PG F2α Receptor: A Promising Therapeutic Target for Cardiovascular Disease

Prostaglandins (PGs), a group of key lipid mediators, are involved in numerous physiological and pathological processes including inflammation and cardiovascular homeostasis. Each PG acts on its specific and distinct cell surface G protein-coupled receptors (GPCRs) or peroxisome proliferator-activated receptors (PPARs). Prostaglandin F2α receptor (FP) is required for female reproductive function such as luteolysis and parturition. It has recently been implicated in blood pressure regulation, atherosclerosis and other inflammation-related disorders. The emerging role of FP in cardiovascular diseases is highlighted and potential therapeutic translation is discussed in the current review

Photocatalytic regio- and stereoselective C(sp3)–H functionalization of benzylic and allylic hydrocarbons as well as unactivated alkanes

C(sp3)–H键的直接官能团化具有原子、步骤经济、原料来源丰富等特点，备受合成化学家的青睐。然而，这些化学键的高键能、低极性等特征使其反应性差；相近能量化学键的存在也使反应的选择性难以控制。因此，C(sp3)–H键的直接、选择性转化一直是有机合成中的难题。课题组基于近期在手性廉价金属配合物催化自由基可控不对称合成方面的工作基础（Nat.Commun.2019,10,3804、J. Am.Chem.Soc.2018,140,15850、Chem.Sci.2018,9,4562），提出了手性铜、镍、钴配合物与商业化醌类可见光氢转移催化剂共催化的策略，在极为温和的光反应条件下，实现了石油、天然气中原材料向高附加值手性化合物的区域、立体选择性转化，为烃类资源的优化利用及药物分子的后期改造提供了有效手段，也为纯烃分子作为反应试剂直接使用提供了新思路。该方法适用于苄基、烯丙基类化合物、环烷烃、链烷烃等40余种烃类分子，也适用于一些药物及生物活性分子（如celebrex、skelaxin等）的后期官能化中。此外，廉价金属/氢转移光催化剂体系也展现了通过改变催化剂金属中心获得手性反转产物的独特现象，为立体发散性合成提供了极为简便的策略。 本工作由龚磊副教授指导，实验部分由2016级博士生李延军和已毕业硕士生雷梦合作完成.The selective functionalization of inert C(sp3)–H bonds is extremely attractive in organic synthesis and catalysis science, but the conversion of hydrocarbons lacking directing groups into chiral molecules through catalytic C(sp3)–H functionalization is formidably challenging. Here, to address this problem, we have developed a photochemical system consisting of a hydrogen atom transfer organophotocatalyst and a chiral catalyst containing an earth-abundant metal. With the cooperative catalysts and imine partners, a wide range of benzylic, allylic hydrocarbons and unactivated alkanes can be converted to functionalized chiral products. The readily tunable bisoxazoline catalysts of copper or other metals exhibit precise regional recognition and asymmetric induction towards these inert C–H bonds. The reactions are applicable to many compounds including small hydrocarbons, branched alkanes, cycloalkanes and more complex medicinal agents. This method provides an economic and rapid construction of optically active compounds, starting from the most basic chemical feedstocks.We gratefully acknowledge funding from the National Natural Science Foundation of China (grant no. 21572184), the Natural Science Foundation of Fujian Province of China (grant no. 2017J06006) and the Fundamental Research Funds for the Central Universities (grant no. 20720190048). 研究工作得到国家自然科学基金（21572184）、福建省杰出青年基金（2017J06006）、南强青年拔尖人才计划（B类）、厦门大学校长基金（20720190048）等项目支持

Socio-demographic association of multiple modifiable lifestyle risk factors and their clustering in a representative urban population of adults: a cross-sectional study in Hangzhou, China

<p>Abstract</p> <p>Background</p> <p>To plan long-term prevention strategies and develop tailored intervention activities, it is important to understand the socio-demographic characteristics of the subpopulations at high risk of developing chronic diseases. This study aimed to examine the socio-demographic characteristics associated with multiple lifestyle risk factors and their clustering.</p> <p>Methods</p> <p>We conducted a simple random sampling survey to assess lifestyle risk factors in three districts of Hangzhou, China between 2008 and 2009. A two-step cluster analysis was used to identify different health-related lifestyle clusters based on tobacco use, physical activity, fruit and vegetable consumption, and out-of-home eating. Multinomial logistic regression was used to model the association between socio-demographic factors and lifestyle clusters.</p> <p>Results</p> <p>A total of 2016 eligible people (977 men and 1039 women, ages 18-64 years) completed the survey. Three distinct clusters were identified from the cluster analysis: an unhealthy (UH) group (25.7%), moderately healthy (MH) group (31.1%), and healthy (H) group (43.1%). UH group was characterised by a high prevalence of current daily smoking, a moderate or low level of PA, low FV consumption with regard to the frequency or servings, and more occurrences of eating out. H group was characterised by no current daily smoking, a moderate level of PA, high FV consumption, and the fewest times of eating out. MH group was characterised by no current daily smoking, a low or high level of PA, and an intermediate level of FV consumption and frequency of eating out. Men were more likely than women to have unhealthy lifestyles. Adults aged 50-64 years were more likely to live healthy lifestyles. Adults aged 40-49 years were more likely to be in the UH group. Adults whose highest level of education was junior high school or below were more likely to be in the UH group. Adults with a high asset index were more likely to be in the MH group.</p> <p>Conclusions</p> <p>This study suggests that Chinese urban people who are middle-aged, men, and less educated are most likely to be part of the cluster with a high-risk profile. Those groups will contribute the most to the future burden of major chronic disease and should be targeted for early prevention programs.</p

Photocatalytic enantioselective α-aminoalkylation of acyclic imine derivatives by a chiral copper catalyst

廉价金属催化的可见光反应为惰性化学键的断裂和重组提供了新的策略，且具有经济、低毒、易操作的特点，是发展绿色合成方法的理想选择。然而，由于这些金属配合物的可见光吸收相对弱、光化学稳定性较差、激发态寿命短等缺点，相关研究较为有限，特别是其催化的可见光不对称合成因涉及自由基等高活性物种转化的立体化学控制，是极具挑战性却有着重大意义的研究方向。课题组在近期工作基础上以易得、易修饰的手性噁唑啉-铜（II）配合物作为催化剂，在可见光照射下实现了非环亚胺的高对映选择性α-胺基烷基化反应，为手性二胺及其衍生物的制备提供了一条经济、便捷的路线。控制实验充分证明了其机理。该项研究利用单一催化剂发挥多重功效，使转化困难的反应在极为简单、温和的条件得以实现，为多功能催化及绿色合成方法的发展提供了新的思路。 该研究由龚磊副教授指导，实验部分由已毕业硕士生韩博闻（第一作者）、博士生李延军、硕士生余莹合作完成。 此文章并被选为Editors’ Highlights论文。Copper-based asymmetric photocatalysis has great potential in the development of green synthetic approaches to chiral molecules. However, there are several formidable challenges associated with such a conception. These include the relatively weak visible light absorption, short excited-state lifetimes, incompatibility of different catalytic cycles, and the difficulty of the stereocontrol. We report here an effective strategy by means of single-electron-transfer (SET) initiated formation of radicals and photoactive intermediates to address the long-standing problems. Through elaborate selection of well-matched reaction partners, the chiral bisoxazoline copper catalyst is engaged in the SET process, photoredox catalysis, Lewis acid activation and asymmetric induction. Accordingly, a highly enantioselective photocatalytic α-aminoalkylation of acyclic imine derivatives has been accessed. This strategy sheds light on how to make use of diverse functions of a single transition metal catalyst in one reaction, and offers an economic and simplified approach to construction of highly valuable chiral vicinal diamines.We gratefully acknowledge funding from the National Natural Science Foundation of China (grant no. 21572184), the Natural Science Foundation of Fujian Province of China (grant no. 2017J06006), and the Fundamental Research Funds for the Central Universities (grant no. 20720190048).研究工作得到国家自然科学基金（21572184）、福建省杰出青年基金（2017J06006）、厦门大学校长基金（20720190048）、南强青年拔尖人才计划（B类）等的支持

Complete revascularization based on angiography derived fractional flow reserve versus incomplete revascularization in patients with ST-segment elevation myocardial infarction

Background: Nearly half of ST-segment elevation myocardial infarction (STEMI) patients present with significant multivessel coronary artery disease, they are at high risk of subsequent adverse events. Whether complete revascularization guided by coronary angiography-derived fractional flow reserve (caFFR) further reduces such events risk is not fully investigated. Methods: In this study, 367 consecutive STEMI patients who underwent successful primary percutaneous coronary intervention (PCI) were enrolled. caFFR of all three coronary vessels were measured, including 367 culprit vessels and 703 non-culprit vessels. Complete revascularization was defined as post-PCI caFFR &gt; 0.8 of all three coronary vessels. The primary endpoint was major adverse cardiovascular events (MACE, a composite of cardiovascular death, non-fatal recurrent myocardial infarction, ischemia-driven revascularization and non-fatal stroke/transient ischemic attacks) during follow-up. Results: At a median follow-up of 3.8 years, MACE had occurred in 39 patients of the 220 (17.7%) in the complete revascularization group as compared with 49 patients of the 131 (37.4%) in the incomplete revascularization group (hazard ratio [HR] 1.9; 95% confidence interval [CI] 1.2–3.0; p = 0.005). The incomplete revascularization in culprit vessels evaluated by caFFR showed the highest risk for MACE occurrence. Conclusions: In STEMI patients with multivessel coronary artery disease, incomplete revascularization based on caFFR might contribute to identifying patients at high-risk

Securing the Future of GenAI: Policy and Technology

The rise of Generative AI (GenAI) brings about transformative potential across sectors, but its dual-use nature also amplifies risks. Governments globally are grappling with the challenge of regulating GenAI, balancing innovation against safety. China, the United States (US), and the European Union (EU) are at the forefront with initiatives like the Management of Algorithmic Recommendations, the Executive Order, and the AI Act, respectively. However, the rapid evolution of GenAI capabilities often outpaces the development of comprehensive safety measures, creating a gap between regulatory needs and technical advancements. A workshop co-organized by Google, University of Wisconsin, Madison (UW-Madison), and Stanford University aimed to bridge this gap between GenAI policy and technology. The diverse stakeholders of the GenAI space—from the public and governments to academia and industry—make any safety measures under consideration more complex, as both technical feasibility and regulatory guidance must be realized. This paper summarizes the discussions during the workshop which addressed questions, such as: How regulation can be designed without hindering technological progress? How technology can evolve to meet regulatory standards? The interplay between legislation and technology is a very vast topic, and we don’t claim that this paper is a comprehensive treatment on this topic. This paper is meant to capture findings based on the workshop, and hopefully, can guide discussion on this topic

Role of gut microbiota and metabolomics in the lipid-lowering efficacy of statins among Chinese patients with coronary heart disease and hypercholesterolemia

BackgroundStatins, being the primary pharmacological intervention for hypercholesterolemia, exhibit a notable degree of interpatient variability in their effectiveness, which may be associated with gut microbiota. This study sought to identify the biomarkers for evaluating differences in statin efficacy.MethodsA quasi case-control study was conducted among participants with hypercholesterolemia and coronary heart disease taking rosuvastatin essential. According to the level of low density lipoprotein cholesterol (LDL-C), participants was divided into the “Up to standard” (US) group and the “Below standard” (BS) group. 16S rDNA sequencing and untargeted metabolomics were applied to detected the information of gut microbiota and related metabolites.ResultsA total of 8 US and 8 BS group matched by age and sex were included in the final analysis. 16S rDNA sequencing results indicated that the characteristic strains of the US group were f-Eubacterium_coprostanoligenes and g-Papillibacter, while the characteristic flora of the BS group were o-C0119, g-Pseudolabrys, s-Dyella-Marensis and f-Xanthobacaceae. Metabolomic results suggested that the levels of chenodeoxycholic acid-3-β-D-glucuronide, 1-methylnicotinamide and acetoacetate in stool samples of the US group were significantly higher than those of the BS group. By identifying the differentially abundant bacterial taxa, the gut microbiota could modulate the efficacy of statins through producing enzymes involved in cholesterol metabolism.ConclusionsThe findings suggest that the difference in statin efficacy may be related to gut microbiota strains that can produce short-chain fatty acids and secondary bile acids and affect the efficacy of statins by regulating the activities of cholesterol metabolite-related proteins. Metabolites related to short-chain fatty acids and secondary bile acids in the gut are expected to be biomarkers indicating the efficacy of statins

Morphological diversity of single neurons in molecularly defined cell types.

Dendritic and axonal morphology reflects the input and output of neurons and is a defining feature of neuronal types1,2, yet our knowledge of its diversity remains limited. Here, to systematically examine complete single-neuron morphologies on a brain-wide scale, we established a pipeline encompassing sparse labelling, whole-brain imaging, reconstruction, registration and analysis. We fully reconstructed 1,741 neurons from cortex, claustrum, thalamus, striatum and other brain regions in mice. We identified 11 major projection neuron types with distinct morphological features and corresponding transcriptomic identities. Extensive projectional diversity was found within each of these major types, on the basis of which some types were clustered into more refined subtypes. This diversity follows a set of generalizable principles that govern long-range axonal projections at different levels, including molecular correspondence, divergent or convergent projection, axon termination pattern, regional specificity, topography, and individual cell variability. Although clear concordance with transcriptomic profiles is evident at the level of major projection type, fine-grained morphological diversity often does not readily correlate with transcriptomic subtypes derived from unsupervised clustering, highlighting the need for single-cell cross-modality studies. Overall, our study demonstrates the crucial need for quantitative description of complete single-cell anatomy in cell-type classification, as single-cell morphological diversity reveals a plethora of ways in which different cell types and their individual members may contribute to the configuration and function of their respective circuits