The chromosome-level genome and functional database accelerate research about biosynthesis of secondary metabolites in Rosa roxburghii.

Rosa roxburghii Tratt, a valuable plant in China with long history, is famous for its fruit. It possesses various secondary metabolites, such as L-ascorbic acid (vitamin C), alkaloids and poly saccharides, which make it a high nutritional and medicinal value. Here we characterized the chromosome-level genome sequence of R. roxburghii, comprising seven pseudo-chromosomes with a total size of 531 Mb and a heterozygosity of 0.25%. We also annotated 45,226 coding gene loci after masking repeat elements. Orthologs for 90.1% of the Complete Single-Copy BUSCOs were found in the R. roxburghii annotation. By aligning with protein sequences from public platform, we annotated 85.89% genes from R. roxburghii. Comparative genomic analysis revealed that R. roxburghii diverged from Rosa chinensis approximately 5.58 to 13.17 million years ago, and no whole-genome duplication event occurred after the divergence from eudicots. To fully utilize this genomic resource, we constructed a genomic database RroFGD with various analysis tools. Otherwise, 69 enzyme genes involved in L-ascorbate biosynthesis were identified and a key enzyme in the biosynthesis of vitamin C, GDH (L-Gal-1-dehydrogenase), is used as an example to introduce the functions of the database. This genome and database will facilitate the future investigations into gene function and molecular breeding in R. roxburghii.

NEW PREDICTIVE BIOMARKERS FOR SCREENING COVID-19 PATIENTS WITH RHABDOMYOLYSIS IN COMBINATION WITH CYSTATIN C.

ABSTRACT: Purpose: Cystatin C (CysC) has been linked to the prognosis of corona virus disease 2019 (COVID-19). The study aims to investigate a predictor correlated with CysC screening for poor prognosis in COVID-19 patients combined with skeletal muscle (SKM) impairment and rhabdomyolysis (RM). Methods: A single-center retrospective cohort analysis was carried out. Demographic information, clinical data, laboratory test results, and clinical outcome data were gathered and analyzed. Results: According to the inclusion and exclusion criteria, 382 patients were included in this study. The subjects were divided into three groups based on CysC tertiles. Multivariate analysis revealed that SaO 2 (hazard ratio [HR], 0.946; 95% confidence interval [CI], 0.906-0.987; P = 0.011), CysC (HR, 2.124; 95% CI, 1.223-3.689; P = 0.008), aspartate aminotransferase (AST) (HR, 1.009; 95% CI, 1.000-1.018; P = 0.041), and hypersensitive C-reactive protein (HR, 1.005; 95% CI, 1.000-1.010; P = 0.045) were significantly associated with survivals. The area under curve (AUC) in the model characterized by RM incidence was 0.819 (0.698-0.941), as shown by CysC receiver operating characteristic curves. LDH*CysC and AST*CysC had better predictive values than CysC and the best prediction for RM, with an AUC of 0.880 (0.796,0.964) for LDH*CysC ( P < 0.05, vs CysC) and 0.925 (0.878,0.972) for AST*CysC ( P < 0.05, vs CysC). Conclusion: CysC is an essential evaluation indicator for COVID-19 patients' prognosis. AST*CysC and LDH*CysC have superior predictive value to CysC for SKM, RM, and death, and optimal classification for RM.

Versatile bubble maneuvering on photopyroelectric slippery surfaces.

Contactless bubble manipulation with a high spatiotemporal resolution brings a qualitative leap forward in a variety of applications. Despite considerable advances, light-induced bubble maneuvering remains challenging in terms of robust transportation, splitting and detachment. Here, a photopyroelectric slippery surface (PESS) with a sandwich structure is constructed to achieve the versatile bubble manipulation. Due to the generated dielectric wetting and nonuniform electric field under the irradiation of near infrared (NIR) light, a bubble is subject to both the Laplace force and dielectrophoresis force, enabling a high-efficiency bubble steering. We demonstrate that the splitting, merging and detachment of underwater bubbles can be achieved with high flexibility and precision, high velocity and agile direction maneuverability. We further extend the capability of bubble control to microrobots for cargo transportation, micropart assembly and transmission of gear structures. We envision this robust bubble manipulation strategy on the PESS would provide a valuable platform for various bubble-involved processes, ranging from microfluidic devices to soft robotics.

Guidongnins I-J: Two New 6,7-seco-7,20-Olide-ent-kaurene Diterpenes with Unusual Structures from Isodon rubescens.

Two undescribed ent-kaurene diterpenes, named guidongnins I (1) and J (2), were isolated from the medicinal plant Isodon rubescens. Compound 1 was determined to contain an unprecedented 23 carbons in the skeleton by bearing an extra isopropyl group at C-17 out of the diterpenoid parent structure, and compound 2 was the first example of 6,7-seco-7,20-olide-ent-kaurenes with two fused-tetrahydrofuran rings formed between C-6 and C-19/C-20 through oxygen bridges. Their structures, including their absolute configurations, were determined using the analyses of the spectroscopic and X-ray diffraction data. Guidongnins I (1) and J (2) were assessed for their anti-cancer activities against the growth of various cancer cell lines, and 2 displayed cytotoxic potency against HepG2 at IC50 27.14 ± 3.43 µM.

Prognostic value of initial routine laboratory blood tests in patients with aneurysmal subarachnoid hemorrhage requiring mechanical ventilation: a retrospective cohort study.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) necessitating mechanical ventilation (MV) presents a serious challenge for intensivists. Laboratory blood tests reflect individual physiological and biochemical states, and provide a useful tool for identifying patients with critical condition and stratifying risk levels of death. This study aimed to determine the prognostic role of initial routine laboratory blood tests in these patients. Methods: This retrospective cohort study included 190 aSAH patients requiring MV in the neurosurgical intensive care unit from December 2019 to March 2022. Follow-up evaluation was performed in May 2022 via routine outpatient appointment or telephone interview. The primary outcomes were death occurring within 7 days after discharge (short-term mortality) or reported at time of follow-up (long-term mortality). Clinico-demographic and radiological characteristics, initial routine laboratory blood tests (e.g., metabolic panels and arterial blood gas analysis), and treatment were analyzed and compared in relation to mortality. Multivariable logistic and Cox regression analyses, with adjustment of other clinical predictors, were performed to determine independent laboratory test predictors for short- and long-term mortality, respectively. Results: The patients had a median age of 62 years, with a median World Federation of Neurosurgical Societies grade (WFNS) score of 5 and a median modified Fisher grade (mFisher) score of 4. The short- and long-term mortality of this cohort were 60.5% and 65.3%, respectively. Compared with survivors, non-survivors had more severe disease upon admission based on neurological status and imaging features and a shorter disease course, and were more likely to receive conservative treatment. Initial ionized calcium was found to be independently associate with both short-term [adjusted odds ratio (OR): 0.92; 95% confidence interval (CI): 0.86 to 0.99; P=0.020] and long-term mortality [adjusted hazard ratio (HR): 0.95; 95% CI: 0.92 to 0.99; P=0.010], after adjusting for potential confounders. Moreover, the admission glucose level was found to be associated only with short-term mortality (adjusted OR: 1.19; 95% CI: 1.06 to 1.34; P=0.004). Conclusions: Laboratory screening may provide a useful tool for the management of aSAH patients requiring MV in stratifying risk levels for mortality and for better clinical decision-making. Further study is needed to validate the effects of calcium supplementation and glucose-lowering therapy on the outcomes in this disease.

Efficient Passive Daytime Radiative Cooling by Hierarchically Designed Films Integrating Robust Durability.

Surfaces with efficient passive daytime radiative cooling (PDRC) are underpinned by maximizing both solar reflection and thermal radiation to the outer space at no additional energy cost. Despite notable progress, their practical applications are of great challenge due to their complicated fabrication processes, easy contamination and damage, and high costs. Herein, we fabricate a hierarchically designed passive daytime radiative cooling film (HPRF) comprising cost-effective Al2O3 particles and poly(dimethylsiloxane) (PDMS) via a simple phase separation method. The designed film possesses a high solar spectrum reflectance of ∼0.96 and a mid-infrared emittance of ∼0.95, achieving a ∼12.4 °C subambient cooling under direct solar irradiation. This excellent PDRC is due to the efficient Mie scattering of sunlight by hierarchical micro-/nanostructures and selected molecular vibrations of PDMS combined with the phonon polariton resonance of Al2O3 particles, respectively. Moreover, the designed HPRF is accompanied with robust durability endowed by superior self-cleaning, flexibility, and anti-ultraviolet radiation that can present substantial application promises of thermal management in various electronic devices and wearable products.

Acquired heat acclimation in rats subjected to physical exercise under environmental heat stress alleviates brain injury caused by exertional heat stroke.

BACKGROUND: Exertional heatstroke (EHS) is an emergency with a high mortality rate, characterized by central nervous system dysfunctions. This study aims to establish a Heat acclimation/acclimatization (HA) rat model in locomotion to recapitulate the physical state of human in severe environment of high temperature and humidity, and investigate the mechanism of organism protection in HA. (2) Methods: Wistar rats were exposed to 36 °C and ran 2 h/d for 21 days, acquired thermal tolerance test was conducted to assess the thermotolerance and exercise ability. Core temperature and consumption of water and food were observed. Expression of HSP70 and HSP90 of different tissues were determined by WB. Pathological structure of brain tissue was detected with HE staining. Proteomics was used to identify the differently expressed proteins in cerebral cortex of different groups. And key molecules were identified by RT-PCR and WB. (3) Results: HA rats displayed stronger thermotolerance and exercised ability on acquired thermal tolerance test. Brain water content of HA + EHS group reduced compared with EHS group. HE staining revealed slighter brain injuries of HA + EHS group than that of EHS. Proteomics focused on cell death-related pathways and key molecules Aquaporin 4 (AQP4) related to cell edema. Identification results showed HA increased AQP4, Bcl-xl, ratio of p-Akt/AKT and Bcl-xl/Bax, down-regulated Cleaved Caspase-3. (4) Conclusions: This HA model can ameliorate brain injury of EHS by reducing cerebral edema and cell apoptosis, offering experimental evidence for EHS prophylaxis.

An electrothermal platform for active droplet manipulation.

The smart control of droplet transport through surface structures and external fields provides exciting opportunities in engineering fields of phase change heat transfer, biomedical chips, and energy harvesting. Here we report the wedge-shaped slippery lubricant-infused porous surface (WS-SLIPS) as an electrothermal platform for active droplet manipulation. WS-SLIPS is fabricated by infusing a wedge-shaped superhydrophobic aluminum plate with phase-changeable paraffin. While the surface wettability of WS-SLIPS can be readily and reversibly switched by the freezing-melting cycle of paraffin, the curvature gradient of the wedge-shaped substrate automatically induces an uneven Laplace pressure inside the droplet, endowing WS-SLIPS the ability to directionally transport droplets without any extra energy input. We demonstrate that WS-SLIPS features spontaneous and controllable droplet transport capability to initiate, brake, lock, and resume the directional motion of various liquid droplets including water, saturated NaCl solution, ethanol solution, and glycerol, under the control of preset DC voltage (∼12 V). In addition, the WS-SLIPS can automatically repair surface scratches or indents when heated and retain the full liquid-manipulating capability afterward. The versatile and robust droplet manipulation platform of WS-SLIPS can be further used in practical scenarios such as laboratory-on-a-chip settings, chemical analysis and microfluidic reactors, paving a new path to develop advanced interface for multifunctional droplet transport.

Ultrasonic tweezer for multifunctional droplet manipulation.

Spatiotemporally controllable droplet manipulation is essential in diverse applications, ranging from thermal management to microfluidics and water harvesting. Despite considerable advances, droplet manipulation without surface or droplet pretreatment is still challenging in terms of response and functional adaptability. Here, a droplet ultrasonic tweezer (DUT) based on phased array is proposed for versatile droplet manipulation. The DUT can generate a twin trap ultrasonic field at the focal point for trapping and maneuvering the droplet by changing the position of the focal point, which enables a highly flexible and precise programmable control. By leveraging the acoustic radiation force resulting from the twin trap, the droplet can pass through a confined slit 2.5 times smaller than its own size, cross a slope with an inclination up to 80°, and even reciprocate in the vertical direction. These findings provide a satisfactory paradigm for robust contactless droplet manipulation in various practical settings including droplet ballistic ejection, droplet dispensing, and surface cleaning.

Bidirectional Underwater Drag Reduction on Bionic Flounder Two-Tier Structural Surfaces.

Engineering marvels found throughout the exclusive structural features of biological surfaces have given rise to the progressive development of skin friction drag reduction. However, despite many previous works reporting forward drag reduction where the bio-inspired surface features are aligned with the flow direction, it is still challenging to achieve bidirectional drag reduction for non-morphable surface structures. Inspired by the flounder ctenoid scales characterized by tilted, millimeter-sized oval fins embedded with sub-millimeter spikes, we fabricate a bionic flounder two-tier structural surface (BFTSS) that can remarkably reduce the forward skin friction drag by ηdr = 19%. Even in the backwards direction, where the flow is completely against the tilting direction of surface structures, BFTSS still exhibits a considerable drag reduction of ηdr = 4.2%. Experiments and numerical simulations reveal that this unique bidirectional drag reduction is attributed to synergistic effects of the two-tier structures of BFTSS. The array of oval fins can distort the boundary layer flow and mitigate the viscous shear, whilst the microscale spikes act to promote the flow separation to relieve the pressure gradient in the viscous sublayer. Notably, the pressure gradient relief effect of microscale spikes remains invariant to the flow direction and is responsible for the backward drag reduction as well. The bidirectional drag reduction of BFTSS can be extensively applied in minimizing the energy consumption of ships and underwater vessels, as well as in pipeline transport.

Gambogic Acid Lysinate-induced Cervical Cancer SiHa Cells Apoptosis in vitro and in vivo.

BACKGROUND: Surgical resection and chemotherapy are the primary treatment options for cervical cancer; however, efficacy of chemotherapy drugs is limited by drug resistance. There is an urgent need to find new compounds. Gambogic acid lysinate (GAL), a new compound made from gambogic acid and lysine, has good anti-tumor activity, however, the effect of GAL on cervical cancer remains undetermined. OBJECTIVE: The present study sought to explore the anti-tumor activity of GAL in SiHa cells. METHODS: Cell viability was detected by means of an MTT assay, a cell growth curve was drawn with Microsoft Excel 2010, the cell cycle and cell apoptosis were evaluated by flow cytometry, and Western blotting was employed to explore the mechanism of GAL. Additionally, the in vivo anti-tumor activity of GAL was studied through a xenograft tumor model in nude mice. RESULTS: GAL inhibited the proliferation of both SiHa cells (IC50 was 0.83 µmol/l and 0.77 µmol/l respectively for 48 h and 72 h) and HeLa cells (IC50 did not reach). In SiHa cells, GAL (1 and 2 µmol/l) inhibited cell proliferation and 2 µmol/l GAL could also induce cell apoptosis and decrease the number of S phase. Both 1 and 2 µmol/l GAL inhibited SiHa cells invasion and increased the number of G0/G1 phase. The results of Western blot assay demonstrated that P53 and P21 were involved in SiHa cells S phase arrest and BCL-2 and BAX were involved in SiHa cells apoptosis. In vivo study showed that the growth of SiHa cell xenograft tumors was inhibited via cell apoptosis induced by GAL (2.5 mg/kg body weight), however, GAL (2.5 mg/kg body weight) had no significant effect on weight gain of mice. CONCLUSION: GAL induced SiHa cells apoptosis by BCL-2 and BAX pathway and SiHa cells S phase arrest by P53 and P21 pathway in vitro and inhibited the growth of SiHa cell xenograft tumors.

Recent advances in superwetting materials for separation of oil/water mixtures.

Engineering surfaces or membranes that allow an efficient oil/water separation is highly desired in a wide spectrum of applications ranging from oily wastewater discharge to offshore oil spill accidents. Recent advances in biomimetics, manufacturing, and characterization techniques have led to remarkable progress in the design of various superwetting materials with special wettability. In spite of exciting progress, formulating a strategy robust enough to guide the design and fabrication of separating surfaces remains a daunting challenge. In this review, we first present an overview of the wettability theory to elucidate how to control the surface morphology and chemistry to regulate oil/water separation. Then, parallel approaches are considered for discussing the separation mechanisms according to different oil/water mixtures, and three separation types were identified including filtration, adsorption and other separation types. Finally, perspectives on the challenges and future research directions in this research area are briefly discussed.

Poly(vinyl alcohol)/sodium alginate polymer membranes as eco-friendly and biodegradable coatings for slow release fertilizers.

BACKGROUND: The use of slow release fertilizers (SRFs) is an effective approach for reducing agriculture cost, environmental and ecological issues simultaneously. The present study provides a series of poly(vinyl alcohol) (PVA)/sodium alginate (SA) polymer membranes as eco-friendly and biodegradable coatings for SRFs. Moreover, polymer-coated urea (PCU) granules were fabricated through coating the urea granules with the resulting membranes. Our first interest was to fabricate three membranes (PS1, PS2, PS3) of different PVA/SA weight ratios (9:1, 8:2, 7:3) using glutaraldehyde as a crosslinking agent, and crosslink the PS3 membrane with a CaCl2 solution further to obtain the PC3 membrane. The chemical properties and morphologies of the membranes were characterized. Second, the nitrogen release behavior of the PCU granules was measured and calculated, respectively. RESULTS: Crosslinking with glutaraldehyde made the PS1, PS2, PS3 membranes uniform and compact, whereas crosslinking with a CaCl2 solution formed an 'egg box' structure inside the PC3 membrane. PS3 membrane with the minimum PVA/SA weight ratio had the highest hydrophily (water uptake: 106.25%, water contact angle: 55.1o ), whereas PC3 membrane had the lowest hydrophily (water uptake: 21.57%, water contact angle: 67.3o ). The biodegradation ratios of the membranes were in the range 44-60% in 90 days, indicating that they had excellent biodegradability. The measured fractional release on the day 30 of the PCU granules ranged from 89.33% to 97.07%. The calculated nitrogen release behavior agreed well with the measured values. CONCLUSION: The resulting eco-friendly and biodegradable PVA/SA membranes are alternative coatings for SRFs. © 2022 Society of Chemical Industry.

[Exploring the mechanisms of ferroptosis in non-obstructive azoospermia based on bioinformatics and machine learning].

OBJECTIVE: To explor the potential mechanisms of ferroptosis involvement in non-obstructive azoospermia based on bioinformatics and machine learning methods. METHODS: To obtain disease-related datasets and ferroptosis-related genes, we utilized the GEO database and FerrDb database, respectively. Using the R software, the disease dataset was subjected to normalization, differential analysis, and GO and KEGG enrichment analysis. The differentially expressed genes from the disease dataset were then intersected with the ferroptosis-related genes to identify common genes. Core genes were selected using three machine learning algorithms, namely LASSO, SVM-RFE, and random forest. Further analysis included exploring immune infiltration correlation, predicting target drugs, and conducting molecular docking simulations. RESULTS: The differential analysis of the GSE45885 dataset yielded 1751 differentially expressed genes, while the GSE145467 dataset yielded 4358 differentially expressed genes. The intersection of these two gene sets resulted in a disease-related gene set consisting of 508 genes. Taking the intersection of the disease-related gene set and the ferroptosis-related gene set, we obtained 17 disease-related ferroptosis genes. After machine learning-based screening, three core genes were identified: GPX4, HSF1, and KLHDC3. CONCLUSION: The mechanism underlying the involvement of ferroptosis in non-obstructive azoospermia may be linked to the downregulation of GPX4, HSF1, and KLHDC3 expression. This finding provides a basis for subsequent in-depth mechanistic and therapeutic studies.

Design, Synthesis and Biological Evaluation of Lophanic Acid Derivatives as Antifungal and Antibacterial Agents.

In order to discover more promising antifungal and antibacterial agents, a series of new derivatives were designed and synthesized by structure modification based on the naturally occurring antimicrobial compound lophanic acid. The structures of all the target compounds were well characterized by spectroscopic data. The stereochemistry of these compounds was further determined through the X-ray diffraction analysis of 6a. The synthetic compounds were evaluated for their antimicrobial activities against filamentous fungi (T. rubrum, T. mentagrophytes), yeasts (C. neoformans, C. albicans) and Gram-positive and Gram-negative bacteria (MRSA, S. mutans, S. sobrinus, and E. coli). Among them, 3d and 3i are found as the most promising leads that showed potent inhibitory effects against all the tested fungal and bacterial strains except for E. coli. The presence of the C-20 carboxylic ester groups and the free hydroxy group at C-13 was found to be essential for the antifungal and antibacterial activities of the lophanic acid derivatives.

One-Step Fabrication of Hot-Water-Repellent Surfaces.

Hot-water repellency is of great challenge on traditional superhydrophobic surfaces due to the condensation of tiny droplets within the cavities of surface textures, which builds liquid bridges to connect the substrate and hot water and thus destroys the surface water-repellence performance. For the unique structural features and scales, current approaches to fabricate surfaces with hot-water repellency are always complicated and modified by fluorocarbon. Here, we propose a facile and fluorine-free one-step vapor-deposition method for fabricating excellent hot-water-repellent surfaces, which at room temperature even repel water droplets of temperature up to 90 °C as well as other normal-temperature droplets with surface tension higher than 48.4 mN/m. We show that whether the unique hot-water repellency is achieved depends on a trade-off between the solid-liquid contact time and hot-vapor condensation time, which determines the probability of formation of liquid bridges between the substrate and hot-water. Moreover, the designed surfaces exhibit excellent self-cleaning performance in some specific situations, such as oil medium, hot water and condensation environments. We envision that this facile and fluorine-free strategy for fabricating excellent hot-water-repellent surfaces could be valuable in popularizing their practical applications.

Designing Robust Two-Electron Storage Extended Bipyridinium Anolytes for pH-Neutral Aqueous Organic Redox Flow Batteries.

Bipyridinium derivatives represent the most extensively explored anolyte materials for pH-neutral aqueous organic redox flow batteries, and most derivatives feature two separate electron-transfer steps that cause a sharp decrease in cell voltage during discharge. Here, we propose a strategy to fulfill the concurrent two-electron electrochemical reaction by designing extended bipyridinium derivatives (exBPs) with a reduced energy difference between the lowest unoccupied molecular orbital of exBPs and the ß-highest occupied molecular orbital of the singly reduced form. To demonstrate, a series of exBPs are synthesized and exhibit a single peak at redox potentials of -0.75 to -0.91 V (vs standard hydrogen electrode (SHE)), as opposed to the two peaks of most bipyridinium derivatives. Cyclic voltammetry along with diffusion-ordered spectroscopy and rotating disk electrode experiments confirm that this peak corresponds to a concurrent two-electron transfer. When examined in full-flowing cells, all exBPs demonstrate one charge/discharge plateau and two-electron storage. Continuous galvanostatic cell cycling reveals the side reactions leading to capacity fading, and we disclose the underlying mechanism by identifying the degradation products. By prohibiting the dimerization/ß-elimination side reactions, we acquire a 0.5 M (1 M e-) exDMeBP/FcNCl cell with a high capacity of 22.35 Ah L-1 and a capacity retention rate of 99.95% per cycle.

Steerable drops on heated concentric microgroove arrays.

Guided drop transport is of great importance in various water and thermal management technologies. Unidirectional drop transport on a hot surface has been widely developed, but a bidirectional reversal is still challenging. Here, we report a steerable transport of drop impinging on heated concentric microgroove arrays, on which the directionality of drop transport is dictated by the drop boiling modes. In the transition boiling state, the driving force originated from the Laplace pressure difference rendered by the microgrooves, which enables the drop rebounding towards the center of curvature. While in the film boiling state, a net force towards the opposite side is generated between the grooves and the penetrated liquid, that drives the drop far away from the center of curvature. Our experimental and theoretical results uncover that the lateral displacement is controlled by both the Weber number and off-center distance. These findings strengthen our fundamental understanding of drop impact dynamics at high temperatures and are essential for effective cooling of hot-spot cores and drop sieving.

3,4-Seco-Isopimarane Diterpenes from the Twigs and Leaves of Isodon Flavidus.

Three isopimarane diterpenes [fladins B (1), C (2), and D (3)] were isolated from the twigs and leaves of Chinese folk medicine, Isodon flavidus. The chemical structures were determined by the analysis of the comprehensive spectroscopic data, and the absolute configuration was confirmed by X-ray crystallographic analysis. The structures of 1-3 were formed from isopimaranes through the rearrangement of ring A by the bond break at C-3 and C-4 to form a new δ-lactone ring system between C-3 and C-9. This structure type represents the first discovery of a natural isopimarane diterpene with an unusual lactone moiety at C-9 and C-10. In the crystal of 1, molecules are linked to each other by intermolecular O-H···O bonds, forming chains along the b axis. Compounds 1-3 were evaluated for their bioactivities against different diseases. None of these compounds displayed cytotoxic activities against HCT116 and A549 cancer cell lines, antifungal activities against Trichophyton rubrum and T. mentagrophytes, or antiviral activities against HIV entry at 20 µg/mL (62.9-66.7) µM. Compounds 1 and 3 did not show antiviral activities against Ebola entry at 20 µg/mL either; only 2 was found to show an 81% inhibitory effect against Ebola entry activity at 20 µg/mL (66.7 µM). The bioactivity evidence suggested that this type of compound could be a valuable antiviral lead for further structure modification to improve the antiviral potential.

Jianpi Qinghua Fomula alleviates insulin resistance via restraining of MAPK pathway to suppress inflammation of the small intestine in DIO mice.

BACKGROUND: Jianpi Qinghua Fomula (JPQHF), a clinically proven prescription,has been applied to cure insulin resistance(IR) and type 2 diabetes (T2DM) for more than 20 years. Here, we will unravel the underlying molecular mechanisms relevant to the therapeutic actions of JPQHF. METHODS: High-fat(HF)diet-induced obesity(DIO)mouse were established in our research, along with insulin resistance. After the administration of JPQHF 5 or 6 weeks, the parameters of the glucose and lipid metabolism were measured. Flow cytometry and Luminex were utilized to assess the inflammation in small intestine,whilst Western blot was used to determine the relative expression levels of the MAPK pathway-related proteins. The glucose and lipid transporter of small intestine was assessed by immunofluorescence and ELISA, and the expression of insulin signaling pathway was detected by Western blot. RESULTS: The metabolic phenotypes of DIO mouse were ameliorated after 6-week oral administration of JPQHF; Meanwhile,JPQHF downregulated levels of IL-1ß,IL-6, TNF-α and IFN-γ but upregulated the ratio of M2/M1 macrophages in the small intestine. The elevated expressions of p-P38 MAPK/P38 MAPK、p-JNK/JNK and p-ERK1/2/ERK1/2 were reversed by JPQHF. Moreover, JPQHF enhanced expression of PI3K,p-AKT/AKT, p-IRS1/ IRS1, p-IRS2/ IRS2 and apoB48 in small intestine, and facilitated the translocation of GLUT2 to the basal side of small intestine epithelial cells. CONCLUSION: JPQHF alleviates insulin resistance in DIO mice, and this effect may be associated with its restraining of inflammation of small intestine via attenuating MAPK pathway, and then diminishes small intestinal glucose and lipid absorption.