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The role of diet in depression is becoming increasingly acknowledged. This umbrella review aimed to summarize comprehensively the current evidence reporting the effects of dietary factors on the prevention and treatment of depression. PubMed, Embase, and the Cochrane Library were searched up to June 2021 to identify relevant meta-analyses of prospective studies. Twenty-eight meta-analyses, with 40 summary estimates on dietary patterns (n = 8), food and beverages (n = 19), and nutrients (n = 13) were eligible. The methodological quality of most meta-analyses was low (50.0%) or very low (25.0%). Quality of evidence was moderate for inverse associations for depression incidence with healthy diet [risk ratio (RR): 0.74, 95% confidential interval (CI), 0.48–0.99, I2 = 89.8%], fish (RR: 0.88, 95% CI, 0.79–0.97, I2 = 0.0%), coffee (RR: 0.89, 95% CI, 0.84–0.94, I2 = 32.9%), dietary zinc (RR: 0.66, 95% CI 0.50–0.82, I2 = 13.9%), light to moderate alcohol (I2 = 20.5%), as well as for positive association with sugar-sweetened beverages (RR: 1.05, 95% CI, 1.01–1.09, I2 = 0.0%). For depression treatment, moderate-quality evidence was identified for the effects of probiotic [standardized mean difference (SMD): −0.31, 95% CI, −0.56 to −0.07, I2 = 48.2%], omega-3 polyunsaturated fatty acid (SMD: −0.28, 95% CI, −0.47 to −0.09, I2 = 75.0%) and acetyl-l-carnitine (SMD: −1.10, 95% CI, −1.65 to −0.56, I2 = 86.0%) supplementations. Overall, the associations between dietary factors and depression had been extensively evaluated, but none of them were rated as high quality of evidence, suggesting further studies are likely to change the summary estimates. Thus, more well-designed research investigating more detailed dietary factors in association with depression is warranted.

Background The biofilm state of pathogens facilitates antimicrobial resistance which makes difficult-to-treat infections. In this regard, it has been found that the compounds screened from plant extracts represent one category of the most promising antibiofilm agents. However, the antibiofilm activities and the active ingredients of plant extracts remain largely unexplored. In this background, the study is (1) to screen out the plant extracts with antibiofilm ability against Pseudomonas aeruginosa, and (2) to identify the active ingredients in the plant extracts and elucidate the underlying mechanism of the antibiofilm activities. Methods Micro-broth dilution method, in vitro biofilm model, LC–MS/MS analysis and P. aeruginosa-mouse infection model were adopted to assess the antibiofilm activity. GC–MS analysis was performed to detect the active ingredients in plasma. RNA-Seq, GO analysis, KEGG analysis and RT-qPCR were adopted to elucidate the underlying mechanism of antibiofilm activities against P. aeruginosa. Results Lonicerae Japonicae Flos (LJF) among 13 plants could exert significant inhibitory effects on bacterial biofilm formation, mobility and toxin release in vitro, and it could exert antibiofilm effect in vivo too. Moreover, quinic acid, as one metabolite of chlorogenic acid, was found as an active ingredient in LJF against the biofilm of P. aeruginosa. The active ingredient significantly inhibited EPS secretion in biofilm formation and maturity and could achieve synergistic antibiofilm effect with levofloxacin. It reduced the biofilm formation by regulating core targets in quorum sensing system. In GO process, it was found that the core targets were significantly enriched in multiple biological processes involving locomotion, chemotaxis and motility mediated by flagellum/cilium, which was related to KEGG pathways such as bacterial chemotaxis, oxidative phosphorylation, ribosome, biofilm formation, cyanoamino acid metabolism and quorum sensing. Finally, the binding of quinic acid with core targets rhlA, rhlR and rhlB were validated by molecular docking and RT-qPCR. Conclusions In summary, the study verified the in vitro and in vivo antibiofilm effects of LJF against P. aeruginosa and elucidated the active ingredients in LJF and its conceivable pharmacological mechanism, indicating that quinic acid could have the potential of an antibiofilm agent against P. aeruginosa and related infections. Graphic abstract

Conjugated linoleic acid (CLA) is an isomer of linoleic acid (LA). The predominant dietary CLA is cis-9, trans-11-CLA (c-9, t-11-CLA), which constitutes up to ~ 90% of total CLA and is thought to be responsible for the positive health benefits associated with CLA. However, the effects of c-9, t-11-CLA on Alzheimer’s disease (AD) remain to be elucidated. In this study, we investigated the effect of dietary intake of c-9, t-11-CLA on the pathogenesis of an AD mouse model. We found that c-9, t-11-CLA diet-fed AD model mice significantly exhibited (1) a decrease in amyloid-β protein (Aβ) levels in the hippocampus, (2) an increase in the number of microglia, and (3) an increase in the number of astrocytes expressing the anti-inflammatory cytokines, interleukin-10 and 19 (IL-10, IL-19), with no change in the total number of astrocytes. In addition, liquid chromatography–tandem mass spectrometry (LC–MS/MS) and gas chromatographic analysis revealed that the levels of lysophosphatidylcholine (LPC) containing c-9, t-11-CLA (CLA-LPC) and free c-9, t-11-CLA were significantly increased in the brain of c-9, t-11-CLA diet-fed mice. Thus, dietary c-9, t-11-CLA entered the brain and appeared to exhibit beneficial effects on AD, including a decrease in Aβ levels and suppression of inflammation.

An effective regiodivergent synthesis toward 1- and 3-thiosugars was achieved through palladium and cobalt catalysis, respectively. β-1-Thiosugars were obtained from 3,4-O-carbonate-glycals and var...

Atomically thin two-dimensional molybdenum disulfide (MoS2) is well known for its excellent lubrication characteristics and is usually used as a solid lubricant in diverse micro/nanoelectromechanical systems (MEMS/NEMS). The friction on atomically thin MoS2 deposited on a SiO2/Si substrate is reduced almost five times to achieve an ultra-low friction state (coefficient of friction nearly 0.0045) by rubbing the surface with an AFM tip under the electric field. The electric field leads to a shift and accumulation of charges at the interface between MoS2 and the SiO2/Si substrate. Then, electronic tight-binding with high interfacial bonding strength is experimentally found by the charges transferring during the rubbing process. The ultra-low friction state of atomically thin MoS2 could attribute to the electronic tight-binding between MoS2 and the SiO2/Si substrate, which suppresses the atomic-scale deformation and limits the local pinning capability of MoS2. The ultra-low friction state on atomically thin MoS2 is patterned further by controllably regulating position, time, and electric field during the rubbing process. This approach can provide an additional channel to achieve ultra-low friction on MoS2 related two-dimensional materials with semiconductor properties. The nanopatterning of ultra-low friction could promote and expand engineering applications of MoS2 as lubricants in various MEMS/NEMS with nano-scale components.

The construction and clinical application of a surface-enhanced Raman scattering (SERS) platform for the early diagnosis of lung cancer could improve the survival rate of patients and would be of great significance. Nevertheless, a sensitive and reusable method for the detection of aldehydes, as biomarkers of lung cancer, in exhaled breath is still an enormous challenge. Aldehydes generally have a low cross section in Raman scattering and have a weak specific affinity to plasmonic nanoparticle surfaces, meaning that sensing them at low concentrations is incredibly difficult. Herein, an ultrasensitive SERS strategy, that can be recycled for further use, for the detection of lung cancer biomarkers in the form of aldehydes was realized by fabrication of a multifunctional Ag NPs@ZIF-67/g-C3N4 solid phase extraction (SPE) membrane. Based on the change in the vibrational fingerprints of 4-ATP before and after reaction with the aldehydes, the SPE membrane was successfully used for the ultrasensitive detection of aldehydes with a detection limit of 1.35 nM. The excellent SERS performance was attributed to the synergistic effect of the densely and closely distributed Ag NPs (providing SERS "hot spots"), ZIF-67 (concentrating the analyte molecules) and g-C3N4 (forming a membrane to prolong the contact time between the aldehydes and the substrate). In addition, recycling of the SPE membrane was achieved by utilizing the self-cleaning ability of the Ag NPs@ZIF-67/g-C3N4 membrane originating from the photocatalytic properties of g-C3N4. The proposed SERS membrane was easy to operate, rapid and portable, thus providing a potential tool for a point-of-care test in clinical and diagnostic practice.

Radiation therapy is widely used to treat a variety of malignant tumors, including non-small-cell lung cancer (NSCLC). However, ionizing radiation (IR) paradoxically promotes radioresistance, metastasis and recurrence by inducing epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs). Here, we developed two NSCLC radioresistant (RR) cell lines (A549-RR and H1299-RR) and characterized their motility, cell cycle distribution, DNA damage, and CSC production using migration/invasion assays, flow cytometry, comet assays, and sphere formation, respectively. We also evaluated their tumorigenicity in vivo using a mouse xenograft model. We found that invasion and spheroid formation by A549-RR and H1299-RR cells were increased as compared to their parental cells. Furthermore, as compared to radiation alone, the combination of β-elemene administration with radiation increased the radiosensitivity of A549 cells and reduced expression of EMT/CSC markers while inhibiting the Prx-1/NF-kB /iNOS signaling pathway. Our findings suggest that NSCLC radioresistance is associated with EMT, enhanced CSC phenotypes, and activation of the Prx-1/NF-kB/iNOS signaling pathway. They also suggest that combining β-elemene with radiation may be an effective means of overcoming radioresistance in NSCLC.

The nanofriction properties of hexagonal boron nitride (h-BN) are vital for its application as a substrate for graphene devices and solid lubricants in micro- and nano-electromechanical devices. In this work, the nanofriction characteristics of h-BN on Si/SiO2 substrates with a bias voltage are explored using a conductive atomic force microscopy (AFM) tip sliding on the h-BN surface under different substrate bias voltages. The results show that the nanofriction on h-BN increases with an increase in the applied bias difference (Vt−s) between the conductive tip and the substrate. The nanofriction under negative Vt−s is larger than that under positive Vt−s. The variation in nanofriction is relevant to the electrostatic interaction caused by the charging effect. The electrostatic force between opposite charges localized on the conductive tip and at the SiO2/Si interface increases with an increase in Vt−s. Owing to the characteristics of p-type silicon, a positive Vt−s will first cause depletion of majority carriers, which results in a difference of nanofriction under positive and negative Vt−s. Our findings provide an approach for manipulating the nanofriction of 2D insulating material surfaces through an applied electric field, and are helpful for designing a substrate for graphene devices.

Alzheimer's disease (AD) is characterized by neuronal loss and accumulation of β-amyloid-protein (Aβ) in the brain parenchyma. Sleep impairment is associated with AD and affects about 25–40% of patients in the mild-to-moderate stages of the disease. Sleep deprivation leads to increased Aβ production; however, its mechanism remains largely unknown. We hypothesized that the increase in core body temperature induced by sleep deprivation may promote Aβ production. Here, we report temperature-dependent regulation of Aβ production. We found that an increase in temperature, from 37 °C to 39 °C, significantly increased Aβ production in amyloid precursor protein-overexpressing cells. We also found that high temperature (39 °C) significantly increased the expression levels of heat shock protein 90 (Hsp90) and the C-terminal fragment of presenilin 1 (PS1-CTF) and promoted γ-secretase complex formation. Interestingly, Hsp90 was associated with the components of the premature γ-secretase complex, anterior pharynx-defective-1 (APH-1), and nicastrin (NCT) but was not associated with PS1-CTF or presenilin enhancer-2. Hsp90 knockdown abolished the increased level of Aβ production and the increased formation of the γ-secretase complex at high temperature in culture. Furthermore, with in vivo experiments, we observed increases in the levels of Hsp90, PS1-CTF, NCT, and the γ-secretase complex in the cortex of mice housed at higher room temperature (30 °C) compared with those housed at standard room temperature (23 °C). Our results suggest that high temperature regulates Aβ production by modulating γ-secretase complex formation through the binding of Hsp90 to NCT/APH-1.

Mammalian carboxylesterases (CES) are key enzymes that participate in the hydrolytic metabolism of various endogenous and exogenous substrates. Human carboxylesterase 2A (hCES2A), mainly distributed in the small intestine and colon, plays a significant role in the hydrolysis of many drugs. In this study, 3-arylisoquinolones 3 h [3-(4-(benzyloxy)-3-methoxyphenyl)-7,8-dimethoxyisoquinolin-1(2H)-one] and 4 a [3-(4-(benzyloxy)-3-methoxyphenyl)-4-bromo-7,8-dimethoxyisoquinolin-1(2H)-one] were found to have potent inhibitory effects on hCES2A (IC50 =0.68 μΜ, Ki =0.36 μΜ) and excellent specificity (more than 147.05-fold over hCES1 A). Moreover, 4 a exhibited threefold improved inhibition on intracellular hCES2A in living HepG2 cells relative to 3 h, with an IC50 value of 0.41 μΜ. Results of inhibition kinetics studies and molecular docking simulations demonstrate that both 3 h and 4 a can bind to multiple sites on hCES2A, functioning as mixed inhibitors. Structure-activity relationship analysis revealed that the lactam moiety on the B ring is crucial for specificity towards hCES2A, while a benzyloxy group is optimal for hCES2A inhibitory potency; the introduction of a bromine atom may enhance cell permeability, thereby increasing the intracellular hCES2A inhibitory activity.

Amyloid-β proteins (A β), including Aβ42 and A β 43, are known pathogenesis factors of Alzheimer's disease (AD). Unwanted substances in the brain, including A β, are generally removed by microglia, astrocytes, or neurons via a phagocytosis receptor. We observed that neurons and astrocytes engulfed A β 42 and A β 43, which are more neurotoxic than A β 40. We previously showed that multiple-EGF like domains 10 (MEGF10) plays an important role in apoptotic cell elimination and is expressed in mammalian neurons and astrocytes. Therefore, we assessed whether MEGF10 is involved in A β42 and A β43 engulfment in MEGF10-expressing neurons and astrocytes. We found that MEGF10-expressing astrocytes and neurons engulfed A β42 and A β43 but not A β40. Furthermore, incubation of the neurons and astrocytes with A β42 and A β43a ugmented MEGF10 phosphorylation; however, incubation with A β40 did not have this augmenting effect. Our findings suggest that MEGF10 plays a phagocytosis receptor function for A β42 and A β43 in neurons and astrocytes.

Background The most common chemotherapeutic drug for triple-negative breast cancer (TNBC) treatment is 5-fluorouracil (5-FU), but its therapeutic index is low due to its toxicity. β-Elemene (ELE) possesses antitumor activity against different cancers, but it has never been used in combination with 5-FU to improve its chemotherapeutic effect against TNBC. Materials and methods We treated MDA-MB-231 and BT549 cells of TNBC with ELE alone, 5-FU alone, or their combination to investigate their treatment effects on cell viability, proliferation, migration, invasion, and colony formation. We verified the molecular mechanisms of our results through confocal immunofluorescence, immunohistochemistry, and Western blot analysis in vitro and in vivo. Results Our result revealed that ELE enhanced the 5-FU effect against cell viability, proliferation, migration, invasion, and colony formation through different mechanisms in MDA-MB-231 and BT549 cell lines. In molecular mechanisms, ELE and 5-FU in combination enhances apoptosis in both cell lines through Bl-2 family protein and caspase cascade modulation, thereby inhibiting NF-kB pathway through IKKβ, IKKα, and p65 downregulation in the cytoplasm and p50 and p65 downregulation in the nucleus. ELE and 5-FU in combination regulated the PI3K/AKT pathway through p-AKT, P-85, p110r, p-PDK1, and p110a protein and RAF-MEK-ERK pathway inhibition through the p-c-raf and p-ERK downregulation. The PI3K inhibitor LY294002 or RAF-MEK-ERK inhibitor U0126 in combination with ELE and 5-FU decreased cell viability in both cell lines significantly, thereby showing the involvement of these pathways in cell apoptosis. In mouse xenograft model, ELE and 5-FU in combination inhibited the tumor growth and modulated its molecular markers. Conclusion The conclusion obtained, considering that the results suggest that the combination may be important specifically in the treatment of TNBC.

A pair of new phenolic bisabolane-type sesquiterpenoid enantiomers (±)- phomoterpenes A and B [(±)-1] and two known analogues (2 and 3), together with two new isocoumarins, phomoisocoumarins C‒D (4‒5), were isolated from an endophytic fungus Phomopsis prunorum (F4-3). Their structures were elucidated by comprehensive spectroscopic analysis. The enantiomeric separation for (±)-1 were achieved by chiral-HPLC, and their absolute configurations were assigned by electronic circular dichroism (ECD) calculation. Compounds (+)-1 and 5 exhibited moderate antibacterial activity against plant pathogenic bacteria Pseudomonas syringae pv. Lachrymans with MIC values of 15.6 μg/mL.

A new methodology of stereoselective C-glycosylation has been developed with 3,4-O-carbonate glycals and boronic acids, catalyzed by 1,2-bis(phenylsulfinyl)ethane palladium(II) acetate under open-air conditions at room temperature. This mild method is simple in operation, wide in substrate range, and tolerant in alcoholic/phenolic hydroxyl and amino groups. High to excellent yields were observed for all substrates tested, with the driving force mainly contributed by decarboxylation. Meanwhile, the high 1,4-trans-selectivity was achieved by steric effects as proposed.

Our previous studies have demonstrated that the total triterpenes from the fruits of Chaenomeles speciosa (CSTT) exhibit effective therapeutic effects on gastric ulcer patients and animals. The present aim is to further investigate the mechanisms involved. The results indicated that CSTT could ameliorate IND-induced gastric injury, which was related to promoting IND-damaged GES-1 cell proliferation and migration, improving the IND-damaged rat GBF, ulcer area, inhibition rate and pathologic changes of gastric mucous tissue, increasing the amount of adhered gastric mucus, attenuating the volume and total acidity of the gastric effluents, and augmenting the gastric pH; further studies showed that CSTT obviously downregulated miR-423-5p mRNA, NAG-1 mRNA and protein expression, Bax, Bad, cytosol cytochrome C, Apaf-1, cleaved-caspase-3, and cleaved-caspase-9 protein expression and cytosol cytochrome C concentration, and upregulated TFF1, TFF2 and TFF3 mRNA and protein expression, Bcl-2, Bcl-xl, pro-caspase-3, and pro-caspase-9 protein expression, mitochondrial viability, mitochondrial cytochrome C concentration and Bcl-2/Bax, Bcl-xl/Bad ratios. These findings demonstrated that CSTT protected against IND-induced gastric damage by depressing miR-423-5p expression and modulating the TFF/NAG-1 pathway, which in turn restrained mitochondrion-mediated apoptosis.

Cisplatin is one of the most potent chemotherapeutic agents for the treatment of colon cancer. Nevertheless, the unavoidability of the notable toxicity and the development of the acquired resistance severely restricted its clinical application. Aspirin and some other non-steroidal anti-inflammatory drugs have been used to prevent colon tumorigenesis as chemopreventive agents. Here, we explored the possibility of aspirin as an adjuvant drug to boost the anti-cancer effect of cisplatin for colon cancer. We found that aspirin significantly enhanced the cisplatin-mediated inhibitions of cell proliferation, migration and invasion and the induction of apoptosis in colon cancer cells. The combined treatment of aspirin and cisplatin suppressed the expression of the anti-apoptotic protein Bcl-2 and the EMT-related proteins, up-regulated the levels of the cleaved PARP and Bax, and blocked the PI3K/AKT and RAF-MEK-ERK signaling pathway. In addition, we demonstrated that the enhanced effect of aspirin on the cisplatin-induced inhibition of tumor cell growth was also mediated through the suppression of the binding activity of NF-κB to the COX-2 promoter. The combination of aspirin and cisplatin effectively attenuated the translocation of NF-κB p65/p50 from the cytoplasm to the nucleus, and abrogated the binding of NF-κB p65/p50 to the COX-2 promoter, thereby down-regulating COX-2 expression and PGE2 synthesis. Moreover, the in vivo study also verified the enhanced anti-tumor activity of such combined therapy in colon cancer by targeting the NF-κB/COX-2 signaling. Our results provided new insights into understanding the molecular mechanisms of aspirin in sensitizing cisplatin-mediated chemotherapeutic effect in colon cancer and indicated a great potential of this combined therapy for cancer treatment.

Currently, best-characterized indicators for Alzheimer's disease (AD) diagnosis are the decreased levels of amyloid-β protein 42 and increased levels of phosphorylated tau in cerebrospinal fluid (CSF). The positron emission tomography (PET) imaging with Pittsburgh compound B (PiB) is also used in AD diagnosis by visualizing amyloid deposition in the brain. These methods are invasive or expensive; therefore, less invasive and easily detectable blood biomarkers are required. Because our previous study showed that flotillin release, a marker of exosomes, was attenuated by Aβ, we designed the present study to determine whether flotillin level could be reduced in CSF and/or serum of patients with AD. In this study, we analyzed flotillin levels in CSF and serum of non-AD controls, patients with AD and mild cognitive impairment (MCI) by western blotting. Flotillin levels in cerebroventricular fluid (CVF) and serum of AD, vascular dementia (VaD), and non-AD autopsy cases were also analyzed. Flotillin levels significantly decreased in the CSF and serum of AD patients compared with those of non-AD controls, respectively. Moreover, in patients with MCI due to AD determined by PiB-PET, CSF and serum flotillin levels significantly decreased compared with those of patients with MCI due to non-AD. Flotillin levels remained unchanged in CVF and serum of autopsy cases diagnosed as VaD. Serum flotillin level is negatively associated with brain amyloid deposition indicated as PiB uptake. These results demonstrate that serum flotillin level can serve as one of the blood markers for estimation of brain amyloid deposition and early diagnosis of AD.

Four new furostanol saponins, named aspidsaponins E-H (1–4) were isolated from the rhizomes of Aspidistra elatior Blume. Their structures were determined based on chemical methods and spectral data. Compounds 1 and 2 were a pair of diastereoisomeric furostanol saponins and possessed the highly oxidized structural feature of 1β, 2β, 3β, 4β, 5β, 26-hexanol-steroids, and compounds 3-4 were steroidal glycosides with a tetra-saccharide chain at C3. The isolated compounds (1–4) were tested in vitro for inhibitory activities against LPS-induced nitric oxide production in RAW264.7 macrophages. Among them, compounds 3 and 4 showed excellent anti-inflammatory activities with IC50 values 82.1 and 65.9 μM, respectively.

RCE-4, a steroidal saponin isolated from Reineckia carnea, has been studied previously and has exhibited promising anti-cervical cancer properties by inducing programmed cell death (PCD) of Ca Ski cells. Considering the cancer cells developed various pathways to evade chemotherapy-induced PCD, there is, therefore, an urgent need to further explore the potential mechanisms underlying its actions. The present study focused on targeting the Bcl-2–Beclin 1 complex, which is known as the key regulator of PCD, to deeply elucidate the molecular mechanism of RCE-4 against cervical cancer. The effects of RCE-4 on the Bcl-2–Beclin 1 complex were investigated by using the co-immunoprecipitation assay. In addition, autophagy-related genes (ATG) were also analyzed due to their special roles in PCD. The results demonstrated that RCE-4 inhibited the formation of the Bcl-2–Beclin 1 complex in Ca Ski cells via various pathways, and ATG 4B proteins involved in this process served as a key co-factor. Furthermore, based on the above, the sensitivity of RCE-4 to Ca Ski cells was significantly enhanced by inhibiting the expression of the ATG 4B by applying the ATG 4B siRNA plasmid.

Exosomes are vesicles secreted by various kinds of cells, and they are rich in cholesterol, sphingomyelin (SM), phosphatidylcholine, and phosphatidylserine. Although cellular sphingolipid-mediated exosome release has been reported, the involvement of other lipid components of cell membranes in the regulation of exosome release is poorly understood. Here, we show that the level of exosome release into conditioned media is significantly reduced in cultured astrocytes prepared from apolipoprotein E (ApoE) knock-out mice when compared to those prepared from wild-type (WT) mice. The reduced level of exosome release was accompanied by elevated levels of cellular cholesterol. The addition of cholesterol to WT astrocytes significantly increased the cellular cholesterol levels and reduced exosome release. PI3K/Akt phosphorylation was enhanced in ApoE-deficient and cholesterol-treated WT astrocytes. In contrast, the depletion of cholesterol in ApoE-deficient astrocytes due to treatment with β-cyclodextrin recovered the exosome release level to a level similar to that in WT astrocytes. In addition, the reduced levels of exosome release due to the addition of cholesterol recovered to the control levels after treatment with a PI3K inhibitor (LY294002). The cholesterol-dependent regulation of exosome release was also confirmed by in vivo experiments; that is, exosome levels were significantly reduced in the CSF and blood serum of WT mice that were fed a high-fat diet and had increased cholesterol levels when compared to those in WT mice that were fed a normal diet. These results suggest that exosome release is regulated by cellular cholesterol via stimulation of the PI3K/Akt signal pathway.

The separation and chemical analysis of mixtures in an emergency situation represent major challenges, especially in remote or poverty-stricken areas. A novel method was developed for the rapid separation and detection of multiple components via paper centrifugal chromatography, which costs as little as $2.26 US. The method was realized based on the combination of portable paper centrifugal chromatography and surface-enhanced Raman scattering (SERS) detection. This coupled technique was successfully implemented for the separation and qualitative analysis of a rhodamine 6G-crystal violet mixture and a colorless aniline-pyrocatechol-benzidine mixture. A chromatographic mobile phase was collected using absorbent cotton, which was demonstrated to have no effect on the SERS results. The optimized device achieved rapid and effective separation of the colorless aniline-pyrocatechol-benzidine mixture with a high centrifugal force (0.3303π2 N). The newly developed method involving multicomponent paper centrifugal chromatography-SERS detection will be of great value for emergency-related substance separation and analysis in remote and poor areas.

Background: In cancers, tumor-associated macrophages (TAMs) play an important role in the progression, evasion of immunity and sensitivity to therapy. Unfortunately, radiation and hypoxia could induce the M2 macrophages infiltration and polarization. Materials and methods: In this study, we investigated the relevance of macrophage recruitment with radiation and hypoxia by transwell. We also evaluated the effect of β-elemene on the infiltration of M2 macrophages and explored its underlying molecular mechanism by a series of in vitro and in vivo experiments. Results: Irradiated or hypoxia lung cancer cells recruit macrophages, and the recruitment is MCP-1 dependent. We also found that radiation and hypoxia-induced MCP-1 secretion follows upregulation of Prx-1, which leads to nuclear accumulation of NF-κB and HIF-1α expression. In addition, β-elemene could effectively suppress this recruitment phenomenon through Prx-1/NF-κB/HIF-1α signaling. Conclusion: Our study showed that radiation and hypoxia significantly promoted the macrophages recruitment. β-elemene could effectively suppress this recruitment phenomenon and MCP-1 expression via inhibiting Prx-1/NF-κB/HIF-1α pathways.

The high cell density culture of baker's yeast FX-2 was investigated in a 50 L(A) automatic bioreactor. Herein, it was found firstly that the Crabtree effect clearly existed in batch fermentation with higher glucose content, then the critical initial glucose content range (≤2.00 g L-1 ) was reasonably ascertained to effectively avoid Crabtree effect. In the next fed-batch fermentations with different strategies, the second strategy (maintain ethanol concentration lower than 0.10% and pH around 4.80) was confirmed to be more beneficial to yeast growth than the first strategy (keep reducing sugar not more than 2.00 g L-1 and control steady Carbon/Nitrogen ratio 3.05:1.00). After that, one optimal control strategy (maintain pH around 4.80 and keep respiratory quotient in the range of 0.90-1.00) was constructed to further enhance cell yield. Under an optimal control strategy, four schemes with the aim of achieving pH-stat were compared, and yeast extract instead of other alkaline materials was selected as a better regulator. As a result, 148.37 g L-1 dry cell weight, 38.25 × 108 mL-1 living cells, and 8.24 g L-1 h-1 productivity were harvested, which respectively elevated 23.74%, 135.38%, and 24.47% compared to that obtained under the traditional scheme (regulate pH with ammonia); meanwhile, the maximum oxygen uptake rate and carbon dioxide excretion rate were both more than 250.00 mmol L-1 min-1 .

Background ErbB2 overexpression identifies a subset of breast cancer as ErbB2-positive and is frequently associated with poor clinical outcomes. As a membrane-embedded receptor tyrosine kinase, cell surface levels of ErbB2 are regulated dynamically by membrane physical properties. The present study aims to investigate the influence of membrane cholesterol contents on ErbB2 status and cellular responses to its tyrosine kinase inhibitors. Methods The cholesterol abundance was examined in ErbB2-positive breast cancer cells using filipin staining. Cellular ErbB2 localizations were investigated by immunofluorescence with altered membrane cholesterol contents. The inhibitory effects of the cholesterol-lowering drug lovastatin were assessed using cell proliferation, apoptosis, immunoblotting and immunofluorescence assays. The synergistic effects of lovastatin with the ErbB2 inhibitor lapatinib were evaluated using an ErbB2-positive breast cancer xenograft mouse model. Results Membrane cholesterol contents positively correlated with cell surface distribution of ErbB2 through increasing the rigidity and decreasing the fluidity of cell membranes. Reduction in cholesterol abundance assisted the internalization and degradation of ErbB2. The cholesterol-lowering drug lovastatin significantly potentiated the inhibitory effects of ErbB2 kinase inhibitors, accompanied with enhanced ErbB2 endocytosis. Lovastatin also synergized with lapatinib to strongly suppress the in vivo growth of ErbB2-positive breast cancer xenografts. Conclusion The cell surface distribution of ErbB2 was closely regulated by membrane physical properties governed by cholesterol contents. The cholesterol-lowering medications can hence be exploited for potential combinatorial therapies with ErbB2 kinase inhibitors in the clinical treatment of ErbB2-positive breast cancer.

Two new thymol derivatives (compounds 1–2) were isolated from the roots of Eupatorium chinense. Their structures were elucidated by analysis of MS data and extensive 1D and 2D NMR spectroscopy (1H-1H COSY, HMBC, HSQC and NOESY). The absolute configuration of compound 1 was assigned based on a comparison of calculated and experimental ECD. Compounds 1–2 were tested in vitro for their cytotoxic activities against three cancer cell lines CNE 2, Caski and HGC-27. Among them, compound 1 showed notable cytotoxic activities against the three cancer cell lines with IC50 values ranging from 4.2 to 11.9 μM.

Human carboxylesterase 2 (hCE2) is one of the most abundant esterases distributed in human small intestine and colon, which participates in the hydrolysis of a variety of ester-bearing drugs and thereby affects the efficacy of these drugs. Herein, a new compound (23o) with a novel skeleton of dihydrooxazolo[2,3-a]isoquinolinium has been discovered with strong inhibition on hCE2 (IC50 = 1.19 μM, Ki = 0.84 μM) and more than 83.89 fold selectivity over hCE1 (IC50 > 100 μM). Furthermore, 23o can inhibit hCE2 activity in living HepG2 cells with the IC50 value of 2.29 μM, indicating that this compound has remarkable cell-membrane permeability and is capable for inhibiting intracellular hCE2. The SAR (structure–activity relationship) analysis and molecular docking results demonstrate that the novel skeleton of oxazolinium is essential for hCEs inhibitory activity and the benzyloxy moiety mainly contributes to the selectivity of hCE2 over hCE1.

The tunable nanofriction of graphene as a lubricant material is important for its application in micro/nano-electromechanical devices. A tunable nanofriction array of graphene on a silicon dioxide/silicon (SiO2/Si) substrate was achieved via functionalization using negative-bias conductive atomic force microscopy by introducing an electron releasing process to avoid electron saturation. Based on the electron releasing process, the functionalization degree of graphene and thus the nanofriction were controllably tuned by the tip voltage. Moreover, the nanofriction of the functionalized array was further enhanced by applying biased tip voltage. The nanofriction on the functionalized array increased with an increase in bias voltage due to the polarization-induced electrostatic force, and the voltage increased the meniscus force. The tuning of the nanofriction of functionalized graphene on an insulating substrate can provide insight into the electric-carrying friction behavior of graphene as a solid lubricant in micro/nano-electromechanical systems (MEMS/NEMS) and the fabrication of nanodevices with a patterned surface.

The chemical modification of the primary amino groups of amino acid derivatives and peptides is an important process in the pharmaceutical industry and the field of chemical biology. However, suitable reactions that can be carried out under mild and environmentally friendly conditions are limited. We present a versatile method to selectively modify primary amino groups using novel dihydrooxazolo[3,2-a]quinoliniums in 1-butanol as solvent under mild and metal-free conditions. The application of this method to peptides with primary amino, secondary amino, amide, alcoholic hydroxyl, phenolic hydroxyl, disulfide bond, ester and cyano groups revealed that only the primary amino groups were selectively modified, suggesting that this method is compatible with other reactive moieties. We also demonstrated that the quinolylation of existing peptides affected peptide bioactivity and stability, indicating that the novel dihydrooxazolo[3,2-a]quinoliniums can be widely applied, especially in medicinal chemistry and chemical biology.

The aim of this study was to elucidate the gastroprotective activity and possible mechanism of involvement of araloside A (ARA) against ethanol- and aspirin-induced gastric ulcer in mice. The experimental mice were randomly divided into control, model, omeprazole (20 mg/kg, orally) and ARA (10, 20 and 40 mg/kg, orally). Gastric ulcer in mice was induced by intragastric administration of 80% ethanol (10 mL/kg) containing 15 mg/mL aspirin 4 h after drug administration on day 7. The results indicated that ARA could significantly raise gastric juice volume and acidity; ameliorate gastric mucosal blood flow, gastric binding mucus volume, ulcer index and ulcer inhibition rate; suppress H+/K+-ATPase activity, which was confirmed by computer-aided docking simulations; inhibit the release of mitochondrial cytochrome c into the cytoplasm; inhibit caspase-9 and caspase-3 activities and down-regulate mRNA expression levels; down-regulate the mRNA and protein expressions of apoptosis protease-activating factor-1 and protein expression of cleaved poly(ADP ribose) polymerase-1; and up-regulate Bcl-2 mRNA and protein expressions and down-regulate Bax mRNA and protein expressions, thus elevating the Bcl-2/Bax ratio in a dose-dependent manner. Histopathological observations further provided supportive evidence for the aforementioned results. The results demonstrated that ARA exerted beneficial gastroprotective effects on alcohol- and aspirin-induced gastric ulcer in mice, which was related to suppressing H+/K+-ATPase activity as well as pro-apoptotic protein expression, and promoting anti-apoptotic protein expression, thus alleviating gastric mucosal injury and cell death.

Four new α-pyrone derivatives, xylariaopyrones A-D (1-4), together with four known compounds were isolated from the PDB broth of endophytic fungus xylariales sp. (HM-1). Their structures were identified by comprehensive analysis of NMR, MS and CD spectra. The absolute configurations of compounds B-D were determined by calculating their ECD spectra. Compound C (3) and D (4) was a pair of epimer with a ketal function group. The eight obtained metabolites were evaluated to four cancer cell lines, but they showed no significative data with IC50 > 50 μg/mL. And the antimicrobial assay results appeared that xylariaopyrones A-D displayed the inhibiting activity with MIC value ranging from 20.5 to 50.6 μg/mL. Finally, the results of brine shrimp inhibiting activity from eight compounds displayed different inhibiting ratio from 40% to 92%.

Fermentation of the endophytic fungus Aplosporella javeedii on solid rice medium in presence of either 3.5% NaNO3 or 3.5% monosodium glutamate caused a significant change of the fungal metabolite pattern compared to fungal controls grown only on rice. Chemical investigation of the former fungal extracts yielded 11 new lactam derivatives, aplosporellins A–K (2–12), in addition to the known compound, pramanicin A (1). All of these compounds were not detected when the fungus was grown on rice medium without these activators thereby indicating the power of this OSMAC approach. The structures of the new compounds were elucidated by one- and two- dimensional NMR spectroscopy, DFT-NMR calculations and by mass spectrometry as well as by comparison with the literature whereas the absolute configuration of the lactam core was determined by TDDFT-ECD and OR calculations. Pramanicin A (1) showed strong cytotoxicity against human lymphoma (Ramos) and leukemia (Jurkat J16) cells with IC50 values of 4.7 and 4.4 μM, respectively. Mechanistic studies indicated that 1 activates caspase-3 and induces apoptotic cell death.

The huge economic loss of citrus fruit after harvest called for safe and efficient preservatives, as chemically synthesized agents threatened the environment and human health. Herein a biocontrol fungus Chaetomium globosum QY-1 near the orchard in riparian area was identified to have antimicrobial, antioxidant and tyrosinase inhibition activity, which meets the requirements of an ideal preservative. Metabolite profiling based on bioassay-guided fractionation was carried out, and eight polyketones were determined by MS and NMR. The most abundant CheA exhibited strong inhibition to Penicillium digitatum, the main pathogen caused citrus fruit rot. Among these metabolites, Epicoccone and Epicoccolide B showed higher antioxidant activity, while Epicoccone and CheA had higher tyrosinase inhibitory activity. All the activities were close to or even better than the positive control (Vc; glutathione; Vc and arbutin; Bellkute), implying that the metabolites of C. globosum had comprehensive effects as natural preservatives.

The extraction, purification, structure and hepatoprotective activity of a homogenous polysaccharide (SPS60) from Sabia parviflora were investigated. SPS60 was screened after purification with Sephadex G-100 and showed the excellent hepatoprotective activity. Its structural characteristics were investigated by Time of flight mass spectrometry (TOF-MS), PMP Pre-column derivatization-HPLC (PMP-HPLC), nuclear magnetic resonance (NMR) spectroscopy and Atomic Force Microscopy (AFM). The results showed that SPS60 possessed the molecular weight of 16900 Da and the monosaccharide component was glucose, as well as a 1 → 6 glycosidic bond. The results of atomic force microscopy (AFM) show that SPS60 is a blocky sphere in solution. Furthermore, the SPS60 could significantly improve the survival rate of LO2 hepatocytes which were damaged by CCl4. Therefore, SPS60 may be an active substance of S. parviflora as a local functional tea.

Direct N-glycosylation between glycals and amides/amines was achieved with exclusive stereoselectivity in moderate to high yields. Various amides, amines, and 3,4-O-carbonate-glycals were tolerated, and unique β-N-glycosides were obtained. The strategy was based on palladium-catalyzed decarboxylative allylation, and the high 1,4-cis-selectivity was proposed because of the hydrogen bonding effect. Notably, all the synthesized products were subjected to preliminary bioactivity studies, revealing that three compounds were cytotoxic to tumor cells and nontoxic to normal human cells.

Alzheimer's disease (AD) is characterized by the formation of extracellular amyloid plaques containing the amyloid β-protein (Aβ) within the parenchyma of the brain. Aβ is considered to be the key pathogenic factor of AD. Recently, we showed that Angiotensin II type 1 receptor (AT1R), which regulates blood pressure, is involved in Aβ production, and that telmisartan (Telm), which is an angiotensin II receptor blocker (ARB), increased Aβ production via AT1R. However, the precise mechanism underlying how AT1R is involved in Aβ production is unknown. Interestingly, AT1R, a G protein-coupled receptor, was strongly suggested to be involved in signal transduction by heterodimerization with β2-adrenergic receptor (β2-AR), which is also shown to be involved in Aβ generation. Therefore, in this study, we aimed to clarify whether the interaction between AT1R and β2-AR is involved in the regulation of Aβ production. To address this, we analyzed whether the increase in Aβ production by Telm treatment is affected by β-AR antagonist using fibroblasts overexpressing amyloid precursor protein (APP). We found that the increase in Aβ production by Telm treatment was decreased by the treatment of β2-AR selective antagonist ICI-118551 more strongly than the treatment of β1-AR selective antagonists. Furthermore, deficiency of AT1R abolished the effect of β2-AR antagonist on the stimulation of Aβ production caused by Telm. Taken together, the interaction between AT1R and β2-AR is likely to be involved in Aβ production.

Five sesterterpenes (1–5) including two new compounds (1 and 2), as well as a new (6) and a known macrolide (7) were isolated from the endophytic fungus Aplosporella javeedii. The structures of the new compounds were elucidated by analysis of their 1D and 2D NMR and HRMS data as well as by comparison with the literature. Compound 4 and its acetyl derivatives 4a, 4b, 4c which were prepared by acetylation of 4 exhibited moderate cytotoxicity against the mouse lymphoma cell line L5178Y with IC50 values ranging from 6.2 to 12.8 μM, respectively. Moreover, 4a and 4c exhibited also cytotoxicity against human leukemia (Jurkat J16) and lymphoma (Ramos) cell lines. Compound 7 showed strong cytotoxicity against the L5178Y cell line, as well as against human Jurkat J16 and Ramos cells with IC50 values of 0.4, 5.8, and 4.4 μM, respectively. Mechanistic studies indicated that 7 induces apoptotic cell death. In addition, compounds 3, 4 and 7 showed low antibacterial activities against Mycobacterium tuberculosis H37Rv and compound 6 against Staphylococcus aureus, respectively, with MICs of 100 μM. Preliminary structure-activity relationships are discussed.

Yeast autolysis refers to the process in which cells degrade and release intracellular contents under specific conditions by endogenous enzymes such as proteases, nucleases and lipid enzymes. Protein-rich baker's yeast is widely used to produce yeast extract in food industry, however, the molecular mechanism related to baker's yeast autolysis is still unclear. In this study, RNA-seq technology and biochemical analysis were performed to analyze the autolysis processes in baker's yeast. The differentially expressed genes (DEGs), 27 autolysis-related euKaryotic Ortholog Groups (KOG) and three types of autolysis-induced Gene Ontology (GO) were identified and analyzed in detail. A total of 143 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways under autolysis were also assigned. Interestingly, the DEGs were significantly enriched in the mitogen-activated protein kinase (MAPK) signaling pathways and metabolic pathways, and key genes MID2, MTL1, SLT2, PTP2, HKR1 and GPD1 may play important roles in autolysis. Further quantitative PCR was performed to verify the expression pattern in baker's yeast autolysis. Together, all these results indicated that MAPK pathways might play an essential role during autolysis process through inhibiting the metabolism and disrupting cell wall in baker's yeast. This result may provide important clues for the in-depth interpretation of the yeast autolysis mechanism.

Chemical investigation of secondary metabolites from the endophytic fungus Pseudopestalotiopsis theae led to the isolation of eighteen new polyketide derivatives, pestalotheols I&ndash, Q (1&ndash, 9) and cytosporins O&ndash, W (15&ndash, 23), together with eight known analogs (10&ndash, 14 and 24&ndash, 26). The structures of the new compounds were elucidated by HRMS and 1D and 2D NMR data, as well as by comparison with literature data. Modified Mosher&rsquo, s method was applied to determine the absolute configuration of some compounds. Compound 23 showed significant cytotoxicity against the mouse lymphoma cell line L5178Y with an IC50 value of 3.0 &mu, M. Furthermore, compounds 22 and 23 showed moderate antibacterial activity against drug-resistant Acinetobacter baumannii (ATCC BAA-1605) in combination with sublethal colistin concentrations.

A new phenylpropanoid, ligulaveitnoid A (1), along with four known compounds, (E)-2,3-dihydroconiferyl p-coumarate (2), dihydroconiferyl ferulate (3), 4-hydroxy-3-methoxybenzaldehyde (4) and (E)-p-coumaric acid (5) were isolated from rhizomes and roots of L. veitchiana. All the structures of compounds were identified by the interpretation of their spectroscopic data and comparison with those reported in the literature. The anti-inflammatory activity of the isolates was examined for their inhibitory effects on LPS-induced NO production in macrophage RAW264.7 cells. Among them, compound 2 showed strong inhibitory activities towards the LPS-induced NO production in macrophage RAW264.7 cells with IC50 value of 8.0 μM.

Penicillium oxalicum has been used as a biocontrol fungus in agriculture for many years, but the antimicrobial substances are still uncertain. Herein, we isolated a linear peptide named Sanxiapeptin in the culture broth of Penicillium oxalicum SG-4 collecting from the Three Gorges riparian zone. Sanxiapeptin exhibited potent inhibitory effect on citrus green mold Penicillium digitatum, the main fungi responsible for postharvest decay. Sanxiapeptin was elucidated as composing of five amino acids, which were β-amino-α-methoxybutyric acid (Amoba), N-Me- l -Thr, d -Thr, N-Me- l -Val and l -Ser. By analyzing three chemically synthesized oligopeptides with similar structures, we found that the first amino acid of Amoba was crucial to the antifungal activity, as was the methylation of peptide bond. Sanxiapeptin may act as an antimicrobial agent by affecting the function of cell membranes or walls. The antimicrobial spectrum, safety and stability analysis supported that Sanxiapeptin was a promising antifungal agent for citrus preservation.

Seven new azaphilones, coniellins A-G (1-7), were obtained from the fungus Coniella fragariae that had been isolated from goose dung. Their structures were elucidated by analysis of 1D and 2D NMR as well as HRESIMS data. TDDFT-ECD calculation was used to determine the absolute configuration of 1, while Mosher's method was applied to determine the absolute configuration of 5. While displaying only moderate cytotoxicity, compound 1 exhibited significant inhibition of NF-κB activation in the triple negative breast cancer cell line MDA-MB-231 with an IC50 value of 4.4 μM. Moreover, compounds 1, 4, and 5 clearly reduced tumor cell migration. Compound 1 was the most active derivative tested in this assay and displayed 60% inhibition of tumor cell migration at a dose of 5 μM and 98% inhibition at 10 μM after 24 h.

The atomic-scale steps are ubiquitous on graphene. The frictional behavior of graphene at atomic-scale steps under different relative humidity (RH) is very important for application of graphene as solid lubricant in complicated environment. Frictional properties at atomic-scale graphene steps were investigated using calibrated atomic force microscopy (AFM) in various RH. Lateral force at uncovered atomic step decreased with the increase of RH, while lateral force at covered step were independent of RH. Uncovered steps possessed higher work function than graphene plane from the scanning Kelvin probe microscopy (SKPM) measurement due to the existence of dangling bonds and oxygen-containing functional groups. Then the adsorption of water molecule on hydrophilic oxygen containing functional groups at uncovered step decreased the work function and reduced the lateral force under high RH. Also, lateral force at steps increased even fast than plane after plasma treatment, because dangling bonds is easier to be oxide functionalization. The studies provide a further understanding of frictional properties at atomic scale steps and could be helpful in the applications of graphene as solid lubricant in humid environment.

The 5 V-cathode material LiNi0.5Mn1.5O4 microspheres with hollow, solid or core-shelled inner structures for the lithium-ion batteries are designed and fabricated by a multi-step synthesis procedure. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), powder X-ray diffraction (XRD) analysis, Fourier transformed infrared (FTIR) are employed to characterize the microstructures. Compared with the hollow and solid inner structures, the core-shell structured LiNi0.5Mn1.5O4 exhibits excellent cycling stability and outstanding rate performance, which delivers a discharge capacity of 111.5 mA h g−1 after 200 cycles at 1 C, and 98 mA h g−1 at 8 C, respectively. Further analyses with cyclic voltammetry and electrochemical impedance spectroscopy demonstrate that the core-shell structure can provide structural stability and shortened lithium diffusion path at both room and elevated temperatures.

Background/Aims: PI3KCA and mutant p53 are associated with tumorigenesis and the development of cancers. NVP-BKM120, a selective pan-PI3K inhibitor, exerts the antitumor activity by suppressing the PI3K signaling pathway. Prima-1 Met , a low molecular weight compound, can rescue the gain-of-function of mutant p53 by restoring its transcriptional function. In this study, we investigated whether PI3K inhibition combined with mutant p53 reactivation could enhance the antitumor effect in thyroid cancer cells. Methods: The effects of BKM120 and Prima-1 Met on the proliferation, apoptosis, migration and invasion of thyroid cancer cells were measured by MTT, colony formation, flow cytometry, wound-healing and transwell assays, respectively. Thyroid differentiation was assessed by detecting the expression levels of specific markers using RT-PCR and Western blot. The in vivo antitumor efficacy was analyzed in a mouse xenograft model. Results: The combinational treatment of BKM120 and Prima-1 Met significantly enhanced the inhibitions of cell viability, colony formation, migration and invasion, and the induction of apoptosis in thyroid cell lines, and synergistically suppressed tumor xenograft growth by inhibiting the PI3K/Akt/mTOR and EMT signaling pathways, up-regulating p53 targeted genes, and triggering the release of cytochrome c. Moreover, the combination of BKM120 and Prima-1 Met suppressed the stemlike traits of thyroid cancer cells and promoted their differentiation by upregulating the expression of thyroid-specific differentiation markers and repressing the expression of cancer stem cell markers. Furthermore, the mechanism study demonstrated that the combinational treatment synergistically abrogated the binding of CPSF4 at the promoter of hTERT and thus suppressed hTERT expression. Consistently, overexpression of hTERT rescued the inhibitions of cell viability, invasion and stem-like traits mediated by the combination of BKM120 and Prima-1 Met . Conclusion: Our results showed that the combination of BKM120 with Prima-1 Met synergistically suppressed the growth of thyroid cancer cells and tumor xenografts via inhibiting PI3K/Akt/mTOR and CPSF4/hTERT signaling and reactivating mutant p53.