Publications by authors named "Ke Xu"

1,883 Publications

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Activation of the P2X7 receptor in the dental pulp tissue contributes to the pain in rats with acute pulpitis.

Mol Pain 2022 Apr;18:17448069221106844

Department of Oral Anatomy and Physiology, School and Hospital of Stomatology, Zunyi Medical University, Zunyi, China.

Treatment of acute pulpitis (AP) is beneficial for pain relief and pulp regeneration. The purinergic P2X7 receptor activation is responsible for the formation and maintenance of inflammation and pain. This study aims to determine the role of the pulp tissue P2X7 receptor to activate the mechanisms of the AP in rats. The Sprague-Dawley rats were divided into groups, namely, normal, normal saline (NS), and lipopolysaccharide (LPS) groups. Alterations in pain behavior were detected through head-withdrawal thresholds (HWTs), and the pathological changes in pulp tissue were studied through hematoxylin and eosin staining. The expression of the P2X7 receptor in pulp tissue was observed through immunohistochemistry and Western Blotting. The effect of the P2X7 receptor antagonist A-740003 on HWTs was also observed. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the pulp tissue of rats were analyzed through enzyme-linked immunosorbent assay. The HWTs were reduced in the rats with AP. Inflammation is formed but was found more severe in the LPS group than the NS group, and the expression levels of the P2X7 receptors in the NS and LPS groups were higher than in the normal group. The periodontal ligament injection of the A-740003 dose-dependant increases the HWTs in rats with AP. The IL-6 and TNF-α levels in the pulp in the NS and LPS groups were increased but reversed by A-740003 injection. In rats with AP, the expression level of the P2X7 receptor and IL-6/TNF-α release was upregulated. The A-740003 can relieve pain and reduce the inflammation progression in rats with AP.
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http://dx.doi.org/10.1177/17448069221106844DOI Listing
April 2022

Recent Progress in Gas Sensor Based on Nanomaterials.

Authors:
Danyang Lun Ke Xu

Micromachines (Basel) 2022 Jun 10;13(6). Epub 2022 Jun 10.

School of Electrical & Control Engineering, Shenyang Jianzhu University, Shenyang 110168, China.

Nanomaterials-based gas sensors have great potential for substance detection. This paper first outlines the research of gas sensors composed of various dimensional nanomaterials. Secondly, nanomaterials may become the development direction of a new generation of gas sensors due to their high sensing efficiency, good detection capability and high sensitivity. Through their excellent characteristics, gas sensors also show high responsiveness and sensing ability, which also plays an increasingly important role in the field of electronic skin. We also reviewed the physical sensors formed from nanomaterials in terms of the methods used, the characteristics of each type of sensor, and the advantages and contributions of each study. According to the different kinds of signals they sense, we especially reviewed research on gas sensors composed of different nanomaterials. We also reviewed the different mechanisms, research processes, and advantages of the different ways of constituting gas sensors after sensing signals. According to the techniques used in each study, we reviewed the differences and advantages between traditional and modern methods in detail. We compared and analyzed the main characteristics of gas sensors with various dimensions of nanomaterials. Finally, we summarized and proposed the development direction of gas sensors based on various dimensions of nanomaterials.
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http://dx.doi.org/10.3390/mi13060919DOI Listing
June 2022

A Novel Classification Model for Lower-Grade Glioma Patients Based on Pyroptosis-Related Genes.

Brain Sci 2022 May 28;12(6). Epub 2022 May 28.

Clinical Molecular Medicine Testing Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.

Recent studies demonstrated that pyroptosis plays a crucial role in shaping the tumor-immune microenvironment. However, the influence of pyroptosis on lower-grade glioma regarding immunotherapy and targeted therapy is still unknown. This study analyzed the variations of 33 pyroptosis-related genes in lower-grade glioma and normal tissues. Our study found considerable genetic and expression alterations in heterogeneity among lower-grade gliomas and normal brain tissues. There are two pyroptosis phenotypes in lower-grade glioma, and they exhibited differences in cell infiltration characteristics and clinical characters. Then, a PyroScore model using the lasso-cox method was constructed to measure the level of pyroptosis in each patient. PyroScore can refine the lower-grade glioma patients with a stratified prognosis and a distinct tumor immune microenvironment. Pyscore may also be an effective factor in predicting potential therapeutic benefits. In silico analysis showed that patients with a lower PyroScore are expected to be more sensitive to targeted therapy and immunotherapy. These findings may enhance our understanding of pyroptosis in lower-grade glioma and might help optimize risk stratification for the survival and personalized management of lower-grade glioma patients.
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http://dx.doi.org/10.3390/brainsci12060700DOI Listing
May 2022

Branched actin networks are organized for asymmetric force production during clathrin-mediated endocytosis in mammalian cells.

Nat Commun 2022 Jun 22;13(1):3578. Epub 2022 Jun 22.

Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.

Actin assembly facilitates vesicle formation in several trafficking pathways, including clathrin-mediated endocytosis (CME). Interestingly, actin does not assemble at all CME sites in mammalian cells. How actin networks are organized with respect to mammalian CME sites and how assembly forces are harnessed, are not fully understood. Here, branched actin network geometry at CME sites was analyzed using three different advanced imaging approaches. When endocytic dynamics of unperturbed CME sites are compared, sites with actin assembly show a distinct signature, a delay between completion of coat expansion and vesicle scission, indicating that actin assembly occurs preferentially at stalled CME sites. In addition, N-WASP and the Arp2/3 complex are recruited to one side of CME sites, where they are positioned to stimulate asymmetric actin assembly and force production. We propose that actin assembles preferentially at stalled CME sites where it pulls vesicles into the cell asymmetrically, much as a bottle opener pulls off a bottle cap.
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http://dx.doi.org/10.1038/s41467-022-31207-5DOI Listing
June 2022

Gamma knife radiosurgery versus transcatheter arterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombus: a propensity score matching study.

Hepatol Int 2022 Jun 21. Epub 2022 Jun 21.

Department of Oncology and Hematology, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000, China.

Background: The optimal locoregional treatment for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) is unclear. This study aimed to investigate the efficacy of Gamma knife radiosurgery (GKR) versus transcatheter arterial chemoembolization (TACE) in HCC patients with PVTT.

Methods: This retrospective study included 544 HCC patients with PVTT (GKR, 202; TACE, 342). Propensity score matching (PSM) analysis identified 171 matched pairs of patients. The primary endpoint was overall survival (OS).

Results: Before PSM, the GKR group exhibited longer median OS (mOS) than the TACE group (17.2 vs. 8.0 months, p < 0.001). We followed the Cheng's classification for PVTT. In the subgroup analysis, GKR was associated with significantly longer mOS for patients with PVTT II-IV (17.5 vs. 8.7 months, p < 0.001; 17.2 vs. 7.8 months, p = 0.001; 14.5 vs. 6.5 months, p = 0.001, respectively) and comparable OS for patients with PVTT I. After PSM, the GKR group had also a longer mOS than the TACE group (15.8 vs. 10.4 months, p < 0.001). In the subgroup analysis, the GKR group demonstrated superior mOS for patients with PVTT II-IV (all p < 0.05) and comparable OS for patients with PVTT I.

Conclusions: GKR was associated better OS than TACE in HCC patients with PVTT, especially for patients with PVTT II-IV.

Clinical Trials Registration: The study was registered in the Chinese Clinical Trials Registry under the registration number ChiCTR2100051057.
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http://dx.doi.org/10.1007/s12072-022-10339-2DOI Listing
June 2022

The Association Between Smoking and Renal Function in People Over 20 Years Old.

Front Med (Lausanne) 2022 3;9:870278. Epub 2022 Jun 3.

Xiangya School of Medicine, Central South University, Changsha, China.

Background: Many conclusions have been reached in renal function studies in direct smokers.

Aim: This study aimed to determine the relationship between smoking and decreased renal function to ensure that reduced chronic kidney disease incidence can be achieved by limiting smoking, we assessed the relationship between cigarette smoking and renal function.

Methods: We recruited 10,267 people from the National Health and Nutrition Program Testing Survey (NHANES) aged over 20 years from 2013 to 2018 to assess smoking exposure by serum cotinine. We estimated the glomerular filtration rate (eGFR) and used multivariate linear regression models and smooth curve fittings to assess the relationship between smoking and renal function.

Results: We found an inverse relationship between serum cotinine and the eGFR. In a subgroup analysis, we found a non-linear relationship between serum cotinine and the eGFR in different ethnic groups or in different sexes. In a subgroup analysis of sex, we found inflection points between men and women for the relationship between serum cotinine and the eGFR (men 183 ng/ml and 465 ng/ml; women 227 ng/ml and 412 ng/ml). However, in a subgroup analysis by age, we found that serum cotinine showed a clear negative correlation with the eGFR in people aged 20-39 years, but in people older than 40 years, a weak correlation was shown. In stratified analysis by ethnicity, we found significant negative associations in Mexican American and Other Hispanic individuals and weaker associations in Non-Hispanic White and Non-Hispanic Black individuals.

Conclusion: Through the negative correlation between serum cotinine and the eGFR, we can conclude that as the smoking quantity increases, smoking leads to a decrease in renal function. The results of the subgroup analysis indicate that in young people, by advocating smoking cessation early, we can very effectively prevent kidney disease in this population and thus reduce the incidence of chronic kidney disease. Smoking should be included as an independent risk factor for chronic kidney disease.
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http://dx.doi.org/10.3389/fmed.2022.870278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205397PMC
June 2022

Circ_0004712 promotes endometriotic epithelial cell proliferation, migration and invasion by regulating miR-488-3p/ROCK1 axis in vitro.

Reprod Biol 2022 Jun 17;22(3):100667. Epub 2022 Jun 17.

Department of Reproductive Center, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou City, Jiangsu Province, China. Electronic address:

Recent evidence indicates that circular RNAs (circRNAs) play crucial regulatory roles in the pathogenesis and development of endometriosis. Circ_0004712 was found to be differentially expressed in endometriosis. However, the detailed function and mechanism of circ_0004712 in endometriosis are still unclear. Quantitative real-time polymerase chain reaction and Western blot were used for the detection of circ_0004712, miR-488-3p and ROCK1 (Rho Associated Coiled-Coil Containing Protein Kinase 1) levels. In vitro experiments in endometrial endothelial cells were performed by cell counting kit-8, EdU, transwell, wound healing assays, and flow cytometry, respectively. The molecular mechanism of circ_0004712 function was investigated using bioinformatics target predication, dual-luciferase reporter, and RNA immunoprecipitation (RIP) assays. The expression of circ_0004712 was higher in endometriotic endometrial tissues and epithelial cells. Knockdown of circ_0004712 suppressed cell proliferation, migration, invasion, EMT process and induced apoptosis in ectopic endometrial epithelial cells in vitro. Mechanistically, circ_0004712 acted as a ceRNA to sponge miR-488-3p, thus elevating the expression of ROCK1, which was confirmed to be a target of miR-488-3p. Rescue experiments suggested that miR-488-3p inhibition reversed the inhibitory effects of circ_0004712 silencing on cell growth and metastasis. Moreover, miR-488-3p restoration restrained the proliferation and metastasis in ectopic endometrial epithelial cells, which were attenuated by ROCK1 overexpression. Circ_0004712 knockdown suppressed the proliferation and metastasis of ectopic endometrial epithelial cells via miR-488-3p/ROCK1 axis in vitro, suggesting a new insight into the pathogenesis of endometriosis.
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http://dx.doi.org/10.1016/j.repbio.2022.100667DOI Listing
June 2022

Bone-Targeted Nanoparticle Drug Delivery System: An Emerging Strategy for Bone-Related Disease.

Front Pharmacol 2022 31;13:909408. Epub 2022 May 31.

Institute of Translational Medicine, Shanghai University, Shanghai, China.

Targeted delivery by either systemic or local targeting of therapeutics to the bone is an attractive treatment for various bone metabolism diseases such as osteoporosis, osteoarthritis, osteosarcoma, osteomyelitis, etc. To overcome the limitations of direct drug delivery, the combination of bone-targeted agents with nanotechnology has the opportunity to provide a more effective therapeutic approach, where engineered nanoparticles cause the drug to accumulate in the bone, thereby improving efficacy and minimizing side effects. Here, we summarize the current advances in systemic or local bone-targeting approaches and nanosystem applications in bone diseases, which may provide new insights into nanocarrier-delivered drugs for the targeted treatment of bone diseases. We envision that novel drug delivery carriers developed based on nanotechnology will be a potential vehicle for the treatment of currently incurable bone diseases and are expected to be translated into clinical applications.
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http://dx.doi.org/10.3389/fphar.2022.909408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9195145PMC
May 2022

Rapid Spontaneous Total Fusion of Neuropathic Arthropathy of the Wrist After Limited Intercarpal Arthrodesis: A Case Report and Brief Literature Review.

Front Surg 2022 30;9:771896. Epub 2022 May 30.

Department of Hand Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.

Background: Previous reports on the treatment of neuropathic arthropathy of the wrist were generally conservative, with few case reports of treatment with osteoarticular surgery.

Case Presentation: A 25-year-old right-handed male complained of unpainful swelling of the dorsal aspect of his right wrist for 3 years. He was at that time diagnosed with synovitis and radiocarpal arthritis. The patient underwent a partial Four-Corner Arthrodesis and Synoviectomy to preserve motor function. Over the next 2 months, his right wrist also developed painful redness, with progressive swelling and stiffness. Rheumatoid arthritis, tuberculosis arthritis, and infectious diseases were ruled out in this case. Magnetic resonance imaging (MRI) indicated that he had Chiari II syringomyelia so the patient was eventually diagnosed with destructive neuropathic arthropathy (syringomyelia). After 2 months of conservative treatment, the patient's right wrist spontaneously and completely fused and the pain disappeared.

Conclusion: Neuropathic arthropathy of the wrist is a rare but clinically significant disease due to its effect on the function of the active limb. Surgeons should rule out a diagnosis of it when treating patients with wrist swelling and osteoarticular abnormalities, otherwise, limited intercarpal arthrodesis should not be taken as a treatment option. Inappropriate partial surgery is likely to lead to rapid total fusion of neuropathic arthropathy of the wrist.
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http://dx.doi.org/10.3389/fsurg.2022.771896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197156PMC
May 2022

Combination of ribociclib and gemcitabine for the treatment of medulloblastoma.

Mol Cancer Ther 2022 Jun 16. Epub 2022 Jun 16.

St. Jude Children's Research Hospital, Memphis, TN, United States.

Group3 (G3) medulloblastoma (MB) is one of the deadliest forms of the disease for which novel treatment is desperately needed. Here we evaluate ribociclib, a highly selective CDK4/6 inhibitor, with gemcitabine in mouse and human G3MBs. Ribociclib central nervous system (CNS) penetration was assessed by in vivo microdialysis and by immunohistochemistry and gene expression studies and found to be CNS-penetrant. Tumors from mice treated with short term oral ribociclib displayed inhibited RB phosphorylation, downregulated E2F target genes, and decreased proliferation. Survival studies to determine the efficacy of ribociclib and gemcitabine combination were performed on mice intracranially implanted with luciferase labelled mouse and human G3MBs. Treatment of mice with the combination of ribociclib and gemcitabine was well tolerated, slowed tumor progression and metastatic spread, and increased survival. Expression-based gene activity and cell state analysis investigated the effects of the combination after short and long-term treatments. Molecular analysis of treated versus untreated tumors showed a significant decrease in the activity and expression of genes involved in cell cycle progression and DNA damage response, and an increase in the activity and expression of genes implicated in neuronal identity and neuronal differentiation. Our findings in both mouse and human patient-derived orthotopic xenograft models, suggest that ribociclib and gemcitabine combination therapy warrants further investigation as a treatment strategy for children with G3MB.
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http://dx.doi.org/10.1158/1535-7163.MCT-21-0598DOI Listing
June 2022

Correlation between salivary HBD-2 and LL-37 expression levels with blood glucose and periodontal status in patients with type 2 diabetes mellitus.

Am J Transl Res 2022 15;14(5):3286-3291. Epub 2022 May 15.

Department of Stomatology, Cangzhou Central Hospital Hebei, China.

Objective: To examine the correlation between salivary human β defensin-2 (HBD-2) and LL-37 expression levels and blood glucose in relationship to periodontal status in patients with type 2 diabetes mellitus (T2DM).

Methods: The trial is available at: https://clinicaltrials.gov/ with ClinicalTrials.gov Identifier: NCT03512675. A total of 89 patients with T2DM with chronic periodontitis (CP) enrolled in our hospital from January 2020 to December 2020 were selected. According to the degree of glycemic control and CP, the patients were randomly divided into four groups, namely the good glycemic control and mild CP group (n=26), good glycemic control with moderate to severe CP group (n=24), poor glycemic control with mild CP group (n=21), and poor glycemic control with moderate to severe CP group (n=18). The periodontal clinical parameters, blood glucose indicators, and saliva HBD-2 and LL-37 expression levels were determined.

Results: The expression levels of HBD-2 and LL-37 in the saliva of T2DM patients with moderate to severe CP and poor blood sugar control were significantly increased (P<0.05). Saliva HBD-2 and LL-37 levels were positively correlated with probing depth, clinical attachment loss, plaque index, and glycosylated hemoglobin. There was a synergistic interaction between blood glucose, periodontal status, and saliva HBD-2, LL-37 levels (P<0.05).

Conclusion: There is a positively correlated relationship between blood glucose and periodontal status with salivary HBD-2 and LL-37 levels.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9185056PMC
May 2022

Metformin Ameliorates Senescence of Adipose-Derived Mesenchymal Stem Cells and Attenuates Osteoarthritis Progression via the AMPK-Dependent Autophagy Pathway.

Oxid Med Cell Longev 2022 3;2022:4620254. Epub 2022 Jun 3.

Department of Orthopedics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Osteoarthritis (OA) is one of the most serious age-related diseases worldwide that drastically affects the quality of life of patients. Despite advancements in the treatment of arthritis, especially with adipose-derived mesenchymal stem cells (ADSCs), senescence-induced alterations in ADSCs negatively affect the treatment outcomes. This study was aimed at mechanistically exploring whether metformin could ameliorate the senescence of ADSCs and at exploring the effect of metformin-preconditioned ADSCs in an experimental OA mouse model. In this study, an HO-induced mouse ADSC senescent model was established. Cell proliferation, senescence, and autophagy were investigated in vitro. Moreover, the effects of intra-articular injection of metformin-preconditioned ADSCs were investigated in vivo. Metformin could promote autophagy and activate the AMPK/mTOR pathway in ADSCs. The metformin-enhanced autophagy could improve the survival and reduce the senescence of ADSCs. The protective effects of metformin against senescence were partially blocked by 3-methyladenine and compound C. Injection of metformin-preconditioned ADSCs slowed OA progression and reduced OA pain in mice. The results suggest that metformin activates the AMPK/mTOR-dependent autophagy pathway in ADSCs against HO-induced senescence, while metformin-preconditioned ADSCs can potentially inhibit OA progression.
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http://dx.doi.org/10.1155/2022/4620254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9187432PMC
June 2022

The strategy of non-intubated spontaneous ventilation anesthesia for upper tracheal surgery: a retrospective case series study.

Transl Lung Cancer Res 2022 May;11(5):880-889

Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: Upper tracheal surgery is used to treat patients who with tracheal tumors or tracheal stenosis. The non-intubated spontaneous ventilation anesthesia (NSVA) may have advantages over endotracheal intubation and surgical cross-field intubation in upper tracheal surgery. This study aimed to illustrate and assess the feasibility of NSVA strategy for upper tracheal surgery.

Methods: This is a retrospective case series study in which 51 patients (from May 2015 to August 2020) who met the criteria in NSVA strategy were analyzed. Anesthesia was performed using total intravenous anesthesia (TIVA) combined with bilateral superficial cervical plexus block (CPB) or thoracic epidural anesthesia (TEA). Patients received spontaneous ventilation through laryngeal mask airway (LMA) during the surgery. Anesthesia conversion technique was applied to patients who met the anesthesia conversion criteria.

Results: In total, 51 patients met the NSVA criteria and were included in this study. Forty-six out of 51 patients (90%) had TIVA + bilateral superficial CPB and five patients (10%) had TIVA + TEA + CPB. During the airway-opened period, 46 patients had stable spontaneous ventilation. Five patients need anesthesia conversion, two patients had high-frequency ventilation (HFV), and three patients required cross-field intubation. Postoperative complications occurred in seven (14%) patients, no reintubation was needed after surgery. The median postoperative hospital stay was 6.31±4.30 days.

Conclusions: This NSVA strategy includes criteria for patient selection, preoperative assessment, surgical technique, airway management, criteria and technique for anesthesia conversion. The NSVA strategy is a feasible procedure in upper tracheal surgery.
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http://dx.doi.org/10.21037/tlcr-22-302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9186174PMC
May 2022

An enhanced antioxidant strategy of astaxanthin encapsulated in ROS-responsive nanoparticles for combating cisplatin-induced ototoxicity.

J Nanobiotechnology 2022 Jun 10;20(1):268. Epub 2022 Jun 10.

Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Excessive accumulation of reactive oxygen species (ROS) has been documented as the crucial cellular mechanism of cisplatin-induced ototoxicity. However, numerous antioxidants have failed in clinical studies partly due to inefficient drug delivery to the cochlea. A drug delivery system is an attractive strategy to overcome this drawback.

Methods And Results: In the present study, we proposed the combination of antioxidant astaxanthin (ATX) and ROS-responsive/consuming nanoparticles (PPS-NP) to combat cisplatin-induced ototoxicity. ATX-PPS-NP were constructed by the self-assembly of an amphiphilic hyperbranched polyphosphoester containing thioketal units, which scavenged ROS and disintegrate to release the encapsulated ATX. The ROS-sensitivity was confirmed by H nuclear magnetic resonance spectroscopy, transmission electron microscopy and an HO ON/OFF stimulated model. Enhanced release profiles stimulated by HO were verified in artificial perilymph, the HEI-OC1 cell line and guinea pigs. In addition, ATX-PPS-NP efficiently inhibited cisplatin-induced HEI-OC1 cell cytotoxicity and apoptosis compared with ATX or PPS-NP alone, suggesting an enhanced effect of the combination of the natural active compound ATX and ROS-consuming PPS-NP. Moreover, ATX-PPS-NP attenuated outer hair cell losses in cultured organ of Corti. In guinea pigs, NiRe-PPS-NP verified a quick penetration across the round window membrane and ATX-PPS-NP showed protective effect on spiral ganglion neurons, which further attenuated cisplatin-induced moderate hearing loss. Further studies revealed that the protective mechanisms involved decreasing excessive ROS generation, reducing inflammatory chemokine (interleukin-6) release, increasing antioxidant glutathione expression and inhibiting the mitochondrial apoptotic pathway.

Conclusions: Thus, this ROS-responsive nanoparticle encapsulating ATX has favorable potential in the prevention of cisplatin-induced hearing loss.
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http://dx.doi.org/10.1186/s12951-022-01485-8DOI Listing
June 2022

Diminished miR-374c-5p negatively regulates IL (interleukin)-6 in unexplained recurrent spontaneous abortion.

J Mol Med (Berl) 2022 Jul 10;100(7):1043-1056. Epub 2022 Jun 10.

Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.

Unexplained recurrent spontaneous abortion (URSA) is commonly observed, and seriously affects women's reproductive health. Excessive interleukin-6 (IL-6) production has been shown to frequently occur and relate to URSA pathogenesis. In this study, the miRNA expression profile in peripheral blood mononuclear cells (PBMCs) from URSA patients and normal pregnant (NP) women was assessed by miRNA microarray and real-time quantitative reverse-transcription polymerase chain reaction (qPCR). MiRNA target prediction tools and luciferase reporter assay were used to detect direct binding between miRNAs and IL6. Functional study of administering anti-IL-6 neutralizing antibody and miR-374c-5p mimics to an URSA animal model was performed to evaluate embryo resorption rates. In the results, compared with NP women, the expression of IL-6 increased markedly in PBMCs and decidual tissues at both mRNA and protein levels, while miR-374c-5p expression decreased significantly. Prediction software and luciferase reporter assay showed that miR-374c-5p binds with IL6 3'UTR via the complementary bases. Transfection of miR-374c-5p mimics into an in vitro HeLa cell line significantly downregulated the expression of IL-6, while transfection of the miR-374c-5p inhibitor induced an opposite result. In the URSA mouse model, miR-374c-5p overexpression reduced the embryo resorption rate significantly, accompanied with decreased expression of IL-6 in the decidua. To sum up, downregulated miR-374c-5p was involved in the pathogenesis of URSA by enhancing IL-6 expression. Modulation of miR-374c-5p expression may be used to regulate IL-6 production for the treatment of URSA.
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http://dx.doi.org/10.1007/s00109-022-02178-3DOI Listing
July 2022

Mirror Detection With the Visual Chirality Cue.

IEEE Trans Pattern Anal Mach Intell 2022 Jun 10;PP. Epub 2022 Jun 10.

Mirror detection is challenging because the visual appearances of mirrors change depending on those of their surroundings. As existing mirror detection methods are mainly based on extracting contextual contrast and relational similarity between mirror and non-mirror regions, they may fail to identify a mirror region if these assumptions are violated. Inspired by a recent study of applying a CNN to help distinguish whether an image is flipped or not based on the visual chirality property, in this paper, we rethink this image-level visual chirality property and reformulate it as a learnable pixel level cue for mirror detection. Specifically, we first propose a novel flipping-convolution-flipping (FCF) transformation to model visual chirality as learnable commutative residual. We then propose a novel visual chirality embedding (VCE) module to exploit this commutative residual in multi-scale feature maps, to embed the visual chirality features into our mirror detection model. Besides, we also propose a visual chirality-guided edge detection (CED) module to integrate the visual chirality features with contextual features for detection refinement. Extensive experiments show that the proposed method outperforms state-of-the-art methods on three benchmark datasets.
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http://dx.doi.org/10.1109/TPAMI.2022.3181030DOI Listing
June 2022

Hypothalamic-related neural mechanism in lifelong premature ejaculation and trends following selective serotonin reuptake inhibitor administration.

CNS Neurosci Ther 2022 Jun 10. Epub 2022 Jun 10.

Life Science Research Center, School of Life Science and Technology, Xidian University, Shaanxi, China.

Lifelong premature ejaculation patients had altered structural and functional parameters of the hypothalamus compared with healthy controls. The patients showed increased hypothalamus-related functional connectivity in several regions one hour after dapoxetine administration. The changing trends of the brain functional connectivity after dapoxetine administration possibly provided important information about the selective serotonin reuptake inhibitor effects on the functional neural system.
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http://dx.doi.org/10.1111/cns.13882DOI Listing
June 2022

Crystallography-Guided Optimizations of the Keap1-Nrf2 Inhibitors on the Solvent Exposed Region: From Symmetric to Asymmetric Naphthalenesulfonamides.

J Med Chem 2022 Jun 10;65(12):8289-8302. Epub 2022 Jun 10.

School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China.

Directly inhibiting the Keap1-Nrf2 protein-protein interaction has been investigated as a promising strategy to activate Nrf2 for anti-inflammation. We previously reported a naphthalensulfonamide Keap1-Nrf2 inhibitor , but have not determined the exact binding mode with Keap1. This symmetric naphthalenesulfonamide compound has relatively low solubility. Herein, we first determined a crystal complex (resolution: 2.3 Å) of human Keap1 Kelch domain with . Further optimizations on the solvent exposed region obtained asymmetric naphthalenesulfonamides and three crystal structures of Keap1 in complex with designed compounds. Among them, the asymmetric piperazinyl-naphthalenesulfonamide with better aqueous solubility showed the best value of 0.21 μM to block the interaction. The productions of ROS and NO and the expression of TNF-α were inhibited by in the in vitro model. This compound could relieve inflammations by significantly increasing the Nrf2 nuclear translocation in the LPS-induced ALI model with promising pharmacokinetic properties.
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http://dx.doi.org/10.1021/acs.jmedchem.2c00170DOI Listing
June 2022

Precision Measurement Method of Large Shaft Diameter Based on Dual Camera System.

Sensors (Basel) 2022 May 24;22(11). Epub 2022 May 24.

Collaborative Innovation Center of Steel Technology, University of Science and Technology Beijing, Beijing 100083, China.

At present, there is a problem that the measurement accuracy and measurement range cannot be balanced in the measurement of shaft diameter by the machine vision method. In this paper, we propose a large-scale shaft diameter precision measurement method based on a dual camera measurement system. The unified world coordinate system of the two cameras is established by analyzing the dual camera imaging model and obtaining the measurement formula. In order to verify the validity of the proposed method, two black blocks in the calibration plate with a known center distance of 100 mm were measured. The mean value was 100.001 mm and the standard deviation was 0.00039 in 10 measurements. Finally, the proposed system was applied to the diameter measurement of a complexed crankshaft. The mean μ95 values of CMM and the proposed method were ±1.02 μm and ±1.07 μm, respectively, indicating that the measurement accuracy of the proposed method is roughly equal to the CMM.
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http://dx.doi.org/10.3390/s22113982DOI Listing
May 2022

Clinical characteristics and risk factors predictive of pulmonary embolism complicated in bronchiectasis patients: a retrospective study.

BMC Pulm Med 2022 Jun 9;22(1):225. Epub 2022 Jun 9.

Department of Infectious Disease, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.

Objective: Pulmonary embolism (PE) is a rare complication in bronchiectasis (BE) patients associated with a high rate of mortality and morbidity. However, data regarding bronchiectasis patients complicated with PE are limited. Early diagnosis of PE in bronchiectasis patients can improve the prognosis, this study aimed to investigate the clinical features and potential risk factors for early diagnosis of PE in bronchiectasis patients.

Methods: Data of Patients were collected from Tongji Hospital of Tongji University of China. Bronchiectasis patients complicated with pulmonary embolism were named as BE/PE group (n = 63), as well as contemporaneous aged- and sex-matched bronchiectasis patients without pulmonary embolism named as BE group (n = 189), at a ratio of 1:3(cases to controls). Clinical parameters and risk factors were analyzed.

Results: Univariate analysis shows that long-term bed rest, chronic lung disease, autoimmune disease, peripheral artery disease (PAD), tuberculosis history, dyspnea, blood homocysteine, CD4/CD8 ratio, or SIQIIITIII syndrome were closely correlated with the incidence of PE in the bronchiectasis patients (p < 0.05). Multivariate logistic regression analysis of significant variables showed that CD4/CD8 ratio (OR 1.409, 95% CI 1.045-1.901) and autoimmune disease (OR 0.264, 95% CI 0.133-0.524) are independent risk factors for BE/PE patients, compared with the BE patients. 53 out of 189 (28.0%) BE patients had hemoptysis, and 15 out of 63 (23.8%) BE/PE patients had hemoptysis (p > 0.05).

Conclusions: The coexistence of pulmonary embolism and bronchiectasis are rarely encountered and easily to be ignored. Early identification of the clinical characteristic and potential risk factors of pulmonary embolism in bronchiectasis patients may help optimize the treatment strategies.
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http://dx.doi.org/10.1186/s12890-022-02016-9DOI Listing
June 2022

Association of Sex Hormones and Sex Hormone-Binding Globulin Levels With Bone Mineral Density in Adolescents Aged 12-19 Years.

Front Endocrinol (Lausanne) 2022 20;13:891217. Epub 2022 May 20.

Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China.

Background: Sex hormones are recognized to play a significant role in increasing bone mineral density (BMD) and promoting bone maturation during adolescence. The purpose of our study was to use a database with large population data to evaluate the association of BMD with sex hormones (including testosterone and estradiol) and sex hormone-binding globulin (SHBG) in adolescent boys and girls aged 12-19 years.

Methods: The data for our study were taken from the National Health and Nutrition Examination Survey 2013-2016, and we used weighted multiple linear regression models to assess the relationship between testosterone, estradiol, and SHBG and total BMD. We use weighted generalized additive models and smooth curve fitting to discover underlying nonlinear relationships.

Results: A total of 1648 teenagers (853 boys, 795 girls) were selected for the final analysis. In boys, testosterone and estradiol levels were positively associated with total BMD, whereas SHBG levels were negatively associated with total BMD after adjusting for covariates [P < 0.05; 95% confidence interval (CI)]. In addition, there was a point between estradiol and total BMD, after which the positive correlation between estradiol and total BMD was relatively insignificant in boys. In girls, there was a positive association between estradiol and total BMD (P < 0.05; 95% CI), but there was no significant association between the testosterone (β 0.0004; 95% CI -0.0001 to 0.0008) or SHBG (β -0.0001; 95% CI -0.0002 to 0.0001) levels and total BMD. We also found an inverted U-shaped association between testosterone and total BMD with the inflection point at 25.4 ng/dL of testosterone.

Conclusions: We found differences in the association of sex hormones with total BMD in boys and girls. Based on our findings, an appropriate increase in serum testosterone levels may be beneficial for skeletal development in girls because of the inverted U-shaped relationship (with the inflection point at 25.4 ng/dL of testosterone), and a high testosterone level might be detrimental to BMD. Furthermore, keeping estradiol levels below a certain level in boys (24.3 pg/mL) may be considered.
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http://dx.doi.org/10.3389/fendo.2022.891217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9163352PMC
June 2022

Immunogenicity and safety of NVSI-06-07 as a heterologous booster after priming with BBIBP-CorV: a phase 2 trial.

Signal Transduct Target Ther 2022 Jun 6;7(1):172. Epub 2022 Jun 6.

Lanzhou Institute of Biological Products Company Limited, Lanzhou, China.

The increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccination. We conducted a randomised, double-blinded, controlled, phase 2 trial to assess the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated COVID-19 vaccine (BBIBP-CorV) followed by a recombinant protein-based vaccine (NVSI-06-07), using homologous boost with BBIBP-CorV as control. Three groups of healthy adults (600 individuals per group) who had completed two-dose BBIBP-CorV vaccinations 1-3 months, 4-6 months and ≥6 months earlier, respectively, were randomly assigned in a 1:1 ratio to receive either NVSI-06-07 or BBIBP-CorV boost. Immunogenicity assays showed that in NVSI-06-07 groups, neutralizing antibody geometric mean titers (GMTs) against the prototype SARS-CoV-2 increased by 21.01-63.85 folds on day 28 after vaccination, whereas only 4.20-16.78 folds of increases were observed in control groups. For Omicron variant, the neutralizing antibody GMT elicited by homologous boost was 37.91 on day 14, however, a significantly higher neutralizing GMT of 292.53 was induced by heterologous booster. Similar results were obtained for other SARS-CoV-2 variants of concerns (VOCs), including Alpha, Beta and Delta. Both heterologous and homologous boosters have a good safety profile. Local and systemic adverse reactions were absent, mild or moderate in most participants, and the overall safety was quite similar between two booster schemes. Our findings indicated that NVSI-06-07 is safe and immunogenic as a heterologous booster in BBIBP-CorV recipients and was immunogenically superior to the homologous booster against not only SARS-CoV-2 prototype strain but also VOCs, including Omicron.
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http://dx.doi.org/10.1038/s41392-022-00984-2DOI Listing
June 2022

Research status and future prospects of extracellular vesicles in primary Sjögren's syndrome.

Stem Cell Res Ther 2022 Jun 3;13(1):230. Epub 2022 Jun 3.

Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China.

Primary Sjögren's syndrome (pSS) is a diffuse connective tissue disease characterized by the invasion of exocrine glands such as lacrimal and salivary glands, abnormal proliferation of T and B lymphocytes, and infiltration of tissue lymphocytes. With the development of modern medicine, although research on the pathogenesis, diagnosis, and treatment of pSS has made significant progress, its pathogenesis has not been fully understood. Meanwhile, in the era of individualized treatment, it remains essential to further explore early diagnosis and treatment methods. Exosomes, small vesicles containing proteins and nucleic acids, are a subtype of extracellular vesicles secreted by various cells and present in various body fluids. Exosomes contribute to a variety of biological functions, including intercellular signal transduction and pathophysiological processes, and may play a role in immune tolerance. Therefore, exosomes are key to understanding the pathogenesis of diseases. Exosomes can also be used as a therapeutic tool for pSS because of their biodegradability, low immunogenicity and toxicity, and the ability to bypass the blood-brain barrier, implying the prospect of a broad application in the context of pSS. Here, we systematically review the isolation, identification, tracing, and mode of action of extracellular vesicles, especially exosomes, as well as the research progress in the pathogenesis, diagnosis, and treatment of pSS.
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http://dx.doi.org/10.1186/s13287-022-02912-1DOI Listing
June 2022

Phenotype-Based Genetic Analysis Reveals Missing Heritability of ABCA4-Related Retinopathy: Deep Intronic Variants and Copy Number Variations.

Invest Ophthalmol Vis Sci 2022 06;63(6)

Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing, China.

Purpose: To identify the missing heritability of ABCA4-related retinopathy in a Chinese cohort.

Methods: We recruited 33 unrelated patients with ABCA4-related retinopathy carrying a monoallelic variant in ABCA4. All patients underwent ophthalmic examinations. Next-generation sequencing of the whole ABCA4 sequence, including coding and noncoding regions, was performed to detect deep intronic variants (DIVs) and copy number variations (CNVs).

Results: We identified eight missing pathogenic ABCA4 variants in 60.6% of the patients (20/33), which comprised five DIVs and three CNVs. The five DIVs, including four novel (c.1555-816T>G, c.2919-169T>G, c.2919-884G>T, and c.5461-1321A>G) and one reported (c.4539+1100A>G), accounted for the missing alleles in 51.5% of the patients. Minigene assays showed that four novel DIVs activated cryptic splice sites leading to the insertions of pseudoexons. The three novel CNVs consisted of one gross deletion of 1273 bp (exon 2) and two gross duplications covering 25.2 kb (exons 28-43) and 9.4 kb (exons 38-44). The microhomology domains were identified at the breakpoints and revealed the potential mechanisms of CNV formation.

Conclusions: DIVs and CNVs explained approximately two-thirds of the unresolved Chinese cases with ABCA4-related retinopathy. Combining results from phenotypic-directed screening, targeting the whole ABCA4 sequencing and in silico tools can help to identify the missing heritability.
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http://dx.doi.org/10.1167/iovs.63.6.5DOI Listing
June 2022

The impact of COVID-19 on autologous stem cell transplantation in multiple myeloma: A single-centre, qualitative evaluation study.

Support Care Cancer 2022 Jun 3. Epub 2022 Jun 3.

Department of Behavioural Science and Health, University College London, 1-19 Torrington Place, London, WC1E 7HB, UK.

Autologous stem cell transplantation (ASCT) is standard of care in biologically fit, newly diagnosed multiple myeloma (MM) patients, offering better therapeutic outcomes and improved quality of life (QoL). However, with the UK's 1st national lockdown on 23/03/2020, several guidelines recommended deferring ASCT due to risks of infection, with resource limitations forcing some units to suspend ASCT entirely. Such changes to patients' treatment plans inevitably altered their lived experience during these uncertain times with expected impact on QoL. We conducted a qualitative study using semi-structured interviews to gain insight into MM patients' understanding of their disease, initial therapy and ASCT, and their response to therapy changes. A clinical snapshot of how COVID-19 affected the MM ASCT service in a single UK institution is also provided, including changes to chemotherapy treatment plans, timing, and prioritisation of ASCT. Framework analysis identified 6 overarching themes: (1) beliefs about ASCT, (2) perceptions of information provided about MM and ASCT, (3) high levels of fear and anxiety due to COVID-19, (4) feelings about ASCT disruption or delay due to COVID-19, (5) perceptions of care, and (6) importance of social support. Example subthemes were beliefs that ASCT would provide a long-remission/best chance of normality including freedom from chemotherapy and associated side-effects, disappointment, and devastation at COVID-related treatment delays (despite high anxiety about infection) and exceptionally high levels of trust in the transplant team. Such insights will help us adjust our service and counselling approaches to be more in tune with patients' priorities and expectations.
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http://dx.doi.org/10.1007/s00520-022-07173-5DOI Listing
June 2022

Correction to "Long-Range Orbital Hybridization in Remote Epitaxy: The Nucleation Mechanism of GaN on Different Substrates Single-Layer Graphene".

ACS Appl Mater Interfaces 2022 Jun 2. Epub 2022 Jun 2.

Suzhou Institute of Nano-Tech and Nano-Bionics (SINANO), Chinese Academy of Sciences (CAS), Suzhou 215123, People's Republic of China.

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http://dx.doi.org/10.1021/acsami.2c08816DOI Listing
June 2022

Comparative analysis of the gut microbiota composition between knee osteoarthritis and Kashin-Beck disease in Northwest China.

Arthritis Res Ther 2022 May 30;24(1):129. Epub 2022 May 30.

School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, Shaanxi, 710061, People's Republic of China.

Background: Osteoarthritis (OA) and Kashin-Beck disease (KBD) both are two severe osteochondral disorders. In this study, we aimed to compare the gut microbiota structure between OA and KBD patients.

Methods: Fecal samples collected from OA and KBD patients were used to characterize the gut microbiota using 16S rDNA gene sequencing. To identify whether gut microbial changes at the species level are associated with the genes or functions of the gut bacteria between OA and KBD groups, metagenomic sequencing of fecal samples from OA and KBD subjects was performed.

Results: The OA group was characterized by elevated Epsilonbacteraeota and Firmicutes levels. A total of 52 genera were identified to be significantly differentially abundant between the two groups. The genera Raoultella, Citrobacter, Flavonifractor, g__Lachnospiraceae_UCG-004, and Burkholderia-Caballeronia-Paraburkholderia were more abundant in the OA group. The KBD group was characterized by higher Prevotella_9, Lactobacillus, Coprococcus_2, Senegalimassilia, and Holdemanella. The metagenomic sequencing showed that the Subdoligranulum_sp._APC924/74, Streptococcus_parasanguinis, and Streptococcus_salivarius were significantly increased in abundance in the OA group compared to those in the KBD group, and the species Prevotella_copri, Prevotella_sp._CAG:386, and Prevotella_stercorea were significantly decreased in abundance in the OA group compared to those in the KBD group by using metagenomic sequencing.

Conclusion: Our study provides a comprehensive landscape of the gut microbiota between OA and KBD patients and provides clues for better understanding the mechanisms underlying the pathogenesis of OA and KBD.
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http://dx.doi.org/10.1186/s13075-022-02819-5DOI Listing
May 2022

B-Cell-Epitope-Based Fluorescent Quantum Dot Biosensors for SARS-CoV-2 Enable Highly Sensitive COVID-19 Antibody Detection.

Viruses 2022 05 12;14(5). Epub 2022 May 12.

State Key Laboratory of Virology, Institute for Vaccine Research, College of Life Sciences, Wuhan University, Wuhan 430072, China.

A new antibody diagnostic assay with more rapid and robust properties is demanded to quantitatively evaluate anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity in a large population. Here, we developed a nanometer-scale fluorescent biosensor system consisting of CdSe-ZnS quantum dots (QDs) coupled with the highly sensitive B-cell epitopes of SARS-CoV-2 that could remarkably identify the corresponding antibody with a detection limit of 100 pM. Intriguingly, we found that fluorescence quenching of QDs was stimulated more obviously when coupled with peptides than the corresponding proteins, indicating that the energy transfer between QDs and peptides was more effective. Compared to the traditional enzyme-linked immunosorbent assay (ELISA), the B-cell-epitope-based QD-biosensor could robustly distinguish coronavirus disease 2019 (COVID-19) antibody-positive patients from uninfected individuals with a higher sensitivity (92.3-98.1% positive rates by QD-biosensor vs. 78.3-83.1% positive rates by ELISAs in 207 COVID-19 patients' sera) in a more rapid (5 min) and labor-saving manner. Taken together, the 'QD-peptides' biosensor provided a novel real-time, quantitative, and high-throughput method for clinical diagnosis and home-use tests.
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http://dx.doi.org/10.3390/v14051031DOI Listing
May 2022

A Broad Antiviral Strategy: Inhibitors of Human DHODH Pave the Way for Host-Targeting Antivirals against Emerging and Re-Emerging Viruses.

Viruses 2022 04 28;14(5). Epub 2022 Apr 28.

State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.

New strategies to rapidly develop broad-spectrum antiviral therapies are urgently required for emerging and re-emerging viruses. Host-targeting antivirals (HTAs) that target the universal host factors necessary for viral replication are the most promising approach, with broad-spectrum, foresighted function, and low resistance. We and others recently identified that host dihydroorotate dehydrogenase (DHODH) is one of the universal host factors essential for the replication of many acute-infectious viruses. DHODH is a rate-limiting enzyme catalyzing the fourth step in pyrimidine synthesis. Therefore, it has also been developed as a therapeutic target for many diseases relying on cellular pyrimidine resources, such as cancers, autoimmune diseases, and viral or bacterial infections. Significantly, the successful use of DHODH inhibitors (DHODHi) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection further supports the application prospects. This review focuses on the advantages of HTAs and the antiviral effects of DHODHi with clinical applications. The multiple functions of DHODHi in inhibiting viral replication, stimulating ISGs expression, and suppressing cytokine storms make DHODHi a potent strategy against viral infection.
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http://dx.doi.org/10.3390/v14050928DOI Listing
April 2022

Progress of Research on the Application of Nanoelectronic Smelling in the Field of Food.

Micromachines (Basel) 2022 May 18;13(5). Epub 2022 May 18.

School of Electrical & Control Engineering, Shenyang Jianzhu University, Shenyang 110168, China.

In the past 20 years, the development of an artificial olfactory system has made great progress and improvements. In recent years, as a new type of sensor, nanoelectronic smelling has been widely used in the food and drug industry because of its advantages of accurate sensitivity and good selectivity. This paper reviews the latest applications and progress of nanoelectronic smelling in animal-, plant-, and microbial-based foods. This includes an analysis of the status of nanoelectronic smelling in animal-based foods, an analysis of its harmful composition in plant-based foods, and an analysis of the microorganism quantity in microbial-based foods. We also conduct a flavor component analysis and an assessment of the advantages of nanoelectronic smelling. On this basis, the principles and structures of nanoelectronic smelling are also analyzed. Finally, the limitations and challenges of nanoelectronic smelling are summarized, and the future development of nanoelectronic smelling is proposed.
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http://dx.doi.org/10.3390/mi13050789DOI Listing
May 2022
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