Publications by authors named "Xin Wei"

956 Publications

Potassium Iodide Doping Strategy for High-Efficiency Perovskite Solar Cells Revealed by Ultrafast Spectroscopy.

J Phys Chem Lett 2022 Jan 13;13(2):711-717. Epub 2022 Jan 13.

Jiangsu Key Lab on Optoelectronic Technology, School of Physics and Technology, Nanjing Normal University, 1 Wenyuan Road, Nanjing 210023, China.

Organic-inorganic halide perovskites are promising materials for high-performance photovoltaics. The doping strategy is considered to be an effective method for regulating the performance of perovskite solar cells, yet its efficiency is still far below what has been anticipated. Here, we systematically investigate the regulatory mechanisms of the performance of perovskites by exploiting potassium iodide (KI) doping. We find that the surface states are passivated apart from the modified lattice structure. Most importantly, carrier recombination and transport are regulated by varying two different trap states when doping KI. The corresponding defect penalty can be effectively restrained at an optimal concentration of added KI (5%). A significant increase in the conductivity and radiative efficiency is achieved under such conditions. Our results provide fundamental insights into defect engineering through doping and a promising route toward highly efficient perovskite solar cells.
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http://dx.doi.org/10.1021/acs.jpclett.1c03830DOI Listing
January 2022

Whole-Genome Sequencing of 117 Chromosome Segment Substitution Lines for Genetic Analyses of Complex Traits in Rice.

Rice (N Y) 2022 Jan 13;15(1). Epub 2022 Jan 13.

Shanghai Key Laboratory of Plant Molecular Sciences, College of Life Sciences, Shanghai Normal University, 100 Guilin Road, Shanghai, 200234, China.

Rice is one of the most important food crops in Asia. Genetic analyses of complex traits and molecular breeding studies in rice greatly rely on the construction of various genetic populations. Chromosome segment substitution lines (CSSLs) serve as a powerful genetic population for quantitative trait locus (QTL) mapping in rice. Moreover, CSSLs containing target genomic regions can be used as improved varieties in rice breeding. In this study, we developed a set of CSSLs consisting of 117 lines derived from the recipient 'Huanghuazhan' (HHZ) and the donor 'Basmati Surkb 89-15' (BAS). The 117 lines were extensively genotyped by whole-genome resequencing, and a high-density genotype map was constructed for the CSSL population. The 117 CSSLs covered 99.78% of the BAS genome. Each line contained a single segment, and the average segment length was 6.02 Mb. Using the CSSL population, we investigated three agronomic traits in Shanghai and Hangzhou, China, and a total of 25 QTLs were detected in both environments. Among those QTLs, we found that RFT1 was the causal gene for heading date variance between HHZ and BAS. RFT1 from BAS was found to contain a loss-of-function allele based on yeast two-hybrid assay, and its causal variation was a P to S change in the 94th amino acid of the RFT1 protein. The combination of high-throughput genotyping and marker-assisted selection (MAS) is a highly efficient way to construct CSSLs in rice, and extensively genotyped CSSLs will be a powerful tool for the genetic mapping of agronomic traits and molecular breeding for target QTLs/genes.
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http://dx.doi.org/10.1186/s12284-022-00550-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8758858PMC
January 2022

A possible mechanism of farnesol tolerance in biofilms implemented by activating the PKC signalling pathway and stabilizing ROS levels.

J Med Microbiol 2022 Jan;71(1)

Department of Operative Dentistry and Endodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, PR China.

Biofilms are the natural growth state for most microorganisms. biofilms are composed of multiple cell types (round budding yeast-form cells, oval pseudohyphal cells, and elongated hyphal cells) encased in an extracellular matrix. biofilms are notorious for resistance to antimicrobial treatments, a property that might be determined by complex mechanisms. Exogenous farnesol exerts a certain antifungal activity against with medical implications. Different from other microbes, biofilms can tolerate exogenous farnesol at high concentration with some cells still surviving and even maintaining proliferation, but the mechanism is unclear. The study hypothesizes that resists farnesol by activating the PKC signalling pathway. The study aims to discuss the molecular mechanism of resistance to farnesol. The ROS levels, the genes and proteins of the PKC pathway were compared between the farnesol-tolerant and non-tolerant groups using ROS levels assay, -RT PCR and Western blot, respectively. Further, the mutant strains (Δ/Δ and Δ/Δ) were constructed, then the survival rates and ROS levels of biofilms exposed to farnesol were compared between mutant and wild strains. The morphological changes were observed using TEM. The survival rates of biofilms decreased rapidly under the lower concentration of farnesol (<0.05), and kept stable (>0.05) as the concentration rose up to 200 µM. The gene expression of the PKC pathway increased, while ROS levels remained stable and even decreased in the farnesol-tolerant biofilms, compared with those in the farnesol-nontolerant biofilms after farnesol treatment (<0.05); and were significantly upregulated by during the development of biofilm tolerance to farnesol. The cell wall and cytoplasm of Δ/Δ and Δ/Δ were damaged, and the ROS level increased (<0.05); meanwhile, the survival rate of biofilms decreased compared with that of wild-type strain under the same farnesol concentrations (<0.05). ROS inhibitors reversed these changes in Δ/Δ and Δ/Δ when the mutant strains exposed to farnesol. biofilms can tolerate high concentrations of farnesol by activating and of the PKC pathway and stabilizing ROS levels. The and are two key genes regulated by in the process of biofilm tolerance to farnesol.
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http://dx.doi.org/10.1099/jmm.0.001476DOI Listing
January 2022

Double-edge sword roles of iron in driving energy production versus instigating ferroptosis.

Cell Death Dis 2022 01 10;13(1):40. Epub 2022 Jan 10.

Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China.

Iron is vital for many physiological functions, including energy production, and dysregulated iron homeostasis underlies a number of pathologies. Ferroptosis is a recently recognized form of regulated cell death that is characterized by iron dependency and lipid peroxidation, and this process has been reported to be involved in multiple diseases. The mechanisms underlying ferroptosis are complex, and involve both well-described pathways (including the iron-induced Fenton reaction, impaired antioxidant capacity, and mitochondrial dysfunction) and novel interactions linked to cellular energy production. In this review, we examine the contribution of iron to diverse metabolic activities and their relationship to ferroptosis. There is an emphasis on the role of iron in driving energy production and its link to ferroptosis under both physiological and pathological conditions. In conclusion, excess reactive oxygen species production driven by disordered iron metabolism, which induces Fenton reaction and/or impairs mitochondrial function and energy metabolism, is a key inducer of ferroptosis.
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http://dx.doi.org/10.1038/s41419-021-04490-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8748693PMC
January 2022

Circulating BAFF as novel biomarker in distinguishing chronic rhinosinusitis with nasal polyps endotypes and predicting postoperative recurrence.

Int Immunopharmacol 2022 Jan 7;104:108515. Epub 2022 Jan 7.

Department of Otorhinolaryngology Head and Neck Surgery, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou 570311, China. Electronic address:

Background: B cell-activating factor (BAFF) is a proinflammatory cytokine involved in inflammatory and allergic diseases, but its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. This study aims to explore the predictive value of circulating BAFF in CRSwNP endotypes and postoperative recurrence.

Methods: We recruited 120 CRSwNP patients, including 68 non-eosinophilic CRSwNP (neCRSwNP) patients, 52 eosinophilic CRSwNP (CRSwNP) patients, and 60 healthy controls (HCs). Circulating BAFF levels of all participants were measured by enzyme-linked immunosorbent assay (ELISA), and receiver-operating characteristic (ROC) and logistic regression analyses were applied to assess the predictive ability of BAFF levels in distinguishing CRSwNP endotypes. All CRSwNP patients were followed for more than 3 years, and the predictive value of circulating BAFF for postoperative recurrence was evaluated.

Results: Serum BAFF levels were elevated in CRSwNP patients compared with the HCs (P < 0.01) and significantly higher in eCRSwNP patients. The increased serum BAFF concentrations positively correlated with blood eosinophil counts and percentages, tissue eosinophil counts, and serum total IgE (P < 0.05). The ROC curve showed that serum BAFF exhibited strong discriminative ability for eCRSwNP. Finally, 99 CRSwNP patients completed the follow-up schedule, 65 patients were classified into non-recurrence group and the other 34 patients were categorized into recurrence group. Serum BAFF levels were significantly higher in recurrence group than non-recurrence group (P < 0.001), and the ROC curve suggested a high predictive value of serum BAFF in predicting postoperative recurrence. Moreover, logistic regression and Kaplan-Meier curves showed that serum BAFF was an independent risk factor for postoperative recurrence (P < 0.05).

Conclusion: Our data suggested that serum BAFF levels were upregulated in CRSwNP patients and correlated with mucosal eosinophil infiltration severity. Serum BAFF seemed to be a novel biomarker for preoperatively distinguishing CRSwNP endotypes and predicting postoperative recurrence.
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http://dx.doi.org/10.1016/j.intimp.2021.108515DOI Listing
January 2022

Genetically Predicted Higher Educational Attainment Decreases the Risk of COVID-19 Susceptibility and Severity: A Mendelian Randomization Study.

Front Public Health 2021;9:731962. Epub 2021 Dec 23.

Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, China.

Prior observational studies indicated that lower educational attainment (EA) is associated with higher COVID-19 risk, while these findings were vulnerable to bias from confounding factors. We aimed to clarify the causal effect of EA on COVID-19 susceptibility, hospitalization, and severity using Mendelian randomization (MR). We identified genetic instruments for EA from a large genome-wide association study (GWAS) ( = 1,131,881). Summary statistics for COVID-19 susceptibility (112,612 cases and 2,474,079 controls), hospitalization (24,274 cases and 2,061,529 controls), and severity (8,779 cases and 1,001,875 controls) were obtained from the COVID-19 Host Genetics Initiative. We used the single-variable MR (SVMR) and the multivariable MR (MVMR) controlling intelligence, income, body mass index, vigorous physical activity, sedentary behavior, smoking, and alcohol consumption to estimate the total and direct effects of EA on COVID-19 outcomes. Inverse variance weighted was the primary analysis method. All the statistical analyses were performed using R software. Results from the SVMR showed that genetically predicted higher EA was correlated with a lower risk of COVID-19 susceptibility [odds ratio (OR) 0.86, 95% CI 0.84-0.89], hospitalization (OR 0.67, 95% CI 0.62-0.73), and severity (OR 0.67, 95% CI 0.58-0.79). EA still maintained its effects in most of the MVMR. Educational attainment is a predictor for susceptibility, hospitalization, and severity of COVID-19 disease. Population with lower EA should be provided with a higher prioritization to public health resources to decrease the morbidity and mortality of COVID-19.
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http://dx.doi.org/10.3389/fpubh.2021.731962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8732991PMC
January 2022

Personalized Online Learning Resource Recommendation Based on Artificial Intelligence and Educational Psychology.

Front Psychol 2021 23;12:767837. Epub 2021 Dec 23.

School of Communications and Information Engineering, Nanjing University of Posts and Telecommunications, Nanjing, China.

The objective of the study is to explore an effective way for providing students with the appropriate learning resources in the remote education scenario. Artificial intelligence (AI) technology and educational psychology theory are applied for designing a personalized online learning resource recommendation scheme to improve students' learning outcomes. First, according to educational psychology, students' learning ability can be obtained by analyzing their learning behaviors. Their identities can be classified into three main groups. Then, features of learning resources such as difficulty degree are extracted, and a LinUCB-based learning resource recommendation algorithm is proposed. In this algorithm, a personalized exploration coefficient is carefully constructed according to student's ability and attention scores. It can adaptively adjust the ratio of exploration and exploitation during recommendation. Finally, experiments are conducted for evaluating the superior performance of the proposed scheme. The experimental results show that the proposed recommendation scheme can find appropriate learning resources which will match the student's ability and satisfy the student's personalized demands. Meanwhile, by comparing with existing state-of-the-art recommendation schemes, the proposed scheme can achieve accurate recommendations, so as to provide students with the most suitable online learning resources and reduce the risk brought by exploration. Therefore, the proposed scheme can not only control the difficulty degree of learning resources within the student's ability but also encourage their potential by providing suitable learning resources.
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http://dx.doi.org/10.3389/fpsyg.2021.767837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8733000PMC
December 2021

A novel reticular node in the brainstem synchronizes neonatal mouse crying with breathing.

Neuron 2021 Dec 30. Epub 2021 Dec 30.

Department of Physiology, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address:

Human speech can be divided into short, rhythmically timed elements, similar to syllables within words. Even our cries and laughs, as well as the vocalizations of other species, are periodic. However, the cellular and molecular mechanisms underlying the tempo of mammalian vocalizations remain unknown. Furthermore, even the core cells that produce vocalizations remain ill-defined. Here, we describe rhythmically timed neonatal mouse vocalizations that occur within single breaths and identify a brainstem node that is necessary for and sufficient to structure these cries, which we name the intermediate reticular oscillator (iRO). We show that the iRO acts autonomously and sends direct inputs to key muscles and the respiratory rhythm generator in order to coordinate neonatal vocalizations with breathing, as well as paces and patterns these cries. These results reveal that a novel mammalian brainstem oscillator embedded within the conserved breathing circuitry plays a central role in the production of neonatal vocalizations.
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http://dx.doi.org/10.1016/j.neuron.2021.12.014DOI Listing
December 2021

The industrial solvent 1,4-dioxane causes hyperalgesia by targeting capsaicin receptor TRPV1.

BMC Biol 2022 Jan 7;20(1):10. Epub 2022 Jan 7.

State Key Laboratory of Virology, College of Life Sciences, Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, 430072, Hubei, China.

Background: The synthetic chemical 1,4-dioxane is used as industrial solvent, food, and care product additive. 1,4-Dioxane has been noted to influence the nervous system in long-term animal experiments and in humans, but the molecular mechanisms underlying its effects on animals were not previously known.

Results: Here, we report that 1,4-dioxane potentiates the capsaicin-sensitive transient receptor potential (TRP) channel TRPV1, thereby causing hyperalgesia in mouse model. This effect was abolished by CRISPR/Cas9-mediated genetic deletion of TRPV1 in sensory neurons, but enhanced under inflammatory conditions. 1,4-Dioxane lowered the temperature threshold for TRPV1 thermal activation and potentiated the channel sensitivity to agonistic stimuli. 1,3-dioxane and tetrahydrofuran which are structurally related to 1,4-dioxane also potentiated TRPV1 activation. The residue M572 in the S4-S5 linker region of TRPV1 was found to be crucial for direct activation of the channel by 1,4-dioxane and its analogs. A single residue mutation M572V abrogated the 1,4-dioxane-evoked currents while largely preserving the capsaicin responses. Our results further demonstrate that this residue exerts a gating effect through hydrophobic interactions and support the existence of discrete domains for multimodal gating of TRPV1 channel.

Conclusions: Our results suggest TRPV1 is a co-receptor for 1,4-dioxane and that this accounts for its ability to dysregulate body nociceptive sensation.
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http://dx.doi.org/10.1186/s12915-021-01211-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742357PMC
January 2022

Initial Experience of Self-Expanding Metal Ureteral Stent in Recurrent Ureteral Stricture After Ureteroplasty.

Front Surg 2021 21;8:765810. Epub 2021 Dec 21.

Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, China.

The aim of this prospective study was to assess the safety and effectiveness of self-expanding metal ureteral stent (MUS) for the treatment of recurrent ureteral stricture after ureteroplasty. We prospectively included 24 patients who underwent MUS implantation between February 2019 and August 2020. The inclusion criteria for the procedure were recurrent ureteral strictures after ureteroplasty. A paired test was used to compare continuous variables before and after surgery. A total of 24 patients were finally included in this study. The stricture site was most common on the proximal ureter 19 (79.2%), followed by distal ureter 4 (16.7%) and middle ureter 1 (4.2%). The median length of ureteral stricture is 2.5 (range 1-18) cm. The median operative time was 51.5 min, and the median hospital stay time after surgery was 3 days. Post-operative complication included pain 1 (4.2%), urinary tract infection 2 (8.3%) and hematuria 2 (8.3%). After a median follow-up of 12 months, 19/24 (83.3%) patients were clinically and radiologically successful. We endoscopically adjusted or exchanged the failed stents. The volume of hydronephrosis (124.7 ± 132.5 vs. 66.4 ± 73.2 cm, = 0.015), blood creatinine level (104.5 ± 45.4 vs. 80.1 ± 23.2 μmol/L, = 0.044) and urea nitrogen level (6.9 ± 2.4 vs. 4.8 ± 1.5 mmol/L, = 0.003) decreased significantly after a median follow-up of 12 months. MUS is a safe and effective way to manage recurrent ureteral strictures after ureteroplasty. This technique provides a new choice for the treatment of recurrent stricture.
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http://dx.doi.org/10.3389/fsurg.2021.765810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724242PMC
December 2021

Assessing the relationship between systemic immune-inflammation index and mortality in patients with hypertrophic cardiomyopathy.

Ups J Med Sci 2021 3;126. Epub 2021 Dec 3.

Department of Cardiology, West China Hospital of Sichuan University, Chengdu, China.

Background: This study investigates the predictive value of the systemic immune-inflammation index (SII), which was calculated as platelet × neutrophil/lymphocyte ratio, for all-cause mortality in patients with hypertrophic cardiomyopathy (HCM).

Methods: A total of 360 HCM patients were enrolled. They were divided into three groups based on the tertiles of baseline SII. The association between SII and all-cause mortality was analyzed.

Results: There were 53 HCM patients who died during a mean follow-up time of 4.8 years (min: 6 days and max: 10.8 years), and the mortality rate was 3.0 per 100 person years. The cumulative mortality rate was significantly different among the three tertiles of SII ( = 0.004), and the mortality rate in tertile 3 was much higher than that in the first two tertiles. In reference to tertile 1, the fully adjusted hazard ratios of all-cause mortality were 1.02 for the tertile 2 (95% confidence interval [CI]: 0.45-2.31,  = 0.966) and 2.31 for tertile 3 (95% CI: 1.10-4.87,  = 0.027). No significant interactions between SII and other variables were observed during subgroup analysis. The discriminative power was better for mid-term outcome than that for short-term or long-term outcomes. Sensitivity analyses including patients with normal platelet and white blood cell count have revealed similar results.

Conclusion: SII was a significant risk factor for all-cause mortality in HCM patients. However, the discriminative power was poor to moderate. It could be used in combination with other risk factors in mortality risk stratification in HCM.
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http://dx.doi.org/10.48101/ujms.v126.8124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8693584PMC
January 2022

Phase 1 study of anti-CD47 monoclonal antibody CC-90002 in patients with relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndromes.

Ann Hematol 2022 Jan 4. Epub 2022 Jan 4.

University of Chicago Medicine, Chicago, IL, USA.

CC-90002 is an anti-CD47 antibody that inhibits CD47-SIRPα interaction and enables macrophage-mediated killing of tumor cells in hematological cancer cell lines. In this first clinical, phase 1, dose-escalation and -expansion study (CC-90002-AML-001; NCT02641002), we evaluated CC-90002 in patients with relapsed/refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS). CC-90002 was administered in escalating doses of 0.1-4.0 mg/kg, using a modified 3 + 3 design. Primary endpoints included dose-limiting toxicities (DLTs), non-tolerated dose (NTD), maximum tolerated dose (MTD), and recommended phase 2 dose. Secondary endpoints included preliminary efficacy, pharmacokinetics, and presence/frequency of anti-drug antibodies (ADAs). Between March 2016 and July 2018, 28 patients were enrolled (24 with AML and 4 with MDS) at 6 sites across the USA. As of July 18, 2018, all patients had discontinued, mainly due to death or progressive disease. The most common treatment-emergent adverse events were diarrhea (46.4%), thrombocytopenia (39.3%), febrile neutropenia (35.7%), and aspartate aminotransferase increase (35.7%). Four patients experienced DLTs (1 patient had grade 4 disseminated intravascular coagulation and grade 5 cerebral hemorrhage, 1 had grade 3 purpura, 1 had grade 4 congestive cardiac failure and grade 5 acute respiratory failure, and another had grade 5 sepsis). The NTD and MTD were not reached. No objective responses occurred. CC-90002 serum exposure was dose-dependent. ADAs were present across all doses, and the proportion of ADA-positive patients in cycle 1 increased over time. Despite no unexpected safety findings, the CC-90002-AML-001 study was discontinued in dose escalation for lack of monotherapy activity and evidence of ADAs. However, as other anti-CD47 agents in clinical trials are showing promising early results for AML and MDS, understanding preclinical and clinical differences between individual agents in this class will be of high importance.
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http://dx.doi.org/10.1007/s00277-021-04734-2DOI Listing
January 2022

New risk score model for identifying individuals at risk for diabetes in southwest China.

Prev Med Rep 2021 Dec 24;24:101618. Epub 2021 Oct 24.

Department of Cardiology, West China Hospital of Sichuan University, Chengdu, China.

The prevalence of diabetes is increasing rapidly and becoming a major public health issue worldwide. We aimed to develop a novel nomogram model for long-term diabetic risk prediction in a Chinese population. A prospective cohort study was performed on 687 nondiabetic individuals who underwent routine physical examination in 1992 and 2007. Using the least absolute shrinkage and selection operator model to optimize feature selection. Multiple Cox regression analysis was performed, and a simple nomogram was constructed. The area under receiver operating characteristic curve (AUC) and calibration plot were conducted to assess the predictive accuracy of the model. The model was subjected to bootstrap internal validation. Of the 687 participants without diabetes at baseline, 74 developed diabetes during the follow-up time. This simple nomogram model was constructed by family history of diabetes, height, waist circumference, triglycerides, fasting plasma glucose and white blood cell count. The AUCs were 0.812 (95% CI: 0.729-0.895) and 0.794 (95% CI: 0.734-0.854) for 10-year and 15-year diabetic risk. The bootstrap corrected c-index was 0.771 (95% CI: 0.721-0.821). The calibration plot also achieved good agreement between observational and actual diabetic incidence. The stratification into different risk groups by optimal cut-off value of 12.8 allowed significant distinction between cumulative diabetic incidence curves in the whole cohort and several subgroups. We established and internally validated a novel nomogram which can provide individual diabetic risk prediction for Chinese population and this practical screening model may help clinicians to identify individuals at high risk of diabetes.
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http://dx.doi.org/10.1016/j.pmedr.2021.101618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8684021PMC
December 2021

Long non-coding RNA MAGI2 inactivates STAT3 pathway to inhibit prostate cancer cell proliferation via acting as a microRNA-424-5p sponge.

J Cancer 2022 1;13(1):343-353. Epub 2022 Jan 1.

Department of Urology, China-Japan Union Hospital of Jilin University, 126 Xiantai Street Changchun 130033, P.R.China.

Aberrant expression of long non-coding RNAs (lncRNAs) that results in sustained activation of cell growth promoting pathways is an important mechanism in driving prostate cancer progression. In the present study, we explored differentially expressed lncRNAs in two microarray datasets of prostate benign and malignant tissues. We found that was one of the most downregulated lncRNAs in prostate tumors, which was further confirmed in our collected clinical samples. The function assays showed that overexpression decreased cell viability and led to obvious cell apoptosis in PC-3 and DU145 prostate cancer cells. Elevation of decreased the activity of STAT3 in PC-3 and DU145. In addition, microRNA-424-5p (miR-424-5p), a positive regulator of STAT3 pathway, was predicted as a target of , furthermore, the interaction between and miR-424-5p was confirmed via reverse-transcript polymerase chain reaction (RT-qPCR), dual luciferase reporter assay and RNA immunoprecipitation (RIP). upregulated miR-424-5p and downregulated COP1 in PC-3 and DU145. More importantly, IL6-induced activation of STAT3 pathway could attenuate the biological effect of in PC-3 and DU145. In clinical samples, levels were negatively correlated with miR-424-5p expression, while positively correlated with mRNA expression. Altogether, the current study revealed as a novel negative regulator of prostate cancer development.
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http://dx.doi.org/10.7150/jca.60749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8692692PMC
January 2022

T Cell-Mediated Autoimmunity in Glaucoma Neurodegeneration.

Front Immunol 2021 16;12:803485. Epub 2021 Dec 16.

Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China.

Glaucoma as the leading neurodegenerative disease leads to blindness in 3.6 million people aged 50 years and older worldwide. For many decades, glaucoma therapy has primarily focused on controlling intraocular pressure (IOP) and sound evidence supports its role in delaying the progress of retinal ganglial cell (RGC) damage and protecting patients from vision loss. Meanwhile, accumulating data point to the immune-mediated attack of the neural retina as the underlying pathological process behind glaucoma that may come independent of raised IOP. Recently, some scholars have suggested autoimmune aspects in glaucoma, with autoreactive T cells mediating the chief pathogenic process. This autoimmune process, as well as the pathological features of glaucoma, largely overlaps with other neurodegenerative diseases in the central nervous system (CNS), including Alzheimer's disease, Parkinson's disease, and multiple sclerosis. In addition, immune modulation therapy, which is regarded as a potential solution for glaucoma, has been boosted in trials in some CNS neurodegenerative diseases. Thus, novel insights into the T cell-mediated immunity and treatment in CNS neurodegenerative diseases may serve as valuable inspirations for ophthalmologists. This review focuses on the role of T cell-mediated immunity in the pathogenesis of glaucoma and discusses potential applications of relevant findings of CNS neurodegenerative diseases in future glaucoma research.
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http://dx.doi.org/10.3389/fimmu.2021.803485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8716691PMC
December 2021

Brain Camp: A Summer Pipeline Program to Increase Diversity in Neurosciences.

Neurologist 2021 Dec 30. Epub 2021 Dec 30.

Department of Neurology, Weill Institute for Neurosciences Office of Post Baccalaureate and Outreach Programs, University of California, San Francisco, San Francisco, CA.

Background: Despite calls to increase diversity in the health care workforce, most medical fields including neurology have seen minimal advances, owing in part to the lack of developing a robust pipeline for trainees from underrepresented backgrounds. We sought to create an immersive, replicable neurology-themed summer camp and longitudinal mentorship program for underrepresented-in-medicine (URM) high-school students to encourage them to enter the training pipeline in neuroscience-related fields.

Methods: We established an annual, no-cost 1-week camp for local URM students with the goals of exposing them to different health care professions within neuroscience while providing them with college application resources and long-term mentorship. A postprogram survey was distributed to assess the students' attitudes towards the camp and their desires to pursue health care careers.

Results: Over the 4 years since the founding of the camp (2016-2020), a total of 96 students participated, of whom 53% were URM, 74% came from very low-income households, and 61% had parents who did not attend college. In total, 87 students (91%) completed the postcamp survey. Nearly all (97%) of the respondents were likely to recommend the camp to their peers, and the vast majority (85%) felt that Brain Camp made them more likely to pursue careers in health care.

Conclusions: Brain Camp seeks to address the unmet need for low barrier-to-entry programs designed for URM high-school students interested in health care careers. We envision that our camp may serve as a blueprint for other similar programs across the nation with the goal of addressing the URM pipeline in neuroscience.
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http://dx.doi.org/10.1097/NRL.0000000000000409DOI Listing
December 2021

Diagnosis of Bone Mineral Density Based on Backscattering Resonance Phenomenon Using Coregistered Functional Laser Photoacoustic and Ultrasonic Probes.

Sensors (Basel) 2021 Dec 9;21(24). Epub 2021 Dec 9.

School of Optoelectronic Science and Engineering, University of Electronic Science and Technology of China, Chengdu 610054, China.

Dual-energy X-ray absorptiometry (DXA) machines based on bone mineral density (BMD) represent the gold standard for osteoporosis diagnosis and assessment of fracture risk, but bone strength and toughness are strongly correlated with bone collagen content (CC). Early detection of osteoporosis combined with BMD and CC will provide improved predictability for avoiding fracture risk. The backscattering resonance (BR) phenomenon is present in both ultrasound (US) and photoacoustic (PA) signal transmissions through bone, and the peak frequencies of BR can be changed with BM and CC. This phenomenon can be explained by the formation of standing waves within the pores. Simulations were then conducted for the same bone µCT images and the resulting resonance frequencies were found to match those predicted using the standing wave hypothesis. Experiments were performed on the same bone sample using an 808 nm wavelength laser as the PA source and 3.5 MHz ultrasonic transducer as the US source. The backscattering resonance effect was observed in the transmitted waves. These results verify our hypothesis that the backscattering resonance phenomenon is present in both US and PA signal transmissions and can be explained using the standing waves model, which will provide a suitable method for the early detection of osteoporosis.
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http://dx.doi.org/10.3390/s21248243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706256PMC
December 2021

New Monoterpenoid Indoles with Osteoclast Activities from .

Molecules 2021 Dec 9;26(24). Epub 2021 Dec 9.

School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China.

The well-known toxic medicine is widely and historically used to treat bone fracture and skin ulcers by the folk people of China. Two new monoterpenoid indole alkaloids, gelselegandines D and E, together with the known analogue gelegamine A were isolated from . Their structures were elucidated by means of spectroscopic techniques and quantum chemical calculations. All isolated compounds were tested for the effects on RANKL-induced osteoclast formation. Interestingly, gelselegandine E and gelegamine A, respectively, showed significant promoting and inhibitory activities on osteoclastogenesis, while gelselegandine D had no activity under the same concentration. This work suggested the different configurations for the carbons near the C-19/20 oxygen rings of the isolated compounds may be the key active groups on osteoclast formation and provided the evidence for the rationality as the traditional treatment for bone-related diseases of .
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http://dx.doi.org/10.3390/molecules26247457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8708120PMC
December 2021

A ReaxFF molecular dynamic study on pyrolysis behavior and sulfur transfer during pyrolysis of vulcanized natural rubber.

Waste Manag 2021 Dec 18;139:39-49. Epub 2021 Dec 18.

State Key Laboratory of Coal Combustion, Huazhong University of Science and Technology, 430074 Wuhan, Hubei, China.

In this work, ReaxFF molecular simulations were performed to study the pyrolysis behavior of chemical cross-linked natural rubber (NR) under non-isothermal and isothermal conditions. Three different sulfur vulcanized NR models were established and simulated to study the effect of inner sulfur structure on NR decomposition behavior and sulfur evolution in comparison with carbon cross-linked structure. To understand the NR decomposition with temperatures, the non-isothermal simulations were performed between 300 and 3800 K at a 50 K ps heating rate. The results reveal that the decomposition process can be classified into four stages: 1) Structure adjustment; 2) Decomposition of the main carbon chains; 3) Secondary decomposition of heavy tar; and 4) Deep decomposition of light tar. Based on the results of non-isothermal pyrolysis, four different temperatures were selected for the isothermal simulations. Compared with carbon cross-linked NR, sulfur cross-linked structures facilitate the generation of CH and CH in the gas phase at low temperatures. At higher temperatures, more heavy tar is generated. Regarding the sulfur evolution, the sulfur-containing products mainly include HS, thiophene, sulfide, and thiol. The distribution of sulfur-containing products with temperatures follows the similar pattern with the product distribution of main compounds. At higher temperatures, most sulfur exists in the form of thiophene compounds. In particular, the structure with single CS cross-links facilitates the generation of HS at low temperatures. The results of this work provide insight into the sulfur transformation and pyrolysis behavior of vulcanized NR.
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http://dx.doi.org/10.1016/j.wasman.2021.12.022DOI Listing
December 2021

SF3B1 mutant-induced missplicing of MAP3K7 causes anemia in myelodysplastic syndromes.

Proc Natl Acad Sci U S A 2022 Jan;119(1)

Irving Cancer Research Center, Columbia University, New York, NY 10032;

SF3B1 is the most frequently mutated RNA splicing factor in cancer, including in ∼25% of myelodysplastic syndromes (MDS) patients. SF3B1-mutated MDS, which is strongly associated with ringed sideroblast morphology, is characterized by ineffective erythropoiesis, leading to severe, often fatal anemia. However, functional evidence linking mutations to the anemia described in MDS patients harboring this genetic aberration is weak, and the underlying mechanism is completely unknown. Using isogenic WT and mutant cell lines, normal human CD34 cells, and MDS patient cells, we define a previously unrecognized role of the kinase MAP3K7, encoded by a known mutant SF3B1-targeted transcript, in controlling proper terminal erythroid differentiation, and show how MAP3K7 missplicing leads to the anemia characteristic of SF3B1-mutated MDS, although not to ringed sideroblast formation. We found that p38 MAPK is deactivated in SF3B1 mutant isogenic and patient cells and that MAP3K7 is an upstream positive effector of p38 MAPK. We demonstrate that disruption of this MAP3K7-p38 MAPK pathway leads to premature down-regulation of GATA1, a master regulator of erythroid differentiation, and that this is sufficient to trigger accelerated differentiation, erythroid hyperplasia, and ultimately apoptosis. Our findings thus define the mechanism leading to the severe anemia found in MDS patients harboring mutations.
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http://dx.doi.org/10.1073/pnas.2111703119DOI Listing
January 2022

Targeting genomic SARS-CoV-2 RNA with siRNAs allows efficient inhibition of viral replication and spread.

Nucleic Acids Res 2022 01;50(1):333-349

Institute of Virology, School of Medicine, Technische Universität München / Helmholtz Zentrum München, Trogerstr. 30, 81675 Munich, Germany.

A promising approach to tackle the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) could be small interfering (si)RNAs. So far it is unclear, which viral replication steps can be efficiently inhibited with siRNAs. Here, we report that siRNAs can target genomic RNA (gRNA) of SARS-CoV-2 after cell entry, and thereby terminate replication before start of transcription and prevent virus-induced cell death. Coronaviruses replicate via negative sense RNA intermediates using a unique discontinuous transcription process. As a result, each viral RNA contains identical sequences at the 5' and 3' end. Surprisingly, siRNAs were not active against intermediate negative sense transcripts. Targeting common sequences shared by all viral transcripts allowed simultaneous suppression of gRNA and subgenomic (sg)RNAs by a single siRNA. The most effective suppression of viral replication and spread, however, was achieved by siRNAs that targeted open reading frame 1 (ORF1) which only exists in gRNA. In contrast, siRNAs that targeted the common regions of transcripts were outcompeted by the highly abundant sgRNAs leading to an impaired antiviral efficacy. Verifying the translational relevance of these findings, we show that a chemically modified siRNA that targets a highly conserved region of ORF1, inhibited SARS-CoV-2 replication ex vivo in explants of the human lung. Our work encourages the development of siRNA-based therapies for COVID-19 and suggests that early therapy start, or prophylactic application, together with specifically targeting gRNA, might be key for high antiviral efficacy.
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http://dx.doi.org/10.1093/nar/gkab1248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8754636PMC
January 2022

Corrigendum: Retinal Organoids: Cultivation, Differentiation, and Transplantation.

Front Cell Neurosci 2021 2;15:810268. Epub 2021 Dec 2.

Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China.

[This corrects the article DOI: 10.3389/fncel.2021.638439.].
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http://dx.doi.org/10.3389/fncel.2021.810268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8678588PMC
December 2021

Vascular thrombosis and vasculitis in the gastrointestinal tract are associated with poor prognosis in patients with COVID-19.

Int J Clin Exp Pathol 2021 15;14(11):1069-1079. Epub 2021 Nov 15.

Department of Pathology, University Hospital Cleveland Medical Center Cleveland, OH 44106, USA.

Aim: To report pathologic findings in the gastrointestinal (GI) tract of coronavirus disease 2019 (COVID-19) patients.

Material And Methods: we evaluated clinical and GI tract histologic findings in six COVID-19 patients that presented with GI symptoms like diarrhea, and abdominal pain. This study includes surgical resection specimens from five patients and two sets of biopsy specimens from one patient.

Results: Idiopathic inflammatory bowel disease was considered in three of six cases based on clinical, radiologic, and endoscopic presentation. Histologically, the enteric mucosa had a spectrum of histologic changes, including active enteritis, chronic active enteritis, and transmural necrosis. Extensive thrombi in vessels and/or vasculitis were identified in three out of the six cases. The presence of extensive vascular thrombi is associated with poor prognosis, and the three patients deceased in a short period of time (ranges from 7-67 days, median 14 days) after admission for GI symptoms. Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) RNA was detected in bowel tissue of one case. The other three patients recovered and were discharged and free of GI symptoms (follow-up period ranges from 235 days to 270 days, median 237 days).

Conclusion: COVID-19 associated enteritis may mimic Crohn's disease clinically, radiologically and endoscopically, and these two entities can be differentiated by pathologic findings. COVID-19 patients with GI symptoms may warrant a workup to evaluate for pathologic changes, as the presence of vasculitis and microthrombi may predict poor clinical outcome.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8661070PMC
November 2021

Systemic pharmacological verification of Baixianfeng decoction regulating TNF-PI3K-Akt-NF-κB pathway in treating rheumatoid arthritis.

Bioorg Chem 2021 Nov 26;119:105519. Epub 2021 Nov 26.

Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, Hefei 230601, PR China. Electronic address:

Traditional Chinese medicine has a long history of treating complex diseases, especially for the conditioning of systemic diseases. It has been reported that Baixianfeng (BXF) decoction used to treat rheumatoid arthritis (RA) may be due to its systemic regulatory effect, but the specific mechanism still remains to be elucidated. The research philosophy and methods of systemic pharmacology were used to explore the mechanism of BXF decoction in treating RA in this study. TCMSP database was used to search the ingredients of BXF decoction and screen the ADME parameters. The parameter index was set as OB ≥ 30%, DL ≥ 0.18, HL ≥ 4 h. The targets of the screened compounds were searched and predicted by TCMSP and Target-Prediction platforms. The disease targets of RA were obtained through the DisGeNET, OMIM, and PharmGkb databases. A series of network construction and analysis relied on Cytoscape 3.2.1 software, and the DAVID database was used for pathway enrichment. The adjuvant arthritis rat model was used for the verification of animal experiments to verify the predicted pathway results in terms of pathological phenotype, inflammatory factors, and pathway protein expression. The results showed that the related targets of 81 active ingredients in the drug crossed 56 targets of RA, and these common targets were enriched in 83 significant pathways, among which the TNF signaling pathway had research significance. Animal experiments have proved that BXF decoction was effective in treating adjuvant arthritis rats. The drug relieved the pathological phenotype of rats in dose-dependent. It reduced the serum content of TNF-α and IL-1β, and reduced the gene expression of TNF-α and IL-6 in spleen tissue. In the cartilage tissue protein of rats, it inhibited the degradation of collagen Ⅱ protein. Further, BXF decoction reduced the activation of p-PI3K, p-Akt, and p-P65 protein, and decreased the overexpression of apoptotic proteins such as cleaved-caspase8 and cleaved-caspase3 in cartilage tissue. Meanwhile, it inhibited the protein expression of MMP9, TNF-α, IL-6, and IL-1β. In conclusion, this study successfully practiced the combination of systemic pharmacology and experimental verification, and clarified that BXF decoction inhibited the progression of adjuvant arthritis rats through the TNF-PI3K-Akt-NF-κB signal axis. It provides new evidence for the study of the mechanism of BXF decoction in treating RA.
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http://dx.doi.org/10.1016/j.bioorg.2021.105519DOI Listing
November 2021

Type of anesthesia and quality of recovery in male patients undergoing lumbar surgery: a randomized trial comparing propofol-remifentanil total i.v. anesthesia with sevoflurane anesthesia.

BMC Anesthesiol 2021 12 1;21(1):300. Epub 2021 Dec 1.

Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230036, China.

Background: Previous studies have shown that women achieve a better quality of postoperative recovery from total intravenous anesthesia (TIVA) than from inhalation anesthesia, but the effect of anesthesia type on recovery in male patients is unclear. This study therefore compared patient recovery between males undergoing lumbar surgery who received TIVA and those who received sevoflurane anesthesia.

Methods: Eighty male patients undergoing elective one- or two-level primary transforaminal lumbar interbody fusion (TLIF) were randomly divided into two groups: the TIVA group (maintenance was achieved with propofol and remifentanil) or sevoflurane group (SEVO group: maintenance was achieved with sevoflurane and remifentanil). The quality of recovery-40 questionnaire (QoR-40) was administered before surgery and on postoperative days 1 and 2 (POD1 and POD2). Pain scores, postoperative nausea and vomiting, postoperative hospital stay, anesthesia consumption, and adverse effects were recorded.

Results: The QoR-40 scores were similar on the three points (Preoperative, POD1 and POD2). Pain scores were significantly lower in the SEVO group than in the TIVA group on POD1 (30.6 vs 31.4; P = 0.01) and POD2 (32 vs 33; P = 0.002). There was no significant difference in the postoperative hospital stay or complications in the postanesthesia care unit between the TIVA group and the SEVO group.

Conclusions: This study demonstrates that the quality of recovery is not significantly different between male TLIF surgery patients who receive TIVA and those who receive sevoflurane anesthesia. Patients in the TIVA group had better postoperative analgesic effect on POD2.

Trial Registration: This was registered at http://www.chictr.org.cn (registration number ChiCTR-IOR-16007987, registration date: 24/02/2016).
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http://dx.doi.org/10.1186/s12871-021-01519-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8638110PMC
December 2021

Preclinical safety profile of RC88-ADC:a novel mesothelin-targeted antibody conjugated with Monomethyl auristatin E.

Drug Chem Toxicol 2021 Nov 28:1-11. Epub 2021 Nov 28.

YanTai University, Yantai, China.

Mesothelin (MSLN) is an attractive therapeutic target for antibody drug conjugates (ADC) because of significant differences in expression pattern between diseased and normal tissues. RC88-ADC is a novel ADC, targeting MSLN, and inhibits tumor growth significantly in mice xenograft models. We performed an 11-week repeated dose toxicity study of RC88-ADC via intravenous injection in Cynomolgus Monkeys with an 8-Week recovery period according to International Conference on Harmonization (ICH) S9 and S6(R1). RC88-ADC was administered to groups of 5 male and 5 female monkeys at dose levels of 2.5, 5, and 10 mg/kg/2 weeks, meanwhile vehicle, naked antibody, small molecule groups were set up as the control. 4 animals died in 10 mg/kg group of RC88-ADC. The clinical symptoms mainly included ocular toxicity, weight loss and food intake decrease in the middle and high dose groups of RC88-ADC. RC88-ADC caused dose-related reversible myelosuppression, manifested as hematologic toxicity, which was consistent with the small molecule toxicity profile of its coupling. The highest non-severely toxic dose of RC88-ADC was 5 mg/kg in monkeys after repeated dosing. Nonetheless, the integrated analysis showed that RC88-ADC demonstrated an acceptable safety profile and provided an improved treatment window. These results pave the way for further investigation of RC88-ADC in humans.
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http://dx.doi.org/10.1080/01480545.2021.2005085DOI Listing
November 2021

Proteomic profiling identifies signatures associated with progression of precancerous gastric lesions and risk of early gastric cancer.

EBioMedicine 2021 Dec 22;74:103714. Epub 2021 Nov 22.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China. Electronic address:

Background: Molecular features underlining the multistage progression of gastric lesions and development of early gastric cancer (GC) are poorly understood, restricting the ability to GC prevention and management.

Methods: We portrayed proteomic landscape and explored proteomic signatures associated with progression of gastric lesions and risk of early GC. Tissue proteomic profiling was conducted for a total of 324 subjects. A case-control study was performed in the discovery stage (n=169) based on populations from Linqu, a known high-risk area for GC in China. We then conducted two-stage validation, including a cohort study from Linqu (n = 56), with prospective follow-up for progression of gastric lesions (280-473 days), and an independent case-control study from Beijing (n = 99).

Findings: There was a clear distinction in proteomic features for precancerous gastric lesions and GC. We derived four molecular subtypes of gastric lesions and identified subtype-S4 with the highest progression risk. We found 104 positively-associated and 113 inversely-associated proteins for early GC, with APOA1BP, PGC, HPX and DDT associated with the risk of gastric lesion progression. Integrating these proteomic signatures, the ability to predict progression of gastric lesions was significantly strengthened (areas-under-the-curve=0.88 (95%CI: 0.78-0.99) vs. 0.56 (0.36-0.76), Delong's P = 0.002). Immunohistochemistry assays and examination at mRNA level validated the findings for four proteins.

Interpretation: We defined proteomic signatures for progression of gastric lesions and risk of early GC, which may have translational significance for identifying particularly high-risk population and detecting GC at an early stage, improving potential for targeted GC prevention.

Funding: The funders are listed in the Acknowledgement.
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http://dx.doi.org/10.1016/j.ebiom.2021.103714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8617343PMC
December 2021

Metabolome and microbiome of chronic periapical periodontitis in permanent anterior teeth: a pilot study.

BMC Oral Health 2021 11 23;21(1):599. Epub 2021 Nov 23.

Jiangsu Province Key Laboratory of Oral Diseases, Department of Conservative Dentistry and Endodontics, Stomatological Hospital, Nanjing Medical University, Nanjing, China.

Background: Periapical periodontitis is a common oral inflammatory disease that affects periapical tissues and is caused by bacteria in the root canal system. The relationship among the local metabolome, the inflammatory grade, and the type and abundance of microorganisms associated with periapical periodontitis is discussed in this study.

Methods: The inflammatory grades of periapical samples from 47 patients with chronic periapical periodontitis in permanent anterior teeth were determined based on the immune cell densities in tissues subjected to haematoxylin and eosin staining. The metabolome was evaluated using ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, followed by principal component analysis and orthogonal partial least squares discriminant analysis. The microbiome was accessed using 16 S rRNA high-throughput sequencing. The differences in the metabolomes and microbiomes of the periapical periodontitis samples were assessed using Spearman's correlation analysis.

Result: N-acetyl-D-glucosamine, L-tryptophan, L-phenylalanine, and 15 other metabolites were identified by the comparison between samples with severe inflammation and mild or moderate inflammation. Four amino acid metabolism pathways and one sugar metabolism pathway were associated with the inflammatory grade of periapical periodontitis. The abundance of Actinomycetes was negatively correlated with the abundance of glucosamine (GlcN), while the abundance of Tannerella was positively correlated with the abundance of L-methionine.

Conclusions: The local metabolome of periapical periodontitis is correlated with the inflammatory grade. The abundance of the local metabolites GlcN and L-methionine is correlated with the abundance of the major microorganisms Actinomycetes and Tannerella, respectively.
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http://dx.doi.org/10.1186/s12903-021-01972-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8609808PMC
November 2021

The incidence and predictors of high-degree atrioventricular block in patients with bicuspid aortic valve receiving self-expandable transcatheter aortic valve implantation.

J Geriatr Cardiol 2021 Oct;18(10):825-835

Department of Cardiac Catheterization Laboratory, West China Hospital, Sichuan University, Sichuan, China.

Background: The high-degree atrioventricular block (HAVB) in patients with bicuspid aortic valve (BAV) treated with transcatheter aortic valve implantation (TAVI) remains high. The study aims to explore this poorly understood subject of mechanisms and predictors for HAVB in BAV self-expandable TAVI patients.

Methods: We retrospectively included 181 BAV patients for analysis. Using computed tomography data, the curvature of ascending aorta (AAo) was quantified by the angle (AAo angle) between annulus and the cross-section at 35 mm above annulus (where the stent interacts with AAo the most). The valvular anatomy and leaflet calcification were also characterized.

Results: The 30-day HAVB rate was 16.0% (median time to HAVB was three days). Type-1 morphology was found in 79 patients (43.6%) (left- and right-coronary cusps fusion comprised 79.7%). Besides implantation below membrane septum, large AAo angle [odds ratio (OR) = 1.08, = 0.016] and type-1 morphology (OR = 4.97, = 0.001) were found as the independent predictors for HAVB. Together with baseline right bundle branch block, these predictors showed strong predictability for HAVB with area under the cure of 0.84 (sensitivity = 62.1%, specificity = 92.8%). Bent AAo and calcified raphe had a synergistic effect in facilitating high implantation, though the former is associated with at-risk deployment (device implanted above annulus + prothesis pop-out, versus straight AAo: 9.9% 2.2%, = 0.031).

Conclusions: AAo curvature and type-1 morphology are novel predictors for HAVB in BAV patients following self-expandable TAVI. For patients with bent AAo or calcified raphe, a progressive approach to implant the device above the lower edge of membrane septum is favored, though should be done cautiously to avoid pop-out.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2021.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558740PMC
October 2021
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