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1.
Mol Cell Biochem ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33011952

RESUMO

Nature polyphenols widely present in plants and foods are promising candidates in cancer chemotherapy. Emerging evidence has shown that plant polyphenols regulate the expression of miRNAs to exert the anti-Multidrug resistance (MDR) activity, which partly attributes to their regulation on miRNAs methylation. Our previous study found that bound polyphenol from foxtail millet bran (BPIS) had potential as an anti-MDR agent for colorectal cancer (CRC), but its mechanism remains unclear. The present findings demonstrated that BPIS upregulated the expression of miR-149 by reducing the methylation of its CpG islands, which subsequently induced the cell cycle arrest in G2/M phase, resulting in enhancing the chemo-sensitivity of HCT-8/Fu cells. Mechanically, BPIS and its active components (FA and p-CA) reduced miR-149 methylation by inhibiting the expression levels of DNA methyltransferases, promoting a remarkable increase of miR-149 expression. Further, the increased miR-149 induced cell cycle arrest in G2/M phase by inhibiting the expression of Akt, Cyclin B1 and CDK1, thus increasing the chemosensitivity of HCT-8/Fu cells. Additionally, a strong inducer of DNA de-methylation (5-aza-dc) treatment markedly increased the chemosensitivity of CRC through elevating miR-149 expression, which indicates the hypermethylation of miR-149 may be the key cause of drug resistance in CRC. The study indicates that the enhanced chemosensitivity of BPIS on CRC is mainly attributed to the increase of miR-149 expression induced by methylation inhibition.

2.
Trials ; 21(1): 834, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028415

RESUMO

BACKGROUND: Although effective results of many studies support the use of spinal cord stimulation in chronic pain patients, no randomized controlled trial has been undertaken in China to date. CITRIP is a multicenter, prospective, randomized, withdrawal study designed to evaluate the clinical effectiveness and safety of spinal cord stimulation plus remote programming management in patients with intractable trunk or limb pain. METHOD: Participants will be recruited in approximately 10 centers across China. Eligible participants with intractable trunk or limb and an average visual analog scale (VAS) score ≥ 5 will undergo a spinal cord stimulation test. Participants with VAS score reduction ≥ 50% could move forward to receive implantation of an implanted pulse generator. In the withdrawal period at 3-month follow-up visit, participants randomized to the experimental group (EG) will undergo continuous stimulation while ceasing the stimulation in the control group (CG). The outcome assessment will occur at baseline and at 1, 3 (pre- and post-randomization), and 6 months. The primary outcome is the difference of maximal VAS score between EG and CG in the withdrawal period compared with baseline before the withdrawal period. Additional outcomes include VAS score change at 1-, 3-, and 6-month follow-ups; responder rate (VAS score improving by 50%); achievement rate of a desirable pain state (VAS score ≤ 4); awake times during sleep; Beck Depression Inventory for depression evaluation; short-form 36 for quality of life evaluation; drug usage; and satisfaction rating of the device. Adverse events will be collected. The primary analysis will follow the intention-to-treat principle. DISCUSSION: The CITRIP study seeks to evaluate the effectiveness and safety of a randomized withdrawal trial of spinal cord stimulation for patients with intractable trunk or limb pain. TRIAL REGISTRATION: ClinicalTrials.gov NCT03858790 . Registered on March 1, 2019, retrospectively registered.

3.
J Med Chem ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33058670

RESUMO

Focal adhesion kinase (FAK) is a nonreceptor intracellular tyrosine kinase that plays an essential role in cancer cell adhesion, survival, proliferation, and migration through both its enzymatic activities and scaffolding functions. Overexpression of FAK has been found in many human cancer cells from different origins, which promotes tumor progression and influences clinical outcomes in different classes of human tumors. Therefore, FAK has been considered as a promising target for small molecule anticancer drug development. Many FAK inhibitors targeting different domains of FAK with various mechanisms of functions have been reported, including kinase domain inhibitors, FERM domain inhibitors, and FAT domain inhibitors. In addition, FAK-targeting PROTACs, which can induce the degradation of FAK, have also been developed. In this Perspective, we summarized the progress in the development of small molecular FAK inhibitors and proposed the perspectives for the future development of agents targeting FAK.

4.
J Neurosci ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33060174

RESUMO

Inhibitory interneurons integrate into developing circuits in specific ratios and distributions. In the neocortex, inhibitory network formation occurs concurrently with the apoptotic elimination of a third of GABAergic interneurons. The cell surface molecules that select interneurons to survive or die are unknown. Here, we report that members of the clustered Protocadherins (cPCDHs) control GABAergic interneuron survival during developmentally-regulated cell death. Conditional deletion of the gene cluster encoding the gamma-Protocadherins (Pcdhgs) from developing GABAergic neurons in mice of either sex causes a severe loss of inhibitory populations in multiple brain regions and results in neurological deficits such as seizures. By focusing on the neocortex and the cerebellar cortex, we demonstrate that reductions of inhibitory interneurons result from elevated apoptosis during the critical postnatal period of programmed cell death. By contrast, cortical interneuron populations are not affected by removal of Pcdhgs from pyramidal neurons or glial cells. Interneuron loss correlates with reduced AKT signaling in Pcdhg mutant interneurons, and is rescued by genetic blockade of the pro-apoptotic factor BAX. Together, these findings identify the PCDHGs as pro-survival transmembrane proteins that select inhibitory interneurons for survival and modulate the extent of programmed cell death. We propose that the PCDHGs contribute to the formation of balanced inhibitory networks by controlling the size of GABAergic interneuron populations in the developing brain.SIGNIFICANCE STATEMENTA pivotal step for establishing appropriate excitatory-inhibitory ratios is adjustment of neuronal populations by cell death. In the mouse neocortex, a third of GABAergic interneurons are eliminated by BAX-dependent apoptosis during the first postnatal week. Interneuron cell death is modulated by neural activity and pro-survival pathways but the cell-surface molecules that select interneurons for survival or death are unknown. We demonstrate that members of the cadherin superfamily, the clustered gamma-Protocadherins (PCDHGs), regulate the survival of inhibitory interneurons and the balance of cell death. Deletion of the Pcdhgs in mice causes inhibitory interneuron loss in the cortex and cerebellum, and leads to motor deficits and seizures. Our findings provide a molecular basis for controlling inhibitory interneuron population size during circuit formation.

5.
J Pharm Sci ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33049258

RESUMO

Ursolic acid (UA) is a common pentacyclic triterpene phytochemical with various pharmacological activities. However, UA is classified as a class IV drug in BCS system and its development as an oral drug is limited. Pulmonary delivery is an effective way to improve the bioavailability of drugs with low absorption. In this study, the differences in pharmacokinetic behaviors of UA after pulmonary and oral administration was explored in rats. Compared with oral administration, the plasma concentration of UA increased rapidly after pulmonary administration, and the bioavailability increased about 80 times. UA instantly accumulated in the lungs after pulmonary administration, and the pulmonary AUC0-t/dose increased by 114 times compared to oral dosing. Incubation experiments showed that the metabolism of UA in rat lung microsomes was significantly reduced compared with that in liver microsomes, in which the clearance rate of phase I and phase II metabolism was reduced by 14.7 times and 1.4 times respectively. These results indicated that pulmonary administration could improve the bioavailability of UA and reduce its metabolism. This study not only provides a preferable route of administration for the application of UA but also offers new insights for the development of phytochemical drug candidates with poor pharmacokinetic properties.

6.
Theranostics ; 10(25): 11607-11621, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33052236

RESUMO

The hypoxic microenvironment in solid tumors severely limits the efficacy of photodynamic therapy (PDT). Therefore, the development of nanocarriers co-loaded with photosensitizers and oxygen, together with imaging guidance ability, is of great significance in cancer therapy. However, previously reported synthetic methods for these multi-functional probes are complicated, and the raw materials used are toxic. Methods: Herein, the human endogenous protein, hemoglobin (Hb), was used for the simultaneous biomimetic synthesis of Gd-based nanostructures and co-loading of Chlorine e6 (Ce6) and oxygen for alleviating the hypoxic environment of tumors and accomplishing magnetic resonance imaging (MRI)-guided enhanced PDT. The Gd@HbCe6-PEG nanoprobes were synthesized via a green and protein biomimetic approach. The physicochemical properties, including relaxivity, oxygen-carrying/release capability, and PDT efficacy of Gd@HbCe6-PEG, were measured in vitro and in vivo on tumor-bearing mice after intravenous injection. Morphologic and functional MRI were carried out to evaluate the efficacy of PDT. Results: The results demonstrated the successful synthesis of compact Gd@HbCe6-PEG nanostructures with desired multi-functionalities. Following treatment with the nanoparticles, the embedded MR moiety was effective in lighting tumor lesions and guiding therapy. The oxygen-carrying capability of Hb after biomimetic synthesis was confirmed by spectroscopic analysis and oxygen detector in vitro. Further, tumor oxygenation for alleviating tumor hypoxia in vivo after intravenous injection of Gd@HbCe6-PEG was verified by photoacoustic imaging and immunofluorescence staining. The potent treatment efficacy of PDT on early-stage was observed by the morphologic and functional MR imaging. Importantly, rapid renal clearance of the particles was observed after treatment. Conclusion: In this study, by using a human endogenous protein, we demonstrated the biomimetic synthesis of multi-functional nanoprobes for simultaneous tumor oxygenation and imaging-guided enhanced PDT. The therapeutic efficacy could be quantitatively confirmed at 6 h post PDT with diffusion-weighted imaging (DWI).

7.
Braz J Med Biol Res ; 53(11): e9798, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33053117

RESUMO

Osteoblast differentiation is an effective way to promote bone formation. Long non-coding RNA taurine upregulated 1 (TUG1) has been identified as a crucial modulator of multiple biological processes. This study was designed to investigate the function of TUG1 in the proliferation and differentiation of osteoblast precursor cells hFOB1.19. In this study, we found that TUG1 promoted hFOB1.19 cell proliferation, while TUG1 knockdown hindered cell proliferation. TUG1 and cannabinoid receptor 2 (CNR2) were upregulated, while miR-545-3p was down-regulated in hFOB1.19 cells undergoing osteoblastic differentiation. TUG1 induced osteoblast differentiation by increasing alkaline phosphatase (ALP) activity and the expression of osteoblastic differentiation markers. TUG1 was a sponge of miR-545-3p and regulated osteoblastic differentiation by modulating miR-545-3p. Moreover, miR-545-3p directly targeted CNR2 and restored the effect of CNR2 on osteoblastic differentiation. In conclusion, TUG1 accelerated the proliferation and differentiation of osteoblasts by sponging miR-545-3p and increasing CNR2 expression, which might provide a new biomarker for bone diseases.

8.
Colloids Surf B Biointerfaces ; 197: 111377, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33022539

RESUMO

Combinational photothermal-chemotherapy offers great advantages for the treatment of cancer. To achieve this goal, the poly-tannic acid (pTA) coated paclitaxel nanocrystals (PNC) were prepared, which was denoted as PNC-pTA. Herein, paclitaxel (PTX) was prepared as nanocrystals acting as chemo-agent for chemotherapy. And the tannic acid formed a pTA layer coated on PNC in the presence of Fe3+ serving as a potential agent for photothermal therapy (PTT). PNC-pTA was around 470 nm in rod shape and the pTA content was determined to be 11.50 ± 0.48 wt% by mass ratio. pTA exhibited photothermal effect upon laser irradiation of 808 nm, and this effect could be strengthened with the increased amount of Fe3+ in pTA. Moreover, pTA showed excellent photostability under repeated laser irradiation. And with the aid of pTA, the cellular uptake of PNC-pTA was greatly enhanced for different cancerous cell lines. PNC-pTA plus laser irradiation showed much stronger cytotoxicity against the 4T1 cell line compared with that without laser irradiation. And the result of animal experiments showed that PNC-pTA exhibited mild photothermal effect in vivo and the strongest tumor inhibition effect upon laser irradiation compared with single photothermal therapy or chemotherapy. These results confirmed the combinational chemo-photothermal effect of PNC-pTA. Our study provided a versatile platform to achieve combined photothermal-chemotherapy with enhanced therapeutic efficacy.

9.
Biopolymers ; : e23404, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33075850

RESUMO

Spiders can produce up to seven different types of silks or glues with different mechanical properties. Of these, flagelliform (Flag) silk is the most elastic, and aciniform (AcSp1) silk is the toughest. To produce a chimeric spider silk (spidroin) FlagR -AcSp1R , we fused one repetitive module of flagelliform silk from Araneus ventricosus and one repetitive module of aciniform silk from Argiope trifasciata. The recombinant protein expressed in E. coli formed silk-like fibers by manual-drawing. CD analysis showed that the secondary structure of FlagR -AcSp1R spidroin remained stable during the gradual reduction of pH from 7.0 to 5.5. The spectrum of FTIR indicated that the secondary structure of FlagR -AcSp1R changed from α-helix to ß-sheet. The conformation change of FlagR -AcSp1R was similar to other spidroins in the fiber formation process. SEM analysis revealed that the mean diameter of the fibers was around 1 ~ 2 µm, and the surface was smooth and uniform. The chimeric fibers exhibited superior toughness (~33.1 MJ/m3 ) and tensile strength (~261.4 MPa). This study provides new insight into design of chimeric spider silks with high mechanical properties.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32893390

RESUMO

Exciplex-forming hosts with thermally activated delayed fluorescence (TADF) provide a viable opportunity to unlock the full potential of the yet-to-be improved power efficiencies (PEs) and stabilities of all-fluorescent white organic light-emitting diodes (WOLEDs), but this, however, is hindered by the lack of stable blue exciplexes. Here, an advanced exciplex system is proposed by incorporating bipolar charge-transport π-spacers into both the electron-donor (D) and the electron-accepter (A) to increase their distance for hypsochromic-shifted emission while maintaining the superior transporting ability. By using spirofluorene as the π-spacer, 3,3'-bicarbazole as the D-unit, and 2,4,6-triphenyl-1,3,5-triazine as the A-unit, a π-D and π-A exciplex with sky-blue emission and fast reverse intersystem crossing process is thereof constructed. Combining this exciplex-forming host, a blue TADF-sensitizer, and a yellow conventional fluorescent dopant in a single-emissive-layer, the fabricated warm-white-emissive device simultaneously exhibits a low driving voltage of 3.08 V, an external quantum efficiency of 21.4%, and a remarkable T80 (time to 80% of the initial luminance) of >8200 h at 1000 cd m-2 , accompanied by a new benchmark PE of 69.6 lm W-1 among all-fluorescent WOLEDs.

12.
Nat Prod Bioprospect ; 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948973

RESUMO

Flavonoids are now considered as an indispensable component in a variety of nutraceutical and pharmaceutical applications. Most recent researches have focused on the health aspects of flavonoids for humans. Especially, different flavonoids have been investigated for their potential antiviral activities, and several natural flavonoids exhibited significant antiviral properties both in vitro and in vivo. This review provides a survey of the literature regarding the evidence for antiviral bioactivities of natural flavonoids, highlights the cellular and molecular mechanisms of natural flavonoids on viruses, and presents the details of most reported flavonoids. Meanwhile, future perspectives on therapeutic applications of flavonoids against viral infections were discussed.

13.
J Clin Lab Anal ; : e23579, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32964536

RESUMO

BACKGROUND: Tracheobronchial foreign body aspiration is a potentially risky medical event, while the condition often requires early detection and rapid intervention to improve respiratory symptoms and prevent major morbidity. Notably, foreign bodies may not be identified and they are likely to be mistaken for neoplastic lesions. However, CEA, as one of tumor markers, presents to be available for assisting in lung cancer diagnosis, especially for non-small-cell lung cancer, while the specificity of CEA is not high. METHODS: Here, we described a case of bronchial opening obstruction with elevated carcinoembryonic antigen (CEA) that was firstly misdiagnosed as lung cancer and proved as foreign body aspiration in the upper lobe bronchus of right lung by bronchoscopy. RESULTS: Carcinoembryonic antigen level increased. CT scan demonstrated a cavitation accompanied by multiple small nodular shadows appeared in the right upper lobe field. Bronchoscopy suggested right upper lobe bronchus was blocked by a brown smooth organism with plenty of purulent materials, which was proved as a rotten vegetable leaf. CONCLUSIONS: Elevated CEA and bronchial obstruction are not typical manifestations of lung cancer. Bronchoscopy is crucial for making a reliable diagnosis.

14.
J Hematol Oncol ; 13(1): 122, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894185

RESUMO

BACKGROUND: Recent evidence suggests that resistance to CD19 chimeric antigen receptor (CAR)-modified T cell therapy may be due to the presence of CD19 isoforms that lose binding to the single-chain variable fragment (scFv) in current use. As such, further investigation of CARs recognize different epitopes of CD19 antigen may be necessary. METHODS: We generated a new CD19 CAR T (HI19α-4-1BB-ζ CAR T, or CNCT19) that includes an scFv that interacts with an epitope of the human CD19 antigen that can be distinguished from that recognized by the current FMC63 clone. A pilot study was undertaken to assess the safety and feasibility of CNCT19-based therapy in both pediatric and adult patients with relapsed/refractory acute lymphoblastic leukemia (R/R B-ALL). RESULTS: Data from our study suggested that 90% of the 20 patients treated with infusions of CNCT19 cells reached complete remission or complete remission with incomplete count recovery (CR/CRi) within 28 days. The CR/CRi rate was 82% when we took into account the fully enrolled 22 patients in an intention-to-treat analysis. Of note, extramedullary leukemia disease of two relapsed patients disappeared completely after CNCT19 cell infusion. After a median follow-up of 10.09 months (range, 0.49-24.02 months), the median overall survival and relapse-free survival for the 20 patients treated with CNCT19 cells was 12.91 months (95% confidence interval [CI], 7.74-18.08 months) and 6.93 months (95% CI, 3.13-10.73 months), respectively. Differences with respect to immune profiles associated with a long-term response following CAR T cell therapy were also addressed. Our results revealed that a relatively low percentage of CD8+ naïve T cells was an independent factor associated with a shorter period of relapse-free survival (p = 0.012, 95% CI, 0.017-0.601). CONCLUSIONS: The results presented in this study indicate that CNCT19 cells have potent anti-leukemic activities in patients with R/R B-ALL. Furthermore, our findings suggest that the percentage of CD8+ naïve T cells may be a useful biomarker to predict the long-term prognosis for patients undergoing CAR T cell therapy. TRIAL REGISTRATION: ClinicalTrials.gov : NCT02975687; registered 29 November, 2016. https://clinicaltrials.gov/ct2/keydates/NCT02975687.

15.
Pharmacol Ther ; : 107686, 2020 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-32961262

RESUMO

Natural products have been the main sources of new drugs. The different strategies have been developed to find the new drugs based on natural products. The traditional and ethic medicines have provided information on the therapeutic effects and resulted in some notable drug discovery of natural products. The special activities of the medicine plants such as the side effects have inspired scientists to develop the novel small molecular. The microorganisms and the endogenous active substances from human or animal also become the important approaches to the drug discovery. The tremendous progress in technology led to the new strategies in drug discovery from natural products. The bioinformation and artificial intelligence have facilitated the research and development of natural products. We will provide a scene of strategies and technologies for drug discovery from natural products in this review.

16.
mBio ; 11(5)2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32900808

RESUMO

This study describes the first direct functional assignment of a highly abundant extracellular protein from a key environmental and biotechnological biofilm performing an anaerobic ammonium oxidation (anammox) process. Expression levels of Brosi_A1236, belonging to a class of proteins previously suggested to be cell surface associated, were in the top one percentile of all genes in the "Candidatus Brocadia sinica"-enriched biofilm. The Brosi_A1236 structure was computationally predicted to consist of immunoglobulin-like anti-parallel ß-strands, and circular dichroism conducted on the isolated surface protein indicated that ß-strands are the dominant higher-order structure. The isolated protein was stained positively by the ß-sheet-specific stain thioflavin T, along with cell surface- and matrix-associated regions of the biofilm. The surface protein has a large unstructured content, including two highly disordered domains at its C terminus. The disordered domains bound to the substratum and thereby facilitated the adhesion of negatively charged latex microspheres, which were used as a proxy for cells. The disordered domains and isolated whole surface protein also underwent liquid-liquid phase separation to form liquid droplets in suspension. Liquid droplets of disordered protein wet the surfaces of microspheres and bacterial cells and facilitated their coalescence. Furthermore, the surface layer protein formed gels as well as ordered crystalline structures. These observations suggest that biophysical remodeling through phase transitions promotes aggregation and biofilm formation.IMPORTANCE By employing biophysical and liquid-liquid phase separation concepts, this study revealed how a highly abundant extracellular protein enhances the key environmental and industrial bioprocess of anaerobic ammonium oxidation (anammox). Extracellular proteins of environmental biofilms are understudied and poorly annotated in public databases. Understanding the function of extracellular proteins is also increasingly important for improving bioprocesses and resource recovery. Here, protein functions were assessed based on theoretical predictions of intrinsically disordered domains, known to promote adhesion and liquid-liquid phase separation, and available surface layer protein properties. A model is thus proposed to explain how the protein promotes aggregation and biofilm formation by extracellular matrix remodeling and phase transitions. This work provides a strong foundation for functional investigations of extracellular proteins involved in biofilm development.

17.
Pharmaceutics ; 12(10)2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32977470

RESUMO

Bexarotene (BEX), a specific retinoic acid X receptor (RXR) agonist granted by Food and Drug Administration (FDA) approval for the clinical treatment of T cell lymphoma, has now been found to exert pharmacological effects in the nervous system, with low bioavailability and poor cerebral distribution limiting its application in treatment on neurological disorders. Pharmaceutical co-crystal was a helpful method to improve the bioavailability and tissue distribution of active pharmaceutical ingredients (APIs). Here, 2bexarotene-ligustrazine (2BEX-LIG), a novel co-crystal system of BEX and ligustrazine (LIG) of which with BEX is an API, was constructed with satisfactory stability and enhanced solubility. The pharmacokinetics characteristics of BEX were detected, and the results showed that the absolute bioavailability and the cerebral concentration of BEX in rats administrated with 2BEX-LIG were enhanced from 22.89% to 42.86% and increased by 3.4-fold, respectively, compared with those in rats administrated an equivalent of BEX. Hence, our present study indicated that the novel co-crystal of 2BEX-LIG contributed to improving BEX oral bioavailability and cerebral distribution, thereby providing significant advantages for clinical application of brain tumors and other neurological diseases.

18.
Pathogens ; 9(10)2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32977715

RESUMO

Handwashing with soap is an effective and economical means to reduce the likelihood of Escherichia coli infection from indirect contact with contaminated surfaces during food preparation. The purpose of this study was to conduct a quantitative microbial risk assessment (QMRA) to evaluate the risk of infection from indirect contact with fomites contaminated with E. coli after hand washing with antimicrobial hand soaps. A Monte Carlo simulation was done with a total of 10,000 simulations to compare the effectiveness of two antimicrobial and one control (non-antimicrobial) bar soaps in reducing the exposure and infection risk compared to no hand washing. The numbers of E. coli on several fomites commonly found in household kitchens, as well as the transfer rates between fomites and onto fingertips, were collected from the literature and experimental data. The sponsor company provided the E. coli survival on hands after washing with antimicrobial and control soaps. A number of scenarios were evaluated at two different exposure doses (high and low). Exposure scenarios included transfer of E. coli between meat-to-cutting board surface-to-hands, meat-to-knife surface-to-hands, and from a countertop surface-to-hands, kitchen sponge-to-hands, hand towel-to-hands, and dishcloth-to-hands. Results showed that the risks of illness after washing with the control soap was reduced approximately 5-fold compared to no handwashing. Washing with antimicrobial soap reduced the risk of E. coli infection by an average of about 40-fold compared with no handwashing. The antimicrobial soaps ranged from 3 to 32 times more effective than the non-antimicrobial soap, depending on the specific exposure scenario. Importance: The Centers for Disease Control and Prevention indicate the yearly incidence rate of Shiga Toxin producing E. coli infections is about 1.7/100,000, with about 10% of cases leading to life-threatening hemolytic uremic syndrome and 3-5% leading to death. Our findings confirm handwashing with soap reduces the risks associated with indirect transmission of E. coli infection from contact with fomites during food preparation. Further, in these exposure scenarios, antimicrobial soaps were more effective overall than the non-antimicrobial soap in reducing exposure to E. coli and risk of infection.

19.
Sci Rep ; 10(1): 15332, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948811

RESUMO

The temperature-dependent mechanical behaviors of open-hole composite plates are essential for composite design and structures. Here, tensile experiments of shallow straight-link-shaped 2.5D woven composites (abbr. 2.5DWC) with/without a center hole are first conducted at different temperatures (20 °C, 180 °C and 240 °C). Failure modes are examined by scanning electron microscope (SEM). Thermal property of QY8911-IV resin is investigated by DMA analysis. It is noted for samples without the center hole that with the increase of temperature, the tensile stress-strain curves exhibit a linear response until that a slight nonlinearity at the end stage. The strength retention rates at 180 °C and 240 °C are totally equal. For the open-hole samples, it is interestingly found that the strength retention rates are higher than that of samples without the hole at 180 °C, resulting from the stress concentration accommodation and fiber-dominated failure mode. Even at 240 °C, there is no necking phenomenon for all the failed samples, but more broom-like damage extent is observed in the cross-section. Due to the primary load-bearing warp yarns and hole-edge stress concentration, obvious pull-out warp yarns emerge near the hole edge.

20.
Eur J Med Chem ; 207: 112818, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32937281

RESUMO

Neuroblastoma (NB) is one of the most common pediatric malignancies. Easy metastasis, poor prognosis, and a high degree of heterogeneity of NB hinder its successful treatment. Several different therapeutic strategies have been developed to overcome these problems, including differentiation and targeted therapy. In this review, we summarize the recent development of differentiation modulators and targeted agents for treating NB. Several promising targets of NB were also discussed.

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