Publications by authors named "Yong-qiang Li"

151 Publications

Gelatinase-responsive release of an antibacterial photodynamic peptide against .

Biomater Sci 2021 May;9(9):3433-3444

Department of Chemistry, the Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.

Staphylococcus aureus (S. aureus) related staphylococcal infection is one of the most common types of hospital-acquired infections, which requires selective and effective treatment in clinical practice. Considering gelatinase as a characteristic feature of S. aureus, gelatinase-responsive release of the antibiotic reagent thereby can target the pathogenic S. aureus while sparing beneficial bacteria in the microflora. In this work, we design a hybrid antibacterial photodynamic peptide (APP, Ce6-GKRWWKWWRRPLGVRGC) based on the polycationic antimicrobial peptide GKRWWKWWRR by introducing a photosensitizer chlorin e6 (Ce6) at the N-terminus, a cysteine residue at the C-terminus, and a gelatinase cleavage site (PLGVRG) inserted between the C-terminal cysteine and the polycationic peptide. This multi-motif peptide assembles with gold nanoclusters (AuNc) via Au-thiol bonding and affords a gelatinase-responsive antibacterial photodynamic nanocomposite (GRAPN). In vitro results show that the gelatinase secreted by S. aureus can cleave and release APP from AuNc, thereby resulting in preferential killing of S. aureus over E. coli. In a mouse model of staphylococcal skin wound infection, by integrating gelatinase-responsive drug release and the synergistic effect of a photodynamic agent and APP, GRAPN exhibits a marked photodynamic antibacterial activity, effectively eradicates S. aureus infection, and promotes rapid healing of the infected wounds.
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http://dx.doi.org/10.1039/d0bm02201bDOI Listing
May 2021

The efficacy and safety of the combination of axitinib and pembrolizumab-activated autologous DC-CIK cell immunotherapy for patients with advanced renal cell carcinoma: a phase 2 study.

Clin Transl Immunology 2021 3;10(3):e1257. Epub 2021 Mar 3.

Collaborative Innovation Center for Cancer Medicine State Key Laboratory of Oncology in South China Sun Yat-sen University Cancer Center Guangzhou China.

Objectives: Although axitinib has achieved a preferable response rate for advanced renal cell carcinoma (RCC), patient survival remains unsatisfactory. In this study, we evaluated the efficacy and safety of a combination treatment of axitinib and a low dose of pembrolizumab-activated autologous dendritic cells-co-cultured cytokine-induced killer cells in patients with advanced RCC.

Methods: All adult patients, including treatment-naive or pretreated with VEGF-targeted agents, were enrolled from May 2016 to March 2019. Patients received axitinib 5 mg twice daily and pembrolizumab-activated dendritic cells-co-cultured cytokine-induced killer cells intravenously weekly for the first four cycles, every 2 weeks for the next four cycles, and every month thereafter.

Results: The 43 patients (22 untreated and 21 previously treated) showed a median progression-free survival (mPFS) of 14.7 months (95% CI, 11.16-18.30). mPFS in treatment-naive patients was 18.2 months, as compared with 14.4 months in pretreated patients (log-rank value = 0.07). Overall response rates were 25.6% (95% CI, 13.5-41.2%). Grade 3 or higher adverse events occurred in 5% of patients included hypertension (11.6%) and palmar-plantar erythrodysesthesia (7.0%). Peripheral blood lymphocyte immunophenotype and serum cytokine profile analyses demonstrated increased antitumor immunity after combination treatment particularly in patients with a long-term survival benefit, while those with a minimal survival benefit demonstrated an elevated proportion of peripheral CD8TIM3 T cells and lower serum-level immunostimulatory cytokine profile.

Conclusions: The combination therapy was active and well tolerated for treatment of advanced RCC, either as first- or second-line treatment following other targeted agents. Changes in immunophenotype and serum cytokine profile may be used as prognostic biomarkers.
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http://dx.doi.org/10.1002/cti2.1257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927618PMC
March 2021

Defect-Induced Double-Stranded DNA Unwinding on Graphene.

J Phys Chem B 2021 03 10;125(11):2833-2840. Epub 2021 Mar 10.

School of Physics and State Key Laboratory of Crystal Materials, Shandong University, Jinan, Shandong 250100, China.

Several works have shown that graphene materials can effectively regulate the double-stranded DNA (dsDNA) structures and are used to remove antibiotic resistance genes in the environment, during which the morphology of the graphene surface plays a key role. However, the mechanism of how different graphene surfaces interact with dsDNA is poorly documented. Here, the interactions of dsDNA with defective graphene (D-Gra) and pristine graphene (P-Gra) have been explored by molecular dynamics simulations. Our data clearly showed that both D-Gra and P-Gra were able to attract dsDNA to form stable bindings. However, the structure evolutions of dsDNA are distinctly different. In detail, D-Gra can initiate quick unwinding of dsDNA and cause significant structural disruption. While for P-Gra, it demonstrated a much weaker capability to disrupt the dsDNA structure. This difference is due to the strong electrostatic interaction between defects and DNA nucleotides. Nucleotides can be highly restricted by the defect while the other parts of dsDNA could move along the transverse directions of D-Gra. This effectively introduces a "pulling force" from the defect that causes the breaking of the hydrogen bonds between dsDNA base pairs. Such force finally leads to the serious unwinding of dsDNA. Our present findings could help us to better understand the molecular mechanism of how the dsDNA canonical B-form was lost upon adsorption to graphene. The findings of the key roles of defects on graphene are beneficial for the design of functional graphenic materials for biological and medical applications through nanostructure engineering.
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http://dx.doi.org/10.1021/acs.jpcb.0c09406DOI Listing
March 2021

A transformable gold nanocluster aggregate-based synergistic strategy for potentiated radiation/gene cancer therapy.

J Mater Chem B 2021 03;9(9):2314-2322

Institute of Advanced Interdisciplinary Science, School of Physics, Shandong University, Jinan 250100, China. and Suzhou Research Institute, Shandong University, Suzhou 215123, China.

Nano-radiosensitizers provide a powerful tool for cancer radiation therapy. However, their limited tumor retention/penetration and the inherent or adaptive radiation resistance of tumor cells hamper the clinical success of radiation therapy. Herein, we report a synergistic strategy for potentiated cancer radiation/gene therapy based on transformable gold nanocluster aggregates loaded with antisense oligonucleotide-targeting survivin mRNA (named AuNC-ASON). AuNC-ASON exhibited acidic pH-triggered structure splitting from a gold nanocluster aggregate (around 80 nm) to gold nanocluster (<2 nm), leading to the tumor microenvironment-responsive size transformation of the nano-radiosensitizer and activated release of the loaded antisense oligonucleotides to perform gene silencing. The in vitro experiments demonstrated that AuNC-ASON could amplify and improve the radio-sensitivity of tumor cells (the sensitization enhancement ratio was about 1.81) as a result of the synergistic effect of the transformable gold nanocluster radiosensitizer and survivin gene interference. Remarkably, the size transformation capability realized the high tumor retention/penetration and renal metabolism of AuNC-ASON in vivo and boosted the radio-susceptibility of cancer cells with the assistance of survivin gene interference, synergistically achieving potentiated tumor radiation/gene therapy. The proposed concept of transformable nano-radiosensitizer aggregate-based synergistic therapy can be utilized as a general strategy to guide the design of activatable multifunctional nanosystems for cancer theranostics.
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http://dx.doi.org/10.1039/d0tb02986fDOI Listing
March 2021

Predicting the Survival Probability of Neuroendocrine Tumor Populations: Developing and Evaluating a New Predictive Nomogram.

Biomed Res Int 2021 28;2021:9126351. Epub 2021 Jan 28.

Department of Medical Oncology, Guangxi Medical University Cancer Hospital, Nanning 530021, China.

Purpose: The purpose of this study was to develop and initially validate a nomogram model in order to predict the 3-year and 5-year survival rates of neuroendocrine tumor patients.

Methods: Accordingly, 348 neuroendocrine tumor patients were enrolled as study objects, of which 244 (70%) patients were included in the training set to establish the nomogram model, while 104 (30%) patients were included in the validation set to verify the robustness of the model. First, the variables related to the survival rate were determined by univariable analysis. In addition, variables that were sufficiently significant were selected for constructing the nomogram model. Furthermore, the concordance index (C-index), receiver operating characteristic (ROC), and calibration curve analysis were used to evaluate the performance of the proposed nomogram model. The survival analysis was then used to evaluate the return to survival probability as well as the indicators of constructing the nomogram model.

Results: According to the multivariable analysis, lymphatic metastasis, international normalized ratio (INR), prothrombin time (PT), tumor differentiation, and the number of tumor metastases were found to be independent predictors of survival rate. Moreover, the C-index results demonstrated that the model was robust in both the training set (0.891) and validation set (0.804). In addition, the ROC results further verified the robustness of the model either in the training set (AUC = 0.823) or training set (AUC = 0.768). Furthermore, the calibration curve results showed that the model can be used to predict the 3-year and 5-year survival probability of neuroendocrine tumor patients. Meaningfully, five variables were found: lymphatic metastasis ( = 0.0095), international standardized ratio ( = 0.024), prothrombin time ( = 0.0036), tumor differentiation ( = 0.0026), and the number of tumor metastases ( = 0.00096), which were all significantly related to the 3-year and 5-year survival probability of neuroendocrine tumor patients.

Conclusion: In summary, a nomogram model was constructed in this study based on five variables (lymphatic metastasis, international normalized ratio (INR), prothrombin time (PT), tumor differentiation, and number of tumor metastases), which was shown to predict the survival probability of patients with neuroendocrine tumors. Additionally, the proposed nomogram exhibited good ability in predicting survival probability, which may be easily adopted for clinical use.
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http://dx.doi.org/10.1155/2021/9126351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864749PMC
May 2021

Role of relaxin in diastasis of the pubic symphysis peripartum.

World J Clin Cases 2021 Jan;9(1):91-101

Department of Rehabilitation, Taian City Central Hospital, Taian 271000, Shandong Province, China.

Background: Separation of the pubic symphysis can occur during the peripartum period. Relaxin (RLX) is a hormone primarily secreted by the corpus luteum that can mediate hemodynamic changes during pregnancy as well as loosen the pelvic ligaments. However, it is unknown whether RLX is associated with peripartum pubic symphysis separation and if the association is affected by other factors.

Aim: To study the association between RLX and peripartum pubic symphysis separation and evaluate other factors that might affect this association.

Methods: We performed a cross-sectional study of pregnant women between April 2019 and January 2020. Baseline demographic characteristics, including gestational age, weight, neonatal weight, delivery mode and duration of the first and second stages of labor, were recorded. The clinical symptoms were used as a screening index during pregnancy, and the patients with pubic symphysis and inguinal pain were examined by color Doppler ultrasonography to determine whether there was pubic symphysis separation. Serum RLX concentrations were evaluated 1 d after delivery using an enzyme-linked immunosorbent assay, and pubic symphysis separation was diagnosed based on postpartum X-ray examination. We used an independent-sample test to analyze the association between serum RLX levels and peripartum pubic symphysis separation. Multivariate regression analysis was used to evaluate whether the association between RLX and peripartum pubic symphysis separation was confounded by other factors, and the association between RLX and the severity of pubic symphysis separation was also assessed. We used Pearson correlation analysis to determine the factors related to RLX levels as well as the correlation between the degree of pubic symphysis separation and activities of daily living (ADL) and pain.

Results: A total of 54 women were enrolled in the study, with 15 exhibiting (observational group) and 39 not exhibiting (control group) peripartum pubic symphysis separation. There were no statistically significant differences in terms of maternal age, gestational age, pre-pregnancy weight, weight gain during pregnancy, delivery modes, or duration of the first or second stages of labor between the 2 groups. We did, however, note a statistically significant difference in serum RLX concentrations and neonatal weight between the observational and control groups (122.3 ± 0.7 µg/mL 170.4 ± 42.3 µg/mL, < 0.05; 3676.000 ± 521.725 g 3379.487 ± 402.420 g, < 0.05, respectively). Multivariate regression analyses showed that serum RLX level [odds ratio (OR): 1.022) and neonatal weight (OR: 1.002) were associated with pubic symphysis separation peripartum. The degree of separation of the pubic symphysis was negatively correlated with ADL and positively correlated with pain. There was no statistically significant association between serum RLX levels and the severity of pubic symphysis separation after adjusting for confounding factors.

Conclusion: Serum RLX levels and neonatal weight were associated with the occurrence, but not the severity, of peripartum pubic symphysis separation.
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http://dx.doi.org/10.12998/wjcc.v9.i1.91DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809669PMC
January 2021

Enhanced hydrolysis of β-cypermethrin caused by deletions in the glycin-rich region of carboxylesterase 001G from Helicoverpa armigera.

Pest Manag Sci 2021 Apr 12;77(4):2129-2141. Epub 2021 Jan 12.

College of Plant Protection, Northwest A&F University, Yangling, China.

Background: Carboxylesterase (CarE) is a major class of enzyme involved in the detoxification of toxic xenobiotics in various insect species. Previous work has shown that the carboxylesterase gene CarE001G found in Helicoverpa armigera is more active and can metabolize synthesized pyrethroids, such as β-cypermethrin, one of the commonly used commercial insecticides for lepidopteran pest control. In addition, CarE001G is very special as it has a very specific glycine-rich region located adjacent to its C-terminal. But whether mutations in this unique sequence can change the biochemistry and function of CarE001G are unknown.

Results: In this study, four variants of CarE001G with different deletions in the glycine-rich region were obtained and functionally expressed in Escherichia coli. The recombinant proteins were purified and confirmed by Western blot and mass spectrometry analyses. These mutant enzymes showed high catalytic efficiency toward the model substrate α-naphthyl acetate. Inhibition study showed that β-cypermethrin had relatively strong inhibition on CarE activities. In vitro metabolism assay showed that the mutant enzymes significantly enhanced their metabolic activities toward β-cypermethrin with specific activities between 4.0 and 5.6 nmol L min mg protein. Molecular docking analyses consistently demonstrated that deletion mutations in the glycine-rich region may facilitate the anchoring of the β-cypermethrin molecule in the active binding pocket of the mutant enzymes.

Conclusion: The data show that deletion mutations can cause qualitative change in the capacity of CarEs in the detoxification of β-cypermethrin. This indicates that deletion mutations in the glycine-rich region may have the potential to cause synthesized pyrethroid (SP) resistance in H. armigera in the future. © 2020 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.6242DOI Listing
April 2021

The Safety and Efficacy of Primary Duct Closure without Endoscopic Nasobiliary Drainage after Laparoscopic Common Bile Duct Exploration.

Gastrointest Tumors 2020 Oct 12;7(4):117-124. Epub 2020 Aug 12.

Department of Hepatobiliary Pancreatic Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou, China.

Background: Primary duct closure (PDC) after laparoscopic common bile duct exploration (LCBDE) has been widely applied for choledocholithiasis. However, there has been controversy over the placement of endoscopic nasobiliary drainage (ENBD) during operation. To date, few studies compare the clinical effect of PDC without and with ENBD. The aim of this study was to assess the safety and efficacy of PDC without ENBD for choledocholithiasis.

Methods: From January 2016 to December 2018, a total of 164 patients meeting the inclusion criteria were enrolled and divided into group A (undergone LCBDE + PDC without ENBD, 81 cases) and group B (undergone LCBDE + PDC with ENBD, 83 cases) in this study. The intraoperative conditions and postoperative complications were compared between the 2 groups.

Results: In group A, the time of operation, postoperative first flatus, extubation, antibiotics, and discharge were shorter than in group B ( = -17.775, = 0.000; = -7.649, = 0.000; = -5.807, = 0.000; = -9.247, = 0.000; = -9.322, = 0.000, respectively). Furthermore, intraoperative blood loss was less ( = -2.199, = 0.029) and hospital costs were lower ( = -6.685, = 0.000). However, there was no significant difference in postoperative complications between the 2 groups ( > 0.05).

Conclusions: In patients who meet the screening criteria, PDC without ENBD after LCBDE is safe and effective and worthy of clinical application.
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http://dx.doi.org/10.1159/000508874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588741PMC
October 2020

Mild lipid extraction and anisotropic cell membrane penetration of α-phase phosphorene carbide nanoribbons by molecular dynamics simulation studies.

Phys Chem Chem Phys 2020 Oct;22(40):23268-23275

School of Physics, State Key Laboratory of Crystal Materials, Shandong University, Jinan, Shandong 250100, China.

A systematic understanding of interactions at the nano-bio interface is critical for the development of bio-functional nanomaterials and nano-agents for medical applications, which essentially require high safety, biocompatibility and therapeutic efficiency. As a new member of the two-dimensional material family, α-phase phosphorene carbide (α-PC) has attracted significant research interest in recent years. Benefitting from the unique buckled structure and its rich physical and chemical features, the future applications of α-PC in biological and medical areas are intriguing. Using molecular dynamics simulations (MDs), herein, we theoretically explore the interactions of α-PC nanoribbons with the cell lipid membrane to evaluate the potential biological toxicity to lipids. Our results clearly demonstrate that the α-PC sheet can only penetrate the membrane along its zigzag direction by attracting the lipids to the groove regions. The membrane undergoes slight structural distortion, but quickly recovers after the penetration. Only localized impacts are detected on the membrane after the penetration. In contrast, the intrusion along armchair direction is highly blocked by lipids. Free energy analysis by the umbrella sampling method revealed that the fatty acid tails of lipids prefer to bind along the groove regions of α-PC rather than across the grooves, resulting in a high anisotropic penetration behavior. The overall attraction of α-PC to lipid is weaker than graphene, and the binding lipids cannot be fully extracted from the membrane environment. The self-equilibration of the membrane is fast enough to prevent lipids from escaping, leading to the well-preserved membrane integrity. Our present findings suggest that α-PC might offer new potential as bio-agents with high membrane-penetrating efficiency and lower cytotoxicity. The unique anisotropic behaviors can be further utilized for the design and fabrication of specialized nanomaterials with the capability of efficient and template-directed molecule delivery.
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http://dx.doi.org/10.1039/d0cp04145aDOI Listing
October 2020

Rhodium(III)-Catalyzed Direct Coupling of Quinoline-8-Carbaldehydes with (Het)Arylboronic Acids for the Synthesis of 8-Aryloylquinolines.

J Org Chem 2020 08 28;85(15):10271-10282. Epub 2020 Jul 28.

State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, People's Republic of China.

Herein, we describe a method for the synthesis of aryl-(het)aryl ketones by Rh(III)-catalyzed direct coupling between quinoline-8-carbaldehydes and (het)arylboronic acids. The method has a broad substrate scope, a high functional group tolerance, and uses commercially available starting materials. Scale-up of the reaction and subsequent synthesis of tubulin polymerization inhibitor demonstrated its utilities. A plausible mechanism was proposed on the basis of the fact that a stable cycloacylrhodium intermediate complex could be used as catalyst, and the complex reacted stoichiometrically with (het)arylboronic acids.
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http://dx.doi.org/10.1021/acs.joc.0c01490DOI Listing
August 2020

Enzyme-responsive turn-on nanoprobes for fluorescence imaging and localized photothermal treatment of multidrug-resistant bacterial infections.

J Mater Chem B 2020 08;8(33):7403-7412

School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou 213164, China.

Sensitive diagnosis and elimination of multidrug-resistant bacterial infections at an early stage remain paramount challenges. Herein, we present a gelatinase-responsive turn-on nanoprobe for in situ near-infrared (NIR) fluorescence imaging and localized photothermal treatment (PTT) of in vivo methicillin-resistant Staphylococcus aureus (MRSA) infections. The designed nanoprobe (named AuNS-Apt-Cy) is based on gold nanostars functionalized with MRSA-identifiable aptamer and gelatinase-responsive heptapeptide linker (CPLGVRG)-cypate complexes. The AuNS-Apt-Cy nanoprobe is non-fluorescent in aqueous environments due to the fluorescence resonance energy transfer between the gold nanostar core and cypate dye. We demonstrate that the AuNS-Apt-Cy nanoprobe can achieve MRSA targeting and accumulation as well as gelatinase (overexpressed in MRSA environments)-responsive turn-on NIR fluorescence due to the cleavage of the CPLGVRG linker and localized in vitro PTT via a mechanism involving bacterial cell wall and membrane disruption. In vivo experiments show that the AuNS-Apt-Cy nanoprobe can enable rapid (1 h post-administration) and in situ turn-on NIR fluorescence imaging with high sensitivity (105 colony-forming units) in diabetic wound and implanted bone plate mouse models. Remarkably, the AuNS-Apt-Cy nanoprobe can afford efficient localized PTT of diabetic wound and implanted bone plate-associated MRSA infections under the guidance of turn-on NIR fluorescence imaging, showing robust capability for early diagnosis and treatment of in vivo MRSA infections. In addition, the nanoprobe exhibits negligible damage to surrounding healthy tissues during PTT due to its targeted accumulation in the MRSA-infected site, guaranteeing its excellent in vivo biocompatibility and solving the main bottlenecks that hinder the clinical application of PTT-based antibacterial strategies.
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http://dx.doi.org/10.1039/d0tb00750aDOI Listing
August 2020

Therapeutic advances in non-alcoholic fatty liver disease: A microbiota-centered view.

World J Gastroenterol 2020 Apr;26(16):1901-1911

Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, Guangdong Province, China.

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent metabolic disorder with steadily increasing incidence rates worldwide, especially in the West. There are no drugs available at present to treat NAFLD, and the primary therapeutic options include weight loss and the combination of healthy diet and exercise. Therefore, novel interventions are required that can target the underlying risk factors. Gut microbiota is an "invisible organ" of the human body and vital for normal metabolism and immuno-modulation. The number and diversity of microbes differ across the gastrointestinal tract from the mouth to the anus, and is most abundant in the intestine. Since dysregulated gut microbiota is an underlying pathological factor of NAFLD, it is a viable therapeutic target that can be modulated by antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and microbial metabolites. In this review, we summarize the most recent advances in gut microbiota-targeted therapies against NAFLD in clinical and experimental studies, and critically evaluate novel targets and strategies for treating NAFLD.
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http://dx.doi.org/10.3748/wjg.v26.i16.1901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201149PMC
April 2020

Efficacy of adjuvant cytokine-induced killer cell immunotherapy in patients with colorectal cancer after radical resection.

Oncoimmunology 2020 17;9(1):1752563. Epub 2020 Apr 17.

Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.

Adjuvant chemotherapy after surgery is the standard treatment modality for stage III and part of stage II or stage IV colorectal cancer (CRC) patients. However, the 5-year overall survival (OS) rate remains unsatisfactory. Thus, developing combination therapies is essential to improve the prognosis of patients with CRC. The present study aimed to determine the effect of a sequential combination of cytokine-induced killer cell (CIK) infusion and chemotherapy for patients with CRC. 122 patients with CRC treated with postoperative adjuvant chemotherapy were retrospectively included in this study. Among them, 62 patients received adjuvant chemotherapy only (control group), while the other 60 patients, with similar demographic and clinical characteristics, received adjuvant chemotherapy and sequential CIK cell immunotherapy (CIK group). Survival analysis showed significantly improved disease free survival (DFS) and OS rates in the CIK group compared with the control group (log-rank test, = .0024; = .008, respectively). Univariate and multivariate analyses indicated that sequential CIK cell treatment was an independent prognostic factor for patients' DFS and OS. Subgroup analyses showed that sequential CIK cell treatment significantly improved the DFS and OS of patients with high-risk T4 stage and insufficient chemotherapy duration. In conclusion, these data indicate that sequential adjuvant CIK cell treatment combined with chemotherapy is an effective therapeutic strategy to prevent disease recurrence and prolong survival of patients with CRC, particularly for patients with high-risk T4 stage and insufficient chemotherapy duration.
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http://dx.doi.org/10.1080/2162402X.2020.1752563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185208PMC
July 2021

Fecal microbiota transplantation ameliorates active ulcerative colitis.

Exp Ther Med 2020 Apr 11;19(4):2650-2660. Epub 2020 Feb 11.

Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China.

Ulcerative colitis (UC) is a complex chronic pathological condition of the gut in which microbiota targeted treatment, such as fecal microbiota transplantation (FMT), has shown an encouraging effect. The aim of the present study was to investigate the efficacy and safety of FMT in patients with mild or moderate UC. A single-center, open-label study was designed, including 47 patients with mild or moderate active UC who received three treatments of fresh FMT via colonic transendoscopic enteral tubing within 1 week. The inflammatory bowel disease questionnaire, partial Mayo scores, colonoscopy, erythrocyte sedimentation rate, C-reactive protein level and procalcitoin values were used to assess the efficacy of FMT and alteration in gut microbiota was detected by 16S ribosomal RNA-sequencing. Before FMT, microbiota () levels were significantly decreased in patients with UC compared with healthy donors (P<0.01). At 4 weeks post-FMT, levels were significantly increased (P<0.05), and the Mayo score was significantly decreased (1.91±1.07 at baseline vs. 4.02±1.47 at week 4; P<0.001) in patients with UC compared with healthy donors. Steroid-free clinical responses were reported in 37 patients (84.1%), and steroid-free clinical remission was achieved in 31 patients (70.5%) at week 4 post-FMT, however, steroid-free remission was not achieved in any patient. No adverse events were reported in 41 (93.2%) patients after FMT or during the 12-week follow-up. Shannon's diversity index and Chao1 estimator were also improved in patients with UC receiving FMT. In conclusion, the results of the present study suggested that FMT resulted in clinical remission in patients with mild to moderate UC, and that the remission may be associated with significant alterations to the intestinal microbiota of patients with UC. Furthermore, may serve as a diagnostic and therapeutic biomarker for the use of FMT in UC.
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http://dx.doi.org/10.3892/etm.2020.8512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086197PMC
April 2020

Functional Characterization of Two Carboxylesterase Genes Involved in Pyrethroid Detoxification in .

J Agric Food Chem 2020 Mar 10;68(11):3390-3402. Epub 2020 Mar 10.

State Key Laboratory of Crop Stress Biology for Arid Areas, College of Plant Protection, Northwest A&F University, Yangling, Shaanxi 712100, China.

Insect carboxylesterases are major enzymes involved in metabolism of xenobiotics including insecticides. Two carboxylesterase genes, and , were cloned from the destructive agricultural pest . Quantitative real-time polymerase chain reaction showed that and were predominantly expressed in fat body and midgut, respectively; developmental expression analyses found that the expression levels of both CarEs were significantly higher in fifth-instar larvae than in other life stages. Recombinant CarE001A and CarE001H expressed in the exhibited high enzymatic activity toward α-naphthyl acetate. Inhibition assays showed that organophosphates had strong inhibition on CarEs activity compared to pyrethroids. Metabolism assays indicated that CarE001A and CarE001H were able to metabolize β-cypermethrin and λcyhalothrin. Homology modeling and molecular docking analyses demonstrated that β-cypermethrin could fit nicely into the active pocket of both carboxylesterases. These results suggested that and could play important roles in the detoxification of pyrehtroids in .
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http://dx.doi.org/10.1021/acs.jafc.9b06690DOI Listing
March 2020

Safeguarding intestine cells against enteropathogenic by intracellular protein reaction, a preventive antibacterial mechanism.

Proc Natl Acad Sci U S A 2020 03 24;117(10):5260-5268. Epub 2020 Feb 24.

Department of Chemistry, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China;

A critical problem in the fight against bacterial infection is the rising rates of resistance and the lack of new antibiotics. The discovery of new targets or new antibacterial mechanisms is a potential solution but is becoming more difficult. Here we report an antibacterial mechanism that safeguards intestine cells from enteropathogenic (EPEC) by shutting down an infection-responsive signal of the host intestine cell. A key step in EPEC infection of intestinal cells involves Tir-induced actin reorganization. Nck mediates this event by binding with Tir through its SH2 domain (Nck-SH2) and with WIP through its second SH3 domain (Nck-SH3.2). Here we report the design of a synthetic peptide that reacts precisely with a unique cysteine of the Nck-SH3.2 domain, blocks the binding site of the Nck protein, and prevents EPEC infection of Caco-2 cells. Oral update of this nontoxic peptide before EPEC administration safeguards mice from EPEC infection and diarrhea. This study demonstrates domain-specific blockage of an SH3 domain of a multidomain adaptor protein inside cells and the inhibition of Tir-induced rearrangement of the host actin cytoskeleton as a previously unknown antibacterial mechanism.
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http://dx.doi.org/10.1073/pnas.1914567117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071885PMC
March 2020

Retrospective analysis of the efficacy of cytokine-induced killer cell immunotherapy combined with first-line chemotherapy in patients with metastatic colorectal cancer.

Clin Transl Immunology 2020 19;9(2):e1113. Epub 2020 Feb 19.

State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat-Sen University Cancer Center Guangzhou China.

Objectives: Fluoropyrimidine-based chemotherapy regimens are the current first-line treatment for metastatic colorectal cancer (mCRC); however, the outcome is often unsatisfactory. The present study aimed to determine the effect of combined cytokine-induced killer (CIK) cell immunotherapy and first-line chemotherapy in patients with mCRC.

Methods: This retrospective study included 252 patients with mCRC treated with first-line chemotherapy. Among them, 126 patients received first-line chemotherapy only (control group), while the other 126 patients, with similar demographic and clinical characteristics, received CIK cell immunotherapy combined with first-line chemotherapy (CIK group). Overall survival (OS) and progression-free survival (PFS) were compared between the two groups using the Kaplan-Meier method.

Results: The median OS for the CIK group was 54.7 versus 24.1 months for the controls, and the median PFS for the CIK group was 25.7 versus 14.6 months for the controls. Univariate and multivariate analyses indicated that CIK cell treatment was an independent prognostic factor for patients' OS and PFS. Subgroup analyses showed that CIK cell treatment significantly improved the OS and PFS of patients with metastatic colon cancer, but not those with metastatic rectal cancer. Additionally, the change in CD3CD56 subsets after the fourth treatment cycle might be an indicator of successful CIK cell treatment: Patients with increased CD3CD56 subsets had better survival than those with decreased CD3CD56 subsets.

Conclusion: Cytokine-induced killer cell immunotherapy combined with first-line chemotherapy could significantly improve the OS and PFS of patients with mCRC, particularly for patients with metastatic colon cancer.
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http://dx.doi.org/10.1002/cti2.1113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029432PMC
February 2020

Anisotropic protein diffusion on nanosurface.

Nanoscale 2020 Feb;12(8):5209-5216

School of Physics and State Key Laboratory of Crystal Materials, Shandong University, Jinan, Shandong 250100, China.

The unique puckered structure of α-phase phosphorene carbide (α-PC) results in anisotropic electronic and thermal transporting properties. In the present work, the interactions between a model protein, villin headpiece sub-domain (HP35), and the surface of α-PC and monolayer black phosphorus (MBP, another puckered nanostructure) were explored by molecular dynamic (MD) simulations. It is found that HP35 diffuses quickly only along the zigzag direction of the α-PC surface. On the MBP surface, HP35 migrates mainly along the zigzag direction but can also easily stride over the ridges and grooves along the armchair direction. Moreover, the mild binding strength between α-PC and HP35 does not cause distortion in the protein structure. The intrinsic biocompatibility of α-PC, which is distinct from several other widely studied nanomaterials, such as carbon nanotubes, graphene and MoS2, makes it a promising candidate in functional biomedical applications.
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http://dx.doi.org/10.1039/c9nr08555fDOI Listing
February 2020

Thermal-Disrupting Interface Mitigates Intercellular Cohesion Loss for Accurate Topical Antibacterial Therapy.

Adv Mater 2020 Mar 19;32(12):e1907030. Epub 2020 Feb 19.

Innovative Centre for Flexible Devices (iFLEX), School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798, Singapore.

Bacterial infections remain a leading threat to global health because of the misuse of antibiotics and the rise in drug-resistant pathogens. Although several strategies such as photothermal therapy and magneto-thermal therapy can suppress bacterial infections, excessive heat often damages host cells and lengthens the healing time. Here, a localized thermal managing strategy, thermal-disrupting interface induced mitigation (TRIM), is reported, to minimize intercellular cohesion loss for accurate antibacterial therapy. The TRIM dressing film is composed of alternative microscale arrangement of heat-responsive hydrogel regions and mechanical support regions, which enables the surface microtopography to have a significant effect on disrupting bacterial colonization upon infrared irradiation. The regulation of the interfacial contact to the attached skin confines the produced heat and minimizes the risk of skin damage during thermoablation. Quantitative mechanobiology studies demonstrate the TRIM dressing film with a critical dimension for surface features plays a critical role in maintaining intercellular cohesion of the epidermis during photothermal therapy. Finally, endowing wound dressing with the TRIM effect via in vivo studies in S. aureus infected mice demonstrates a promising strategy for mitigating the side effects of photothermal therapy against a wide spectrum of bacterial infections, promoting future biointerface design for antibacterial therapy.
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http://dx.doi.org/10.1002/adma.201907030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7702719PMC
March 2020

CIK cell cytotoxicity is a predictive biomarker for CIK cell immunotherapy in postoperative patients with hepatocellular carcinoma.

Cancer Immunol Immunother 2020 May 14;69(5):825-834. Epub 2020 Feb 14.

Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China.

Adjuvant cytokine-induced killer (CIK) cell immunotherapy has shown potential in improving the prognosis of hepatocellular carcinoma (HCC) patients after curative resection. However, whether an individual could obtain survival benefit from CIK cell treatment remains unknown. In the present study, we focused on the characteristics of CIK cells and aimed to identify the best predictive biomarker for adjuvant CIK cell treatment in patients with HCC after surgery. This study included 48 patients with HCC treated with postoperative adjuvant CIK cell immunotherapy. The phenotype activity and cytotoxic activity of CIK cells were determined by flow cytometry and xCELLigence™ Real-Time Cell Analysis (RTCA) system, respectively. Correlation analysis revealed that the cytotoxic activity of CIK cells was significantly negative correlated with the percentage of CD3+ CD4+ cell subsets, but significantly positive correlated with CD3-CD56+ and CD3+ CD56+ cell subsets. Survival analysis showed that there were no significant associations between patients' prognosis and the phenotype of CIK cells. By contrast, there was statistically significant improvement in recurrence-free survival (RFS) and overall survival (OS) for patients with high cytotoxic activity of CIK cells as compared with those with low cytotoxic activity of CIK cells. Univariate and multivariate analyses indicated that CIK cell cytotoxicity was an independent prognostic factor for RFS and OS. In conclusion, a high cytotoxic activity of CIK cells can serve as a valuable biomarker for adjuvant CIK cell immunotherapy of HCC patients after surgery.
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http://dx.doi.org/10.1007/s00262-020-02486-yDOI Listing
May 2020

Synthesis of Glutathione (GSH)-Responsive Amphiphilic Duplexes and their Application in Gene Delivery.

Chempluschem 2019 08;84(8):1060-1069

National Institute for Food and Drug Control, Institute of Chemical Drug Control, TianTan XiLi 2, Beijing, 100050, China.

Oligoamide molecular strands with hydrogen-bonding sequences DADDAD and guanidine (O-1) or 1,5,9-triazacyclododecane ([12]aneN ; O-2) side chains and oligoamides with hydrogen-bonding sequences ADAADA and octyl moieties (O-3), were synthesized. Two duplexes (D-1 and D-2) were prepared by conjugating the hydrophilic O-1 or O-2 and hydrophobic O-3 through sequence-specific hydrogen-bond association and cross-linked disulfide bonds. Electrophoresis measurements indicated that O-1, O-2, D-1, and D-2 were able to completely retard the DNA mobiliy at concentrations of 30, 30, 10, and 20 μM, respectively. Reversible DNA release in O-1 and O-2 complexes can be achieved in the presence of heparin sodium, whereas the presence of GSH greatly improved DNA release in D-1 and D-2 complexes. The particles formed were in a size range of 50-170 nm with positively charged surfaces. D-1 and D-2 transfected pEGFP-N1 into HeLa cells successfully.
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http://dx.doi.org/10.1002/cplu.201900295DOI Listing
August 2019

Marine-natural-products for biocides development: first discovery of meridianin alkaloids as antiviral and anti-phytopathogenic-fungus agents.

Pest Manag Sci 2020 Oct 11;76(10):3369-3376. Epub 2019 Dec 11.

State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, College of Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, China.

Background: Food is an important strategic material related to national economy and people's livelihood. Plant diseases seriously affect crop yield and quality. Marine natural products are an important source for novel drugs discovery. In this work, meridianin alkaloids were selected as the parent structure. A series of meridianin alkaloid analogues were rationally designed, synthesized and evaluated for their antiviral activities and fungicidal activities.

Result: These compounds were found to have good antiviral and fungicidal activities for the first time. The structure-activity relationship (SAR) research revealed that introducing bromine atom at the 5-position of indole ring is beneficial to antiviral activity, but introducing methoxy group is not conducive. Introducing bromine atom at the 6-position of indole ring or nitrogen atom at the 7-position of the indole ring resulted in lower antiviral activity. Most of the meridianin derivatives showed higher anti-TMV activities at 500 μg mL than Ribavirin, especially for compounds 6c, 8a and 10a. All of the compounds also displayed broad spectrum fungicidal activities against 14 kinds of phytopathogenic fungi at 50 μg mL .

Conclusion: Compound 6c with relatively simple structure and excellent antiviral activity, which is similar to that of Ningnanmycin, emerged as novel anti-TMV lead compound. Compound 5d with broad spectrum and high effect fungicidal activity emerged as a new fungicidal lead compound. Current research lays a solid foundation for the application of meridianin alkaloids in crop protection. © 2019 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.5690DOI Listing
October 2020

A nanowire-integrated thermoresponsive microfluidic platform for on-demand enrichment and colorimetric detection of pathogenic bacteria.

J Mater Chem B 2019 12 13;7(46):7301-7305. Epub 2019 Nov 13.

School of Physics, Shandong University, Jinan 250100, China.

A nanowire-integrated thermoresponsive microfluidic platform is developed for bacterial enrichment and on-demand release. This microfluidic platform can enable selective and highly sensitive S. aureus detection in blood samples down to trace concentrations (40 CFU mL) by the naked eye with the help of a click reaction-assisted colorimetric assay.
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http://dx.doi.org/10.1039/c9tb01923eDOI Listing
December 2019

pH-Switchable Antimicrobial Nanofiber Networks of Hydrogel Eradicate Biofilm and Rescue Stalled Healing in Chronic Wounds.

ACS Nano 2019 10 10;13(10):11686-11697. Epub 2019 Sep 10.

School of Physics , Shandong University , Jinan 250100 , China.

Biofilm infections can induce chronic inflammation and stall the normal orchestrated course of wound-healing cascades. Herein, pH-switchable antimicrobial hydrogel with nanofiber networks for biofilm eradication and rescuing stalled healing in chronic wounds is reported on the basis of the self-assembly of a designed octapeptide (IKFQFHFD) at neutral pH. This hydrogel is biocompatible and exhibits an acidic pH (pathological environment of infected chronic wounds)-switchable broad-spectrum antimicrobial effect via a mechanism involving cell wall and membrane disruption. The antimicrobial activity of hydrogel is derived from its acidic pH-dependent nanofiber network destabilization and activated release of IKFQFHFD, which is antimicrobial only at acidic pH due to the antimicrobial peptide-like molecular structure. In addition, supramolecular nanofiber networks loaded with drugs of cypate (photothermal agent) and proline (procollagen component) are further developed. experiments show that loaded drugs exhibit acidic pH (pH ∼ 5.5)-responsive release profiles, and synergistic biofilm eradication and subsequent healing cascade activation of cells proliferation are achieved on the basis of the supramolecular nanofiber networks. Remarkably, the nanofiber networks of hydrogel enable complete healing of MRSA biofilm infected wound in diabetic mice within 20 days, showing great potential as promising chronic wound dressings. The proposed synergistic strategy for eradicating biofilm and activating subsequent healing cascades may offer a powerful modality for the management of clinical chronic wounds.
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http://dx.doi.org/10.1021/acsnano.9b05608DOI Listing
October 2019

Bacteria-Instructed Click Chemistry between Functionalized Gold Nanoparticles for Point-of-Care Microbial Detection.

ACS Appl Mater Interfaces 2019 Jul 24;11(26):23093-23101. Epub 2019 Jun 24.

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions , Soochow University , Suzhou 215123 , China.

Bacterial infections pose mounting public health concerns and cause an enormous medical and financial burden today. Rapid and sensitive detection of pathogenic bacteria at the point of care (POC) remains a paramount challenge. Here, we report a novel concept of bacteria-instructed click chemistry and employ it for POC microbial sensing. In this concept of bacteria-instructed click chemistry, we demonstrate for the first time that pathogenic bacteria can capture and reduce exogenous Cu to Cu by leveraging their unique metabolic processes. The produced Cu subsequently acts as a catalyst to trigger the click reaction between gold nanoparticles (AuNPs) modified with azide and alkyne functional molecules, resulting in the aggregation of nanoparticles with a color change of the solution from red to blue. In this process, signal amplification from click chemistry is complied with the aggregation of functionalized AuNPs, thus presenting a robust colorimetric strategy for sensitive POC sensing of pathogenic bacteria. Notably, this colorimetric strategy is easily integrated in a smartphone app as a portable platform to achieve one-click detection in a mobile way. Moreover, with the help of the magnetic preseparation process, this smartphone app-assisted platform enables rapid (within 1 h) detection of Escherichia coli with high sensitivity (40 colony-forming units/mL) in the complex artificial sepsis blood samples, showing great potential for clinical early diagnosis of bacterial infections.
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http://dx.doi.org/10.1021/acsami.9b09279DOI Listing
July 2019

Identification and biochemical characterization of carboxylesterase 001G associated with insecticide detoxification in Helicoverpa armigera.

Pestic Biochem Physiol 2019 Jun 14;157:69-79. Epub 2019 Mar 14.

College of Plant Protection, Northwest A&F University, Yangling 712100, Shaanxi, China. Electronic address:

Carboxylesterases (CarEs) are a major class of detoxification enzymes involved in insecticide resistance in various insect species. In this study, a novel CarE 001G was isolated from the cotton bollworm Helicoverpa armigera, one of the most destructive agricultural insect pests. The open reading frame of 001G has 2244 nucleotides and putatively encodes 747 amino acid residues. The deduced CarE possessed the highly conserved catalytic triads(Ser-Glu-His) and pentapeptide motifs (Gly-X-Ser-X-Gly), suggesting 001G is biologically active. The truncated 001G was successfully expressed in Escherichia coli, and the recombinant proteins were purified and tested. The enzyme kinetic assay showed the purified proteins could catalyze two model substrates, α-naphthyl acetate and β-naphthyl acetate, with a kcat of 8.8 and 2.3 s, a Km of 9.6 and 16.2 μM, respectively. The inhibition study with pyrethroid, organophosphate and neonicotinoid insecticides showed different inhibition profile against the purified CarE. The HPLC assay demonstrated that the purified proteins were able to metabolize β-cypermethrin, λ-cyhalothrin and fenvalerate insecticides, exhibiting respective specific activities of 1.7, 1.4 and 0.5 nM/min/mg protein. However, the purified proteins were not able to metabolize the chlorpyrifos, parathion-methyl, paraoxon-ethyl and imidacloprid. The modeling and docking analyses consistently demonstrated that the pyrethroid molecule fits snugly into the catalytic pocket of the CarE 001G. Collectively, our results suggest that 001G may play a role in pyrethroids detoxification in H. armigera.
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http://dx.doi.org/10.1016/j.pestbp.2019.03.009DOI Listing
June 2019

Relief of irritable bowel syndrome by fecal microbiota transplantation is associated with changes in diversity and composition of the gut microbiota.

J Dig Dis 2019 Aug 7;20(8):401-408. Epub 2019 Jul 7.

Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, China.

Objective: To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for refractory irritable bowel syndrome (IBS).

Methods: Microbiota suspensions from feces of the donors were injected into the intestines of 30 Chinese patients with refractory IBS. Microbiota composition analysis and genomic DNA extraction of fecal samples obtained from these patients at baseline and 1 month after FMT were performed. Clinical efficacy and safety of FMT were assessed using questionnaires covering four aspects of IBS therapeutic efficacy and assessment of adverse effects during a 6-month follow-up.

Results: FMT improved IBS gastrointestinal symptoms and alleviated depression and anxiety, as shown by the improved IBS-QOL, IBS-SSS, GSRS, HAMA and HAMD scores at 1 month and 3 months after FMT. A total adverse event rate of FMT was 6.7% (2/30). Gut microbiota analysis revealed that FMT responders had a significantly higher Shannon diversity index before FMT than non-responders. In addition, analysis of differences in bacterial composition before and after FMT in responders showed specific abundance of the phyla Verrucomincrobia and Euryarchaeota at 1 month after FMT. At the genus level, Methanobrevibacter and Akkermansia were the most abundant fecal microbiota 1 month after FMT compared with those before FMT.

Conclusions: FMT may be an effective and safe therapeutic strategy for treating IBS that achieves a sustained clinical response 3-6 months after the first procedure. Changes in the diversity and dominant flora may contribute to its therapeutic effect.
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http://dx.doi.org/10.1111/1751-2980.12756DOI Listing
August 2019

The HDA19 histone deacetylase complex is involved in the regulation of flowering time in a photoperiod-dependent manner.

Plant J 2019 05 3;98(3):448-464. Epub 2019 Mar 3.

National Institute of Biological Sciences, Beijing, 102206, China.

Chromatin modifications are known to affect flowering time in plants, but little is known about how these modifications regulate flowering time in response to environmental signals like photoperiod. In Arabidopsis thaliana, HDC1, a conserved subunit of the RPD3-like histone deacetylase (HDAC) complex, was previously reported to regulate flowering time via the same mechanism as does the HDAC HDA6. Here, we demonstrate that HDC1, SNLs and MSI1 are shared subunits of the HDA6 and HDA19 HDAC complexes. While the late-flowering phenotype of the hda6 mutant is independent of photoperiod, the hda19, hdc1 and snl2/3/4 mutants flower later than or at a similar time to the wild-type in long-day conditions but flower earlier than the wild-type in short-day conditions. Our genome-wide analyses indicate that the effect of hdc1 on histone acetylation and transcription is comparable with that of hda19 but is different from that of hda6. Especially, we demonstrate that the HDA19 complex directly regulates the expression of two flowering repressor genes related to the gibberellin signaling pathway. Thus, the study reveals a photoperiod-dependent role of the HDA19 HDAC complex in the regulation of flowering time.
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http://dx.doi.org/10.1111/tpj.14229DOI Listing
May 2019

Resolving quantum dots and peptide assembly and disassembly using bending capillary electrophoresis.

Electrophoresis 2019 04 20;40(7):1019-1026. Epub 2018 Dec 20.

School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou, P. R. China.

Despite the numerous techniques developed for the studying nanoparticle and peptide interaction nowadays, sensitive and convenient assay in the process of flow, especially to simulate the self-assembly of quantum dots (QDs) and peptide inflow in blood vessels, still remains big challenges. Here, we report a novel assay for studying the self-assembly of QDs and peptide, based on CE using a bending capillary. We demonstrate that the semicircles numbers of the bending capillary affect the self-assembly kinetics of CdSe/ZnS QDs and ATTO-D LVPRGSGP G H peptide. Moreover, benefitting from this novel assay, the effect of the position on the self-assembly has also been realized. More importantly, we also demonstrate that this novel assay can be used for studying the stability of the QDs-peptide complex inflow. We believe that our novel assay proposed in this work could be further used as a general strategy for the studying nanoparticle-biomolecule interaction or biomolecule-biomolecule interaction.
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http://dx.doi.org/10.1002/elps.201800466DOI Listing
April 2019

Functional Magnetic Resonance Imaging in the Diagnosis of Locally Recurrent Prostate Cancer: Are All Pulse Sequences Helpful?

Korean J Radiol 2018 Nov-Dec;19(6):1110-1118. Epub 2018 Oct 18.

Department of Breast Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China.

Objective: To perform a meta-analysis to quantitatively assess functional magnetic resonance imaging (MRI) in the diagnosis of locally recurrent prostate cancer.

Materials And Methods: A comprehensive search of the PubMed, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews was conducted from January 1, 1995 to December 31, 2016. Diagnostic accuracy was quantitatively pooled for all studies by using hierarchical logistic regression modeling, including bivariate modeling and hierarchical summary receiver operating characteristic (HSROC) curves (AUCs). The Z test was used to determine whether adding functional MRI to T2-weighted imaging (T2WI) results in significantly increased diagnostic sensitivity and specificity.

Results: Meta-analysis of 13 studies involving 826 patients who underwent radical prostatectomy showed a pooled sensitivity and specificity of 91%, and the AUC was 0.96. Meta-analysis of 7 studies involving 329 patients who underwent radiotherapy showed a pooled sensitivity of 80% and specificity of 81%, and the AUC was 0.88. Meta-analysis of 11 studies reporting 1669 sextant biopsies from patients who underwent radiotherapy showed a pooled sensitivity of 54% and specificity of 91%, and the AUC was 0.85. Sensitivity after radiotherapy was significantly higher when diffusion-weighted MRI data were combined with T2WI than when only T2WI results were used. This was true when meta-analysis was performed on a per-patient basis ( = 0.027) or per sextant biopsy ( = 0.046). A similar result was found when H-magnetic resonance spectroscopy (H-MRS) data were combined with T2WI and sextant biopsy was the unit of analysis ( = 0.036).

Conclusion: Functional MRI data may not strengthen the ability of T2WI to detect locally recurrent prostate cancer in patients who have undergone radical prostatectomy. By contrast, diffusion-weight MRI and H-MRS data may improve the sensitivity of T2WI for patients who have undergone radiotherapy.
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http://dx.doi.org/10.3348/kjr.2018.19.6.1110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201967PMC
April 2019