz), and temperature-independent out-of-phase signals are observed. Above 8.1 K, temperature-dependent behavior is observed. Furthermore, we examined the AC magnetic susceptibility behavior under external magnetic fields ranging from 300 to 4000 G. The effect of QTM is significantly reduced in the presence of an external magnetic field. Temperature-dependent behavior is primarily governed by Raman relaxation. Through structural analysis of compound 1 and a series of pure nitrogen-coordinated single-ion magnets (SIMs), we propose that the oxo substituents from the double-deprotonated form of the 2,2'-bipyridine-6,6'-diol ligands donate their negative charge to the pyridine ring, forming amido anion sites. This triggers a more pronounced out-of-phase signal than that observed in pure pyridine-coordinated compounds. Moreover, we observed intermolecular interactions, including intermolecular hydrogen bonding, which, to some extent, influenced the slow relaxation of molecules. Therefore, we speculate that the slow relaxation phenomenon of compound 1 may be attributed to the combination of oxo back-donating effects and intermolecular interactions.

A near-infrared spectroscopy dataset of coal and coal-measure rock under diverse conditions.

The identification technology for coal and coal-measure rock is required across multiple stages of coal exploration, mining, separation, and tailings management. However, the construction of identification models necessitates substantial data support. To this end, we have established a near-infrared spectral dataset for coal and coal-measure rock, which includes the reflectance spectra of 24 different types of coal and coal-measure rock. For each type of sample, 11 sub-samples of different granularities were created, and reflectance spectra were collected from sub-samples at five different detection azimuths, 18 different detection zeniths, and under eight different light source zenith conditions. The quality and usability of the dataset were verified using quantitative regression and classification machine learning algorithms. Primarily, this dataset is used to train artificial intelligence-based models for identifying coal and coal-measure rock. Still, it can also be utilized for regression studies using the industrial analysis results contained within the dataset.

Effects of priming glycosyltransferase genes cps 2E and cps 4E on the exopolysaccharide biosynthesis by Lactiplantibacillus plantarum YM-4-3 strain.

Microbial exopolysaccharides (EPS) have various physiological functions such as antioxidant, anti-tumor, cholesterol lowering, and immune regulation. However, improving traditional fermentation conditions to increase the production of EPS from Lactiplantibacillus plantarum (L. plantarum) is limited. In this study, we aimed to better improve EPS production and physiological functions of L. plantarum YM-4-3 strain by overexpressing and knocking out the priming glycosyltransferase genes cps 2E and cps 4E for the first time. As a result, the EPS production of the overexpression strain was 30.15 %, 26.84 % and 36.29 % higher than WT, respectively. The EPS production of the knockout strain was significantly lower than that of the WT. At the same time, transcriptome data showed that the gene expression levels of each experimental strain had changed. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways found that the glycolysis/gluconeogenesis pathway had the highest gene enrichment in the metabolic pathway. The monosaccharide components of the EPS of each experimental strain were different from those of the WT and the EPS of the experimental strain showed stronger activity against oxidation. In conclusion, this study contributes to the efficient production and application of L. plantarum EPS and helps to understand the mechanism of EPS regulation in L. plantarum.

Biomimetic Chiral Nanomaterials with Selective Catalysis Activity.

Chiral nanomaterials with unique chiral configurations and biocompatible ligands have been booming over the past decade for their interesting chiroptical effect, unique catalytical activity, and related bioapplications. The catalytic activity and selectivity of chiral nanomaterials have emerged as important topics, that can be potentially controlled and optimized by the rational biochemical design of nanomaterials. In this review, chiral nanomaterials synthesis, composition, and catalytic performances of different biohybrid chiral nanomaterials are discussed. The construction of chiral nanomaterials with multiscale chiral geometries along with the underlying principles for enhancing chiroptical responses are highlighted. Various biochemical approaches to regulate the selectivity and catalytic activity of chiral nanomaterials for biocatalysis are also summarized. Furthermore, attention is paid to specific chiral ligands, materials compositions, structure characteristics, and so on for introducing selective catalytic activities of representative chiral nanomaterials, with emphasis on substrates including small molecules, biological macromolecule, and in-site catalysis in living systems. Promising progress has also been emphasized in chiral nanomaterials featuring structural versatility and improved chiral responses that gave rise to unprecedented chances to utilize light for biocatalytic applications. In summary, the challenges, future trends, and prospects associated with chiral nanomaterials for catalysis are comprehensively proposed.

Subjective social status, health and well-being among older adults in China and South Korea: a cross-sectional analysis.

INTRODUCTION: Social status, which encompasses various psychosocial dimensions, such as income, education and social relationships, can have a significant impact on physical and mental health outcomes. The study aims to explore the association among subjective social status, health and well-being among individuals aged 55 years and older in China and South Korea. PARTICIPANTS: Sample population included individuals aged 55 years and older: China (n=1779) and South Korea (n=421). OUTCOME MEASURES: Outcome measures included self-reported health status and well-being which were assessed by life satisfaction and general happiness. RESULTS: The percentage of participants who reported a 'very good' health condition was higher in South Korea (14.5%) than in China (11.0%). The percentage of participants who reported feeling very satisfied (14.7%) with their life was lower in South Korea (11.8%). In China, 6.7% of the respondents reported their health as 'very bad' (rating 5), while in South Korea, this percentage was higher at 18.1%. Regression analysis revealed an inverse association among higher social status and poorer health, lower life satisfaction and lower happiness levels. For example, individuals who placed themselves in the highest social status category had 0.26 times lower odds (95% CI=0.13 to 0.55) of reporting poorer self-rated health status than those in the lowest category. Similarly, compared with individuals who place themselves in the lowest social status category, those who place themselves in the highest social status category have 0.03 times lower odds of reporting lower life satisfaction (95% CI=0.02 to 0.07). CONCLUSION: Overall, the results highlight a significant association among social status, subjective health, life satisfaction and general happiness in both the countries. Health policymakers should identify effective strategies to promote healthy ageing and reduce disparities in health and well-being outcomes among older adults from different social backgrounds.

Targeting the nuclear long noncoding transcript LSP1P5 abrogates extracellular matrix deposition by trans-upregulating CEBPA in keloids.

Keloids are characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix (ECM) and are a major global health care burden among cutaneous diseases. However, the function of long noncoding RNA (lncRNA)-mediated ECM remodeling during the pathogenesis of keloids is still unclear. Herein, we identified a long noncoding transcript, namely, lymphocyte-specific protein 1 pseudogene 5 (LSP1P5), that modulates ECM component deposition in keloids. First, high-throughput transcriptome analysis showed that LSP1P5 was selectively upregulated in keloids and correlated with more severe disease in a clinical keloid cohort. Therapeutically, the attenuation of LSP1P5 significantly decreased the expression of ECM markers (COL1, COL3, and FN1) both in vitro and in vivo. Intriguingly, an antifibrotic gene, CCAAT enhancer binding protein alpha (CEBPA), is a functional downstream candidate of LSP1P5. Mechanistically, LSP1P5 represses CEBPA expression by hijacking Suppressor of Zeste 12 to the promoter of CEBPA, thereby enhancing the polycomb repressive complex 2-mediated H3K27me3 and changing the chromosomal opening status of CEBPA. Taken together, these findings indicate that targeting LSP1P5 abrogates fibrosis in keloids through epigenetic regulation of CEBPA, revealing a novel antifibrotic therapeutic strategy that bridges our current understanding of lncRNA regulation, histone modification and ECM remodeling in keloids.

Palladium-catalyzed enantioselective arylation of trichloro- or tri-/difluoroacetaldimine precursors.

A palladium-catalyzed asymmetric α-arylation of N-carbamoyl imine precursors containing CCl3, CF3 and CF2H is presented. This protocol provides facile access to a series of chiral α-aryl trichloroethylamines bearing various functional groups, with moderate to high yields (40-82% yield) and high enantioselectivity (80-99% ee).

Nutritional status and nutritional intervention of older inpatients in China.

BACKGROUND: Malnutrition is a critical issue among older inpatients, yet limited large-scale research related to this issue has been conducted in China. This study aimed to examine the nutritional status and support of older inpatients in China, assess the associations between disease categories and malnutrition on admission, and explore effective nutritional intervention. METHODS: A total of 24,139 older participants from the China Nutrition Fundamental Data 2020 Project were included. Malnutrition was measured by the Global Leadership Initiative on Malnutrition criteria. Adjusted odds ratios (aORs) were calculated using logistic analysis. RESULTS: The overall frequency of malnutrition on admission was 18.9%. Participants with infections were more likely to have malnutrition (aOR = 1.929, 95% CI 1.486-2.504). Risks that were also noted for malnutrition included neoplasms (aOR = 1.822, 95% CI 1.697-1.957), hemic and lymphatic diseases (aOR = 1.671, 95% CI 1.361-2.051), nervous system diseases (aOR = 1.222, 95% CI 1.126-1.326), respiratory diseases (aOR = 1.613, 95% CI 1.490-1.746), and digestive system diseases (aOR = 1.462, 95% CI 1.357-1.577). Further, 32.26% inpatients with malnutrition during hospitalization didn't receive nutritional support. Oral nutrition supplements, enteral tube feeding, and parenteral nutrition were associated with stable or improved nutritional status. CONCLUSIONS: Older inpatients were at a high risk for malnutrition but did not receive adequate nutritional intervention. More resources and attention need to be devoted to the nutritional status of older inpatients and targeted nutritional support.

Flower colour and size-signals vary with altitude and resulting climate on the tropical-subtropical islands of Taiwan.

The diversity of flower colours in nature provides quantifiable evidence for how visitations by colour sensing insect pollinators can drive the evolution of angiosperm visual signalling. Recent research shows that both biotic and abiotic factors may influence flower signalling, and that harsher climate conditions may also promote salient signalling to entice scarcer pollinators to visit. In parallel, a more sophisticated appreciation of the visual task foragers face reveals that bees have a complex visual system that uses achromatic vision when moving fast, whilst colour vision requires slower, more careful inspection of targets. Spectra of 714 native flowering species across Taiwan from sea level to mountainous regions 3,300 m above sea level (a.s.l.) were measured. We modelled how the visual system of key bee pollinators process signals, including flower size. By using phylogenetically informed analyses, we observed that at lower altitudes including foothills and submontane landscapes, there is a significant relationship between colour contrast and achromatic signals. Overall, the frequency of flowers with high colour contrast increases with altitude, whilst flower size decreases. The evidence that flower colour signaling becomes increasingly salient in higher altitude conditions supports that abiotic factors influence pollinator foraging in a way that directly influences how flowering plants need to advertise.

Salvaging Complex Lower Extremity Injury with Laparoscopically Harvested Omental Flaps.

Background: Traumatic injuries to the lower extremities are frequently accompanied by extensive soft tissue loss, combined with vascular damage or exposure of bony tissues, making it difficult to reconstruct; consequently, patients are commonly at risk of amputation. Due to its superior anatomical and biochemical properties, the omental flap has been used to reconstruct soft tissue defects for decades. However, few studies have reported the omental flap's effectiveness in treating severe and complex lower extremity deformities. We attempted to use a laparoscopically harvested omental flap in conjunction with a second-stage skin graft to reduce infections during limb preservation, increase flap survival probability, and restore the aesthetic and functional integrity of the affected extremity. Methods: Seventeen patients with severe lower extremity wounds underwent omental flap transplantation and were followed up for 6 to 12 months to check for surgical complications, evaluate cosmetic results, and ensure proper limb function. Results: There were no complications, such as intestinal adhesion, intestinal volvulus, and peritonitis, with any of the omental grafts. The affected extremities were well-functioning and aesthetically pleasing. Conclusion: Laparoscopically harvested omental flap transplantation with skin grafting is an alternative reconstruction technique for severe lower extremity injuries with massive soft tissue loss and exposed bones and tendons.