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Rheumatoid arthritis (RA) is an autoimmune disease that generally affects the joints. In the face of inflammation-induced cartilage and bone damage, RA treatment remains insufficient. While research evidence indicates that acupuncture can exert anti-inflammatory and analgesic effects, improve the joint function of RA patients, and delay the disease, data on whether it can promote RA repair are lacking. Findings from the present work demonstrated that both the antigen-induced arthritis (AIA) and collagen-induced arthritis (CIA) models can simulate joint swelling of RA. The AIA model was more stable than the CIA model, with a higher incidence of successful arthritis modeling. Moreover, the AIA mice model could simulate the signal molecules and related pathological processes of the autoimmune response in RA, as well as major pathways related to RA and antigen immune response mechanisms. Manual acupuncture (MA) at Zusanli (ST36) significantly improved paw redness and swelling, pain, and inflammatory cell infiltration in the joints in AIA mice. The therapeutic effect of MA on AIA is achieved primarily through the regulation of steroid hormone biosynthesis, cell metabolism, and tissue repair processes. MA at ST36 can increase the gene contents of tissue repair growth factors, including PEG3, GADD45A, GDF5, FGF5, SOX2, and ATP6V1C2 in the inflammatory side joints of AIA mice, as well as the gene expression of the anti-inflammatory cytokine IL-10. In conclusion, acupuncture may alleviate RA in the joints via modulating the tissue healing process.

Postharvest pathogens can affect a wide range of fresh fruit and vegetables, including grapes, resulting in significant profit loss. Isoquinoline alkaloids of Mahoniafortunei, a Chinese herbal medicine, have been used to treat infectious microbes, which might be effective against postharvest pathogens. The phytochemical and bioactive investigation of this plant led to the isolation of 18 alkaloids, of which 9 compounds inhibited the growth of Botrytiscinerea and 4 compounds against Penicilliumitalicum. The antifungal alkaloids could change the mycelium morphology, the total lipid content, and leak the cell contents of B.cinerea. Furthermore, the two most potent antifungal alkaloids, berberine (13) completely inhibited effect on gray mold of table grape at 512 mg L−1, while jatrorrhizine (18) exhibited an inhibition rate > 90% on grape rot at the same concentration, with lower cytotoxicity and residue than chlorothalonil, which suggested that ingredients of M.fortunei might be a low-toxicity, low-residue, eco-friendly botanical fungicide against postharvest pathogens. Graphical Abstract

Confining nano-bimetals in porous metal silicate materials could improve the stabiliy and facilitate electron and charge transfer in catalysis, demonstrating great potential to replace noble metal-based catalysts for industrial applications.

Phytochemical investigation on the roots ofAsparagus cochinchinensisled to the isolation of one new furostanol saponin, named 26-O-β-d-glucopyranosyl-22α-hydroxyl-(25R)-Δ5(6)-furost-3β,26-diol-3-O-α-l-rhamnopyranosyl-(1 → 2)-[β-d-glucopyranosyl-(1 → 4)-α-l-rhamnopyranosyl-(1 → 4)]-β-d-glucopyranoside (1), along with three known congeners (2‒4). The structure of new saponin was elucidated via comprehensive inspection of its HRMS and NMR spectral data as well as chemical technology, whereas those of known ones were identified by comparison of their NMR and MS spectral data with those reported in literatures. All isolated saponins were evaluated for their cytotoxic effects on two human liver (MHCC97H) and lung adenocarcinoma (H1299) cancer cells in vitro. Among them, both1and2showed significant cytotoxicity against above mentioned cell lines. Further studies revealed that these two saponins could significantly inhibit their proliferation of MHCC97H and H1299 cells.Graphic Abstract

Acupoint is the initial response site of acupuncture stimulus and also the source link of the effect onset of acupuncture. Acupuncture is a mechanical physical stimulus. How is the mechanical force of acupuncture transduced into neuroelectrical and biochemical signals at acupoint? How does the physiochemical information of acupoint launch acupuncture effect? All of these remain the common and crucial questions in the study of acupuncture effect mechanism. Physical changes are induced in the local tissue of acupoint by needling techniques, such as the deformation and displacement of muscle fibers, which may act on the nerve ending receptors and produce electroneurographic signals. Besides, these changes may activate the mechanosensitive ion channels of the cytomembrane in acupoint site. Through cellular signal transduction, the physical signals may be transformed into chemical ones to trigger the physiochemical coupling response of acupoint microenvironment. Eventually, acupuncture effect is generated via nerves and body fluids. "The mechanical force of acupuncture", through "the physiochemical transduction", promotes the body's perception and transmits acupuncture signals. It suggests that acupoint is the "transducer" in the physiochemical information coupling response of acupuncture.穴位是针刺刺激的初始应答部位，也是针刺起效的源头环节。针刺作为一种机械性物理刺激，其机械力在穴位如何转导为神经电信号和生物化学信号，穴位局部的理化信号如何启动针刺效应，是针刺作用原理研究中的共性、关键性源头问题。针刺手法引起穴位局部组织物理变化，如肌纤维的形变位移等，可作用于神经末梢感受器，产生神经电信号；也可激活穴区细胞膜上的机械敏感性离子通道，经细胞信号转导将物理信号转化为化学信号，触发穴位微环境理化耦合应答，通过神经和体液途径产生针刺效应。“针刺机械力”在穴位局部通过“理化换能”，促进机体感知并传递针刺信号，表明穴位是针刺物理化学信息耦合应答的“换能器”。.

Background. Agarwood has been used for centuries, especially for treatment of gastrointestinal diseases. Earlier studies of our laboratory suggested that agarwood alcohol extracts (AAEs) provided gastric mucosal protection. This study aims to investigate the ameliorative effect of AAEs on ethanol-induced gastric ulcers and its mechanism. Methods. Mice were given agarwood induced by the whole-tree agarwood-inducing technique alcohol extract (WTAAE, 0.71, 1.42, and 2.84 g/kg), wild agarwood induced by axe wounds alcohol extract (WAAE, 2.84 g/kg), and burning-chisel-drilling agarwood alcohol extract (FBAAE, 2.84 g/kg) orally, respectively. After 7 days’ pretreatment with AAEs, the gastric ulcers were induced by absolute ethanol. The ulcer index, gastric histopathology, biochemical parameters, and inflammatory proteins were evaluated. Results. Pharmacological results showed AAEs (1.42 and 2.84 g/kg) reduced the gastric occurrence and ulcer inhibition rates up to more than 60%. AAEs decreased the level of nitric oxide (NO) and increased glutathione (GSH) and superoxide dismutase (SOD) levels. Besides, AAEs decreased the levels of interleukin-1β (IL-1β) and interleukin-6 (IL-6), but the interleukin-10 (IL-10) was upregulated. The expressions of nuclear factor kappa B (NF-κB) and phosphorylated protein 38 (p-P38) were inhibited. The effect of WTAAE was better than that of FBAAE and similar to that of WAAE at the dose of 2.84 g/kg. Conclusions. These results demonstrate that agarwood alleviates the occurrence and development of gastric ulcers via inhibiting oxidation and inflammation.

Cartilage damage is the key pathological mechanism in the progressive development of osteoarthritis(OA). Slowing down cartilage damage and accelerating cartilage repair are strategies for effective treatment of OA. Acupuncture and moxibustion therapies are widely used in relieving symptoms of OA and have a protective effect on cartilage. In this paper, we reviewed the mechanisms of acupuncture and moxibustion underlying relieving cartilage damage from three aspects: 1) promoting chondrocyte homeostasis by inhibiting apoptosis and improving cellular autophagy, 2) regulating extracellular matrix (ECM) metabolism (inhibiting decomposition and promoting synthesis) by suppressing the release of inflammatory factors and the activity of proteolytic enzymes, and 3) improving OA microenvironment by reducing the number of macrophagocyte 1 (M1) and increasing the ratio of M2/M1 in the local inflammatory locus. In addition, most studies on the mechanisms of acupuncture and moxibustion underlying remission of OA focus on the improvement of pathological changes, such as joint histopathology, cartilage morphology, synovial inflammatory reaction and infiltration, subchondral bone remodeling, etc., thus, the exact functions of acupuncture and moxibustion in ameliorating cartilage injury remain unknown. In view of the important role of mitochondrial dysfunction in promoting OA development and cartilage damage and the current use of tissue engineering methods of chondrocytes and mesenchymal stem cells to repair articular cartilage injury, it is highly recommended that future studies should pay more attention to these aspects.软骨损伤是骨关节炎(OA)进行性发展的关键病理机制。减缓软骨损伤, 加速软骨修复是治疗OA的有效策略。针灸广泛用于OA的治疗, 具有软骨保护作用。本文从软骨细胞稳态、细胞外基质代谢以及OA微环境3个方面, 就针灸抑制软骨损伤的机制进行综述, 并提出线粒体内源性途径及外泌体工程作为针灸治疗OA的研究方向, 可为后续研究提供参考。.

Extracellular vesicles are tiny lipid bilayer-enclosed membrane particles, including apoptotic bodies, micro vesicles, and exosomes. Organisms of all life forms can secrete extracellular vesicles into their surrounding environment, which serve as important communication tools between cells and between cells and the environment, and participate in a variety of physiological processes. According to new evidence, plant extracellular vesicles play an important role in the regulation of transboundary molecules with interacting organisms. In addition to carrying signaling molecules (nucleic acids, proteins, metabolic wastes, etc.) to mediate cellular communication, plant cells External vesicles themselves can also function as functional molecules in the cellular microenvironment across cell boundaries. This review introduces the source and extraction of plant extracellular vesicles, and attempts to clarify its anti-tumor mechanism by summarizing the current research on plant extracellular vesicles for disease treatment. We speculate that the continued development of plant extracellular vesicle-based therapeutic and drug delivery platforms will benefit their clinical applications.

The endoplasmic reticulum-localized DnaJ family 3B (ERdj3B), is a component of the stromal cell-derived factor 2 (SDF2)–ERdj3B–binding immunoglobulin protein (BiP) chaperone complex, which functions in protein folding, translocation, and quality control. We found that ERdj3B mutations affected integument development in the Ler ecotype but not in the Col-0 ecotype of Arabidopsis (Arabidopsis thaliana). Map-based cloning identified the ERECTA (ER) gene as a natural modifier of ERdj3B. The double mutation of ERdj3B and ER caused a major defect in the inner integument under heat stress. Additional mutation of the ER paralog ERECTA-LIKE 1 (ERL1) or ERL2 to the erdj3b er double mutant exacerbated the defective integument phenotype. The double mutation of ER and SDF2, the other component of the SDF2–ERdj3B–BiP complex, resulted in similar defects in the inner integument. Furthermore, both the protein abundance and plasma membrane partitioning of ER, ERL1, and ERL2 were markedly reduced in erdj3b plants, indicating that the SDF2–ERdj3B–BiP chaperone complex might control the translocation of ERECTA-family proteins from the endoplasmic reticulum to the plasma membrane. Our results suggest that the SDF2–ERdj3B–BiP complex functions in ovule development and the heat stress response in coordination with ERECTA-family receptor kinases.

Glutamate excitotoxicity in cerebral ischemia/reperfusion is an important cause of neurological damage. The aim of this study was to investigate the mechanism of Na+, K+-ATPase (NKA) involved in l ow concentration of ouabain (Oua, activating NKA)-induced protection of rat cerebral ischemia-reperfusion injury. The 2,3,5-triphenyltetrazolium chloride (TTC) staining and neurological deficit scores (NDS) were performed to evaluate rat cerebral injury degree respectively at 2 h, 6 h, 1 d and 3 d after reperfusion of middle cerebral artery occlusion (MCAO) 2 h in rats. NKA α1/α2 subunits and glutamate transporter-1 (GLT-1) protein expression were investigated by Western blotting. The cerebral infarct volume ratio were evidently decreased in Oua group vs MCAO/R group at 1 d and 3 d after reperfusion of 2 h MCAO in rats (*p ＜ 0.05 ). Moreover, NDS were not significantly different (p ＞ 0.05 ). NKA α1 was decreased at 6 h and 1 d after reperfusion of 2 h MCAO in rats, and was improved in Oua group. However, NKA α1 and α2 were increased at 3 d after reperfusion of 2 h MCAO in rats, and was decreased in Oua group. GLT-1 was decreased at 6 h, 1 d and 3 d after reperfusion of 2 h MCAO in rats, and was improved in Oua group. These data indicated that l ow concentration of Oua could improve MCAO/R injury through probably changing NKA α1/α2 and GLT-1 protein expression, then increasing GLT-1 function and promoting Glu transport and absorption, which could be useful to determine potential therapeutic strategies for patients with stroke. Low concentration of Oua improved rat MCAO/R injury via NKA α1/α2 and GLT-1.

Porous metal silicate (PMS) material PMS-11, consisting of uniformly distributed multi-metallic species inside the pores, is synthesized by using a discrete multi-metal coordination complex as the template, demonstrating high catalytic activity and selectivity in hydrogenation of halogenated nitrobenzenes by synergistically activating different reactant molecules via Ni and Co transition metal centers, while GdIII Lewis acid sites play a role in tuning the catalytic properties.

A bacterial strain designated NYYP31T was isolated from the leaves of an annual halophytes, Suaeda corniculata Bunge, collected from the southern edge of the Gurbantunggut desert, north-west China. Strain NYYP31T was Gram-staining negative, strictly aerobic, rod-shaped, non-motile, and non-spore-forming. Growth was observed at 4–42 °C, at pH 5.0–10.0, in the presence of up to 8% (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences and coding sequences of 92 protein clusters showed that strain NYYP31T should be assigned to the genus Sphingobacterium. 16S rRNA gene sequence similarity analysis showed that strain NYYP31T was most closely related to the type strain of Sphingobacterium daejeonense (97.9%) and Sphingobacterium lactis (97.7%). The predominant isoprenoid quinone was MK-7. The major fatty acids were identified as iso-C15:0, iso-C17:0 3-OH and summed feature 3 (C16:1 ω7c and/or C16:1 ω6c). The polar lipids were phosphatidylethanolamine, two unidentified phospholipids, three unidentified lipids, three unidentified amino phospholipids, and two unidentified glycolipids. The genomic DNA G + C content was 36.4 mol%. The average nucleotide identity (ANI) values for strain NYYP31T to the type strains of S. daejeonense and S. lactis were 77.9 and 74.1%, respectively, which were below the cut-off level (95–96%) for species delineation. Based on the above results, strain NYYP31T represents a novel species of the genus Sphingobacterium, for which the name Sphingobacterium endophyticum sp. nov. is proposed. The type strain is NYYP31T (= CGMCC 1.16979T = NBRC 114258T).

Agarwood is a traditional medicine used for treating some diseases, including painful and ischemic diseases. This study was carried out to investigate the potential cardioprotective effect of the whole-tree agarwood-inducing technique-produced agarwood alcohol extract (WTAAE) on isoproterenol- (ISO-) induced myocardial ischemia (MI) in rats and explore the underlying molecular mechanisms. Compared to the MI group, WTAAE pretreatment significantly improved ST wave abnormal-elevation, mitigated myocardial histological damage; decreased creatinine kinase (CK), lactate dehydrogenase (LDH), alanine transaminase (ALT), and aspartate transaminase (AST) levels; reduced hydrogen peroxide (H2O2) and lipid peroxide (LPO) production; and increased total antioxidant capacity (T-AOC) and catalase (CAT) activities. Moreover, agarwood alcohol extracts (AAEs) markedly enhanced the mRNA levels of Nrf2-ARE pathway, and Bcl-2 reduced the apoptotic Bax family mRNA expressions. In addition, the effect of WTAAE was greater than that of wild agarwood alcohol extract (WAAE) and burning-chisel-drilling agarwood alcohol extract (FBAAE). All of these data indicate that WTAAE exerted the protective effects of MI, and its mechanism was associated with upregulating Nrf2-ARE and suppressing Bcl-2 pathways.

In this paper we study the complete space-like λ-surfaces in the three dimensional Minkowski space $$ℝ_1^3$$. As the result, we obtain a complete classification theorem for all the complete space-like λ-surfaces $$x:{M^2} \to ℝ_1^3$$ with the second fundamental form of constant length. This is a natural extension to the λ-surfaces in $$ℝ_1^3$$ of a recent interesting classification theorem by Cheng and Wei for λ-surfaces in the Euclidean space ℝ3.

Two naphthoquinone-derived heterodimers with unprecedented carbon skeletons, eleucanainones A (1) and B (2), were isolated from the bulbs of Eleutherine americana. Their structures were elucidated ...

2-(2-Phenylethyl)chromone derivatives are regarded as key components in agarwood. An oxygen-containing heterocycle with a benzoannelated γ-pyrone moiety form the bioactive core of 2-(2-phenylethyl)chromones. With different substituents and positions, 2-(2-phenylethyl)chromone derivatives exhibit diverse biological properties, such as antioxidant, antimicrobial, neuroprotective, anti-inflammatory, and acetylcholinesterase inhibitory activities. In this review, we summarized the studies (from January 1976 to September 2021) on phytochemistry, bioactivity and quality control of 2-(2-phenylethyl)chromones. These studies aimed to clarify the chemical specificity, diversity and structure-activity relationship of 2-(2-phenylethyl)chromones. In addition, we assumed that diverse factors such as tree species, induction methods and formation time contribute to the chemical diversity of 2-(2-phenylethyl)chromones. Furthermore, this review contends that different types of 2-(2-phenylethyl)chromones should be utilized in the quality control methods of agarwood.

Metal-halide perovskite solar cells (PSCs) have attracted considerable attention during the past decade. However, due to the existence of non-radiative recombination losses, the best power conversion efficiency (PCE) is still lower than the theoretical limit defined by Shockley-Queser theory. In this work, we investigate 1,2,3-oxathiazin-4(3h)-one, 6-methyl-2,2-dioxide (acesulfame potassium, abbreviated as AK) as a additional dopant for the 2,2′,7,7′-tetrakis(N,N-di-p-methoxyphenyl-amine)-9,9′-spirobifluorene (Spiro-OMeTAD) and fabricate PSCs in the air. It is found that 12 mol% fraction of AK relative to lithium bis((trifluoromethyl)sulfonyl)-amide (Li-TFSI) reduces the non-radiative recombination from 86.05% to 69.23%, resulting in an average 0.08 V of Voc enhancement. The champion solar cell gives a perovskite solar cells up to 21.9% and over 84% retention of the initial value during 720 h aging in dry air with 20%–30% humidity.

A bacterial strain, designated YZGR15T, was isolated from the root of an annual halophyte Suaeda aralocaspica, collected from the southern edge of the Gurbantunggut desert, north-west PR China. Cells of the isolate were Gram-stain-positive, facultatively anaerobic, irregular rods. Growth occurred at 4–42 °C (optimum, 30–37 °C), at pH 6.0–9.0 (optimum, pH 7.0–7.5) and in the presence of 0–9 % (w/v) NaCl (optimum, 2–5 %). Phylogenetic analysis using 16S rRNA gene sequences indicated that strain YZGR15T showed the highest sequence similarity to Sanguibacter keddieii (98.27 %), Sanguibacter antarcticus (98.20 %) and Sanguibacter inulinus (98.06 %). Results of genome analyses of strain YZGR15T indicated that the genome size was 3.16 Mb, with a genomic DNA G+C content of 71.9 mol%. Average nucleotide identity and digital DNA–DNA hybridization values between strain YZGR15Tand three type strains were in the range of 76.5–77.8 % and 20.0–22.2 %, respectively. Analysis of the cellular component of strain YZGR15T revealed that the primary fatty acids were anteiso-C15 : 0, C16 : 0, C14 : 0 and iso-C16 : 0 and the polar lipids included diphosphatidylglycerol, phosphatidylglycerol, three unidentified phospholipids and two unidentified glycolipids. The cell-wall characteristic amino acids were glutamic acid, alanine and an unknown amino acid. The whole-cell sugars for the strain were mannose, ribose, rhamnose, glucose and an unidentified sugar. The predominant respiratory quinone was MK-9(H4). Based on the results of genomic, phylogenetic, phenotypic and chemotaxonomic analyses, strain YZGR15T represents a novel species of the genus Sanguibacter , for which the name Sanguibacter suaedae sp. nov. is proposed. The type strain is YZGR15T (=CGMCC 1.18691T=KCTC 49659T)

Background: Colon adenocarcinoma (COAD), a type of colon cancer, is among the most common malignant diseases afflicting people globally. Heat shock protein family, including HSPA8, are involved in tumor progression in numerous human cancers, however the association between HSPA8 and COAD has not been explored.Methods: RNA sequencing data and clinical characteristics from TCGA and GTEx, as well as protein data from CPTAC were obtained for analysis of HSPA8 expression in COAD. Furthermore, functional enrichment analysis of HSPA8-related differentially expressed genes (DEGs) was performed via GO/KEGG, immune infiltration analysis, and protein-protein interaction (PPI) network. In addition, the clinical significance of HSPA8 was analyzed by Kaplan-Meier Cox regression and prognosis assessment. R package was employed to analyze incorporated studies.Results: Compared with normal samples, the expression of HSPA8 increased remarkably in various tumors, including COAD, Moreover, high HSPA8 expression was associated with good prognosis in COAD, as well as subgroups with male, T2-T4 stage, no lymphatic and perineural invasion. (P < 0.05). High HSPA8 was a prognostic factor in Cox regression analysis. The diagnostic efficacy of HSPA8 in COAD analyzed by ROC (AUC: 0.889). Furthermore, a total of 3321 DEGs were identified between the high- and the low-expression group, of which 9 genes were up-regulated and 3312 genes were down-regulated.Conclusions: High HSPA8 expression is a potential biomarker for favorable outcomes in COAD. the results might provide clues and guidance for developing novel diagnosis, targeted therapy and prognosis of HSPA8 in COAD.

Objectives Microbiota dysbiosis in inflammatory bowel disease (IBD) has been widely reported. The gut microbiota connect diet to the metabolism by producing small molecules via diverse metabolic pathways. In this study we aimed to investigate the dietary preferences of IBD patients, and to explore the interactions among gut microbiota composition, dietary components, and metabolites in relation to IBD. Methods Dietary preferences of IBD patients (including those with ulcerative colitis [UC] and Crohn's disease [CD]) and health controls were investigated, and their gut microbiota were analyzed using 16S rRNA gene sequencing and metagenomic analyses of fecal and biopsy samples. The metabolite profiles of the samples were then analyzed using gas and liquid chromatography-mass spectrometry analyses. Results The daily intake of folic acid, niacin, vitamins C and D, calcium, and selenium differed significantly between patients with IBD and healthy controls. A decrease in long-chain (such as arachidic, and oleic acid) and medium-chain fatty acids (sebacic acid and isocaproic acid) as well as bile acid was observed in patients with IBD. Compared with healthy controls, 22 microbial species (including Sulfolobus acidocaldarius, and Clostridium clostridioforme CAG132) in the UC group and 37 microbial species (such as Bacteroides fragilis and Fusobacterium nucleatum) in the CD group were found to be correlated to diet and metabolites. Bacteroides fragilis was enriched in patients with IBD and associated with multi-nutrients, and 21 metabolites including 25-hydroxyvitamin D3 and taurolithocholic acid. Conclusions This study provides an interaction network to identify key micronutrients, microbiota components and metabolites that contribute to IBD.

A “smart” molecular imprinted photonic crystal (MIPC) sensor has been developed based on the combination of photonic crystal (PC) and molecular imprinting technique (MIT). It can give rise to readable optical signals and color changes upon sensing benzocaine with detection limit of 16.5 μg/ml. In fish sample detection, the developed MIPC sensor shows satisfied result accuracy with HPLC. With the advantage of satisfactory specificity, rapid responsiveness and excellent recoverability, this MIPC material shows great potential towards on-site screening and visual detection of trace benzocaine in real sample.

Silicon carbide (SiC) has good chemical resistance, excellent mechanical properties, thermal conductivity, especially in extreme conditions of application, and has proved to be a very promising electromagnetic absorption material. However, single silicon carbide cannot meet the increasing demand for high performance of absorbing materials. It has become an important research direction to combine it with other absorbing materials to improve its absorbing performance. In this study, a composite absorber material was prepared by 50 wt.% micron-sized beta-silicon carbide (β-sic) powder, mixed with a 0.2 wt.% multiwalled carbon nanotubes (MWCNTs) and 50 wt.% polyurethane (PU) substrate. The mixture was stirred and deaerated to form a slurry, and sprayed onto synthetic fabric. The results showed that the composite material was flexible, with a thickness of less than 2 mm and favorable adhesion. The results obtained by reflection graph of the radar waves, indicated that the return loss within the X-band range (8–12 GHz) was less than −40 dB, indicating favorable radar wave absorption. Therefore, composite materials could thus be used successfully as radar wave absorbers, and was suitable for stealth materials in “asymmetric warfare”.

Acute lung injury (ALI), a severe respiratory disorder, frequently develops into acute respiratory distress syndrome (ARDS) without timely treatment and scores highly in terms of morbidity and mortality rates. Fritillaria hupehensis is a famous traditional Chinese medicine with antitussive, expectorant and anti-asthmatic effect. Here, the effects of F. hupehensis extracts on lipopolysaccharide (LPS)-induced ALI mice were evaluated for the first time. We showed ethyl acetate fraction (EAF) significantly reduced the leukocytes and neutrophils of bronchoalveolar lavage fluid (BALF) and the lung index as well as pro-inflammatory cytokines (TNF-α and IL-6) of lung homogenates but increasing the anti-inflammatory cytokines (IL-4 and IL-10). Additionally, the alleviation of EAF treatment on lung injury was verified through histopathological observations. Subsequent phytochemical investigation on bioactive fraction led to isolation of 17 compounds including two new, in which compounds 2, 5 and 6 exhibited better anti-inflammatory effect on LPS-induced 16 human airway epithelial (16HBE) cells model by inhibiting the production of CRP and PCT. Furthermore, compound 2 suppressed the LPS-induced upregulation of proteins containing p-p65, COX-2, Caspase-1 and IL-18. In summary, F. hupehensis alleviating LPS-induced ALI in mice may be associated with the anti-inflammatory activity of steroidal alkaloids by suppressing the NF-κB-regulated pro-inflammatory proteins.

As recorded, agarwood has the function of improving qi reception and relieving asthma, but the underlying mechanism is unclear and rarely reported. Therefore, this study explored the anti-asthmatic effect of the alcohol extract of agarwood produced by the whole-tree agarwood-inducing technique(Agar-Wit) in the asthma mouse model induced by intraperitoneal injection of ovalbumin(OVA) + Al(OH)_3 combined with intranasal administration of OVA and the mechanism, and compared the anti-asthmatic effects of agarwood induced with different methods. Firstly, the anti-inflammatory and anti-asthmatic effects of Agar-Wit agarwood in mice were evaluated based on the asthma frequency, lung tissue injury, and peripheral inflammatory white blood cell(WBC) count and eosinophil count. Then, the levels of interleukin-1β(IL-1β), IL-17, and IL-10 in serum of mice were detected by enzyme-linked immunoassay(ELISA) and the expression of inflammation-and apoptosis-related genes in tissues was measured by reverse transcription polyme-rase chain reaction(RT-PCR) so as to preliminarily explore the anti-asthmatic mechanism. RESULTS:: showed that the alcohol extract of Agar-Wit agarwood significantly reduced asthma frequency, relieved pathological injury, improved peripheral WBC count and eosinophil count, decreased the levels of inflammatory cytokines IL-1β and IL-17, elevated the level of anti-inflammatory cytokine IL-10, and down-regulated the mRNA expression of IL-1 R, tumor necrosis factor receptor R(TNFR), nuclear transcription factor-kappa B(NF-κB), Bax, and caspase 3, but had no significant influence on the expression of high-mobility group box 1(HMGB1) protein, caspase 8, and Bcl-2. The effect of Agar-Wit agarwood alcohol extract was better than that of wild agarwood alcohol extract and alcohol extract of agarwood induced with the burning-chisel-drilling method at the same dose. In conclusion, Agar-Wit agarwood can significantly alleviate inflammation and asthma, which is related to its anti-inflammation and anti-apoptosis activity.

Eight undescribed 3,4-seco-norlabdane diterpenoids, callnudoids A-H, as well as two known analogues were isolated from the leaves of Callicarpa nudiflora. The structures were elucidated using spectroscopic methods and were compared with published NMR spectroscopic data. The absolute configurations of callnudoids D and E were defined based on ECD data or single-crystal X-ray diffraction. Callnudoids A-C are the highly modified labdane diterpenoids featuring rearranged 3,4-seco-ring and the formation of an undescribed cyclohexene moiety via C2-C18 cyclization. They only contain 15 carbon atoms on the carbon skeleton. Callnudoid D represents the unusual 3,4-seco-15,16-norlabdane diterpenoid with C13-C17 cyclization, and a putative biosynthesis pathway for callnudoids A, B, D, and E was proposed. All compounds were evaluated for their anti-inflammatory activities by inhibiting the lipopolysaccharide (LPS)-induced nitric oxide (NO) released in RAW264.7 cells; callnudoids A-E and H, and methylcallicarpate obviously inhibited pro-inflammatory cytokines TNF-α and IL-1β in a dose-dependent manner.

In recent years, the T-cell therapy and immune checkpoint inhibitors toward CTLA-4 and PD-1/PD-L1 axis antibody therapy have acquired encouraging success. However, most of patients were still not benefited with lots of troubles, such as low penetration of tissues/cells, strong immunogenicity and cytokine release syndrome, and long manufacturing process and expensive costs. By contrast, the immune-modulating small molecules possessed natural advantages to overcome these obstacles and might achieve greater success.Exploring the potent immune-modulating natural small molecules and revealing what kinds of molecules or structures with the immunomodulatory activity against cancers.A novel non-cytotoxic T-cell immunomodulating screening model was used to identify the cytotoxic/selective/immunomodulatory bioactivity for 148 natural steroidal saponins. The structure-activity relationships (SARs) research was used to reveal the key groups for immunomodulation/cytotoxicity/selectivity. The negative selection was used to isolate and purify the T-cell. The cell viability assay was used to measure the anti-cancer effect in vitro. The ELISA assay was used to detect the cytokines for IL-1β, IL-6, TNF-α, IFN-γ, IL-12, perforin and granzyme B (GZMB). The western blotting assay was used to research the immunomodulatory mechanism. The siRNA knockdown was used to generate the IFN-γ resistant melanoma cells. The NOG immune-deficient mice were used to evaluate the anti-tumor efficacy in vivo. The peripheral blood samples from 10 cancer patients were used to detect the broad population anti-tumor efficacy.It was reported that the correlation among structures and immunomodulation/ cytotoxicity/selectivity, in which opening ring-F with 26-O-glucopyranosyl, disaccharide and trisaccharide chains at C-3, steric hindrance and polarity of C-22 were key immunomodulatory groups. Moreover, taccaoside A was identified as the most potent candidate against cancer cells, including non-small cell lung cancer, triple negative breast cancer, and the IFN-γ resistant melanoma, partly through enhancing T lymphocyte mTORC1-Blimp-1 signal to secrete GZMB. Besides, 10 patients derived T-cell also would be modulated against cancer cells in vitro. Moreover, the overall survival was great extended (140 days vs 93 days) with nearly 100% tumor burden disappearance (0 mmThis work demonstrated one possibility for this concerned purpose, and identified a potent immune-modulating natural molecule taccaoside A, which might contribute to cancer immunotherapy in future.

A self-nanoemulsifying drug delivery system (SNEDDS) was developed to enhance the absorption of heparin after oral administration, in which heparin was compounded with phospholipids to achieve better fat solubility in the form of heparin-phospholipid (HEP-Pc) complex. HEP-Pc complex was prepared using the solvent evaporation method, which increased the solubility of heparin in n-octanol. The successful preparation of HEP-Pc complex was confirmed by differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, NMR, and SEM. A heparin lipid microemulsion (HEP-LM) was prepared by high-pressure homogenization and characterized. HEP-LM can enhance the absorption of heparin after oral administration, significantly prolong activated partial thromboplastin time (APTT) and thrombin time (TT) in mice, and reduce fibrinogen (FIB) content. All these outcomes indicate that HEP-LM has great potential as an oral heparin formulation.

Wild Chi-Nan agarwood is regarded as the highest quality agarwood from Aquilaria spp. However, the comprehensive research on chemical composition of wild Chi-Nan agarwood is limited. An integrated strategy using SHS-GC-MS and UPLC-Q/Tof-MS was applied to explore the phytochemical characteristics of a kind of agarwood induced from a newly identified germplasm of Chi-Nan A. sinensis. Progenesis QI and MS-Dial were used to preprocess the UPLC-Q/Tof-MS and GC-MS raw data, respectively. Principle component analysis (PCA) and orthogonal partial least squares to latent structure-discriminant analysis (OPLS-DA) models were built to discriminate Chi-Nan agarwood from ordinary agarwood and to screen potential distinguishing components between them. In this study, we clarified the distinguishing differences between Chi-Nan agarwood and ordinary agarwood. The difference is mainly manifested in the average contents of 2-(2-phenylethyl)chromone and 2-[2-(4′-methoxybenzene)ethyl]chromone, which are 170 and 420 times higher in Chi-Nan agarwood than in ordinary agarwood, respectively, while the contents of 5,6,7,8-diepoxy-2-(2-phenylethyl)chromones(DEPECs), 5,6-epoxy-2-(2-phenylethyl)chromones(EPECs), and 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromones(THPECs) such as agarotetrol are extremely low. The content of the main sesquiterpenes in Chi-Nan agarwood was higher than that in ordinary agarwood, especially in regard to guaiane and eudesmane derivatives. In addition, there were significant differences in the contents of low-molecular-weight aromatic compounds such as 2-methyl-4H-1-benzopyran-4-one, 4-methoxybenzaldehyde, and 2-hydroxybenzaldehyde between Chi-Nan agarwood and ordinary agarwood. All the mentioned main chemical characteristics of this new Chi-Nan agarwood were coincident with those of the rare wild Chi-Nan agarwood from A. malaccensis, A. sinensis, and A. crassna. We reported differences in 2-(2-phenylethyl)chromones, sesquiterpenes, and low-molecular-weight aromatic compounds between Chi-Nan agarwood and ordinary agarwood from A. sinensis for the first time; it is necessary to evaluate the agarwood from the new-found Chi-Nan germplasm.

With the increasing number of vehicles, it is more and more important to monitor the concentration of automobile exhaust gas. In order to detect the concentration of main gas components in exhaust gas, a set of automobile exhaust simulation detection device based on photoacoustic spectroscopy technology was designed by using laser as the light source, combined with the self-designed photoacoustic cell and gas distribution system. The system adopts wavelength modulation technology, which effectively overcomes the interference and influence of traditional mechanical chopping modulation. The experimental results show that the system can detect different concentrations of CO, NO and NO2 with stable operation, which can meet the requirements of vehicle exhaust detection.

Glutamate excitotoxicity in cerebral ischemia/reperfusion is an important cause of neurological damage. The aim of this study was to investigate the mechanism of Na+, K+-ATPase (NKA) involved in l ow concentration of ouabain (Oua, activating NKA)-induced protection of rat cerebral ischemia-reperfusion injury. The 2,3,5-triphenyltetrazolium chloride (TTC) staining and neurological deficit scores (NDS) were performed to evaluate rat cerebral injury degree respectively at 2 h, 6 h, 1 d and 3 d after reperfusion of middle cerebral artery occlusion (MCAO) 2 h in rats. NKA α1/α2 subunits and glutamate transporter-1 (GLT-1) protein expression were investigated by Western blotting. The cerebral infarct volume ratio were evidently decreased in Oua group vs MCAO/R group at 1 d and 3 d after reperfusion of 2 h MCAO in rats (*p ＜ 0.05 ). Moreover, NDS were not significantly different (p ＞ 0.05 ). NKA α1 was decreased at 6 h and 1 d after reperfusion of 2 h MCAO in rats, and was improved in Oua group. However, NKA α1 and α2 were increased at 3 d after reperfusion of 2 h MCAO in rats, and was decreased in Oua group. GLT-1 was decreased at 6 h, 1 d and 3 d after reperfusion of 2 h MCAO in rats, and was improved in Oua group. These data indicated that l ow concentration of Oua could improve MCAO/R injury through probably changing NKA α1/α2 and GLT-1 protein expression, then increasing GLT-1 function and promoting Glu transport and absorption, which could be useful to determine potential therapeutic strategies for patients with stroke. Low concentration of Oua improved rat MCAO/R injury via NKA α1/α2 and GLT-1.

To identify the prominent molecular signaling in acupoints and explore their roles in initiating the analgesia effect of manual acupuncture (MA).A three-step study was conducted, the experiment 1 was a genome-wide analysis of the tissue at acupoint Zusanli (ST 36), including 12 Wistar rats which were divided into control, control+MA1, and control+MA7 groups. In the experiment 2, the paw withdrawal latency (PWL), immunohistochemistry and Western blot analysis of phospho-nuclear factor kappa B (NFκB) p65 (p-p65), phospho-NFκB p50 (p-p50) at ST 36 were performed on rats of saline, saline+MA, and complete Freund's adjuvant (CFA)+MA groups (n=6). In experiment 3, 24 rats were divided into saline+DMSO, CFA+DMSO, CFA+DMSO+MA, and CFA+BAY 11-7082+MA groups, the PWL and immunofluorescence assay of NFκB p65 at ST 36 was conducted.(1) The gene: inhibitor of NFκB (Nfkbia), interleukin-1β (Il1b), interleukin-6 (Il6), chemokine c-x-c motif ligand 1 (Cxcl1), monocyte chemoattractant protein-1 (MCP-1/Ccl2) expressions in the control+MA7 group were significantly increased (P0.05 or P0.01), and the expression of NFκB p65 (Rela), NFκB p50 (Nfkb1) were increased in the control+MA7 group (P0.05). (2) CFA+MA groups showed increased PWL from day 1 to 7 (P0.01 vs. CFA), and the Western blot results were consistent with immunohistochemistry, the expression of NFκB p-p65 and NFκB p-p50 were significantly increased in the MA-related groups compared with control and CFA groups (P0.05). (3) Compared with the CFA+DMSO+MA group, the PWL of the CFA+ BAY 11-7082+MA group decreased significantly and continued until day 5 and 7 (P0.05 and P0.01, respectively), and the NFκB p65 expression of CFA+BAY 11-7082+MA was significantly reduced compared with CFA+DMSO+MA (P0.01).Local NFκB signaling cascade in acupoint caused by MA is an important step in initiating the analgesic effect, which would provide new evidence for the initiation of MA-effect and improve the understanding of the scientific basis of acupuncture analgesia.

Introduction Chromones are the major constituents of agarwood and are considered to be directly related to its quality. Agarotetrol, a chromone derivative, is a Chinese Pharmacopoeia content detection index. However, comprehensive high-performance liquid chromatography (HPLC), quantitative analysis of multiple components by a single marker (QAMS), and ultra-performance liquid chromatography mass spectrometry (UPLC-MS) analyses of this pharmacopeial plant material have never been performed. Moreover, reports regarding the separation and detection of multiple active 2-(2-phenylethyl)chromone analogues from this plant material are surprisingly scarce. Objective To establish a simple, reliable, and effective HPLC method utilising both diode array and MS detection for the simultaneous determination of multiple active chromone analogues in agarwood. Methods Four 2-(2-phenylethyl)chromones were isolated from methanol extracts of agarwood. After optimising the extraction, separation, and analytical conditions, validation of the developed analytical method indicated good linearity, satisfactory precision, and good recovery. On this basis, a method for the quantitative analysis of multiple components by a single marker was established. The four 2-(2-phenylethyl)chromones were identified by nuclear magnetic resonance spectroscopic analysis and UPLC coupled to electrospray ionisation quadrupole-time-of-flight MS. Conclusions The behaviour of the chromones characterised by MS fragmentation indicated a loss of molecular CO and the formation of m/z 121 compounds by the cleavage of CH2 -CH2 bonds between the chromone and phenyl moieties. Three detection methods were successfully used in this study for agarwood detection, and this protocol may potentially be used as a tool for the quality control of agarwood.

Sweet potato (Ipomoea batatas L.) is one of the leading crops worldwide, containing high nutritional components such as fiber and polyphenols. Root tuber of Simon 1 (SIMON), a cultivar of sweet potato, is a folk food in China with a hemostasis function but lacking experimental data support.Now the protective effect of SIMON on chemotherapy-induced thrombocytopenia (CIT), a serious complication of cancer treatment, is investigated for the first time by a CIT mouse model induced by intraperitoneal injection of carboplatin. As a result, SIMON raises the number of peripheral platelets, white blood cells, and bone marrow nucleated cells in CIT mice significantly. Besides, carboplatin-induced atrophy of the thymus, spleen, and disordered metabolism of the inflammatory immune system and glycerophospholipids are also reversed by SIMON. Phytochemical analysis of SIMON indicates 16 compounds including eight phenolic derivatives, which might be associated with its anti-CIT bioactivity.Sweet potato (SIMON) may be an efficient function food in the prevention of bleeding disorders.

Two new sesquiterpenoids, named dalodorin A (1) and dalodorin B (2), together with four known sesquiterpenoids, were isolated from the heartwood of Dalbergia odorifera. Their structures wer...

It has been widely accepted that cell culture in two-dimensional (2D) conditions may not be able to represent growth in three-dimensional (3D) conditions. Systematic comparisons between 2D and 3D cell cultures are needed to appropriately use the existing 2D results. In this work, we conducted a comparative study between 2D and 3D cell cultures of MC3T3-E1 using the same type of material (a mixture of silk fibroin (SF) and chitosan (CS)). Our results showed 3D SF/CS scaffold exhibited different effects on cell culture compared with the 2D cases. 1) The cells grown in 3D scaffold showed multiple morphologies. 2) The proliferation of cells in 3D scaffold was long-term and sustainable. 3) Cell differentiation occurred throughout the entire 3D scaffold. The results showed that cell culture in 3D SF/CS scaffold exhibited different features than 2D cases and 3D SF/CS scaffold could be a promising material for 3D cell culture.

The complete mitochondrial genome (mitogenome) of Epicauta impressicornis Pic (Coleoptera: Meloidae) was determined. The circular genome is 15,713-bp long, and encodes 13 protein-coding genes (PCGs), 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and a control region (CR). The 13 PCGs start with the typical ATN codon and terminate with the typical stop codon TAA (ND2, ND4L, ND6, ATP6, ATP8, and CYTB), TAG (ND1 and ND3), and T- (COX1, COX2, COX3, ND4, and ND5). The two rRNA genes (rrn12S and rrn16S) are encoded on the minority strand. All tRNAs genes except trnS1 (AGN) are predicted to fold into the typical cloverleaf structure. The longest overlap (10 bp) is observed between ATP8 and ATP6. CR mainly harbors a conserved poly-T stretch (15 bp), a short repeat unit (17 bp), some universal microsatellite-like repeats, and a canonical poly-A tail. Phylogenetic analysis using Bayesian inferences and maximum likelihood based on nucleotide and corresponding amino acid sequences of the 13 PCGs showed that E. impressicornis is closely related to E. chinensis, this relationship is and supported within Cucujiformia belonging to Meloidae (Tenebrionoidea). Our results further confirmed the monophyly of Tenebrionoidea, Lymexyloidea, Curculionoidea, Chrysomeloidea, Cucujoidea, Coccinelloidea, and Cleroidea within Cucujiformia, and revealed the sister relationships of (Cleroidea + Coccinelloidea), (Lymexyloidea + Tenebrionoidea), and ((Chrysomeloidea + Cucujoidea) + Curculionoidea). We believe that the complete mitogenome of E. impressicornis will contribute to further studies on molecular bases for the classification and phylogeny of Meloidae or even Cucujiformia.

Zinc is a biodegradable metal, which exhibits more moderate biodegradability than magnesium and iron, so that it has great application potential in the field of biomedical materials. Alloying of zinc and iron may lead to producing a new type of implant material Zn—Fe alloy, which might be able to meet the requirements for a moderate degradation rate. However, due to the huge difference in the melting point between zinc and iron, the preparation of Zn—Fe alloy is quite challenging and hence rarely reported. In this study, we show that Zn—Fe alloys can be successfully prepared by electrodeposition technology. The microstructures, composition, degradation properties and biocompatibility of the Zn—Fe alloys were systematically studied. The results showed that the content of iron in the alloys ranged from 0 to 8 wt%, depending on the concentration of Fe ions and the current density. In the alloys, the major's phases were η, δ and Г1, and they were mainly affected by the ion concentration in the electrolyte. In the in vitro immersion tests, the Zn—Fe alloy ZF2–1 showed the highest immersion corrosion rate, while ZF3–1 showed the highest electrochemical corrosion rate. Moreover, we found that the corrosion rates of the alloys were significantly higher than that of the pure Fe. In the in vivo experiments, we confirmed that the Zn—Fe alloy possessed good biocompatibility. These results demonstrate that the electrodeposition technology is a good method to prepare Zn—Fe alloys, and the Zn—Fe alloys prepared by this method are potentially promising materials for biomedical applications.

Background More than 2500 species belong to the Meloidae family (Coleoptera: Tenebrionoidea), members of which produce the potent defensive blistering agent cantharidin and are commonly known as blister beetles or Spanishflies. Cantharidin has recently been used for cancer therapy. Hycleus cichorii and Hycleus phaleratus have been used in traditional Chinese medicine for more than 2000 years due to their ability to biosynthesize cantharidin. To understand the role of the chemosensory system in beetle evolution, we comparatively analysed the chemosensory receptor families of both blister beetle species and compared them with those of other beetles. Results We identified 89 odorant receptors (ORs), 86 gustatory receptors (GRs), and 45 ionotropic receptors (IRs) in H. phaleratus and 149 ORs, 102 GRs and 50 IRs in H. cichorii. Nine groups of beetle ORs were recovered, and a similar pattern of ORs in Coleoptera emerged. Two evident expanded clades in Hycleus (Groups 5A and 3) were reconstructed in the phylogenetic tree. Four of eight genes with evidence of positive selection were clustered in the expanded clades of Group 5A. Three, eight and three orthologous pairs of CO2, sugar and fructose receptors, respectively, were identified in both blister beetles. Two evident expanded clades of putative bitter GRs in Hycleus were also found, and the GR in one clade had notably low divergence. Interestingly, IR41a was specifically expanded in blister beetles compared to other insects identified to date, and IR75 was also clearly expanded in both blister beetles based on our phylogenetic tree analysis. Moreover, evidence of positive selection was detected for eight ORs, three GRs and two IRs, half of which were from five duplicate clades. Conclusions We first annotated the chemosensory receptor families in a pair of sister beetle genomes (Meloidae: Hycleus), which facilitated evolutionary analysis of chemosensory receptors between sibling species in the Coleoptera group. Our analysis suggests that changes in chemosensory receptors have a possible role in chemical-based species evolution in blister beetles. Future studies should include more species to verify this correlation, which will help us understand the evolution of blister beetles.

To investigate the clinical manifestations and laboratory features of B-ALL patients with EP300-ZNF384 fusion gene positive, so as to improve the understanding of this subtype disease.The clinical data of 3 B-ALL patients with EP300-ZNF384 fusion gene positive admitted in Department of Hematology, the first medical center of Chinese PLA general hospital from February 2017 to February 2018 were collected and analyzed retrospectively. The clinical and laboratory characteristics as well as the therapentic outcome in B-ALL patients with EP300-ZNF384 fusion gene positive were analyzed.The fusion gene of EP300-ZNF384 was detected in 8.1%(3/37) of B-ALL patients. All cases showed the normal karyotype and aberrant CD13 and/or CD33 expression for immunophenotype. 3 patients were sensitive to traditional chemotherapy.The B-ALL with EEP300-ZNF384 fusion gene positive may be a subgroup of B-ALL with a uniqe clinical characteristis and laboatorial features. EP300-ZNF384 positive patients show a good response to conventional chemotherapy, suggesting a favorable prognosis.伴EP300-ZNF384融合基因阳性的急性B淋巴细胞白血病临床特点分析.探讨与分析对EP300-ZNF384融合基因阳性的急性B淋巴细胞白血病（B-ALL）患者的临床及实验室特征，以期提高对此少见类型疾病的认识.收集并回顾性分析本院自2017年2月至2018年2月收治的37例B-ALL的临床资料，对检出EP300-ZNF384融合基因阳性3例患者的临床、实验室特征及治疗情况进行深入分析.8.1％的B-ALL患者检测出EP300-ZNF384融合基因。3例患者R显带核型分析均为正常核型，在免疫分型上均表达有CD13或CD33等髓系标志。3例患者均对于传统化疗敏感.EP300-ZNF384阳性的B-ALL可能是一类具有独特临床特点与实验室检测特征的B-ALL亚型，可能对当前化疗方案敏感，可能预后良好.