Publications by authors named "Kai Zheng"

583 Publications

Three-dimensional laser scanner as a new tool for measuring lower limb volume in patients with chronic venous diseases.

J Vasc Surg Venous Lymphat Disord 2022 Aug 5. Epub 2022 Aug 5.

Department of Vascular Surgery, Beijing Chaoyang Hospital, Capital Medical University, No.8 Gongti South Road, Beijing 100020, China; School of Integrated Circuits, Tsinghua University, Beijing 100084, China. Electronic address:

Objective: Measurement of lower limb volume in patients with chronic venous disease (CVD) is necessary for assessing severity at the time of diagnosis and evaluating response to therapy administered. Existing methods have some limitations in clinical application and accuracy. The study aimed to investigate the reliability and validity of a three-dimensional laser scanner (3DLS) in measuring the lower limb volume of patients with CVD.

Method: A total of 30 patients with CVD (mean age, 55.6±8.07 years, mean body mass index, 24.61±1.87) were recruited in a vascular surgery clinic. The lower limb volumes of all participants were measured using 3DLS and circumferential method (CM). Statistical analysis was conducted to compare the 3DLS and CM.

Results: There was a strong correlation between the CM and 3DLS method (r=0.9065). The 3DLS had a high intra- and inter-operator reliability. The Bland-Altman plot showed satisfactory agreement between the two methods. The 3DLS demonstrated greater bilateral limb differences than CM.

Conclusions: There was a satisfactory agreement between the two investigated methods. The 3DLS method was confirmed to be accurate, repeatable, and rapid in measuring the lower limb volume in patients with CVD, and was therefore suitable for clinical environments.
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http://dx.doi.org/10.1016/j.jvsv.2022.06.010DOI Listing
August 2022

Preoperative Body Composition Combined with Tumor Metabolism Analysis by PET/CT Is Associated with Disease-Free Survival in Patients with NSCLC.

Contrast Media Mol Imaging 2022 13;2022:7429319. Epub 2022 Jul 13.

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

Objective: To evaluate the relationship between preoperative primary tumor metabolism and body composition in patients with NSCLC and analyze their effects on DFS.

Method: A retrospective study was conducted on 154 patients with NSCLC. All patients were scanned by baseline 18F-FDG PET/CT. SUVmax (maximum standard uptake value) of primary tumor, liver SUVmean (mean standard uptake value), and spleen SUVmean were measured by AW workstation. The skeletal muscle area (SMA), skeletal muscle mass index (SMI), skeletal muscle radiation density (SMD), visceral fat area (VFA), visceral adipose tissue index (VATI), and skeletal muscle visceral fat ratio (SVR) were measured by ImageJ software. Kaplan-Meier survival analysis was used to evaluate the impact of the above parameters on DFS.

Results: Compared with the low SUVmax group of primary tumors, the mean values of SMA, VFA, and VATI in the high SUVmax group were significantly higher. In addition, there were obvious differences in histopathological type, pathological differentiation, AJCC stage, and T stage between the two groups. Univariate analysis of DFS showed that VFA, VATI, pathological differentiation, tumor SUVmax, AJCC stage, tumor T stage, and N stage all affected the DFS of patients except for the parameters reflecting skeletal muscle content. Multivariate regression analysis showed that only VFA and SUVmax were associated with DFS. Kaplan-Meier survival analysis showed that high SUVmax, low VFA, high T stage, and high N stage were related to the decrease of DFS.

Conclusion: :Preoperative F-FDG PET/CT could comprehensively evaluate the primary tumor SUVmax, skeletal muscle, and visceral fat in patients with NSCLC. The combination of primary tumor SUVmax and visceral fat area can well evaluate the prognosis of patients with NSCLC.
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http://dx.doi.org/10.1155/2022/7429319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300276PMC
August 2022

Successful limb salvage in progressive proximal tibia osteosarcoma following denosumab chemotherapy: A case report.

Medicine (Baltimore) 2022 Jul 29;101(30):e29812. Epub 2022 Jul 29.

Department of Orthopedics, The 960th Hospital of the People's Liberation Army, Jinan, Shandong, China.

Rationale: Osteosarcoma (OS) is a primary malignant bone tumor that originates in the mesenchymal tissue. It is the most common type of pleomorphic tumor occurring in children and adolescents. Currently, there is no established systematic treatment for OS that progresses during standard preoperative chemotherapy.

Patient Concerns And Diagnoses: We describe a 14-year-old male patient with a 4-month history of pain in the upper right leg. Based on the results of percutaneous biopsy, a diagnosis of OS was made. After admission, the patient was treated with first-line chemotherapy agents. After a single course of treatment, the tumor progressed locally and no limb salvage was feasible.

Interventions And Outcomes: Intervention with denosumab combined with chemotherapy led to a significant reduction in tumor volume and ossification of soft tissue, which successfully resulted in limb salvage rather than amputation. The patient showed no evidence of recurrent or distant metastasis at 6-month follow-up.

Lessons: Treatment with receptor activator of nuclear factor-ĸB ligand inhibitor denosumab combined with standard chemotherapy is effective for advanced OS progressing after chemotherapy. We recommend denosumab therapy for successful limb salvage in patients with high-grade OS associated with osteolytic bone destruction and refractory to preoperative neoadjuvant chemotherapy.
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http://dx.doi.org/10.1097/MD.0000000000029812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9333532PMC
July 2022

A Dramatic Response to Toripalimab With Chemotherapy and Antiangiogenic Agent Followed by Surgery in a Stage IIIB Lung Adenocarcinoma Patient With an Uncommon Mutation: A Case Report.

Front Oncol 2022 11;12:915628. Epub 2022 Jul 11.

Department of Cardiothoracic Surgery, Tianjin Medical University General Hospital, Tianjin, China.

Lung cancer patients with high programmed cell death-ligand 1 (PD-L1) expression in tumor cells and () mutations are rare, but there is no clinical standard for which treatment such patients should receive. Here, we report a 52-year-old male smoker who was diagnosed with stage IIIB lung adenocarcinoma. A rare G719A mutation was detected in the lymph node samples by next-generation sequencing (NGS), and a high PD-L1 expression was found by immunohistochemistry (IHC). After 10 cycles of induction therapy (toripalimab plus pemetrexed plus nedaplatin plus apatinib), surgery was successfully performed, followed by 2 cycles of consolidation therapy (toripalimab plus pemetrexed) and 4 cycles of maintenance therapy (toripalimab). A progression-free survival (PFS) of 7 months was achieved. In this case, we showed that the programmed cell death protein 1 (PD-1) inhibitor toripalimab plus chemotherapy and apatinib was effective and tolerable in a locally advanced -mutant non-small cell lung cancer (NSCLC) patient with a positive PD-L1 expression.
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http://dx.doi.org/10.3389/fonc.2022.915628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309724PMC
July 2022

Impact of Copper-Doped Mesoporous Bioactive Glass Nanospheres on the Polymerisation Kinetics and Shrinkage Stress of Dental Resin Composites.

Int J Mol Sci 2022 Jul 25;23(15). Epub 2022 Jul 25.

Department of Materials Science and Engineering, Institute of Biomaterials, University of Erlangen-Nuremberg, 91058 Erlangen, Germany.

We embedded copper-doped mesoporous bioactive glass nanospheres (Cu-MBGN) with antibacterial and ion-releasing properties into experimental dental composites and investigated the effect of Cu-MBGN on the polymerisation properties. We prepared seven composites with a BisGMA/TEGDMA (60/40) matrix and 65 wt.% total filler content, added Cu-MBGN or a combination of Cu-MBGN and silanised silica to the silanised barium glass base, and examined nine parameters: light transmittance, degree of conversion (DC), maximum polymerisation rate (R), time to reach R, linear shrinkage, shrinkage stress (PSS), maximum PSS rate, time to reach maximum PSS rate, and depth of cure. Cu-MBGN without silica accelerated polymerisation, reduced light transmission, and had the highest DC (58.8 ± 0.9%) and R (9.8 ± 0.2%/s), but lower shrinkage (3 ± 0.05%) and similar PSS (0.89 ± 0.07 MPa) versus the inert reference (0.83 ± 0.13 MPa). Combined Cu-MBGN and silica slowed the R and achieved a similar DC but resulted in higher shrinkage. However, using a combined 5 wt.% Cu-MBGN and silica, the PSS resembled that of the inert reference. The synergistic action of 5 wt.% Cu-MBGN and silanised silica in combination with silanised barium glass resulted in a material with the highest likelihood for dental applications in future.
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http://dx.doi.org/10.3390/ijms23158195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332616PMC
July 2022

Analysis of transcriptome data and quantitative trait loci enables identification of candidate genes responsible for fiber strength in Gossypium barbadense.

G3 (Bethesda) 2022 Jul 26. Epub 2022 Jul 26.

College of Agronomy, Xinjiang Agricultural University, Urumqi, Xinjiang, China, 830052.

Gossypium barbadense possesses a superior fiber quality because of its fiber length and strength. An in-depth analysis of the underlying genetic mechanism could aid in filling the gap in research regarding fiber strength and could provide helpful information for G. barbadense breeding. Three quantitative trait loci related to fiber strength were identified from a G. barbadense recombinant inbred line (PimaS-7 × 5917) for further analysis. RNA sequencing was performed in the fiber tissues of PimaS-7 × 5917 0-35 days post-anthesis. Four specific modules closely related to the secondary wall-thickening stage were obtained using weighted gene co-expression network analysis. In total, 55 genes were identified as differentially expressed from four specific modules. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes were used for enrichment analysis, and Gbar_D11G032910, Gbar_D08G020540, Gbar_D08G013370, Gbar_D11G033670 and Gbar_D11G029020 were found to regulate fiber strength by playing a role in the composition of structural constituents of cytoskeleton and microtubules during fiber development. qRT-PCR results confirmed the accuracy of the transcriptome data. This study provides a quick strategy for exploring candidate genes and provides new insights for improving fiber strength in cotton.
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http://dx.doi.org/10.1093/g3journal/jkac167DOI Listing
July 2022

Horizon of exosome-mediated bone tissue regeneration: The all-rounder role in biomaterial engineering.

Mater Today Bio 2022 Dec 11;16:100355. Epub 2022 Jul 11.

Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu, China.

Bone injury repair has always been a tricky problem in clinic, the recent emergence of bone tissue engineering provides a new direction for the repair of bone injury. However, some bone tissue processes fail to achieve satisfactory results mainly due to insufficient vascularization or cellular immune rejection. Exosomes with the ability of vesicle-mediated intercellular signal transmission have gained worldwide attention and can achieve cell-free therapy. Exosomes are small vesicles that are secreted by cells, which contain genetic material, lipids, proteins and other substances. It has been found to play the function of material exchange between cells. It is widely used in bone tissue engineering to achieve cell-free therapy because it not only does not produce some immune rejection like cells, but also can play a cell-like function. Exosomes from different sources can bind to scaffolds in various ways and affect osteoblast, angioblast, and macrophage polarization to promote bone regeneration. This article reviews the recent research progress of exosome-loaded tissue engineering, focusing on the mechanism of exosomes from different sources and the application of exosome-loaded scaffolds in promoting bone regeneration. Finally, the existing deficiencies and challenges, future development directions and prospects are summarized.
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http://dx.doi.org/10.1016/j.mtbio.2022.100355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304878PMC
December 2022

Microglial mitophagy integrates the microbiota-gut-brain axis to restrain neuroinflammation during neurotropic herpesvirus infection.

Autophagy 2022 Jul 23:1-3. Epub 2022 Jul 23.

School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, Guangdong, China.

Herpes simplex encephalitis (HSE), mainly caused by herpes simplex virus type 1 (HSV-1), is a severe central nervous system disease commonly followed by cognitive impairment, behavioral changes, and focal neurological signs. Although increasing evidence implicates the central role of microglia in HSE progression, the intrinsic restrictors or the acquired environmental factors that balance the beneficial or detrimental immune responses in microglia remain unclear. In a recent study, we find that a gut microbial metabolite activates mitophagy to regulate microglia-mediated neuroinflammation and to mitigate HSE progression. HSV-1 neurotropic infection causes gut microbiota dysbiosis and microglial antiviral immune response, whereas depletion of gut microbiota by oral antibiotics treatment further results in hyperactivated microglia and exacerbated HSE pathology. Notably, exogenous administration of nicotinamide n-oxide (NAMO), an oxidative product of nicotinamide mainly produced by intestinal neomycin-sensitive bacteria, especially Lactobacillus gasseri and Lactobacillus reuteri, can significantly suppress HSE progression. Mechanistically, HSV-1 infection causes mitochondrial dysfunction and impairs mitophagy to activate microglia and promote proinflammatory cytokine production, whereas NAMO restores NAD+-dependent mitophagy to restrain microglial over-activation and to prevent HSV-1 early infection in neuronal cells. This work reveals a novel function of gut microbial metabolites as intrinsic regulators of microglia homeostasis and neuroinflammation via mitophagy. AD: Alzheimer disease; ABX: antibiotics; HSE: herpes simplex encephalitis; HSV-1: herpes simplex virus type 1; NAD: nicotinamide adenine dinucleotide; NAMO: nicotinamide n-oxide; SCFAs: short-chain fatty acids.
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http://dx.doi.org/10.1080/15548627.2022.2102309DOI Listing
July 2022

They May Not Work! An evaluation of eleven sentiment analysis tools on seven social media datasets.

J Biomed Inform 2022 Jul 11;132:104142. Epub 2022 Jul 11.

Department of Informatics, Donald Bren School of Information and Computer Science, University of California, Irvine, Irvine, CA, United States; Department of Emergency Medicine, School of Medicine, University of California, Irvine, Irvine, CA, United States. Electronic address:

Objective: Sentiment analysis is an important method for understanding emotions and opinions expressed through social media exchanges. Little work has been done to evaluate the performance of existing sentiment analysis tools on social media datasets, particularly those related to health, healthcare, or public health. This study aims to address the gap.

Material And Methods: We evaluated 11 commonly used sentiment analysis tools on five health-related social media datasets curated in previously published studies. These datasets include Human Papillomavirus Vaccine, Health Care Reform, COVID-19 Masking, Vitals.com Physician Reviews, and the Breast Cancer Forum from MedHelp.org. For comparison, we also analyzed two non-health datasets based on movie reviews and generic tweets. We conducted a qualitative error analysis on the social media posts that were incorrectly classified by all tools.

Results: The existing sentiment analysis tools performed poorly with an average weighted F1 score below 0.6. The inter-tool agreement was also low; the average Fleiss Kappa score is 0.066. The qualitative error analysis identified two major causes for misclassification: (1) correct sentiment but on wrong subject(s) and (2) failure to properly interpret inexplicit/indirect sentiment expressions.

Discussion And Conclusion: The performance of the existing sentiment analysis tools is insufficient to generate accurate sentiment classification results. The low inter-tool agreement suggests that the conclusion of a study could be entirely driven by the idiosyncrasies of the tool selected, rather than by the data. This is very concerning especially if the results may be used to inform important policy decisions such as mask or vaccination mandates.
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http://dx.doi.org/10.1016/j.jbi.2022.104142DOI Listing
July 2022

Circadian Clock Genes Act as Diagnostic and Prognostic Biomarkers of Glioma: Clinic Implications for Chronotherapy.

Biomed Res Int 2022 4;2022:9774879. Epub 2022 Jul 4.

School of Pharmaceutical Sciences, Shenzhen University Health Science Center, Shenzhen 518000, China.

Gliomas are the most common primary intracranial tumors and closely related to circadian clock. Due to the high mortality and morbidity of gliomas, exploring novel diagnostic and early prognostic markers is necessary. Circadian clock genes (CCGs) play important roles in regulating the daily oscillation of biological processes and the development of tumor. Therefore, we explored the influences that the oscillations of circadian clock genes (CCGs) on diagnosis and prognosis of gliomas using bioinformatics. In this work, we systematically analyzed the rhythmic expression of CCGs in brain and found that some CCGs had strong rhythmic expression; the expression levels were significantly different between day and night. Four CCGs (, , , and ) with rhythmic expression were not only identified as differentially expressed genes but also had significant independent prognostic ability in the overall survival of glioma patients and were highly correlated with glioma prognosis in COX analysis. Besides, we found that CCG-based predictive model demonstrated higher predictive accuracy than that of the traditional grade-based model; this new prediction model can greatly improve the accuracy of glioma prognosis. Importantly, based on the four CCGs' circadian oscillations, we revealed that patients sampled at night had higher predictive ability. This may help detect glioma as early as possible, leading to early cancer intervention. In addition, we explored the mechanism of CCGs affecting the prognosis of glioma. CCGs regulated the cell cycle, DNA damage, Wnt, mTOR, and MAPK signaling pathways. In addition, it also affects prognosis through gene coexpression and immune infiltration. Importantly, can rhythmically modulated the cellular sensitivity to clinic drugs, temozolomide. The optimal point of temozolomide administration should be when expression is highest, that is, the effect is better at night. In summary, our study provided a basis for optimizing clinical dosing regimens and chronotherapy for glioma. The four key CCGs can serve as potential diagnostic and prognostic biomarkers for glioma patients, and also has obvious advantages in the direction of glioma chronotherapy.
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http://dx.doi.org/10.1155/2022/9774879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273445PMC
July 2022

The interplay of collagen/bioactive glass nanoparticle coatings and electrical stimulation regimes distinctly enhanced osteogenic differentiation of human mesenchymal stem cells.

Acta Biomater 2022 Jul 9. Epub 2022 Jul 9.

Max Bergmann Centre of Biomaterials, Institute of Materials Science, Faculty of Mechanical Science and Engineering, Technische Universität Dresden, Budapesterstraße 27, Dresden, Saxony 01069, Germany. Electronic address:

Increasing research has incorporated bioactive glass nanoparticles (BGN) and electric field (EF) stimulation for bone tissue engineering and regeneration applications. However, their interplay and the effects of different EF stimulation regimes on osteogenic differentiation of human mesenchymal stem cells (hMSC) are less investigated. In this study, we introduced EF with negligible magnetic field strength through a well-characterized transformer-like coupling (TLC) system, and applied EF disrupted (4/4) or consecutive (12/12) regime on type I collagen (Col) coatings with/without BGN over 28 days. Additionally, dexamethasone was excluded to enable an accurate interpretation of BGN and EF in supporting osteogenic differentiation. Here, we demonstrated the influences of BGN and EF on collagen topography and maintaining coating stability. Coupled with the release profile of Si ions from the BGN, cell proliferation and calcium deposition were enhanced in the Col-BGN samples after 28 days. Further, osteogenic differentiation was initiated as early as d 7, and each EF regime was shown to activate distinct pathways. The disrupted (4/4) regime was associated with the BMP/Smad4 pathways that up-regulate Runx2/OCN gene expression on d 7, with a lesser effect on ALP activity. In contrast, the canonical Wnt/β-Catenin signaling pathway activated through mechanotransduction cues is associated with the consecutive (12/12) regime, with significantly elevated ALP activity and Sp7 gene expression reported on d 7. In summary, our results illustrated the synergistic effects of BGN and EF in different stimulation regimes on osteogenic differentiation that can be further exploited to enhance current bone tissue engineering and regeneration approaches. STATEMENT OF SIGNIFICANCE: The unique release mechanisms of silica from bioactive glass nanoparticles (BGN) were coupled with pulsatile electric field (EF) stimulation to support hMSC osteogenic differentiation, in the absence of dexamethasone. Furthermore, the interplay with consecutive (12/12) and disrupted (4/4) stimulation regimes was investigated. The reported physical, mechanical and topographical effects of BGN and EF on the collagen coating, hMSC and the distinct progression of osteogenic differentiation (canonical Wnt/β-Catenin and BMP/Smad) triggered by respective stimulation regime were not explicitly reported previously. These results provide the fundamentals for further exploitations on BGN composites with metal ions and rotation of EF regimes to enhance osteogenic differentiation. The goal is sustaining continual osteogenic differentiation and achieving a more physiologically-relevant state and bone constructs in vitro.
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http://dx.doi.org/10.1016/j.actbio.2022.06.045DOI Listing
July 2022

Borate Bioactive Glasses (BBG): Bone Regeneration, Wound Healing Applications, and Future Directions.

ACS Appl Bio Mater 2022 Jul 11. Epub 2022 Jul 11.

Department of Materials Science and Engineering, Institute of Biomaterials, University of Erlangen-Nuremberg, 91058 Erlangen, Germany.

Since the early 2000s, borate bioactive glasses (BBGs) have been extensively investigated for biomedical applications. The research so far indicates that BBGs frequently exhibit superior bioactivity and bone healing capacity compared to silicate glasses. They are also suitable candidates as drug delivery devices for infection or disease treatment such as osteoporosis. Additionally, BBGs are also an excellent option for wound healing applications, which includes the availability of commercial (FDA approved) microfibrous BBG dressings to treat chronic wounds. By addition of modifying ions, the bone or wound healing capacity of BBGs can be enhanced. For instance, addition of copper ions into BBGs was shown to drastically increase blood vessel formation for wound healing applications. Moreover, addition of ions such as magnesium, strontium, and cobalt improves bone healing. Other recent research interest related to BBGs is focused on nerve and muscle regeneration applications, while cartilage regeneration is also suggested as a potential application field for BBGs. BBGs are commonly produced by melt-quenching; however, sol-gel processing of BBGs is emerging and appears to be a promising alternative. In this review paper, the physical and biological characteristics of BBGs are analyzed based on the available literature, the applications of BBGs are discussed, and future research directions are suggested.
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http://dx.doi.org/10.1021/acsabm.2c00384DOI Listing
July 2022

Study on the Influence of Vent Shape and Blockage Ratio on the Premixed Gas Explosion in the Chamber with a Small Aspect Ratio.

ACS Omega 2022 Jul 17;7(26):22787-22796. Epub 2022 Jun 17.

State Key Laboratory Cultivation Base for Gas Geology and Gas Control, Henan Polytechnic University, Jiaozuo 454000, China.

Given the current situation of deflagration caused by gas leakage for domestic use and the study of the single shape of the vent, the differential change law of vent parameters on the small aspect ratio of the chamber explosion flame evolution and explosion overpressure and other effects were experimentally investigated. Based on the theory of geometric similarity, the experimental platform of a small length-diameter ratio explosion chamber was designed and built, and the premixed gas explosion experiment was carried out by changing the shape (square and rectangle) and blockage ratio (0.1, 0.3, 0.5, 0.7, and 0.9). The explosion flame structure, flame front position, flame propagation speed, explosion pressure waveform, overpressure peak value, and so on were tested and analyzed. The results showed that the blockage ratio had the most significant effect on flame propagation and explosion flame evolution. With the increase of blockage ratio, the stretching degree of the flame became more and more obvious, the flame front became sharper and sharper, and the sharp flame changed from the lower part to the upper part. The position of the flame front increased rapidly, and the steepness and peak value of explosion overpressure became larger. The oscillation of the flame propagation velocity was more violent after the turn, and the speed of propagation to the outside of the chamber gradually accelerated. In the same blockage ratio, there was a difference in the time point at which the flame propagation velocity turned under the rectangular and square shape of the vent. In blockage ratios of 0.1, 0.3, 0.5, and 0.9, the peak overpressure reduction under the shape of the blast square relative to the rectangle was 41.3, 47.9, 1.03, and 27.6%. This indicated that the explosion relief effect of the square was better than that of a rectangle. The research results can provide a reference and basis for the reasonable deployment of explosion venting and explosion decompression work.
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http://dx.doi.org/10.1021/acsomega.2c02367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260893PMC
July 2022

Mesoscale Study on Splitting Tensile Damage Characteristics of Concrete Based on X-ray Computed Tomography and Digital Image Correlation Technology.

Materials (Basel) 2022 Jun 22;15(13). Epub 2022 Jun 22.

College of Civil and Transportation Engineering, Hohai University, Nanjing 210009, China.

In this paper, the mesoscale damage properties of concrete and mortar were studied experimentally under Brazilian disc splitting tensile tests combining X-ray computed tomography (CT) and digital image correlation (DIC) technology. Considering the factors of water/cement ratios and loading rates, the influence of meso components on the macro tensile properties and failure modes of concrete were studied. The experimental results and analysis indicate that the following: (1) the existence of coarse aggregate makes the tensile strength of concrete lower than that of mortar and reduces the sensitivity of tensile strength to the loading rates; (2) the failure modes of mortar and concrete Brazilian discs differ in the crack initiation positions and localization phenomena. Under high loading rates, the local failure plays a critical role in the strength improvement of concrete; (3) for concrete, interface failure and mortar failure are the main failure modes under low loading rates, whereas aggregate failure gradually becomes the main failure mode with increasing loading rates. The decrease in water/cement ratios improves the strength of the mortar matrix and interfacial bonding performance, leading to more serious aggregate damage and higher strength.
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http://dx.doi.org/10.3390/ma15134416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9267466PMC
June 2022

The intestinal microbial metabolite nicotinamide n-oxide prevents herpes simplex encephalitis via activating mitophagy in microglia.

Gut Microbes 2022 Jan-Dec;14(1):2096989

Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong, China.

Herpes simplex encephalitis (HSE), a complication of herpes simplex virus type I (HSV-1) infection causes neurological disorder or even death in immunocompromised adults and newborns. However, the intrinsic factors controlling the HSE outcome remain unclear. Here, we show that HSE mice exhibit gut microbiota dysbiosis and altered metabolite configuration and tryptophan-nicotinamide metabolism. HSV-1 neurotropic infection activated microglia, with changed immune properties and cell numbers, to stimulate antiviral immune response and contribute substantially to HSE. In addition, depletion of gut microbiota by oral antibiotics (ABX)-treatment triggered the hyper-activation of microglia, which in turn enhanced inflammatory immune response, and cytokine production, resulting in aggregated viral burden and HSE pathology. Furthermore, exogenous administration of nicotinamide n-oxide (NAMO), an oxidative product of nicotinamide derived from gut microbiota, to ABX-treated or untreated HSE mice significantly diminished microglia-mediated proinflammatory response and limited HSV-1 infection in CNS. Mechanistic study revealed that HSV-1 activates microglia by increasing mitochondrial damage via defective mitophagy, whereas microbial metabolite NAMO restores NAD+-dependent mitophagy to inhibit microglia activation and HSE progression. NAMO also prevented neuronal cell death triggered by HSV-1 infection or microglia-mediated microenvironmental toxicity. Finally, we show that NAMO is mainly generated by neomycin-sensitive bacteria, especially and . Together, these data demonstrate that gut microbial metabolites act as intrinsic restrictive factors against HSE progression via regulating mitophagy in microglia, implying further exploration of bacterial or nutritional approaches for treating neurotropic virus-related neurodegenerative diseases.
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http://dx.doi.org/10.1080/19490976.2022.2096989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262364PMC
July 2022

The intestinal microbial metabolite nicotinamide n-oxide prevents herpes simplex encephalitis via activating mitophagy in microglia.

Gut Microbes 2022 Jan-Dec;14(1):2096989

Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong, China.

Herpes simplex encephalitis (HSE), a complication of herpes simplex virus type I (HSV-1) infection causes neurological disorder or even death in immunocompromised adults and newborns. However, the intrinsic factors controlling the HSE outcome remain unclear. Here, we show that HSE mice exhibit gut microbiota dysbiosis and altered metabolite configuration and tryptophan-nicotinamide metabolism. HSV-1 neurotropic infection activated microglia, with changed immune properties and cell numbers, to stimulate antiviral immune response and contribute substantially to HSE. In addition, depletion of gut microbiota by oral antibiotics (ABX)-treatment triggered the hyper-activation of microglia, which in turn enhanced inflammatory immune response, and cytokine production, resulting in aggregated viral burden and HSE pathology. Furthermore, exogenous administration of nicotinamide n-oxide (NAMO), an oxidative product of nicotinamide derived from gut microbiota, to ABX-treated or untreated HSE mice significantly diminished microglia-mediated proinflammatory response and limited HSV-1 infection in CNS. Mechanistic study revealed that HSV-1 activates microglia by increasing mitochondrial damage via defective mitophagy, whereas microbial metabolite NAMO restores NAD+-dependent mitophagy to inhibit microglia activation and HSE progression. NAMO also prevented neuronal cell death triggered by HSV-1 infection or microglia-mediated microenvironmental toxicity. Finally, we show that NAMO is mainly generated by neomycin-sensitive bacteria, especially and . Together, these data demonstrate that gut microbial metabolites act as intrinsic restrictive factors against HSE progression via regulating mitophagy in microglia, implying further exploration of bacterial or nutritional approaches for treating neurotropic virus-related neurodegenerative diseases.
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http://dx.doi.org/10.1080/19490976.2022.2096989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262364PMC
July 2022

Total Knee Arthroplasty Using Adjusted Restricted Kinematic Alignment for the Treatment of Severe Varus Deformity: Technical Note.

Orthop Surg 2022 Aug 29;14(8):1892-1901. Epub 2022 Jun 29.

Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, China.

Objective: To describe a new alignment technique of adjusted restricted kinematic alignment (arKA) for the treatment of severe varus deformity in total knee arthroplasty.

Methods: Three female patients (three severe varus knees) who underwent navigation-assisted total knee arthroplasty (TKA) using arKA from April 2020 to September 2020 were included in this study, with an average age of 71.33 years (range, 61 to 80 years). General anesthesia was given to all patients. Intraoperative observations including tibia resection angle, frontal femoral angle, axial femoral angle, medial and lateral gap in the extension and flexion positions and joint line translation were recorded. Also, operation duration and drainage volume were recorded. Radiographic parameters including the mechanical axis (α), coronal femoral component angle (β), coronal tibial component angle (γ), sagittal femoral component angle (δ), tibial posterior slope angle (ε), femoral-patella angle (θ), and femoral notching were assessed. Clinical evaluation was performed using the Hospital for Special Surgery (HSS) Score and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Score. Both individual and mean measurement data were displayed.

Results: The mean tibial resection was 4.00° varus (range, 3° to 5°), and the mean frontal femoral angle was 3.67° varus (range, 3° to 4°) in extension. The flexion lateral gap was wider than the medial gap with a mean laxity of 1.34 mm. Moreover, the mean axial femoral angle was 2.67° external (range, 0° to 6°) in flexion, and the mean joint line translation was 1.00 mm proximal (range, 0 to 3 mm). In addition, the mean preoperative mechanical axis was 156.22° (range, 153.65° to 158.90°) and the mean postoperative mechanical axis was 174.04° (range, 173.83° to 174.17°) with a mean correction of 17.82°. The mean femoral angle was 92.60° (range, 91.29° to 93.30°) and the mean tibial angle was 86.95° (range, 86.83° to 87.04°) in coronal plane. The HSS score improved from an average of 46.67 points (range, 42 to 51) preoperatively to 83.67 points (range, 81 to 86) at 3 months postoperatively. The mean WOMAC score was 16.33 points at 3 months postoperatively.

Conclusions: The new alignment technique of arKA aims to balance the flexion and extension gap without extensive releases of soft tissue and restore the native pre-arthritic alignment, may be a promising alignment strategy for treating severe varus deformity. However, further study and comparison with other alignment techniques is needed.
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http://dx.doi.org/10.1111/os.13354DOI Listing
August 2022

A sensitive photoluminescent sensor based on highly charged monoruthenium(II) complexes for dopamine detection.

J Inorg Biochem 2022 Sep 15;234:111902. Epub 2022 Jun 15.

Ministry of Education Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, State Key Laboratory of Photocatalysis on Energy and Environment, Department of Chemistry, Fuzhou University, Fuzhou 350116, PR China. Electronic address:

A sensitive and selective photoluminescent sensor based on the highly charged monoruthenium(II) complex was designed to detect dopamine (DA) in aqueous samples. Two novel highly charged cationic ruthenium(II) complexes [Ru(bpy)(bpy-N)]X (bpy = 2,2'-bipyridine, bpy-N = 4,4'-bis[N,N,N-triethyl-(methylamino)]-2,2'-bipyridine, X = [PF] (1a) or Cl (1b) and [Ru(bpy)(bpy-N)]X (X = [PF] (2a) or Cl(2b)) can be assembled with anionic surfactant sodium dodecylbenzene sulfonate (SDBS), leading to an enhancement of photoluminescence intensity. Upon addition of DA to the system, the photoluminescence intensity of the assembled system was quenched due to the energy transfer effect. It exhibited a wide linear range (0.1-50 μM) and low detection limit (10 nM). The sensor demonstrated a high selectivity toward DA, especially in the presence of adrenaline (Adr) and norepinephrine (NE), whose structures are similar to DA in biological systems. With the merits of simple operation, obvious phenomenon and fast response speed, the sensor had a potential application prospect in human urine sample.
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http://dx.doi.org/10.1016/j.jinorgbio.2022.111902DOI Listing
September 2022

Room-Temperature Photooxidation of CH to CHOH with Nearly 100% Selectivity over Hetero-ZnO/FeO Porous Nanosheets.

J Am Chem Soc 2022 Jul 28;144(27):12357-12366. Epub 2022 Jun 28.

Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230026, China.

The huge challenge for CH photooxidation into CHOH lies in the activation of the inert C-H bond and the inhibition of CHOH overoxidation. Herein, we design two-dimensional in-plane -scheme heterostructures composed of two different metal oxides, with efforts to polarize the symmetrical CH molecules and strengthen the O-H bond in CHOH. As a prototype, we first fabricate ZnO/FeO porous nanosheets, where high-resolution transmission electron microscopy and X-ray photoelectron spectroscopy affirm their in-plane -scheme heterostructure. Fourier transform infrared spectra and electron paramagnetic resonance spectra demonstrate their higher amount of ·CH radicals relative to the pristine ZnO porous nanosheets, in which density functional theory calculations validate that the high local charge accumulation on Fe sites lowers the CH adsorption energy from 0.14 to 0.06 eV. Moreover, the charge-accumulated Fe sites strengthen the polarity of the O-H bond in CHOH through transferring electrons to the O atoms, confirmed by the increased barrier from 0.30 to 2.63 eV for *CHO formation, which inhibits the homolytic O-H bond cleavage and thus suppresses CHOH overoxidation. Accordingly, the CHOH selectivity over ZnO/FeO porous nanosheets reaches up to nearly 100% with an activity of 178.3 μmol g, outperforming previously reported photocatalysts without adding any oxidants under room temperature and ambient pressure.
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http://dx.doi.org/10.1021/jacs.2c03866DOI Listing
July 2022

Clinical and Gene Features of SARS-CoV-2-Positive Recurrence in Patients Recovered From COVID-19.

Front Mol Biosci 2022 8;9:875418. Epub 2022 Jun 8.

Department of Pharmacy, Shenzhen Key Laboratory of Prevention and Treatment of Severe Infection, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China.

There are still frequent reports that a number of recovered coronavirus disease 2019 (COVID-19) patients following discharge have re-detectable positive (RP) results by RT-PCR. Understanding the clinical and molecular characteristics of RP patients may have implications for curbing the COVID-19 pandemic. In this study, 318 COVID-19 convalescent patients, including 59 RP patients and 259 non-RP (NRP) patients, were enrolled. Among RP patients, women accounted for a significantly high proportion (67.8%), and the titers of IgG and IgM antibodies in this group were also significantly high. Differentially expressed genes (DEGs), including 692 upregulated and 383 downregulated genes, overlapped in two public GEO datasets containing RP and NRP blood cell samples. Enrichment analysis indicated that these DEGs were related to several key signaling pathways, such as viral infection, immune activation, and inflammatory responses. Importantly, 59 indicator genes constituting the core network exhibited high diagnostic values and were correlated with markers of different immune cells. Among these, 12 drug-related genes were associated with the RP results. Our work suggests that, in addition to clinically available features, blood cell transcriptome sequencing can be performed to obtain gene signatures for diagnosis of RP patients.
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http://dx.doi.org/10.3389/fmolb.2022.875418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9217101PMC
June 2022

The MAI score: A novel score to early predict shunt-dependent hydrocephalus in patients with aneurysmal subarachnoid hemorrhage after surgery.

Clin Neurol Neurosurg 2022 Aug 31;219:107317. Epub 2022 May 31.

Department of Neurosurgery, First Affiliated Hospital of Medical University, Harbin, PR China. Electronic address:

Objective: As a chronic complication of aneurysmal subarachnoid hemorrhage(aSAH), Shunt dependent hydrocephalus (SDHC) often leads to severe neurological deficits. At present, risk factors of SDHC after aSAH are being refined. So this study aims to investigate independent risk factors and develop a novel score to identify early the patients who require a permanent shunt.

Method: Five hundred twenty-four patients treated in the first affiliated hospital of Harbin medical university from March 2019 to March 2021 were analyzed. We collected clinical and radiographic data of patients within 72 h after the ictus. The relevant factors were firstly analyzed by univariate analysis, and the significant factors (p < 0.05) were included in the multivariate logistic regression analysis to obtain the independent risk factors with statistical differences. The MAI score was established based on the contribution of different independent risk factors to the outcome. the new score was validated in another cohort (97 patients with aSAH from April and June 2021).

Result: We enrolled 524 aneurysm patients and 41(7.82%) patients who underwent ventriculoperitoneal shunt (VPS) after aneurysm treatment. Based on univariate and multivariate analysis, Acute Hydrocephalus (OR 6.498,:95% confidence interval (CI) 1.98-21.33, p = 0.002), Intraventricular hemorrhage (OR 3.55,:95%CI 1.189-10.599, p = 0.023) and Modified Fisher score ≥ 3 (OR 5.846, 95%CI 2.649-12.900, p = 0.001) were independent risk factors. The novel score was assigned according to the contribution of different independent risk factors to the results. The MAI score: Modified Fisher grade ≥ 3 (1 point), Acute Hydrocephalus (1 point), Intraventricular hemorrhage (1 point). In the receiver operating characteristic curve analysis, the area under the curve (AUC) for the MAI score is 0.773 (p < 0.0001, 95%CI 0.686-0.861). Patients scoring 2-3 MAI points showed a 10-fold higher risk for shunt dependency than patients scoring 0-1 MAI points (p < 0.001). We performed internal validation of the MAI scoring system. The scoring system reliably predicted SDHC after aSAH. The AUC of the internal validation was 0.950 (p = 0.002, 95%CI 0.863-1.000).

Conclusion: We develop a novel score based on univariate and multivariate analysis. The effectiveness of the MAI score has been confirmed in this study, which can more accurately predict SDHC after aASH and can be widely used in clinical practice. Prospective studies are needed for validation in the future.
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http://dx.doi.org/10.1016/j.clineuro.2022.107317DOI Listing
August 2022

Extracellular Adenosine Triphosphate Binding to P2Y1 Receptors Prevents Glutamate-Induced Excitotoxicity: Involvement of Erk1/2 Signaling Pathway to Suppress Autophagy.

Front Neurosci 2022 7;16:901688. Epub 2022 Jun 7.

School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, China.

Glutamate-induced neuroexcitotoxicity could be related to the pathophysiology of some neurodegenerative diseases including Parkinson's disease and Alzheimer's disease. Extracellular ATP exerts a wide variety of functions, such as attenuating Aβ-mediated toxicity, inhibiting -Methyl-D-Aspartate (NMDA) receptor subunit combinations, and aggravating ischemic brain injury. However, the effect of extracellular ATP on glutamate-induced neuroexcitotoxicity remains largely unknown. Herein, we showed that extracellular ATP prevented the glutamate-induced excitotoxicity binding to its P2Y1 receptors. We found that excessive glutamate triggered cellular reactive oxygen species (ROS) overproduction and mitochondrial membrane potential damage, which were significantly attenuated by extracellular ATP. Besides, glutamate activated autophagy, as illustrated by the increased protein level of autophagic marker LC3II and decreased level of p62, and glutamate-induced neuroexcitotoxicity could be completely abolished by autophagy inhibitor chloroquine. In addition, we revealed that extracellular ATP activated Erk1/2 signaling to suppress autophagy and to exert its neuroprotective effects, which was further reduced by autophagy agonist rapamycin and the selective Erk1/2 inhibitor PD0325901. Taken together, our findings suggest that extracellular ATP binding to P2Y1 receptors protected against glutamate-induced excitotoxicity Erk1/2-mediated autophagy inhibition, implying the potential of ATP for the treatment of neurodegenerative disorders.
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http://dx.doi.org/10.3389/fnins.2022.901688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9209742PMC
June 2022

Oleanolic Acid Derivative AXX-18 Exerts Antiviral Activity by Inhibiting the Expression of HSV-1 Viral Genes UL8 and UL52.

Viruses 2022 06 13;14(6). Epub 2022 Jun 13.

Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.

Two-thirds of the world's population is infected with HSV-1, which is closely associated with many diseases, such as Gingival stomatitis and viral encephalitis. However, the drugs that are currently clinically effective in treating HSV-1 are Acyclovir (ACV), Ganciclovir, and Valacyclovir. Due to the widespread use of ACV, the number of drug-resistant strains of ACV is increasing, so searching for new anti-HSV-1 drugs is urgent. The oleanolic-acid derivative AXX-18 showed a CC value of 44.69 μM for toxicity to HaCaT cells and an EC value of 1.47 μM for anti-HSV-1/F. In addition, AXX-18 showed significant inhibition of ACV-resistant strains 153, 106, and Blue, and the anti-HSV-1 activity of AXX-18 was higher than that of oleanolic acid. The mechanism of action of AXX-18 was found to be similar to that of oleanolic acid, except that AXX-18 could act on both the UL8 and UL52 proteins of the uncoupling helicase-primase enzyme, whereas oleanolic acid could only act on the UL8 protein. We have elucidated the antiviral mechanism of AXX-18 in detail and, finally, found that AXX-18 significantly inhibited the formation of skin herpes. In conclusion, we have explored the anti-HSV-1 activity of AXX-18 in vitro and in vivo as well as identification of its potential target proteins, which will provide a theoretical basis for the development of subsequent anti-HSV-1 drugs.
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http://dx.doi.org/10.3390/v14061287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227917PMC
June 2022

Cerebellar Continuous Theta Burst Stimulation for Aphasia Rehabilitation: Study Protocol for a Randomized Controlled Trial.

Front Aging Neurosci 2022 2;14:909733. Epub 2022 Jun 2.

Department of Neurorehabilitation, Wuxi Tongren Rehabilitation Hospital, Wuxi, China.

Background: Language recovery is limited in moderate to severe post-stroke aphasia patients. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising tool in improving language dysfunctions caused by post-stroke aphasia, but the treatment outcome is as yet mixed. Considerable evidence has demonstrated the essential involvement of the cerebellum in a variety of language functions, suggesting that it may be a potential stimulation target of TMS for the treatment of post-stroke aphasia. Theta burst stimulation (TBS) is a specific pattern of rTMS with shorter stimulation times and better therapeutic effects. The effect of continuous TBS (cTBS) on the cerebellum in patients with aphasia with chronic stroke needs further exploration.

Methods: In this randomized, sham-controlled clinical trial, patients ( = 40) with chronic post-stroke aphasia received 10 sessions of real cTBS ( = 20) or sham cTBS ( = 20) over the right cerebellar Crus I+ a 30-min speech-language therapy. The Western Aphasia Battery (WAB) serves as the primary measure of the treatment outcome. The secondary outcome measures include the Boston Diagnostic Aphasia Examination, Boston Naming Test and speech acoustic parameters. Resting-state fMRI data were also obtained to examine treatment-induced changes in functional connectivity of the cerebro-cerebellar network. These outcome measures are assessed before, immediately after, and 12 weeks after cerebellar cTBS intervention.

Discussion: This protocol holds promise that cerebellar cTBS is a potential strategy to improve language functions in chronic post-stroke aphasia. The resting-state fMRI may explore the neural mechanism underlying the aphasia rehabilitation with cerebellar cTBS.
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http://dx.doi.org/10.3389/fnagi.2022.909733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201405PMC
June 2022

Genetically predicted higher educational attainment decreases the risk of stroke: a multivariable Mendelian randomization study.

BMC Cardiovasc Disord 2022 06 16;22(1):269. Epub 2022 Jun 16.

Department of Neurosurgery, The Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guizhou, 610041, China.

Background: The causal association between educational attainment (EA) and stroke remains unclear. Hence, a novel multivariable Mendelian randomization (MVMR) approach was applied to solve this issue.

Methods: The single nucleotide polymorphisms (SNPs) from a recent genome-wide association study (GWAS) on years of schooling served as instruments. Univariable mendelian randomization (MR) and MVMR analyses were performed to detect the relationship between genetically predicted EA and the stroke risk. In the MVMR, cigarette consumption, alcohol consumption, body mass index (BMI), intelligence, and hypertension were adjusted. The summary statistics for stroke from the MEGASTROKE consortium included 446,696 participants (40,585 cases of stroke and 34,217 cases of ischemic stroke), most of whom were of European descent.

Results: In the univariable MR, genetically predicated EA could decrease the risks of total stroke (OR = 0.66, 95% CI 0.61-0.72, P = 2.70 × 10), ischemic stroke (OR = 0.67, 95% CI 0.61-0.73, P = 2.58 × 10), large artery atherosclerosis (OR = 0.51, 95% CI 0.40-0.64, P = 1.80 × 10), small vessel stroke (OR = 0.60, 95% CI 0.49-0.73, P = 5.59 × 10), and cardioembolic stroke (OR = 0.81, 95% CI 0.68-0.96, P = 1.46 × 10) using the inverse-variance weighted (IVW) estimator. Higher EA might be negatively correlated with the odds of total stroke (OR = 0.62, 95% CI 0.50-0.77, P = 1.44 × 10), ischemic stroke (OR = 0.63, 95% CI 0.50-0.80, P = 1.41 × 10), and cardioembolic stroke (OR = 0.59, 95% CI 0.39-0.90, P = 0.01), but was not significant in large artery atherosclerosis (OR = 0.65, 95% CI 0.37-1.15, P = 0.14) and small vessel stroke (OR = 0.68, 95% CI 0.41-1.13, P = 0.14) after controlling other exposures.

Conclusions: We found that genetically predicated higher EA decreased the risks of total stroke, ischemic stroke, and cardioembolic stroke, independent of smoking, alcohol consumption, BMI, intelligence, and hypertension.
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http://dx.doi.org/10.1186/s12872-022-02713-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205080PMC
June 2022

Urolithin B suppressed osteoclast activation and reduced bone loss of osteoporosis via inhibiting ERK/NF-κB pathway.

Cell Prolif 2022 Jun 16:e13291. Epub 2022 Jun 16.

Translational Medical Innovation Center, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, China.

Objectives: The main target of current drugs for alleviating bone loss is osteoclasts. However, the long-term application of such drugs will also cause side effects. Therefore, it is of great need to develop new and safer therapeutics for osteoporosis. In recent years, drug development based on gut microbiota has gradually attracted attention. This manuscript investigates the inhibitory effect of urolithin B (UB) on osteoclastogenesis and differentiation in vitro and in ovariectomized (OVX) mice.

Materials And Methods: CCK-8 was used to analyse the cytotoxicity of UB; BMMs cells were differentiated into osteoclasts by RANKL, and respectively treated with 1, 5, and 25 μmol/L UB during this process. After one week of intervention, tartrate-resistant acid phosphatase (TRAP) staining was used to analyse the number and average area of osteoclasts. F-actin staining and immunofluorescence staining were conducted to evaluate the morphology and function of osteoclasts. Bone resorption function of osteoclasts was detected by Pit Formation Assay. The expression of osteoclast-related protein genes in RAW264.7 cells were investigated via western blot and RT-PCR assays. Western blot analysis of RANKL-mediated activation of MAPK/NF-κB pathway after 0, 5, 15, 30, 60 min of intervention. For in vivo experiments, OVX mice received intraperitoneal injection of 10, 50 mg/kg every two days, 8 weeks later, the femurs of mice were taken for morphological analysis, and the serum content of CTX-1, a bone metabolism index, was analysed.

Results: UB could inhibit the osteoclast differentiation of rankl-induced bone marrow macrophages (BMMs) and RAW264.7 cells in vitro, suppress the uptake activity of hydroxyapatite and expression of osteoclast-related gene MMP9, CTSK, NFATc1 and c-fos. Furthermore, UB repressed the rankl-induced phosphorylation and degradation of IκB and the phosphorylation of P65 in the NF-κB pathway of RAW264.7 cells, and also down-regulated the phosphorylation level of ERK in the MAPK pathway. For in vivo studies, UB-treated OVX mice showed more significant improved various parameters of distal femur compared with the control group, with fewer NFATc1, MMP9 and TRAP-positive osteoclasts in bone tissues, and less serum content of CTX-1.

Conclusion: Urolithin B attenuated bone loss in OVX mice by inhibiting the formation and activation of osteoclasts via down-regulation of the ERK/NF-κB signalling pathway.
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http://dx.doi.org/10.1111/cpr.13291DOI Listing
June 2022

Nanotubes from Ternary WSSe Alloys: Stoichiometry Modulated Tunable Optical Properties.

J Am Chem Soc 2022 Jun 3;144(23):10530-10542. Epub 2022 Jun 3.

Department of Molecular Chemistry and Materials Science, Weizmann Institute of Science, Rehovot 7610001, Israel.

Nanotubes of transition metal dichalcogenides such as WS and MoS offer unique quasi-1D properties and numerous potential applications. Replacing sulfur by selenium would yield ternary WSSe (0 ≤ ≤ 1; WSSe) nanotubes, which are expected to reveal strong modulation in their absorption edge as a function of selenium content, . Solid WO oxide nanowhiskers were employed as a sacrificial template to gain a high yield of the nanotubes with a rather uniform size distribution. Though sulfur and selenium belong to the same period, their chemical reactivity with oxide nanowhiskers differed appreciably. Here, the closed ampoule technique was utilized to achieve the completion of the solid-vapor reaction in short time scales instead of the conventional flow reactor method. The structure and chemical composition of the nanotubes were analyzed in detail. X-ray and electron diffractions indicated a systematic modulation of the WSSe lattice upon increasing the selenium content. Detailed chemical mapping showed that the sulfur and selenium atoms are distributed in random positions on the anion lattice site of the nanotubes. The optical excitonic features and absorption edges of the WSSe nanotubes do not vary linearly with the composition , which was further confirmed by density functional theory calculations. The WSSe nanotubes were shown to exhibit strong light-matter interactions forming exciton-polariton quasiparticles, which was corroborated by finite-difference time-domain simulations. Transient absorption analysis permitted following the excited state dynamics and elucidating the mechanism of the strong coupling. Thus, nanotubes of the ternary WSSe alloys offer strong band gap tunability, which would be useful for multispectral vision devices and other optoelectronic applications.
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http://dx.doi.org/10.1021/jacs.2c03187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204813PMC
June 2022

Effectiveness and Safety of Biologic Therapy in Hispanic Vs Non-Hispanic Patients With Inflammatory Bowel Diseases: A CA-IBD Cohort Study.

Clin Gastroenterol Hepatol 2022 May 27. Epub 2022 May 27.

Division of Gastroenterology, Department of Medicine, UC San Diego, La Jolla, California; Division of Biomedical Informatics, Department of Medicine, UC San Diego, La Jolla, California. Electronic address:

Background & Aims: There are limited data on outcomes of biologic therapy in Hispanic patients with inflammatory bowel diseases (IBDs). We compared risk of hospitalization, surgery, and serious infections in Hispanic vs non-Hispanic patients with IBD in a multicenter, electronic health record-based cohort of biologic-treated patients.

Methods: We identified adult patients with IBD who were new users of biologic agents (tumor necrosis factor α [TNF-α] antagonists, ustekinumab, vedolizumab) from 5 academic institutions in California between 2010 and 2017. We compared the risk of all-cause hospitalization, IBD-related surgery, and serious infections in Hispanic vs non-Hispanic patients using 1:4 propensity score matching and survival analysis.

Results: We compared 240 Hispanic patients (53% male; 45% with ulcerative colitis; 73% TNF-α antagonist-treated; 20% with prior biologic exposure) with 960 non-Hispanic patients (51% male; 44% with ulcerative colitis; 67% TNF-α antagonist-treated; 27% with prior biologic exposure). After propensity score matching, Hispanic patients were younger (37 ± 15 vs 40 ± 16 y; P = .02) and had a higher burden of comorbidities (Elixhauser index, >0; 37% vs 26%; P < .01), without any differences in patterns of medication use, burden of inflammation, and hospitalizations. Within 1 year of biologic initiation, Hispanic patients had higher rates of hospitalizations (31% vs 23%; adjusted hazard ratio [aHR], 1.32; 95% CI, 1.01-1.74) and IBD-related surgery (7.1% vs 4.6%; aHR, 2.00; 95% CI, 1.07-3.72), with a trend toward higher risk of serious infections (8.8% vs 4.9%; aHR, 1.74; 95% CI, 0.99-3.05).

Conclusions: In a multicenter, propensity score-matched cohort of biologic-treated patients with IBD, Hispanic patients experienced higher rates of hospitalization, surgery, and serious infections. Future studies are needed to investigate the biological, social, and environmental drivers of these differences.
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http://dx.doi.org/10.1016/j.cgh.2022.05.008DOI Listing
May 2022

Hemostatic biomarkers and antithrombotic strategy in percutaneous left atrial interventions: State-of-the-art review.

Thromb Res 2022 Jul 20;215:41-51. Epub 2022 May 20.

Department of Cardiology, St. Antonius Hospital, Nieuwegein, the Netherlands; Department of Cardiology, Amsterdam University Medical Center, Amsterdam, the Netherlands.

Atrial septal defect, persistent foramen ovale and the left atrial appendage are nowadays often percutaneously closed with implantable devices. These interventions may be complicated by thromboembolic events and the perfect post-procedural antithrombotic management is still under investigation. The mechanisms leading to left atrial device-related thrombus and thromboembolic complications are not fully understood. Biomarkers of coagulation activation are elevated following percutaneous device placement, peaking within one month and returning to baseline values after three months. By contrast, platelet reactivity shows no post-procedural increase. This suggests that an optimal antithrombotic regimen should perhaps include (oral) anticoagulation therapy rather than the currently more frequently prescribed antiplatelet-based regimen. Furthermore, biomarkers of endothelial activation, fibrinolysis, and on-treatment platelet reactivity may be of value in predicting device-related thrombus and bleeding and guide future medical strategy, facilitating personalized medicine.
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http://dx.doi.org/10.1016/j.thromres.2022.05.009DOI Listing
July 2022

Motor Imagery Classification via Kernel-Based Domain Adaptation on an SPD Manifold.

Brain Sci 2022 May 18;12(5). Epub 2022 May 18.

School of Advanced Manufacturing Engineering, Chongqing University of Posts and Telecommunications, Chongqing 400065, China.

Background: Recording the calibration data of a brain-computer interface is a laborious process and is an unpleasant experience for the subjects. Domain adaptation is an effective technology to remedy the shortage of target data by leveraging rich labeled data from the sources. However, most prior methods have needed to extract the features of the EEG signal first, which triggers another challenge in BCI classification, due to small sample sets or a lack of labels for the target.

Methods: In this paper, we propose a novel domain adaptation framework, referred to as kernel-based Riemannian manifold domain adaptation (KMDA). KMDA circumvents the tedious feature extraction process by analyzing the covariance matrices of electroencephalogram (EEG) signals. Covariance matrices define a symmetric positive definite space (SPD) that can be described by Riemannian metrics. In KMDA, the covariance matrices are aligned in the Riemannian manifold, and then are mapped to a high dimensional space by a log-Euclidean metric Gaussian kernel, where subspace learning is performed by minimizing the conditional distribution distance between the sources and the target while preserving the target discriminative information. We also present an approach to convert the EEG trials into 2D frames (E-frames) to further lower the dimension of covariance descriptors.

Results: Experiments on three EEG datasets demonstrated that KMDA outperforms several state-of-the-art domain adaptation methods in classification accuracy, with an average Kappa of 0.56 for BCI competition IV dataset IIa, 0.75 for BCI competition IV dataset IIIa, and an average accuracy of 81.56% for BCI competition III dataset IVa. Additionally, the overall accuracy was further improved by 5.28% with the E-frames. KMDA showed potential in addressing subject dependence and shortening the calibration time of motor imagery-based brain-computer interfaces.
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http://dx.doi.org/10.3390/brainsci12050659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9139384PMC
May 2022
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