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1.
Updates Surg ; 2020 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-32980964

RESUMO

Reversal of loop ileostomy after colorectal surgery in obese patients can be challenging and total laparoscopic (TLAP) approach may be beneficial. This study aims to compare short-term outcomes of TLAP and open approaches in obese patients undergoing loop ileostomy reversal after laparoscopic-assisted colorectal surgery. A retrospective review was performed for consecutive patients who underwent laparoscopic-assisted colorectal surgery previously and underwent loop ileostomy reversal between January 2017 and April 2020. TLAP and open cases performed in obese patients were identified and compared for the following outcomes: baseline characteristics, operative outcomes, postoperative recovery, and postoperative complications. TLAP or open-loop ileostomy reversal was performed on 30 and 34 patients, respectively. TLAP approach was associated with a similar operation time and blood loss compared with an open approach (P > 0.05). The median length of incision for stoma removal was significantly shorter in the TLAP group than in the open group (6.5 cm vs. 8.5 cm; P < 0.05), and a lower incidence of incisional infection was also noted in the TLAP group (6.7% vs. 26.5%; P < 0.05). The groups were comparable as regards the time to ground activities and length of hospitalization (P > 0.05), but the time to first flatus was decreased (2.0 vs. 3.0 days; P < 0.05). This retrospective study demonstrated that TLAP loop ileostomy reversal may have a satisfactory short-term outcome for obese patients after laparoscopic-assisted colorectal surgery, with a shorter incisional length and a lower incidence of incisional infection as well as an earlier time to first flatus.

2.
PLoS One ; 15(9): e0239768, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32960923

RESUMO

[This corrects the article DOI: 10.1371/journal.pone.0097342.].

3.
Sci Rep ; 10(1): 15345, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948794

RESUMO

The van der Waals ferromagnet Fe5GeTe2 has a Curie temperature TC of about 270 K, which is tunable through controlling the Fe deficiency content and can even reach above room temperature. To achieve insights into its ferromagnetic exchange that gives the high TC, the critical behavior has been investigated by measuring the magnetization in Fe5GeTe2 crystal around the ferromagnetic ordering temperature. The analysis of the measured magnetization by using various techniques harmonically reached to a set of reliable critical exponents with TC = 273.7 K, ß = 0.3457 ± 0.001, γ = 1.40617 ± 0.003, and δ = 5.021 ± 0.001. By comparing these critical exponents with those predicted by various models, it seems that the magnetic properties of Fe5GeTe2 could be interpreted by a three-dimensional magnetic exchange with the exchange distance decaying as J(r) ≈ r-4.916, close to that of a three-dimensional Heisenberg model with long-range magnetic coupling.

4.
Biomaterials ; 262: 120338, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32916604

RESUMO

Despite advancements in antibody-based therapies for non-Hodgkin lymphoma (NHL), at least two major therapeutic needs remain unmet: i) heterogenous activation of host immunity towards B cell NHL; and ii) lack of antibody-based therapeutics for T cell NHL. This study explores the molecular characteristics of an adaptable modality called antibody Nanoworms and demonstrates their receptor clustering activity as a means to overcome and address abovementioned needs. To test this, four selected therapeutic receptors of B cell (CD19, CD20, HLA-DR10) and T cell (CD3) NHL were targeted by Nanoworms. Regardless of the target or the cell type, Nanoworms inherently clustered bound receptors on the cell-surface through their multivalency and activated intracellular signaling without any secondary crosslinker. As a sole agent, Nanoworms induced apoptosis by clustering CD20 or HLA-DR10, and arrested the cell cycle upon CD19 clustering. Interestingly, CD3 clustering was particularly advantageous in inducing activation-induced cell death (AICD) in an aggressive form of T cell NHL named Sézary syndrome that is fatal, limited in antibody-based therapeutics, and has poor outcomes to traditional chemotherapy. As Nanoworms can be easily designed to target any receptor for which a scFv is available, they may provide solutions and add therapeutic novelty to underserved diseases.

5.
Food Res Int ; 136: 109329, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32846528

RESUMO

Hong Qu glutinous rice wine (HQGRW) is produced from glutinous rice with the addition of the traditional fermentation starter Hong Qu (mainly Gutian Hong Qu and Wuyi Hong Qu) has been added. It is unpalatable and rejected by consumers because the bitter and umami tastes are too high. The objective of this study was to compare the dynamics of the microbial communities and amino acids especially those in the different traditional fermentation starters used during HQGRW fermentation, and elucidate the key microbes responsible for amino acids. Three widely-used types of Hong Qu starters were used which can make different bitterness and umami in our previous studies, namely, black Wuyi Hong Qu (WB), red Wuyi Hong Qu (WR), and Gutian Hong Qu (GT). The living dynamics of fungal and bacterial communities during the fermentation were determined by high-throughput sequencing and rRNA gene sequencing technology for the first time. The content of amino acids in the HQGRW were determined by reverse-phase high-performance liquid chromatography analysis. The results showed that there were differences between fungal communities during the fermentation process in Wuyi Hong Qu and Gutian Hong Qu starters and between bacterial communities during the fermentation process in the three types of starters. The amino acid content of the samples showed an increasing trend in each group. The total amino acids, as well as the bitter, sweet, umami, astringent amino acids, in the GT Hong Qu group increased more slowly during fermentation, as comparerd to those in WB and WR groups. Furthermore, Meyerozyma, Saccharomyces, Bacillus, Rhizopus, Pediococcus, Monascus, and Halomonas were strongly positively correlated with the content of bitter and umami amino acids (|r| > 0.6 with FDR adjusted P < 0.05) by Spearman's correlation analysis. To conclude, these findings may contribute to a better understanding of the bitter and umami amino acid production mechanism during traditional fermentation and helpful in improving the taste of HQGRW.

6.
J Cell Mol Med ; 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32757458

RESUMO

Cardiomyocyte dysfunction is attributed to excess oxidative damage, but the molecular pathways involved in this process have not been completely elucidated. Evidence indicates that isosteviol sodium (STVNa) has cardioprotective effects. We therefore aimed to identify the effect of STVNa on cardiomyocytes, as well as the potential mechanisms involved in this process. We established two myocardial hypertrophy models by treating H9c2 cells with high glucose (HG) and isoprenaline (ISO). Our results showed that STVNa reduced H9c2 mitochondrial damage by attenuating oxidative damage and altering the morphology of mitochondria. The results also indicated that STVNa had a positive effect on HG- and ISO-induced damages via mitochondrial biogenesis. The protective effects of STVNa on cardiomyocytes were associated with the regulation of the SIRT1/PGC-1α signalling pathway. Importantly, the effects of STVNa involved different methods of regulation in the two models, which was confirmed by experiments using an inhibitor and activator of SIRT1. Together, the results provide the basis for using STVNa as a therapy for the prevention of cardiomyocyte dysfunctions.

7.
ACS Nano ; 14(8): 10083-10094, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32806082

RESUMO

Local chemotherapy is a clinically proven strategy in treating malignant brain tumors. Its benefits, however, are largely limited by the rapid release and clearance of therapeutic agents and the inability to penetrate through tumor tissues. We report here on a supramolecular tubustecan (TT) hydrogel as both a therapeutic and drug carrier that enables long-term, sustained drug release and improved tumor tissue penetration. Covalent linkage of a tissue penetrating cyclic peptide to two camptothecin drug units creates a TT prodrug amphiphile that can associate into tubular supramolecular polymers and subsequently form a well-defined sphere-shaped hydrogel after injection into tumor tissues. The hollow nature of the resultant tubular assemblies allows for encapsulation of doxorubicin or curcumin for combination therapy. Our in vitro and in vivo studies reveal that these dual drug-bearing supramolecular hydrogels enhance tumor retention and penetration, serving as a local therapeutic depot for potent tumor regression, inhibition of tumor metastasis and recurrence, and mitigation of the off-target side effects.

8.
Chem Commun (Camb) ; 56(76): 11287-11290, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32839790

RESUMO

Pyridinium ylides are usually considered nucleophiles that can undergo various reactions involving electron pairs. However, it was found that ylides resulting from deprotonation of N-alkyl-substituted pyridinium salts exhibit radical characters, with no discernable NMR signals but decent EPR spectra in both solution and the solid state. An observed correlation between lowered π* energy level of the pyridinium ring and increased EPR activity indicates that thermally induced electron-transfer processes could be involved, where the variable-temperature EPR spectrum indicates a singlet ground state and a thermally activated triplet state for the ylide. The fact that the high-resolution mass spectrum confirms the presence of oligomers of a less sterically hindered pyridinium ylide further points to a radical mechanism.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32815710

RESUMO

Detection of γ-rays is of vital significance in various areas such as high-energy physics, nuclear medicine, national security, and space exploration. However, many current spectrometry methods are based on ionization effects, which are limited to electron counting and related techniques such as ionization-induced luminescence. Herein, we report an alternative, quantifiable γ-ray chemosensor based on a secondary effect from this ionizing radiation, that is, it was discovered that poly(methyl methacrylate) (PMMA) and polyvinyl chloride (PVC) are more sensitive to a γ-ray-induced acid generation process by surveying a series of commercially available polymers. Accordingly, a pH-sensitive fluorescent quinoline derivative is designed and embedded in PMMA or PVC films, which exhibits dramatic emission shift from blue (λem = 460-480 nm) to red (λem = 570-620 nm) upon exposure to γ-irradiation. A linear response of ratiometric fluorescence intensity (Ired/Iblue) to γ-ray dosage in a wide range (80-4060 Gy) was established, which can be used as a practical visual dosimeter complementary to current techniques.

10.
Nat Biomed Eng ; 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32778697

RESUMO

Tumours with an immunosuppressive microenvironment respond poorly to therapy. Activation of the stimulator of interferon genes (STING) pathway can enhance intratumoural immune activation, but STING agonists are associated with high toxicity and degrade prematurely, which limits their effectiveness. Here, we show that the extended intratumoural release of the STING agonist cyclic di-AMP transforms the tumour microenvironment from immunosuppressive to immunostimulatory, increasing the efficacy of antitumour therapies. The STING agonist was electrostatically complexed with nanotubes comprising a peptide-drug conjugate (a peptide that binds to the protein neuropilin-1, which is highly expressed in tumours, and the chemotherapeutic agent camptothecin) that self-assemble in situ into a supramolecular hydrogel. In multiple mouse models of murine tumours, a single low dose of the STING agonist led to tumour regression and increased animal survival, and to long-term immunological memory and systemic immune surveillance, which protected the mice against tumour recurrence and the formation of metastases. Locally delivered STING agonists could help to reduce tumour immunosuppression and enhance the efficacy of a wide range of cancer therapies.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32840291

RESUMO

Skin epidermal stem cells (EpSCs) play an important role in wound healing. Quercetin is a phytoestrogen reported to accelerate skin wound healing, but its effect on EpSCs is unknown. In this study, we investigated the effect of quercetin on human EpSC proliferation and explored the underlying mechanisms. We found that quercetin at 0.1~1 µM significantly promoted EpSC proliferation and increased the number of cells in S phase. The pro-proliferative effect of quercetin on EpSCs was confirmed in cultured human skin tissue. Mechanistic studies showed that quercetin significantly upregulated the expressions of ß-catenin, c-Myc, and cyclins A2 and E1. Inhibitor for ß-catenin or c-Myc significantly inhibited quercetin-induced EpSC proliferation. The ß-catenin inhibitor XAV-939 suppressed quercetin-induced expressions of ß-catenin, c-Myc, and cyclins A2 and E1. The c-Myc inhibitor 10058-F4 inhibited the upregulation of c-Myc and cyclin A2 by quercetin. Pretreatment of EpSCs with estrogen receptor (ER) antagonist ICI182780, but not the G protein-coupled ER1 antagonist G15, reversed quercetin-induced cell proliferation and upregulation of ß-catenin, c-Myc, and cyclin A2. Collectively, these results indicate that quercetin promotes EpSC proliferation through ER-mediated activation of ß-catenin/c-Myc/cyclinA2 signaling pathway and ER-independent upregulation of cyclin E1 and that quercetin may accelerate skin wound healing through promoting EpSC proliferation. As EpSCs are used not only in clinic to treat skin wounds but also as seed cells in skin tissue engineering, quercetin is a useful reagent to expand EpSCs for basic research, skin wound treatment, and skin tissue engineering.

12.
Artigo em Inglês | MEDLINE | ID: mdl-32705794

RESUMO

A promising route to the synthesis of protein-mimetic materials that are capable of strong mechanics and complex functions is provided by intermolecular ß-sheet stacking. An understanding of the assembly mechanism on ß-sheet stacking at molecular-level and the related influencing factors determine the potential to design polymorphs of such biomaterials towards broad applications. Herein, we quantitatively reveal the air/water interface (AWI) parameters regulating the transformation from crowding amorphous aggregates to ordered phase and show that the polymorph diversity of ß-sheet stacking is regulated by the chain relaxation-crystallization mechanism. An amorphous macroscale amyloid-like nanofilm is formed at the AWI, in which unfolded protein chains are aligned in a short-range manner to form randomly packed ß-sheets. The subsequent biopolymer chain relaxation-crystallization to form nanocrystals is further triggered by removing the limitations of energy and space at the AWI.

13.
World J Surg Oncol ; 18(1): 159, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32635945

RESUMO

BACKGROUND: To evaluate the feasibility and safety of a new surgical method, complete laparoscopic extended right hemicolectomy with preservation of the ileocecal junction in right-transverse colon cancer. METHODS: We retrospectively analyzed and compared the data of consecutive patients with right-transverse colon cancer who underwent complete laparoscopic extended right hemicolectomy with preservation of the ileocecal junction (n = 23) and conventional complete laparoscopic extended right hemicolectomy (n = 34) in our hospital between October 2017 to May 2019, respectively. RESULTS: The overall operation time of the ileocecal junction-preserved group was significantly shorter than that of the control group (p = 0.048). There was no difference in the number of harvested lymph nodes, metastatic lymph nodes, and rate of metastatic lymph nodes (p > 0.05). The ileocecal junction-preserved group showed shorter time of first flatus, lower frequency of postoperative diarrhea, and shorter duration of postoperative hospitalization. Furthermore, it also showed that the defecation frequency was lower in the ileocecal junction-preserved group than the control group on the 1st, 3rd, and 6th month (p < 0.05), and the number of patients who defecated at night or defecated four times or more a day was less in the ileocecal junction-preserved group than control group on the 1st month (p < 0.05). CONCLUSION: The complete laparoscopic extended right hemicolectomy with preservation of the ileocecal junction promises as a safe and feasible surgical procedure for right-transverse colon cancer, associated with earlier recovery of bowel function, shorter operation time, and similar pathological outcomes when compared to the conventional laparoscopic procedure.

14.
Genes (Basel) ; 11(6)2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32604723

RESUMO

BACKGROUND: So far, numerous meta-analyses have been published regarding the correlation between peroxisome proliferator-activated receptor gamma (PPARG) proline 12 alanine (Pro12Ala) gene polymorphism and chronic kidney disease (CKD); however, the results appear to be contradictory. Hence, this study is formulated with the objective of using existing meta-analysis data together with our research population to study the correlation between PPARG Pro12Ala gene polymorphism and CKD and evaluate whether an accurate result can be obtained. METHODS: First, literature related to CKD and PPARG Pro12Ala available on the PubMed and EMBASE databases up to December 2016 was gathered from 20 publications. Then, the gathered results were combined with our case-control study of 1693 enrolled subjects and a trial sequential analysis (TSA) was performed to verify existing evidence and determine whether a firm conclusion can be drawn. RESULTS: The TSA results showed that the cumulative sample size for the Asian sample was 6078 and was sufficient to support a definite result. The results of this study confirmed that there is no obvious correlation between PPARG Pro12Ala and CKD for Asians (OR = 0.82 (95% CI = 0.66-1.02), I2 = 63.1%), but this was not confirmed for Caucasians. Furthermore, the case-control sample in our study was shown to be the key for reaching this conclusion. CONCLUSIONS: The meta-analysis results of this study suggest no significant correlation between PPARG Pro12Ala gene polymorphism and CKD for Asians after adding our samples, but not for Caucasian.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32627526

RESUMO

Solid polymer electrolyte (SPE) is one of the choices for many ionic devices, including organic transistors, ion batteries, memristors, and more. However, uncontrollable conductive filament formation seriously affects the performance of the device. In this paper, the PEDOT:PSS was doped to improve the electronic and ionic conductivity of amorphous polymer electrolyte poly(vinylpyrrolidone) (PVP), realizing the transition of the filaments growth from cathode to anode in atomic switch memristors. Based on the difference in ion and electron mobility and scanning electron microscope observation, the in situ reductions of metal ions inside the dielectric layer can effectively prevent the formation of uncontrollable filaments. The formation of uniformly distributed metal particles in the dielectric layer is similar to co-sputter doping technology, which enables the device to exhibit excellent performance, such as smaller set/reset bias distribution, endurance, and retention. Obviously, this innovative way improves the conductive mechanism of ionic devices.

16.
Medicine (Baltimore) ; 99(29): e21045, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702845

RESUMO

BACKGROUND: Previous meta-analyses have explored the association between the C677T polymorphism of methyltetrahydrofolate reductase (MTHFR) and chronic kidney disease (CKD) but there were no studies with a decisive conclusion. Furthermore, the high heterogeneity among different populations is not yet interpreted. OBJECTIVES: This study used trial sequential analysis (TSA) to evaluate whether the nowadays conclusion supported by current cumulative samples. We also applied case-weighted meta-regression to explore the potential gene-environment interactions. METHODS: For the first stage of this study we conducted a case-control study involving 847 dialysis patients from 7 hemodialysis centers in Taipei during 2015 to 2018 and 755 normal controls from a health center in the Tri-Service General Hospital. The second stage combined the results from the first stage with previous studies. The previous studies were collected from PubMed, EMBASE, and Web of Science databases before January 2018. RESULTS: From the case-control study, the T allele of MTHFR C677T appeared to have a protective effect on end-stage renal disease compared with the C allele [odds ratio (OR): 0.80, 95% CI (confidence interval) = 0.69-0.93]. However, the meta-analysis contradicted the results in Asian (OR = 1.12, 95% CI = 0.96-1.30). The same analysis was also applied in Caucasian and presented similar results from Asian (OR = 1.18, 95% CI = 0.98-1.42). The TSA showed our case-control study to be the decisive sample leading to a null association among Asian population. The high heterogeneity (I = 75%) could explain the contradictory results between the case-control study and the meta-analysis. However, further case-weighted meta-regression did not find any significant interaction between measured factors and MTHFR C677T on CKD. CONCLUSIONS: High heterogeneities were found in both Caucasian and Asian, which caused the null relationship in meta-analysis while there were significant effects in individual studies. Future studies should further explore the high heterogeneity that might be hidden in unmeasured gene-environment interactions, to explain the diverse findings among different populations.


Assuntos
Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Insuficiência Renal Crônica/genética , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Humanos , Masculino , Taiwan
17.
Biomater Sci ; 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32648884

RESUMO

Therapeutic constructs with imaging modalities hold great promise for improving the treatment efficacy for cancer and many other diseases. We report here the design and synthesis of a self-assembling prodrug (SAPD) by the direct linkage of camptothecin (CPT), an anticancer drug, to a metal-chelating agent, DOTA. We found that under physiological conditions the DOTA-conjugated CPT prodrug can self-assemble into tubular supramolecular polymers (SPs) with a length of several micrometers. Our studies also suggest that the resultant assemblies were stable in biological environments and exhibited a fast drug release rate in the presence of intracellular glutathione. Furthermore, the SAPD exhibited remarkable in vitro efficacy against various cancer cell lines and effectively inhibited the growth of tumor spheroids. We believe that the design and optimization of self-assembling theranostic conjugates could provide a robust yet simple platform for the development of new imaging-guided drug delivery systems.

18.
Curr Pharm Des ; 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503400

RESUMO

BACKGROUND & AIMS: Nowadays, world is facing a common problem that population aging process is accelerating. How to delay metabolic disorders in middle-aged and elderly people has become a hot scientific and social issue worthy of attention. The liver plays an important role in lipid metabolism, and abnormal lipid metabolism may lead to liver diseases. Exercise is an easily controlled and implemented intervention, which has attracted extensive attention in improving the health of liver lipid metabolism in the elderly. This article reviewed body aging process, changes of lipid metabolism in aging liver, and mechanism and effects of different interventions on lipid metabolism in aging liver, especially focus on exercise intervention. METHODS: A literature search was performed using PubMed-NCBI, EBSCO Host and Web of Science, and also a report from WHO. Totally, 143 studies were included from 1986 to 15 February 2020. CONCLUSION: Nutritional and pharmacological interventions can improve liver disorders, and nutritional interventions are less risky relatively. Exercise intervention can prevent and improve age-related liver disease, especially the best high-intensity interval training intensity and duration is expected to be one of the research direction in the future.

19.
Sci Adv ; 6(18): eaaz8985, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32490201

RESUMO

Immune checkpoint blockers (ICBs) have shown great promise at harnessing immune system to combat cancer. However, only a fraction of patients can directly benefit from the anti-programmed cell death protein 1 (aPD1) therapy, and the treatment often leads to immune-related adverse effects. In this context, we developed a prodrug hydrogelator for local delivery of ICBs to boost the host's immune system against tumor. We found that this carrier-free therapeutic system can serve as a reservoir for extended tumoral release of camptothecin and aPD1 antibody, resulting in an immune-stimulating tumor microenvironment for boosted PD-1 blockade immune response. Our in vivo results revealed that this combination chemoimmunotherapy elicits robust and durable systemic anticancer immunity, inducing tumor regression and inhibiting tumor recurrence and metastasis. This work sheds important light into the use of small-molecule prodrugs as both chemotherapeutic and carrier to awaken and enhance antitumor immune system for improved ICBs therapy.

20.
ChemSusChem ; 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32538543

RESUMO

Cobalt sulfides have been popularly used in energy storage because of their high theoretical capacity and abundant redox reactions. However, poor reaction kinetics, rapid capacity decay, and severe polarization owing to volume changes during electrochemical reaction are still huge challenges for cobalt sulfides in practical applications. Herein, cobalt sulfide yolk-shell spheres were synthesized by phosphorus doping (P-CoS) to stabilize the structure of cobalt sulfides and improve their electronic/ion conductivity. Kinetic tests and density functional theory calculations confirm that the introduction of phosphorus into cobalt sulfides greatly reduces the diffusion barrier of Li+ in the intrinsic structure, thereby improving the reaction kinetics of electrode materials during the Li+ insertion/extraction process. In consequence, the P-CoS electrode delivers a high lithium storage capacity (781 mAh g-1 after 100 cycles at 0.2 A g-1 ), excellent rate capability (489 mAh g-1 at 10 A g-1 ), and outstanding cycling stability (no significant capacity decay over 4000 cycles at 5 A g-1 ). Especially for sodium-ion battery application, the P-CoS electrode expresses a striking capacity of approximately 260 mAh g-1 at 2 A g-1 after 900 cycles.

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