Loss of Bcl-3 regulates macrophage polarization by promoting macrophage glycolysis.

M1/M2 macrophage polarization plays an important role in regulating the balance of the microenvironment within tissues. Moreover, macrophage polarization involves the reprogramming of metabolism, such as glucose and lipid metabolism. Transcriptional coactivator B-cell lymphoma-3 (Bcl-3) is an atypical member of the IκB family that controls inflammatory factor levels in macrophages by regulating nuclear factor kappa B pathway activation. However, the relationship between Bcl-3 and macrophage polarization and metabolism remains unclear. In this study, we show that the knockdown of Bcl-3 in macrophages can regulate glycolysis-related gene expression by promoting the activation of the nuclear factor kappa B pathway. Furthermore, the loss of Bcl-3 was able to promote the interferon gamma/lipopolysaccharide-induced M1 macrophage polarization by accelerating glycolysis. Taken together, these results suggest that Bcl-3 may be a candidate gene for regulating M1 polarization in macrophages.

Mechanistic Investigation on the Regioselectivity of Electrochemical Co(II)-Catalyzed [2 + 2 + 2] Cycloaddition of Terminal Acetylenes.

In this paper, the regioselectivity of electrochemical Co(II)-catalyzed [2 + 2 + 2] cycloaddition of terminal alkynes was investigated using density functional theory. We explored in detail the energy profiles for both 1,2,4- and 1,3,5-regioselectivity pathways and revealed the origin of the regioselectivity. Two kinds of conformational isomers derived from the different coordination modes of alkynes with cobaltacyclopentadiene have been found, which were formed through electrochemically mediated redox processes. The regioselectivity of the reaction depends on the two coordination modes. When the Co(II) center attacks α-C of the third alkyne, while ß2-C in cyclopentadiene bonds to ß-C of the alkyne, the reaction favors the formation of 1,2,4-products. In contrast, when the Co(II) center connects to ß-C of the alkyne, it forms only the 1,3,5-products via [4 + 2] cycloaddition because of the steric repulsion between the bulky ligand on Co(II) and the phenyl group in the alkyne.

DRP1 knockdown and atorvastatin alleviate ox-LDL-induced vascular endothelial cells injury: DRP1 is a potential target for preventing atherosclerosis.

Vascular endothelial cells (VECs) injury is the first step in the pathogenesis of atherosclerosis (AS). Mitochondrial dysfunction plays a significant role in VECs injury, but the underlying mechanisms are still unclear. Here, the human umbilical vein endothelial cells were exposed to 100 µg/mL oxidized low-density lipoprotein for 24 h to establish AS model in vitro. We reported that mitochondrial dynamics disorder is a prominent feature of VECs in AS models and associated with mitochondrial dysfunction. Moreover, the knockdown of dynamin-related protein 1 (DRP1) in AS model significantly alleviated the mitochondrial dynamics disorder and VECs injury. On the contrary, DRP1 overexpression significantly aggravated this injury. Interestingly, atorvastatin (ATV), a classical anti-atherosclerotic drug, prominently inhibited the expression of DRP1 in AS models and similarly alleviated the mitochondrial dynamics disorder and VECs injury in vitro and in vivo. At the same time, we found that ATV alleviated VECs damage but did not significantly reduce lipid concentration in vivo. Our findings provide a potential therapeutic target of AS and a new mechanism of the anti-atherosclerotic effect of ATV.

Dynamics of bacterioplankton communities in the estuary areas of the Taihu Lake: Distinct ecological mechanisms of abundant and rare communities.

As the crucial confluences of rivers and lakes, the estuary areas with varied hydrodynamic exchanges intensively affect the bacterioplankton communities, whereas the ecological characteristics of the bacterioplankton in the areas have not been well understood. Here, the distribution patterns and assembly mechanisms of bacterioplankton communities in the estuary areas of the Taihu Lake were investigated using high-throughput sequencing and multivariate statistical analyses. Our results showed obvious seasonal variations in bacterioplankton diversity and community composition, which had significant correlations with water temperature. Neutral and null models together revealed that stochastic processes (especially dispersal limitation) were the major processes in shaping the communities across different seasons. By contrast, heterogeneous selection in deterministic processes exhibited increased impacts on community assembly during summer and autumn, which was significantly related to the comprehensive water quality index (WQI) rather than any single factor. In this study, rare communities displayed more pronounced seasonal dynamics compared to abundant communities, likely due to their sensitivity towards environmental factors. Accordingly, the heterogeneous selection of deterministic processes largely shaped the rare communities. These results enriched our understanding of the assembly mechanisms of bacterioplankton communities in estuary areas and emphasized the specific co-occurrence patterns of abundant and rare communities.

Knowledge, attitudes and practices of nurses regarding airway clearance in neurocritical illness patients: A cross-sectional study.

AIM: We aimed to assess the level of knowledge, attitudes and practices regarding airway clearance among nurses and explore the factors affecting the knowledge, attitudes and practices. DESIGN: A questionnaire-based cross-sectional study. BACKGROUND: Airway clearance is an important method of eliminating excess secretions. In neuroscience nursing, nurses are important executors of airway management, and their knowledge, attitudes and practices can influence the effectiveness of airway clearance. METHODS: This study was conducted from July to September 2023 in four hospitals in Jiangsu Province, China. A structured questionnaire about airway clearance was designed and used to collect the data. The nurses used this questionnaire to self-rate. The STROBE checklist for cross-sectional studies was followed. RESULTS: The age, work experience, highest educational attainment and technical title of the nurses can significantly influence their knowledge. The age, highest educational attainment and technical title of the nurses can significantly impact their attitudes. Practice scores were significantly influenced by age, work experience, technical title, whether the nurses had received any training on airway clearance techniques, and whether the department developed procedures for implementing the airway clearance technology. Nurses' attitudes were significantly associated with knowledge and practice, and there was no significant correlation between knowledge and practice. CONCLUSION: This study showed that age, work experience, highest educational attainment and training were related to knowledge, attitudes and practices. These findings suggest that nursing managers can conduct airway clearance training according to age group, working experience and education level of the nurses. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. IMPACT: The findings show that the level of knowledge, attitudes and practices related to airway clearance in neuroscience nursing among nurses were acceptable, which means that nurses can better perform airway management on patients. These findings serve as a significant reference for designing an airway clearance education for nurses and meet the needs of nurses in clinical nursing practice.

Towards a Green Equal City: Measuring and matching the supply-demand of green exposure in urban center.

Exposure to green environments is crucial for human health. However, urbanization has reduced the contact of urban residents with natural environments, causing a mismatch between the supply and demand for green exposure. Research in this field is hindered by the lack of long-term, reliable data sources and methodologies, leading to insufficient consideration of temporal variations in green exposure. This study presented a comprehensive methodology for assessing green exposure at a fine scale utilizing satellite images for urban tree canopy identification. We conducted a case study in the core area of Beijing from 2010 to 2020 and examined the effects of urban renewal and alleviation efforts. The results revealed a slight decrease in green exposure for the elderly over the decade, with minimal changes in equity. In contrast, green exposure for children has increased, with increasing inequality. Moreover, urban renewal has improved green exposure for nearly half of the low-supply blocks. However, a significant mismatch was observed between supply and demand for blocks with increased demand but limited supply. This study enhances the assessment of green exposure and provides guidance for planning and constructing a "Green Equal City".

First-Principles Investigation of Phosphorus-Doped Graphitic Carbon Nitride as Anchoring Material for the Lithium-Sulfur Battery.

The utilization of lithium-sulfur battery is hindered by various challenges, including the "shuttle effect", limited sulfur utilization, and the sluggish conversion kinetics of lithium polysulfides (LiPSs). In the present work, a theoretical design for the viability of graphitic carbon nitride (g-C3N4) and phosphorus-doping graphitic carbon nitride substrates (P-g-C3N4) as promising host materials in a Li-S battery was conducted utilizing first-principles calculations. The PDOS shows that when the P atom is introduced, the 2p of the N atom is affected by the 2p orbital of the P atom, which increases the energy band of phosphorus-doping substrates. The energy bands of PC and Pi are 0.12 eV and 0.20 eV, respectively. When the lithium polysulfides are adsorbed on four substrates, the overall adsorption energy of PC is 48-77% higher than that of graphitic carbon nitride, in which the charge transfer of long-chain lithium polysulfides increase by more than 1.5-fold. It is found that there are powerful Li-N bonds between lithium polysulfides and P-g-C3N4 substrates. Compared with the graphitic carbon nitride monolayer, the anchoring effect of the LiPSs@P-g-C3N4 substrate is enhanced, which is beneficial for inhibiting the shuttle of high-order lithium polysulfides. Furthermore, the catalytic performance of the P-g-C3N4 substrate is assessed in terms of the S8 reduction pathway and the decomposition of Li2S; the decomposition energy barrier of the P-g-C3N4 substrate decrease by 10% to 18%. The calculated results show that P-g-C3N4 can promote the reduction of S8 molecules and Li-S bond cleavage within Li2S, thus improving the utilization of sulfur-active substances and the ability of rapid reaction kinetics. Therefore, the P-g-C3N4 substrates are a promising high-performance lithium-sulfur battery anchoring material.

Application of CRISPR/Cas12i.3 for targeted mutagenesis in broomcorn millet (Panicum miliaceum L.).

In the present study, we have successfully established a gene editing platform in broomcorn millet, one of the oldest crops originating from China, by using our CRISPR/Cas12i.3, and we also created new elite germplasm for this crop.

PUS7 promotes the proliferation of colorectal cancer cells by directly stabilizing SIRT1 to activate the Wnt/ß-catenin pathway.

Pseudouridine synthase 7 (PUS7) may play key roles in cancer development. However, few studies have been conducted in this area. In the present study, we explored the function and potential mechanisms of PUS7 in colorectal cancer (CRC) progression. We found that PUS7 had higher expression in CRC tissues and cell lines. Clinically, high expression of PUS7 was associated with an unfavorable prognosis for CRC patients. Functionally, knockdown of PUS7 suppressed the proliferation of CRC cells in vitro and inhibited tumorigenicity in vivo. Mechanistically, RNA sequencing and coimmunoprecipitation (Co-IP) indicated that PUS7 exhibited oncogenic functions through the interaction of Sirtuin 1 (SIRT1) and activated the Wnt/ß-catenin signaling pathway. Thus, our findings suggest that PUS7 promotes the proliferation of CRC cells by directly stabilizing SIRT1 to activate the Wnt/ß-catenin pathway.

Optical coherence tomography-derived predictors of stent expansion in calcified lesions.

BACKGROUND: Severe coronary artery calcification is associated with stent underexpansion and subsequent stent failure. AIMS: We aimed to identify optical coherence tomography (OCT)-derived predictors of absolute (minimal stent area [MSA]) and relative stent expansion in calcified lesions. METHODS: This retrospective cohort study included patients who underwent percutaneous coronary intervention (PCI) with OCT assessment before and after stent implantation between May 2008 and April 2022. Pre-PCI OCT was used to assess calcium burden and post-PCI OCT was used to assess absolute and relative stent expansion. RESULTS: A total of 361 lesions in 336 patients were analyzed. Target lesion calcification (defined as OCT-detected maximum calcium angle ≥ 30°) was present in 242 (67.0%) lesions. Following PCI, median MSA was 5.37 mm2 in calcified lesions and 6.24 mm2 in noncalcified lesions (p < 0.001). Median stent expansion was 78% in calcified lesions and 83% in noncalcified lesions (p = 0.325). In the subset of calcified lesions, average stent diameter, preprocedural minimal lumen area, and total calcium length were independent predictors of MSA in multivariable analysis (mean difference 2.69 mm2 /mm2 , 0.52 mm2 /mm, and -0.28 mm2 /5 mm, respectively, all p < 0.001). Total stent length was the only independent predictor of relative stent expansion (mean difference -0.465% per mm, p < 0.001). Calcium angle, thickness, and the presence of nodular calcification were not significantly associated with MSA or stent expansion in multivariable analyses. CONCLUSION: Calcium length appeared to be the most important OCT-derived predictor of MSA, whereas stent expansion was mainly determined by total stent length.

The effect of aging on beef taste, aroma and texture, and the role of microorganisms: a review.

The present review summarizes the advantages and disadvantages of three different aging methods (traditional dry aging, wet aging in vacuum shrink pack and dry aging in a highly moisture-permeable bag), discusses the effects of aging on beef which focus on the formation of taste-active compounds and aroma-active compounds and texture changes, and speculates the role of microbes. All these three aging methods can improve the aroma, flavor and texture of beef to varying degrees. It is concluded that the improvement in the taste during aging may be attributed to the following three aspects: First, the release of reducing sugars from the transition of glycogen and ATP; Second, the formation of free amino acids (FAAs) and peptides through proteolysis; Third, IMP, GMP, inosine and hypoxanthine which are produced by the degradation of nucleotides. The improvement of aroma is related to the volatile aroma-active components, which are produced by the thermal oxidation/degradation of fatty acids and the Maillard reaction between amino acids and reducing sugars during aging. And the change of texture is mainly owing to the degradation of cytoskeletal myofibrin and collagen with intramural connective tissue in meat by the endogenous proteolysis system. The role of microorganism in aging will be the main direction of further research.

miR-183 and miR-96 orchestrate both glucose and fat utilization in skeletal muscle.

Our knowledge of the coordination of fuel usage in skeletal muscle is incomplete. Whether and how microRNAs are involved in the substrate selection for oxidation is largely unknown. Here we show that mice lacking miR-183 and miR-96 have enhanced muscle oxidative phenotype and altered glucose/lipid homeostasis. Moreover, loss of miR-183 and miR-96 results in a shift in substrate utilization toward fat relative to carbohydrates in mice. Mechanistically, loss of miR-183 and miR-96 suppresses glucose utilization in skeletal muscle by increasing PDHA1 phosphorylation via targeting FoxO1 and PDK4. On the other hand, loss of miR-183 and miR-96 promotes fat usage in skeletal muscle by enhancing intramuscular lipolysis via targeting FoxO1 and ATGL. Thus, our study establishes miR-183 and miR-96 as master coordinators of fuel selection and metabolic homeostasis owing to their capability of modulating both glucose utilization and fat catabolism. Lastly, we show that loss of miR-183 and miR-96 can alleviate obesity and improve glucose metabolism in high-fat diet-induced mice, suggesting that miR-183 and miR-96 may serve as therapeutic targets for metabolic diseases.

The correlation between different antihypertensive treatments and prognosis of cardiovascular disease in hypertensive patients.

OBJECTIVE: To determine the association between different antihypertensive regimens and cardiovascular disease (CVD) outcomes in hypertensive patients. METHOD: This single center retrospective cohort study analyzed 602 hypertensive patients with complete medical records at Zhongnan Hospital of Wuhan University, China, from January 2016 to November 2022. Baseline data and follow-up data of the included patients were collected, including demographic and clinical characteristics and laboratory results. RESULTS: During the 5-year follow-up period, CVD outcomes occurred in 244 hypertensive patients (40.53%). Compared with patients receiving regular antihypertensive treatment, the incidence of adverse cardiovascular events in patients receiving irregular antihypertensive treatment was significantly higher (62 [55.86%] vs 182 [37.07%], HR 1.642, 95% CI 1.227-2.197, p < 0.001). In subgroup analysis, the results showed that the incidence of CVD was not identical (χ2 = 9.170, p = 0.010). The incidence of adverse cardiovascular events was highest in the single-drug antihypertensive treatment group (43.60%), followed by the multi-drug combination group (41.51%), and lowest in the two-drug combination group (29.58%). Kaplan-Meier curve showed that hypertensive patients treated with two-drug combination antihypertensive had longer overall survival time. We further compared the incidence of CVD between standard blood pressure and intensive blood pressure control, and found no significant difference in the incidence of adverse cardiovascular events between treatment to a systolic blood pressure (SBP) target of less than 140 mmHg compared with a SBP target of less than 120 mmHg (105 [43.93%] vs 35 [29.66%], HR 1.334, 95% CI 0.908-1.961, p = 0.142). CONCLUSION: The incidence of adverse cardiovascular events was significantly different among different antihypertension treatments. Kaplan-Meier survival curve showed that hypertensive patients receiving two-drug combination antihypertensive treatment had longer overall survival time.

Factors associated with quality of life in Chinese people with psoriasis: a cross-sectional study.

BACKGROUND: The ultimate goal of medical care is to eradicate disease and restore normality to a person's life. Quality of life (QOL) is a concern as dermatologists and researchers strive to find better drug treatments. However, there have been few reports on the factors associated with QOL among Chinese people with psoriasis. METHODS: A total of 185 people with psoriasis were surveyed to assess their sociodemographic status, disease-related information, psychosocial status, and QOL. The questionnaires included a sociodemographic questionnaire, the Athens Insomnia Scale, the Hospital Anxiety and Depression Scale, the Perceived Social Support Scale, the Psychosocial Adaptation Questionnaire of Chronic Skin Disease and the Dermatology Life Quality Index. Multiple stepwise regression and path analysis were used to study the factors associated with QOL among Chinese people with psoriasis and to analyse the relationship between them. RESULTS: The results showed that the presence of anxiety/depression, lesion area, sleep disorders, psychosocial adaptation, and sex could jointly predict 62.1% of the variance in QOL among Chinese people with psoriasis. According to previous theories and the literature, a path model was established for five variables. Four internal variables could be effectively explained. The values of the explanatory variables were 62.1% (F(1056) = 61.020, p = 0.000) for QOL, 71.8% (F(2433) = 117.370, p = 0.000) for anxiety/depression, 44.0% (F(660) = 36.935, p = 0.000) for sleep disorders, and 66.9% (F(6886) = 93.556, p = 0.000) for psychosocial adaptation. The path analysis confirmed that 9 paths were consistent with the predicted path, and 3 paths were not confirmed. CONCLUSION: To improve QOL among Chinese people with psoriasis, attention should be given to the presence of anxiety/depression, lesion area, sleep disorders, psychosocial adaptation and sex differences. Therefore, health care programs for psoriasis should include physical, psychological and social aspects.

The correlation between T-wave abnormalities and adverse cardiovascular events and echocardiographic changes in hypertensive patients.

BACKGROUND: Major adverse cardiovascular events (MACE) are common in patients with hypertension and are associated with higher mortality. METHODS: This study aimed to observe the incidence of MACE in hypertensive patients and the correlation between the electrocardiogram (ECG) T-wave abnormalities and echocardiographic changes. This retrospective cohort study analyzed the incidence of adverse cardiovascular events and changes in echocardiographic features in 430 hypertensive patients admitted to Zhongnan Hospital of Wuhan University from January 2016 to January 2022. Patients were grouped according to a diagnosis of electrocardiographic T-wave abnormalities. RESULTS: Compared with the normal T-wave group, the incidence of adverse cardiovascular events was significantly higher in hypertensive patients with abnormal T-wave (141 [54.9%] vs 120 [69.4%], x^2 = 9.113, P = .003). However, Kaplan-Meier survival curve showed that no survival advantage was observed in the normal T-wave group at all in the hypertensive patients (P = .83). Echocardiographic values associated with cardiac structural markers, including ascending aorta diameter (AAO), left atrial diameter (LA), and interventricular septal thickness (IVS), were significantly higher in the group with abnormal T-wave than those in the group with normal T-wave at baseline and follow-up (P <.05 for all). In addition, in an exploratory Cox regression analysis model stratified by clinical characteristics of hypertensive patients, the forest plot indicated that the variables, including the age (>65 years), hypertension history (>5 years), premature atrial beats, and severe valvular regurgitation were significantly associated with adverse cardiovascular events (P <.05). CONCLUSION: Hypertensive patients with abnormal T-wave show a higher incidence of adverse cardiovascular events. The values of cardiac structural markers were significantly higher in the group with abnormal T-wave.

An AIE Metal Iridium Complex: Photophysical Properties and Singlet Oxygen Generation Capacity.

Photodynamic therapy (PDT) has garnered significant attention in the fields of cancer treatment and drug-resistant bacteria eradication due to its non-invasive nature and spatiotemporal controllability. Iridium complexes have captivated researchers owing to their tunable structure, exceptional optical properties, and substantial Stokes displacement. However, most of these complexes suffer from aggregation-induced quenching, leading to diminished luminous efficiency. In contrast to conventional photosensitizers, photosensitizers exhibiting aggregation-induced luminescence (AIE) properties retain the ability to generate a large number of reactive oxygen species when aggregated. To overcome these limitations, we designed and synthesized a novel iridium complex named Ir-TPA in this study. It incorporates quinoline triphenylamine cyclomethylated ligands that confer AIE characteristics for Ir-TPA. We systematically investigated the photophysical properties, AIE behavior, spectral features, and reactive oxygen generation capacity of Ir-TPA. The results demonstrate that Ir-TPA exhibits excellent optical properties with pronounced AIE phenomenon and robust capability for producing singlet oxygen species. This work not only introduces a new class of metal iridium complex photosensitizer with AIE attributes but also holds promise for achieving remarkable photodynamic therapeutic effects in future cellular experiments and biological studies.

Enzymatic Synthesis of the Unnatural Nucleotide 2'-Deoxyisoguanosine 5'-Monophosphate.

Naturally occurring DNA contains four canonical bases, forming two Watson-Crick base pairs (adenine-thymine, guanine-cytosine). Efforts over the past decades have led to the development of several unnatural base pairs, enabling the synthesis of unnatural DNA with an expanded genetic alphabet. The engineering of organisms capable of de novo biosynthesis of unnatural DNA would have significant technological and philosophical implications, but remains a challenge. Here we report the enzymatic conversion of 2'-deoxyxanthosine 5'-monophosphate (dXMP) into deoxyisoguanosine monophosphate (dBMP), a precursor of the unnatural isoguanine-isocytosine base pair. The reaction is catalyzed by the bacteriophage enzyme PurZ and bacterial PurB, and is a key addition to the toolbox for de novo biosynthesis of unnatural DNA.

Origins of Stereospecificity and Divergent Reactivity of Pd-Catalyzed Cross Coupling with α,α-Disubstituted Alkenyl Hydrazones.

This article presents an exploration of stereospecificity and divergent reactivity of Pd-catalyzed α,α-disubstituted alkenyl hydrazones to synthesize 1,4-dienes in the Z configuration and vinylcyclopropane. We calculated the energy profiles of four α,α-disubstituted alkenyl hydrazones. The results show that the energy profiles of the whole catalytic cycle are basically the same before the syn-carbopalladation step. Subsequent syn-ß-C elimination yields skipping dienes, or direct ß-H elimination yields vinylcyclopropane. Current theoretical calculations reveal that the stereospecificity and the divergent reactivity of reactions result from the competition between syn-ß-C elimination and ß-H elimination. The C-C bond rotation and subsequent syn-ß-C elimination step control the stereospecificity of the reaction by changing the olefin stereostructure from E to Z configuration. The steric factor of α-substituted groups mediates the transformation between syn-ß-C elimination and ß-H elimination. The results are of great significance for the scientific design of substrates to achieve accurate synthesis of target products.

Monoglycocalix[4]arene-based nanoparticles for tumor selective drug delivery via GLUT1 recognition of hyperglycolytic cancers.

We have developed a new strategy of tumor-specific glucose transporter (GLUT)-mediated selective drug delivery using amphiphilic fluorescent monoglycocalix[4]arene in docetaxel (DTX) encapsulated nanoparticles (NPs) that leads to significant improvement in cytotoxic activity against a panel of human cancer cells. The fluorescent tracer conjugation in the calixarene enables the self-probed tumor targeting analysis and makes the system potentially suitable for tumor diagnostic imaging.

LaCl3 treatment improves Agrobacterium-mediated immature embryo genetic transformation frequency of maize.

KEY MESSAGE: We report an optimized transformation system that uses a LaCl3 pretreatment (a Ca2+ channel blocker) for enhancing Agrobacterium-mediated infection of immature embryos and improving the genetic transformation frequency of maize. Agrobacterium-mediated genetic transformation of immature embryos is important for gene-function studies and molecular breeding of maize. However, the relatively low genetic transformation frequency remains a bottleneck for applicability of this method, especially on commercial scale. We report that pretreatment of immature embryos with LaCl3 (a Ca2+ channel blocker) improves the infection frequency of Agrobacterium tumefaciens, increases the proportion of positive callus, yields more positive regenerated plantlets, and increases the transformation frequency from 8.40 to 17.60% for maize. This optimization is a novel method for improving the frequency of plant genetic transformations mediated by Agrobacterium tumefaciens.