Publications by authors named "Wei Hong"

921 Publications

On-demand pH-sensitive surface charge-switchable polymeric micelles for targeting Pseudomonas aeruginosa biofilms development.

J Nanobiotechnology 2021 Apr 9;19(1):99. Epub 2021 Apr 9.

School of Pharmacy, Shandong New Drug Loading & Release Technology and Preparation Engineering Laboratory, Binzhou Medical University, 346 Guanhai Road, Yantai, 264003, People's Republic of China.

Bacterial biofilm is the complicated clinical issues, which usually results in bacterial resistance and reduce the therapeutic efficacy of antibiotics. Although micelles have been drawn attention in treatment of the biofilms, the micelles effectively permeate and retain in biofilms still facing a big challenge. In this study, we fabricated on-demand pH-sensitive surface charge-switchable azithromycin (AZM)-encapsulated micelles (denoted as AZM-SCSMs), aiming to act as therapeutic agent for treating Pseudomonas aeruginosa (P. aeruginosa) biofilms. The AZM-SCSMs was composed of poly(L-lactide)-polyetherimide-hyd-methoxy polyethylene glycol (PLA-PEI-hyd-mPEG). It was noteworthy that the pH-sensitive acylhydrazone bond could be cleaved in acidic biofilm microenvironment, releasing the secondary AZM-loaded cationic micelles based on PLA-PEI (AZM-SCMs) without destroying the micellar integrity, which could tailor drug-bacterium interaction using micelles through electrostatic attraction. The results proved that positively charged AZM-SCMs could facilitate the enhanced penetration and retention inside biofilms, improved binding affinity with bacterial membrane, and added drug internalization, thus characterized as potential anti-biofilm agent. The excellent in vivo therapeutic performance of AZM-SCSMs was confirmed by the targeting delivery to the infected tissue and reduced bacterial burden in the abscess-bearing mice model. This study not only developed a novel method for construction non-depolymerized pH-sensitive SCSMs, but also provided an effective means for the treatment of biofilm-related infections.
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http://dx.doi.org/10.1186/s12951-021-00845-0DOI Listing
April 2021

NOX4-Derived ROS Promotes Collagen I Deposition in Bronchial Smooth Muscle Cells by Activating Noncanonical p38MAPK/Akt-Mediated TGF- Signaling.

Oxid Med Cell Longev 2021 19;2021:6668971. Epub 2021 Mar 19.

Department of Pulmonary and Critical Care Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China.

Background: Airway smooth muscle (ASM) remodeling is a hallmark in chronic obstructive pulmonary disease (COPD). NADPH oxidase 4- (NOX4-) mediated reactive oxygen species (ROS) production plays a crucial role in cell differentiation and extracellular matrix (ECM) synthesis in ASM remodeling. However, the precise mechanisms underpinning its pathogenic roles remain elusive.

Methods: The expression of NOX4 and TGF- in the airway of the lung was measured in COPD patients and the control group. Cigarette smoke- (CS-) induced emphysema mice were generated, and the alteration of -SMA, NOX4, TGF-, and collagen I was accessed. The changes of the expression of ECM markers, NOX4, components of TGF-/Smad, and MAPK/Akt signaling in human bronchial smooth muscle cells (HBSMCs) were ascertained for delineating mechanisms of NOX4-mediated ROS production on cell differentiation and remodeling in human ASM cells.

Results: An increased abundance of NOX4 and TGF- proteins in the epithelial cells and ASM of lung was observed in COPD patients compared with the control group. Additionally, an increased abundance expression of NOX4 and -SMA was observed in the lungs of the CS-induced emphysema mouse model. TGF- displayed abilities to increase the oxidative burden and collagen I production, along with enhanced phosphorylation of ERK, p38MAPK, and p-Akt473 in HBSMCs. These effects of TGF- could be inhibited by the ROS scavenger N-acetylcysteine (NAC), siRNA-mediated knockdown of Smad3 and NOX4, and pharmacological inhibitors SB203580 (p38MAPK inhibitor) and LY294002 (Akt inhibitor).

Conclusions: NOX4-mediated ROS production alters TGF--induced cell differentiation and collagen I protein synthesis in HBSMCs in part through the p38MAPK/Akt signaling pathway in a Smad-dependent manner.
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http://dx.doi.org/10.1155/2021/6668971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007363PMC
March 2021

Fecal Microbiome Transplantation from Children with Autism Spectrum Disorder Modulates Tryptophan and Serotonergic Synapse Metabolism and Induces Altered Behaviors in Germ-Free Mice.

mSystems 2021 Apr 6;6(2). Epub 2021 Apr 6.

Children's Nutrition Research Center, Children's Hospital of Chongqing Medical University, Chongqing Key Laboratory of Childhood Nutrition and Health, Chongqing, China

To determine the relationship of the gut microbiota and its metabolites with autism spectrum disorder (ASD)-like behaviors and preliminarily explore the potential molecular mechanisms, the fecal microbiota from donors with ASD and typically developing (TD) donors were transferred into germ-free (GF) mice to obtain ASD-FMT mice and TD-FMT mice, respectively. Behavioral tests were conducted on these mice after 3 weeks. 16S rRNA gene sequencing of the cecal contents and untargeted metabolomic analysis of the cecum, serum, and prefrontal cortex were performed. Untargeted metabolomics was also used to analyze fecal samples of TD and ASD children. Western blotting detected the protein expression levels of tryptophan hydroxylase 1 (TPH1), serotonin transporter (SERT), and serotonin 1A receptor (5-HT1AR) in the colon and TPH2, SERT, and 5-HT1AR in the prefrontal cortex of mice. ASD-FMT mice showed ASD-like behavior and a microbial community structure different from that of TD-FMT mice. Tryptophan and serotonin metabolisms were altered in both ASD and TD children and ASD-FMT and TD-FMT mice. Some microbiota may be related to tryptophan and serotonin metabolism. Compared with TD-FMT mice, ASD-FMT mice showed low SERT and 5-HT1AR and high TPH1 expression levels in the colon. In the prefrontal cortex, the expression levels of TPH2 and SERT were increased in the ASD-FMT group relative to the TD-FMT group. Therefore, the fecal microbiome of ASD children can lead to ASD-like behaviors, different microbial community structures, and altered tryptophan and serotonin metabolism in GF mice. These changes may be related to changes in some key proteins involved in the synthesis and transport of serotonin. The relationship between the gut microbiota and ASD is not yet fully understood. Numerous studies have focused on the differences in intestinal microbial and metabolism profiles between TD and ASD children. However, it is still not clear if these microbes and metabolites cause the development of ASD symptoms. Here, we collected fecal samples from TD and ASD children, transplanted them into GF mice, and found that the fecal microbiome of ASD children can lead to ASD-like behaviors, different microbial community structures, and altered tryptophan and serotonin metabolism in GF mice. We also demonstrated that tryptophan and serotonin metabolism was also altered in ASD and TD children. Together, these findings confirm that the microbiome from children with ASD may lead to ASD-like behavior of GF mice through metabolites, especially tryptophan and serotonin metabolism.
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http://dx.doi.org/10.1128/mSystems.01343-20DOI Listing
April 2021

Bacteria Co-colonizing with in Two Asymptomatic Patients.

Open Life Sci 2019 Jan 31;14:628-637. Epub 2019 Dec 31.

School of Basic Medical Science, Guizhou Medical University, Guiyang, 550025, China Guiyang 550025, Guizhou, China.

Background: infection (CDI) is the leading cause of nosocomial diarrhea. Co-colonization of key bacterial taxa may prevent the transition from asymptomatic colonization to CDI. However, little is known about the composition of key bacterial taxa in asymptomatic patients.

Methods: In the present study, the culture method was used to examine the composition of stool microbiota in two asymptomatic patients from Guizhou, China.

Results: A total of 111 strains were isolated and phylogenetic relationships were determined by 16S ribosomal gene sequencing and Molecular Evolutionary Genetics Analysis version 7. The results demonstrated that (33.3%, 37/111), (24.3%, 27/111) and (11.7%, 13/111) exhibited a high ratio in asymptomatic patients. These isolates derived from two phyla: (51.3%, 57/111) and (44.1%, 49/111). In addition, co-colonization of human pathogens , , , and with was identified. To the best of our knowledge, these pathogens have not been co-isolated with previously.

Conclusions: In summary, the present study identified the composition of fecal microbiota in two asymptomatic patients in Guizhou, China. These results suggested that co-infection with human pathogens may be ubiquitous during CDI progression.
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http://dx.doi.org/10.1515/biol-2019-0071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874806PMC
January 2019

Imaging Biomarkers to Predict and Evaluate the Effectiveness of Immunotherapy in Advanced Non-Small-Cell Lung Cancer.

Front Oncol 2021 19;11:657615. Epub 2021 Mar 19.

Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China.

Objective: We aimed to identify imaging biomarkers to assess predictive capacity of radiomics nomogram regarding treatment response status (responder/non-responder) in patients with advanced NSCLC undergoing anti-PD1 immunotherapy.

Methods: 197 eligible patients with histologically confirmed NSCLC were retrospectively enrolled from nine hospitals. We carried out a radiomics characterization from target lesions (TL) approach and largest target lesion (LL) approach on baseline and first follow-up (TP1) CT imaging data. Delta-radiomics feature was calculated as the relative net change in radiomics feature between baseline and TP1. Minimum Redundancy Maximum Relevance (mRMR) and Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression were applied for feature selection and radiomics signature construction.

Results: Radiomics signature at baseline did not show significant predictive value regarding response status for LL approach ( = 0.10), nor in terms of TL approach ( = 0.27). A combined Delta-radiomics nomogram incorporating Delta-radiomics signature with clinical factor of distant metastasis for target lesions had satisfactory performance in distinguishing responders from non-responders with AUCs of 0.83 (95% CI: 0.75-0.91) and 0.81 (95% CI: 0.68-0.95) in the training and test sets respectively, which was comparable with that from LL approach ( = 0.92, = 0.97). Among a subset of those patients with available pretreatment PD-L1 expression status (n = 66), models that incorporating Delta-radiomics features showed superior predictive accuracy than that of PD-L1 expression status alone (0.001).

Conclusion: Early response assessment using combined Delta-radiomics nomograms have potential advantages to identify patients that were more likely to benefit from immunotherapy, and help oncologists modify treatments tailored individually to each patient under therapy.
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http://dx.doi.org/10.3389/fonc.2021.657615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017283PMC
March 2021

Neutrophil-to-Lymphocyte Ratio Predicts Development of Immune-Related Adverse Events and Outcomes from Immune Checkpoint Blockade: A Case-Control Study.

Cancers (Basel) 2021 Mar 15;13(6). Epub 2021 Mar 15.

Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.

The utility of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) utility in predicting immune-related adverse events (irAEs) and survival have not been well studied in the context of treatment with immune checkpoint inhibitors (ICIs). We performed a case-control study of cancer patients who received at least one dose of ICI in a tertiary hospital. We examined NLR and PLR in irAE cases and controls. Logistic and Cox regression models were used to identify independent risk factors for irAEs, progression-free survival (PFS), and overall survival (OS). The study included 91 patients with irAEs and 56 controls. Multiple logistic regression showed that NLR < 3 at baseline was associated with higher occurrence of irAEs. Multivariate Cox regression showed that development of irAEs and reduction in NLR from baseline to week 6 were associated with longer PFS. Higher NLR values at baseline and/or week 6 were independently associated with shorter OS. A reduction in NLR from baseline to week 6 was associated with longer OS. In this study of cancer patients treated with ICIs, NLR has a bidirectional relationship with adverse outcomes. Lower NLR was associated with increased occurrence of irAEs while higher NLR values were associated with worse clinical outcomes.
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http://dx.doi.org/10.3390/cancers13061308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001500PMC
March 2021

Reconstructable Gradient Structures and Reprogrammable 3D Deformations of Hydrogels with Coumarin Units as the Photolabile Crosslinks.

Adv Mater 2021 Mar 31:e2008057. Epub 2021 Mar 31.

Ministry of Education Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China.

Morphing hydrogels have versatile applications in soft robotics, flexible electronics, and biomedical devices. Controlling component distribution and internal stress within a hydrogel is crucial for shape-changing. However, existing gradient structures of hydrogels are usually non-reconstructable, once encoded by chemical reactions and covalent bonds. Fabricating hydrogels with distinct gradient structures is inevitable for every new configuration, resulting in poor reusability, adaptability, and sustainability that are disadvantageous for diverse applications. Herein, a hydrogel containing reversible photo-crosslinks that enable reprogramming of the gradient structures and 3D deformations into various configurations is reported. The hydrogel is prepared by micellar polymerization of hydrophobic coumarin monomer and hydrophilic acrylic acid. The presence of hexadecyltrimethylammonium chloride micelles increases the local concentration of coumarin units and also improves the mechanical properties of the hydrogel by forming robust polyelectrolyte/surfactant complexes that serve as the physical crosslinks. High-efficiency photodimerization and photocleavage reactions of coumarins are realized under 365 and 254 nm light irradiation, respectively, affording reversible tuning of the network structure of the hydrogel. Through photolithography, different gradient structures are sequentially patterned in one hydrogel that direct the deformations into distinct configurations. Such a strategy should be applicable for other photolabile hydrogels toward reprogrammable control of network structures and versatile functions.
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http://dx.doi.org/10.1002/adma.202008057DOI Listing
March 2021

Molecular mechanism of abnormally large nonsoftening deformation in a tough hydrogel.

Proc Natl Acad Sci U S A 2021 Apr;118(14)

Global Institution for Collaborative Research and Education, Hokkaido University, 001-0021 Sapporo, Japan;

Tough soft materials usually show strain softening and inelastic deformation. Here, we study the molecular mechanism of abnormally large nonsoftening, quasi-linear but inelastic deformation in tough hydrogels made of hyperconnective physical network and linear polymers as molecular glues to the network. The interplay of hyperconnectivity of network and effective load transfer by molecular glues prevents stress concentration, which is revealed by an affine deformation of the network to the bulk deformation up to sample failure. The suppression of local stress concentration and strain amplification plays a key role in avoiding necking or strain softening and endows the gels with a unique large nonsoftening, quasi-linear but inelastic deformation.
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http://dx.doi.org/10.1073/pnas.2014694118DOI Listing
April 2021

Vascular Endothelial Function as a Valid Predictor of Variations in Pulmonary Function in T2DM Patients Without Related Complications.

Front Endocrinol (Lausanne) 2021 11;12:622768. Epub 2021 Mar 11.

Key Laboratory of Ministry of Education for Traditional Chinese Medicine Visera-State Theory and Application, Liaoning University of Traditional Chinese Medicine, Shenyang, China.

To assess the variations in pulmonary function and vascular endothelial function in their early stages (without related complications). A total of 162 type 2 diabetes mellitus (T2DM) patients without diabetes complications and 55 healthy people were selected, comprising the T2DM group and the control group, respectively, to evaluate changes in vascular endothelial function and lung function and determine the correlation between them. In this study, the T2DM group exhibited significantly lower pulmonary function than that of the control group ( < 0.05). The T2DM group also showed significantly lower flow-mediated dilation (FMD) and nitric oxide (NO) ( < 0.05) than those of the control group. Pulmonary functional indexes correlated positively with FMD and NO ( < 0.05) and correlated negatively with endothelin-1 (ET-1) ( < 0.05). FMD and NO correlated negatively with diabetes duration/HbA1c ( < 0.05), whereas ET-1 correlated positively with glycosylated hemoglobinA1c (HbA1c)/diabetes duration ( < 0.05). Pulmonary functional indexes negatively correlated with HbA1c/diabetes duration ( < 0.05). Multiple linear regression was used to analyze the relationship between vascular endothelial function indexes (FMD, ET-1, and NO) and pulmonary functional indexes. The results indicated that each vascular endothelial function index (FMD, ET-1, and NO) was significantly correlated with the pulmonary functional index ( < 0.05). The patients with T2DM presented changes in the subclinical vascular endothelial and pulmonary function. They also had impaired vascular endothelial functions, which were characterized by reduced vascular endothelial function relative to those of healthy people. Regulating glycemia may improve vascular endothelial and pulmonary functions. Moreover, microvascular lesions in preclinical stages, vascular endothelial function indexes (FMD, ET-1, and NO) were valid predictors of alterations in pulmonary function in T2DM patients without related complications.

Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03575988.
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http://dx.doi.org/10.3389/fendo.2021.622768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991996PMC
March 2021

Proteomic Profiling of Lysine Acetylation Indicates Mitochondrial Dysfunction in the Hippocampus of Gut Microbiota-Absent Mice.

Front Mol Neurosci 2021 11;14:594332. Epub 2021 Mar 11.

The Ministry of Education, Key Laboratory of Laboratory Medical Diagnostics, The College of Laboratory Medicine, Chongqing Medical University, Chongqing, China.

Major depressive disorder (MDD) is a leading cause of disability around the world and contributes greatly to the global burden of disease. Mounting evidence suggests that gut microbiota dysbiosis may be involved in the pathophysiology of MDD through the microbiota-gut-brain axis. Recent research suggests that epigenetic modifications might relate to depression. However, our knowledge of the role of epigenetics in host-microbe interactions remains limited. In the present study, we used a combination of affinity enrichment and high-resolution liquid chromatography tandem mass spectrometry analysis to identify hippocampal acetylated proteins in germ-free and specific pathogen-free mice. In total, 986 lysine acetylation sites in 543 proteins were identified, of which 747 sites in 427 proteins were quantified. Motif analysis identified several conserved sequences surrounding the acetylation sites, including DKac, DKac, KacY, KacD, and DKac. Gene ontology annotations revealed that these differentially expressed acetylated proteins were involved in multiple biological functions and were mainly located in mitochondria. In addition, pathway enrichment analysis demonstrated that oxidative phosphorylation and the tricarboxylic acid cycle II (eukaryotic), both of which are exclusively localized to the mitochondria, were the primarily disturbed functions. Taken together, this study indicates that lysine acetylation alterations may play a pivotal role in mitochondrial dysfunction and may be a mechanism by which gut microbiota regulate brain function and behavioral phenotypes.
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http://dx.doi.org/10.3389/fnmol.2021.594332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991600PMC
March 2021

Direct interactions between cationic liposomes and bacterial cells ameliorate the systemic treatment of invasive multidrug-resistant Staphylococcus aureus infections.

Nanomedicine 2021 Mar 23:102382. Epub 2021 Mar 23.

School of Pharmacy, Shandong New Drug Loading & Release Technology and Preparation Engineering Laboratory, Binzhou Medical University, 346 Guanhai Road, Yantai, 264003, PR China. Electronic address:

Invasive infections caused by antibiotic-resistant Staphylococcus aureus have posed a great threat to human health. To tackle this problem, a cationic liposomal Curcumin (C-LS/Cur) was developed and its effect against antibiotic-resistant S. aureus was investigated in this study. As expected, C-LS/Cur exhibited greater bactericidal capacity compared with its counterparts, probably because the negative charged S. aureus favors electrostatic interactions rather than intercalation with cationic liposomal vesicles at the beginning of endocytic process, thereby effectively delivering Cur to its targets. We confirmed this hypothesis by monitoring zeta potential variation, collecting visual evidences through CLSM, FCM and TEM, and determining binding kinetics by BLI. Moreover, an excellent therapeutic efficacy of C-LS/Cur against invasive murine infection was also observed, which was due to the enhanced accumulation and retention in the targets. Therefore, cationic liposomes have great potential for the clinical application in the treatment of invasive antibiotic-resistant S. aureus infections.
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http://dx.doi.org/10.1016/j.nano.2021.102382DOI Listing
March 2021

Phenotypic similarities in pigs with SOX10 and SOX10 mutations implied the correlation of SOX10 haploinsufficiency with Waardenburg syndrome.

J Genet Genomics 2021 Feb 17. Epub 2021 Feb 17.

Department of Laboratory Animal Science, College of Basic Medical Science, Army Medical University, Chongqing 400038, China. Electronic address:

SOX10 is a causative gene of Waardenburg syndrome (WS), a rare genetic disorder characterized by hearing loss and pigment disturbance. More than 100 mutations of SOX10 have been found in patients with Type 2 WS (WS2), Type 4 WS (WS4), and more complex syndromes. However, no mutation hotspot has been detected in SOX10, and most cases are sporadic, making it difficult to establish a correlation between the high phenotypic and genetic variability. In this study, a duplication of the 321th cytosine (c.321dupC) was introduced into SOX10 in pigs, which induced premature termination of the translation of SOX10 (p.K108QfsX45). The premature stop codon in Exon 3 triggered the degradation of mutant mRNA through nonsense-mediated mRNA decay. However, SOX10 induced a highly similar phenotype of WS2 with heterogeneous inner ear malformation compared with its adjacent missense mutation SOX10. In addition, a site-saturation mutation analysis of the SOX10 N-terminal nuclear localization signal (n-NLS), where these two mutations located, revealed the correlation between SOX10 haploinsufficiency and WS by an in vitro reporter assay. The analysis combining the in vitro assay with clinical cases may provide a clue to clinical diagnoses.
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http://dx.doi.org/10.1016/j.jgg.2020.12.003DOI Listing
February 2021

Linear epitope landscape of the SARS-CoV-2 Spike protein constructed from 1,051 COVID-19 patients.

Cell Rep 2021 03 12;34(13):108915. Epub 2021 Mar 12.

Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China. Electronic address:

To fully decipher the immunogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein, it is essential to assess which part is highly immunogenic in a systematic way. We generate a linear epitope landscape of the Spike protein by analyzing the serum immunoglobulin G (IgG) response of 1,051 coronavirus disease 2019 (COVID-19) patients with a peptide microarray. We reveal two regions rich in linear epitopes, i.e., C-terminal domain (CTD) and a region close to the S2' cleavage site and fusion peptide. Unexpectedly, we find that the receptor binding domain (RBD) lacks linear epitope. We reveal that the number of responsive peptides is highly variable among patients and correlates with disease severity. Some peptides are moderately associated with severity and clinical outcome. By immunizing mice, we obtain linear-epitope-specific antibodies; however, no significant neutralizing activity against the authentic virus is observed for these antibodies. This landscape will facilitate our understanding of SARS-CoV-2-specific humoral responses and might be useful for vaccine refinement.
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http://dx.doi.org/10.1016/j.celrep.2021.108915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953450PMC
March 2021

Clinical analysis and long-term treatment monitoring of 3 patients with glycogen storage disease type Ib.

BMC Med Genomics 2021 Mar 17;14(1):81. Epub 2021 Mar 17.

Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Background: To investigate the clinical and genetic characteristics of patients with glycogen storage disease type Ib (GSD Ib).

Case Presentation: This report retrospectively analyzed the clinical data of 3 patients with GSD Ib admitted into our hospital, and summarized their onset characteristics, clinical manifestations, related examinations and treatment as well as mutational spectrum. After gene sequencing, the diagnosis of GSD Ib was confirmed in all 3 patients. Five variants of SLC37A4 gene were detected, of which c. 572C > T was the common variant and c. 680G > A was a novel variant. The 3 cases of GSD Ib were mainly affected by liver enlargement, growth retardation, etc., and all had a history of repeated infections. At the onset, patients mainly manifested as mildly elevated alanine-aminotransferase (ALT), accompanied by decreased absolute neutrophil count (ANC), hypertriglyceridemia, and metabolic disorders (hypoglycemia, hyperlactic acidemia, metabolic acidosis, etc.). After long-term treatment by oral uncooked cornstarch, the abnormal liver enzymes gradually returned to normal, and metabolic abnormalities were basically controlled most of the time. With increasing age, ANC of 2 patients decreased progressively, whereas the times of infections was reduced.

Conclusions: We reported 3 cases with GSD Ib and a novel SLC37A4 variant. The possibility of GSD type Ib should be kept on alert when a patient suffers recurrent infections, accompanied by hepatomegaly, elevated liver enzymes, hypoglycemia, dyslipidemia, and metabolic disorders.
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http://dx.doi.org/10.1186/s12920-021-00936-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972195PMC
March 2021

Cancer Clinical Trial Versus Real-World Outcomes for Standard of Care First-Line Treatment in the Advanced Disease Setting.

Int J Cancer 2021 Mar 17. Epub 2021 Mar 17.

Department of Medical Oncology, Western Health, Victoria, Australia.

Clinical trials have strict eligibility criteria, potentially limiting external validity. However, while often discussed this has seldom been explored, particularly across cancer types and at variable time frames post trial completion. We examined comprehensive registry data (January 2014 to June 2019) for standard first-line treatments for metastatic colorectal cancer (CRC), advanced pancreatic cancer (PC), metastatic HER2-amplified breast cancer (BC) and castrate-resistant prostate cancer (CaP). Registry patient characteristics and outcomes were compared to the practice-changing trial. Registry patients were older than the matched trial cohort by a median of 2-6 years (all p=< 0.01) for the CRC, BC and PC cohorts. The proportion of Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 patients was lower for CRC (94.1% vs 99.2%, p=0.001) and BC (94.9% vs 99.3%, p=0.001). Progression-free survival (PFS) for registry patients was similar to the trial patients or significantly longer (CaP, HR = 0.65, p=<0.001). Overall survival (OS) was also similar or significantly longer (CaP, HR 0.49, p=< 0.001). In conclusion, despite real-world patients sometimes being older or having inferior PS to trial cohorts, the survival outcomes achieved were consistently equal or superior to those reported for the same treatment in the trial. We suggest that this is potentially due to optimised use of each treatment over time, improved multidisciplinary care and increased post-progression options. We can reassure clinicians and patients that outcomes matching or exceeding those reported in trials are possible. The potential for survival gains over time should routinely be factored into future trial statistical plans.
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http://dx.doi.org/10.1002/ijc.33568DOI Listing
March 2021

Effect of a Humanized Diet Profile on Colonization Efficiency and Gut Microbial Diversity in Human Flora-Associated Mice.

Front Nutr 2021 23;8:633738. Epub 2021 Feb 23.

College of Food Science, South China Agricultural University, Guangzhou, China.

Human flora-associated (HFA) mouse models allow us to design interventions for human disease research to test specific hypotheses and explore the complex commensal microbiome while avoiding the ethical limitations of using humans as models to directly study intestinal flora diseases. However, few studies have investigated the effect of a humanized diet profile (coarse-feed diet; CFD) on colonization efficiency and gut microbial diversity in HFA mice. We tested the colonization efficiency and gut microbial diversity in germ-free Kunming (KM) mice fed a CFD or a purified feed diet (PFD) at 1, 2, and 4 weeks. Although the colonization efficiencies differed significantly (67.50-70.00% vs. 72.69-85.96%) in the HFA mice, the colonization efficiency of the PFD-fed HFA mice (85.96%) was significantly higher than that of the CFD-fed mice (69.61%) at 2 weeks. At 4 weeks, the colonization efficiency of the PFD-fed mice (72.69%) was comparable to that of the CFD-fed mice (70.00%). Additionally, the gut microbial diversity of the CFD-fed HFA mice was similar to that of a human fecal donor. Regarding the Kyoto Encyclopedia of Genes and Genomes colonic microbiota metabolic pathways, the CFD-fed HFA mice showed more similarities to the human donor than to the PFD-fed mice in amino sugar and nucleotide sugar metabolism, biosynthesis of amino acids, carbon metabolism, purine metabolism, and phosphotransferase systems. In conclusion, the humanized diet profiles of the CFD and PFD could help establish human microbiotas in mice. Constructing HFA mouse models fed a CFD for 4 weeks may be useful in researching human-derived intestinal diseases.
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http://dx.doi.org/10.3389/fnut.2021.633738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940529PMC
February 2021

Cross-Country Differences in Stay-at-Home Behaviors during Peaks in the COVID-19 Pandemic in China and the United States: The Roles of Health Beliefs and Behavioral Intention.

Int J Environ Res Public Health 2021 02 21;18(4). Epub 2021 Feb 21.

Beijing Key Laboratory of Applied Experimental Psychology, National Demonstration Center for Experimental Psychology Education (Beijing Normal University), Faculty of Psychology, Beijing Normal University, Beijing 100875, China.

The novel coronavirus disease 2019 (COVID-19) rapidly escalated to a global pandemic. To control the rate of transmission, governments advocated that the public practice social distancing, which included staying at home. However, compliance with stay-at-home orders has varied between countries such as China and the United States, and little is known about the mechanisms underlying the national differences. Based on the health belief model, the theory of reasoned action, and the technology acceptance model, health beliefs and behavioral intention are suggested as possible explanations. A total of 498 Chinese and 292 American college students were recruited to complete an online survey. The structural equation modeling results showed that health beliefs (i.e., perceived susceptibility, severity, and barriers) and behavioral intention played multiple mediating roles in the association between nationality and actual stay-at-home behaviors. Notably, the effect via perceived barriers → behavioral intention was stronger than the effects via perceived susceptibility and severity → behavioral intention. That is, American participants perceived high levels of susceptibility whereas Chinese participants perceived high levels of severity, especially few barriers, which further led to increased behavioral intention and more frequent stay-at-home behaviors. These findings not only facilitate a comprehensive understanding of cross-country differences in compliance with stay-at-home orders during peaks in the COVID-19 pandemic but also lend support for mitigation of the current global crisis and future disease prevention and health promotion efforts.
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http://dx.doi.org/10.3390/ijerph18042104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927070PMC
February 2021

Nucleolar and spindle‑associated protein 1 promotes non‑small cell lung cancer progression and serves as an effector of myocyte enhancer factor 2D.

Oncol Rep 2021 Mar 30;45(3):1044-1058. Epub 2020 Dec 30.

Department of Thoracic Surgery, Chongqing General Hospital, Chongqing 400013, P.R. China.

As a potential oncogene, nucleolar and spindle‑associated protein 1 (NUSAP1) is involved in the regulation of tumor cell proliferation, metastasis and drug resistance. However, the role of NUSAP1 in non‑small cell lung cancer (NSCLC) remains unclear. The present study aimed to investigate the biological function and underlying molecular mechanisms of NUSAP1 in NSCLC. NUSAP1 expression was measured in NSCLC tissues and cell lines via immunohistochemistry and western blotting, respectively. NSCLC cell lines stably inhibiting NUSAP1 were established to investigate its effects on cell proliferation, colony formation and invasion, and on in vivo tumorigenicity. Additionally, the upstream and downstream mechanisms of NUSAP1 in regulating NSCLC progression were investigated. The results indicated that NUSAP1 expression was upregulated in NSCLC tissues and cell lines. High NUSAP1 expression was associated with tumor size, TNM stage, lymph node metastasis and poor patient survival, whereas knockdown of NUSAP1 inhibited NSCLC cell proliferation, colony formation and invasion. Furthermore, downregulation of NUSAP1 decreased the growth of NSCLC xenografts in vivo. In addition, myocyte enhancer factor 2D (MEF2D) directly targeted the NUSAP1 promoter, thereby enhancing the mRNA and protein expression levels of NUSAP1. Moreover, the results demonstrated that MEF2D expression was upregulated in NSCLC tissues and was positively correlated with NUSAP1 expression. MEF2D‑knockdown decreased NSCLC cell proliferation, colony formation and invasion. NUSAP1 upregulation reversed the effects of MEF2D‑knockdown on NSCLC progression. Furthermore, it was observed that MEF2D‑knockdown inhibited the accumulation and nuclear translocation of β‑catenin, thereby repressing the activation of the Wnt/β‑catenin signaling pathway in NSCLC cells, whereas NUSAP1 upregulation rescued the effects of MEF2D‑knockdown on the activation of the Wnt/β‑catenin signaling pathway. In conclusion, the findings of the present study indicated that the MEF2D/NUSAP1 signaling pathway promoted NSCLC progression by inducing the activation of Wnt/β‑catenin signaling, and this novel mechanism may represent a potential treatment target for patients with NSCLC.
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http://dx.doi.org/10.3892/or.2020.7918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859992PMC
March 2021

Cell penetrating peptide TAT-functionalized liposomes for efficient ophthalmic delivery of flurbiprofen: Penetration and its underlying mechanism, retention, anti-inflammation and biocompatibility.

Int J Pharm 2021 Apr 26;598:120405. Epub 2021 Feb 26.

School of Pharmacy, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, PR China. Electronic address:

In treating eye diseases, topical administration on the ocular surface is the most convenient and acceptable route. However, the intraocular efficiency of non-invasive drug delivery systems is still considerably hampered by the eye's defense barriers. In this work, cell-penetrating peptide TAT-functionalized, flurbiprofen-loaded liposomes (TAT-FB-Lip) were designed to enable transcorneal drug delivery and prolong ocular surface retention. The corneal penetration-promoting properties of TAT-functionalized liposomes (TAT-Lip) were confirmed in vitro using a corneal permeability assay and the HCE-T cell sphere model and in vivo by aqueous humor pharmacokinetics assessment. TAT-Lip induced an increase in intracellular calcium ion concentration and membrane potential depolarization. F-actin images of HCE-T cells treated with TAT-Lip show the tight junctions between cells partly opened. The cellular internalization pathway mainly depended on the electrostatic interaction between TAT-Lip and the cell membrane, and there is a certain degree of energy dependence. The pharmacokinetics of flurbiprofen in tears demonstrated TAT-Lip could reduce the drug loss rate. Moreover, the anti-inflammatory effect of TAT-FB-Lip was enhanced by markedly suppressing PGE, IL-6, and TNF-α production in tears and aqueous humor in a rabbit conjunctivitis model. In conclusion, this work demonstrates that TAT-Lip is an effective ocular drug carrier system that facilitates transcorneal delivery.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120405DOI Listing
April 2021

Squalene Epoxidase Induces Nonalcoholic Steatohepatitis Via Binding to Carbonic Anhydrase 3 and is a Therapeutic Target.

Gastroenterology 2021 Feb 27. Epub 2021 Feb 27.

Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, People's Republic of China. Electronic address:

Backgrounds & Aims: Squalene epoxidase (SQLE) is the rate-limiting enzyme for cholesterol biosynthesis. We elucidated the functional significance, molecular mechanisms, and clinical impact of SQLE in nonalcoholic steatohepatitis (NASH).

Methods: We performed studies with hepatocyte-specific Sqle overexpression transgenic (Sqle tg) mice and mice given high-fat high-cholesterol (HFHC) or methionine- and choline-deficient (MCD) diet to induce NASH. SQLE downstream target carbonic anhydrase 3 (CA3) was identified using co-immunoprecipitation and Western Blot. Some mice were given SQLE inhibitor (terbinafine) and CA3 inhibitor (acetazolamide) to study the therapeutic effects in NASH. Human samples (n = 217) including 65 steatoses, 80 NASH, and 72 healthy controls were analyzed for SQLE levels in liver tissue and in serum.

Results: SQLE is highly up-regulated in human NASH and mouse models of NASH. Sqle tg mice triggered spontaneous insulin resistance, hepatic steatosis, liver injury, and accelerated HFHC or MCD diet-induced NASH development. Mechanistically, SQLE tg mice caused hepatic cholesterol accumulation, thereby triggering proinflammatory NF-κB signaling and steatohepatitis. SQLE directly bound to CA3, which induced sterol regulatory element-binding protein 1C activation, acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase1 expression and de novo hepatic lipogenesis. Combined targeting SQLE (terbinafine) and CA3 (acetazolamide) synergistically ameliorated NASH in mice with superior efficacy to either drug alone. Serum SQLE with CA3 could distinguish patients with NASH from steatosis and healthy controls (area under the receiver operating characteristic curve, 0.815; 95% confidence interval, 0.758-0.871).

Conclusions: SQLE drives the initiation and progression of NASH through inducing cholesterol biosynthesis, and SQLE/CA3 axis-mediated lipogenesis. Combined targeting of SQLE and CA3 confers therapeutic benefit in NASH. Serum SQLE and CA3 are novel biomarkers for the noninvasive diagnosis of patients with NASH.
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http://dx.doi.org/10.1053/j.gastro.2021.02.051DOI Listing
February 2021

Application of germ-free NOD-scid IL2rg mice as a humanized model for tumor microbiome precision medicine.

Sci China Life Sci 2021 Apr 24;64(4):644-647. Epub 2021 Feb 24.

Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.

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http://dx.doi.org/10.1007/s11427-020-1876-1DOI Listing
April 2021

Construction of Nanocrystalline Cellulose-Based Composite Fiber Films with Excellent Porosity Performances via an Electrospinning Strategy.

ACS Omega 2021 Feb 11;6(7):4958-4967. Epub 2021 Feb 11.

State Key Laboratory of Metastable Materials Science and Technology, Yanshan University, Qinhuangdao 066004, P. R. China.

Cellulose nanocrystals (CNCs) not only have environmental protection characteristics of being lightweight, degradable, green, and renewable but also have some nanocharacteristics of high strength, large specific surface area, and obvious small size effect, so they are often used as a reinforcing agent in various polymers. However, the hydrogen bonding between CNC molecules is relatively strong, and they can easily aggregate and get entangled with each other. In this work, several large-porosity composite nanofiber films, KH550-CNC/waterborne polyurethane (WPU)/poly(vinyl alcohol) (PVAL) with KH550-modified CNCs, are prepared using poly(vinyl alcohol) (PVAL) solution and electrospinning technology. A variety of characterization methods are used to discuss and analyze the nanofiber materials, and the effects of the added amount of CNCs modified with KH550, spinning voltage, curing distance, and advancing speed on the morphology and performance of composite fibers are discussed separately. The results show that when the content of KH550-CNC is 1%, the composite fiber film obtained has the most regular morphology and the best spinnability, which is convenient for the specific application of fiber materials in a later period. In addition, the porosity of the obtained composite fiber film is 62.61%. Therefore, this work provides a theoretical basis and research strategy for the preparation of higher-porosity composite films as well as the development of new textile materials.
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http://dx.doi.org/10.1021/acsomega.0c06002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905938PMC
February 2021

Proteomic analysis of decidua in patients with recurrent pregnancy loss (RPL) reveals mitochondrial oxidative stress dysfunction.

Clin Proteomics 2021 Feb 22;18(1). Epub 2021 Feb 22.

Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.

Background: Pregnancy is a complicated physiological process. The multifaceted regulation of maternal-fetal interface is of great importance for maintaining normal pregnancy and avoiding fetal rejection and secondary abortion. Previous studies have focused on the clinical features or pathological biomarkers of fetal rejection and abortion. However, no significant breakthrough has been made. Therefore, it is important to understand the molecular mechanisms of recurrent pregnancy loss (RPL) to identify potential therapeutic strategies. The aim of this study was to investigate the pathogenesis of RPL.

Methods: In this study, Relative and absolute quantitation (iTRAQ) technology integrated with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was used to identify differentially expressed proteins in decidual from RPL patients and matched normal controls. Further, Molecules NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3 (ndufb3) and cyclooxygenase-2 (COX-2) were validated by immunohistochemistry (IHC), Western blotting, CCK8 and mitochondrial red fluorescent probe (Mito-Tracker Red CMXRos).

Results: A total of 456 proteins reached the threshold of a 1.5-fold change were identified for further bioinformatics analysis. Upon mapping the differentially expressed proteins using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways database, iTRAQ results were confirmed by assessing NDUFB3 and COX-2 protein levels in specimens of decidual tissue by Western blotting. Our study indicates that the level of COX-2 and NDUFB3 were significantly increased in decidual cell from RPL patients. Overexpression of NDUFB3 inhibited cell vitality and oxidative stress of decimal cell. Further, our found that overexpression NDUFBD3 in decidual cell decreased the mitochondrial membrane potential expression levels. These results suggest that NDUFB3 might play an important role in promote the pathological process of RPL.

Conclusions: This comprehensive analysis of RPL proteomics reveals novel candidate: NDUFB3, which could be further investigated for explanation of the pathological mechanism of RPL.
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http://dx.doi.org/10.1186/s12014-021-09312-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898782PMC
February 2021

An inexpensive anaerobic chamber for the genetic manipulation of strictly anaerobic bacteria.

Anaerobe 2021 Feb 18;69:102349. Epub 2021 Feb 18.

Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education and School of Basic Medical Science, Guizhou Medical University, Guiyang 550004, Guizhou, China. Electronic address:

Strictly anaerobic bacteria are important to both human health and industrial usage. These bacteria are sensitive to oxygen, therefore, it is preferable to manipulate these microbes in an anaerobic chamber. However, commercial anaerobic chambers (CACs) are expensive, making them less accessible to scientists with a limited budget, especially to those in developing countries. The high price of commercial chambers has hindered, at least partially, the progress of research on anaerobes in developing countries. In the research presented here, we developed an inexpensive and reliable anaerobic chamber and successfully achieved routine maintenance of eleven strictly anaerobic bacterial strains. Furthermore, genetic manipulation examples have been set for both Clostridioidesdifficile 630 and Clostridiumbeijerinckii NCIMB 8052 strains to validate that the chamber could applied to advanced genetic engineering of strictly anaerobes. C. difficile and C. beijerinckii were both genetically manipulated in this chamber, showing it's utility for the genetic engineering of anaerobes. Most importantly, the anaerobic chamber was 76% - 88% less expensive than a CACs and has similar functionality with regards to the cultivation and manipulation of strictly anaerobic bacteria. The anaerobic chamber described in this study will promote the research of anaerobes in developing counties and scientists who have limited research budgets.
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http://dx.doi.org/10.1016/j.anaerobe.2021.102349DOI Listing
February 2021

BRAFV600E Mutations Arising from a Left-Side Primary in Metastatic Colorectal Cancer: Are They a Distinct Subset?

Target Oncol 2021 03 18;16(2):227-236. Epub 2021 Feb 18.

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.

Background: B-Raf proto-oncogene (BRAF)-V600E mutations (BRAFmt) in colorectal cancer (CRC) predominantly occur in right-side (RS) primaries. In metastatic CRC (mCRC), there is substantial overlap between the reported features of BRAFmt and of an RS primary.

Objectives: To explore the significance of BRAFmt in a left-side (LS) primary, we analysed data from a multi-site mCRC registry. Tumours distal to the splenic flexure were considered LS.

Results: Of 3380 patients enrolled from June 2009 to June 2020, 214 (13%) of 1657 with known status were BRAFmt: 127 (24%) of 524 RS and 87 (8%) of 1133 LS. LS versus RS BRAFmt were younger (mean 59.5 vs. 65.1 years; p = 0.01), whereas sex (48 vs. 59% female; p = 0.13), mismatch repair-deficiency (dMMR) (16 vs. 21%; p = 0.47), and overall survival (OS) (median 15.1 vs. 17.7 months; p = 0.98) were similar. LS BRAFmt versus LS BRAF wildtype (wt) were of similar age (59.5 vs. 61.3 years; p = 0.28) with more females (48 vs. 37%; p = 0.04), more dMMR (16 vs. 1%; p < 0.0001), and inferior OS (median 15.1 vs. 36.6 months; p < 0.0001). Initial treatment with chemotherapy plus an epidermal growth factor receptor inhibitor produced median progression-free survival (PFS) of 4.3 versus 12.3 months (p = 0.20) for LS BRAFmt (n = 9) versus LS BRAFwt (n = 104). Initial chemotherapy and bevacizumab produced a median PFS of 7.6 versus 11.6 months (p = 0.02) for LS BRAFmt (n = 36) versus LS BRAFwt (n = 438), respectively.

Conclusion: LS BRAFmt cancers share many features with RS BRAFmt cancers, including poor survival outcomes. Mature data on the activity of BRAF-targeted therapies in the first-line setting are eagerly awaited.
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http://dx.doi.org/10.1007/s11523-021-00793-7DOI Listing
March 2021

Amphiphilic Janus nanoparticles for imaging-guided synergistic chemo-photothermal hepatocellular carcinoma therapy in the second near-infrared window.

Nanoscale 2021 Feb;13(7):3974-3982

Department of Chemistry, Northeast Normal University, 5268 Renmin Street, Changchun, Jilin 130024, P. R. China.

Hepatocellular carcinoma (HCC) is one of the most common and deadly malignant tumors worldwide. With unsatisfactory effects of traditional systematic chemotherapy for HCC owing to its drug resistance, novel therapeutic strategies based on nanomaterials for HCC treatments are promising solutions. To solve the challenges of nanoparticles (NPs)-based drug delivery systems for potential clinical applications, we designed water soluble amphiphilic oleic acid-NaYF4:Yb,Er/polydopamine Au nanoflower Janus NPs (OA-UCNPs/PDA-AuF JNPs) with discrete multi compartment nanostructures as dual-drug delivery systems (DDDSs). This unique nanostructure meets the requirements for containing hydrophobic hydroxycamptothecin/hydrophilic doxorubicin in divided spaces and releasing each drug from non-interfering channels under pH/near-infrared (NIR) dual-stimuli. The amphiphilic DDDSs were utilized to eradicate the tumor burden on a high-fidelity HCC model of a patient-derived xenograft (PDX), and represented an efficient strategy for defeating HCC using multi-modal imaging-guided dual-drug chemo-photothermal therapy in the second NIR window. In addition, the potential mechanisms of action for the DDDSs were evaluated.
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http://dx.doi.org/10.1039/d0nr09017dDOI Listing
February 2021

Rare deleterious germline variants and risk of lung cancer.

NPJ Precis Oncol 2021 Feb 16;5(1):12. Epub 2021 Feb 16.

Dan L. Duncan Comprehensive Cancer Center, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.

Recent studies suggest that rare variants exhibit stronger effect sizes and might play a crucial role in the etiology of lung cancers (LC). Whole exome plus targeted sequencing of germline DNA was performed on 1045 LC cases and 885 controls in the discovery set. To unveil the inherited causal variants, we focused on rare and predicted deleterious variants and small indels enriched in cases or controls. Promising candidates were further validated in a series of 26,803 LCs and 555,107 controls. During discovery, we identified 25 rare deleterious variants associated with LC susceptibility, including 13 reported in ClinVar. Of the five validated candidates, we discovered two pathogenic variants in known LC susceptibility loci, ATM p.V2716A (Odds Ratio [OR] 19.55, 95%CI 5.04-75.6) and MPZL2 p.I24M frameshift deletion (OR 3.88, 95%CI 1.71-8.8); and three in novel LC susceptibility genes, POMC c.*28delT at 3' UTR (OR 4.33, 95%CI 2.03-9.24), STAU2 p.N364M frameshift deletion (OR 4.48, 95%CI 1.73-11.55), and MLNR p.Q334V frameshift deletion (OR 2.69, 95%CI 1.33-5.43). The potential cancer-promoting role of selected candidate genes and variants was further supported by endogenous DNA damage assays. Our analyses led to the identification of new rare deleterious variants with LC susceptibility. However, in-depth mechanistic studies are still needed to evaluate the pathogenic effects of these specific alleles.
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http://dx.doi.org/10.1038/s41698-021-00146-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887261PMC
February 2021

An Ultrafast WSe Photodiode Based on a Lateral Homojunction.

ACS Nano 2021 Mar 15;15(3):4405-4415. Epub 2021 Feb 15.

MOE Key Laboratory of Fundamental Physical Quantities Measurement & Hubei Key Laboratory of Gravitation and Quantum Physics, PGMF and School of Physics, Huazhong University of Science and Technology, Wuhan 430074, P. R. China.

High-quality homogeneous junctions are of great significance for developing transition metal dichalcogenides (TMDs) based electronic and optoelectronic devices. Here, we demonstrate a lateral type/intrinsic/type () homojunction based multilayer WSe diode. The photodiode is formed through selective doping, more specifically by utilizing self-aligning surface plasma treatment at the contact regions, while keeping the WSe channel intrinsic. Electrical measurements of such a diode reveal an ideal rectifying behavior with a current on/off ratio as high as 1.2 × 10 and an ideality factor of 1.14. While operating in the photovoltaic mode, the diode presents an excellent photodetecting performance under 450 nm light illumination, including an open-circuit voltage of 340 mV, a responsivity of 0.1 A W, and a specific detectivity of 2.2 × 10 Jones. Furthermore, benefiting from the lateral configuration, the slow photoresponse dynamics including the photocarrier diffusion in undepleted regions and photocarrier trapping/detrapping due to dopants or doping process induced defect states are significantly suppressed. Consequently, a record-breaking response time of 264 ns and a 3 dB bandwidth of 1.9 MHz are realized, compared with the previously reported TMDs based photodetectors. The above-mentioned desirable properties, together with CMOS compatible processes, make this WSe junction diode promising for future applications in self-powered high-frequency weak signal photodetection.
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http://dx.doi.org/10.1021/acsnano.0c08075DOI Listing
March 2021

Genomic monitoring of SARS-CoV-2 uncovers an Nsp1 deletion variant that modulates type I interferon response.

Cell Host Microbe 2021 03 29;29(3):489-502.e8. Epub 2021 Jan 29.

Department of Laboratory Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, China; Department of Laboratory Medicine and Department of Pediatric Infectious Diseases, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu 610041, China. Electronic address:

The SARS-CoV-2 virus, the causative agent of COVID-19, is undergoing constant mutation. Here, we utilized an integrative approach combining epidemiology, virus genome sequencing, clinical phenotyping, and experimental validation to locate mutations of clinical importance. We identified 35 recurrent variants, some of which are associated with clinical phenotypes related to severity. One variant, containing a deletion in the Nsp1-coding region (Δ500-532), was found in more than 20% of our sequenced samples and associates with higher RT-PCR cycle thresholds and lower serum IFN-β levels of infected patients. Deletion variants in this locus were found in 37 countries worldwide, and viruses isolated from clinical samples or engineered by reverse genetics with related deletions in Nsp1 also induce lower IFN-β responses in infected Calu-3 cells. Taken together, our virologic surveillance characterizes recurrent genetic diversity and identified mutations in Nsp1 of biological and clinical importance, which collectively may aid molecular diagnostics and drug design.
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http://dx.doi.org/10.1016/j.chom.2021.01.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846228PMC
March 2021

A Prediction Nomogram for Acute Kidney Injury in Very-Low-Birth-Weight Infants: A Retrospective Study.

Front Pediatr 2020 15;8:575097. Epub 2021 Jan 15.

Department of Nephrology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Infection and Immunity, Chongqing, China.

Acute kidney injury (AKI) is recognized as an independent predictor for mortality in very-low-birth-weight (VLBW) infants and is reported to have a high incidence. In this study, we sought to identify the predictors for AKI in VLBW infants and thereby develop a prediction nomogram for the early detection and management of VLBW infants at high risk of developing AKI. We designed a retrospective study wherein we investigated the baseline hospitalization data of VLBW infants treated at our hospital between January 2012 and October 2018. Independent predictors of AKI in VLBW infants, as identified by multivariate logistic regression, were incorporated into a model. Hosmer-Lemeshow test was used to test the goodness of fit of the model, and a receiver operating characteristic (ROC) curve was plotted to assess the discriminative ability of the model. The model was internally validated using the 10-fold cross-validation method. A nomogram was plotted to predict the risk of AKI in VLBW infants on the basis of the results of multivariate logistic regression analysis. We investigated the data of 604 VLBW infants, of which 144 (23.8%) developed AKI; in 111 (77.1%) of these infants, AKI occurred within 7 days of birth. Multivariate logistic regression analysis identified the following as predictive factors for AKI in VLBW infants: gestational age, red blood cell count within 3 days of birth, serum calcium concentration within 3 days of birth, maternal age of ≥35 years, and pulmonary arterial hypertension or myocardial injury. Furthermore, the nomogram was found to be effective in estimating the risk of AKI in VLBW infants, with an area under the curve (AUC) of 0.794 [95% confidence interval (CI): 0.754-0.834; < 0.001]. Internal validation done by cross-validation showed that the average AUC was 0.788. The nomogram developed in this study was found to be sensitive and specific for the preoperative prediction of AKI in VLBW infants, as per the Kidney Disease: Improving Global Outcomes (KDIGO) criteria modified for neonates.
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http://dx.doi.org/10.3389/fped.2020.575097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844316PMC
January 2021