Publications by authors named "Hao Zeng"

468 Publications

Exposure to barium and blood pressure in children and adolescents: results from the 2003-2018 National Health and Nutrition Examination Survey.

Environ Sci Pollut Res Int 2022 May 11. Epub 2022 May 11.

School of Public Health, North China University of Science and Technology, No.21 Bohai Road, Caofeidian, Tangshan, 063210, Hebei, China.

Barium (Ba) is ubiquitous in the environment, and humans are primarily exposed to it through ingestion of drinking water. Previous studies focused on the exposure to lead, cadmium, and arsenic, but have not focused on exposure to Ba. Recent studies found a significant association between Ba exposure and elevated blood pressure in pregnant women and adults. However, there are no studies regarding the effect of Ba exposure on blood pressure in children and adolescents, and the potential biological mechanisms remain unclear. We evaluated the associations between urinary Ba and systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) among 8- to 17-year-old participants (n = 3707) of the 2003-2018 National Health and Nutrition Examination Survey. Furthermore, the potential roles of inflammation in these associations were explored. Weighted linear regression was used to analyze the association between urinary Ba and blood pressure, and mediation analyses were used to estimate the potential role of white blood cell count (WBC) in these associations. Quantile g-computation models were used to explore the effect of co-exposure to Ba and other metals on blood pressure. After adjusting for covariates, a two-fold increase in urinary Ba concentration was associated with a 0.41 (95% CI 0.12, 0.70) mmHg increase in SBP, a 1.04 (95% CI 0.55, 1.53) mmHg increase in PP, but a -0.63 (95% CI -1.04, -0.22) mmHg decrease in DBP. WBC significantly mediated 6% of the association between urinary Ba and SBP. Quantile g-computation models suggested that urinary Ba was the main contributor to the elevation of SBP and PP in the urinary metal mixture. Our findings revealed that exposure to Ba was associated with elevated SBP and PP among children and adolescents. Inflammation may play an important role in the associations of Ba exposure with SBP.
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http://dx.doi.org/10.1007/s11356-022-20507-4DOI Listing
May 2022

2D-3D graphene-coated diatomite as a support toward growing ZnO for advanced photocatalytic degradation of methylene blue.

RSC Adv 2021 Nov 30;11(61):38505-38514. Epub 2021 Nov 30.

College of Materials Science and Engineering, Chongqing University Chongqing PR China 400044

In this work, a [email protected]@ZnO (ZGD) photocatalyst was synthesized by chemical vapor deposition and hydrothermal methods and used for the photocatalytic degradation of methylene blue. The characterization of the prepared nanocomposite was performed by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, X-ray diffraction (XRD), and N adsorption-desorption techniques. Ultraviolet-visible diffuse reflectance spectroscopy (DRS) showed that the prepared ZGD photocatalyst enhanced the absorption of visible light and induced a red-shift. Photoluminescence spectroscopy (PL) revealed that the recombination of electron and hole pairs can be effectively suppressed. Besides, the synergistic effect of diatomite and graphene avoids the agglomeration of ZnO, increases the number of surface adsorption sites, and limits the electron transport, consequently improving the photocatalytic activity of ZnO. When ZGD-3 was UV-irradiated ( = 663 nm) for 90 minutes, the degradation effectiveness of methylene blue (MB) was 100%. After the fifth repetition, the photocatalytic degradation efficiency was always greater than 95%. Simply put, the ZGD nanocatalyst can be used as an efficient photocatalyst for dye wastewater treatment.
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http://dx.doi.org/10.1039/d1ra07708bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9044178PMC
November 2021

Evaluation of a recombinant five-antigen Staphylococcus aureus vaccine: The randomized, single-centre phase 1a/1b clinical trials.

Vaccine 2022 May 23;40(23):3216-3227. Epub 2022 Apr 23.

Third Military Medical University, Chongqing 400038, China. Electronic address:

Background: Staphylococcus aureus is an important pathogen that causes hospital and community infections. To control Staphylococcus aureus infection and reduce the usage of antibiotics, we evaluated the safety and immunogenicity of a recombinant five-antigen Staphylococcus aureus vaccine (rFSAV) in healthy adults.

Methods: We conducted a randomized, double-blind, placebo-controlled phase 1a study and a randomized, open-label phase 1b study. In phase 1a, we randomly allocated 144 healthy participants in a ratio of 1:1:1:1 to receive the low-(60 μg), middle-(120 μg), and high-dose (240 μg) vaccine or placebo at day 0, 3, 7 and 14. In phase 1b, 144 healthy participants were randomly allocated at a ratio of 1:1:1:1 to receive 0-3-7, 0/0-7, 0/0-3-7, 0/0-7-14 regimens to estimate the optimal strategy. The primary study endpoint was the incidence of solicited adverse events post-vaccination. The immunogenicity endpoints included the level of specific antibodies to five antigens after vaccination, as well as the cellular immune responses and functional antibodies.

Results: There were 31 (86%), 30 (83%), and 32 (89%) of 36 participants in the low-, middle-, and high-dose group reported solicited adverse events, respectively, most of the adverse events were mild or moderate. In phase 1b, the dose-adjusted rFSAV (90 μg) showed a better safety profile in the four immune procedures, and no vaccine-related serious adverse events were reported. The antigen-specific binding antibodies started to increase at day 7 and reached the peak around day 14 to 21. The cellular immune responses and functional antibodies also were substantially above background levels.

Conclusions: rFSAV is safe, well tolerated in healthy adults, elicits rapid and robust specific humoral and cellular immune responses with unconventional immunization procedure in phase 1a and 1b. It deserves to be noted and further explored.

Clinical Trials Registration: NCT02804711 and NCT03966040.
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http://dx.doi.org/10.1016/j.vaccine.2022.04.034DOI Listing
May 2022

Upregulated LINC00922 Promotes Epithelial-Mesenchymal Transition and Indicates a Dismal Prognosis in Gastric Cancer.

J Oncol 2022 11;2022:1608936. Epub 2022 Apr 11.

Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.

Background: LINC00922 has been found to promote epithelial-mesenchymal transition (EMT) in a variety of tumors. But its functions in gastric cancer (GC) remain unclear. We attempt to investigate the correlation between LINC00922 and GC via bioinformatics analysis, in vitro and in vivo experiments.

Methods: TCGA and GTEx databases were utilized to obtain the RNAseq and clinical data of GC, and then, identified the correlation of LINC00922 with patients' clinicopathological characteristics and prognosis. GSEA and GO/KEGG enrichment analyses were performed to explore the potential functions or signaling pathways that LINC00922 participated in GC. Infiltration levels of immune cells were employed by ssGSEA algorithm, and then Wilcoxon rank sum test was applied to analyze their correlations with LINC00922. Scratch and transwell assays were conducted to detect the invasion and migration abilities of GC cells. Western blot was performed to explore the expression level of EMT-related proteins. Furthermore, we constructed the xenograft tumor model and metastatic tumor model in nude mice to explore the effect of LINC00922 downregulating on metastasis of GC cells in vivo.

Results: Compared with normal tissues, LINC00922 was highly expressed in GC tissues and positively correlated with poor prognosis. The correlation existed between LINC00922 and immune infiltration in GC. Downregulation of LINC00922 inhibited the EMT process of GC cells. In addition, both in vitro and in vivo experiments showed that LINC00922 affects the invasion and migration abilities of GC.

Conclusions: LINC00922 promotes the migration, invasion, and EMT in GC and has the potential to be used as a prognostic biomarker and therapeutic target for GC.
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http://dx.doi.org/10.1155/2022/1608936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9015875PMC
April 2022

Effects of titanium dioxide microparticles and nanoparticles on cytoskeletal organization, cell adhesion, migration, and proliferation in human gingival fibroblasts in the presence of lipopolysaccharide.

J Periodontal Res 2022 Apr 19. Epub 2022 Apr 19.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, Wuhan, China.

Background And Objective: Titanium wear particles may participate in the etiology of peri-implantitis. However, the influence of titanium wear particles on biological behavior of human gingival fibroblasts (HGFs) in the presence of LPS is still not clear. The present study demonstrated the effects of titanium dioxide micro- and nanoparticles (TiO  MPs and NPs) on HGF cell viability, cytoskeletal organization, adhesion, migration, and proliferation in vitro, and LPS was used to mimic the in vivo condition.

Methods: Primary HGFs were treated with TiO MPs (primary particle size <5 μm, 0.1 mg/ml) and NPs (primary particle size <100 nm, 0.1 mg/ml) with or without 1 μg/ml LPS. The effects of TiO MPs and NPs on HGFs cell viability was measured by CCK-8 assay. The proliferation of HGF was detected by Ki67 nuclear staining. The confocal laser scanning microscope (CLSM) was used to detect the internalization of TiO MPs and NPs in HGFs as well as the arrangement of F-actin, vinculin, and vimentin organization. Wound healing assay and transwell assay were performed to measure the migration of HGFs induced by TiO MPs and NPs. Cell adhesion was measured using fibronectin-coated plates. The relative mRNA and protein expression of adhesion relative protein such as focal adhesion kinase (FAK), fibronectin (FN), and type I collagen (COL1) were measured using quantitative RT-PCR and western blot analysis. One-way analysis of variance (ANOVA) and Student's t-test were used to analyze the statistical significance, and p < .05 was considered statistically significant.

Results: TiO NPs significantly inhibited HGF cell viability, proliferation, and migration compared with TiO MPs group and control group. Compared with control group (2.64 ± 0.09), the mean absorbance of the cells in 1 mg/ml TiO MPs group and 0.25 mg/ml TiO NPs group were significantly decreased to 1.93 ± 0.33 (p < .05) and 2.22 ± 0.18 (p < .01), respectively. The cytoskeleton disruption was found in TiO NPs group. The mRNA and protein expression were significantly downregulated by TiO NPs. Furthermore, both TiO NPs and MPs induced more adverse effects on HGFs in the presence of LPS.

Conclusion: Our results indicate that TiO NPs but not TiO MPs significantly disrupt the cytoskeletal organization and inhibited cell adhesion, migration, and proliferation of HGFs. However, in the presence of LPS, TiO MPs, and TiO NPs enhance these negative effects in HGFs. Titanium wear particles are probably involved in the initiation and progression of peri-implant diseases.
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http://dx.doi.org/10.1111/jre.12993DOI Listing
April 2022

A primary rectal neoplasm with novel DDX5-TFEB fusion.

Virchows Arch 2022 Apr 9. Epub 2022 Apr 9.

Pathology Department and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.

We report a case of primary rectal neoplasm with a novel DDX5-TFEB fusion in a 14-year-old boy. Histologically, the neoplasm was composed of epithelioid tumor cells with abundant clear to eosinophilic cytoplasm, arranged in nests with rich stromal capillary vasculature. Immunohistochemically, the tumor cells were positive for transcription factor EB (TFEB) and negative for PAX8, TFE3, HMB45, and PCK. TFEB gene rearrangement and low-level amplification were identified using break-apart fluorescence in situ hybridization. Next-generation sequencing identified a heretofore unreported DDX5-TFEB gene fusion, which was confirmed by using reverse transcription-polymerase chain reaction and Sanger sequencing. The major morphological differential diagnoses include perivascular epithelioid cell tumor, microphthalmia-associated transcriptional factor family translocation renal cell carcinoma, and alveolar soft part sarcoma. The morphological, immumophenotypical, and genetic characteristics of this tumor did not fit well with current classification, but it may represent an unusual PEComa-like tumor with a novel DDX5-TFEB fusion.
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http://dx.doi.org/10.1007/s00428-022-03316-5DOI Listing
April 2022

Transition metal dichalcogenide graded alloy monolayers by chemical vapor deposition and comparison to 2D Ising model.

J Chem Phys 2022 Apr;156(13):134704

Department of Physics, University at Buffalo, The State University of New York, Buffalo, New York 14260, USA.

In this work, a chemical vapor deposition (CVD) method was developed for the synthesis of transition metal dichalcogenide alloy monolayers, with a composition gradient in the radial direction. The composition gradient was achieved by controlling the substrate cooling rate during the CVD growth. The two types of alloys, namely, WSSe and MoSSe, were found to exhibit an opposite composition gradient. This is attributed to their different cohesive energies. A two-dimensional Ising model is used to explain the growth mechanism, where two ends of the composition were modeled as a magnetically ordered phase and a paramagnetic phase. The composition as a function of substrate temperature is then represented by the thermal magnetization curve.
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http://dx.doi.org/10.1063/5.0081929DOI Listing
April 2022

Pretreatment Inflammatory Markers Predict Outcomes and Prognosis in Colorectal Cancer Patients With Synchronous Liver Metastasis.

Clin Med Insights Oncol 2022 25;16:11795549221084851. Epub 2022 Mar 25.

Department of Biotherapy, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

Introduction: Pretreatment inflammatory markers were applied to predict the prognosis of colorectal cancer. However, the role of these markers in predicting survival in patients with synchronous colorectal liver metastasis (CLM) is rarely reported. Notably, lymphocyte-to-monocyte ratio (LMR) was mainly reported in hematologic malignancies and is worth to be further explored to predict the survival of synchronous CLM.

Methods: Totally, 196 patients who were diagnosed with synchronous CLM were enrolled. Their clinical and laboratory data before treatment were collected, retrospectively. Univariate and multivariate analyses were performed to analyze the inflammatory biomarkers.

Results: LMR ( = .002) and lactate dehydrogenase (LDH) ( = .017) were significantly related to the progression-free survival (PFS). More factors such as neutrophil-to-lymphocyte ratio (NLR) ( = .011), carbohydrate antigen 19-9 (CA19-9) ( = .001), number of metastatic foci ( = .006), and adjuvant chemotherapy ( = .027) were correlated with overall survival (OS). In multivariate analysis, LMR remained statistically associated with PFS ( = .003). Regarding OS, LMR ( = .016) and LDH ( = .013) were significantly independent predictive factors.

Conclusions: The higher LMR and lower LDH were strongly correlated with better survival in synchronous CLM patients. In addition, the result also indicated that enhanced LMR was related to better PFS. The LMR and LDH can be used to predict prognosis of the synchronous CLM.
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http://dx.doi.org/10.1177/11795549221084851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8958682PMC
March 2022

The Predictive Value of PAK7 Mutation for Immune Checkpoint Inhibitors Therapy in Non-Small Cell Cancer.

Front Immunol 2022 3;13:834142. Epub 2022 Feb 3.

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: To date, immunotherapy has improved the 5-year survival rate of patients with advanced non-small cell lung cancer (NSCLC) from 4% to 15%. However, only 30%-50% of the NSCLC patients respond to immune checkpoint inhibitors (ICIs) immunotherapy. Therefore, screening patients for potential benefit with precise biomarkers may be of great value.

Methods: First, an immunotherapy NSCLC cohort was analyzed to identify the gene mutations associated with the prognosis of ICI treatment. Further analyses were conducted using NSCLC cohort in The Cancer Genome Atlas (TCGA) project to validate the correlations between the specific gene mutations and tumor immunogenicity, antitumor immunity, and alterations in the tumor-related pathways using Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) and Gene set enrichment analysis (GSEA).

Results: In the immunotherapy NSCLC cohort (n = 266), significantly longer overall survival (OS) rates were observed in the -mutant type (PAK7-MT) group (n = 13) than the -wild type (PAK7-WT) group (n = 253) ( = 0.049, HR = 0.43, 95%CI = 0.23-0.79). In the TCGA cohort, mutations were correlated with the higher tumor mutation burden (TMB) (14.18 7.13, 0.001), increased neoantigen load (NAL) (7.52 4.30, 0.001), lower copy number variation (CNV), and higher mutation rate in the DNA damage response (DDR)-related pathways. In addition, mutations were also positively correlated with immune-related genes expressions and infiltrating CD8+ T cells (0.079 0.054, = 0.005). GSEA results showed that several tumor-related pathways varied in the PAK7-MT group, suggesting the potential mechanisms that regulate the tumor immune-microenvironment.

Conclusions: This study suggested that the mutations might be a potential biomarker to predict the efficacy of immunotherapy for NSCLC patients. Considering the heterogeneity among the patients and other confounding factors, a prospective clinical trial is proposed to further validate the impact of mutation on the immunotherapy outcomes in NSCLC.
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http://dx.doi.org/10.3389/fimmu.2022.834142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8886445PMC
May 2022

Randomized controlled trial: neostigmine for intra-abdominal hypertension in acute pancreatitis.

Crit Care 2022 03 3;26(1):52. Epub 2022 Mar 3.

Pancreatic Intensive Care Unit, Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, China.

Background: Intra-abdominal hypertension (IAH) in acute pancreatitis (AP) is associated with deterioration in organ function. This trial aimed to assess the efficacy of neostigmine for IAH in patients with AP.

Methods: In this single-center, randomized trial, consenting patients with IAH within 2 weeks of AP onset received conventional treatment for 24 h. Patients with sustained intra-abdominal pressure (IAP) ≥ 12 mmHg were randomized to receive intramuscular neostigmine (1 mg every 12 h increased to every 8 h or every 6 h, depending on response) or continue conventional treatment for 7 days. The primary outcome was the percent change of IAP at 24 h after randomization.

Results: A total of 80 patients were recruited to neostigmine (n = 40) or conventional treatment (n = 40). There was no significant difference in baseline parameters. The rate of decrease in IAP was significantly faster in the neostigmine group compared to the conventional group by 24 h (median with 25th-75th percentile: -18.7% [- 28.4 to - 4.7%] vs. - 5.4% [- 18.0% to 0], P = 0.017). This effect was more pronounced in patients with baseline IAP ≥ 15 mmHg (P = 0.018). Per-protocol analysis confirmed these results (P = 0.03). Stool volume was consistently higher in the neostigmine group during the 7-day observational period (all P < 0.05). Other secondary outcomes were not significantly different between neostigmine and conventional treatment groups.

Conclusion: Neostigmine reduced IAP and promoted defecation in patients with AP and IAH. These results warrant a larger, placebo-controlled, double-blind phase III trial. Trial registration Clinical Trial No: NCT02543658 (registered August /27, 2015).
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http://dx.doi.org/10.1186/s13054-022-03922-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8892692PMC
March 2022

Dative Epitaxy of Commensurate Monocrystalline Covalent van der Waals Moiré Supercrystal.

Adv Mater 2022 Apr 22;34(17):e2200117. Epub 2022 Mar 22.

Department of Physics, University at Buffalo, State University of New York, Buffalo, NY, 14260, USA.

Realizing van der Waals (vdW) epitaxy in the 1980s represents a breakthrough that circumvents the stringent lattice matching and processing compatibility requirements in conventional covalent heteroepitaxy. However, due to the weak vdW interactions, there is little control over film qualities by the substrate. Typically, discrete domains with a spread of misorientation angles are formed, limiting the applicability of vdW epitaxy. Here, the epitaxial growth of monocrystalline, covalent Cr Te 2D crystals on monolayer vdW WSe by chemical vapor deposition is reported, driven by interfacial dative bond formation. The lattice of Cr Te , with a lateral dimension of a few tens of micrometers, is fully commensurate with that of WSe via 3 × 3 (Cr Te )/7 × 7 (WSe ) supercell matching, forming a single-crystalline moiré superlattice. This work establishes a conceptually distinct paradigm of thin-film epitaxy, termed "dative epitaxy", which takes full advantage of covalent epitaxy with chemical bonding for fixing the atomic registry and crystal orientation, while circumventing its stringent lattice matching and processing compatibility requirements; conversely, it ensures the full flexibility of vdW epitaxy, while avoiding its poor orientation control. Cr Te 2D crystals grown by dative epitaxy exhibit square magnetic hysteresis, suggesting minimized interfacial defects that can serve as pinning sites.
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http://dx.doi.org/10.1002/adma.202200117DOI Listing
April 2022

Edge-Topological Regulation for Fabrication of Bridging Nanosensors.

Nano Lett 2022 03 28;22(6):2569-2577. Epub 2022 Feb 28.

Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.

fabrication of well-defined bridging nanostructures is an interesting and unique approach to three-dimensionally design nanosensor structures, which are hardly attainable by other methods. Here, we demonstrate the significant effect of edge-topological regulation on fabrication of ZnO bridging nanosensors. When employing seed layers with a sharp edge, which is a well-defined structure in conventional lithography, the bridging angles and electrical resistances between two opposing electrodes were randomly distributed. The stochastic nature of bridging growth direction at the sharp edges inherently causes such unintentional variation of structural and electrical properties. We propose an edgeless seed layer structure using a two-layers resist method to solve the above uncontrollability of bridging nanosensors. Such bridging nanosensors not only substantially improved the uniformity of structural and electrical properties between two opposing electrodes but also significantly enhanced the sensing responses for NO with the smaller variance and the lower limit of detection via controlled electrical contacts.
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http://dx.doi.org/10.1021/acs.nanolett.1c04600DOI Listing
March 2022

Efficacy of second-line ICIs combined with TKIs among patients with metastatic renal cell carcinoma: a real-world study.

Immunotherapy 2022 04 21;14(5):309-320. Epub 2022 Feb 21.

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, China.

To evaluate the efficacy of immune checkpoint inhibitors (ICIs) plus tyrosine kinase inhibitors (TKIs) as second-line treatment in patients with metastatic renal cell carcinoma (mRCC). Baseline and follow-up data from patients with mRCC treated with second-line ICIs plus TKIs or TKIs alone from a single institution were retrospectively gathered. A total of 110 patients were included. The objective response rate was higher among patients treated with ICIs plus TKIs than those treated with TKIs alone (36.5 vs 12.1%; p = 0.002). Treatment with ICIs plus TKIs was associated with longer progression-free survival (15.0 vs 9.0 months; p = 0.009) and overall survival (not reached vs 16.0 months; p = 0.018) than TKI monotherapy. The survival rates at 2 (83.0 vs 74.4%; p = 0.426) and 3 years (58.1 vs 47.5%; p = 0.214) between the two groups were not statistically different. Notably, patients with certain clinicopathological features tended to gain more survival benefits with combined therapy. ICIs plus TKIs showed superior progression-free survival time and tumor response rate over TKIs alone as second-line treatment in patients with mRCC. Future randomized prospective trials are necessary to validate these preliminary findings.
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http://dx.doi.org/10.2217/imt-2021-0108DOI Listing
April 2022

The transcriptional elongation factor CTR9 demarcates PRC2-mediated H3K27me3 domains by altering PRC2 subtype equilibrium.

Nucleic Acids Res 2022 02;50(4):1969-1992

McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI 53706, USA.

CTR9 is the scaffold subunit in polymerase-associated factor complex (PAFc), a multifunctional complex employed in multiple steps of RNA Polymerase II (RNAPII)-mediated transcription. CTR9/PAFc is well known as an evolutionarily conserved elongation factor that regulates gene activation via coupling with histone modifications enzymes. However, little is known about its function to restrain repressive histone markers. Using inducible and stable CTR9 knockdown breast cancer cell lines, we discovered that the H3K27me3 levels are strictly controlled by CTR9. Quantitative profiling of histone modifications revealed a striking increase of H3K27me3 levels upon loss of CTR9. Moreover, loss of CTR9 leads to genome-wide expansion of H3K27me3, as well as increased recruitment of PRC2 on chromatin, which can be reversed by CTR9 restoration. Further, CTR9 depletion triggers a PRC2 subtype switch from the less active PRC2.2, to the more active PRC2.1 with higher methyltransferase activity. As a consequence, CTR9 depletion generates vulnerability that renders breast cancer cells hypersensitive to PRC2 inhibitors. Our findings that CTR9 demarcates PRC2-mediated H3K27me3 levels and genomic distribution provide a unique mechanism that explains the transition from transcriptionally active chromatin states to repressive chromatin states and sheds light on the biological functions of CTR9 in development and cancer.
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http://dx.doi.org/10.1093/nar/gkac047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8887485PMC
February 2022

Comparison of Systemic Treatments for Metastatic Castration-Resistant Prostate Cancer After Docetaxel Failure: A Systematic Review and Network Meta-analysis.

Front Pharmacol 2021 18;12:789319. Epub 2022 Jan 18.

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.

Lacking head-to-head trial, the optimal treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel failure is unclear. This study is to compare the efficacy and safety of systemic treatments in patients who progressed after docetaxel to aid clinical decision-making. Databases including MEDLINE, EMBASE, and the Cochrane Library were searched from inception to June 15th, 2021. The outcomes of interest include overall survival (OS), biochemical progression-free survival (bPFS), and serious adverse events (SAEs). The Cochrane risk of bias tools were used to assess study quality. Indirect comparisons of competing treatments were performed via Bayesian network meta-analysis. Five trials with 3,862 patients comparing four treatments (abiraterone, enzalutamide, cabazitaxel, and radium-223) were identified. All the four treatments were associated with improved OS and bPFS relative to best supportive care. Among them, enzalutamide (hazard ratio [HR] = 0.58, 95% credible interval [Crl]: 0.49-0.69) had the highest probability of ranking first in terms of OS, followed by cabazitaxel (HR = 0.70, 95% Crl: 0.59-0.83), radium-223 (HR = 0.71, 95% Crl: 0.56-0.90) and abiraterone (HR = 0.73, 95% Crl: 0.63-0.84). Similarly, enzalutamide (HR = 0.25, 95% Crl: 0.20-0.31) showed the greatest improvement of bPFS, followed by abiraterone (HR = 0.60, 95% Crl: 0.51-0.71) and cabazitaxel (HR = 0.75, 95% Crl: 0.63-0.89). In terms of safety, treatments ranked from the safest to the least safe were radium-223 (OR = 0.58, 95% Crl: 0.20-1.68), enzalutamide (OR = 0.80, 95% Crl: 0.28-2.29), abiraterone (OR = 0.94, 95% Crl: 0.39-2.27) and cabazitaxel (OR = 2.50, 95% Crl: 0.84-7.44). For patients with mCRPC who progressed after docetaxel, enzalutamide may offer the most significant survival benefits and satisfying safety. Cabazitaxel is effective in post-docetaxel settings but associated with a high risk of SAEs. Although network meta-analysis provides indirect comparisons and ranking probabilities, the results should be treated with caution as it cannot replace randomized direct comparison. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020223040, identifier CRD42020223040.
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http://dx.doi.org/10.3389/fphar.2021.789319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8804311PMC
January 2022

TLR4-Dependent DUOX2 Activation Triggered Oxidative Stress and Promoted HMGB1 Release in Dry Eye.

Front Med (Lausanne) 2021 13;8:781616. Epub 2022 Jan 13.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou, China.

Dry eye disease (DED) is one of the most common ocular surface diseases worldwide. DED has been characterized by excessive accumulation of reactive oxygen species (ROS), following significant corneal epithelial cell death and ocular surface inflammation. However, the key regulatory factor remains unclear. In this study, we tended to explore whether DUOX2 contributed to DED development and the underlying mechanism. Human corneal epithelial (HCE) cells were treated with hyperosmolarity, C57BL/6 mice were injected of subcutaneous scopolamine to imitate DED. Expression of mRNA was investigated by RNA sequencing (RNA-seq) and quantitative real-time PCR (qPCR). Protein changes and distribution of DUOX2, high mobility group box 1 (HMGB1), Toll-like receptor 4 (TLR4), and 4-hydroxynonenal (4-HNE) were evaluated by western blot assays and immunofluorescence. Cell death was assessed by Cell Counting Kit-8 (CCK8), lactate dehydrogenase (LDH) release, and propidium iodide (PI) staining. Cellular ROS levels and mitochondrial membrane potential (MMP) were analyzed by flow cytometry. RNA-seq and western blot assay indicated a significant increase of DUOX2 dependent of TLR4 activation in DED both and . Immunofluorescence revealed significant translocation of HMGB1 within corneal epithelial cells under hyperosmolar stress. Interestingly, after ablated DUOX2 expression by siRNA, we found a remarkable decrease of ROS level and recovered MMP in HCE cells. Moreover, knockdown of DUOX2 greatly inhibited HMGB1 release, protected cell viability and abolished inflammatory activation. Taken together, our data here suggest that upregulation of DUOX2 plays a crucial role in ROS production, thereafter, induce HMGB1 release and cell death, which triggers ocular surface inflammation in DED.
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http://dx.doi.org/10.3389/fmed.2021.781616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8793023PMC
January 2022

Impact of Lateral SnO Nanofilm Channel Geometry on a 1024 Crossbar Chemical Sensor Array.

ACS Sens 2022 02 23;7(2):460-468. Epub 2022 Jan 23.

Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8656, Japan.

We propose a rational strategy to fabricate thermally robust, highly integrated molecular and gas sensors utilizing a lateral SnO nanofilm channel geometry on a 1024 crossbar sensor array. The proposed lateral channel geometry substantially suppresses the detrimental effects of parasitic interconnect wire resistances compared with those of a conventional vertical sandwich-type crossbar array because of its excellent resistance controllability. A conductive oxide top-contact electrode on the lateral SnO nanofilm channel enhances the thermal stability at temperatures of up to 500 °C in ambient air. Integrating this lateral SnO nanofilm geometry with analog circuits enables the operation of a 1024 crossbar sensor array without selector devices to avoid sneak currents. The developed 1024 crossbar sensor array system detects the local spatial distribution of the molecular gas concentration. The spatial data of molecular concentrations include molecule-specific data to distinguish various volatile molecules based on their vapor pressures. Thus, this integrated crossbar sensor array system using lateral nanofilm geometry offers a platform for robust, reliable, highly integrated molecular and gas sensors.
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http://dx.doi.org/10.1021/acssensors.1c02173DOI Listing
February 2022

A NAC Transcription Factor TuNAC69 Contributes to ANK-NLR-WRKY NLR-Mediated Stripe Rust Resistance in the Diploid Wheat .

Int J Mol Sci 2022 Jan 5;23(1). Epub 2022 Jan 5.

State Key Laboratory of Ecological Control of Fujian-Taiwan Crop Pests, Key Laboratory of Ministry of Education for Genetics, Breeding and Multiple Utilization of Crops, Plant Immunity Center, Fujian Agriculture and Forestry University, Fuzhou 350002, China.

Stripe rust is one of the most devastating diseases in wheat. Nucleotide-binding site (NBS) and leucine-rich repeat (LRR) domain receptors (NLRs) recognize pathogenic effectors and trigger plant immunity. We previously identified a unique NLR protein YrU1 in the diploid wheat , which contains an N-terminal ANK domain and a C-terminal WRKY domain and confers disease resistance to stripe rust fungus   f. sp. (). However, how YrU1 functions in disease resistance is not clear. In this study, through the RNA-seq analysis, we found that the expression of a NAC member was significantly up-regulated after inoculation with in the presence of YrU1. TuNAC69 was mainly localized in the nucleus and showed transcriptional activation in yeast. Knockdown in diploid wheat PI428309 that contains YrU1 by virus-induced gene silencing reduced the resistance to stripe rust. In addition, overexpression of in enhanced the resistance to powdery mildew . In summary, our study indicates that TuNAC69 participates in the immune response mediated by NLR protein YrU1, and likely plays an important role in disease resistance to other pathogens.
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http://dx.doi.org/10.3390/ijms23010564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8745140PMC
January 2022

Combined effects of exposure to polycyclic aromatic hydrocarbons and metals on oxidative stress among healthy adults in Caofeidian, China.

Ecotoxicol Environ Saf 2022 Jan 6;230:113168. Epub 2022 Jan 6.

Department of Clinical Medicine, Tangshan Vocational and Technical College, No. 120 Xinhua West Road, Tangshan 063000, China.

Exposure to polycyclic aromatic hydrocarbons (PAHs) and metals is associated with many adverse effects on human health, accompanied by oxidative stress. This study aimed to investigate the effects of co-exposure to PAHs and metals on oxidative stress in healthy adults. A preliminary longitudinal panel study was conducted between 2017 and 2018 in 45 healthy college students in Caofeidian, China. Six urinary monohydroxylated-PAHs (OH-PAHs), ten metals, 8-hydroxydeoxyguanosine (8-OHdG), and 8-iso-prostaglandin-F2α (8-iso-PGF2α) were measured. Linear mixed effects (LME) models and Bayesian kernel machine regression (BKMR) models were used to explore the associations of urinary OH-PAHs and metals with 8-OHdG and 8-iso-PGF2α. LME models showed that most urinary OH-PAHs and metals were positively associated with 8-OHdG and 8-iso-PGF2α. For example, a one-unit increase in the ln-transformed level of 1-hydroxypyrene (1-OHPyr) and vanadium (V) was associated with an increase of 143.8% (95% CI: 105.7 - 188.9%) and 105.8% (95% CI: 79.2-136.4%) in 8-OHdG; 8-iso-PGF2α increased by 118.9% (95% CI: 99.2-140.5%) and 83.9% (95% CI: 67.2-102.2%) with a one-unit increase in the ln-transformed level of 3-hydroxyphenanthrene (3-OHPhe) and aluminum (Al). BKMR models indicated the overall positive associations of the mixture of six OH-PAHs, ten metals, or six OH-PAHs and ten metals with 8-OHdG and 8-iso-PGF2α. Urinary 1-OHPyr and V were identified as the major contributors to the increased urinary 8-OHdG levels, while urinary 3-OHPhe and Al were the most vital contributors to the increased urinary 8-iso-PGF2α levels. The results revealed the longitudinal dose-response relationships of urinary OH-PAHs and metals with oxidative stress among healthy adults in Caofeidian; this finding serves as an evidence regarding the early health hazard caused by exposure to PAHs and metals and has implications for the environmental management of PAH and metal emissions in this area.
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http://dx.doi.org/10.1016/j.ecoenv.2022.113168DOI Listing
January 2022

Co-circulation and evolution of genogroups I and II of respiratory and enteric feline calicivirus isolates in cats.

Transbound Emerg Dis 2022 Jan 4. Epub 2022 Jan 4.

Laboratory of Animal Infectious Diseases and Molecular Immunology, College of Animal Science and Technology, Guangxi University, Nanning, P. R. China.

Feline calicivirus (FCV) is a highly infectious pathogen that causes upper respiratory tract disease (URTD), but the enteric FCVs raise concerns regarding their role of an enteric pathogen. In this study, between 2019 and 2020, 101 clinical samples from domestic cats with symptoms of URTD, with or without enteritis, were collected for FCV-specific detection. The FCV-positive rate reached to 42.4% (28/66) in cats with respiratory symptoms. The rates were 11.1% (3/27) and 12.5% (1/8) when faeces and serum samples were measured using reverse transcription polymerase chain reaction (RT-PCR), respectively. Ten FCV strains were successfully isolated from respiratory and enteric sources in domestic cats from Guangxi. Phylogenetic analysis based on the genome sequences of 11 isolates (including GX01-13 isolated in 2013) indicated that the newly characterized FCV strains had two recombinant events in comparison with other FCVs and were of respiratory and enteric origins. These strains displayed high genetic diversity, and they were divided into two genogroups (I and II). Of these, the GXNN02-19 isolate was grouped with previously published Chinese isolates that were identified as genogroup II, which contained three specific amino acid residues (377K, 539V and 557S) in the VP1 protein. In addition, the three enteric viruses appeared genetically heterogeneous to each other. All isolates were found to be more sensitive when exposed to low pH conditions, but they were resistant to treatment with trypsin and bile salts. Furthermore, there were no significant differences between the respiratory and enteric FCVs. Our results showed that the genetically distinct FCV strains with genogroups I and II from respiratory and enteric origins were co-circulating in this geographical area. Also, it was revealed that the potential recombinant events between the enteric and respiratory FCVs suggested an important role of enteric FCV during the evolution.
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http://dx.doi.org/10.1111/tbed.14447DOI Listing
January 2022

Corrigendum to "Ovarian metastasis risk factors in endometrial carcinoma: A systematic review and meta-analysis" [Eur J Obstet Gynecol Reprod Biol 267 (2021) 245-255].

Eur J Obstet Gynecol Reprod Biol 2022 Feb 29;269:83. Epub 2021 Dec 29.

Department of Gynecology, Guangxi Medical University First Affiliated Hospital, Nanning, Guangxi, China. Electronic address:

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http://dx.doi.org/10.1016/j.ejogrb.2021.12.005DOI Listing
February 2022

Photoelastic plasmonic metasurfaces with ultra-large near infrared spectral tuning.

Mater Horiz 2022 03 7;9(3):942-951. Epub 2022 Mar 7.

Department of Electrical and Electronic Engineering, Southern University of Science and Technology, Shenzhen 518055, China.

Metasurfaces, consisting of artificially fabricated sub-wavelength -atoms with pre-designable electromagnetic properties, provide novel opportunities to a variety of applications such as light detectors/sensors, local field imaging and optical displays. Currently, the tuning of most metasurfaces requires redesigning and reproducing the entire structure, rendering them ineligible for post-fabrication shape-morphing or spectral reconfigurability. Here, we report a photoelastic metasurface with an all-optical and reversible resonance tuning in the near infrared range. The photoelastic metasurface consists of hexagonal gold nanoarrays deposited on a deformable substrate made of a liquid crystalline network. Upon photo-actuation, the substrate deforms, causing the lattice to change and, as a result, the plasmon resonance to shift. The centre wavelength of the plasmon resonance exhibits an ultra-large spectral tuning of over 245 nm, from 1490 to 1245 nm, while the anisotropic deformability also endows light-switchable sensitivity in probing polarization. The proposed concept establishes a light-controlled soft platform that is of great potential for tunable/reconfigurable photonic devices, such as nano-filters, -couplers, -holograms, and displays with structural colors.
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http://dx.doi.org/10.1039/d1mh01377gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8900491PMC
March 2022

Analysis of Clinical Characteristics of 556 Spinal Tuberculosis Patients in Two Tertiary Teaching Hospitals in Guangxi Province.

Biomed Res Int 2021 10;2021:1344496. Epub 2021 Dec 10.

Department of Spine and Osteopathy Surgery, Guangxi Medical University First Affiliated Hospital, 6#Shuangyong Rd, Nanning, 530000 Guangxi, China.

Spinal tuberculosis (STB), which accounts for half of musculoskeletal tuberculosis, is among the leading causes of extrapulmonary tuberculosis. Guangxi Province, located in southern China, is among the most severely affected provinces in China. In this study, we collected and analyzed data from 2 Class-A tertiary teaching hospitals in Nanning City, Guangxi Province, from 2011 to 2019, with the aim of providing reference points for the prevention, diagnosis, treatment, and prognosis analysis of STB, using the epidemiological characteristics of 556 STB cases. Our results revealed that males had a slightly higher incidence (50.17%) compared to females (49.83%), with 64.93% of cases falling between the ages of 18 and 45 years. Cases from rural communities accounted for 63.49% of the reviewed cases. The average time between onset of symptoms and hospitalization was 18.0 months (range: 1 day-220 months). The most commonly reported symptoms were lower back pain (78.60%), radicular pain (51.98%), and systemic toxemia (43.53%). Additionally, 53.98% of the reviewed cases had varying degrees of neurological impairment. The main pathological lesion locations were the lumbar spine (43.53%) and thoracic spine (32.55%). Among them, 72.66% of cases involved at least 2 vertebral segments, and 62.77% of cases presented with paravertebral abscesses. Among the cases reviewed, 90.65% underwent antituberculosis chemotherapy prior to surgery. Following treatment, the cure rate was 78.41%, while 3.78% of patients had postoperative relapse. There were cases of concomitant illnesses among the cases reviewed, 40.65% of patients also had pulmonary tuberculosis, 15.29% had hepatitis B, 13.30% had diabetes, and 7.91% had hypertension. Our results still demonstrate that spinal tuberculosis remains a serious public health problem in Guangxi Province. Thus, preventive measures should be directed towards rural residents with comorbidities such as the elderly and diabetic.
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http://dx.doi.org/10.1155/2021/1344496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8683179PMC
January 2022

Stimulus-driven liquid metal and liquid crystal network actuators for programmable soft robotics.

Mater Horiz 2021 08 31;8(9):2475-2484. Epub 2021 Aug 31.

Advanced Materials and Liquid Crystal Institute and Chemical Physics Interdisciplinary Program, Kent State University, Kent, OH 44242, USA.

Sophisticated soft matter engineering has been endorsed as an emerging paradigm for developing untethered soft robots with built-in electronic functions and biomimetic adaptation capacities. However, the integration of flexible electronic components into soft robotic actuators is challenging due to strain mismatch and material incompatibilities. Herein, we report a general strategy to integrate electrically conductive liquid metals (LMs) and shape-morphing liquid crystal networks (LCNs) towards multifunctional and programmable soft robotics. A unique colloidal LM ink with superior adhesion and photothermal conversion efficiency was judiciously designed and fabricated by ultrasonicating LMs and miniature carboxylated gold nanorods (MiniGNR-COOH) in an aqueous suspension of biological bacterial cellulose. The designed nanocellulose-based colloidal LM ink is used for shape-deformable and electrically conductive LM-LCN soft robots that can be electro- and photo-thermally actuated. As proof-of-concept demonstrations, we present a light-fueled soft oscillator, an inchworm-inspired soft crawler and programmable robotic Shadow Play exhibiting multifunctional controllability. The strategy disclosed here could open up a new technological arena for advanced multifunctional soft materials with potential utility in bioinspired soft machines, integrated soft electronics, human-computer interaction and beyond.
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http://dx.doi.org/10.1039/d1mh00623aDOI Listing
August 2021

Bone Tumor Suppression in Rabbits by Hyperthermia below the Clinical Safety Limit Using Aligned Magnetic Bone Cement.

Small 2022 01 4;18(3):e2104626. Epub 2021 Dec 4.

Department of Physics, University at Buffalo, SUNY, Buffalo, NY, 14260, USA.

Demonstrating highly efficient alternating current (AC) magnetic field heating of nanoparticles in physiological environments under clinically safe field parameters has remained a great challenge, hindering clinical applications of magnetic hyperthermia. In this work, exceptionally high loss power of magnetic bone cement under the clinical safety limit of AC field parameters, incorporating direct current field-aligned soft magnetic Zn Fe O nanoparticles with low concentration, is reported. Under an AC field of 4 kA m at 430 kHz, the aligned bone cement with 0.2 wt% nanoparticles achieves a temperature increase of 30 °C in 180 s. This amounts to a specific loss power value of 327 W and an intrinsic loss power of 47 nHm kg , which is enhanced by 50-fold compared to randomly oriented samples. The high-performance magnetic bone cement allows for the demonstration of effective hyperthermia suppression of tumor growth in the bone marrow cavity of New Zealand White Rabbits subjected to rapid cooling due to blood circulation, and significant enhancement of survival rate.
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http://dx.doi.org/10.1002/smll.202104626DOI Listing
January 2022

Ovarian metastasis risk factors in endometrial carcinoma: A systematic review and meta-analysis.

Eur J Obstet Gynecol Reprod Biol 2021 Dec 13;267:245-255. Epub 2021 Nov 13.

Department of Gynecology, Guangxi Medical University First Affiliated Hospital, Nanning, Guangxi, China. Electronic address:

Objective: To investigate the incidence of ovarian metastasis in endometrial carcinoma (EC) and analyze its risk factors and provide a theoretical basis for whether retention of the ovary in patients with EC.

Methods: A systematic search using synonyms of 'ovarian cancer' and 'metastasis' was conducted in PubMed, Cochrane database, Embase, Google Scholar, and WOS database. Meta-analysis was performed on 7 included studies, comprising 4281 clinical-stage I-IV EC patients. Studies were assessed using the Newcastle-Ottawa Scale (NOS) criteria. Odds risks (OR) and 95% confidence intervals (CI) were calculated using an inverse variance weighted random-effects model.

Results: The ovarian metastasis risk of EC was significantly higher for patients with myometrial invasion >1/2 (OR = 18.19, 95% CI 5.34 to 61.96 compared to myometrial invasion ≤1/2), any pelvic lymph node invasion (PLNI) (OR = 5.41, 95% CI 2.60-10.97 compared to without PLNI), G3 pathological grade (OR = 2.66, 95%CI 1.35-5.24 compared to G1-G2), non-endometrioid pathological type (OR = 6.46, 95% CI 3.25 to 12.83 compared to endometrioid), lymphatic vascular space invasion (LVSI) (OR = 6.46, 95% CI 3.25 to 12.83 compare to without LVSI), age >45 (OR = 2.01, 95% CI 0.29 to 14.11 compared to age ≤45), and cervical invasion (OR = 4.12, 95% CI 1.87 to 9.08 compared to without cervical invasion).

Conclusion: About 4.95% of EC patients develop ovarian metastasis. Age >45, myometrial invasion >1/2, cervical invasion, PLNI, pathological type, G3 pathological grade, and LVSI were the high-risk factors for ovarian metastasis of EC. Ovarian preservation should be carefully selected for patients with EC, and preoperative and intraoperative evaluations should be entirely performed.
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http://dx.doi.org/10.1016/j.ejogrb.2021.11.016DOI Listing
December 2021

Light-driven bimorph soft actuators: design, fabrication, and properties.

Mater Horiz 2021 03 7;8(3):728-757. Epub 2020 Dec 7.

School of Materials Science and Engineering, Tianjin University, Tianjin 300350, P. R. China.

Soft robots that can move like living organisms and adapt to their surroundings are currently in the limelight from fundamental studies to technological applications, due to their advances in material flexibility, human-friendly interaction, and biological adaptation that surpass conventional rigid machines. Light-fueled smart actuators based on responsive soft materials are considered to be one of the most promising candidates to promote the field of untethered soft robotics, thereby attracting considerable attention amongst materials scientists and microroboticists to investigate photomechanics, photoswitch, bioinspired design, and actuation realization. In this review, we discuss the recent state-of-the-art advances in light-driven bimorph soft actuators, with the focus on bilayer strategy, i.e., integration between photoactive and passive layers within a single material system. Bilayer structures can endow soft actuators with unprecedented features such as ultrasensitivity, programmability, superior compatibility, robustness, and sophistication in controllability. We begin with an explanation about the working principle of bimorph soft actuators and introduction of a synthesis pathway toward light-responsive materials for soft robotics. Then, photothermal and photochemical bimorph soft actuators are sequentially introduced, with an emphasis on the design strategy, actuation performance, underlying mechanism, and emerging applications. Finally, this review is concluded with a perspective on the existing challenges and future opportunities in this nascent research Frontier.
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http://dx.doi.org/10.1039/d0mh01406kDOI Listing
March 2021

HIV-1 Vif suppresses antiviral immunity by targeting STING.

Cell Mol Immunol 2022 01 22;19(1):108-121. Epub 2021 Nov 22.

Department of Immunology, School of Basic Medical Sciences, Shanghai Institute of Infectious Disease and Biosecurity & Shanghai Public Health Clinical Center, Fudan University, Shanghai, 200032, China.

HIV-1 infection-induced cGAS-STING-TBK1-IRF3 signaling activates innate immunity to produce type I interferon (IFN). The HIV-1 nonstructural protein viral infectivity factor (Vif) is essential in HIV-1 replication, as it degrades the host restriction factor APOBEC3G. However, whether and how it regulates the host immune response remains to be determined. In this study, we found that Vif inhibited the production of type I IFN to promote immune evasion. HIV-1 infection induced the activation of the host tyrosine kinase FRK, which subsequently phosphorylated the immunoreceptor tyrosine-based inhibitory motif (ITIM) of Vif and enhanced the interaction between Vif and the cellular tyrosine phosphatase SHP-1 to inhibit type I IFN. Mechanistically, the association of Vif with SHP-1 facilitated SHP-1 recruitment to STING and inhibited the K63-linked ubiquitination of STING at Lys337 by dephosphorylating STING at Tyr162. However, the FRK inhibitor D-65495 counteracted the phosphorylation of Vif to block the immune evasion of HIV-1 and antagonize infection. These findings reveal a previously unknown mechanism through which HIV-1 evades antiviral immunity via the ITIM-containing protein to inhibit the posttranslational modification of STING. These results provide a molecular basis for the development of new therapeutic strategies to treat HIV-1 infection.
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http://dx.doi.org/10.1038/s41423-021-00802-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8752805PMC
January 2022

Match of the Bimaxillary Basal Bone Arches and Its Variations among Individuals.

Scanning 2021 5;2021:9625893. Epub 2021 Nov 5.

Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China.

Introduction: This study is aimed at illustrating the bimaxillary basal bone contours, to clarify the match of the basal bone arches of the upper and lower, especially the posterior segments, including the second molar and retromolar region.

Methods: Based on 100 cone-beam computed tomography (CBCT) images (50 males and 50 females), we obtained 100 pairs of basal bone arches, which were the horizontal inner cortex contours passing the furcation of the first molar paralleled to the lower occlusal plane. The Generalized Procrustes Analysis (GPA) was applied to depict average contours and calculate the ratio and difference width of both upper and lower dental arches in different positions. Variations of the basal bone morphology among individuals were revealed using Principal Component Analysis (PCA).

Results: The width discrepancy occurred at 7-7 segment (male: upper 65.62 mm and lower 68.81 mm and female: upper 62.98 mm and lower 68.38 mm) and the retromolar region (male: upper 64.67 mm and lower 71.96 mm and female: upper 62.34 mm and lower 71.44 mm). The ratio ( = 0.006) and difference value ( = 0.009) of 7-7 segment and the ratio of retromolar region ( = 0.044) differed in genders. Setting 2 mm overjet, the upper basal bone arch was wider than the lower by approximate 2 mm on both sides, except the second molar and retromolar region. According to PCA, the variation of basal bone arches appeared mainly at terminal segments.

Conclusions: For both male and female, the bimaxillary basal bone matched except terminal segments. Mismatch of female bimaxillary posterior basal bone was more pronounced than male. The basal bone arches of male were wider and longer than that of female.
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http://dx.doi.org/10.1155/2021/9625893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8589518PMC
November 2021

Alterations of the Human Lung and Gut Microbiomes in Non-Small Cell Lung Carcinomas and Distant Metastasis.

Microbiol Spectr 2021 12 17;9(3):e0080221. Epub 2021 Nov 17.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Although dysbiosis of the lung and gut microbiota have been associated with NSCLC, their relative contributions are unclear; in addition, their roles in distant metastasis (DM) are still illusive. We recruited in total 121 participants, including 87 newly diagnosed treatment-naive NSCLC patients of various stages and 34 healthy volunteers, and surveyed their fecal and sputum microbiota. We compared the microbial profiles between groups, identified microbial biomarkers, and generated machine learning models for distinguishing healthy individuals from patients with NSCLC and patients of various stages. We found significant perturbations of gut and sputum microbiota in patients with NSCLC and DM. A machine learning model combining both microbiota (combined model) performed better than an individual data set in patient stratification, with the highest area under the curve (AUC) value of 0.896. Sputum and gut microbiota both contributed to the combined model; in most cases, sputum-only models performed similar to the combined models. Several microbial biomarkers were shared by both microbiotas, indicating their similar roles at distinct body sites. Microbial biomarkers of distinct disease stages were mostly shared, suggesting biomarkers for DM could be acquired early. Furthermore, Pseudomonas aeruginosa, a species previously associated with wound infections, was significantly more abundant in brain metastasis, indicating that distinct types of DMs could have different microbes. Our results indicate that alterations of the sputum microbiota have stronger relationships with NSCLC and DM than the gut and strongly support the feasibility of metagenome-based noninvasive disease diagnosis and risk evaluation. (This study has been registered at ClinicalTrials.gov under registration no. NCT03454685). Our survey on gut and sputum microbiota revealed that both were significantly disturbed in non-small cell lung cancer (NSCLC) and associated with distant metastasis (DM) while only the sputum microbiota was associated with non-DM NSCLC. The lung microbiota could therefore have a stronger association with (and thus may contribute more to) disease development than the gut microbiota. Mathematic models using both microbiotas performed better in patient stratification than using individual microbiota. Sputum models, however, performed similar to the combined models, suggesting a convenient, noninvasive diagnostic for NSCLC. Microbial biomarkers of distinct disease stages were mostly shared, suggesting that the same set of microbes were underlying disease progression, and the signals for distant metastasis could be acquired at early stages of the disease. Our results strongly support the feasibility of noninvasive diagnosis of NSCLC, including distant metastasis, are of clinical importance, and should warrant further research on the underlying molecular mechanisms.
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http://dx.doi.org/10.1128/Spectrum.00802-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8597645PMC
December 2021
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