Publications by authors named "Chen Zhao"

1,544 Publications

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Cholecystokinin 1 receptor activation restores normal mTORC1 signaling and is protective to Purkinje cells of SCA mice.

Cell Rep 2021 Oct;37(2):109831

Institute of Translational Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address:

Spinocerebellar ataxias (SCAs) are a group of genetic diseases characterized by progressive ataxia and neurodegeneration, often in cerebellar Purkinje neurons. A SCA1 mouse model, Pcp2-ATXN1[30Q]D776, has severe ataxia in absence of progressive Purkinje neuron degeneration and death. Previous RNA-seq analyses identify cerebellar upregulation of the peptide hormone cholecystokinin (Cck) in Pcp2-ATXN1[30Q]D776 mice. Importantly, absence of Cck1 receptor (Cck1R) in Pcp2-ATXN1[30Q]D776 mice confers a progressive disease with Purkinje neuron death. Administration of a Cck1R agonist, A71623, to Pcp2-ATXN1[30Q]D776;Cck and Pcp2-AXTN1[82Q] mice dampens Purkinje neuron pathology and associated deficits in motor performance. In addition, A71623 administration improves motor performance of Pcp2-ATXN2[127Q] SCA2 mice. Moreover, the Cck1R agonist A71623 corrects mTORC1 signaling and improves expression of calbindin in cerebella of AXTN1[82Q] and ATXN2[127Q] mice. These results indicate that manipulation of the Cck-Cck1R pathway is a potential therapeutic target for treatment of diseases involving Purkinje neuron degeneration.
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http://dx.doi.org/10.1016/j.celrep.2021.109831DOI Listing
October 2021

Synthetic azobenzene-containing metal-organic framework ion channels toward efficient light-gated ion transport at the subnanoscale.

Nanoscale 2021 Oct 13. Epub 2021 Oct 13.

Chemical and Environmental Engineering, School of Engineering, RMIT University, Melbourne, Victoria 3000, Australia.

Artificial nanochannels with diverse responsive properties have been widely developed to replicate the smart gating functionalities of biological ion channels. However, in these traditional nanochannels, common responsive molecules are usually too small to efficiently block the large channels under the closed states, leading to weak gating performances. Herein, we report carboxylated azobenzene-coordinated metal-organic-framework (AZO-MOF) ion channels with impressive light-gating properties. The AZO-MOF ion channels were synthesized by the confined growth of AZO-MOFs, composed of light-responsive AZO-containing ligands, non-responsive ligands and metal clusters, into ion-track-etched polymer nanochannels. The AZO-MOF ion channels with an appropriate number of AZO ligands showed a well-maintained crystalline and three-dimensional porous structure, including nanoscale cavities and subnanoscale windows for LiCl conduction. Meanwhile, the AZO-containing ligands bend and stretch upon light irradiation to open and close the pathways, thus gating the ion flux through the AZO-MOF ion channels with high on-off ratios up to 40.2, which is ∼2.3-30 times those of AZO-encapsulated MOF ion channels and AZO-modified nanochannels. This work suggests ways to achieve subnanoscaled gating of ion transport by angstrom-porous MOFs coordinated by stimuli-responsive ligands.
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http://dx.doi.org/10.1039/d1nr04595dDOI Listing
October 2021

Transforming approach for assessing the performance and applicability of rice arsenic contamination forecasting models based on regression and probability methods.

J Hazard Mater 2021 Sep 29;424(Pt B):127375. Epub 2021 Sep 29.

Center for Environmental Remediation, Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences, 11 A Datun Road, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Probability models are preferred over regression models recently in contamination evaluation but lacking proper performance comparison between two model types. Linear regression, logistic regression, XGBoost-based regression, and probability models were built considering soil arsenic and certain soil physicochemical properties of 287 samples to predict arsenic in rice grains. The outputs of all models were binarily classified uniformly for comparison. The complex algorithm-based models--XGBoost-based regression (R =0.046 ± 0.036) and probability models (cross-entropy = 0.697 ± 0.020)-did not surpass the simple linear regression (R =0.046 ± 0.031) and logistic regression models (cross-entropy = 0.694 ± 0.021). Accuracy, sensitivity, specificity, precision, and F1 score showed that the probability models exhibit no advantage on regression models, although the indicators above did not serve as proper scoring rules for the probability model. When discretizing the contaminant concentration in grains for probabilistic modeling, the limit concentration was considered as the splitting point but not the structure of the datasets, which would reduce the inherent advantage of the probability model. When predicting the contamination of crops, the probability model cannot eliminate the regression model, and simple but robust algorithm-based models are preferred when the quality and quantity of the dataset are undesirable.
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http://dx.doi.org/10.1016/j.jhazmat.2021.127375DOI Listing
September 2021

Comparative transcriptomic analysis of THP-1-derived macrophages infected with Mycobacterium tuberculosis H37Rv, H37Ra and BCG.

J Cell Mol Med 2021 Oct 10. Epub 2021 Oct 10.

State Key Laboratory of Analytical Chemistry for Life Science, Medical School of Nanjing University, Nanjing, China.

Tuberculosis (TB) remains a worldwide healthcare concern, and the exploration of the host-pathogen interaction is essential to develop therapeutic modalities and strategies to control Mycobacterium tuberculosis (M.tb). In this study, RNA sequencing (transcriptome sequencing) was employed to investigate the global transcriptome changes in the macrophages during the different strains of M.tb infection. THP-1 cells derived from macrophages were exposed to the virulent M.tb strain H37Rv (Rv) or the avirulent M.tb strain H37Ra (Ra), and the M.tb BCG vaccine strain was used as a control. The cDNA libraries were prepared from M.tb-infected macrophages and then sequenced. To assess the transcriptional differences between the expressed genes, the bioinformatics analysis was performed using a standard pipeline of quality control, reference mapping, differential expression analysis, protein-protein interaction (PPI) networks, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Q-PCR and Western blot assays were also performed to validate the data. Our findings indicated that, when compared to BCG or M.tb H37Ra infection, the transcriptome analysis identified 66 differentially expressed genes in the M.tb H37Rv-infected macrophages, out of which 36 genes were up-regulated, and 30 genes were down-regulated. The up-regulated genes were associated with immune response regulation, chemokine secretion, and leucocyte chemotaxis. In contrast, the down-regulated genes were associated with amino acid biosynthetic and energy metabolism, connective tissue development and extracellular matrix organization. The Q-PCR and Western blot assays confirmed increased expression of pro-inflammatory factors, altered energy metabolic processes, enhanced activation of pro-inflammatory signalling pathways and increased pyroptosis in H37Rv-infected macrophage. Overall, our RNA sequencing-based transcriptome study successfully identified a comprehensive, in-depth gene expression/regulation profile in M.tb-infected macrophages. The results demonstrated that virulent M.tb strain H37Rv infection triggers a more severe inflammatory immune response associated with increased tissue damage, which helps in understanding the host-pathogen interaction dynamics and pathogenesis features in different strains of M.tb infection.
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http://dx.doi.org/10.1111/jcmm.16980DOI Listing
October 2021

[Effect of moxibustion at "Zusanli" (ST 36) and "Shenshu" (BL 23) on intestinal flora in adjuvant arthritis rats].

Zhongguo Zhen Jiu 2021 Oct;41(10):1119-25

Graduate School of Anhui University of CM.

Objective: To observe the effect of moxibustion at "Zusanli" (ST 36) and "Shenshu" (BL 23) on inflammatory factors and intestinal flora in the rats with adjuvant arthritis.

Methods: A total of 36 Wistar rats were randomized into a normal group, a model group and a moxibustion group, 12 rats in each one. In the model group and the moxibustion group, the adjuvant arthritis model was established by a compound method, including the environmental factors, i.e. wind, cold and damp, and Freund's complete adjuvant. In the moxibustion group, moxibustion intervention was exerted at "Zusanli" (ST 36) and "Shenshu" (BL 23), for 20 min at each acupoint, once daily, consecutively for 21 days. The paw swelling degree and arthritis index (AI) score were observed before and after intervention in the rats of each group. Using real-time fluorescence quantitative PCR method (real-time PCR) and Western blot method, the mRNA and protein expressions of inflammatory factors of colon tissue, i.e. interleukin (IL) 1β, tumor necrosis factor-α (TNF-α), IL-6, were detected after intervention in the rats of each group. The intestinal flora was detected with 16SrRNA sequencing technology after intervention in the rats of each group.

Results: Compared with the normal group, the paw swelling degree and AI score were increased in the rats of the model group (<0.05); after intervention, compared with the model group, the paw swelling degree and AI score were reduced in the rats of the moxibustion group (<0.05). Compared with the normal group, the expressions of IL-1β, TNF-α and IL-6 mRNA, as well as proteins were increased in the colon tissue of the rats in the model group (<0.05); compared with the model group, the expressions of IL-1β, TNF-α and IL-6 mRNA, as well as proteins were reduced in the colon tissue of the rats in the moxibustion group (<0.05). Compared with the normal group, OTUs count was reduced in the rats of the model group (<0.05); and compared with the model group, OTUs count was increased in the rats of the moxibustion group (<0.05). Compared with the normal group, Simpson index was increased, Chao1 and Ace were reduced in the rats of the model group (<0.05); while, compared with the model group, Chao1 and Ace were increased in the rats of the moxibustion group (<0.05). Compared with the normal group, the relative abundance of uncategorized , , , uncategorized and uncategorized was increased (<0.05), and the relative abundance of uncategorized was reduced in the model group (<0.05). While, compared with the model group, the relative abundance of uncategorized , , uncategorized was reduced in the moxibustion group (<0.05) and that of uncategorized was increased (<0.05).

Conclusion: Moxibustion at "Zusanli" (ST 36) and "Shenshu" (BL 23) relieves the joint symptoms of adjuvant arthritis rats and inhibits the expressions of inflammatory factors, which is probably related to the regulation of the structure of intestinal flora.
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http://dx.doi.org/10.13703/j.0255-2930.20201010-k0003DOI Listing
October 2021

Subxiphoid thoracoscopic thymectomy for myasthenia gravis.

Interact Cardiovasc Thorac Surg 2021 Oct 9. Epub 2021 Oct 9.

Department of Cardiothoracic Surgery, Xuzhou Central Hospital, Xuzhou, China.

We investigated the efficacy of subxiphoid thoracoscopic thymectomy in patients with myasthenia gravis. The data of 37 consecutive cases were reviewed. 2 cases of postoperative myasthenia gravis crisis and 4 cases of residual mediastinal fat tissue were recorded. Moreover, 29 patients presented the neurological outcomes, and complete stable remission was achieved in 5 (17.2%) cases. Subxiphoid thymectomy is technically feasible. High-quality evidence is warranted before this approach can be recommended.
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http://dx.doi.org/10.1093/icvts/ivab262DOI Listing
October 2021

Digital Nativity, Computer Self-Efficacy, and Technology Adoption: A Study Among University Faculties in China.

Authors:
Chen Zhao Lei Zhao

Front Psychol 2021 21;12:746292. Epub 2021 Sep 21.

College of Science and Information Science, Qingdao Agricultural University, Qingdao, China.

Technology acceptance and usage become obligatory for people when their work modes change as a result of an unexpected but irresistible force. This is especially true for teachers who are reluctant technology adopters compared with their students. During the COVID-19 pandemic, the Chinese government issued national policies to enforce online teaching and learning. As the success of online teaching largely depends on university faculties' readiness and intentions, how they perceive and practice technology adoption becomes an issue that warrants in-depth research. Unlike their students who grow up with technology and can be seen as digital natives, university faculties may lack competence in using technology, whether to teach or do other tasks. Previous studies on faculties' technology adoption were all conducted in situations where they made volitional decisions to use technology, but their mandatory technology use received scant attention. In addition, although studies suggested that teachers demonstrated features of digital natives, it remains unknown whether or to what extent their digital nativity correlates with technology intentions. To address these research gaps, the current study examined Chinese university faculties' intentions to use technology for online teaching by incorporating digital nativity and computer self-efficacy as key determinants into technology acceptance variables. Results suggested that digital nativity was a key factor that affected university faculties' online teaching, as evidenced by the fact that 67% of the variance could be explained by perceived usefulness, attitudes and digital nativity. In addition, it was also found that computer efficacy significantly influenced perceived ease of use.
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http://dx.doi.org/10.3389/fpsyg.2021.746292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490612PMC
September 2021

Simultaneously blocking chemical crosstalk and internal short circuit via gel-stretching derived nanoporous non-shrinkage separator for safe lithium-ion batteries.

Adv Mater 2021 Oct 7:e2106335. Epub 2021 Oct 7.

Institute of Nuclear and New Energy Technology, Tsinghua University, Beijing, 100084, China.

Separator, an ionic permeable and electronic insulating membrane between cathode and anode, plays a crucial role in the electrochemical and safety performance of batteries. However, the commercial polyolefin separators not only suffer from inevitable thermal shrinkage at elevated temperature, but also fail to inhibit the hidden chemical crosstalk of reactive gases such as O , leading to often reported thermal runaway (TR) and hence preventing large-scale implementation of high-energy-density lithium-ion batteries. Herein, a nanoporous non-shrinkage separator (GS-PI) was fabricated via a novel gel-stretching orientation approach to eliminate TR. In situ synchrotron small angle X-ray scattering during heating clearly showed that the as-prepared thin GS-PI separator exhibits superior mechanical tolerance at high temperature, thus effectively preventing internal short circuit. Meanwhile, the unique nanoporous structure design further blocks chemical crosstalk and the associated exothermic reactions. Accelerating Rate Calorimetry test revealed that the practical 1 Ah LiNi Co Mn O (NCM622)/graphite pouch cell using GS-PI nanoporous separator show a maximum temperature rise (dT/dt ) of only 3.7 °C s compared to 131.6 °C s in the case of Al O @PE macroporous separator. Moreover, despite the reduced pore size, the GS-PI separator demonstrates better cycling stability than conventional Al O @PE separator at high temperature without sacrificing specific capacity and rate capability. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/adma.202106335DOI Listing
October 2021

Conditioned CAR-T cells by hypoxia-inducible transcription amplification (HiTA) system significantly enhances systemic safety and retains antitumor efficacy.

J Immunother Cancer 2021 Oct;9(10)

Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, China

Background: Hypoxia is a striking feature of most solid tumors and could be used to discriminate tumors from normoxic tissues. Therefore, the design of hypoxia-conditioned Chimeric Antigen Receptor (CAR) T cells is a promising strategy to reduce on-target off-tumor toxicity in adoptive cell therapy. However, existing hypoxia-conditioned CAR-T designs have been only partially successful in enhancing safety profile but accompanied with reduced cytotoxic efficacy. Our goal is to further improve safety profile with retained excellent antitumor efficacy.

Methods: In this study, we designed and constructed a hypoxia-inducible transcription amplification system (HiTA-system) to control the expression of CAR in T (HiTA-CAR-T) cells. CAR expression was determined by Flow cytometry, and the activation and cytotoxicity of HiTA-CAR-T cells in vitro were evaluated in response to antigenic stimulations under hypoxic or normoxic conditions. The safety of HiTA-CAR-T cells was profiled in a mouse model for its on-target toxicity to normal liver and other tissues, and antitumor efficacy in vivo was monitored in murine xenograft models.

Results: Our results showed that HiTA-CAR-T cells are highly restricted to hypoxia for their CAR expression, activation and cytotoxicity to tumor cells in vitro. In a mouse model in vivo, HiTA-CAR-T cells targeting Her2 antigen showed undetectable CAR expression in all different normoxic tissues including human Her2-expresing liver, accordingly, no liver and systemic toxicity were observed; In contrast, regular CAR-T cells targeting Her2 displayed significant toxicity on human Her2-expression liver. Importantly, HiTA-CAR-T cells were able to achieve significant tumor suppression in murine xenograft models.

Conclusion: Our HiTA system showed a remarkable improvement in hypoxia-restricted transgene expression in comparison with currently available systems. HiTA-CAR-T cells presented significant antitumor activities in absence of any significant liver or systemic toxicity in vivo. This approach could be also applied to design CAR-T cell targeting other tumor antigens.
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http://dx.doi.org/10.1136/jitc-2021-002755DOI Listing
October 2021

Zero drift suppression method of a distributed feedback fiber laser hydrophone.

Appl Opt 2021 Sep;60(25):7628-7633

A zero drift suppression method of a distributed feedback (DFB) fiber laser hydrophone is studied. The working principle of the DFB fiber laser hydrophone and the cause, phenomenon, and influence of zero drift are briefly introduced. The design idea and implementation method of the zero drift suppression method are described in detail. The differential cross-multiplication demodulation method is improved by adding closed-loop feedback control to the appropriate stage, and the zero drift problem is solved without any hardware modification. Simulation analysis and experiments are performed to verify the feasibility and effectiveness of the method. The experimental results show that the zero drift suppression method can effectively stabilize the static operating point of the DFB fiber laser hydrophone.
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http://dx.doi.org/10.1364/AO.430311DOI Listing
September 2021

Aligning Tumor Mutational Burden (TMB) quantification across diagnostic platforms: Phase 2 of the Friends of Cancer Research TMB Harmonization Project.

Ann Oncol 2021 Oct 1. Epub 2021 Oct 1.

Biodesix, Inc., Boulder, CO, USA.

Background: Tumor Mutational Burden (TMB) measurements aid in identifying patients who are likely to benefit from immunotherapy; however, there is empirical variability across panel assays and factors contributing to this variability have not been comprehensively investigated. Identifying sources of variability and the development and use of a calibration tool that can help facilitate comparability across different panel assays may aid in broader adoption of panels assays and development of clinical applications.

Materials And Methods: Twenty-nine tumor samples and ten human-derived cell lines were processed and distributed to 16 laboratories; each used their own bioinformatics pipelines to calculate TMB and compare to whole exome results. Additionally, theoretical positive percent agreement (PPA) and negative percent agreement (NPA) of TMB were estimated. The impact of filtering pathogenic and germline variants on TMB estimates was assessed. Calibration curves specific to each panel assay were developed to facilitate translation of panel TMB values to whole exome sequencing (WES) TMB values.

Results: Panel sizes greater than 667Kb are necessary to maintain adequate PPA and NPA for calling TMB high versus TMB low across the range of cutoffs used in practice. Failure to filter out pathogenic variants when estimating panel TMB resulted in overestimating TMB relative to WES for all assays. Filtering out potential germline variants at >0% population minor allele frequency (pMAF) resulted in the strongest correlation to WES TMB. Application of a calibration approach derived from TCGA data, tailored to each panel assay, reduced the spread of panel TMB values around the WES TMB as reflected in lower root mean squared error (RMSE) for 26/29 (90%) of the clinical samples, although RMSE across samples at the laboratory level was less often reduced.

Conclusions: Estimation of TMB varies across different panels, with panel size, gene content, and bioinformatics pipelines contributing to empirical variability. Statistical calibration can achieve more consistent results across panels and allows for comparison of TMB values across various panel assays. To promote reproducibility and comparability across assays, a software tool was developed and made publicly available.
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http://dx.doi.org/10.1016/j.annonc.2021.09.016DOI Listing
October 2021

Chinese Medicine Formula Huashibaidu Granule Early Treatment for Mild COVID-19 Patients: An Unblinded, Cluster-Randomized Clinical Trial.

Front Med (Lausanne) 2021 16;8:696976. Epub 2021 Sep 16.

Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Previous research suggested that Chinese Medicine (CM) Formula Huashibaidu granule might shorten the disease course in coronavirus disease 2019 (COVID-19) patients. This research aimed to investigate the early treatment effect of Huashibaidu granule in well-managed patients with mild COVID-19. An unblinded cluster-randomized clinical trial was conducted at the Dongxihu FangCang hospital. Two cabins were randomly allocated to a CM or control group, with 204 mild COVID-19 participants in each cabin. All participants received conventional treatment over a 7 day period, while the ones in CM group were additionally given Huashibaidu granule 10 g twice daily. Participants were followed up to their clinical endpoint. The primary outcome was worsening symptoms before the clinical endpoint. The secondary outcomes were cure and discharge before the clinical endpoint and alleviation of composite symptoms after the 7 days of treatment. All 408 participants were followed up to their clinical endpoint and included in statistical analysis. Baseline characteristics were comparable between the two groups ( > 0.05). The number of worsening patients in the CM group was 5 (2.5%), and that in the control group was 16 (7.8%) with a significant difference between groups ( = 0.014). Eight foreseeable mild adverse events occurred without statistical difference between groups ( = 0.151). Seven days of early treatment with Huashibaidu granule reduced the likelihood of worsening symptoms in patients with mild COVID-19. Our study supports Huashibaidu granule as an active option for early treatment of mild COVID-19 in similar well-managed medical environments. www.chictr.org.cn/showproj.aspx?proj=49408, identifier: ChiCTR2000029763.
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http://dx.doi.org/10.3389/fmed.2021.696976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481869PMC
September 2021

Respiratory exposure to PM2.5 soluble extract induced chronic lung injury by disturbing the phagocytosis function of macrophage.

Environ Sci Pollut Res Int 2021 Oct 2. Epub 2021 Oct 2.

State Key Laboratory of Analytical Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, 210093, People's Republic of China.

Exposure to airborne urban particles is a contributing factor for the development of multiple types of respiratory diseases; its pathological role as a cause of lung injury is still unclear. In this study, PM2.5 soluble extract was collected, and its toxicological effect on lung pathological changes was examined. To assess its pathological mechanism, Human Monocyte-Like Cell Line, THP-1, and mouse macrophage, RAW264.7, were used to determine the effects of PM2.5 soluble extract on cell toxicity, phagocytosis, and transcriptome. We found that PM2.5 soluble extract exposure activated NF-κB and MAPK signaling pathways, then induces the production of pro-inflammatory cytokines. RNA-seq results showed that the transcription profiles, including 1213 genes, have been changed in responses to PM2.5 exposure. Additionally, PM2.5 led to phagocytic dysfunction, which may exacerbate the cause of lung injury. Exposure to PM2.5 soluble extract triggers the death of respiratory macrophages, impairs its phagocytosis capacity, thus delaying the inflammatory cell clearance in the lung, which results in chronic lung injury.
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http://dx.doi.org/10.1007/s11356-021-16797-9DOI Listing
October 2021

Genetic determinants of stress resistance in desiccated .

Appl Environ Microbiol 2021 Sep 29:AEM0168321. Epub 2021 Sep 29.

University of Alberta, Dept. of Agricultural, Food, and Nutritional Science, Edmonton, AB, Canada.

Enteric pathogens including are capable of long-term survival after desiccation, and resist heat treatment that are lethal to hydrated cells. The mechanisms of dry-heat resistance differ from wet heat resistance. To elucidate the mechanisms of dry-heat resistance in , screening of the dry-heat resistance of 108 strains representing 39 serotypes identified the 22 most resistant and the 8 most sensitive strains for comparative genome analysis. A total of 289 genes of the accessory genome were differently distributed between resistant and sensitive strains. Among these genes, 28 proteins with a putative relationship to stress resistance were selected for to quantify relative gene expression before and after desiccation, and expression by solid-state cultures on agar plates relative to cultures growing in liquid culture media. Of these 28 genes, 15 genes were upregulated (<0.05) after desiccation, or by solid-state cultures on agar plates. These 15 genes were cloned into the low-copy vector pRK767 under control of the promoter. The expression of 6 of these 15 genes of these genes increased (<0.05) resistance to dry-heat and to treatment with 500 MPa. Our finding extends the knowledge of mechanisms of stress resistance in desiccated to improve their control in dry food. This study directly targeted an increasing threat to food safety and developed knowledge and targeted strategies that can be used by the food industry to help reduce the risk of foodborne illness in their dry products and thereby reduce the overall burden of foodborne illness. Genomic and physiological analyses have elucidated mechanisms of bacterial resistance to many food preservation technologies including heat, pressure, disinfection chemicals, and UV light; however, information on bacterial mechanisms of resistance to dry-heat is scarce. Mechanisms of tolerance to desiccation likely also contribute to resistance to dry-heat but this assumption has not been verified experimentally. It remains unclear how mechanisms of resistance to wet heat relate to dry-heat resistance. This study will thus fill a knowledge gap to improve the safety of dry foods.
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http://dx.doi.org/10.1128/AEM.01683-21DOI Listing
September 2021

Low-dose radiation therapy for hand osteoarthritis: shaking hands again?

Clin Transl Oncol 2021 Sep 29. Epub 2021 Sep 29.

Department of Radiation Oncology, HM Hospitales, Calle Oña 10, 28050, Madrid, Spain.

Background: Hand osteoarthritis (HOA) is one of the most common causes of pain and functional disability in western countries and there is still no definitive cure. Low-dose radiation therapy (LDRT) has anti-inflammatory properties that have shown to be effective in the symptomatic relief of various degenerative musculoskeletal disorders. We designed a clinical protocol using LDRT for symptomatic HOA and present results and tolerance in the first 100 patients included.

Materials And Methods: Between April 2015 and March 2021, 100 patients with a median age of 60 were treated. Fifty-seven patients suffering from proximal/distal interphalangeal joint pain, 40 patients with thumb arthritis, 2 patients with radiocarpal joint affection and 1 patient with metacarpophalangeal joint pain were enrolled. LDRT comprised of 6 fractions of 0.5-1 Gy on every other day up to a total dose of 3-6 Gy. Clinical response was evaluated according to the visual analog scale (VAS) for pain level and the von Pannewitz score (VPS) for joint functionality. Any patients not achieving subjective adequate pain relief after 8 weeks of treatment were offered a second identical LDRT course.

Results: With a median follow-up of 10.5 months (range 7.55-12.45), 94% reported an improvement in the pain, with a significant reduction in the VAS level after 3, 6 and 12 months (p < 0.001). Sixty-three patients needed a second course of treatment at a median time interval of 12 weeks (range 9-14). The mean VAS score before treatment was 8 (range 3-10). After treatment, it was 5 (range 1-10). After 3, 6 and 12 months, the mean VAS scores were 4 (range 0-9), 3 (range 0-9) and 3.5 (range 0-9), respectively. Seventy patients reported functionality improvements after LDRT according to the von Pannewitz score. No acute or late complications were observed.

Conclusion: LDRT appears to be safe and useful for HOA and is associated with good rates of pain relief and functionality improvements. However, further studies are necessary to confirm these promising results.
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http://dx.doi.org/10.1007/s12094-021-02710-wDOI Listing
September 2021

Influence of porous tantalum scaffold pore size on osteogenesis and osteointegration: A comprehensive study based on 3D-printing technology.

Mater Sci Eng C Mater Biol Appl 2021 Oct 19;129:112382. Epub 2021 Aug 19.

Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address:

The emerging role of porous tantalum (Ta) scaffold for bone tissue engineering is noticed due to its outstanding biological properties. However, it is controversial which pore size and porosity are more conducive for bone defect repair. In the present work, porous tantalum scaffolds with pore sizes of 100-200, 200-400, 400-600 and 600-800 μm and corresponding porosities of 25%, 55%, 75%, and 85% were constructed, using computer aided design and 3D printing technologies, then comprehensively studied by in vitro and in vivo studies. We found that Ta scaffold with pore size of 400-600 μm showed stronger ability in facilitating cell adhesion, proliferation, and osteogenic differentiation in vitro. In vivo tests identified that porous tantalum scaffolds with pore size of 400-600 μm showed better performance of bone ingrowth and integration. In mechanism, computational fluid dynamics analysis proved porous tantalum scaffolds with pore size of 400-600 μm hold appropriate permeability and surface area, which facilitated cell adhesion and proliferation. Our results strongly indicate that pore size and porosity are essential for further applications of porous tantalum scaffolds, and porous tantalum scaffolds with pore size 400-600 μm are conducive to osteogenesis and osseointegration. These findings provide new evidence for further application of porous tantalum scaffolds for bone defect repair.
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http://dx.doi.org/10.1016/j.msec.2021.112382DOI Listing
October 2021

Persistence of and NRRL B-2354 on Baby Spinach Subjected to Temperature Abuse after Exposure to Sub-Lethal Stresses.

Foods 2021 Sep 10;10(9). Epub 2021 Sep 10.

Joint Institute for Food Safety and Applied Nutrition, University of Maryland, College Park, MD 20742, USA.

The exposure of foodborne pathogens such as to a sub-lethal stress may protect bacterial cells against distinct stresses during the production of leafy greens, which can constitute potential health hazards to consumers. In this study, we evaluated how the prior exposure of to sub-lethal food processing-related stresses influenced its subsequent persistence on baby spinach under cold (4 °C for 7 days) and temperature abuse (37 °C for 2 h + 4 °C for 7 days) conditions. We also compared the survival characteristics of pre-stressed and NRRL B-2354 as its surrogate on baby spinach. A cocktail of three serovars, as well as Typhimurium ATCC 14028 wild type and its Δ mutant, and NRRL B-2354, was first exposed to sub-lethal desiccation, oxidation, heat shock, and acid stresses. Afterward, baby spinach was inoculated with unstressed or pre-stressed cells at 7.0 log CFU/sample unit, followed by 7-day storage under cold and temperature abuse conditions. The unstressed (fresh cells in sterile 0.85% saline) decreased rapidly within the first day and thereafter persisted around 5.5 log CFU/sample unit under both conditions. The desiccation-stressed showed the highest bacterial counts ( < 0.05) compared to other conditions. The unstressed survived better ( < 0.05) than the oxidation- and acid-stressed , while there were no significant differences ( > 0.05) between the unstressed and heat-shocked . Unlike the wild type, temperature abuse did not lead to the enhanced survival of the Δ mutant after exposure to desiccation stress, indicating that the gene could play a critical role in the persistence of desiccation-stressed subjected to temperature abuse. NRRL B-2354 was more persistent ( < 0.05) than the pre-stressed under both conditions, suggesting its use as a suitable surrogate for pre-stressed by providing a sufficient safety margin. Our results demonstrate the merit of considering the prior exposure of foodborne pathogens to sub-lethal stresses when validating the storage conditions for leafy greens.
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http://dx.doi.org/10.3390/foods10092141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472226PMC
September 2021

Adipose/Connective Tissue From Thyroid-Associated Ophthalmopathy Uncovers Interdependence Between Methylation and Disease Pathogenesis: A Genome-Wide Methylation Analysis.

Front Cell Dev Biol 2021 8;9:716871. Epub 2021 Sep 8.

Eye Institute and Department of Ophthalmology, Eye and ENT Hospital, Fudan University, Shanghai, China.

In response to pathological stimulation, methylation status conversion of the genome drives changes of cell feature and is able to promote disease development. Yet the role of methylation in the development of thyroid-associated ophthalmopathy (TAO) remains to be evaluated. Overexpansion of orbital tissue is the key feature of TAO. In this study, the methylation profile of orbital adipose/connective tissue from TAO patients and normal individuals were compared. After screening 3,739 differentially methylated probes, the distribution and properties of these probes were analyzed. Furthermore, enriched biological functions of these genes associated with differential methylation and the relationship between their methylation status and expression profile were also identified, including PTPRU and VCAM-1. According to our results, methylation was involved in disregulated immune response and inflammation in TAO and might contribute to activation of fibroblast and adipogenesis, leading to the expansion of orbital tissue. Neuropathy and neurobehavioral symptoms were also potentially associated with methylation. These results may help to extend the understanding of methylation in TAO and provide more insights into diagnosis and treatment of patients.
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http://dx.doi.org/10.3389/fcell.2021.716871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457400PMC
September 2021

Effect of CAG repeats on the age at onset of patients with spinocerebellar ataxia type 2 in China.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 Aug;46(8):793-799

Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008.

Objectives: Spinocerebellar ataxia type 2 (SCA2) is one of the most common autosomal dominant ataxias in the world. Several reports revealed that CAG repeats in some polyQ-containing genes may affect the age at onset (AAO) of patients with SCA2, however, little studies were conducted among Chinese patients with SCA2. Thus, the aim of this study is to evaluate the effect of CAG repeats on the AAO of patients with SCA2 in China.

Methods: A total of 119 patients with SCA2 were enrolled and were divided into 2 groups according to their major phenotype: 17 patients from 9 families with Parkinson's syndrome were grouped as the Parkinson's disease-SCA2 (PD-SAC2); 91 patients from 66 SCA2 families and 11 sporadic SCA2 patients were grouped as the ataxia-SCA2 (A-SCA2). Blood samples were obtained from the subjects, and the CAG repeat length in ATXN2 and other (CAG)-containing genes was screened using fluorescent PCR. The Spearman's rank correlation between the CAG repeat length in (CAG)-containing genes and AAO was analyzed. Regression analysis was performed to investigate whether the CAG repeat length could explain the variant of AAO. A -test was used to compare the difference of CAG repeat length in (CAG)-containing genes between the PD-SAC2 and A-SCA2 groups.

Results: The CAG repeat length in the longer allele of ATXN2 was negatively correlated with AAO of SCA2 (=-0.251, <0.05), and the CAG repeat length could explain 41.7% of the variation of AAO. AAO negatively correlated with the CAG repeat length in the shorter allele of ATXN7 (=-0.251, =0.006) or in the longer allele of TBP gene (=-0.197, =0.034). A tendency of delay in the AAO was also observed in patients with SCA2 carrying the CAG repeat within the ATXN3, CACNA1A, ATXN7, TBP, and RAI1. In addition, we found that the CAG repeat length in ATXN7 and ATXN2 between the A-SCA2 and the PD-SCA2 groups was significantly different (both <0.05).

Conclusions: The CAG repeat in ATXN2 is a major genetic factor for the AAO of patients with SCA2 in China. The CAG repeat length in ATXN3, CACNA1A, ATXN7, TBP, and RAI1 genes might be a potential factor associated with the AAO of SCA2. The CAG repeat in ATXN7 might be a potential factor affecting the Parkinson's syndrome in SCA2.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2021.210230DOI Listing
August 2021

Vein-first versus artery-first ligation procedure for lung cancer surgery: An updated review.

J Cardiothorac Surg 2021 Sep 26;16(1):272. Epub 2021 Sep 26.

Department of Thoracic Surgery, Xuzhou Central Hospital, 199 Jiefang South Road, Xuzhou, 221009, China.

Background: The optimal sequence of pulmonary vessel interruption during lung cancer resection remains controversial. This review aimed to elucidate the association of vein-first versus artery-first ligation and survival of the patients.

Methods: We searched PubMed, Web of Science, Scopus, Embase, Cochrane Library and Google Scholar from their inception to September 2021 for published articles that compared vein-first (the pulmonary vein was interrupted first) and artery-first procedure (the pulmonary artery was ligated first) during lung cancer surgery.

Results: Finally, a total of 13 full articles were obtained. First, 7 studies with survival information were included for meta-analyses. As compared with the artery-first ligation, vein-first approach did not decrease the risk of local recurrence (risk ratio [RR] 0.92 in favour of vein-first; 95% confidence interval [CI] 0.61-1.39, p = 0.68) or distant metastasis (RR 0.92; 95% CI 0.30-2.85, p = 0.89); but it was associated with better disease-free survival (RR 0.52; 95% CI 0.37-0.73, p < 0.01) as well as 5-year overall survival (RR 0.60; 95% CI 0.41-0.86, p < 0.01). In addition, the operative time, intraoperative blood loss, total complications, and length of postoperative stay were mainly comparable between the two groups. Second, 7 studies provided the data of tumor cells indicated by different biomarkers and detection methods; and 3 of these reports showed that vein-first ligation decreased the extent of intraoperative tumor dissemination. However, a quantitative meta-analysis was not possible due to the significant heterogeneity.

Conclusion: Vein-first ligation in lung cancer surgery may be associated with improved survival of the patients, which might be ascribed to potentially lower risk of tumor cell dissemination. Well-designed, large-scale trials are warranted to clarify these occasional findings.
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http://dx.doi.org/10.1186/s13019-021-01658-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474918PMC
September 2021

Clinico-genetic findings in 509 frontotemporal dementia patients.

Mol Psychiatry 2021 Sep 24. Epub 2021 Sep 24.

Department of Neurology, University of Ulm, Ulm, Germany.

Frontotemporal dementia (FTD) is a clinically and genetically heterogeneous disorder. To which extent genetic aberrations dictate clinical presentation remains elusive. We investigated the spectrum of genetic causes and assessed the genotype-driven differences in biomarker profiles, disease severity and clinical manifestation by recruiting 509 FTD patients from different centers of the German FTLD consortium where individuals were clinically assessed including biomarker analysis. Exome sequencing as well as C9orf72 repeat analysis were performed in all patients. These genetic analyses resulted in a diagnostic yield of 18.1%. Pathogenic variants in C9orf72 (n = 47), GRN (n = 26), MAPT (n = 11), TBK1 (n = 5), FUS (n = 1), TARDBP (n = 1), and CTSF (n = 1) were identified across all clinical subtypes of FTD. TBK1-associated FTD was frequent accounting for 5.4% of solved cases. Detection of a homozygous missense variant verified CTSF as an FTD gene. ABCA7 was identified as a candidate gene for monogenic FTD. The distribution of APOE alleles did not differ significantly between FTD patients and the average population. Male sex was weakly associated with clinical manifestation of the behavioral variant of FTD. Age of onset was lowest in MAPT patients. Further, high CSF neurofilament light chain levels were found to be related to GRN-associated FTD. Our study provides large-scale retrospective clinico-genetic data such as on disease manifestation and progression of FTD. These data will be relevant for counseling patients and their families.
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http://dx.doi.org/10.1038/s41380-021-01271-2DOI Listing
September 2021

Factors associated with exclusive breastfeeding practice among mothers in nine community health centres in Nanning city, China: a cross-sectional study.

Int Breastfeed J 2021 09 23;16(1):71. Epub 2021 Sep 23.

Department of Maternal and Child Health, School of Public Health, Peking University, Beijing, China.

Background: The prevalence of exclusive breastfeeding (EBF) is suboptimal in China. There is limited evidence of effective interventions to increase EBF in China. Therefore, it is urgent to explore the potential factors that may be effective in promoting exclusive breastfeeding. Previous studies have mainly focused on socio-demographic factors and the Han ethnic group. This study explores more modifiable influencing factors of EBF in the Guangxi Zhuang Autonomous Region of China.

Methods: The cross-sectional data used in this study were collected to provide baseline information on EBF prevalence for a breastfeeding promotion project. A total of 494 mothers of infants aged 0-5 months were recruited from nine community health centres in Nanning, China, in October 2019. Data were collected through face-to-face interviews using structured questionnaires. Infant feeding was measured by 24-h recall. The Chinese version of the Breastfeeding Self-Efficacy Scale-Short Form was used to examine the maternal breastfeeding self-efficacy. Univariate and multivariate logistic regressions were used to examine the factors associated with EBF practices.

Results: In the present study, the prevalence of exclusive breastfeeding was 37.0%. Higher breastfeeding self-efficacy scores (adjusted odds ratio [AOR] 1.93; 95% confidence interval [CI] 1.25, 2.98), a college degree or above (AOR 2.15; 95% CI 1.24, 3.71), and early initiation of breastfeeding (AOR 2.06; 95% CI 1.29, 3.29) were positively associated with EBF practice. However, the preparation for infant formula before childbirth (AOR 0.30; 95% CI 0.17, 0.52) and premature birth (AOR 0.30; 95% CI 0.10, 0.87) were negatively associated with EBF practice.

Conclusions: Exclusive breastfeeding practice was suboptimal and associated with various factors in the study area. The prevalence of EBF was positively associated with higher breastfeeding self-efficacy, education level of mothers, and early initiation of breastfeeding, whereas premature birth and preparation for infant formula before childbirth were barriers to exclusive breastfeeding. Future intervention projects should target mothers with premature babies, lower levels of education, and breastfeeding self-efficacy. Breastfeeding-friendly practices, such as the early initiation of breastfeeding and regulations on breastmilk substitutes, should also be encouraged.
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http://dx.doi.org/10.1186/s13006-021-00416-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461910PMC
September 2021

Serum and synovial biomarkers for distinguishing between chronic periprosthetic joint infections and rheumatoid arthritis: a prospective cohort study.

J Arthroplasty 2021 Sep 20. Epub 2021 Sep 20.

Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address:

Background: Inflammatory responses in patients with active rheumatoid arthritis (RA) may lead to the current serum and synovial fluid biomarkers that misidentify chronic periprosthetic joint infection (PJI). We sought to investigate the expression of serum and synovial biomarkers in patients with active RA and to calculate thresholds for valuable biomarkers that distinguish between chronic PJI and active RA.

Methods: This prospective study was initiated to enroll 70 patients undergoing revision arthroplasty from January 2019 to January 2021, and 30 patients with active RA cumulative knee from August 2020 to March 2021. The Musculoskeletal Infection Society (MSIS) definition of PJI was utilized for the classification of cases as aseptic or infected. Serum D-dimer, ESR, CRP and IL-6, as well as synovial IL-6, PMN% and CD64 index level were measured preoperatively.

Results: An increase in biomarkers concentrations were observed in group C (active RA). Synovial fluid CD64 index exhibited good discriminatory power between group B (chronic PJI) and group C with an area under curve of 0.930. For the diagnosis of chronic PJI in the presence of active RA, the optimal threshold value of synovial CD64 index was 0.87, with a sensitivity of 82.86%, and a specificity of 93.33%.

Conclusions: Current serum biomarkers (ESR, CRP, IL-6 and D-Dimer) did not apply to the diagnosis of suspected PJI with active RA. Fortunately, satisfactory results can be achieved by adjusting the threshold of synovial fluid biomarkers.
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http://dx.doi.org/10.1016/j.arth.2021.09.009DOI Listing
September 2021

Vascular transplantation with dual-biofunctional ePTFE vascular grafts in a porcine model.

J Mater Chem B 2021 Sep 22;9(36):7409-7422. Epub 2021 Sep 22.

Key Laboratory for Biomechanics and Mechanobiology (Beihang University) of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, P. R. China.

Cardiovascular disease (CVD) poses serious health concerns worldwide. The lack of transplantable vascular grafts is an unmet clinical need in the surgical treatment of CVD. Although expanded polytetrafluoroethylene (ePTFE) vascular grafts have been used in clinical practice, a low long-term patency rate in small-diameter transplantation application is still the biggest challenge. Thus, surface modification of ePTFE is sought after. In this study, polydopamine (PDA) was used to improve the hydrophilia and provide immobilization sites in ePTFE. Bivalirudin (BVLD), a direct thrombin inhibitor, was used to enhance the anti-thrombotic activity of ePTFE. The peptides derived from extracellular matrix proteins were used to elevate the bioactivity of ePTFE. The morphology, chemical composition, peptide modified strength, wettability, and hemocompatibility of modified ePTFE vascular grafts were investigated. Then, an endothelial cell proliferation assay was used to evaluate the best co-modification strategy of the ePTFE vascular graft . Since a large animal could relatively better mimic human physiology, we chose a porcine carotid artery replacement model in the current study. The results showed that the BVLD/REDV co-modified ePTFE vascular grafts had a satisfactory patency rate (66.7%) and a higher endothelial cell coverage ratio (70%) at 12 weeks after implantation. This may offer an opportunity to produce a multi-biofunctional ePTFE vascular graft, thereby yielding a potent product to meet the clinical needs.
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http://dx.doi.org/10.1039/d1tb01398jDOI Listing
September 2021

The role of immunotherapy for management of advanced thymic epithelial tumors: a narrative review.

Mediastinum 2021 Sep 25;5. Epub 2021 Sep 25.

Thoracic and Gastrointestinal Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

The emergence of immunotherapy as a modern pillar of cancer treatment has changed the treatment landscape for various cancers. Immune checkpoint inhibitors directed at programed death-1 (PD-1) or its ligand (PD-L1), in particular, have found widespread clinical applications and have resulted in durable responses and an improvement in survival of patients with advanced or metastatic disease. Tumor cell PD-L1 expression and tumor mutation burden (TMB) are biomarkers of response and efforts are underway to identify other biomarkers that might predict benefit with these drugs. Most patients tolerate immunotherapy well, although a subset of patients develop immune-mediated toxicity due to excessive immune stimulation. Thymic epithelial tumors (TETs) have a unique biology which can predispose to development of autoimmune paraneoplastic disease, especially in patients with thymoma. Due to defects in immunological self-tolerance, the use of immunotherapy in TET patients is associated with an increased risk of immune-mediated adverse events, which can be potentially life-threatening. Development of biomarkers of response and toxicity is particularly important for the treatment of TETs since it is important to identify patients who might benefit from treatment and be at low risk for development of severe immune toxicity. The use of immunotherapy in patients with autoimmune disorders and those who have previously experienced immune-mediated toxicity is currently an area of active research. Various risk mitigation strategies are under evaluation in prospective clinical trials, including trials of immune checkpoint inhibitors in patients with thymic cancers.
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http://dx.doi.org/10.21037/med-20-62DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445513PMC
September 2021

Wetting Dynamics in an Angular Channel.

Langmuir 2021 Sep 19;37(38):11276-11280. Epub 2021 Sep 19.

Center of Soft Matter Physics and its Applications, Beihang University, Beijing 100191, China.

We analyze the dynamics of liquid filling in a thin, slightly inflated rectangular channel driven by capillary forces. We show that although the amount of liquid in the channel increases in time following the classical Lucas-Washburn law, ∝ , the prefactor is very sensitive to the deformation of the channel because the filling takes place by the growth of two parts, the bulk part (where the cross section is completely filled by the liquid), and the finger part (where the cross section is partially filled). We calculate the time dependence of accounting for the coupling between the two parts and show that the prefactor for the filling can be reduced significantly by a slight deformation of the rectangular channel, e.g., the prefactor is reduced 50% for a strain of 0.1%. This offers an explanation for the large deviation on the value of the prefactor reported previously.
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http://dx.doi.org/10.1021/acs.langmuir.1c01755DOI Listing
September 2021

CRISPR/Cas9 mediated gene correction ameliorates abnormal phenotypes in spinocerebellar ataxia type 3 patient-derived induced pluripotent stem cells.

Transl Psychiatry 2021 09 17;11(1):479. Epub 2021 Sep 17.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is a progressive autosomal dominant neurodegenerative disease caused by abnormal CAG repeats in the exon 10 of ATXN3. The accumulation of the mutant ataxin-3 proteins carrying expanded polyglutamine (polyQ) leads to selective degeneration of neurons. Since the pathogenesis of SCA3 has not been fully elucidated, and no effective therapies have been identified, it is crucial to investigate the pathogenesis and seek new therapeutic strategies of SCA3. Induced pluripotent stem cells (iPSCs) can be used as the ideal cell model for the molecular pathogenesis of polyQ diseases. Abnormal CAG expansions mediated by CRISPR/Cas9 genome engineering technologies have shown promising potential for the treatment of polyQ diseases, including SCA3. In this study, SCA3-iPSCs can be corrected by the replacement of the abnormal CAG expansions (74 CAG) with normal repeats (17 CAG) using CRISPR/Cas9-mediated homologous recombination (HR) strategy. Besides, corrected SCA3-iPSCs retained pluripotent and normal karyotype, which can be differentiated into a neural stem cell (NSCs) and neuronal cells, and maintained electrophysiological characteristics. The expression of differentiation markers and electrophysiological characteristics were similar among the neuronal differentiation from normal control iPSCs (Ctrl-iPSCs), SCA3-iPSCs, and isogenic control SCA3-iPSCs. Furthermore, this study proved that the phenotypic abnormalities in SCA3 neurons, including aggregated IC2-polyQ protein, decreased mitochondrial membrane potential (MMP) and glutathione expressions, increased reactive oxygen species (ROS), intracellular Ca concentrations, and lipid peroxidase malondialdehyde (MDA) levels, all were rescued in the corrected SCA3-NCs. For the first time, this study demonstrated the feasibility of CRISPR/Cas9-mediated HR strategy to precisely repair SCA3-iPSCs, and reverse the corresponding abnormal disease phenotypes. In addition, the importance of genetic control using CRISPR/Cas9-mediated iPSCs for disease modeling. Our work may contribute to providing a potential ideal model for molecular mechanism research and autologous stem cell therapy of SCA3 or other polyQ diseases, and offer a good gene therapy strategy for future treatment.
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http://dx.doi.org/10.1038/s41398-021-01605-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448778PMC
September 2021

Pharmacologic approaches to amino acid depletion for cancer therapy.

Mol Carcinog 2021 Sep 17. Epub 2021 Sep 17.

Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas, USA.

Cancer cells undergo metabolic reprogramming to support increased demands in bioenergetics and biosynthesis and to maintain reactive oxygen species at optimum levels. As metabolic alterations are broadly observed across many cancer types, metabolic reprogramming is considered a hallmark of cancer. A metabolic alteration commonly seen in cancer cells is an increased demand for certain amino acids. Amino acids are involved in a wide range of cellular functions, including proliferation, redox balance, bioenergetic and biosynthesis support, and homeostatic functions. Thus, targeting amino acid dependency in cancer is an attractive strategy for a number of cancers. In particular, pharmacologically mediated amino acid depletion has been evaluated as a cancer treatment option for several cancers. Amino acids that have been investigated for the feasibility of drug-induced depletion in preclinical and clinical studies for cancer treatment include arginine, asparagine, cysteine, glutamine, lysine, and methionine. In this review, we will summarize the status of current research on pharmacologically mediated amino acid depletion as a strategy for cancer treatment and potential chemotherapeutic combinations that synergize with amino acid depletion to further inhibit tumor growth and progression.
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http://dx.doi.org/10.1002/mc.23349DOI Listing
September 2021
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