PPAR-α inhibits DHEA-induced ferroptosis in granulosa cells through upregulation of FADS2.

BACKGROUND: Polycystic ovary syndrome (PCOS), a prevalent endocrine disorder among women of reproductive age, is characterized by disturbances in hormone levels and ovarian dysfunction. Ferroptosis, a unique form of regulated cell death characterized by iron-dependent lipid peroxidation. Emerging evidence indicates that ferroptosis may have a significant role in the pathogenesis of PCOS, highlighting the importance of studying this mechanism to better understand the disorder and potentially develop novel therapeutic interventions. METHODS: To create an in vivo PCOS model, mice were injected with dehydroepiandrosterone (DHEA) and the success of the model was confirmed through further assessments. Ferroptosis levels were evaluated through detecting ferroptosis-related indicators. Ferroptosis-related genes were found through bioinformatic analysis and identified by experiments. An in vitro PCOS model was also established using DHEA treated KGN cells. The molecular binding relationship was confirmed using a chromatin immunoprecipitation (ChIP) assay. RESULTS: In PCOS model, various ferroptosis-related indicators such as MDA, Fe2+, and lipid ROS showed an increase, while GSH, GPX4, and TFR1 exhibited a decrease. These findings indicate an elevated level of ferroptosis in the PCOS model. The ferroptosis-related gene FADS2 was identified and validated. FADS2 and PPAR-α were shown to be highly expressed in ovarian tissue and primary granulosa cells (GCs) of PCOS mice. Furthermore, the overexpression of both FADS2 and PPAR-α in KGN cells effectively suppressed the DHEA-induced increase in ferroptosis-related indicators (MDA, Fe2+, and lipid ROS) and the decrease in GSH, GPX4, and TFR1 levels. The ferroptosis agonist erastin reversed the suppressive effect, suggesting the involvement of ferroptosis in this process. Additionally, the FADS2 inhibitor SC26196 was found to inhibit the effect of PPAR-α on ferroptosis. Moreover, the binding of PPAR-α to the FADS2 promoter region was predicted and confirmed. This indicates the regulatory relationship between PPAR-α and FADS2 in the context of ferroptosis. CONCLUSIONS: Our study indicates that PPAR-α may have an inhibitory effect on DHEA-induced ferroptosis in GCs by enhancing the expression of FADS2. This discovery provides valuable insights into the pathophysiology and potential therapeutic targets for PCOS.

Selenium-catalyzed allylic C-H phosphoramidation of alkenes.

We report herein a synthesis of allylic phosphoramidates from alkenes by selenium-catalyzed allylic C-H derivatization. This method features mild conditions, broad substrate scope, and high functional group tolerance, enabling late-stage modification of a number of complex substrates. In addition, this protocol was applied to modify caryophyllene and produced a photoaffinity probe capable of proteomic target labeling in live HeLa cells.

Engineering Structural Janus MXene-nanofibrils Aerogels for Season-Adaptive Radiative Thermal Regulation.

Aerogels have provided a significant platform for passive radiation-enabled thermal regulation, arousing extensive interest due to their capabilities of radiative cooling or heating. However, there still remains challenge of developing functionally integrated aerogels for sustainable thermal regulation in both hot and cold environment. Here, Janus structured MXene-nanofibrils aerogel (JMNA) is rationally designed via a facile and efficient way. The achieved aerogel presents the characteristic of high porosity (≈98.2%), good mechanical strength (tensile stress of ≈2 MPa, compressive stress of ≈115 kPa), and macroscopic shaping property. Based on the asymmetric structure, the JMNA with switchable functional layers can alternatively enable passive radiative heating and cooling in winter and summer, respectively. As a proof of concept, JMNA can function as a switchable thermal-regulated roof to effectively enable the inner house model to maintain >25 °C in winter and <30 °C in hot summer. This design of Janus structured aerogels with compatible and expandable capabilities is promising to widely benefit the low-energy thermal regulation in changeable climate.

Research on radiotherapy related genes and prognostic target identification of rectal cancer based on multi-omics.

BACKGROUND: Radiosensitivity of rectal cancer is related to the radiotherapy efficacy and prognosis of patients with rectal cancer, and the genes and molecular mechanisms related to radiosensitivity of rectal cancer have not been clarified. We explored the radiosensitivity related genes of rectal cancer at a multi omics level. METHODS: mRNA expression data and rectum adenocarcinoma (READ) data were obtained from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus Database (GEO) (GSE150082, GSE60331, GSE46862, GSE46862). Differentially expressed genes between radiotherapy sensitive group and radiotherapy insensitive group were screened. GO analysis and KEGG pathway analysis were performed for differentially expressed genes. Among the differentially expressed genes, five core genes associated with rectal cancer prognosis were selected using random survival forest analysis. For these five core genes, drug sensitivity analysis, immune cell infiltration analysis, TISIDB database immune gene correlation analysis, GSEA enrichment analysis, construction of Nomogram prediction model, transcriptional regulatory network analysis, and qRT-PCR validation was performed on human rectal adenocarcinoma tissue. RESULTS: We found that 600 up-regulated genes and 553 down-regulated genes were significantly different between radiotherapy sensitive group and radiotherapy insensitive group in rectal cancer. Five key genes, TOP2A, MATR3, APOL6, JOSD1, and HOXC6, were finally screened by random survival forest analysis. These five key genes were associated with different immune cell infiltration, immune-related genes, and chemosensitivity. A comprehensive transcriptional regulatory network was constructed based on these five core genes. qRT-PCR revealed that MATR3 expression was different in rectal cancer tissues and adjacent non-cancerous tissues, while APOL6, HOXC6, JOSD1, and TOP2A expression was not different. CONCLUSION: Five radiosensitivity-related genes related to the prognosis of rectal cancer: TOP2A, MATR3, APOL6, JOSD1, HOXC6, are involved in multiple processes such as immune cell infiltration, immune-related genes, chemosensitivity, signaling pathways and transcriptional regulatory networks and may be potential biomarkers for radiotherapy of rectal cancer.

Identification of immunotherapy-related lncRNA signature for predicting prognosis, immunotherapy responses and drug candidates in bladder cancer.

BACKGROUND: Bladder cancer (BC) is one of the most common malignant diseases and the most common causes of cancer death worldwide. Immunotherapy has opened new avenues for precision treatment of bladder tumours, and immune checkpoint inhibitors (ICIs) have revolutionized the clinical treatment strategy of bladder tumours. In addition, long non-coding RNA (lncRNA) plays an important role in regulating tumour development and immunotherapy efficacy. METHODS: We obtained genes with significant differences between anti-PD-L1 response and non-response from the Imvogor210 data set and combined with the bladder cancer expression data in the TCGA cohort to obtain immunotherapy-related lncRNA. Based on these lncRNAs, the prognostic risk model of bladder cancer was constructed and verified by GEO external data set. The characterization of immune cell infiltration and immunotherapy effects between high-risk and low-risk groups were then analysed. We predicted the ceRNA network and performed molecular docking of key target proteins. The functional experiments verified the function of SBF2-AS1. RESULTS: Three immunotherapy-related lncRNAs were identified as independent prognostic biomarkers for bladder cancer and a prognostic model of immunotherapy-related prognosis was constructed. Prognosis, immune cell infiltration, and immunotherapy efficacy were significantly different between high- and low-risk groups based on risk scores. Additionally, we established a ceRNA network of lncRNA(SBF2-AS1)-miRNA(has-miR-582-5p)-mRNA (HNRNPA2B1). Targeting the protein HNRNPA2B1 identified the top eight small molecule drugs with the highest affinity. CONCLUSION: We developed a prognostic risk score model based on immune-therapy-related lncRNA, which was subsequently determined to be significantly associated with immune cell infiltration and immunotherapy response. This study not only helps to promote our understanding of immunotherapy-related lncRNA in the prognosis of BC, but also provides new ideas for clinical immunotherapy and the development of novel therapeutic drugs for patients.

Engineering Biomimetic Nanostructured "Melanosome" Textiles for Advanced Solar-to-Thermal Devices.

In nature, deep-sea fish featured with close-packed melanosomes can remarkably lower light reflection, which have inspired us to design ultrablack coatings for enhanced solar-to-thermal conversion. Herein, a biomimetic ultrablack textile is developed enabled by the formation of hierarchical polypyrrole (Ppy) nanospheres. The fabricated textile exhibits prominently suppressed reflectance of lower than 4% and highly enhanced absorption of up to 96%. Further experimental results and molecular dynamics (MD) simulation evidence the formation process of hierarchical nanospheres. Based on high-efficient solar-to-thermal conversion, the biomimetic textile with desirable conductivity allows the development of a salt-free solar evaporator, enabling a sustainable seawater evaporation rate of up to 1.54 kg m-2 h-1 under 1 sun. Furthermore, the biomimetic hierarchical textile exhibits good superhydrophobicity, enhanced photothermal property, and high electrothermal conversion, demonstrating significant potential in wearable thermal management (rescue vests) in water conditions.

[Arctigenin mitigates vascular endothelial injury in rats with pregnancy-induced hypertension via autophagy-NLRP3 inflammasome pathway].

This study aims to investigate the effect and mechanism of arctigenin(ARC) in the treatment of vascular endothelial injury in rats with pregnancy-induced hypertension(PIH). Fifty SD rats pregnant for 12 days were randomly assigned into a control group, a model group, an ARC group, a rapamycin(RAP, autophagy inducer) group, and an ARC+3-methyladenine(3-MA, autophagy inhibitor) group, with 10 rats in each group. The rats in the other groups except the control group were intraperitoneally injected with nitrosyl-L-arginine methyl ester(50 mg·kg~(-1)·d~(-1)) to establish the PIH model on the 13th day of pregnancy. On the 15th day of pregnancy, the rats in ARC, RAP, and ARC+3-MA groups were intraperitoneally injected with ARC(50 mg·kg~(-1)·d~(-1)), RAP(1 mg·kg~(-1)·d~(-1)), and 3-MA(15 mg·kg~(-1)·d~(-1))+ARC(50 mg·kg~(-1)·d~(-1)), respectively. The pregnant rats in the control group and the model group were intraperitoneally injected with the same amount of normal saline. The blood pressure and 24 h urine protein(24 h-UP) of pregnant rats in each group were measured before and after intervention. Cesarean section was performed to terminate pregnancy on day 21, and the body weight and body length of fetal rats were compared among groups. Hematoxylin-eosin(HE) staining was employed to observe the pathological changes of placenta. The expression of endothelin-1(ET-1) and endothelial nitric oxide synthase(eNOS) in placenta was detected by immunohistochemistry. The serum levels of ET-1 and nitric oxide(NO) were determined with corresponding kits. The expression of microtubule-associated protein 1 light chain 3(LC3), Beclin-1, NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein with CARD domain(ASC), caspase-1, interleukin(IL)-1ß, and IL-18 was determined by immunofluorescence and Western blot. The level of reactive oxygen species(ROS) in placenta was measured by fluorescence staining. The results showed that on day 12 of pregnancy, the blood pressure and 24 h-UP had no significant differences among groups. On days 15, 19, and 21, the blood pressure and 24 h-UP in the model group were higher than those in the control group(P<0.05). On days 19 and 21, the blood pressure and 24 h-UP in ARC group and RAP group were lower than those in the model group(P<0.05), and they were higher in the ARC+3-MA group than in the ARC group(P<0.05). On day 21, the model group had lower body weight and body length of fetal rats(P<0.05), higher serum level of ET-1, and lower serum level of NO(P<0.05) than the control group. Moreover, the placental tissue showed typical pathological damage, down-regulated expression of LC3-Ⅱ/LC3-Ⅰ, Beclin-1 and eNOS(P<0.05), up-regulated expression of ET-1, NLRP3, ASC, caspase-1, IL-1ß, and IL-18(P<0.05), and elevated ROS level. Compared with the model group, ARC and RAP groups showed increased body weight and body length of fetal rats(P<0.05), lowered serum level of ET-1, elevated serum level of NO(P<0.05), reduced pathological damage of placental tissue, up-regulated expression of LC3-Ⅱ/LC3-Ⅰ, Beclin-1, and eNOS(P<0.05), down-regulated expression of ET-1, NLRP3, ASC, caspase-1, IL-1ß, and IL-18(P<0.05), and lowered ROS level. Compared with ARC group, 3-MA reversed the effects of ARC on the above indicators. In conclusion, ARC can inhibit the activation of NLRP3 inflammasome and mitigate vascular endothelial damage in PIH rats by inducing autophagy of vascular endothelial cells.

Synthesis and antidepressant activity of novel 1-(1-benzoylpiperidin-4-yl) methanamine derivatives selectively targeting SSRI/5-HT1A.

A series of novel 1-(1-benzoylpiperidin-4-yl) methanamine derivatives were synthesized and evaluated for the serotonin reuptake inhibitory abilities and binding affinities to the 5-HT1A receptor. The metabolic stabilities of these compounds were measured in vitro using human or mouse liver microsomes and the antidepressant activities were explored In vivo using the forced swimming test (FST) and tail suspension test (TST) in mice. The results indicated that the compound 12a exhibited strongest serotonin reuptake inhibition (IC50 = 8.2 nM) and marked 5-HT1A receptor affinity (Ki = 0.069 nM), which were significantly superior to lead compounds Ⅰ and Ⅱ. Meanwhile, compound 12a showed good metabolic stability in vitro and exhibited potential antidepressant-like effects in the FST and TST in mice.

Potential Risk of Calcified Nanoparticles for Recurrent Urinary Tract Infection after Minimally Invasive Percutaneous Nephrolithotomy for Renal Calculi.

Among urolithiasis, urolithiasis is a more extensive and difficult to treat disease. In recent years, with the development of endoscopic equipment and related surgical methods, a new treatment, namely minimally invasive percutaneous nephrolithotomy, appears and is widely used in the treatment of renal calculi. It has been developed for more than 50 years since its appearance. Its advantages are a high stone clearance rate, small surgical trauma, fewer intraoperative and postoperative complications, and a short recovery time for postoperative patients. It is widely used in clinical treatment. The purpose of this paper is to study the potential risk factors of recurrence and the possibility of urinary tract infection in patients with renal calculi after minimally invasive percutaneous nephrolithotomy (MPCNL) with calcified nanoparticles, so as to obtain correct nursing knowledge and reduce recurrence and infection. In order to explore the renal calculi caused by calcified nanoparticles (CNPs), we established a rat model of renal calculi, injected CNPs into rats, collected experimental samples after a specified time, and determined NGAL, OPN and MCP-1 by enzyme-linked immunosorbent assay (ELISA) and compared them with the formation of crystallization. In the study of the possible influencing factors of septic shock after PCNL, we established a multivariate regression analysis and model, used statistical methods and professional statistical software, and used the method of classified data analysis to find out the influencing factors. After the experiment, we found that positive urine culture (P < 0.05) and preoperative urinary tract infection (P < 0.05) were significant influencing factors, and the total accuracy was 99.2%. At the same time, it is concluded that calcium nanoparticles can promote the retention, adhesion and aggregation of calcium salt crystals in the kidney, and then lead to the formation of stones.

Novel compound heterozygous variants of DNAH17 in a Chinese infertile man with multiple morphological abnormalities of sperm flagella.

Multiple morphological abnormalities of the sperm flagellum (MMAF) have been reported to be an important cause of male infertility and reflect a heterogeneous genetic disorder. Previous studies have identified dozens of candidate pathogenic genes for MMAF, but the aetiology in approximately 50% of cases remains unexplained. The present study aimed to identify novel potentially pathogenic gene variants of MMAF. A Chinese family with a 32-year-old infertile proband presenting with MMAF was recruited, and sperm morphology of the patient was examined by Papanicolaou staining. Whole exome sequencing was performed on the proband and Sanger sequencing was used to identify genetic variants in the family. The frequencies of variants were assessed using public databases and the effects on protein structure and function were predicted by online bioinformatics tools. The patient exhibited asthenozoospermia and a MMAF phenotype. Novel compound heterozygous variants (c.5368C > T, p.R1790C and c.13183C > T, p.R4395W) of the DNAH17 gene were identified in the patient, and showed autosomal recessive inheritance in this family. These variants were very rare in the GnomAD database. The two mutated amino acids were located in a highly conserved region of the DNAH17 protein. In silico analysis revealed that the compound heterozygous variants may compromise the function of DNAH17. Our findings expand upon the spectrum of pathogenic DNAH17 variants that are responsible for MMAF, and provide new knowledge for genetic counselling of male infertility due to MMAF.

Ivermectin Attenuates CCl4-Induced Liver Fibrosis in Mice by Suppressing Hepatic Stellate Cell Activation.

Liver fibrosis, a common liver dysfunction with high morbidity and mortality rates, is the leading cause of cirrhosis and hepatocellular carcinoma, for which there are no effective therapies. Ivermectin is an antiparasitic drug that also has been showing therapeutic actions in many other diseases, including antiviral and anticancer actions, as well as treating metabolic diseases. Herein, we evaluated the function of ivermectin in regulating liver fibrosis. Firstly, carbon tetrachloride (CCl4)-injected Balb/c mice were used to assess the antifibrosis effects of ivermectin in vivo. Further, CFSC, a rat hepatic stellate cell (HSC) line, was used to explore the function of ivermectin in HSC activation in vitro. The in vivo data showed that ivermectin administration alleviated histopathological changes, improved liver function, reduced collagen deposition, and downregulated the expression of profibrotic genes. Mechanistically, the ivermectin treatment inhibited intrahepatic macrophage accumulation and suppressed the production of proinflammatory factors. Importantly, the ivermectin administration significantly decreased the protein levels of α-smooth muscle actin (α-SMA) both in vivo and in vitro, suggesting that the antifibrotic effects of ivermectin are mainly due to the promotion of HSC deactivation. The present study demonstrates that ivermectin may be a potential therapeutic agent for the prevention of hepatic fibrosis.

A Facile Synthesis of 2-Oxazolines via Dehydrative Cyclization Promoted by Triflic Acid.

2-oxazolines are common moieties in numerous natural products, pharmaceuticals, and functional copolymers. Current methods for synthesizing 2-oxazolines mainly rely on stoichiometric dehydration agents or catalytic dehydration promoted by specific catalysts. These conditions either generate stoichiometric amounts of waste or require forcing azeotropic reflux conditions. As such, a practical and robust method that promotes dehydrative cyclization while generating no byproducts would be attractive to oxazoline production. Herein, we report a triflic acid (TfOH)-promoted dehydrative cyclization of N-(2-hydroxyethyl)amides for synthesizing 2-oxazolines. This reaction tolerates various functional groups and generates water as the only byproduct. This method affords oxazoline with inversion of α-hydroxyl stereochemistry, suggesting that alcohol is activated as a leaving group under these conditions. Furthermore, the one-pot synthesis protocol of 2-oxazolines directly from carboxylic acids and amino alcohols is also provided.

One-pot synthesis and multiple MS/MS fragmentation studies of phospholysine peptides.

RATIONALE: Compared with phosphorylation of arginine and histidine, the study of phosphorylation of lysine lags far behind. The major challenges toward the current study of phosphorylation of lysine include synthesis and unambiguous phosphosite identification. This study provided a simple chemical synthesis method to construct phospholysine peptides (pLys peptides) and investigated their fragmentation under multiple activation types. METHODS: Herein, we developed a synthetic method for pLys peptides in aqueous solution within one pot. Two peptides were lysine-phosphorylated using this method. The purified pLys peptides were first characterized using NMR, then were subjected to nano-liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) analysis under multiple fragmentation method including collision-induced dissociation (CID), higher energy collisional dissociation (HCD), electron transfer dissociation (ETD), electron transfer/higher energy collisional dissociation (EThcD), and ultraviolet photodissociation (UVPD) fragmentation to investigate the relevant diagnostic ions. RESULTS: Two pLys peptides were synthesized with a moderate yield following an easily handled experimental protocol. NMR spectra showed the phosphorylation occurred on ε-NH2 of lysine but not other groups. As for the fragmentation, in general, pLys immonium ions and phosphate-related neutral losses were ubiquitous among spectra derived from these activation types except for ETD. Using these ions as diagnostic ions, the misassigned phosphosites by algorithm could be recorrected. UVPD-generated spectra owned good sequence-coverage and abundant fragment ions, with pLys immonium ions and neutral losses of weak intensity. CONCLUSIONS: A synthetic method was developed for pLys peptides in aqueous solution within one pot. The characteristic pLys immonium ions and phosphate-related neutral loss could serve as the diagnostic ions for unambiguous phosphosite identification of pLys peptides. In addition, UVPD was promising for the identification of pLys peptides.

Mini-incision Blepharoplasty with Pretarsal Fasciectomy for Double-Eyelid Surgery.

BACKGROUND: Double-eyelid surgery has been one of the most popular aesthetic surgeries in oriental populations. The objective of this study was to introduce a simple procedure for double-eyelid surgery. METHODS: The mini-incision blepharoplasty with pretarsal fasciectomy technique is described and illustrated. Blepharoplasty cases in our practice from June 2018 to December 2019 were retrospectively reviewed. Patients who underwent mini-incision blepharoplasty with pretarsal fasciectomy were followed up for at least 6 months. RESULTS: Of 280 blepharoplasty cases, 32 patients underwent mini-incision blepharoplasty with pretarsal fasciectomy on both upper eyelids. Nineteen patients experienced resolve of swelling within 5 days postoperatively. No loss of fold was observed during follow-up. The satisfaction rate was 93.8%. CONCLUSIONS: The mini-incision blepharoplasty with pretarsal fasciectomy is ideal for selected patients requesting double-eyelid surgery. It provides stable, natural, scarless result with minimum complication and rapid recovery. LEVEL OF EVIDENCE: IV.

Contribution of rescue in-vitro maturation versus double ovarian stimulation in ovarian stimulation cycles of poor-prognosis women.

RESEARCH QUESTION: Maximizing the number of oocytes and embryos obtained in the shortest possible time is of considerable potential clinical significance for women with poor prognosis. The aim of this study was to develop a clinically applicable strategy to obtain more oocytes and viable embryos in one menstrual cycle for poor-prognosis women. DESIGN: Prospective cohort study of 146 women with poor prognosis who received rescue in-vitro maturation (IVM) (n = 50) or double ovarian stimulation (DuoStim) (n = 96) between December 2015 and February 2018. Outcomes, number of oocytes retrieved and matured, and embryo developmental potential were compared between the two groups. RESULTS: The rates of mature oocytes, available embryos and top-quality embryos from luteal phase stimulation (LPS) of DuoStim were all significantly higher than those derived from the immature oocytes of rescue IVM (P < 0.05). The relative contributions of LPS in the DuoStim group for proportion of mature oocytes, available embryos and top-quality embryos were all significantly higher than IVM in the rescue IVM group (P < 0.001). The overall cancellation rate of no oocyte or available embryo significantly decreased from 30.21% to 9.38% (P < 0.001) when DuoStim was carried out, which decreased from 24.00% to 12.00% with no significant difference in the rescue IVM group when immature sibling oocytes were matured in vitro. CONCLUSION: Rescue IVM and DuoStim can contribute more competent oocytes and viable embryos in the shortest possible time for poor-prognosis women, of which DuoStim may be more efficient.

[Grade evaluation of Sophorae Tonkinensis Radix et Rhizoma based on quality constant evaluation method].

The traditional Chinese medicine(TCM) quality constant herbal slices evaluation method was applied to evaluate the grade of Sophorae Tonkinensis Radix et Rhizoma based on the combination of traditional character identification and modern scientific and technological methods. The TCM quality constant evaluation method was used to determine the appearance and index content of medicinal slices, calculate the quality constant and percentile quality constant of Sophorae Tonkinensis Radix et Rhizoma from different sources, and discuss their classification. The quality constants of 15 batches of Sophorae Tonkinensis Radix et Rhizoma slices were between 0.004 and 0.063. The slices with the percentage quality constant ≥80% were classified as the first grade; those with the percentage quality constant ≥50% and <80% were classified as the second grade; and those with the percentage quality constant <50% were classified as the third grade. Then the slices with the quality constant ≥0.050 were classified as the first grade; those with the quality constant ≥0.032 and <0.050 were classified as the second grade; and those with the quality constant <0.032 were classified as the third grade. According to the results, the 15 batches of Sophorae Tonkinensis Radix et Rhizoma slices were divided into 1 batch of the first grade, 4 batches of the second grade, and 10 batches of the third grade. The quality constant evaluation method established is scientific, objective, simple and feasible. The application of the method in Sophorae Tonkinensis Radix et Rhizoma slices has reasonable results, which is helpful to promote the classification of Sophorae Tonkinensis Radix et Rhizoma and promotes the high-quality application of Sophorae Tonkinensis Radix et Rhizoma.

[Current studies on quality of Chinese patent drugs with consistency as core and discussions on new high-quality evaluation model].

The consistency of quality on Chinese patent drugs is a hotspot and difficulty in the control of traditional Chinese medicine preparations, and has become one of the bottlenecks restricting its internationalization. Based on the analysis of current studies on quality and problems of Chinese patent drugs, this paper explored relevant methods of quality evaluation on Chinese patent drugs and possible factors affecting the consistency of quality in the pharmaceutical cycle by consulting relevant literatures about quality evaluation methods and consistency control techniques of large-scale Chinese patent drugs. And it put forward the evaluation system on high-quality Chinese patent drugs with "consistency" as the core, so as to promote the overall improvement of the quality of Chinese patent drugs, guide the rational price of Chinese patent drugs of the same species, and provide a new reference model for the quality evaluation of Chinese patent drug.

[Evaluation and analysis of high-quality products of Liuwei Dihuang Pills].

Liuwei Dihuang Pills is a typical traditional Chinese medicine with "the same product made by many manufacturers". The quality and price of products made in various factories was different obviously. In this study, the quality differences of Liuwei Dihuang Pills were evaluated over multi-dimensions and throughout the whole production cycle involving raw materials, production process, quality control and post-marketing re-studies based on the "Chinese patent medicine evaluation standard with quality at the core" established earlier by our research group. The research results showed that the product quality of various manufacturers was significantly different, and the product quality was positively correlated with the market shares of enterprises, indicating that enterprises with more market shares paid more attention to product quality; and the sales determined the concern degree of enterprises on products, which was in line with general cognition. During the single-item evaluation of Liuwei Dihuang Pills, the score of raw material selection was relatively low, and the enterprises paid less attention to the initial raw materials. The whole production process was better, and the national compulsory implementation of "Production Quality Management Standard"(GMP) had a positive effect in improving product quality. Quality control could basically guarantee product quality. Intelligent manufacturing promoted by the government was beneficial to ensure product uniformity. The score rate of "quality evaluation" item was basically qualified, which indicated that the quality control level of Liuwei Dihuang Pills was acceptable as a whole, but there was still room for improvement. "Re-evaluation and Brand Construction" had the lowest scores, reflecting that enterprises did not pay enough attention to in-depth study and re-evaluation of "the same product made by many manufacturers". The evaluation results were in line with expectations, provided a reference example for the evaluation of high-quality Chinese patent medicine, a basis for the high-quality and good price of Chinese patent medicine, scientific data for improving medical insurance bidding, and thus facilitated promoting the healthy development of the traditional Chinese medicine industry.

Tillandsia-Inspired Hygroscopic Photothermal Organogels for Efficient Atmospheric Water Harvesting.

Tillandsia species with degenerated roots have evolved into hygroscopic leaves that absorb moisture from air. This interesting biological adaptability has inspired us to develop an integrated hygroscopic photothermal organogel (POG) to achieve a solar-powered atmospheric water harvesting (AWH). The well-designed hydrophilic co-polymeric skeleton is fabricated to accommodate hygroscopic glycerin medium, which enables the POG self-contained property, mechanically flexibility and synergistic enhancement of moisture sorption. The integration of interpenetrated photothermal component of poly-pyrrole-dopamine (P-Py-DA) can endow the POG an efficient solar-to-thermal property for controllable solar-driven interfacial water releasing. The integrated POG has an equilibrium moisture sorption of 16.01 kg m-2 at the RH of 90 %, and daily water production as high as 2.43 kg m-2 day-1 is achieved in actual outdoor experiments.

Synthesis and Target Identification of a Novel Electrophilic Warhead, 2-Chloromethylquinoline.

Despite its power in identifying highly potent ligands for select protein targets, conventional medicinal chemistry is limited by its low throughput and lack of proteomic selectivity information. We seek to develop a chemoproteomic approach for discovering covalent ligands for protein targets in an unbiased, high-throughput manner. Tripartite probe compounds composed of a heterocyclic core, an electrophilic "warhead", and an alkyne tag have been designed and synthesized for covalently labeling and identifying targets in cells. We have developed a novel condensation reaction to prepare 2-chloromethylquinoline (2-CMQ), an electrophilic heterocycle. These chloromethylquinolines potently and covalently bind to a number of cellular protein targets, including prostaglandin E synthase 2 (PTGES2), a critical regulator of cell proliferation, apoptosis, angiogenesis, inflammation, and immune surveillance. The 2-CMQs that we have developed here are novel PTGES2 binders that have the potential to serve as therapies for the treatment of human diseases such as inflammation.