Publications by authors named "Wei Chen"

9,816 Publications

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Phocaeicola faecalis sp. nov., a strictly anaerobic bacterial strain adapted to the human gut ecosystem.

Antonie Van Leeuwenhoek 2021 Jun 15. Epub 2021 Jun 15.

State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Avenue, Binhu District, Wuxi, 214122, Jiangsu, China.

A novel strictly anaerobic, Gram-negative bacterium, designated as strain FXJYN30E22, was isolated from the feces of a healthy woman in Yining county, Xinjiang province, China. This strain was non-spore-forming, bile-resistant, non-motile and rod-shaped. It was found to belong to a single separate group in the Phocaeicola genus based on its 16 S ribosomal RNA (rRNA) gene sequence. Alignments of 16 S rRNA gene sequences showed only a low sequence identity (≤  95.5 %) between strain FXJYN30E22 and all other Phocaeicola strains in public data bases. The genome (43.0% GC) of strain FXJYN30E22 was sequenced, and used for phylogenetic analysis which showed that strain FXJYN30E22 was most closely related to the type strain Phocaeicola massiliensis JCM 13223. The average nucleotide identity (ANI) value and digital DNA-DNA hybridization (dDDH) between FXJYN30E22 and P. massiliensis JCM 13223 were 90.4 and 41.9 %, which were lower than the generally accepted species boundaries (94.0 and 70 %, respectively). The major cellular fatty acids and polar lipids were anteiso-branched C and phosphatidylethanolamine, respectively. The result of genome annotation and KEGG analysis showed that strain FXJYN30E22 contains a number of genes in polysaccharide and fatty acid synthesis that indicated adaptation to the human gut system. Furthermore, a pbpE (penicillin-binding protein) gene was found in the genome of strain FXJYN30E22 but in no other Phocaeicola species, which suggested this gene might be contribute to the adaptive capacity of strain FXJYN30E22. Based on our data, strain FXJYN30E22 (= CGMCC1.17870/KCTC25195) was classified as a novel Phocaeicola species, and the name Phocaeicola faecalis sp. nov., was proposed.
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http://dx.doi.org/10.1007/s10482-021-01595-7DOI Listing
June 2021

Research advances in bioactive components and health benefits of jujube ( Mill.) fruit.

J Zhejiang Univ Sci B 2021 Jun;22(6):431-449

Department of Food Science and Nutrition, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang University, Hangzhou 310058, China.

Jujube ( Mill.), a highly nutritious and functional fruit, is reported to have various health benefits and has been extensively planted worldwide, especially in China. Many studies have shown that bioactive components derived from jujube fruit have significant nutritional and potential biological effects. In this paper, the latest progress in research on major bioactive compounds obtained from jujube is reviewed, and the potential biological functions of jujube fruit resources are discussed. As a dietary supplement, jujube fruit is well recognized as a healthy food which contains a variety of bioactive substances, such as polysaccharides, polyphenols, amino acids, nucleotides, fatty acids, dietary fiber, alkaloids, and other nutrients. These nutrients and non-nutritive phytochemicals obtained from jujube fruit have physiological functions including anticancer, antioxidant, anti-inflammatory, anti-hyperlipidemic, anti-hyperglycemic, immunoregulatory, neuroprotective, sedative, and antiviral functions. Of note is that new constituents, including alkaloids, dietary fiber, and other bioactive substances, as well as the antiviral, hypoglycemic, lipid-lowering, and neuroprotective effects of jujube fruit, are systematically reviewed here for the first time. Meanwhile, problems affecting the exploitation of jujube fruit resources are discussed and further research directions proposed. Therefore, this review provides a useful bibliography for the future development of jujube-based products and the utilization of jujube nutritional components in functional foods.
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http://dx.doi.org/10.1631/jzus.B2000594DOI Listing
June 2021

The expression and clinical prognostic value of protein phosphatase 1 catalytic subunit beta in pancreatic cancer.

Bioengineered 2021 Dec;12(1):2763-2778

Bengbu Medical College, Bengbu, Anhui P.R. China.

Pancreatic cancer (PAAD) is a common malignancy with a poor survival rate. The identification of novel biomarkers could improve clinical outcomes for patients with PAAD. Here we evaluated the expression and clinical significance of in PAAD. expression was higher in PAAD tissue than in matched paracancerous tissue (). We predicted a network of regulatory targets and protein interaction partners of , and identified a PPI network consisting of 39 node genes. The expression of 33 node genes was higher in PAAD tissue than in matching paracancerous tissue. High expression of the node genes , and was associated with improved overall survival (). SiRNA knockdown of significantly reduced the migration and invasion of PAAD cells. A immunohistochemical staining was performed using a tissue microarray (TMA), consisting of tumor samples collected from 91 patients with PAAD (88 of which contained matched paracancerous tissues). The expression of in PAAD was significantly higher than in the matched paracancerous tissue, (). High expression was associated with patient sex (), alcohol use (), CEA ), N stage ), and invasion of nerve (). Furthermore, high expression was associated with significantly poorer overall survival (). Our data demonstrate that is associated with the migration and invasion of PAAD cells, and may be useful as an independent prognostic indicator for clinical outcome in patients with PAAD.
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http://dx.doi.org/10.1080/21655979.2021.1934243DOI Listing
December 2021

Binding of Benzo[]pyrene Alters the Bioreactivity of Fine Biochar Particles toward Macrophages Leading to Deregulated Macrophagic Defense and Autophagy.

ACS Nano 2021 Jun 14. Epub 2021 Jun 14.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

Contaminant-bearing fine biochar particles (FBPs) may exert significantly different toxicity profiles from their contaminant-free counterparts. While the role of FBPs in promoting contaminant uptake has been recognized, it is unclear whether the binding of contaminants can modify the biochemical reactivity and toxicological profiles of FBPs. Here, we show that binding of benzo[]pyrene (B()P, a model polycyclic aromatic hydrocarbon) at environmentally relevant exposure concentrations markedly alters the cytotoxicity of FBPs to macrophages, an important line of innate immune defense against airborne particulate matters (PMs). Specifically, B()P-bearing FBPs elicit more severe disruption of the phospholipid membrane, endocytosis, oxidative stress, autophagy, and compromised innate immune defense, as evidenced by blunted proinflammatory effects, compared with B()P-free FBPs. Notably, the altered cytotoxicity cannot be attributed to the dissolution of B()P from the B()P-bearing FBPs, but appears to be related to B()P adsorption-induced changes of FBPs bioreactivity toward macrophages. Our findings highlight the significance of environmental chemical transformation in altering the bioreactivity and toxicity of PMs and call for further studies on other types of carbonaceous nanoparticles and additional exposure scenarios.
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http://dx.doi.org/10.1021/acsnano.1c00324DOI Listing
June 2021

Development and Validation of a Risk Score for Predicting Post-acute Myocardial Infarction Infection in Patients Undergoing Percutaneous Coronary Intervention: Study Protocol for an Observational Study.

Front Cardiovasc Med 2021 28;8:675142. Epub 2021 May 28.

Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Post-acute myocardial infarction (post-AMI) infection is an infrequent but important and serious complication in patients with ST-segment elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI). Predicting its occurrence is essential for future prevention. However, little is known about the prediction of post-AMI infection in such patients to date. This study aims to develop and validate a new risk score based on risk factors for early prediction of infection in STEMI patients undergoing PCI. This prospective, multi-center and observational study assesses the predictive value of risk score for post-AMI infection among a cohort of patients hospitalized due to STEMI. The STEMI patients undergoing PCI enrolled between January 1st 2010 and May 31st 2016 were served as a development cohort while those enrolled from June 1st 2016 to May 31st 2018 were served as validation cohort. The primary endpoint was post-AMI infection during hospitalization, defined as infection requiring antibiotics (reflecting the clinical influence of infection compatible with the necessity for additional treatment), and all-cause death and major adverse cardiovascular events (MACE) including all-cause death, recurrent myocardial infarction, target vessel revascularization, and stroke were considered as secondary endpoints. The risk score model based on risk factors was established using stepwise logistic regression, and will be validated in other centers and external patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). This study will provide evidence on prognostic property, reliability of scoring, comparative performance, and suitability of the novel model for screening purpose in order to be recommended for clinical practice. Our study is designed to develop and validate a clinical risk score for predicting infection in participants with STEMI who have undergone PCI. This simple tool may therefore improve evaluation of post-AMI infection and enhance future researches into the best practices to prevent or reduce infection in such patients. www.chictr.org.cn, identifier: ChiCTR1900028278.
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http://dx.doi.org/10.3389/fcvm.2021.675142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193038PMC
May 2021

Visible light driven deuteration of formyl C-H and hydridic C(sp)-H bonds in feedstock chemicals and pharmaceutical molecules.

Chem Sci 2020 Aug 5;11(33):8912-8918. Epub 2020 Aug 5.

Department of Chemistry, National University of Singapore 3 Science Drive 3 117543 Republic of Singapore

Deuterium labelled compounds are of significant importance in chemical mechanism investigations, mass spectrometric studies, diagnoses of drug metabolisms, and pharmaceutical discovery. Herein, we report an efficient hydrogen deuterium exchange reaction using deuterium oxide (DO) as the deuterium source, enabled by merging a tetra--butylammonium decatungstate (TBADT) hydrogen atom transfer photocatalyst and a thiol catalyst under light irradiation at 390 nm. This deuteration protocol is effective with formyl C-H bonds and a wide range of hydridic C(sp)-H bonds ( α-oxy, α-thioxy, α-amino, benzylic, and unactivated tertiary C(sp)-H bonds). It has been successfully applied to the high incorporation of deuterium in 38 feedstock chemicals, 15 pharmaceutical compounds, and 6 drug precursors. Sequential deuteration between formyl C-H bonds of aldehydes and other activated hydridic C(sp)-H bonds can be achieved in a selective manner.
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http://dx.doi.org/10.1039/d0sc02661aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163369PMC
August 2020

Blood Vessel Segmentation of Fundus Retinal Images Based on Improved Frangi and Mathematical Morphology.

Comput Math Methods Med 2021 26;2021:4761517. Epub 2021 May 26.

College of Communication and Information Engineering, Xi'an University of Science and Technology, Xi'an 710054, China.

An improved blood vessel segmentation algorithm on the basis of traditional Frangi filtering and the mathematical morphological method was proposed to solve the low accuracy of automatic blood vessel segmentation of fundus retinal images and high complexity of algorithms. First, a global enhanced image was generated by using the contrast-limited adaptive histogram equalization algorithm of the retinal image. An improved Frangi Hessian model was constructed by introducing the scale equivalence factor and eigenvector direction angle of the Hessian matrix into the traditional Frangi filtering algorithm to enhance blood vessels of the global enhanced image. Next, noise interferences surrounding small blood vessels were eliminated through the improved mathematical morphological method. Then, blood vessels were segmented using the Otsu threshold method. The improved algorithm was tested by the public DRIVE and STARE data sets. According to the test results, the average segmentation accuracy, sensitivity, and specificity of retinal images in DRIVE and STARE are 95.54%, 69.42%, and 98.02% and 94.92%, 70.19%, and 97.71%, respectively. The improved algorithm achieved high average segmentation accuracy and low complexity while promising segmentation sensitivity. This improved algorithm can segment retinal vessels more accurately than other algorithms.
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http://dx.doi.org/10.1155/2021/4761517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172282PMC
May 2021

Combined Histopathologic Risk Score using TP53 Protein Expression, CD8+ T-cell Density, and Intratumoural Budding is an Independent Predictor of Neoadjuvant Therapy Response in Rectal Adenocarcinoma.

Histopathology 2021 Jun 14. Epub 2021 Jun 14.

Department of Pathology, University of Pittsburgh Medical Center, USA.

Aims: Neoadjuvant therapy is the recommended treatment for locally advanced rectal adenocarcinoma; however, there remains significant variability in response to therapy. TP53 has been associated with therapy response and prognosis with conflicting data. Recently, we demonstrated that immune cell density and intratumoural budding (ITB) are predictive factors in rectal cancer. We investigated the predictive value of TP53 immunohistochemistry with CD8+ T-cell density and ITB on pre-treatment biopsies of rectal adenocarcinoma for response to neoadjuvant therapy.

Methods And Results: Pre-treatment biopsies of rectal adenocarcinoma from 117 patients with neoadjuvant therapy were analyzed for TP53 expression by immunohistochemistry, ITB, CD8+ T-cell density, and mismatch repair protein (MMR) status. Most rectal adenocarcinomas displayed aberrant TP53 expression (86/117, 74%). Compared to TP53 wild-type, aberrant TP53 expression was associated with proficient MMR status (P=0.003) and low CD8+ T-cell density (P=0.001). Aberrant TP53 was significantly associated with a partial to poor response to neoadjuvant therapy (OR=2.42, 95% CI 1.04-5.62, P=0.04). A combined histopathologic risk score (HRS) was created using CD8+ T-cell density, ITB, and TP53 expression. Patients were separated into low (0-1 factors) and high (2-3 factors) HRS categories. In the multivariable model, patients with a high HRS were 3.25-fold more likely to have a partial or poor response to neoadjuvant therapy (95% CI 1.48-7.11, P=0.003).

Conclusions: Our study demonstrates that aberrant TP53 expression, high ITB, and low CD8+ T-cell density in pre-treatment biopsies can help predict response to neoadjuvant therapy. These biomarkers may be helpful in identifying patients at risk for therapy resistance.
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http://dx.doi.org/10.1111/his.14430DOI Listing
June 2021

Comparison between robotic-assisted and laparoscopic left hemi-hepatectomy.

Asian J Surg 2021 Jun 10. Epub 2021 Jun 10.

Department of Pancreatobiliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. Electronic address:

Objective: To compare the safety and short-term outcomes between robotic-assisted and laparoscopic left hemi-hepatectomies in a single academic medical center.

Methods: A cohort of 52 patients, who underwent robotic-assisted or laparoscopic left hemi-hepatectomies between April 2015 and January 2020 in Department of Pancreatobiliary Surgery, the First Affiliated Hospital of Sun Yat-Sen University was recruited into the study. Their clinicopathological features and short-term outcomes were analyzed retrospectively.

Results: There were 25 robotic-assisted and 27 laparoscopic cases, with a median age of 55 years (34-77 years). There was one conversion to open in laparoscopic group. There were no significant differences in clinicopathological features between two groups, except robotic group had higher body mass index (23.9 vs. 22.0 kg/m, p = 0.047). Robotic-assisted and laparoscopic groups had similar operative time (300 vs. 310 min, p = 0.515), length of hospital stay (8 vs. 8 days, p = 0.981) and complication rates (4.0% vs. 14.8%, p = 0.395), but the former had less blood loss (100 vs. 200 ml, p < 0.001) and lower incidence of blood transfusion (0% vs. 22.2%, p = 0.023) in comparison with laparoscopic group. R0 resection was achieved for all patients with malignancies. There was no perioperative mortality in both groups. The cost of robotic group was higher than laparoscopic group (105,870 vs. 64,191 RMB yuan, p = 0.02).

Conclusion: The robotic-assisted and laparoscopic approaches had similar safety and short-term outcomes in left hemi-hepatectomy, and the former can reduce operative blood loss and blood transfusion. However, the costs were higher in robotic group.
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http://dx.doi.org/10.1016/j.asjsur.2021.05.017DOI Listing
June 2021

The role and related microbial processes of Mn-dependent anaerobic methane oxidation in reducing methane emissions from constructed wetland-microbial fuel cell.

J Environ Manage 2021 Jun 10;294:112935. Epub 2021 Jun 10.

College of Civil Engineering, Sichuan Agricultural University, Dujiangyan, 611830, PR China.

Anaerobic oxidation of methane (AOM) plays an important role in global carbon cycle and greenhouse gas emission reduction. In this study, an effective green technology to reduce methane emissions was proposed by introducing Mn-dependent anaerobic oxidation of methane (Mn-AOM) and microbial fuel cell (MFC) technology into constructed wetland (CW). The results indicate that the combination of biological methods and bioelectrochemical methods can more effectively control the methane emission from CW than the reported methods. The role of dissimilated metal reduction in methane control in CW and the biochemical process associated with Mn-AOM were also investigated. The results demonstrated that using Mn ore as the matrix and operating MFC effectively reduced methane emissions from CW, and higher COD removal rate was obtained in CW-MFC (Mn) during the 200 days of operation. Methane emission from CW-MFC (Mn) (53.76 mg/m/h) was 55.61% lower than that of CW (121.12 mg/m/h). The highest COD removal rate (99.85%) in CW-MFC (Mn) was obtained. As the dissimilative metal-reducing microorganisms, Geobacter (5.10%) was found enriched in CW-MFC (Mn). The results also showed that the presence of Mn ore was beneficial to the biodiversity of CW-MFCs and the growth of electrochemically active bacteria (EAB) including Proteobacteria (35.32%), Actinobacteria (2.38%) and Acidobacteria (2.06%), while the growth of hydrogenotrophic methanogens Methanobacterium was effectively inhibited. This study proposed an effective way to reduce methane from CW. It also provided reference for low carbon technology of wastewater treatment.
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http://dx.doi.org/10.1016/j.jenvman.2021.112935DOI Listing
June 2021

Brain structural alterations in MDD patients with gastrointestinal symptoms: Evidence from the REST-meta-MDD project.

Prog Neuropsychopharmacol Biol Psychiatry 2021 Jun 11;111:110386. Epub 2021 Jun 11.

Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.

Objective: While gastrointestinal (GI) symptoms are very common in patients with major depressive disorder (MDD), few studies have investigated the neural basis behind these symptoms. In this study, we sought to elucidate the neural basis of GI symptoms in MDD patients by analyzing the changes in regional gray matter volume (GMV) and gray matter density (GMD) in brain structure.

Method: Subjects were recruited from 13 clinical centers and categorized into three groups, each of which is based on the presence or absence of GI symptoms: the GI symptoms group (MDD patients with at least one GI symptom), the non-GI symptoms group (MDD patients without any GI symptoms), and the healthy control group (HCs). Structural magnetic resonance images (MRI) were collected of 335 patients in the GI symptoms group, 149 patients in the non-GI symptoms group, and 446 patients in the healthy control group. The 17-item Hamilton Depression Rating Scale (HAMD-17) was administered to all patients. Correlation analysis and logistic regression analysis were used to determine if there was a correlation between the altered brain regions and the clinical symptoms.

Results: There were significantly higher HAMD-17 scores in the GI symptoms group than that of the non-GI symptoms group (P < 0.001). Both GMV and GMD were significant different among the three groups for the bilateral superior temporal gyrus, bilateral middle temporal gyrus, left lingual gyrus, bilateral caudate nucleus, right Fusiform gyrus and bilateral Thalamus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the HC group, the GI symptoms group demonstrated increased GMV and GMD in the bilateral superior temporal gyrus, and the non-GI symptoms group demonstrated an increased GMV and GMD in the right superior temporal gyrus, right fusiform gyrus and decreased GMV in the right Caudate nucleus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the non-GI symptoms group, the GI symptoms group demonstrated significantly increased GMV and GMD in the bilateral thalamus, as well as decreased GMV in the bilateral superior temporal gyrus and bilateral insula lobe (GRF correction, cluster-P < 0.01, voxel-P < 0.001). While these changed brain areas had significantly association with GI symptoms (P < 0.001), they were not correlated with depressive symptoms (P > 0.05). Risk factors for gastrointestinal symptoms in MDD patients (p < 0.05) included age, increased GMD in the right thalamus, and decreased GMV in the bilateral superior temporal gyrus and left Insula lobe.

Conclusion: MDD patients with GI symptoms have more severe depressive symptoms. MDD patients with GI symptoms exhibited larger GMV and GMD in the bilateral thalamus, and smaller GMV in the bilateral superior temporal gyrus and bilateral insula lobe that were correlated with GI symptoms, and some of them and age may contribute to the presence of GI symptoms in MDD patients.
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http://dx.doi.org/10.1016/j.pnpbp.2021.110386DOI Listing
June 2021

Lipopolysaccharides increase the risk of colorectal cancer recurrence and metastasis due to the induction of neutrophil extracellular traps after curative resection.

J Cancer Res Clin Oncol 2021 Jun 11. Epub 2021 Jun 11.

Department of Laboratory Medicine, Shanghai Tongji Hospital, Shanghai, 200065, People's Republic of China.

Background: Intra-abdominal infection after curative surgery for colorectal cancer is a serious complication associated with an increased risk of recurrence. Lipopolysaccharides (LPS)-an essential component of the cell wall of Gram-negative bacteria-were found to exert a protumorigenic effect by stimulating the inflammatory pathology and formation of neutrophil extracellular traps (NETs). This study was conducted to test whether LPS-induced formation of NETs promotes the development of cancer and metastasis.

Methods: The clinical characteristics, incidence of relapse, and serum myeloperoxidase-DNA complexes of 40 patients with infection and 40 patients without infection after curative surgery were analyzed. The effects of LPS on the induction of NETs were evaluated in a mouse model of colorectal cancer and liver metastasis. The toll-like receptor 9 (TLR9)-a DNA receptor-was knocked down to assess its effect on the mitogen-activated protein kinase pathway and activities implicated in the formation of NETs.

Results: Analysis of the clinical data obtained from these patients showed the significant relation of the formation of NETs and incidence of metastasis and survival rates. Subsequent in vitro experiments revealed an increased level of citrullinated-histone H3 and myeloperoxidase-DNA in LPS-injected mice with colorectal cancer. In the mimic metastatic model, injection of LPS enhanced the metastatic capacity, which was then attenuated by DNase I. This suggested that the formation of NETs was activated by LPS. Injection of TLR9-knockdown HCT116 cells in mice, followed by induction through LPS, mitigated the level of citrullinated-histone H3 and myeloperoxidase-DNA. This finding implied that the formation of NETs was suppressed.

Conclusion: These findings shed light on the mechanism underlying the relationship between the elevated rate of colorectal cancer recurrence in patients who underwent surgery and the incidence of infection. This mechanism involves the protumorigenic activities of LPS-induced formation of NETs. The NETs which could be mediated by the TLR9 and the mitogen-activated protein kinase signaling pathway.
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http://dx.doi.org/10.1007/s00432-021-03682-8DOI Listing
June 2021

Search for Light Dark Matter-Electron Scattering in the PandaX-II Experiment.

Phys Rev Lett 2021 May;126(21):211803

Research Center for Particle Science and Technology, Institute of Frontier and Interdisciplinary Science, Shandong University, Qingdao 266237, Shandong, China.

We report constraints on light dark matter through its interactions with shell electrons in the PandaX-II liquid xenon detector with a total 46.9  tonnes/day exposure. To effectively search for these very low energy electron recoils, ionization-only signals are selected from the data. 1821 candidates are identified within an ionization signal range between 50 and 75 photoelectrons, corresponding to a mean electronic recoil energy from 0.08 to 0.15 keV. The 90% C.L. exclusion limit on the scattering cross section between the dark matter and electron is calculated with systematic uncertainties properly taken into account. Under the assumption of point interaction, we provide the world's most stringent limit within the dark matter mass range from 15 to 30  MeV/c^{2}, with the corresponding cross section from 2.5×10^{-37} to 3.1×10^{-38}  cm^{2}.
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http://dx.doi.org/10.1103/PhysRevLett.126.211803DOI Listing
May 2021

Exploring the molecular basis of UG-rich RNA recognition by the human splicing factor TDP-43 using molecular dynamics simulation and free energy calculation.

J Comput Chem 2021 Jun 9. Epub 2021 Jun 9.

College of Chemistry and Chemical Engineering, Qiqihar University, Qiqihar, China.

Transactivation response element RNA/DNA-binding protein 43 (TDP-43) is involved in the regulation of alternative splicing of human neurodegenerative disease-related genes through binding to long UG-rich RNA sequences. Mutations in TDP-43, most in the homeodomain, cause neurological disorders such as amyotrophic lateral sclerosis and fronto temporal lobar degeneration. Several mutants destabilize the structure and disrupt RNA-binding activity. The biological functions of these mutants have been characterized, but the structural basis behind the loss of RNA-binding activity is unclear. Focused on the specific TDP-43-ssRNA complex (PDB code 4BS2), we applied molecular dynamics simulations and the molecular mechanics Poisson-Boltzmann surface area free energy calculation to characterize and explore the structural and dynamic effects between ssRNA and TDP-43. The energetic analysis indicated that the intermolecular van der Waals interaction and nonpolar solvation energy play an important role in the binding process of TDP-43 and ssRNA. Compared with the wild-type TDP-43, the reduction of the polar or non-polar interaction between all the mutants F149A, D105A/S254A, R171A/D174A, F147L/F149L/F229L/F231L and ssRNA is the main reason for the reduction of its binding free energy. Decomposing energies suggested that the extensive interactions between TDP-43 and the nitrogenous bases of ssRNA are responsible for the specific ssRNA recognition by TDP-43. These results elucidated the TDP-43-ssRNA interaction comprehensively and further extended our understanding of the previous experimental data. The uncovering of TDP-43-ssRNA recognition mechanism will provide us useful insights and new chances for the development of anti-neurodegenerative drugs.
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http://dx.doi.org/10.1002/jcc.26704DOI Listing
June 2021

Glycosylation at Asn254 Is Required for the Activation of the PDGF-C Protein.

Front Mol Biosci 2021 24;8:665552. Epub 2021 May 24.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China.

Platelet-derived growth factor C (PDGF-C) is a member of the PDGF/VEGF (vascular endothelial growth factor) family, which includes proteins that are well known for their mitogenic effects on multiple cell types. Glycosylation is one of the most important forms of posttranslational modification that has a significant impact on secreted and membrane proteins. Glycosylation has many well-characterized roles in facilitating protein processing and contributes to appropriate folding, conformation, distribution, and stability of proteins that are synthesized intracellularly in the endoplasmic reticulum (ER) and Golgi apparatus. Although the general process and functions of glycosylation are well documented, there are most likely others yet to be discovered, as the glycosylation of many potential substrates has not been characterized. In this study, we report that the PDGF-C protein is glycosylated at three sites, including Asn25, Asn55, and Asn254. However, we found that mutations at any of these sites do not affect the protein expression or secretion. Similarly, disruption of PDGF-C glycosylation had no impact on its progression through the ER and Golgi apparatus. However, the introduction of a mutation at Asn254 (N254 A) prevents the activation of full-length PDGF-C and its capacity for signaling the PDGF receptor. Our findings reveal that glycosylation affects PDGF-C activation rather than the protein synthesis or processing. This study characterizes a crucial modification of the PDGF-C protein, and may shed new light on the process and function of glycosylation.
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http://dx.doi.org/10.3389/fmolb.2021.665552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181125PMC
May 2021

Ultrasonic activation of inert poly(tetrafluoroethylene) enables piezocatalytic generation of reactive oxygen species.

Nat Commun 2021 06 9;12(1):3508. Epub 2021 Jun 9.

State Key Laboratory of Pollution Control and Resource Reuse, School of Environment, Nanjing University, Nanjing, China.

Controlled generation of reactive oxygen species (ROS) is essential in biological, chemical, and environmental fields, and piezoelectric catalysis is an emerging method to generate ROS, especially in sonodynamic therapy due to its high tissue penetrability, directed orientation, and ability to trigger in situ ROS generation. However, due to the low piezoelectric coefficient, and environmental safety and chemical stability concerns of current piezoelectric ROS catalysts, novel piezoelectric materials are urgently needed. Here, we demonstrate a method to induce polarization of inert poly(tetrafluoroethylene) (PTFE) particles ( ~ 1-5 μm) into piezoelectric electrets with a mild and convenient ultrasound process. Continued ultrasonic irradiation of the PTFE electrets generates ROS including hydroxyl radicals (•OH), superoxide (•O) and singlet oxygen O) at rates significantly faster than previously reported piezoelectric catalysts. In summary, ultrasonic activation of inert PTFE particles is a simple method to induce permanent PTFE polarization and to piezocatalytically generate aqueous ROS that is desirable in a wide-range of applications from environmental pollution control to biomedical therapy.
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http://dx.doi.org/10.1038/s41467-021-23921-3DOI Listing
June 2021

DINs: Deep Interactive Networks for Neurofibroma Segmentation in Neurofibromatosis Type 1 on Whole-Body MRI.

IEEE J Biomed Health Inform 2021 Jun 9;PP. Epub 2021 Jun 9.

Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor predisposition syndrome that involves the central and peripheral nervous systems. Accurate detection and segmentation of neurofibromas are essential for assessing tumor burden and longitudinal tumor size changes. Automatic convolutional neural networks (CNNs) are sensitive and vulnerable as tumors' variable anatomical location and heterogeneous appearance on MRI. In this study, we propose deep interactive networks (DINs) to address the above limitations. User interactions guide the model to recognize complicated tumors and quickly adapt to heterogeneous tumors. We introduce a simple but effective Exponential Distance Transform (ExpDT) that converts user interactions into guide maps regarded as the spatial and appearance prior. Comparing with popular Euclidean and geodesic distances, ExpDT is more robust to various image sizes, which reserves the distribution of interactive inputs. Furthermore, to enhance the tumor-related features, we design a deep interactive module to propagate the guides into deeper layers. We train and evaluate DINs on three MRI data sets from NF1 patients. The experiment results yield significant improvements of 44% and 14% in DSC comparing with automated and other interactive methods, respectively. We also experimentally demonstrate the efficiency of DINs in reducing user burden when comparing with conventional interactive methods.
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http://dx.doi.org/10.1109/JBHI.2021.3087735DOI Listing
June 2021

Endoscopic coblation treatment for congenital pyriform sinus fistula in children.

Medicine (Baltimore) 2021 May;100(19):e25942

Department of Otolaryngology-Head and Neck Surgery, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.

Abstract: Congenital pyriform sinus fistula (CPSF) is a very rare branchial apparatus malformation. Traditional open surgery for fistulectomy might fail to excise the lesion completely, leading to continual recurrence. Herein, we report our experience of endoscopic coblation technique for treatment of CPSF in children.To observe the clinical efficacy of endoscopic coblation treatment of CPSF in children, especially for those in acute infection stage.Retrospective case series with 54 patients (including 20 cases in acute infection stage and 34 cases in non infection stage) who were diagnosed with CPSF between October 2017 to November 2019, all patients were treated with endoscopic coblation to close the piriform fossa fistula, neck abscess incision and drainage performed simultaneously for acute infection stage cases. Data collected including age of diagnosis, presenting symptoms, diagnostic methods, prior and subsequent treatments, length of hospitalization, and recurrence were analyzed.Of the 20 cases in acute infection stage, there were 3 children with transient vocal cord paresis all of which resolved with 1 month. Four children of the 34 cases in non infection stage appeared reddish swelling of the neck on the 4th, 5th, 6th, and 7th days after coblation and then underwent abscess incision and drainage. All cases experienced no recurrence, vocal cord paralysis, pharyngeal fistula and massive hemorrhage after their first endoscopic coblation of the sinus tract in the follow up of 3 to 28 months.Endoscopic coblation is an effective and safe approach for children with CPSF, neck abscess incision and drainage could be performed simultaneously in acute infection stage. We advocate using this minimally invasive technique as first line of treatment for CPSF.
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http://dx.doi.org/10.1097/MD.0000000000025942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133172PMC
May 2021

An optimized culture medium to isolate strains from the human intestinal tract.

Food Funct 2021 Jun 9. Epub 2021 Jun 9.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, P. R China. and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China and (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China.

Research studies have shown that Lactobacillus fermentum generally exists in the human gut and has potential health benefits on host health due to its antimicrobial and antioxidant properties. However, the lack of an effective culture medium for the isolation of L. fermentum has presented a significant obstacle on the path to screen L. fermentum strains from the human intestinal tract with a large diversity of commensal microbes. In this study, a total of 51 Lactobacillus species are detected in 200 human fecal samples and we aim to distinguish L. fermentum from these common existing Lactobacillus species and design a more efficient culture medium for isolating L. fermentum strains from the human gut. Based on antibiotic susceptibility and sugar utilization tests, a new optimized medium called LFMATA containing arabinose as the carbon source and 20 mg L-1 vancomycin, 64 mg L-1 gentamicin and 256 mg L-1 streptomycin was developed. Genotype and phenotype analysis for antibiotic resistance and carbohydrate metabolism showed that though glycometabolism-related genes (araA, xylA, manX, bglX, treP and rbsK) correlated with the carbon utilization of Lactobacillus, the genes conferring resistance to streptomycin (gidB and rpsL) and gentamicin (tlyA) were not directly associated with the antibiotic resistance of Lactobacillus strains. This new selective medium greatly increased the efficiency of screening L. fermentum strains from human fecal samples, with the rate of L. fermentum isolation on LFMATA being 10-fold higher than that on LAMVAB.
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http://dx.doi.org/10.1039/d1fo00209kDOI Listing
June 2021

A Pan-cancer Analysis Reveals the Abnormal Expression and Drug Sensitivity of CSF1.

Anticancer Agents Med Chem 2021 Jun 7. Epub 2021 Jun 7.

Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province 450001, China.

Background: Colony-stimulating factor-1 (CSF1) is a cytokine that is closely related to normal organ growth and development as well as tumor progression.

Objective: We aimed to summarize and clarify the reasons for the abnormal expression of CSF1 in tumors and explore the role of CSF1 in tumor progression. Furthermore, drug response analysis may provide a reference for clinical medication.

Methods: The expression of CSF1 was analyzed by TCGA and CCLE. Besides, cBioPortal and MethSurv databases were used to conduct mutation and DNA methylation analyses. Further, correlations between CSF1 expression and tumor stage, survival, immune infiltration, drug sensitivity and enrichment analyses were validated via UALCAN, Kaplan-Meier plotter, TIMER, CTRP and Coexperia databases.

Results: CSF1 is expressed in a variety of tissues, meaningfully, it can be detected in blood. Compared with normal tissues, CSF1 expression was significantly decreased in most tumors. The missense mutation and DNA methylation of CSF1 may cause the downregulated expression. Moreover, decreased CSF1 expression was related with higher tumor stage and worse survival. Further, the promoter DNA methylation level of CSF1 was prognostically significant in most tumors. Besides, CSF1 was closely related to immune infiltration, especially macrophages. Importantly, CSF1 expression was associated with a good response to VEGFRs inhibitors, which may be due to the possible involvement of CSF1 in tumor angiogenesis and metastasis processes.

Conclusion: The abnormal expression of CSF1 could serve as a promising biomarker of tumor progression and prognosis in pan-cancer. Significantly, angiogenesis and metastasis inhibitors may show a good response to CSF1-related tumors.
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http://dx.doi.org/10.2174/1871520621666210608105357DOI Listing
June 2021

Mining genome traits that determine the different gut colonization potential of and species.

Microb Genom 2021 Jun;7(6)

National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu 214122, PR China.

Although the beneficial effects of probiotics are likely to be associated with their ability to colonize the gut, little is known about the characteristics of good colonizers. In a systematic analysis of the comparative genomics, we tried to elucidate the genomic contents that account for the distinct host adaptability patterns of and species. The species, with species-level phylogenetic structures affected by recombination among strains, broad mucin-foraging activity, and dietary-fibre-degrading ability, represented niche conservatism and tended to be host-adapted. The species stretched across three lifestyles, namely free-living, nomadic and host-adapted, as characterized by the variations of bacterial occurrence time, guanine-cytosine (GC) content and genome size, evolution event frequency, and the presence of human-adapted bacterial genes. The numbers and activity of host-adapted factors, such as bile salt hydrolase and intestinal tissue-anchored elements, were distinctly distributed among the three lifestyles. The strains of the three lifestyles could be separated with such a collection of colonization-related genomic content (genes, genome size and GC content). Thus, our work provided valuable information for rational selection and gut engraftment prediction of probiotics. Here, we have found many interesting predictive results for bacterial gut fitness, which will be validated and .
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http://dx.doi.org/10.1099/mgen.0.000581DOI Listing
June 2021

Clinicopathological features of sclerosing angiomatoid nodular transformation of the spleen.

Pathol Res Pract 2021 May 24;224:153490. Epub 2021 May 24.

Department of Pathology, the First Medical Center of the Chinese People's Liberation Army (PLA) General Hospital, Beijing, 100083, China. Electronic address:

Purpose: To explore the clinicopathological features of sclerosing angiomatoid nodular transformation (SANT) of the spleen.

Methods: The clinicopathological data of 26 SANT patients were analyzed.

Result: There were 15 men and 11 women, aged 23-62 years (mean: 43.9 years; median: 43 years). Twenty patients were found during health check-ups. Magnetic resonance imaging had significantly higher specificity than other imaging modes in the diagnosis of SANT. Macroscopically, the lesions were gray-red and gray-white, along with well-demarcated nodules. Microscopy showed multiple angiomatoid nodules embedded in hyperplastic fibrous tissues and dense collagen fiber; the angiomatoid structures inside the nodules had varied morphology. Patchy and nodular fresh and old hemorrhages were observed in each lesion. Proliferative fibroblasts were seen in the stroma, along with infiltration of a few mixed inflammatory cells. Serum tumor markers were negative. Fourteen patients (53.8 %) had benign or malignant lesions in other parts of the body, including the liver, kidneys, and adrenal and pituitary glands which were similar to von Hippel-Lindau (VHL) syndrome. The reasons for occurrence of SANT may be as follows: hemangioma/lymphangioma or splenic congestion with extensive hemorrhage and secondary changes.

Conclusions: SANT is a rare benign vascular lesion with some clinical manifestations similar to VHL syndrome. Patients have good prognosis after tumor removal.
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http://dx.doi.org/10.1016/j.prp.2021.153490DOI Listing
May 2021

DevOmics: an integrated multi-omics database of human and mouse early embryo.

Brief Bioinform 2021 Jun 7. Epub 2021 Jun 7.

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.

Transcriptomic and epigenetic alterations during early embryo development have been proven to play essential roles in regulating the cell fate. Nowadays, advances in single-cell transcriptomics and epigenomics profiling techniques provide large volumes of data for understanding the molecular regulatory mechanisms in early embryos and facilitate the investigation of assisted reproductive technology as well as preimplantation genetic testing. However, the lack of integrated data collection and unified analytic procedures greatly limits their usage in scientific research and clinical application. Hence, it is necessary to establish a database integrating the regulatory information of human and mouse early embryos with unified analytic procedures. Here, we introduce DevOmics (http://devomics.cn/), which contains normalized gene expression, DNA methylation, histone modifications (H3K4me3, H3K9me3, H3K27me3, H3K27ac), chromatin accessibility and 3D chromatin architecture profiles of human and mouse early embryos spanning six developmental stages (zygote, 2cell, 4cell, 8cell, morula and blastocyst (ICM, TE)). The current version of DevOmics provides Search and Advanced Search for retrieving genes a researcher is interested in, Analysis Tools including the differentially expressed genes (DEGs) analysis for acquiring DEGs between different types of samples, allelic explorer for displaying allele-specific gene expression as well as epigenetic modifications and correlation analysis for showing the dynamic changes in different layers of data across developmental stages, as well as Genome Browser and Ortholog for visualization. DevOmics offers a user-friendly website for biologists and clinicians to decipher molecular regulatory mechanisms of human and mouse early embryos.
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http://dx.doi.org/10.1093/bib/bbab208DOI Listing
June 2021

OPLS4: Improving Force Field Accuracy on Challenging Regimes of Chemical Space.

J Chem Theory Comput 2021 Jun 7. Epub 2021 Jun 7.

Schrodinger, Incorporated, 120 West 45th Street, New York, New York 10036, United States.

We report on the development and validation of the OPLS4 force field. OPLS4 builds upon our previous work with OPLS3e to improve model accuracy on challenging regimes of drug-like chemical space that includes molecular ions and sulfur-containing moieties. A novel parametrization strategy for charged species, which can be extended to other systems, is introduced. OPLS4 leads to improved accuracy on benchmarks that assess small-molecule solvation and protein-ligand binding.
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http://dx.doi.org/10.1021/acs.jctc.1c00302DOI Listing
June 2021

Tunable Dual-Effector Allostery System for Nucleic Acid Analysis with Enhanced Sensitivity and an Extended Dynamic Range.

Anal Chem 2021 Jun 6;93(23):8170-8177. Epub 2021 Jun 6.

Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou 350108, P. R. China.

In the last few years, studies have demonstrated the existence of dual-effector allosteric cooperativity in nature and the mechanism underlying enhanced activation/inhibition performance. In this work, we design an artificial dual-effector allostery system for the construction of a dynamic biosensor that can achieve nucleic acid detection with superior sensitivity and across an extraordinary broad detection range. Our dual-effector allostery-regulated biosensor is based on the multibranched hybridization chain reaction (mHCR) involving three hairpins (H1, H2, and H3). In the presence of the target nucleic acid, the mHCR is initiated via cascading strand displacement events. The products of mHCR are then captured on the electrode surface based on the mechanism of the multivalent proximity ligation assay (mPLA) and the multivalent binding assay (mBA). The subsequent conjugation of streptavidin-modified horseradish peroxidase (SA-HRP) can lead to an increase in the electrochemical signal. Importantly, two distinct allosteric activation sites and two distinct allosteric inhibition sites in H1 are designed to fine-tune the nucleic acid detection sensitivity and the dynamic range. Using this new dual-effector allostery tool, we report the detection of nucleic acid at a dynamic range spanning 10-10 aM, 11 orders of magnitude showing the broadest dynamic range reported to date with an allosteric regulation biosensor construct.
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http://dx.doi.org/10.1021/acs.analchem.1c00055DOI Listing
June 2021

Multimerized self-assembled caged siRNA nanoparticles for photomodulation of RNAi-induced gene silencing.

Chem Sci 2020 Oct 12;11(45):12289-12297. Epub 2020 Oct 12.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Beijing 100191 China

We rationally designed and developed caged siRNA nanoparticles (Multi-Chol-siRNA) self-assembled with cholesterol-modified multimerized caged siRNAs for photomodulation of siRNA gene silencing activity. Strong resistance to serum nuclease and RNase A was observed for these cholesterol-modified caged siRNA nanoparticles due to the formation of nanostructures with high intensity of siRNA. These caged Multi-Chol-siRNA self-assembled nanoparticles were successfully used to achieve photochemical regulation of both exogenous GFP and endogenous Eg5 gene expressions with a GFP/RFP transient transfection system and Eg5-associated assays, respectively. Further, caged Multi-Chol-siGFP/siEg5 self-assembled nanoparticles simultaneously targeting GFP and Eg5 genes were also developed. The caged Multi-Chol-siRNA self-assembled nanoparticles have demonstrated the effectiveness of enhancing photomodulation of multiple RNAi-induced gene silencing activities in cells.
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http://dx.doi.org/10.1039/d0sc03562aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162473PMC
October 2020

Foldable semi-ladder polymers: novel aggregation behavior and high-performance solution-processed organic light-emitting transistors.

Chem Sci 2020 Sep 24;11(41):11315-11321. Epub 2020 Sep 24.

Department of Chemistry, The James Franck Institute, The University of Chicago 929 E 57th Street Chicago Illinois 60601 USA

A critical issue in developing high-performance organic light-emitting transistors (OLETs) is to balance the trade-off between charge transport and light emission in a semiconducting material. Although traditional materials for organic light-emitting diodes (OLEDs) or organic field-effect transistors (OFETs) have shown modest performance in OLET devices, design strategies towards high-performance OLET materials and the crucial structure-performance relationship remain unclear. Our research effort in developing cross-conjugated weak acceptor-weak donor copolymers for luminescent properties lead us to an unintentional discovery that these copolymers form coiled foldamers with intramolecular H-aggregation, leading to their exceptional OLET properties. An impressive external quantum efficiency (EQE) of 6.9% in solution-processed multi-layer OLET devices was achieved.
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http://dx.doi.org/10.1039/d0sc04068aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162540PMC
September 2020

Molecular latent space simulators.

Chem Sci 2020 Aug 26;11(35):9459-9467. Epub 2020 Aug 26.

Pritzker School of Molecular Engineering, University of Chicago Chicago USA

Small integration time steps limit molecular dynamics (MD) simulations to millisecond time scales. Markov state models (MSMs) and equation-free approaches learn low-dimensional kinetic models from MD simulation data by performing configurational or dynamical coarse-graining of the state space. The learned kinetic models enable the efficient generation of dynamical trajectories over vastly longer time scales than are accessible by MD, but the discretization of configurational space and/or absence of a means to reconstruct molecular configurations precludes the generation of continuous atomistic molecular trajectories. We propose latent space simulators (LSS) to learn kinetic models for continuous atomistic simulation trajectories by training three deep learning networks to (i) learn the slow collective variables of the molecular system, (ii) propagate the system dynamics within this slow latent space, and (iii) generatively reconstruct molecular configurations. We demonstrate the approach in an application to Trp-cage miniprotein to produce novel ultra-long synthetic folding trajectories that accurately reproduce atomistic molecular structure, thermodynamics, and kinetics at six orders of magnitude lower cost than MD. The dramatically lower cost of trajectory generation enables greatly improved sampling and greatly reduced statistical uncertainties in estimated thermodynamic averages and kinetic rates.
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http://dx.doi.org/10.1039/d0sc03635hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162036PMC
August 2020

Docking-based generation of antibodies mimicking Cry1A/1B protein binding sites as potential insecticidal agents against diamondback moth (Plutella xylostella).

Pest Manag Sci 2021 Jun 6. Epub 2021 Jun 6.

Key Lab of Food Quality and Safety of Jiangsu Province-State Key Laboratory Breeding Base, Key Laboratory of Control Technology and Standard for Agro-product Safety and Quality, Ministry of Agriculture, Institute of Food Safety and Nutrition, Jiangsu Academy of Agricultural Sciences, 210014, Nanjing, China.

Background: Broad use of insecticidal Cry proteins from Bacillus thuringiensis in biopesticides and transgenic crops has resulted in cases of practical field resistance, highlighting the need for novel approaches to insect control. Previously we described an anti-Cry1Ab idiotypic-antibody (B12-scFv) displaying toxicity against rice leafroller (Cnaphalocrocis medinalis) larvae, supporting the potential of antibodies for pest control. The goal of the present study was to generate insecticidal antibodies against diamondback moth (Plutella xylostella) larvae.

Results: Four genetically engineered antibodies (GEAbs) were designed in silico from B12-scFv using 3D structure and docking predictions to alkaline phosphatase (ALP) as a Cry1Ac receptor in P. xylostella. Among these GEAbs, the GEAb-dV antibody consisting of two light chains had overlapping binding sites with Cry1A and Cry1B proteins and displayed high binding affinity to P. xylostella midgut brush border membrane (BBM) proteins. Proteins in BBM identified by pull-down assays as binding to GEAb-dV included an ABC transporter and V-ATPase subunit A protein. Despite lacking the α-helical structures in Cry1A that are responsible for pore formation, ingestion of GEAb-dV disrupted the P. xylostella larval midgut epithelium and resulted in toxicity. Apoptotic genes were activated in gut cells upon treatment with GEAb-dV .

Conclusion: This study describes the first insecticidal GEAb targeting P. xylostella by mimicking Cry proteins. Data support that GEAb-dV toxicity is associated to activation of intracellular cell death pathways, in contrast to pore-formation associated toxicity of Cry proteins. This work provides a foundation for the design of novel insecticidal antibodies for insect control.
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http://dx.doi.org/10.1002/ps.6499DOI Listing
June 2021

Lactic acid bacteria that activate immune gene expression in Caenorhabditis elegans can antagonise Campylobacter jejuni infection in nematodes, chickens and mice.

BMC Microbiol 2021 Jun 5;21(1):169. Epub 2021 Jun 5.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, P. R. China.

Background: Campylobacter jejuni is the major micro-bacillary pathogen responsible for human coloenteritis. Lactic acid bacteria (LAB) have been shown to protect against Campylobacter infection. However, LAB with a good ability to inhibit the growth of C. jejuni in vitro are less effective in animals and animal models, and have the disadvantages of high cost, a long cycle, cumbersome operation and insignificant immune response indicators. Caenorhabditis elegans is increasingly used to screen probiotics for their anti-pathogenic properties. However, no research on the use of C. elegans to screen for probiotic candidates antagonistic to C. jejuni has been conducted to date.

Results: This study established a lifespan model of C. elegans, enabling the preselection of LAB to counter C. jejuni infection. A potential protective mechanism of LAB was identified. Some distinct LAB species offered a high level of protection to C. elegans against C. jejuni. The LAB strains with a high protection rate reduced the load of C. jejuni in C. elegans. The transcription of antibacterial peptide genes, MAPK and Daf-16 signalling pathway-related genes was elevated using the LAB isolates with a high protection rate. The reliability of the lifespan model of C. elegans was verified using mice and chickens infected with C. jejuni.

Conclusions: The results showed that different LAB had different abilities to protect C. elegans against C. jejuni. C. elegans provides a reliable model for researchers to screen for LAB that are antagonistic to C. jejuni on a large scale.
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http://dx.doi.org/10.1186/s12866-021-02226-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180125PMC
June 2021