Palladium-Catalyzed Hydrocyanation of Ynoates: En Route to the Stereodivergent Synthesis of ß-Cyanated α,ß-Unsaturated Esters via Ligand Controlled Regio- and Stereoselectivity.

A Pd-catalyzed highly regio- and stereoselective hydrocyanation was developed, providing a novel approach to the stereodivergent synthesis of ß-cyano-substituted acrylates in good yields with a wide substrate scope. The judicious selection of ligands was crucial for elegant control over the stereodivergence. Furthermore, the success of the E-hydrocyanation hinges on the right matching of Pd and L1, which not only ensured the catalytic activity but also prevented the formation of α-cyanation products.

[Research progress on processing history evolution, chemical constituents, and pharmacological action of Scorpio].

Scorpio is a valuable Chinese animal medicine commonly used in clinical practice in China. It is the main drug in the treatment of liver wind internal movement caused by various reasons throughout the history of traditional Chinese medicine(TCM), with the effects of relieving wind and spasm, dredging collaterals, relieving pain, and eliminating toxin and mass. Scorpio is poisonous and often used as medicine after processing. There are records of its processing as early as the Song Dynasty. Afterward, there were more than 15 processing methods, including frying with vinegar, neat processing, and stir-frying. After processing, the fishy smell could be removed to correct the taste, and the toxicity could be reduced, which was beneficial to clinical application. At present, the main reported components in Scorpio are protein polypeptides, alkaloids, and lipids, with many pharmacological effects, such as anti-cancer, anti-coagulation, anti-thrombosis, anti-atherosclerosis, and anti-bacteria. In this study, the historical evolution of processing, chemical constituents, and pharmacological action of Scorpio were discussed in order to provide references for the related research on Scorpio.

Access to 2,4-Disubstituted Pyrrole-Based Polymer with Long-Wavelength and Stimuli-Responsive Properties via Copper-Catalyzed [3+2] Polycycloaddition.

Pyrrole-based polymers (PBPs), a type of fascinating functional polymers, play a crucial role in materials science. However, efficient synthetic strategies of PBPs with diverse structures are mainly focused on conjugated polypyrroles and still remain challenging. Herein, an atom and step economy protocol is described to access various 2,4-disubstituted PBPs by in situ formation of pyrrole core structure via copper-catalyzed [3+2] polycycloaddition of dialkynones and diisocyanoacetates. A series of PBPs is prepared with high molecular weight (Mw up to 18 200 Da) and moderate to good yield (up to 87%), which possesses a fluorescent emission located in the green to yellow light region. Blending the PBPs with polyvinyl alcohol, the stretchable composite films exhibit a significant strengthening of the mechanical properties (tensile stress up to 59 MPa, elongation at break >400%) and an unprecedented stress-responsive luminescence enhancement that over fourfold fluorescent emission intensity is maintained upon stretching up to 100%. On the basis of computational studies, the unique photophysical and mechanical properties are attributed to the substitution of carbonyl chromophores on the pyrrole unit.

Scalable expansion of human pluripotent stem cells under suspension culture condition with human platelet lysate supplementation.

The large-scale production of human pluripotent stem cells (hPSCs), including both embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), shows potential for advancing the translational realization of hPSC technology. Among multiple cell culture methods, suspension culture, also known as three-dimensional (3D) culture, stands out as a promising method to fulfill the large-scale production requirements. Under this 3D culture condition, cell expansion and the preservation of pluripotency and identity during long-term culture heavily relies on the culture medium. However, the xenogeneic supplements in culture medium remains an obstacle for the translation of cell and gene therapy applications from bench to bedside. Here, we tested human platelet lysate (hPL), a xeno-free and serum-free biological material, as a supplement in the 3D culture of hPSCs. We observed reduced intercellular variability and enhanced proliferation in both hESC and hiPSC lines. These cells, after extended culture in the hPL-supplemented system, maintained pluripotency marker expression, the capacity to differentiate into cells of all three germ layers, and normal karyotype, confirming the practicability and safety of hPL supplementation. Furthermore, through RNA-sequencing analysis, we found an upregulation of genes associated with cell cycle regulations in hPL-treated cells, consistent with the improved cellular division efficiency. Taken together, our findings underscore the potential of hPL as a xeno-free and serum-free supplement for the large-scale production of hPSCs, which holds promise for advancing clinical applications of these cells.

Transcriptional variation in Babesia gibsoni (Wuhan isolate) between in vivo and in vitro cultures in blood stage.

BACKGROUND: Babesia gibsoni, the causative agent of canine babesiosis, belongs to the phylum Apicomplexa. The development of in vitro culture technology has driven research progress in various kinds of omics studies, including transcriptomic analysis of Plasmodium spp. between in vitro and in vivo environments, which has prompted the observation of diagnostic antigens and vaccine development. Nevertheless, no information on Babesia spp. could be obtained in this respect, which greatly hinders the further understanding of parasite growth and development in the blood stage. METHODS: In this study, considerable changes in the morphology and infectivity of continuous in vitro cultured B. gibsoni (Wuhan isolate) were observed compared to in vivo parasites. Based on these changes, B. gibsoni (Wuhan isolate) was collected from both in vivo and in vitro cultures, followed by total RNA extraction and Illumina transcriptome sequencing. The acquired differentially expressed genes (DEGs) were validated using qRT-PCR, and then functionally annotated through several databases. The gene with the greatest upregulation after in vitro culture was cloned from the genome of B. gibsoni (Wuhan isolate) and characterized by western blotting and indirect immunofluorescence assay for detecting the native form and cellular localization. RESULTS: Through laboratory cultivation, multiple forms of parasites were observed, and the infectivity of in vitro cultured parasites in dogs was found to be lower. Based on these changes, Illumina transcriptome sequencing was conducted, showing that 377 unigenes were upregulated and 334 unigenes were downregulated. Notably, an AP2 transcription factor family, essential for all developmental stages of parasites, was screened, and the transcriptional changes in these family members were tested. Thus, the novel AP2 transcription factor gene (BgAP2-M) with the highest upregulated expression after in vitro adaptation was selected. This gene comprises an open reading frame (ORF) of 1989 base pairs encoding a full-length protein of 662 amino acids. BgAP2-M contains one AP2 domain and one ACDC conserved domain, which may be involved in the nuclear biology of parasites. The prepared polyclonal antibodies against the BgAP2-M peptides further detected a native size of ~ 73 kDa and were localized to the nuclei of B. gibsoni. CONCLUSION: This study presents a thorough transcriptome analysis of B. gibsoni in vivo and in vitro for the first time, contributing to a detailed understanding of the effects of environmental changes on the growth and development of parasites in the blood stage. Moreover, it also provides a deeper investigation for the different members of the ApiAP2 transcription factor family as various life stage regulators in Babesia spp.

[Research progress on processing historical evolution, chemical constituents, and pharmacological action of Bombyx Batryticatus].

Bombyx Batryticatus is a precious traditional Chinese animal drug commonly used in clinical practice in China, which has the effects of extinguishing wind, stopping convulsions, dispelling wind, relieving pain, resolving phlegm, and dissipating mass. The processing of Bombyx Batryticatus has a long history. As early as in the Liu Song period of the Southern and Northern Dynasties, there was a record of the processing of Bombyx Batryticatus with rice swill. In addition to the processing with bran, honey bran, and ginger juice, which are still used today, there are also processing methods such as rendering, flour processing, wine processing, salt processing, oil processing, charcoal, and red dates processing in ancient times. After processing, the fishy smell of Bombyx Batryticatus can be removed, and avoid nausea and vomiting caused by the direct taking. Furthermore, processing can also facilitate the removal of surface hairs and toxicity reduction, making the medicinal material crispy and easy to crush. Previous studies have shown that the main chemical constituents of Bombyx Batryticatus include protein polypeptides, sterols, and flavonoids, with anticonvulsant, anticoagulation, antithrombotic, anti-cancer, hypnotic, hypoglycemic, and other pharmacological effects. This paper reviewed the processing historical evolution, chemical constituents, and pharmacological effects of Bombyx Batryticatus to lay a foundation for the research on the processing mechanism, quality control, and active core substances of Bombyx Batryticatus.

Establishment of Continuous In Vitro Culture of Babesia gibsoni by Using VP-SFM Medium with Low-Concentration Serum.

The establishment of in vitro culture methods has greatly facilitated the research of Babesia. However, the current Babesia gibsoni in vitro culture medium requires high concentrations of canine serum, which intensively limits the culture and is unable to satisfy the demands of long-term studies. In this study, AlbuMAX I (2 mg/mL) and 2.5% dog serum (vol/vol) were added to VP-SFM medium to develop a low-concentration serum culture medium named VP-SFMAD (2.5%), and the effectiveness of this medium was assessed by the growth of B. gibsoni. The results showed that VP-SFMAD (2.5%) could support the continuous growth of the parasite, and the parasitemia has no difference with the cultivation in RPMI 1640 with 20% dog serum. In contrast, either a low concentration of dog serum or absence of AlbuMAX I will significantly lower the parasite growth or fail to maintain B. gibsoni growth in the long term. The strategy of reducing the hematocrit was also evaluated, and VP-SFMAD (2.5%) improved the parasitemia to over 50% within 5 days. The high parasitemia is helpful for larger numbers of parasite collection, which is valuable for studying the biology, pathogenesis, and virulence of Babesia and other intraerythrocytic parasites. In addition, VP-SFMAD (2.5%) medium was successfully used for monoclonal parasite screening, which obtained monoclonal strains with parasitized erythrocytes about 3%, which is similar to RPMI-1640D (20%) medium that obtains monoclonal strains on the 18th day. Those results showed that VP-SFMAD can be applied to B. gibsoni continuous long-term, expansion culture, and subclone culture. IMPORTANCE The VP-SFM as a base medium supplemented with AlbuMAX I and a low concentration of canine serum (2.5%) allowed the continuous in vitro culture of Babesia gibsoni at both small and large volumes, which was to meet different experimental needs, such as long-term culture and obtaining high parasitemia and subclone culture. The establishment of in vitro culture systems allows researchers to better understand the metabolism and growth patterns of Babesia. Importantly, several technical problems impeding such studies have been overcome.

Poaceae-specific ß-1,3;1,4-d-glucans link jasmonate signalling to OsLecRK1-mediated defence response during rice-brown planthopper interactions.

Brown planthopper (BPH, Nilaparvata lugens), a highly destructive insect pest, poses a serious threat to rice (Oryza sativa) production worldwide. Jasmonates are key phytohormones that regulate plant defences against BPH; however, the molecular link between jasmonates and BPH responses in rice remains largely unknown. Here, we discovered a Poaceae-specific metabolite, mixed-linkage ß-1,3;1,4-d-glucan (MLG), which contributes to jasmonate-mediated BPH resistance. MLG levels in rice significantly increased upon BPH attack. Overexpressing OsCslF6, which encodes a glucan synthase that catalyses MLG biosynthesis, significantly enhanced BPH resistance and cell wall thickness in vascular bundles, whereas knockout of OsCslF6 reduced BPH resistance and vascular wall thickness. OsMYC2, a master transcription factor of jasmonate signalling, directly controlled the upregulation of OsCslF6 in response to BPH feeding. The AT-rich domain of the OsCslF6 promoter varies in rice varieties from different locations and natural variants in this domain were associated with BPH resistance. MLG-derived oligosaccharides bound to the plasma membrane-anchored LECTIN RECEPTOR KINASE1 OsLecRK1 and modulated its activity. Thus, our findings suggest that the OsMYC2-OsCslF6 module regulates pest resistance by modulating MLG production to enhance vascular wall thickness and OsLecRK1-mediated defence signalling during rice-BPH interactions.

Circ-C16orf62 Regulates Oxidized low-density Lipoprotein-induced Apoptosis, Inflammation, Oxidative Stress and Cholesterol Accumulation of Macrophages via Mediating RAB22A Expression by Targeting miR-377.

Atherosclerosis (AS) is one of the most common and important vascular diseases. It is believed that the abnormal expression of circular RNAs (circRNAs) plays an important role in AS. Hence, we investigate the function and mechanism of circ-C16orf62 in AS development.In this study, oxidized low-density lipoprotein (ox-LDL)-treated human macrophages (THP-1) were used as pathological conditions of AS in vitro. The expression of circ-C16orf62, miR-377 and Ras-related protein (RAB22A) mRNA was detected by real-time quantitative polymerase chain reaction (RT-qPCR) or western blot. Cell viability or cell apoptosis was assessed by cell counting kit-8 (CCK-8) assay or flow cytometry assay. The releases of proinflammatory factors were investigated using enzyme-linked immunosorbent assay (ELISA). The production of malondialdehyde (MDA) and superoxide dismutase (SOD) was examined to assess oxidative stress. Total cholesterol (T-CHO) level was detected, and cholesterol efflux level was tested using a liquid scintillation counter. The putative relationship between miR-377 and circ-C16orf62 or RAB22A was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay.circ-C16orf62 expression was elevated in AS serum samples and ox-LDL-treated THP-1 cells. Apoptosis, inflammation, oxidative stress and cholesterol accumulation induced by ox-LDL were suppressed by circ-C16orf62 knockdown. Circ-C16orf62 could bind to miR-377 and thus increased the expression level of RAB22A. Rescued experiments showed that circ-C16orf62 knockdown alleviated ox-LDL-induced THP-1 cell injuries by increasing miR-377 expression, and miR-377 overexpression lessened ox-LDL-induced THP-1 cell injuries by degrading RAB22A level.In conclusion, circ-C16orf62 played a crucial role in the regulation of apoptosis, inflammation, oxidative stress and cholesterol accumulation in ox-LDL-treated human macrophages via mediating the miR-377/RAB22A axis, hinting that circ-C16orf62 might be involved in AS progression.

Optimization of protein removal process of Lonicera japonica polysaccharide and its immunomodulatory mechanism in cyclophosphamide-induced mice by metabolomics and network pharmacology.

In this study, TCA-n-butanol was chosen as the best deproteinization method for Lonicera japonica polysaccharide (LJP) by comparing the polysaccharide retention rate and the protein clearance rate of five different methods. The response surface methodology (RSM) based on the Box-Behnken design (BBD) was used to optimize the deproteinization conditions as follows: TCA: n-butanol = 1: 5.1, polysaccharide solution: (TCA-n-butanol) = 1: 2.8, and shook for 33 min. LJP could promote the thymus and spleen indexes of cyclophosphamide (CTX)-induced immune-deficient mice. Besides, the contents of cytokine interleukin-2 (IL-2) and hemolysin in mice serum were augmented after treatment with LJP. Based on serum metabolomics analysis, a total of 14 metabolites (VIP >1.0, FC >2 or FC <0.5, and p value < .05) were selected as the potential biological biomarkers related to the LJP for treating CTX-induced mice. After the pathway enrichment analysis, these metabolites were mainly involved in the relevant pathways of arginine biosynthesis, Citrate cycle, and other metabolic pathways. Network pharmacology further showed that there were 57 key targeting proteins in the intersection of the potential biological biomarkers and immunodeficiency-related targeting proteins according to protein-protein interactions analysis (PPI). The biological function analysis indicated that the potential biological processes were mainly associated with tricarboxylic acid (TCA) cycle, phospholipid metabolic process, metabolic process, and so on. In conclusion, serum metabolomics combined with network pharmacology could be helpful to clarify the immunomodulatory mechanism of LJP and provide a literature basis for further clinical research on the therapeutic mechanism of LJP.

[Research progress on processing history evolution, chemical constituents, and pharmacological effects of Hirudo].

As a traditional animal drug, Hirudo is slightly toxic and has the effects of breaking blood stasis, dredging meridians, expelling stasis, and resolving mass. It has a long history of processing, and the early boiling records can be traced back to the Han Dynasty. More than ten processing methods such as frying, roasting, and lime processing appeared later. After processing, Hirudo is deodorized and modified in taste and becomes crispy, which is conducive to crushing and clinical application. At present, the reported components in Hirudo mainly include protein polypeptides, pteridines, and lipids, which have anti-coagulant, anti-thrombotic, anti-atherosclerotic, anti-tumor, and other pharmacological effects. This study reviewed the processing history evolution, chemical consti-tuents, and pharmacological effects of Hirudo to provide a reference for the related research on Hirudo.

Epigenetic regulation of aging: implications for interventions of aging and diseases.

Aging is accompanied by the decline of organismal functions and a series of prominent hallmarks, including genetic and epigenetic alterations. These aging-associated epigenetic changes include DNA methylation, histone modification, chromatin remodeling, non-coding RNA (ncRNA) regulation, and RNA modification, all of which participate in the regulation of the aging process, and hence contribute to aging-related diseases. Therefore, understanding the epigenetic mechanisms in aging will provide new avenues to develop strategies to delay aging. Indeed, aging interventions based on manipulating epigenetic mechanisms have led to the alleviation of aging or the extension of the lifespan in animal models. Small molecule-based therapies and reprogramming strategies that enable epigenetic rejuvenation have been developed for ameliorating or reversing aging-related conditions. In addition, adopting health-promoting activities, such as caloric restriction, exercise, and calibrating circadian rhythm, has been demonstrated to delay aging. Furthermore, various clinical trials for aging intervention are ongoing, providing more evidence of the safety and efficacy of these therapies. Here, we review recent work on the epigenetic regulation of aging and outline the advances in intervention strategies for aging and age-associated diseases. A better understanding of the critical roles of epigenetics in the aging process will lead to more clinical advances in the prevention of human aging and therapy of aging-related diseases.

Membrane fouling behaviors in a full-scale zero liquid discharge system for cold-rolling wastewater brine treatment: A comprehensive analysis on multiple membrane processes.

The challenge of water scarcity drives zero liquid discharge (ZLD) treatment to maximize reuse of industrial wastewater. Deciphering the characteristics and mechanisms of membrane fouling in the membrane-based ZLD system is crucial for the development of effective fouling control strategies. However, current studies only focused on the membrane fouling of single step, lacking in-depth understanding on the ZLD systems using multiple membrane processes. Herein, membrane fouling characteristics and mechanisms in a full-scale ZLD system for cold-rolling wastewater brine treatment were investigated via a comprehensive analysis on multiple nanofiltration (NF) and reverse osmosis (RO) membrane processes. The membrane fouling behaviors showed distinct characteristics along the wastewater flow direction in the ZLD system. Increasing amounts of foulants were deposited on the membrane surfaces with the sequence of the 1st pass RO, 1st stage NF, and 2nd stage NF processes. The organic fouling and silica scaling were more intensive in the 1st stage NF and 2nd stage NF for treating the brine of the 1st pass RO, as the foulants were rejected and concentrated by previous membrane processes. Severe inorganic fouling, containing amorphous SiO2, Al2O3, and Al2SiO5, occurred on the membrane surface of the 2nd pass RO membrane, due to the recirculated high-concentration silica, high water recovery, and concentration polarization. For the 3rd pass RO process, both the amounts of organic and inorganic foulants decreased dramatically, due to the low foulant concentration in its influent. This work provides a comprehensive understanding of membrane fouling in a membrane-based ZLD system, facilitating the development of membrane fouling control strategies for multiple membrane processes.

A novel promising diagnostic candidate selected by screening the transcriptome of Babesia gibsoni (Wuhan isolate) asexual stages in infected beagles.

BACKGROUND: Babesia gibsoni is one of the causative agents of canine babesiosis worldwide. Some dogs infected with B. gibsoni show severe clinical signs with progressive anemia, hemoglobinuria and splenomegaly. However, most infected dogs present a state of chronic infection and thereby may be a persistent pathogen carrier, increasing the risk of pathogen spreading. To date, little is known about this pathogen, with genomic and transcriptomic data in particular generally unavailable. This lack of knowledge extensively limits the development of effective diagnostic strategies and vaccines. METHODS: High-throughput RNA sequencing of total RNA of B. gibsoni asexual stages collected from infected beagles was performed. The unigenes were annotated in seven databases. The genes were sorted according to their fragments per kilobase per million (FPKM) value, which was used as an indicator for expression level. The gene with the highest FPKM value was cloned from the genome of B. gibsoni and further tested for immunogenicity, cellular localization and efficacy as a potential diagnostic candidate for detecting B. gibsoni in sera collected from beagles. RESULTS: A total of 62,580,653 clean reads were screened from the 64,336,475 raw reads, and the corresponding 70,134 transcripts and 36,587 unigenes were obtained. The gene with the highest FPKM value was screened from the unigenes; its full length was 1276 bp, and it was named BgP30. The BgP30 gene comprised three exons and two introns, with a 786-bp open reading frame, and encoded 261 amino acids with a predicted molecular weight of 30 kDa. The cellular localization assay confirmed the existence of P30 protein in B. gibsoni parasites. Moreover, P30 was detected in the serum of experimentally B. gibsoni-infected beagles, from 15 days up to 422 days post-infection, suggesting its usefulness as a diagnostic candidate for both acute and chronic infections. CONCLUSIONS: We sequenced the transcriptome of B. gibsoni asexual stages for the first time. The BgP30 gene was highly expressed in the transcriptome screening experiments, with further studies demonstrating that it could induce immune response in B. gibsoni-infected dogs. These results lead us to suggest that bgP30 may be a good diagnostic candidate marker to detect both acute and chronic B. gibsoni infections.

Single-Shot Object Detection via Feature Enhancement and Channel Attention.

Features play a critical role in computer vision tasks. Deep learning methods have resulted in significant breakthroughs in the field of object detection, but it is still an extremely challenging obstacle when an object is very small. In this work, we propose a feature-enhancement- and channel-attention-guided single-shot detector called the FCSSD with four modules to improve object detection performance. Specifically, inspired by the structure of atrous convolution, we built an efficient feature-extraction module (EFM) in order to explore contextual information along the spatial dimension, and then pyramidal aggregation module (PAM) is presented to explore the semantic features of deep layers, thus reducing the semantic gap between multi-scale features. Furthermore, we construct an effective feature pyramid refinement fusion (FPRF) to refine the multi-scale features and create benefits for richer object knowledge. Finally, an attention-guided module (AGM) is developed to balance the channel weights and optimize the final integrated features on each level; this alleviates the aliasing effects of the FPN with negligible computational costs. The FCSSD exploits richer information of shallow layers and higher layers by using our designed modules, thus accomplishing excellent detection performance for multi-scale object detection and reaching a better tradeoff between accuracy and inference time. Experiments on PASCAL VOC and MS COCO datasets were conducted to evaluate the performance, showing that our FCSSD achieves competitive detection performance compared with existing mainstream object detection methods.

Tuning Proapoptotic Activity of a Phosphoric-Acid-Tethered Tetraphenylethene by Visible-Light-Triggered Isomerization and Switchable Protein Interactions for Cancer Therapy.

We herein report a phosphoric-acid-substituted tetraphenylethene (T-P) capable of adapting its geometric configuration and biological activity to the microenvironment upon light irradiation for apoptosis modulation. Different from most ultraviolet-responsive isomerization, T-P undergoes cis-trans isomerization under visible light irradiation, which is biocompatible and thus photo-modulation is possible in living biosystems. By using alkaline phosphatase (ALP) and albumin as dual targets, T-P isomers display different protein binding selectivity, cancer-cell internalization efficiency and apoptosis-inducing ability. The proapoptotic activity was found to be kinetically controlled by the enzymatic reaction with ALP and regulated by co-existing albumin. Motivated by these findings, two-way modulation of proapoptotic effect and on-demand boosting anticancer efficacy were realized in vitro and in vivo using light and endogenous proteins as multiple non-invasive switching stimuli.

A flexible, robust and multifunctional montmorillonite/aramid nanofibers@MXene electromagnetic shielding nanocomposite with an alternating structure for enhanced Joule heating and fire-resistant protective performance.

With the rapidly increasing development of portable devices and flexible electronic devices, multifunctional composites with excellent mechanical strength, great electromagnetic interference shielding, great Joule heating performance and strong fire-resistant protective performance are noticeably required. Herein, inspired by the sandwich structure, we have designed a montmorillonite/aramid nanofibers@MXene (MMT/ANFs@MXene) nanocomposite with an alternating multilayered structure via a simple AVF process. In this nanocomposite, the ANFs/MMT (AT) layer acts as a mechanically reinforced and insulation protection layer, while the MXene layer maintains a complete conductive network. The superior alternating multilayered structure endows the nanocomposite with outstanding mechanical properties (154.66 MPa, 14.22%) and excellent EMI shielding effectiveness values (58.4 dB). In addition, the fire-resistant protective performance of the nanocomposite improves its safety and reliability, especially, the EMI shielding effectiveness is maintained at ∼34 dB after burning for 30 s. Besides, the MMT/ANFs@MXene nanocomposite shows excellent Joule heating performance with a fast thermal response, low driving voltage and long-time temperature stability, which could reach 110.2 °C at only 3 V applied voltage within 10 s. As a result, this work presents a novel strategy for constructing multifunctional composites with outstanding overall performance, which will broaden application areas and prospects in thermal management and EMI shielding in wearable products.

Hsa_circ_0010729 regulates H2O2-induced myocardial injury by regulating miR-1184/RIPK1 axis.

BACKGROUND: Ischemia-reperfusion (I/R) is an important risk factor for cardiovascular diseases (CVDs) and cardiac transplantation, as I/R can cause myocardial cell hypoxia/reoxygenation (H/R) injury. Recent research has shown that circular RNAs (circRNAs) may affect the progress of H/R-induced myocardial injury, but the mechanism remains unknown. Our work explored the role of circ_0010729 in H2O2-induced myocardial injury. METHODS: The levels of circ_0010729, microRNA-1184 (miR-1184) and mRNA of receptor interacting serine/threonine kinase 1 (RIPK1) were indicated by quantitative real-time polymerase chain reaction (qRT-PCR) in human cardiac myocytes (HCMs). Meanwhile, the protein level of RIPK1 was quantified by western blot analysis. Besides, the cell functions were examined by 5-Ethynyl-29-deoxyuridine (EdU) assay, flow cytometry assay, western blot and antioxidant indexes analysis. Furthermore, the interplay between miR-1184 and circ_0010729 or RIPK1 was detected by dual-luciferase reporter assay. Eventually, the in vivo experiments were applied to measure the role of circ_0010729. RESULTS: The levels of circ_0010729 RNA and RIPK1 protein were increased, and the miR-1184 was decreased in HCMs exposed to H2O2. In functional analysis, circ_0010729 deficiency restrained cell apoptosis and oxidative stress, whereas promoted cell proliferation in HCMs under H2O2 exposure. Moreover, miR-1184 inhibited the H2O2-induced myocardial injury by targeting RIPK1. Mechanistically, circ_0010729 acted as a miR-1184 sponge to regulate the level of RIPK1. CONCLUSION: Circ_0010729 promotes H2O2-induced myocardial injury, and thus circ_001729 may be targeted as a potential therapy for H/R-induced myocardial injury.

[Simultaneous determination of 11 active components in Lonicera japonica flowers and leaves at different development stages by HPLC-DAD].

This study aims to develop an HPLC-DAD method for simultaneous determination of 11 components(6 phenolic acids and 5 iridoids) in Lonicera japonica flowers(LjF) and leaves(LjL), and compare the content differences of LjF at different development stages, LjL at different maturity levels, and between LjF and LjL. One-way ANOVA, principal component analysis(PCA), and orthogonal partial least-squares discriminant analysis(OPLS-DA) were employed to compare the content of the 11 components. The content of total phenolic acids, total iridoid glycosides, and total 11 components in LjF showed an overall downward trend with the development of flowers. The content of total phenolic acids, total iridoid glycosides, and total 11 components in young leaves were higher than those in mature leaves. The results of PCA showed that the samples at different flowering stages had distinguishable differences in component content. The VIP value of OPLS-DA showed that isochlorogenic acid A, chlorogenic acid, and secologanic acid were the main differential components of LjF at different development stages or LjL with different maturity levels. LjF and LjL have certain similarities in chemical composition while significant differences in component content. The content of total phenolic acids in young leaves was significantly higher than that in LjF at various development stages. The content of total iridoid glycosides in young leaves was similar to that in LjF before white flower bud stage. The total content of 11 components in young leaves was significantly higher than that in LjF at green flower bud stage, before and during completely white flower bud stage. LjL have great potential for development. Follow-up research on the pharmacodynamic equivalence of LjF and LjL(especially young leaves) should be carried out to speed up the development and application of LjL.

[Analysis of heavy metal pollution in Lonicerae Japonicae Flos and its health risk assessment].

In this study, the content of five heavy metals(Pb, Cd, As, Hg, and Cu) in 59 batches of Lonicerae Japonicae Flos(LJF) medicinal materials and pieces were determined by inductively coupled plasma mass spectrometry(ICP-MS). The health risk assessment was processed using the maximum estimated daily intake(EDI), target hazard quotients(THQ), and carcinogenic risks(CR) assessment models. With reference to the limit standard for heavy metal content in LJF specified in 2020 edition of Chinese Pharmacopoeia, five batches produced in Hebei were found to contain excessive Pb, and the remaining 54 batches met the specifications, with the unqualified rate of 8.47%. Comparative analysis of heavy metal content in LJF samples from three different producing areas, namely Shandong, Henan, and Hebei showed that the levels of Pb, As, and Hg in LJF from Hebei were significantly higher than those from Henan and Shandong. The samples produced in Shandong contained the highest content of Cd. The samples from Hebei contained the highest content of Cu while those from Shandong had the lowest content of Cu. As demonstrated by health risk assessment based on the EDI, THQ and CR models, these 59 batches of LJF samples did not cause significant health hazards for the exposed population, and there was no potential non-carcinogenic or carcinogenic risk. In conclusion, a few of LJF samples contained excessive heavy metals, so some measures, including controlling production environment, cultivating management mode, and optimizing processing methods, should be taken for ensuring the medication safety of LJF.