Publications by authors named "Lin Xu"

2,762 Publications

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Melanopsin retinal ganglion cells mediate light-promoted brain development.

Cell 2022 Aug 8. Epub 2022 Aug 8.

Brain Research Center, Third Military Medical University, and Chongqing Institute for Brain and Intelligence, Guangyang Bay Laboratory, Chongqing 400038, China.

During development, melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) become light sensitive much earlier than rods and cones. IpRGCs project to many subcortical areas, whereas physiological functions of these projections are yet to be fully elucidated. Here, we found that ipRGC-mediated light sensation promotes synaptogenesis of pyramidal neurons in various cortices and the hippocampus. This phenomenon depends on activation of ipRGCs and is mediated by the release of oxytocin from the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) into cerebral-spinal fluid. We further characterized a direct connection between ipRGCs and oxytocin neurons in the SON and mutual projections between oxytocin neurons in the SON and PVN. Moreover, we showed that the lack of ipRGC-mediated, light-promoted early cortical synaptogenesis compromised learning ability in adult mice. Our results highlight the importance of light sensation early in life on the development of learning ability and therefore call attention to suitable light environment for infant care.
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http://dx.doi.org/10.1016/j.cell.2022.07.009DOI Listing
August 2022

αSMA-Cre-mediated Ogt deletion leads to heart failure and vascular smooth muscle cell dysfunction in mice.

Biochem Biophys Res Commun 2022 Jul 31;625:31-37. Epub 2022 Jul 31.

School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan, China. Electronic address:

Dilated cardiomyopathy, a type of heart muscle disease defined by the presence of left ventricular dilatation and contractile dysfunction, is an important cause of sudden cardiac death and heart failure. O-GlcNAcylation is an important post-translational modification of proteins by the addition of O-GlcNAc moieties at serine or threonine residues. Several studies have shown that proper control of O-GlcNAcylation is required for maintaining physiological function of heart by using Ogt (O-GlcNAc transferase) cardiomyocyte-specific knockout mouse models. In this study, we generated a new mouse model (αSMA-Ogt KO) in which Ogt was deleted in both cardiomyocytes and smooth muscle cells by crossing Ogt floxed mice with αSMA-Cre mice. αSMA-Cre-mediated Ogt deletion in mice led to severe postnatal lethality; the survived mice were smaller than control mice, had dilated hearts, and showed observable signs of heart failure. Moreover, the αSMA-Ogt KO heart had more apoptotic cells and fibrosis. The arteries of αSMA-Ogt KO mice exhibited significantly reduced expression of contractile genes and a trend towards arterial stiffness. In conclusion, our data emphasize the importance of OGT in maintaining normal heart function and reveal a novel role of OGT in regulating arterial contractility.
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http://dx.doi.org/10.1016/j.bbrc.2022.07.106DOI Listing
July 2022

Development and validation of a machine learning-derived radiomics model for diagnosis of osteoporosis and osteopenia using quantitative computed tomography.

BMC Med Imaging 2022 Aug 8;22(1):140. Epub 2022 Aug 8.

Department of Clinical Research Center, Dazhou Central Hospital, No.56 Nanyuemiao Street, Tongchuan District, Dazhou, 635000, Sichuan, China.

Background: To develop and validate a quantitative computed tomography (QCT) based radiomics model for discriminating osteoporosis and osteopenia.

Methods: A total of 635 patients underwent QCT were retrospectively included from November 2016 to November 2019. The patients with osteopenia or osteoporosis (N = 590) were divided into a training cohort (N = 414) and a test cohort (N = 176). Radiomics features were extracted from the QCT images of the third lumbar vertebra. Minimum redundancy and maximum relevance and least absolute shrinkage and selection operator were used for data dimensional reduction, features selection and radiomics model building. Multivariable logistic regression was applied to construct the combined clinical-radiomic model that incorporated radiomics signatures and clinical characteristics. The performance of the combined clinical-radiomic model was evaluated by the area under the curve of receiver operator characteristic curve (ROC-AUC), accuracy, specificity, sensitivity, positive predictive value, and negative predictive value.

Results: The patients with osteopenia or osteoporosis were randomly divided into training and test cohort with a ratio of 7:3. Six more predictive radiomics signatures, age, alkaline phosphatase and homocysteine were selected to construct the combined clinical-radiomic model for diagnosis of osteoporosis and osteopenia. The AUC of the combined clinical-radiomic model was 0.96 (95% confidence interval (CI), 0.95 to 0.98) in the training cohort and 0.96 (95% CI 0.92 to 1.00) in the test cohort, which were superior to the clinical model alone (training-AUC = 0.81, test-AUC = 0.79). The calibration curve demonstrated that the radiomics nomogram had good agreement between prediction and observation and decision curve analysis confirmed clinically useful.

Conclusions: The combined clinical-radiomic model that incorporates the radiomics score and clinical risk factors, can serve as a reliable and powerful tool for discriminating osteoporosis and osteopenia.
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http://dx.doi.org/10.1186/s12880-022-00868-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9358842PMC
August 2022

Construction of an Artificial Light-Harvesting System with Efficient Photocatalytic Activity in an Aqueous Solution Based on a FRET-Featuring Metallacage.

Inorg Chem 2022 Aug 8. Epub 2022 Aug 8.

Shanghai Key Laboratory of Green Chemistry and Chemical Processes, Shanghai Frontiers Science Center of Molecule Intelligent Syntheses, School of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, P. R. China.

Over the past few decades, the design and construction of high-efficiency artificial light-harvesting systems (LHSs) involving multistep fluorescence-resonance energy transfer (FRET) processes have gradually received considerable attention within wide fields ranging from supramolecular chemistry to chemical biology and even materials science. Herein, through coordination-driven self-assembly, a novel tetragonal prismatic metallacage featuring a FRET process using tetraphenylethene (TPE) units as donors and BODIPY units as acceptors has been conveniently synthesized. Subsequently, taking advantage of supramolecular hydrophobic interactions, a promising artificial LHS involving two-step FRET processes from TPE to BODIPY and then to Nile Red (NiR) has been successfully fabricated in an aqueous solution using the FRET-featuring metallacage, NiR, and an amphiphilic polymer (mPEG-DSPE). Notably, this obtained aqueous LHS exhibits highly efficient photocatalytic activity in the dehalogenation of a bromoacetophenone derivate. This study provides a unique strategy for fabricating artificial LHSs in aqueous solutions with multistep FRET processes and further promotes the future development of mimicking the photosynthesis process.
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http://dx.doi.org/10.1021/acs.inorgchem.2c01869DOI Listing
August 2022

Immune-Related Biomarkers Improve Performance of Risk Prediction Models for Survival in Patients With Hepatocellular Carcinoma.

Front Oncol 2022 22;12:925362. Epub 2022 Jul 22.

Department of Liver Surgery and Liver Transplantation, West China Hospital, Sichuan University, Chengdu, China.

Object: The prediction of hepatocellular carcinoma (HCC) prognosis faced great challenge due to tumor heterogeneity. The purpose of this study was to explore the correlation between the immune infiltrate and prognosis. Moreover, we aimed to establish a risk prediction model for survival in HCC patients based on clinicopathological and immune indicators.

Methods: In this study, 316 patients with HCC who underwent radical resection in West China Hospital from 2009 to 2014 were included. Clinicopathological data and pathological specimens were collected. H&E staining and immunohistochemical staining were performed on the pathological tissue sections. The evaluation of tumor-infiltrating lymphocyte (TIL) density was based on H&E slices, and the assessment of the expressions of CD8, CD68, Lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin domain and mucin domain-3 (TIM-3), Programmed Cell Death Protein 1 (PD-1), Programmed Cell Death Ligand 1 (PD-L1), OX40, CD66b, and Tryptase. was performed on the immunohistochemical slices. A risk prediction model for survival in HCC patients was established by integrating immune-related biomarkers and clinicopathological indicators.

Results: The Barcelona Clinic Liver Cancer (BCLC) stage; the microvascular invasion status; the density of TILs; the expressing levels of CD66b, OX40, and PD-L1 in the immune cell; CD68; and CD8 were the predictors of patients' overall survival (OS). The BCLC stage; the density of TILs; and the expressions of OX40, CD68, and CD8 were associated with disease-free survival (DFS). The expressions of CD66b, CD68, OX40, and CD8 had a cumulative effect on prognosis. The area under the curve of the prediction model for OS based on clinicopathological features was improved from 0.62 to 0.74 by adding to CD8, OX40, CD68, CD66b, and TILs, whereas it was improved from 0.59 to 0.73 for the DFS prediction model.

Conclusion: Our results, if confirmed, indicated that immune-related biomarkers should be taken into account or stratified in survival analysis for HCC.
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http://dx.doi.org/10.3389/fonc.2022.925362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353009PMC
July 2022

Exon skipping in genes encoding lineage-defining myogenic transcription factors in rhabdomyosarcoma.

Cold Spring Harb Mol Case Stud 2022 Aug 6. Epub 2022 Aug 6.

University of Texas Southwestern Medical Center.

Rhabdomyosarcoma (RMS) is a childhood sarcoma composed of myoblast-like cells, which suggests a defect in terminal skeletal muscle differentiation. To explore potential defects in the differentiation program, we searched for mRNA splicing variants in genes encoding transcription factors driving skeletal muscle lineage commitment and differentiation. We studied two RMS cases and identified altered splicing resulting in "skipping" the second of three exons in MYOD1. RNA-Seq data from 42 tumors and additional RMS cell lines revealed exon 2 skipping in both MYOD1 and MYF5 but not in MYF6 or MYOG. Complementary molecular analysis of MYOD1 mRNA found evidence for exon skipping in 5 additional RMS cases. Functional studies showed that so-called MYODΔEx2 protein failed to robustly induce muscle-specific genes, and its ectopic expression conferred a selective advantage in cultured fibroblasts and an RMS xenograft. In summary, we present previously unrecognized exon skipping within MYOD1 and MYF5 in RMS, and we propose that alternative splicing can represent a mechanism to alter the function of these two transcription factors in RMS.
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http://dx.doi.org/10.1101/mcs.a006190DOI Listing
August 2022

A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids.

Am J Hum Genet 2022 08;109(8):1366-1387

Division of Genome Science, Department of Precision Medicine, National Institute of Health, Chungbuk, South Korea.

A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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http://dx.doi.org/10.1016/j.ajhg.2022.06.012DOI Listing
August 2022

A NIR-II light-modulated injectable self-healing hydrogel for synergistic photothermal/chemodynamic/chemo-therapy of melanoma and wound healing promotion.

J Mater Chem B 2022 Aug 3. Epub 2022 Aug 3.

State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Science, Guangxi Normal University, Guilin, 541001, China.

The development of an injectable multifunctional hydrogel with tumor therapy, antibacterial treatment and wound healing properties is essential for simultaneously eradicating melanoma and promoting wound healing of tumor-initiated skin defects. Herein, iron ion-doped polyaniline (PANI(Fe)) tethered with guar gum (GG) chains is employed for the first time as a building unit for constructing a superior hydrogel ([email protected](Fe)-borax) crosslinked by borate/didiol bonds. Due to the dynamic and reversible properties of boronate ester bonds, the [email protected](Fe)-borax hydrogels had convenient injectability, rapid self-healing ability, and reversible gel-sol transformations under thermal- or pH-stimuli. More importantly, they took advantage of the second near-infrared (NIR-II) responsive photothermal conversion capability, accompanied by the photothermal-enhanced high cytotoxic ˙OH generation in the HO-enriched tumor microenvironment induced by iron-doped PANI. The as-prepared hydrogels exhibited excellent photothermal effects and controllable NIR-triggered drug release, leading to distinctly synergistic photothermal/chemodynamic/chemo-therapy effects of melanoma both (98.2%) and (98.8%). In addition, the obtained hydrogels also exhibited good anti-bacterial activity (>97.1%) against both Gram-positive () and Gram-negative () bacteria because they were based on PANI(Fe) and borax, which exhibit antibacterial activity. Furthermore, these [email protected](Fe)-incorporated scaffolds could improve fibroblast cell proliferation and angiogenesis for accelerating wound repair in tumor-bearing and infected wound mice. Taken together, [email protected](Fe)-borax hydrogels may be used simultaneously for eradication of skin-tumor cells, inhibiting infection and accelerating wound healing. This work offers an effective and facile strategy to fabricate an "all-in-one" multifunctional hydrogel platform for synergetic multimodal integrated therapy of tumors.
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http://dx.doi.org/10.1039/d2tb00923dDOI Listing
August 2022

Comparison and Integration of Voltage and Charge Amplifiers for Capacitive ECG Measurements.

IEEE Trans Biomed Eng 2022 Aug 2;PP. Epub 2022 Aug 2.

Objective: Sensing with capacitive electrodes is of interest for long-term, comfortable bio-potential measurements (e.g., ECG). However, due to the small body-to-electrode capacitance (C), the design of the associated front-end amplifier remains a challenge. Both voltage amplifiers (VA) and charge amplifiers (CA) can be employed. While basic comparisons of both typologies were done before, this paper extends the comparison to their responses to artifacts (caused by motion or interference). Further, a VA-CA-switchable amplifier is proposed, allowing to adapt the amplifier type to different situations, and enabling to estimate the body-to-electrode capacitance C in a passive way.

Methods: A VA-CA switchable amplifier was implemented in a 180 nm CMOS process. The responses to artifacts for VA and CA were studied by modelling, simulations and experiments using the custom IC. The proposed C estimation method was validated by electrical tests and in-vivo tests.

Results: VAs are less affected by C variation artifacts, while CAs recover faster from triboelectricity artifacts. In a VA, these two artifacts are multiplicative and get modulated if they occur simultaneously, but in a CA they remain independent.

Conclusion: The combined VA-CA amplifier has the potential for optimal amplifier selection according to the properties of the recorded signal, the value of C and the actual presence of artifacts. Moreover, it can estimate C without extra hardware.

Significance: The proposed VA-CA switchable structure is superior to an individual VA or CA, thanks its adaptability to signal quality and artifacts, and it provides extra information on the body-to-electrode interface quality (C).
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http://dx.doi.org/10.1109/TBME.2022.3195771DOI Listing
August 2022

Genomic evidence for divergent co-infections of co-circulating SARS-CoV-2 lineages.

Comput Struct Biotechnol J 2022 28;20:4015-4024. Epub 2022 Jul 28.

Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.

Co-infection of RNA viruses may contribute to their recombination and cause severe clinical symptoms. However, the tracking and identification of SARS-CoV-2 co-infection persist as challenges. Due to the lack of methods for detecting co-infected samples in a large amount of deep sequencing data, the lineage composition, spatial-temporal distribution, and frequency of SARS-CoV-2 co-infection events in the population remains unclear. Here, we propose a hypergeometric distribution-based method named Cov2Coinfect with the ability to decode the lineage composition from 50,809 deep sequencing data. By resolving the mutational patterns in each sample, Cov2Coinfect can precisely determine the co-infected SARS-CoV-2 variants from deep sequencing data. Results from two independent and parallel projects in the United States achieved a similar co-infection rate of 0.3-0.5 % in SARS-CoV-2 positive samples. Notably, all co-infected variants were highly consistent with the co-circulating SARS-CoV-2 lineages in the regional epidemiology, demonstrating that the co-circulation of different variants is an essential prerequisite for co-infection. Overall, our study not only provides a robust method to identify the co-infected SARS-CoV-2 variants from sequencing samples, but also highlights the urgent need to pay more attention to co-infected patients for better disease prevention and control.
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http://dx.doi.org/10.1016/j.csbj.2022.07.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330581PMC
July 2022

Short-Term Surgical Outcomes for Lobectomy Between Robot-Assisted Thoracic Surgery and Uniportal Video-Assisted Thoracoscopic Surgery.

Front Oncol 2022 13;12:914059. Epub 2022 Jul 13.

Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

Objectives: To evaluate the short-term outcomes of uniportal video-assisted thoracoscopic surgery (UVATS) and Da Vinci robot-assisted thoracoscopic surgery (RATS) in lobectomy and lymph node (LN) dissection.

Methods: The two groups of patients with primary non-small cell lung cancer (NSCLC; RATS group, UVATS group) were matched by the propensity score to compare LN dissection and recent clinical outcomes. The results were analyzed by univariate analysis. From November 2020 to November 2021, 412 NSCLC patients (54 RATS and 358 UVATS) from a single institution of the Provincial Hospital affiliated with Shandong First Medical University were included in the analysis. Age, sex, lung lobe, surgical resection scope, solid nodules, and core tumor ratios were matched according to different surgical methods.

Results: From November 2020 to November 2021, 412 patients with NSCLC (54 RATS, 358 UVATS) from the Provincial Hospital affiliated with Shandong First Medical University were included in the analysis. According to our matching results, LN dissection was more thorough in the RATS group.

Conclusion: RATS has potential advantages over UVATS in radical lung cancer surgery.
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http://dx.doi.org/10.3389/fonc.2022.914059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326123PMC
July 2022

Potential Value of Serum Uric Acid in the Identification of Postoperative Delirium in Geriatric Patients Undergoing Knee Replacement.

Front Aging Neurosci 2022 14;14:909738. Epub 2022 Jul 14.

Department of Anesthesiology, Qingdao Municipal Hospital Affiliated to Qingdao University, Qingdao, China.

Objectives: The relationship between preoperative serum uric acid (SUA) and cerebrospinal fluid (CSF) Alzheimer-related biomarkers were investigated to determine whether high SUA is a potential risk factor for postoperative delirium (POD) and to evaluate its predictive efficacy.

Methods: The participants were selected from the Perioperative Neurocognitive Disorder Risk Factor and Prognosis (PNDRFAP) study and the Perioperative Neurocognitive Disorder and Biomarker Lifestyle (PNDABLE) study. The logistic regression equation was used to analyze the risk factors and protective factors of POD. The interaction term (SUA × Sex) was introduced into the linear model to explore the potential modification effects of sex on the identified correlations. We analyzed the mediating effects of Alzheimer-related biomarkers. Finally, we constructed the receiver operating characteristic (ROC) curve and the nomogram model to evaluate the efficacy of SUA and Alzheimer-related biomarkers in predicting POD.

Results: Patients with POD had elevated SUA level (PNDRFAP: = 0.002, PNDABLE: < 0.001). Preoperative SUA level was positively correlated with CSF phosphorylated tau (P-tau) ( = 0.027) and β-amyloid42 (Aβ)/P-tau ( = 0.023). Interaction analysis did not find any modification effect of sex. The relationship between SUA and POD was partially mediated by CSF P-tau (15.3%). ROC curve showed that the model combining SUA and Alzheimer-related biomarkers had better performance in predicting POD [area under the curve (AUC) = 0.880; < 0.001], and the predictive model is accurate.

Conclusions: High SUA may enhance CSF P-tau level, thus increasing the risk of POD, and the model combining SUA and Alzheimer-related biomarkers can accurately predict the occurrence of POD.
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http://dx.doi.org/10.3389/fnagi.2022.909738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329914PMC
July 2022

Suppresses Plant Defense Responses by Disrupting Chlorophyll Biosynthesis and Photosynthesis in Foxtail Millet.

Front Plant Sci 2022 12;13:928040. Epub 2022 Jul 12.

College of Agriculture, Shanxi Agricultural University, Taiyuan, China.

Downy mildew of foxtail millet is an important oomycete disease caused by , affecting the yield and quality of the crop. Foxtail millet infected with exhibit symptoms of leaf yellowing and leaf cracking. To uncover the pathogenic mechanism of this disease, we explored the effects on chlorophyll synthesis and photosynthesis of foxtail millet leaves infected by . An elite foxtail millet variety, JG21, susceptible to , was used as for this study. inhibited chlorophyll synthesis and caused loose mesophyll cell arrangement. In addition, some cells were severely vacuolated in -infected foxtail millet leaves at the early stages of infection. could invade the mesophyll cells through haustoria which destroyed the chloroplast structure at the middle stages of infection causing significant accumulation of osmiophilic particles (OPs) and disintegrated chloroplast grana lamellae. Furthermore, foxtail millet leaves split longitudinally at the later stages of infection. Chlorophyll and carotenoid contents in infected leaves decreased significantly compared with those in the control. Net photosynthetic rate (Pn) of leaves and stomatal conductance showed a downward trend, and intercellular carbon dioxide concentrations increased significantly following the infection with . A total of 1,618 differentially expressed genes (DEGs) were detected between the control group and the treatment groups using RNA sequencing (RNA-Seq) among S1-S5 stages. DEGs associated with "photosynthesis" and "light reaction" were enriched. Gene expression patterns showed that 91.3% of 23 genes related to chlorophyll synthesis and photosynthesis, were significantly down-regulated than the control during S1-S5 stages. Based on the gene expression dataset, weighed gene co-expression network analysis (WGCNA) with 19 gene co-expression modules related to photosynthesis revealed six hub genes related to chlorophyll synthesis, which were suppressed during infection. The results suggest that infection of led to weak chlorophyll synthesis and rapid chloroplasts disappearance in foxtail millet. The defense responses and resistance of foxtail millet to were inhibited because chloroplast structure and function were destroyed in leaves, and the sexual reproduction in could be completed rapidly.
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http://dx.doi.org/10.3389/fpls.2022.928040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317951PMC
July 2022

Development of the Nurses' Willingness to Engage in Palliative Care Scale.

J Hosp Palliat Nurs 2022 Jul 28. Epub 2022 Jul 28.

Nurses play an important role in palliative care, and their willingness to engage in such work is thus crucial. The purpose of this study was to develop, and test the reliability and validity of, the Nurses' Willingness to Engage in Palliative Care Scale. The sample consisted of 224 Chinese nurses with a mean age of 32.36 (SD, 5.986) years. The critical ratio method was used for item analysis. Reliability was assessed by calculating Cronbach α. Content validity was assessed by calculating a content validity index based on ratings from 5 nursing experts. Structural validity was calculated by exploratory factor analysis. The developed scale consists of 20 items over 4 dimensions (attitude toward the behavior, subjective norms, perceived behavioral control, and behavioral intention) and has high content validity (0.97). The reliability of the scale was found to be sufficient (Cronbach α = .896). Four common factors were extracted from exploratory factor analysis, and the cumulative variance explained was 68.938%. The Nurses' Willingness to Engage in Palliative Care Scale has good reliability and validity and can be used to assess nurses' willingness to work in palliative care units.
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http://dx.doi.org/10.1097/NJH.0000000000000898DOI Listing
July 2022

Chimeric RNA TNNI2-ACTA1-V1 Regulates Cell Proliferation by Regulating the Expression of NCOA3.

Front Vet Sci 2022 8;9:895190. Epub 2022 Jul 8.

College of Animal Sciences and Technology, Northeast Agricultural University, Harbin, China.

Chimeric RNA is a crucial target for tumor diagnosis and drug therapy, also having its unique biological role in normal tissues. (), a chimeric RNA discovered by our laboratory in porcine muscle tissue, can inhibit the proliferation of Porcine Skeletal Muscle Satellite Cells (PSCs). The regulatory mechanism of in PSCs remains unclear, but we speculate that and may be the target genes of . In this study, we explored the effects of and on cell viability and cell proliferation by CCK-8 assay, EdU staining and flow cytometry. Furthermore, the regulatory pathway of proliferation in PSCs mediated by through or was elucidated by co-transfection and co-immunoprecipitation (Co-IP). The results revealed that overexpression of significantly increased cell viability and the expression level of , and also promotes cell proliferation by changing cells from the G1 phase to the S phase. In addition, inhibiting the expression of substantially reduced cell viability and inhibited cell proliferation. Overexpression of and had no significant effect on cell viability and proliferation. Co-transfection experiments showed that could rescue the proliferation inhibition of PSCs caused by . Co-IP assay indicated that directly interacts with . Our study explores the hypothesis that directly regulates , indirectly regulating , thereby regulating PSCs proliferation. We provide new putative mechanisms of porcine skeletal muscle growth and lay the foundation for the study of chimeric RNA in normal tissues.
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http://dx.doi.org/10.3389/fvets.2022.895190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309209PMC
July 2022

Hearing loss and depressive symptoms in older Chinese: whether social isolation plays a role.

BMC Geriatr 2022 07 26;22(1):620. Epub 2022 Jul 26.

School of Public Health, Sun Yat-Sen University, No. 74 Zhongshan 2ndRoad, Guangzhou, Guangdong Province, China.

Background: Existing evidence links hearing loss to depressive symptoms, with the extent of association and underlying mechanisms remaining inconclusive. We conducted a cross-sectional study to examine the association of hearing loss with depressive symptoms and explored whether social isolation mediated the association.

Methods: Eight thousand nine hundred sixty-two participants from Guangzhou Biobank Cohort Study were included. Data on self-reported hearing status, the 15-item Geriatric Depression Scale (GDS-15), social isolation and potential confounders were collected by face-to-face interview.

Results: The mean (standard deviation) age of participants was 60.2 (7.8) years. The prevalence of poor and fair hearing was 6.8% and 60.8%, respectively. After adjusting for age, sex, household income, education, occupation, smoking, alcohol use, self-rated health, comorbidities, compared with participants who had normal hearing, those with poor hearing (β = 0.74, 95% confidence interval (CI) 0.54, 0.94) and fair hearing (β = 0.59, 95% CI 0.48, 0.69) had higher scores of GDS-15. After similar adjustment, those with poor hearing (odds ratio (OR) = 2.13, 95% CI 1.65, 2.74) or fair hearing (OR = 1.68, 95% CI 1.43, 1.99) also showed higher odds of depressive symptoms. The association of poor and fair hearing with depressive symptoms attenuated slightly but not substantially after additionally adjusting for social isolation. In the mediation analysis, the adjusted proportion of the association mediated through social isolation was 9% (95% CI: 6%, 22%).

Conclusion: Poor hearing was associated with a higher risk of depressive symptoms, which was only partly mediated by social isolation. Further investigation of the underlying mechanisms is warranted.
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http://dx.doi.org/10.1186/s12877-022-03311-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316428PMC
July 2022

Predicting patient experience of Invisalign treatment: An analysis using artificial neural network.

Korean J Orthod 2022 Jul 7;52(4):268-277. Epub 2022 Mar 7.

Department of Orthodontics, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Objective: Poor experience with Invisalign treatment affects patient compliance and, thus, treatment outcome. Knowing the potential discomfort level in advance can help orthodontists better prepare the patient to overcome the difficult stage. This study aimed to construct artificial neural networks (ANNs) to predict patient experience in the early stages of Invisalign treatment.

Methods: In total, 196 patients were enrolled. Data collection included questionnaires on pain, anxiety, and quality of life (QoL). A four-layer fully connected multilayer perception with three backpropagations was constructed to predict patient experience of the treatment. The input data comprised 17 clinical features. The partial derivative method was used to calculate the relative contributions of each input in the ANNs.

Results: The predictive success rates for pain, anxiety, and QoL were 87.7%, 93.4%, and 92.4%, respectively. ANNs for predicting pain, anxiety, and QoL yielded areas under the curve of 0.963, 0.992, and 0.982, respectively. The number of teeth with lingual attachments was the most important factor affecting the outcome of negative experience, followed by the number of lingual buttons and upper incisors with attachments.

Conclusions: The constructed ANNs in this preliminary study show good accuracy in predicting patient experience (i.e., pain, anxiety, and QoL) of Invisalign treatment. Artificial intelligence system developed for predicting patient comfort has potential for clinical application to enhance patient compliance.
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http://dx.doi.org/10.4041/kjod21.255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314214PMC
July 2022

The Moderating Effect of Learning Experience on Learning Motivation and Learning Outcomes of International Students.

Front Psychol 2022 28;13:913982. Epub 2022 Jun 28.

School of Engineering, London South Bank University, London, United Kingdom.

With the increasing level of internationalization in higher education, the number of international students in mainland China is rapidly increasing. However, limited research has considered that student results may be affected by a reduced motivation to learn. Therefore, the aim of this research is to explore the effect of the learning motivation on the learning outcomes of international students and the moderating role of learning experience. A sample of 130 international students from 23 countries studying in mainland China was analyzed. The study found a significant correlation between the learning motivations and international students' learning outcomes. It was also determined that learning experience has significantly enhances the relationship between learning motivation and the learning outcomes of international students. This study contributes to the higher education literature on learning motivation by students and learning outcomes.
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http://dx.doi.org/10.3389/fpsyg.2022.913982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9306406PMC
June 2022

The Hepatoprotective Effect of Leonurine Hydrochloride Against Alcoholic Liver Disease Based on Transcriptomic and Metabolomic Analysis.

Front Nutr 2022 7;9:904557. Epub 2022 Jul 7.

Key Laboratory for Deep Processing of Major Grain and Oil of Ministry of Education, Wuhan Polytechnic University, Wuhan, China.

Excessive alcohol consumption can eventually progress to alcoholic liver disease (ALD). The underlying mechanism of ALD toxicity is primarily associated with oxidative damage. Many alkaloids have been reported to possess potential antioxidative efficacy, while the mechanism of their hepatoprotective activity against ALD is still not clear. In this study, eight alkaloids were selected from a monomer library of Traditional Chinese Medicine and evaluated for their antioxidant activity against ALD by the evaluation of Glutathione (GSH) and Malondialdehyde (MDA). The result suggested that Leonurine hydrochloride (LH) was a potent antioxidant that could reduce alcoholic liver damage. To further investigate the underlying mechanism of LH against ALD, the molecular pathway induced by LH was identified by RNA-seq analyses. Transcriptome data revealed the principal mechanism for the protective effect of LH against ALD might be attributed to the differentially expressed genes (DEGs) of PI3K-AKT, AMPK, and HIF-1 signaling pathways involved in the lipid metabolism. Given the hepatoprotective mechanism of LH is involved in lipid metabolism, the lipid metabolism induced by LH was further analyzed by UHPLC-MS/MS. Metabolome analysis indicated that LH significantly regulated glycerophospholipid metabolism including phosphatidylcholine, 1-acyl-sn-glycero-3-phosphocholine, phosphatidylethanolamine and 1-acyl-sn-glycero-3-phosphoethanolamine in the liver. Overall, this study revealed that the hepatoprotective mechanism of LH against alcoholic liver damage might be associated with the genes involved in glycerophospholipid metabolism.
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http://dx.doi.org/10.3389/fnut.2022.904557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301321PMC
July 2022

Preparation of solvent-free starch-based carbon dots for the selective detection of Ru ions.

RSC Adv 2022 Jun 28;12(29):18779-18783. Epub 2022 Jun 28.

Yunnan Key Laboratory of Wood Adhesives and Glued Products National Joint Engineering Research Center for Highly-Efficient Utilization of Forest Biomass Resources, Southwest Forestry University 300 Bailong Road Kunming 650224 Yunnan Province China

A simple, green, and solvent-free pyrolysis method for the preparation of starch-based carbon dots (CDs) was developed. The CDs prepared at 300 °C exhibited a highest quantum yield of 21.0%, which was mainly due to the high degree of graphitisation of the CDs. The CDs were selective for the detection of Ru ion solutions.
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http://dx.doi.org/10.1039/d2ra03277eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9237645PMC
June 2022

Solvent-Free Pyrolysis Strategy for the Preparation of Biomass Carbon Dots for the Selective Detection of Fe Ions.

Front Chem 2022 6;10:940398. Epub 2022 Jul 6.

Yunnan Key Laboratory of Wood Adhesives and Glued Products National Joint Engineering Research Center for Highly-Efficient Utilization of Forest Biomass Resources, Southwest Forestry University, Kunming, China.

Biomass carbon dots (BCDs) have the advantages of being nontoxic, low cost and simple to prepare, have excellent optical properties, good biocompatibility and stability, and therefore have broad application prospects in areas such as heavy metal ion detection and optoelectronic devices. Herein, a simple, green, solvent-free method of preparing BCDs was developed. CDs with certain fluorescence properties were prepared by a solvent-free pyrolysis method at different temperatures using two abundant components (cellulose and lignin) of biomass resources as carbon sources. Both the cellulose CDs prepared at 300°C and the lignin CDs prepared at 350°C exhibited high quantum yields of 11.7% and 23.4%, respectively, a result that was mainly due to the high degree of graphitization. The analysis and results demonstrated the selectivity of CDs for the detection of various metal ion solutions. In particular, CDs are sensitive to Fe and can be used as a fluorescent sensor for the detection of Fe, providing a more efficient, sustainable alternative for metal ion detection.
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http://dx.doi.org/10.3389/fchem.2022.940398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9298851PMC
July 2022

Activating Connexin43 gap junctions primes adipose tissue for therapeutic intervention.

Acta Pharm Sin B 2022 Jul 26;12(7):3063-3072. Epub 2022 Feb 26.

Touchstone Diabetes Center, Department of Internal Medicine, the University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.

Adipose tissue is a promising target for treating obesity and metabolic diseases. However, pharmacological agents usually fail to effectively engage adipocytes due to their extraordinarily large size and insufficient vascularization, especially in obese subjects. We have previously shown that during cold exposure, connexin43 (Cx43) gap junctions are induced and activated to connect neighboring adipocytes to share limited sympathetic neuronal input amongst multiple cells. We reason the same mechanism may be leveraged to improve the efficacy of various pharmacological agents that target adipose tissue. Using an adipose tissue-specific Cx43 overexpression mouse model, we demonstrate effectiveness in connecting adipocytes to augment metabolic efficacy of the -adrenergic receptor agonist Mirabegron and FGF21. Additionally, combing those molecules with the Cx43 gap junction channel activator danegaptide shows a similar enhanced efficacy. In light of these findings, we propose a model in which connecting adipocytes Cx43 gap junction channels primes adipose tissue to pharmacological agents designed to engage it. Thus, Cx43 gap junction activators hold great potential for combination with additional agents targeting adipose tissue.
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http://dx.doi.org/10.1016/j.apsb.2022.02.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293664PMC
July 2022

Predicted Immune-Related Genes and Subtypes in Systemic Lupus Erythematosus Based on Immune Infiltration Analysis.

Dis Markers 2022 12;2022:8911321. Epub 2022 Jul 12.

Department of Rheumatology Immunology, The Second Affiliated Hospital of Shandong First Medical University, Shandong Province, China.

Objective: The present investigation is aimed at identifying key immune-related genes linked with SLE and their roles using integrative analysis of publically available gene expression datasets.

Methods: Four gene expression datasets pertaining to SLE, 2 from whole blood and 2 experimental PMBC, were sourced from GEO. Shared differentially expressed genes (DEG) were determined as SLE-related genes. Immune cell infiltration analysis was performed using CIBERSORT, and case samples were subjected to -means cluster analysis using high-abundance immune cells. Key immune-related SLE genes were identified using correlation analysis with high-abundance immune cells and subjected to functional enrichment analysis for enriched Gene Ontology Biological Processes and KEGG pathways. A PPI network of genes interacting with the key immune-related SLE genes was constructed. LASSO regression analysis was performed to identify the most significant key immune-related SLE genes, and correlation with clinicopathological features was examined.

Results: 309 SLE-related genes were identified and found functionally enriched in several pathways related to regulation of viral defenses and T cell functions. -means cluster analysis identified 2 sample clusters which significantly differed in monocytes, dendritic cell resting, and neutrophil abundance. 65 immune-related SLE genes were identified, functionally enriched in immune response-related signaling, antigen receptor-mediated signaling, and T cell receptor signaling, along with Th17, Th1, and Th2 cell differentiation, IL-17, NF-kappa B, and VEGF signaling pathways. LASSO regression identified 9 key immune-related genes: DUSP7, DYSF, KCNA3, P2RY10, S100A12, SLC38A1, TLR2, TSR2, and TXN. Imputed neutrophil percentage was consistent with their expression pattern, whereas anti-Ro showed the inverse pattern as gene expression.

Conclusions: Comprehensive bioinformatics analyses revealed 9 key immune-related genes and their associated functions highly pertinent to SLE pathogenesis, subtypes, and identified valuable candidates for experimental research.
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http://dx.doi.org/10.1155/2022/8911321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296307PMC
July 2022

Percutaneous endoscopic interlaminar discectomy via inner border of inferior pedicle approach for downmigrated disc herniation: a retrospective study.

J Orthop Surg Res 2022 Jul 21;17(1):359. Epub 2022 Jul 21.

Department of Spine Surgery and Traumatology Surgery, Zigong Fourth People's Hospital, Zigong, 643000, Sichuan, People's Republic of China.

Objective: To evaluate the efficacy and feasibility of percutaneous endoscopic interlaminar discectomy (PEID) via the inner border of the inferior pedicle approach for downmigrated disc herniation.

Methods: Seventeen patients who had downmigrated disc herniation were included in this study from May 2020 to February 2021. After PEID via the inner border of the inferior pedicle approach, a retrospective study was conducted on all patients. Radiologic findings were investigated, and based on the level of migration seen on preoperative magnetic resonance imaging (MRI), participants were divided into two types (high-grade and low-grade migrations). Preoperative, 1st post-operative day, 3rd post-operative month, and the final follow-up visual analogue scale (VAS) assessments for back and leg pain and preoperative, 3rd post-operative month, and the final follow-up Oswestry disability index (ODI) evaluations were performed. The clinical effects at the final follow-up were assessed by the modified MacNab criterion.

Results: All patients successfully completed surgery. There were 10 males and 7 females in the group. These patients were 42 years old on average (range, 25-68 years). Four and 13 patients had downmigrated disc herniation with high-grade and low-grade, respectively, on MRI. The mean follow-up duration was 10.47 ± 1.84 months (range, 8-14 months). The mean VAS score for back and leg improved from 5.18 ± 0.81 preoperatively to 1.35 ± 0.49 at the final follow-up (P < 0.05) and 6.94 ± 0.66 preoperatively to 1.47 ± 0.51 at the final follow-up (P < 0.05), respectively. The mean ODI score improved from 48.00 ± 3.64 preoperatively to 18.71 ± 1.31 at the final follow-up (P < 0.05). According to the modified MacNab criterion, 15 patients (88.2%) obtained excellent, while the rest 2 patients (11.8%) reported good outcomes.

Conclusion: PEID via the inner border of the inferior pedicle approach could be a good alternative option for the treatment of downmigrated disc herniation.
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http://dx.doi.org/10.1186/s13018-022-03245-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9306037PMC
July 2022

Influence of epidemic situation on COVID-19 vaccination between urban and rural residents in China-Vietnam border area: A cross-sectional survey.

PLoS One 2022 21;17(7):e0270345. Epub 2022 Jul 21.

The Fifth Affiliated Hospital of Kunming Medical University, Diannan Central Hospital of Honghe Prefecture (Gejiu People's Hospital), Gejiu, Yunnan, China.

Background: The situation of the COVID-19 outbreak in the border areas of China and Vietnam is complex, and its progress may affect the willingness of urban and rural residents to receive the vaccine.

Objective: This study aims to understand the influence of the COVID-19 epidemic situation on the willingness of urban and rural residents in China-Vietnam border areas to get vaccinated and the factors that affect the vaccinations.

Methods: A cross-sectional survey was conducted in Hani-Yi Autonomous Prefecture of Honghe, a border area between China and Vietnam, using online and paper questionnaires from April 1 to June 4, 2021. A total of 8849 valid questionnaires were surveyed to compare the differences in the willingness of urban and rural residents to receive the COVID-19 vaccine. Single factor analysis and multivariate logistic regression analysis were used to explore the influence of the epidemic situation on the willingness to be vaccinated.

Results: In the border areas between China and Vietnam in Yunnan Province, both urban and rural residents had a high willingness (> 90%) to receive the COVID-19 vaccination, with a higher level of willingness in urban than in rural areas and a higher willingness among residents aged ≥ 56 years. Rural residents mainly concerned about the vaccination were different from urban residents (p< 0.05). About 54.8% of urban respondents and 59.2% of rural respondents indicated that their willingness to get COVID-19 vaccine would be affected by new COVID-19 cases. Respondents who were divorced, had an occupation other than farming, had contraindications to vaccination, were concerned about the safety of vaccines and worried about virus mutation, thought that the epidemic situation would not affect their willingness to get vaccinated (p< 0.05).

Conclusion: The prevention and control of epidemics in border areas is of considerable importance. It is necessary to conduct targeted health education and vaccine knowledge popularization among urban and rural residents to increase the vaccination rate and consolidate the epidemic prevention and control at the border.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0270345PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302727PMC
July 2022

Locomotion of an untethered, worm-inspired soft robot driven by a shape-memory alloy skeleton.

Sci Rep 2022 Jul 20;12(1):12392. Epub 2022 Jul 20.

Department of Mechanical Engineering & Material Science and Engineering Program, University of Colorado at Boulder, Boulder, 80309-0428, USA.

Soft, worm-like robots show promise in complex and constrained environments due to their robust, yet simple movement patterns. Although many such robots have been developed, they either rely on tethered power supplies and complex designs or cannot move external loads. To address these issues, we here introduce a novel, maggot-inspired, magnetically driven "mag-bot" that utilizes shape memory alloy-induced, thermoresponsive actuation and surface pattern-induced anisotropic friction to achieve locomotion inspired by fly larvae. This simple, untethered design can carry cargo that weighs up to three times its own weight with only a 17% reduction in speed over unloaded conditions thereby demonstrating, for the first time, how soft, untethered robots may be used to carry loads in controlled environments. Given their small scale and low cost, we expect that these mag-bots may be used in remote, confined spaces for small objects handling or as components in more complex designs.
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http://dx.doi.org/10.1038/s41598-022-16087-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300706PMC
July 2022

Reply to KR Short.

Authors:
Liang Sun Xu Lin

J Nutr 2022 Aug;152(8):2005-2006

From the Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

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http://dx.doi.org/10.1093/jn/nxac139DOI Listing
August 2022

[The effect of axis pedicle and intra-axial vertebral artery on C pedicle screw placement].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2022 Jul;36(7):866-872

Department of Spine and Trauma Surgery, Zigong Fourth People's Hospital, Zigong Sichuan, 643000, P. R. China.

Objective: To investigate the influence of axis pedicle and intra-axial vertebral artery (IAVA) alignment on C pedicle screw placement by measuring the data of head and neck CT angiography.

Methods: The axis pedicle diameter (D), isthmus height (H), isthmus thickness (T), and IAVA alignment types were measured in 116 patients (232 sides) who underwent head and neck CT angiography examinations between January 2020 and June 2020. Defined the IAVA offset direction by referencing the vertical line through the center of C transverse foramen on the coronal scan, it was divided into lateral (L), neutral (N), and medial (M). Defined the IAVA high-riding degree by referencing the horizontal line through the outlet of the C transverse foramen, it was divided into below (B), within (W), and above (A). The rate of pedicle stenosis, high-riding vertebral artery, and different IAVA types were calculated, and their relationships were analysed. Simulative C pedicle screws were implanted by Mimics 19.0 software, and the interrelation among the rates of pedicle stenosis, high-riding vertebral artery, IAVA types, and vertebral artery injury were analyzed.

Results: The rate of C pedicle stenosis was 33.6% (78/232), and the rate of high-riding vertebral artery was 35.3% (82/232). According to the offset direction and the degree of riding, IAVA was divided into 9 types, among which the N-W type (29.3%) was the most, followed by the L-W type (19.0%) and the L-B type (12.9%), accounting for 60.9%. The vertebral artery injury rate of simulative implanted C pedicle screws was 35.3% (82/232). The vertebral artery injury rate in patients with pedicle stenosis and high-riding vertebral artery was significantly higher than that who were not ( <0.001). The rate of pedicle stenosis, high-riding vertebral artery, and vertebral artery injury were significantly different among IAVA types ( <0.001), and M-A type was the most common.

Conclusion: Vertebral artery injury is more common in pedicle stenosis and/or high-riding vertebral artery and/or IAVA M-A type. Preoperative head and neck CT angiography examination has clinical guiding significance.
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http://dx.doi.org/10.7507/1002-1892.202202008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9288901PMC
July 2022

Impact of Agroclimatic Variables on Proteogenomics in Sugar Cane ( spp.) Plant Productivity.

ACS Omega 2022 Jul 29;7(27):22997-23008. Epub 2022 Jun 29.

Sugarcane Research Institute, Guangxi Academy of Agricultural Sciences/, Key Laboratory of Sugarcane Biotechnology and Genetic Improvement (Guangxi), Ministry of Agriculture and Rural Affairs/Guangxi Key Laboratory of Sugarcane Genetic Improvement Nanning, 530007 Guangxi, China.

Sugar cane ( spp. hybrids) is a major crop for sugar and renewable bioenergy worldwide, grown in arid and semiarid regions. China, the world's fourth-largest sugar producer after Brazil, India, and the European Union, all share ∼80% of the global production, and the remaining ∼20% of sugar comes from sugar beets, mostly grown in the temperate regions of the Northern Hemisphere, also used as a raw material in production of bioethanol for renewable energy. In view of carboxylation strategies, sugar cane qualifies as one of the best C crop. It has dual CO concentrating mechanisms located in its unique Krantz anatomy, having dimorphic chloroplasts located in mesophylls and bundle sheath cells for integrated operation of C and C carbon fixation cycles, regulated by enzymes to upgrade/sustain an ability for improved carbon assimilation to acquire an optimum carbon economy by producing enhanced plant biomass along with sugar yield under elevated temperature and strong irradiance with improved water-use efficiency. These superior intrinsic physiological carbon metabolisms encouraged us to reveal and recollect the facts for moving ahead with the molecular approaches to reveal the expression of proteogenomics linked with plant productivity under abiotic stress during its cultivation in specific agrizones globally.
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http://dx.doi.org/10.1021/acsomega.2c01395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9280927PMC
July 2022

A breakthrough trial of an artificial liver without systemic heparinization in hyperbilirubinemia beagle models.

Bioact Mater 2023 Feb 6;20:651-662. Epub 2022 Jul 6.

College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, 610065, China.

The development of wearable artificial livers was restricted to device miniaturization and bleeding risk with water-soluble anticoagulants. Herein, a double-deck column filled with solid anticoagulant microspheres and Kevlar porous microspheres (KPMs, bilirubin adsorbents) was connected with the principle machine of wearable artificial liver (approximately 9 kg) to treat hyperbilirubinemia beagles for the first time. With the initial normal dose of heparin, the double-deck column could afford 3 h hemoperfusion in whole blood without thrombus formation. The removal efficiency of the double-deck column for total bilirubin (TBIL) was 31.4%. Interestingly, the excessive amounts of hepatocyte metabolites were also decreased by approximately 25%. The "anticoagulant + column" realized safe and effective whole blood hemoperfusion without the plasma separation system and heparin pump; however, the proposed principle machine of wearable artificial liver and "anticoagulant + column" cannot completely replace the bio-liver now. The intelligence of the device and the versatility of the adsorbent need to be improved; moreover, advanced experimental techniques need to be developed to validate the survival rates in animals. Overall, this study is a meaningful trial for the development of wearable artificial livers in the future.
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http://dx.doi.org/10.1016/j.bioactmat.2022.06.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263408PMC
February 2023
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