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Exosomal miRNAs, as potential biomarkers in liquid biopsy for cancer early diagnosis, have aroused widespread concern. Herein, an electrochemical biosensor based on DNA “nano-bridge” was designed and applied to detect exosomal microRNA-21 (miR-21) derived from breast cancer cells. In brief, the target miR-21 can specifically open the hairpin probe 1(HP1) labeled on the gold electrode (GE) surface through strand displacement reaction. Thus the exposed loop region of HP1 can act as an initiator sequence to activate the hybridization chain reaction (HCR) between two kinetically trapped hairpin probes: HP2 immobilized on the GE surface and biotin labeled HP3 in solution. Cascade HCR leads to the formation of DNA “nano-bridge” tethered to the GE surface with a great deal of “piers”. Upon addition of avidin-modified horseradish peroxidase (HRP), numerous HRP were bound to the formed “nano-bridge” through biotin-avidin interaction to arouse tremendous current signal. In theory, only a single miR-21 is able to trigger the continuous HCR between HP2 and HP3 until all of the HP2 are exhausted. Therefore the proposed biosensor achieved ultrahigh sensitivity toward miR-21 with the detection limit down to 168 amol/L, as well as little cross-hybridization even at the single-base-mismatched level. Successful attempts were also made in the detection of exosomal miR-21 obtained from the MCF-7 of breast cancer cell line. To our knowledge, this is the first attempt to built horizontal DNA nano-structure on the electrode surface for exosomal miRNAs detection. In a word, the high sensitivity, selectivity, low cost make the proposed method hold great potential application for early point-of-care (POC) diagnostics of cancer.

Schwann cells (SCs) have important roles in supporting and repairing peripheral neurons, and thus have great potential for nerve injury treatment. Adipose tissue-derived stem cells (ADSCs) can be reliably induced to differentiate into SCs. However, the underlying molecular mechanisms are unclear. We explored the roles of MEG3/let-7a-5p/RBPJ axis in the differentiation into SCs from ADSCs. Primary ADSCs were induced to differentiate into SCs by appropriate reagents. ELISA, immunostaining, Western blotting, and qRT-PCR were employed to examine levels of SC-markers such as S100, GFAP, SOX10, p75NTR, GAP43, MPZ, β-NGF, BDNF, and NCAM and let-7 family, MEG3, RBPJ, and Notch signaling related proteins. Dual luciferase assay and RNA immunoprecipitation were performed to validate interactions of let-7a-5p/RBPJ mRNA and MEG3/let-7a-5p. Cultured ADSCs could be induced to differentiate into functional SCs. Let-7a-5p and let-7d-5p were elevated during the differentiation while MEG3 and RBPJ/Notch-signaling were suppressed. Let-7a-5p mimics promoted ADSC differentiation into SCs and up-regulated the levels of SC-related markers including S100, GFAP, SOX10, p75NTR, GAP43, MPZ, β-NGF, and NCAM, while RBPJ or MEG3 overexpression retarded the differentiation and reduced those levels. Let-7a-5p directly targeted RBPJ and MEG3 disinhibited Notch-RBPJ signaling via sponging let-7a-5p. RBPJ overexpression reversed the acceleration of let-7a-5p mimics on SC differentiation while let-7a-5p mimics blocked MEG3-mediated suppression on SC differentiation. Let-7a-5p sponged by MEG3 promotes differentiation of ADSCs into SCs via suppressing Notch signaling by targeting RBPJ. These findings shed light on mechanisms underlying the differentiation of ADSCs to SCs and provide avenues to accelerate the process.

In this study, conductive polymer composites and conductive functional fabrics are combined to serve as electromagnetic shielding planks. Polypropylene (PP), carbon black (CB), and short carbon fibers (SCF) are blended at different ratios to form conductive polymer composites (i.e. PCS series). The mechanical property, electrical property, morphology, and electromagnetic interference shielding effectiveness (EMI SE) of the PCS series are evaluated. The test results show that with 20 wt% of conductive fillers (i.e. CB and SCF), PCS20 exhibits the optimal tensile strength, flexural strength, and electrical property that is 7 order of magnitude higher than that of pure PP plates. Moreover, the EMI SE of this group also reaches −30 dB, which meets level one of civil EMI SE standard. Therefore, PCS20 is used to combine with four conductive sandwiches. The resulting multilayered functional PCS-sandwich planks are tested in terms of mechanical property, morphology, and EMI SE. The test results show that the planks composed of a pure conductive woven sandwich have the maximum tensile property and significantly improved impact resistance. All of the multilayered functional planks have EMI SE that is higher than −50dB and are qualified for the protection level of standard EMI SE electronic devices.

Enzymatic degradation of emerging contaminants has gained great interest for the past few years. However, free enzyme often incurs high costs in practice. The immobilized laccase on the polyethylenimine (PEI)‐functionalized magnetic nanoparticles (Fe3O4–NH2–PEI–laccase) was fabricated to efficiently degrade phenolic compounds continuously in a newly fixed bed reactor under a high‐gradient magnetic field. The degradation rate of continuous treatment in the bed after 18 h was 2.38 times as high as that of batch treatment after six successive operations with the same treatment duration. Under the optimal conditions of volume fraction of nickel wires mesh, flow rate of phenol solution, phenol concentration, and Fe3O4–NH2–PEI–laccase amount, the degradation rate of phenol kept over 70.30% in 48 h continuous treatment. The fixed bed reactor filled with Fe3O4–NH2–PEI–laccase provided a promising avenue for the continuous biodegradation of phenolic compounds for industrial wastewater in practice.

Carbon-based composites have gained extensive attention as microwave absorbing materials due to the lighter weight compared with other materials. In this work, Co/C nanocomposites with Co nanoparticles uniformly distributed in amorphous carbon sheets are prepared by a freezing dry and carbothermic reduction process. Hierarchical porous microstructures (micropores, mesopores, macropores) are achieved by ice template and huge amounts of gas during carbothermal reduction. Excellent absorption performance is achieved at a very low Co/C content (10% and 15%), which is a great success to design ultralight absorbers. At 10% content level, the effective absorption bandwidth is 5.0 GHz with a thin thickness of 1.8 mm, while the absorption bandwidth is 4.7 GHz with a thin thickness of 1.5 mm at 15% Co/C content level. The excellent absorption performance is attributed to excellent impedance matching resulting from synergy of cobalt and carbon and strong interfacial polarization induced by the hierarchical porous microstructures. This work provides a new pathway of designing ultralight absorbers with the advantage of thin thickness and wide bandwidth. Excellent absorption performance is achieved at only 10% Co/C content level, a success to design ultralight absorbers.

The combination of ultraviolet (UV) light and H2O2 is generally considered a promising technology for removing atrazine from the aqueous environment due to its high degradation efficiency, but the ...

Two-dimensional (2D) materials with a surface hierarchy and heterostructure offer infusive opportunities as high-rate electrodes in energy-storage/-conversion technologies due to their largely exposed active sites and shortened diffusion distance that are beneficial for mass/ion transfer. However, these 2D materials are still difficult to be synthesized due to the lack of a rational approach to design a surficial hierarchical heterostructure on 2D nanostructures. Herein, we explore a top-down strategy for the simple synthesis of surface-engineered TiO2 nanosheets with a large surface area, abundant open pores and TiO2-B/anatase heterointerfaces under mild conditions. Benefiting from the structural features of high electrode/electrolyte contact areas and short Li+/electron transport pathways, the surface-engineered TiO2 nanosheet material, tested as the lithium-storage electrode, show fast lithium uptake/release properties. A specific capacity of 149 mA h g−1 is observed at a high rate of 10 A g−1, and long-term operating stability is shown by delivering 110 mA h g−1 at 6 A g−1 upon 1000 cycles. Furthermore, the as-assembled lithium-ion capacitor using surface-engineered TiO2 nanosheets exhibits high energy density at high rates and possesses very stable cycling performance (∼80% capacity retention at 4 A g−1 after 10 000 cycles). This study may pave a new way for designing novel 2D nanoarchitectures with a surface hierarchical structure for high-power energy-storage applications.

In this paper, bis (indol-3-yl) methanes (BIMs) were synthesised and evaluated for their inhibitory activity against α-glucosidase and α-amylase. All synthesised compounds showed potential α-glucosidase and α-amylase inhibitory activities. Compounds 5 g (IC50: 7.54 ± 1.10 μM), 5e (IC50: 9.00 ± 0.97 μM), and 5 h (IC50: 9.57 ± 0.62 μM) presented strongest inhibitory activities against α-glucosidase, that were ∼ 30 times stronger than acarbose. Compounds 5 g (IC50: 32.18 ± 1.66 µM), 5 h (IC50: 31.47 ± 1.42 µM), and 5 s (IC50: 30.91 ± 0.86 µM) showed strongest inhibitory activities towards α-amylase, ∼ 2.5 times stronger than acarbose. The mechanisms and docking simulation of the compounds were also studied. Compounds 5 g and 5 h exhibited bifunctional inhibitory activity against these two enzymes. Furthermore, compounds showed no toxicity against 3T3-L1 cells and HepG2 cells.HighlightsA series of bis (indol-3-yl) methanes (BIMs) were synthesised and evaluated inhibitory activities against α-glucosidase and α-amylase.Compound 5g exhibited promising activity (IC50 = 7.54 ± 1.10 μM) against α-glucosidase.Compound 5s exhibited promising activity (IC50 = 30.91 ± 0.86 μM) against α-amylase.In silico studies were performed to confirm the binding interactions of synthetic compounds with the enzyme active site., Graphical Abstract

Four new compounds were isolated from G. nutans. Compounds 1–2 are two rare monoterpene indole alkaloids with the glucosyl moiety located at C-12 and represent the first two examples of enantiomer of ajmaline type monoterpene indole alkaloids.

Graphene and its derivatives have emerged as a promising nanomaterial in biomedical applications. However, their impact on biosafety continues to be a concern in the field, particularly, their potential cytotoxicity to our immune system. In this study, we used all-atom molecular dynamics simulations to investigate the potential interference of graphene nanosheets in antigen presentation and recognition in immune response. For the illustrated human immunodeficiency virus (HIV) antigen peptide KK10, human leukocyte antigen (HLA), and T cell receptor (TCR) ternary complex, we found that the graphene nanosheet could disrupt the critical protein–protein interactions between TCR and peptide-HLA and impair the antigen recognition by TCR, leaving the antigen presentation unaffected. Moreover, the hydrophobic interaction and van der Waals potential energy collectively drive the spontaneous separation of TCR from the peptide-HLA complex by graphene nanosheets. Our findings demonstrated theoretically how the graphene nanosheet could interfere with the immune response and provided useful insights for reducing the risk of graphene-based nanomaterials in biomedical applications.

A psychrotolerant actinobacterium, designated strain J5903T, was isolated from an alkaline soil sample from the rhizosphere of Suaeda salsa collected in desertification land surrounding Jiuliancheng Nur in Hebei Province, PR China. Cells of the isolate were Gram-stain-positive, aerobic, non-motile and non-spore-forming cocci. Strain J5903T grew optimally at 20‒25 °C, at pH 7.0‒7.5 and with d-2,4-diaminobutyric acid and l-2,4-diaminobutyric acid as diagnostic amino acids. The muramyl residue was acetyl type. The menaquinones were MK-11, MK-12, MK-10 and MK-13. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and one unidentified glycolipid. The major whole-cell fatty acids were anteiso-C15 : 0, iso-C16 : 0 and anteiso-C17 : 0. The genomic DNA G+C content was 69.1 mol%. It shared the highest average nucleotide identity and digital DNA–DNA hybridization values with Planctomonas deserti 13S1-3T. Phylogenies based on genome sequence showed that strain J5903T and P. deserti 13S1-3T formed a robust cluster with high bootstrap support. Strain J5903T shared typical chemotaxonomic characteristics with P. deserti 13S1-3T. Combining the polyphasic taxonomic evidence, strain J5903T represents a novel species of the genus Planctomonas , for which the name Planctomonas psychrotolerans sp. nov. is proposed. The type strain is J5903T (=DSM 101894T=CGMCC 1.15523T).

Following renal ischemia-reperfusion injury (RIRI), because of the decrease in oxygen supply to the kidney, a large amount of oxygen-free radicals is generated, and in severe cases, tissue cells will undergo apoptosis or even die. Normobaric hyperoxia (NBHO) is a very common clinical adjuvant treatment. It restores the oxygen supply after renal ischemia and combats oxidative stress in tissues, thus playing a protective role. In this study, our aim is to elucidate the protective mechanism of NBHO inhalation in a rat RIRI model. We performed a surgical excision of the left kidney of the rat and established a right kidney solitary kidney model. Later, the right renal pedicle of the rat was clamped using a non-invasive vascular clamp for 45 min. After the vascular clamp was released and reperfused for 24 h, the rat was placed in a closed oxygen chamber. It was subjected to inhalation of high-concentration oxygen (50%–55%), 2 h daily, for 7 days.RIRI induces postoperative weight loss, impaired renal function, increased oxygen free radicals, reduced antioxidant substances, increased histopathological damage, and increased levels of apoptosis. These effects were significantly improved after treatment with NBHO. At the same time, NBHO significantly increased the expression levels of Nrf2 and HO-1 in the tissues after RIRI. To verify whether HO-1 induced by Nrf2 is involved in the resistance to oxidative stress, after the rat RIRI and before inhaling NBHO, we intraperitoneally injected HO-1 specific inhibitor zinc protoporphyrin (ZnPP) (45 μmol/Kg). However, we found that ZnPP reversed the protective effect of NBHO on RIRI in rats. Combining all the results, we have demonstrated the protective effect of NBHO on RIRI, which can be at least partially attributed to the activation of the Nrf2/HO-1 antioxidative stress pathway.

Xanthomonas oryzae pv. oryzae (Xoo) is an offensive phytopathogen that can invade a wide range of plant hosts to develop bacterial diseases, including the well-known rice bacterial leaf blight. However, few agrochemicals have been identified to effectively prevent and eliminate Xoo-induced diseases. Thus, designing novel antibacterial compounds on the basis of the potential targets from Xoo may lead to the discovery of highly efficient and innovative anti-Xoo agents. Filamentous temperature-sensitive protein Z (FtsZ), an important functional protein in the progression of cell division, has been widely reported and exploited as a target for creating antibacterial drugs in the field of medicine. Therefore, the fabrication of innovative frameworks targeting XooFtsZ may be an effective method for managing bacterial leaf blight diseases via blocking the binary division and reproduction of Xoo. As such, a series of novel N-(cinnamoyl)-N'-(substituted)acryloyl hydrazide derivatives containing pyridinium moieties were designed, and the anti-Xoo activity was determined. The bioassay results showed that compound A7 had excellent anti-Xoo activity (EC50 = 0.99 mg L-1) in vitro and distinct curative activity (63.2% at 200 mg L-1) in vivo. Further studies revealed that these designed compounds were XooFtsZ inhibitors, validating by the reduced GTPase activity of recombinant XooFtsZ, the nonfilamentous XooFtsZ assembly observed in the TEM images, and the prolonged Xoo cells from the fluorescence patterns. Computational docking studies showed that compound A7 had strong interactions with ASN34, GLN193, and GLN197 residues located in the α helix regions of XooFtsZ. The present study demonstrates the developed FtsZ inhibitors can serve as agents to control Xoo-induced infections.

A new facile method for determination of anesthetic drug propofol based on quenching of electrochemiluminescence (ECL) was presented. When propofol was introduced to tris(2,2’-bipyridyl)-ruthenium (II)/tripropylamine system, an obvious decrease of ECL signal was observed due to the energy transfer between the excited state of Ru(bpy)32+ * and the electro-oxidation products of propofol. Under optimum conditions, the inhibited ECL response was linearly with the propofol concentration in the range of 20–8000 ng/mL with a detection limit of 10 ng/mL (S/N = 3). Moreover, the proposed sensing platform showed good reproducibility with relative standard deviation of 5.6% for 5 µg/mL propofol (n = 5). Finally, the proposed method was applied for detection of propofol in human serum with satisfactory recoveries. As a sensitive, rapid, simple and cost-effective method, the sensing platform holds great potential in determination of propofol.

One new long-chain ester derivative of trans-ferulic acid 1 and one natural tirucallane-type triterpenoid 2, together with forty known compounds (3-42), were isolated from the barks of Melia azedarach. Their structures were established on the basis of spectroscopic data interpretation. Compounds 7, 9, 10, 12, 13 showed significant inhibitory activities against PTP1B with IC50 values of 13.82 ± 1.29 μM, 13.29 ± 2.26 μM, 20.27 ± 0.52 μM, 24.36 ± 1.25 μM, 15.23 ± 0.6 μM, respectively.

Backgrounds and Aims It is well known that angiogenesis contributes to the progression of chronic obstructive pulmonary disease (COPD) by initiating the remodeling of bronchial vasculature. However, the specific molecular mechanisms are incompletely understood. This research aimed to explore whether endostatin, a member of endogenous antiangiogenic proteins, is a biomarker in COPD and plays a role in the angiogenesis of COPD. Methods 100 stable COPD patients, 130 patients with acute exacerbation (AECOPD) and 68 healthy volunteers were recruited in this research. Lung function test was conducted in the healthy people and stable COPD patients. Serum endostatin, C-reactive protein (CRP) and vascular endothelial growth factor (VEGF) of all the subjects were measured by Human Magnetic Luminex Screening Assay. Results Serum endostatin level was significantly higher in stable COPD compared with healthy control and even more in AECOPD patients (P

Objective To evaluate the expression of inducible nitric oxide synthases (iNOS/NOS2) in human glioma and its correlation with patients’ prognoses. Methods IiNOS/NOS2 expression in tumor and corresponding normal tissues of glioma patients was analyzed using the TCGA database and the online analysis tool GEPIA. The mutation statuses of iNOS/NOS2 genes were also explored in the TCGA database using cBioPortal. Co-expressed genes relevant to iNOS/NOS2 were screened by LinkedOmics. Gene ontology (GO) and KEGG pathway enrichment for iNOS/NOS2 and co-expressed genes was performed using LinkedOmics. Overall survival (OS) and disease-free survival (DFS) outcomes between iNOS/NOS2 mRNA high and low expression groups were compared using a log-rank test. Twenty-two glioma patients who underwent operation were included in the present work. A real-time PCR assay was used to detect iNOS/NOS2 mRNA expression in tumor tissue and normal brain tissue. Results There was no statistical difference in iNOS/NOS2 mRNA expression levelss between tumor and normal tissues of glioma. A real-time PCR assay indicated that iNOS/NOS2 mRNA expression in tumor tissue and normal brain tissues were not statistical difference (p>0.05). A mutation rate of 0.8% for the iNOS/NOS2 gene was found using 1044 glioma patients from two datasets. The mutation types include deep deletion (0.4%), truncating (0.2%) and missense (0.2%). The top positive and negative co-expressed gene with iNOS/NOS2 were COL25A1 (rpearson=0.4734, ppearson=0.4734, p Conclusion OS and DFS were significantly decreased in high iNOS/NOS2 mRNA expression groups. iNOS/NOS2 can be used as a poor prognostic biomarker for glioma.

A facile and effective impregnation combined with photo-deposition approach was adopted to deposit cadmium sulfide (CdS) nanoparticles on CTF-1, a covalent triazine-based frameworks (CTFs). In this system, CTF-1 not only acted as supporter but also served as photocatalyst and electron donor. The performance of the obtained CdS deposited CTF-1 (CdS-CTF-1) nanocomposite was evaluated by H2 evolution reaction under visible light irradiation. As a result, CdS-CTF-1 exhibited high H2 production from water, far surpassing the CdS/CTF-1 nanocomposite, in which CdS was deposited via solvothermal method. The high activity of CdS-CTF-1 was attributed to the confined CdS nanoparticles with small size, leading to expose more active sites. In addition, time-resolved spectroscopy indicated that the superior performance of CdS-CTF-1 also can be ascribed to the fast electron transfer rate and injection efficiency (KET = 0.18 × 109 s−1, ηinj = 39.38%) between CdS and CTF-1 layers, which are 3.83 times faster and 4.84 times higher than that of CdS/CTF-1 nanocomposite. This work represents the first example on using covalent organic frameworks (COFs) as a support and electron-donor for fabricating novel CdS-COF nanocomposite system and its potential application in solar energy transformations.

Objective This study was conducted to evaluate the difference in acid inhibition function among lansoprazole (LPZ), pantoprazole (PPZ), and their respective stereoisomers following single and multiple intravenous doses in healthy Chinese subjects. Materials and methods The dosage groups were set as follows: 30 mg single and multiple intravenous administrations of LPZ or R-LPZ, 40 mg single and multiple intravenous administrations of PPZ or S-PPZ. Subjects received an intravenous infusion of LPZ, R-LPZ, PPZ, or S-PPZ injection in sterile saline solution (100 mL/h, 60 minutes), respectively. The intragastric pH was sampled every second for 24 hours at baseline and for 24 hours after drug administration. The baseline-adjusted pharmacodynamic (PD) parameters include ΔMean (pH), ΔMedian (pH), ΔTpH≥3 (%), ΔTpH≥4 (%), ΔTpH≥6 (%), and ΔAUECph-tτ1-τ2. The PD parameters were evaluated in different time intervals (0 - 24 hours, 0 - 4 hours and 14 - 24 hours). Results After a single dose, the ΔTpH≥4 (%) of R-LPZ, LPZ, S-PPZ and PPZ was 56.6 ± 19.6, 53.1 ± 23.3, 35.6 ± 24.9 and 26.8 ± 30.2, respectively. The ΔTpH≥6 (%) was 50.7 ± 26.1, 41.4 ± 26.2, 25.4 ± 24.9 and 22.1 ± 27.6, respectively. The ΔAUECph-τ1-τ was 45,564 ± 16,107, 41,798 ± 16,153, 31,914 ± 17,304 and 20,744 ± 21,500, respectively. Statistically significant differences were found with R-LPZ vs. S-PPZ, R-LPZ vs. PPZ, LPZ vs. S-PPZ and LPZ vs. PPZ. The average TpH≥4 of R-LPZ, LPZ, S-PPZ, and PPZ was (47.2 ± 26.1) minutes, (49.6 ± 19.3) minutes, (56.1 ± 23.7) minutes, and (72.1 ± 27.3) minutes, respectively. Statistically significant differences were found with R-LPZ vs. PPZ (p = 0.009) and LPZ vs. PPZ (p = 0.019). After multiple doses, the ΔTpH≥4 (%) of R-LPZ, LPZ, S-PPZ, and PPZ was 71.7 ± 20.2, 63.5 ± 19.4, 59.5 ± 17.8 and 64.0 ± 22.4, respectively. The ΔTpH≥6 (%) was 64.0 ± 22.2, 52.0 ± 19.2, 49.6 ± 20.4 and 50.9 ± 23.8, respectively. The ΔAUECph-τ1-τ was 326,149 ± 94,839, 288,565 ± 93,279, 296,189 ± 83,412 and 300,960 ± 108,057, respectively. No statistically significant differences were found in baseline-adjusted PD parameters during all time periods after multiple doses. Conclusion After a single dose, the mean gastric pH inhibition value of R-LPZ was the highest, followed by LPZ, then S-PPZ and PPZ. R-LPZ and LPZ provided significantly better pH control compared with PPZ and S-PPZ in healthy subjects. The onset time of R-LPZ was the fastest and R-LPZ can provide better acid inhibition during sleeping time. After multiple doses, the mean values in all PD parameters of R-LPZ were the highest, the values of LPZ, S-PPZ, and PPZ were similar. However, no significant difference was found in acid inhibition among these four drugs after multiple doses.

In recent years, air filtration has been gaining much attention, and now people are much more concerned about antibacterial filters due to the spreading of COVID-19. The electret polypropylene (PP) nonwoven fabrics possess excellent filtration efficiency but a limited antibacterial effect against S. aureus and E. coli, and therefore triclosan is used in this study. Serving as an antibacterial agent, triclosan with a low molecular weight is an effective additive for the test results, indicating that the presence of triclosan strengthens the antibacterial effects of the filters. In addition, triclosan also strengthens the PP’s crystallinity, which in turn betters the filtration efficiency of the filters concurrently. Demonstrating powerful filtration and antibacterial performances, the antibacterial electret PP filters are highly qualified for filter applications.

Unintended pregnancy is a situation that every woman may encounter, and medical abortion is the first choice for women, but abortion often brings many sequelae.Angelica sinensisRadix (Danggui) andLeonuriHerba (Yimucao) are widely used in the treatment of gynecological diseases, which can regulate menstrual disorders, amenorrhea, dysmenorrhea, and promote blood circulation and remove blood stasis, but the mechanism for the treatment of abortion is not clear. We determined the ability of Danggui and Yimucao herb pair (DY) to regulate the Th1/Th2 paradigm by detecting the level of progesterone in the serum and the expression of T-bet and GATA-3 in the spleen and uterus. Then, we detected the level of metabolites in the serum and enriched multiple metabolic pathways. The arachidonic acid pathway can directly regulate the differentiation of Th1/Th2 cells. This may be one of the potential mechanisms of DY in the treatment of abortion.

A recent phenomenal study discovered that the extension domain of secreted amyloid-β precursor protein (sAPP) can bind to the intrinsically disordered sushi 1 domain of the γ-aminobutyric acid type B receptor subunit 1a (GABABR1a) and modulate its synaptic transmission. The work provided an important structural foundation for the modulation of GABABR1a; however, the detailed molecular interaction mechanism, crucial for future drug design, remains elusive. Here, we further investigated the dynamical interactions between sAPP peptides and the natively unstructured sushi 1 domain using all-atom molecular dynamics simulations, for both the 17-residue sAPP peptide (APP 17-mer) and its minimally active 9 residue segment (APP 9-mer). We then explored mutations of the APP 9-mer with rigorous free energy perturbation (FEP) calculations. Our in silico mutagenesis studies revealed key residues (D4, W6, and W7) responsible for the binding with the sushi 1 domain. More importantly, one double mutation based on different vertebrate APP sequences from evolution exhibited a stronger binding (ΔΔG = −1.91 ± 0.66 kcal mol−1), indicating a potentially enhanced GABABR1a modulator. These large-scale simulations may provide new insights into the binding mechanism between sAPP and the sushi 1 domain, which could open new avenues in the development of future GABABR1a-specific therapeutics., A recent phenomenal study discovered that the extension domain of secreted amyloid-β precursor protein (sAPP) can bind to the intrinsically disordered sushi 1 domain of the γ-aminobutyric acid type B receptor subunit 1a (GABABR1a) and modulate its synaptic transmission.

BackgroundResistin is an endogenous ligand of Toll-like receptor 4 that activates several inflammatory signals. But the physiological function of resistin in community-acquired pneumonia (CAP) remains unknown. The goal of this research was to explore the associations between serum resistin and the severity and prognosis in CAP patients through a retrospective cohort study.MethodsAll 212 CAP patients and 106 healthy cases were enrolled. Demographic characteristics were extracted. Serum resistin was determined via enzyme-linked immunosorbent assay. The prognosis was tracked in CAP patients.ResultsSerum resistin on admission was raised in CAP patients compared with control cases. The level of resistin was gradually increased in parallel with CAP severity scores in CAP patients. Pearson and Spearman analyses revealed that serum resistin was positively correlated with CAP severity scores, white blood cells, urea nitrogen, creatinine, and inflammatory cytokines among CAP patients. There were negative relationships between resistin and hematocrit and albumin in CAP patients. Besides, linear and logistic regression analyses further indicated that serum resistin on admission was positively associated with CAP severity scores among CAP patients. Follow-up research revealed that serum resistin elevation on admission prolonged hospital stay in CAP patients.ConclusionSerum resistin on admission is positively correlated with the severity and hospital stay in CAP patients, indicating that resistin may be involved in the physiological process of CAP. Serum resistin may be a potential biomarker in the diagnosis and prognosis for CAP.

Although compatibility is highly advocated in traditional Chinese medicine (TCM), inappropriate combination of some herbs may reduce the therapeutic action and even produce toxic effects. Kansui and licorice, one of TCM “Eighteen Incompatible Medicaments”, are the most representative cases of improper herbal combination, which may still be applied simultaneously under given conditions. However, the potential mechanism of their compatibility and incompatibility is unclear. In the present study, two different ratios of kansui and licorice, representing their compatibility and incompatibility respectively, were designed to elucidate their interaction by comparative plasma/tissue metabolomics and a heatmap with relative fold change. As a result, glycocholic acid, prostaglandin F2a, dihydroceramide and sphinganine were screened out as the principal alternative biomarkers of compatibility group; sphinganine, dihydroceramide, arachidonic acid, leukotriene B4, acetoacetic acid and linoleic acid were those of incompatibility group. Based on the values of biomarkers in each tissue, the liver was identified as the compatible target organ, while the heart, liver, and kidney were the incompatible target organs. Furthermore, important pathways for compatibility and incompatibility were also constructed. These results help us to better understand and utilize the two herbs, and the study was the first to reveal some innate characters of herbs related to TCM “Eighteen Incompatible Medicaments”., Graphical abstract Image 1, Highlights • Comparative metabolomics was employed to dissect the compatibility and incompatibility mechanism of kansui and licorice. • An interactive heatmap with relative fold change was created to explore complex metabolomics data of herb-herb interaction. • The study first revealed some innate important characters of herbs related TCM “Eighteen Incompatible Medicaments”.

Aquatic animals are now recognized to be major hosts of potentially pathogenic Laribacter hongkongensis. A comparative study was carried out among extended-spectrum β-lactamase (ESBL)-producing L. hongkongensis isolated from frogs (47 isolates) and fish (41 isolates) to examine phenotypic and genotypic antimicrobial resistance profiles, integrons, virulence factors, and genetic relatedness. Isolates from frogs showed a higher incidence of antibiotic resistance compared with those from fish for most of the antimicrobials tested, especially trimethoprim-sulfamethoxazole, tetracycline, ciprofloxacin, levofloxacin, and streptomycin. Multidrug-resistant strains were also found more frequently among frog isolates (5.44 traits on average) than among fish isolates (3.29 traits). In frog isolates, class 1 integrons and the resistance genes sul1, sul2, tetA, tetR, and aac(6')-Ib-cr showed a clearly higher incidence compared with isolates from fish. In contrast, blaTEM-1 was higher in fish isolates than in frog isolates. Correlation analysis showed that sul1, sul2, tetA, and tetR were significantly associated with class 1 integrons in frog isolates. The correlations indicated a potential co-selection risk of bacterial resistance to antibiotics. In addition, the distribution of three virulence-associated determinants for the type IV bundle-forming pili gene (bfpA), ferric aerobactin receptor gene (iucD), and iron-responsive element gene (ireA) was markedly higher in strains isolated from frogs than in those isolated from fish. No obvious genetic relatedness was observed between both populations. The large differences found in the incidence of antibiotic resistance, integrons along with the multiple resistance genes, virulence factors, and genetic fingerprints determined by pulsed-field gel electrophoresis suggest a high degree of antibiotic resistance and pathogenicity potential of ESBL-producing L. hongkongensis from isolates found in frogs.

The AgI/2D-La2Ti2O7 hybrids were obtained via a facile method at room temperature. Rhodamine B, as an organic dye, was used to determine the photocatalytic activity of the samples. The photocatalytic degradation mechanism was also analyzed. Experimental results display that AgI can broaden the light absorption of La2Ti2O7 under the visible light irradiation. The photocatalytic degradation efficiency of the as-synthesized hybrids appears the tendency of first increasing and then decreasing with increasing the usage of La2Ti2O7. When the usage of La2Ti2O7 is 10%, within 60 min, the as-synthesized hybrids possess the maximum of 93.1%. This is higher than 2.1% of La2Ti2O7 and 80.9% of AgI. Moreover, the improved photocatalytic activity can be attributed to AgI particles conjugating with 2D-La2Ti2O7 nanosheets via chemical-bonds, which can enhance the separation and transformation of the photo-generated holes and electrons. In addition, the dominating role is superoxide radicals during the photocatalytic process.

In the present work, wrinkled n-type WS2 nanosheets were synthesized and then used to construct the In2.77S4/WS2 p-n heterojunction photocatalyst. Experimental results reveal that the as-prepared hybrids present excellent photocatalytic activity for Cr(VI) reduction and tetracycline oxidation under visible and infrared light irritation. The photocatalytic efficiency of the as-prepared catalysts is found to increase initially followed by the decrease with the more weight content of WS2. When WS2 is up to 4 wt%, the as-prepared photocatalysts exhibit the highest photocatalytic activity, and are capable of reducing 99.1% of Cr(VI) in 60 min and oxidizing 87.5% of tetracycline in 20 min, much higher than 86.6 and 40.0% of pure In2.77S4, respectively. This enhanced photocatalytic activity is attributed to the construction of In2.77S4/WS2 p-n heterojunction between p-In2.77S4 and n-WS2. The detailed clarification of photocatalytic mechanism is also elaborated in the paper.

Full-spectrum-responsive AgI/WS2 composites as an efficient photocatalyst have been synthesised by an in-situ growth of AgI on the surfaces of WS2 nanosheets. The photocatalytic activities of the samples were evaluated by degradation of rhodamine B dilute solution under visible light irradiation. Experimental results showed that the introduction of WS2 nanosheets could enhance light absorption, photocatalytic activity, and recyclability of the pure AgI in the region of visible and infrared light. Moreover, the degradation efficiency of the as-synthesised AgI/WS2 composites exhibited the trend of first increased and then decreased with increasing the amount of WS2 nanosheets. When the usage of WS2 nanosheets was 7 wt%, the as-prepared composites possessed the maximum of 91.2% in 30 min. Furthermore, after three cycles of degradation, it could still degrade 89.0% of rhodamine B, obviously higher than 11.4% of pure AgI. In addition, a possible degradation mechanism of the as-synthesised AgI/WS2 hybrids was provided.

Antibody binding to a vulnerable site of HIV envelope glycoprotein (Env), the eight N-terminal residues of the gp41 fusion peptide, renders robust HIV neutralization. Here, we theoretically investigate HIV-1 fusion peptide binding to the neutralizing antibody N123-VRC34.01. We explore numerous fusion peptide mutations using all-atom molecular dynamics simulation with explicit-solvent models. Simulation results show that the hydrophobic interaction between Ile515 in the HIV-1 fusion peptide and the antibody VRC34.01 Fab plays an important role in antibody binding. Furthermore, we verify by free energy perturbation (FEP) calculations that two point mutations of Ile515Thr or Ile515Ala can dramatically weaken the binding affinity. Our findings provide new insights into fusion peptide-VRC34.01 binding, which can ultimately be utilized to design effective HIV vaccines.

In this paper, the self-made MoS2 nanosheets were attempted to be modified with oleic diethanolamide borate (ODAB) through a simple one-step route. The as-modified MoS2 nanosheets were confirmed by a series of characterizations. The results showed that the MoS2 nanosheets could be chemically well capped by ODAB to form C-S bonds. Furthermore, the tribological experimental results indicated that the ODAB-MoS2 nanosheets as lubricant additives could improve the friction properties of base oil. At the optimal adding content of 0.06 wt%, the average friction coefficient, average wear scar diameter and extreme pressure performance of the ODAB-MoS2-based oil were decreased by about 27.9%, 22.9% and 17.4% as compared to base oil, respectively. Finally, the friction mechanism was discussed and proposed.

To date, the overall response rate to checkpoint blockade remains unsatisfactory, partially due to the limited understanding of the tumor immune microenvironment. The retinoic acid-related orphan receptor γt (RORγt) is the key transcription factor of T helper cell 17 (Th17) cells and plays an essential role in tumor immunity. In this study, we used JG-1, a potent and selective small-molecule RORγt agonist to evaluate the therapeutic potential and mechanism of action of targeting RORγt in tumor immunity. JG-1 promotes Th17 cells differentiation and inhibition of regulatory T (Treg) cells differentiation. JG-1 demonstrates robust tumor growth inhibition in multiple syngeneic models and shows a synergic effect with the Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) antibody. In tumors, JG-1 not only promotes Th17 cells differentiation and increases C-C Motif Chemokine Receptor 6 (CCR6)- Chemokine (C-C motif) ligand 20 (CCL20) expression, but also inhibits both the expression of transforming growth factor-β1 (TGF-β1) and the differentiation and infiltration of Treg cells. In summary, JG-1 is a lead compound showing a potent activity in vitro and robust tumor growth inhibition in vivo with synergetic effects with anti-CTLA-4.

BACKGROUND MicroRNAs (miRNAs) are novel biomarkers that are important in tumorigenesis and cancer treatment resistance. miR-451 is expressed in human papillary thyroid carcinoma (PTC) tissues and is associated with tumor progression. This study investigated the molecular mechanism associated with the effects of miR-451 on B-CPAP human PTC cells in vitro. MATERIAL AND METHODS Binding of miRNAs to the 3' untranslated region (3'UTR) of messenger RNA (mRNA) was determined with a luciferase reporter assay. miRNAs and plasmids were transfected into human PTC B-CPAP cells with Lipofectamine 2000 Transfection Reagent. Cell viability was tested with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay. The levels of miRNAs and mRNA were determined with quantitative polymerase chain reaction and protein levels were analyzed with immunoblotting. RESULTS miR-451 bound to wild-type but not mutant 3'-UTR of activating transcription factor 2 (ATF2). MiR-451 mimics inhibited the growth of B-CPAP cells and reduced mRNA and protein levels in ATF2, whereas miR-451 inhibitors promoted the growth of B-CPAP cells and increased mRNA and protein levels in ATF2. CONCLUSIONS miR-451 directly bound to the 3'UTR of ATF2, decreased mRNA and protein levels in ATF2, and inhibited growth of B-CPAP cells. Our findings suggest that miR-451 may be a potential therapeutic target for PTC.