Traditional Chinese medicine lowering lipid levels and cardiovascular events across baseline lipid levels among coronary heart disease: a meta-analysis of randomized controlled trials.

Background: Dyslipidemia is a critical driver in the development of coronary heart disease (CHD), which further exacerbates the risk of major adverse cardiovascular events (MACEs). Chinese herbal medicine (CHM) plays an important role in the regulation of lipid levels and improvement of prognosis. However, few systematic reviews report whether the efficacy of CHM therapy for regulating lipid levels and lowering cardiovascular events is associated with baseline lipid levels. Methods: Randomized controlled trials assessing efficacy of CHM for lipid profiles and MACEs among patients with CHD were searched in six databases. Two authors independently extracted studies according to a predesigned form. Cochrane risk of bias tool and Grading of Recommendations Assessment, Development, and Evaluation system were used to assess the methodological quality of the included studies. The primary outcomes were blood lipid levels and MACEs including cardiovascular mortality, non-fatal myocardial infarction, revascularization, angina pectoris, heart failure, and non-fatal stroke across baseline lipid levels. The secondary outcomes were individual components of the primary outcomes. Results: A total of 23 trials with 7,316 participants were included in this study. Altogether 377 cardiovascular events occurred in 3,670 patients in the CHM group, while 717 events occurred in 3,646 patients in the Western medicine-alone group. Compared with the Western medicine alone, additional CHM significantly lowered low-density lipoprotein cholesterol (LDL-C) [MD = -0.46, 95% CI (-0.60 to -0.32), P < 0.00001, I 2 = 96%]. The risk reduction in MACEs associated with CHM vs. Western medicine therapy was 0.52 [95% CI (0.47-0.58), P < 0.00001, I 2 = 0%], but varied by baseline LDL-C level (P = 0.03 for interaction). Triglycerides (TG) level was also significantly lowered by additional CHM vs. Western medicine alone [MD = -0.27, 95% CI (-0.34 to -0.20), P < 0.00001, I 2 = 81%], and risk reduction for MACEs also varied with baseline TG, with greater risk reduction in higher baseline TG subgroups (P = 0.03 for interaction). Similar results were observed with total cholesterol and high-density lipoprotein cholesterol. Conclusion: Compared with Western medicine alone, additional CHM was associated with lower risk of cardiovascular events and improvement of lipid profiles. Risk reduction for cardiovascular events was associated with baseline LDL-C and TG levels. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023425791.

Environmental Uncertainty, Environmental Regulation and Enterprises' Green Technological Innovation.

This paper examines the impact of environmental uncertainty and environmental regulation on enterprises' green technological innovation, using a panel data of Chinese A-share listed companies in Shanghai and Shenzhen from 2005 to 2019 to conduct an empirical study using an OLS model and Poisson regression model. We employ environmental complexity and environmental dynamism to measure environmental uncertainty, and we have the following findings: first, both environmental uncertainty and environmental regulation promote enterprises' green technological innovation, while environmental regulation has positive moderating effects on the relationship between environmental uncertainty and enterprises' green technological innovation; second, environmental complexity positively affects enterprises' green technological innovation, while environmental dynamism has negative effects on enterprises' green technological innovation; third, environmental regulation accentuates the relationship between environmental complexity and green technological innovation, while it weakens the relationship between environmental dynamism and green technological innovation.

Facilely prepared aggregation-induced emission (AIE) nanocrystals with deep-red emission for super-resolution imaging.

Organic nanocrystals (NCs) with high brightness are highly desirable for biological imaging. However, the preparation of NCs by a facile and fast method is still challenging. Herein, an aggregation-induced emission (AIE) luminogen of 4,4'-(5,6-difluorobenzo[c][1,2,5]thiadiazole-4,7-diyl)bis(N,N-bis(4-methoxyphenyl)aniline) (DTPA-BT-F) in the deep-red region is designed with intensive crystalline features to obtain NCs by kinetically controlled nanoprecipitation. The prepared AIE NCs with high brightness and good photo-stability are then applied in super-resolution imaging via stimulated emission depletion (STED) nanoscopy. As observed, the nanostructures in lysosomes of both fixed and live cells are well visualized with superior lateral resolutions under STED nanoscopy (full width at half maximum values, 107 and 108 nm) in contrast to that in confocal imaging (548 and 740 nm). More importantly, dynamic monitoring and long-term tracking of lysosomal movements in live HeLa cells, such as lysosomal contact, can also be carried out by using DTPA-BT-F NCs at a superior resolution. To the best of our knowledge, this is the first case of AIE NCs prepared by nanoprecipitation for STED nanoscopy, thus providing a new strategy to develop high performance imaging agents for super-resolution imaging.

The Impact of Environmental Uncertainty on Corporate Innovation: Empirical Evidence from an Emerging Economy.

The paper analyzes the effect of environmental uncertainty on corporate technological innovation from the perspective of an innovation value chain under the institutional background of China. This paper not only discusses the intermediary effect of agency problems on environmental uncertainty and corporate technological innovation but also deeply explores the influence of information transparency, government subsidies, and other mechanisms to alleviate agency problems on environmental uncertainty and corporate technological innovation. We use the data of listed companies in China from 2008 to 2019 as the research sample, and the results show that, in general, environmental uncertainty has a negative effect on both input and output of technological innovation, and the negative effect can last for two years. Further research shows that the agency problem has an intermediary effect on the environmental uncertainty and corporate technology innovation, and the environmental uncertainty aggravates the agency problem, which hinders the input and output of corporate technology innovation. As an important mechanism to alleviate the agency problems, information transparency and government subsidies can effectively alleviate the agency conflict, thus reducing the inhibition of environmental uncertainty on the input and output of technological innovation. Our findings contribute to the discussion of driving factors for technological innovation in the context of China's system. Our results provide useful insights into the link between environmental uncertainty and corporate innovation for economic academics and practitioners alike.

Deep-Red Fluorescent Organic Nanoparticles with High Brightness and Photostability for Super-Resolution in Vitro and in Vivo Imaging Using STED Nanoscopy.

To achieve super-resolution imaging in biological research using stimulated emission depletion (STED) nanoscopy, organic luminescent materials and their corresponding fluorescent nanoparticles with high brightness and photostability are of great significance. Herein, donor-acceptor-typed DBTBT-4C8 bearing flexible alkyl chains was developed, not only to afford deep-red emission from 600 to 800 nm but also to obtain high fluorescent brightness with the absolute photoluminescence quantum yields of 25%. After that, well-defined and monodispersed spherical nanoparticles using DBTBT-4C8 with bright emission, excellent biocompatibility, and photostability, which can easily mix with amphipathic block polymers, were then produced for super-resolution in vitro and in vivo imaging using STED nanoscopy. The observations showed that in contrast to confocal microscopy with a full width at half-maximum (FWHM) value of ≈400 nm, superior resolution with a significantly improved FWHM value of only 100 nm was achieved in biomedical cell imaging, which was also used to reconstruct three-dimensional images of stained HeLa cells at an ultrahigh resolution. More importantly, by using the prepared fluorescent organic nanoparticles (FONPs) in STED nanoscopy, in vivo imaging in glass catfish with largely enhanced resolution was also successfully achieved, demonstrating that these developed deep-red FONPs here are highly suitable for super-resolution in vitro and in vivo imaging using STED nanoscopy.

A Strategy of "Self-Isolated Enhanced Emission" to Achieve Highly Emissive Dual-State Emission for Organic Luminescent Materials.

Currently, the commonly developed organic luminescent materials (OLMs) usually exhibit poor luminescent performance in aggregated solid states compared with their well-dissolved solution states, making it a tough goal to achieve the highly emissive dual-state emission. To overcome this limitation, a "self-isolated enhanced emission" (SIEE) strategy through flexible alkyl chains to suppress the emission-quenched π-π stacking in solids is proposed here and, based on this guideline, remarkable emission efficiency with photoluminescence quantum yields up to 99.72 % in solution and 77.46 % in the solid state are achieved for the SIEE constructed DBBT-C8, which is then successfully used in solid-state displays and data encryption.

Somatostatin receptor-1 induces cell cycle arrest and inhibits tumor growth in pancreatic cancer.

Functional somatostatin receptors (SSTR) are lost in human pancreatic cancer. Transfection of SSTR-1 inhibited pancreatic cancer cell proliferation in vitro. We hypothesize that stable transfection of SSTR-1 may inhibit pancreatic cancer growth in vivo possibly through cell cycle arrest. In this study, we examined the expression of SSTR-1 mRNA in human pancreatic cancer tissue specimens, and investigated the effect of SSTR-1 overexpression on cell proliferation, cell cycle, and tumor growth in a subcutaneous nude mouse model. We found that SSTR-1 mRNA was downregulated in the majority of pancreatic cancer tissue specimens. Transfection of SSTR-1 caused cell cycle arrest at the G(0)/G(1) growth phase, with a corresponding decline of cells in the S (mitotic) phase. The overexpression of SSTR-1 significantly inhibited subcutaneous tumor size by 71% and 43% (n = 5, P < 0.05, Student's t-test), and inhibited tumor weight by 69% and 47% (n = 5, P < 0.05, Student's t-test), in Panc-SSTR-1 and MIA-SSTR-1 groups, respectively, indicating the potent inhibitory effect of SSTR-1 on pancreatic cancer growth. Our data demonstrate that overexpression of SSTR-1 significantly inhibits pancreatic cancer growth possibly through cell cycle arrest. This study suggests that gene therapy with SSTR-1 may be a potential adjuvant treatment for pancreatic cancer.

Caveats in the design of MHC class I tetramer/antigen-specific T lymphocytes dissociation assays.

Relative avidities of antigen-specific T cells for major histocompatibility complex peptide complexes (MHCp) have recently been measured by MHC tetramer dissociation assays, but there is no consensus on the methodologies used for these experiments. While we do not question the conclusions reached in previous studies, in this paper we discuss the caveats that are present in the design of all MHCp tetramer dissociation protocols, and we propose a set of criteria that should be met in the evaluation of appropriate methodologies. We find that it is necessary to use specific reagents to compete with rebinding of the labeled tetramer, but that when either intact anti-MHC antibodies or cold MHC tetramers are used, the dissociation rates are dependent upon the concentrations of the competitor. In contrast, we demonstrate that apparent dissociation rates are independent of the competitor concentration when blocking anti-MHC Fab fragments are used, suggesting that these are the most appropriate reagents to use for tetramer dissociation experiments.

Estimating the precursor frequency of naive antigen-specific CD8 T cells.

The constraint of fitting a diverse repertoire of antigen specificities in a limited total population of lymphocytes results in the frequency of naive cells specific for any given antigen (defined as the precursor frequency) being below the limit of detection by direct measurement. We have estimated this precursor frequency by titrating a known quantity of antigen-specific cells into naive recipients. Adoptive transfer of naive antigen-specific T cell receptor transgenic cells into syngeneic nontransgenic recipients, followed by stimulation with specific antigen, results in activation and expansion of both donor and endogenous antigen-specific cells in a dose-dependent manner. The precursor frequency is equal to the number of transferred cells when the transgenic and endogenous responses are of equal magnitude. Using this method we have estimated the precursor frequency of naive CD8 T cells specific for the H-2D(b)-restricted GP33-41 epitope of LCMV to be 1 in 2 x 10(5). Thus, in an uninfected mouse containing approximately 2-4 x 10(7) naive CD8 T cells we estimate there to be 100-200 epitope-specific cells. After LCMV infection these 100-200 GP33-specific naive CD8 T cells divide >14 times in 1 wk to reach a total of approximately 10(7) cells. Approximately 5% of these activated GP33-specific effector CD8 T cells survive to generate a memory pool consisting of approximately 5 x 10(5) cells. Thus, an acute LCMV infection results in a >1,000-fold increase in precursor frequency of D(b)GP33-specific CD8 T cells from 2 x 10(2) naive cells in uninfected mice to 5 x 10(5) memory cells in immunized mice.