In this work, starting from 4-hydroxycoumarin, three series of 22 coumarin derivatives, among which 8 have not been reported in the literature, were synthesized and their in vitro anti-inflammatory activities and mechanisms of action were preliminarily investigated using mouse macrophage model. The results showed that most of the derivatives could significantly inhibit the production of pro-inflammatory factor NO, with compounds 2e, 2f, 2g, 2h, 2i, 2j, 4e, and 4f showing better anti-inflammatory activity than the positive control drug dexamethasone. Further experiments showed that compounds 2h and 4f significantly inhibited the production of pro-inflammatory factors IL-6, TNF-α and IL-1β in RAW264.7 macrophages, and could, therefore, be used as lead compounds for further studies.

Background::Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD.Methods::In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort.Results::In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone.Conclusion::ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE.Trial Registration::Chictr.org.cn: ChiCTR2200059599.

Cell-free transcription and translation (TXTL) system is a cell extract-based system for rapid in vitro protein expression. The system bypasses routine laboratory processes such as bacterial transformation, clonal screening and cell lysis, which allows more precise and convenient control of reaction substrates, reduces the impact of bacteria on protein production, and provides a high degree of versatility and flexibility. In recent years, TXTL has been widely used as an emerging platform in clusterd regularly interspaced short palindromic repeat (CRISPR) technologies, enabling more rapid and convenient characterization of CRISPR/Cas systems, including screening highly specific gRNAs as well as anti-CRISPR proteins. Furthermore, TXTL-based CRISPR biosensors combined with biological materials and gene circuits are able to detect pathogens through validation of related antibiotics and nucleic acid-based markers, respectively. The reagents can be freeze-dried to improve portability and achieve point-of-care testing with high sensitivity. In addition, combinations of the sensor with programmable circuit elements and other technologies provide a non-biological alternative to whole-cell biosensors, which can improve biosafety and accelerate its application for approval. Here, this review discusses the TXTL-based characterization of CRISPR and their applications in biosensors, to facilitate the development of TXTL-based CRISPR/Cas systems in biosensors.
CRISPR-Cas Systems ; Bacteria

The passing of ethical review is a necessary conditions and prerequisite for the development of life science and medical research involving humans. At present, some medical and health institutions have no or insufficient ethical review capabilities. The lack of ethical review ability has become a bottleneck restricting the development of life science and medical research involving humans. According to documents such as Opinions on Deepening the Reform of the Review and Approval System and Encouraging the Innovation of Pharmaceutical and Medical Devices, Opinions on Strengthening the Ethical Governance of Science and Technology, institutions can entrust competent institutional ethics review committees or regional ethics review committees in writing to conduct ethical review. Entrustment ethical review provides a viable solution for institutions that need to carry out life science and medical research involving humans but do not have an ethics (review) committee or the ethics (review) committee is not competent to review. To conduct the entrustment ethical review, the entrustment between the principal and the trustee is required. According to The Measures for Ethical Review of Life Sciences and Medical Research Involving Humans, if medical and health institutions and their ethical review committees do not accept the formal entrustment to provide the ethical review opinions for other institutions, the local health authorities at or above the county level will impose administrative penalties and sanctions on the relevant institutions and personnel in accordance with the law. Signing the entrustment ethical review contract, implementing legal compliance entrusted ethical review to protect the rights and interests of the trustee and the principal, and protect the research participants.

Objective:To improve the prognosis stratification, especially early mortality(EM), of elderly patients with newly diagnosed multiple myeloma(NDMM).Methods:In this retrospective study, univariate and multivariate Cox regression analysis were conducted to identify the independent prognostic factors associated with overall survival(OS)and the chi-square test and multivariate Logistic analysis were used to identify the prognostic factors associated with EM in 223 elderly patients(age≥65 years)with NDMM from three centers in the country.Results:Increased NT-pro-BNP(≥300 pg/ml), ECOG-PS≥2 and stage Ⅲ R-ISS were identified as three independent adverse prognostic factors of OS.The rates of EM3, EM6, EM12 and EM24 were 12.1%, 20.1%, 32.2% and 60%, respectively.The most common cause for EM6(particularly EM3)was disease-related complications resulting from ineligibility for treatment due to poor physical performance, severe organ dysfunction or treatment discontinuation due to treatment intolerance, while the most common cause for EM12(particularly EM24)was disease progression or relapse mainly as a result of inadequate treatment.R-ISS staging failed to predict EM, while decreased eGFR, ECOG-PS≥2, and increased NT-pro-BNP were able to estimate the risk of EM, with increased NT-pro-BNP as a common independent factor for EM12( P=0.03)and EM24( P=0.015). Conclusions:R-ISS staging, which primarily reflects MM biology, cannot predict EM.However, factors such as NT-pro-BNP, eGFR and ECOG-PS associated with frailty and impairment of organ functions can be used to estimate the risk of EM, among which NT-pro-BNP may be the most important independent factor for EM.Therefore, incorporation of these frailty-related biomarkers into R-ISS staging may be able to more precisely estimate the prognosis and particularly early death of elderly patients with NDMM.

Respiratory diseases are a group of different conditions affecting the airways, including acute lung injury, asthma, chronic obstructive pulmonary disorder, and idiopathic pulmonary fibrosis. Recent studies have demonstrated the extracellular vesicles (EVs) produced and secreted by autologous cells are able to induce inflammatory responses and immune activation in respiratory diseases. Exosomes, a type of EVs (30-150 nm) containing nuclear acids, proteins, lipids, and metabolites, can transfer bioactive cargo and have potential implications for disease pathogenesis. Although the biological functions of exosomes in cancer and cardiovascular diseases have been widely addressed, their pathophysiological mechanisms in respiratory disorders are still not completely understood. In this review, we first presented current methodologies in use for exosomes isolation and characterization from biological fluids, such as bronchoalveolar lavage fluid, nasal lavage fluid, exhaled breath condensate, sputum supernatant, and blood. And then, we critically discussed the crucial role of exosomes in respiratory diseases, not only focusing on their involvement in the development of airway diseases, but also on their diagnostic and therapeutic potential. A better understanding of these mechanisms will provide opportunities for research on respiratory diseases induced by environmental and occupational exposure to particulate matter in which exosomes contribute to the disease development.

Primary aldosteronism (PA) is a kind of disease caused by excessive aldosterone secretion from the adrenal cortex, the reason of which include bilateral adrenal hyperplasia, aldosteronoma, unilateral adrenal hyperplasia, etc. Surgical treatment is the first choice for unilateral adrenal lesions. In this article, we report a patient who underwent left adrenal surgery but did not achieve the expected results. This case suggests that clinicians need to further improve the level of diagnosis and treatment of primary aldosteronism, especially the surgical methods.

Tetrapyrrole compounds are a class of compounds with important functions. They exist in living organisms and have been widely used in agriculture, food, medicine, and other fields. The cumbersome process and high cost of chemical synthesis, as well as the shortcomings of unstable quality of animal and plant extraction methods, greatly hampered the industrial production and applications of tetrapyrrole compounds. In recent years, the rapid development of synthetic biology has provided new tools for microorganisms to efficiently synthesize tetrapyrrole compounds from renewable biomass resources. This article summarizes various strategies for the biosynthesis of tetrapyrrole compounds, discusses methods to improve its biosynthesis efficiency and future prospects, with the aim to facilitate the research on biosynthesis of tetrapyrrole compounds.
Biomass ; Plants/genetics* ; Synthetic Biology ; Tetrapyrroles

Objective: To evaluate snack consumption and the influencing factors associated with student participation in the Nutrition Improvement Program, and to provide a scientific basis for improving the program. Methods: Among the 50 monitoring counties that implemented the Compulsory Education Student Nutrition Improvement Program, two primary schools and two junior schools were randomly selected according to different food supply patterns (i.e., school, company, and mix). This study randomly selected one or two classes from each grade, which ranged from grade 3 to grade 9. A questionnaire, which addressed snack consumption and choice, was distributed to 27 374 students. Results: The findings revealed that 14.0% of students from poor rural areas in central and western regions consumed snacks two or more times per day, and 21.6% of students spent 3 yuan or more on snacks each day. The top three choices of snacks included fruit and vegetables (50.6%), biscuits and bread (50.1%), and puffed food (40.0%). Students who had mothers who worked outside the home, parents who worked outside the home, who consumed corporate meals, and who had access to a small shop on campus were more likely to consume snacks one or more times per day(OR=1.35，1.19，1.11，1.51，P<0.05). Conclusion The phenomenon of snack consumption among primary and middle school students from poor rural areas in central and western regions is common, and the selection of unhealthy snacks was identified as a problem. A health education system with comprehensive support and guidance from individuals, families, schools, and society should be established to guide students to opt for healthier snacks.

Objective: To evaluate temporal trend in food supply among pilot schools involved in the National Nutrition Improvement Program for Rural Compulsory Education Students (NNIPRCES). Methods: Ten percent of pilot schools were randomly selected and asked to report the information on food supplies. Daily intake of energy, carbohydrates and protein for each student were calculated and compared with the reference value in Nutrition Guidelines of School Meals (WS/T 554-2017). Results: Energy and protein supply increased among those pilot schools. The supply of energy increased from 1 566.5 kcal in 2012 to 1 927.4 kcal in 2017, protein increased from 49.0 g to 61.0 g. The energy ratio of fat increased from 31.9% to 34.9%, while energy ratio of carbohydrate decreased significantly (F=83.38, 128.36, 20.27 and 17.28, all P<0.05). The proportion of reasonable energy supply from carbohydrate and fat in 2017 were 17.5% and 26.8%, respectively. Conclusion The supply of energy and macronutrients in the pilot areas were unreasonable, more measures including dietary guide and monitoring need to be adopted to improve students nutrition status among rural areas.