Publications by authors named "Chun Zhou"

309 Publications

Associations of serum cystatin C and its change with new-onset cardiovascular disease in Chinese general population.

Nutr Metab Cardiovasc Dis 2022 May 29. Epub 2022 May 29.

Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510515, China. Electronic address:

Background And Aims: The relation of serum cystatin C with new-onset cardiovascular disease (CVD) remains uncertain. We aimed to evaluate the prospective associations of serum cystatin C and its change with new-onset CVD in Chinese general population.

Methods And Results: A total of 7064 participants free of CVD at baseline were enrolled from the China Health and Retirement Longitudinal Study. The change in serum cystatin C was calculated as cystatin C concentration at 2015 wave minus that at baseline (2011 wave). The primary outcome was new-onset CVD, defined as self-reported physician-diagnosed heart disease, stroke, or both during follow-up. The secondary outcomes were new-onset heart disease, and new-onset stroke. During a median follow-up duration of 7.0 years, a total of 1116 (15.8%) subjects developed new-onset CVD. Overall, after the adjustments for eGFR and other important covariates, there was a positive association between serum cystatin C and new-onset CVD (per SD mg/L increment; adjusted HR, 1.13; 95%CI: 1.08,1.18). When cystatin C was assessed as quintiles, the adjusted HRs for participants in the second, third, fourth and fifth quintiles were 1.15 (95%CI: 0.93, 1.41), 1.37 (95%CI: 1.11, 1.68), 1.47 (95%CI: 1.19, 1.81), and 2.03 (95%CI: 1.60, 2.56), respectively, compared with those in quintile 1 (P for trend<0.001). Furthermore, there was a positive association between the increase in cystatin C concentration and the subsequent new-onset CVD (per SD mg/L increment; adjusted HR, 1.14; 95%CI: 1.02,1.27).

Conclusion: Both serum cystatin C and its increase were positively associated with new-onset CVD among Chinese general population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.numecd.2022.05.016DOI Listing
May 2022

Mechanistic insights on cytotoxicity of KOLR, Cinnamomum pauciflorum Nees leaf derived active ingredient, by targeting signaling complexes of phosphodiesterase 3B and rap guanine nucleotide exchange factor 3.

Phytother Res 2022 Jun 15. Epub 2022 Jun 15.

Cancer Institute of Integrated tradition Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China.

Protein signaling complexes play important roles in prevention of several cancer types and can be used for development of targeted therapy. The roles of signaling complexes of phosphodiesterase 3B (PDE3B) and Rap guanine nucleotide exchange factor 3 (RAPGEF3), which are two important enzymes of cyclic adenosine monophosphate (cAMP) metabolism, in cancer have not been fully explored. In the current study, a natural product Kaempferol-3-O-(3'',4''-di-E-p-coumaroyl)-α-L-rhamnopyranoside designated as KOLR was extracted from Cinnamomum pauciflorum Nees leaves. KOLR exhibited higher cytotoxic effects against BxCP-3 pancreatic cancer cell line. In BxPC-3 cells, the KOLR could enhance the formation of RAPGEF 3/ PDE3B protein complex to inhibit the activation of Rap-1 and PI3K-AKT pathway, thereby promoting cell apoptosis and inhibiting cell metastasis. Mutation of RAPGEF3 G557A or low expression of PDE3B inactivated the binding action of KOLR resulting in KOLR resistance. The findings of this study show that PDE3B/RAPGEF3 complex is a potential therapeutic cancer target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ptr.7521DOI Listing
June 2022

Association of urinary albumin:creatinine ratio with incident frailty in older populations.

Clin Kidney J 2022 Jun 8;15(6):1093-1099. Epub 2022 Jan 8.

Division of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China.

Background: The longitudinal relationship of albuminuria with incident frailty remains unknown. Therefore we aimed to evaluate the relation of albuminuria with the risk of incident frailty in older adults.

Methods: A total of 1115 participants ≥65 years of age (average age 80.3 years) who were free of frailty in the Chinese Longitudinal Healthy Longevity Survey were included. The outcome was incident frailty, defined as a frailty index ≥0.25 during follow-up. Cox proportional hazards models were used to assess the association of the urinary albumin:creatinine ratio (UACR) with frailty.

Results: During a median follow-up duration of 5.3 years, 295 (26.5%) participants developed incident frailty. Overall, the UACR was significantly positively associated with the risk of incident frailty (P for trend = 0.005), with a significantly higher risk of incident frailty in participants in the quartile 4 of UACR {≥13.43 mg/g; hazard ratio [HR] 1.64 [95% confidence interval (CI) 1.13-2.37]} compared with those in quartile 1 (<0.73 mg/g). Consistently, when UACRs were assessed as clinical categories, compared with participants with UACR <10 mg/g, those with UACR ≥30 mg/g had a higher HR of incident frailty [HR 1.61 (95% CI 1.17-2.20)]. Accounting for the competing risk of death also did not substantially change the results. In addition, a stronger positive association between UACR and incident frailty was found in those with a higher high-sensitivity C-reactive protein level (hs-CRP) (P for interaction = 0.045).

Conclusion: Albuminuria was positively associated with the risk of incident frailty, particularly in those with higher hs-CRP, emphasizing the importance of managing both albuminuria and inflammation for primary prevention of frailty.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ckj/sfac002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9155239PMC
June 2022

Active and Smart Terahertz Electro-Optic Modulator Based on VO Structure.

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

Anhui Key Laboratory of Condensed Matter Physics at Extreme Conditions, High Magnetic Field Laboratory, HFIPS, Anhui, Chinese Academy of Sciences, Hefei 230031, P. R. China.

Modulating terahertz (THz) waves actively and smartly through an external field is highly desired in the development of THz spectroscopic devices. Here, we demonstrate an active and smart electro-optic THz modulator based on a strongly correlated electron oxide vanadium dioxide (VO). With milliampere current excitation on the VO thin film, the transmission, reflection, absorption, and phase of THz waves can be modulated efficiently. In particular, the antireflection condition can be actively achieved and the modulation depth reaches 99.9%, accompanied by a 180° phase switching. Repeated and current scanning experiments confirm the high stability and multibit modulation of this electro-optic modulation. Most strikingly, by utilizing a feedback loop of "THz-electro-THz" geometry, a smart electro-optic THz control is realized. For instance, the antireflection condition can be stabilized precisely no matter what the initial condition is and how the external environment changes. The proposed electro-optic THz modulation method, taking advantage of strongly correlated electron material, opens up avenues for the realization of THz smart devices.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.2c04736DOI Listing
June 2022

Rice LEAFY COTYLEDON1 Hinders Embryo Greening During the Seed Development.

Front Plant Sci 2022 10;13:887980. Epub 2022 May 10.

College of Life Sciences, Zhejiang University, Hangzhou, China.

LEAFY COTYLEDON1 (LEC1) is the central regulator of seed development in Arabidopsis, while its function in monocots is largely elusive. We generated mutants using CRISPR/Cas9 technology. mutant seeds lost desiccation tolerance and triggered embryo greening at the early development stage. Transcriptome analysis demonstrated that mutation altered diverse hormonal pathways and stress response in seed maturation, and promoted a series of photosynthesis-related genes. Further, genome-wide identification of OsLEC1-binding sites demonstrated that OsLEC1 bound to genes involved in photosynthesis, photomorphogenesis, as well as abscisic acid (ABA) and gibberellin (GA) pathways, involved in seed maturation. We illustrated an OsLEC1-regulating gene network during seed development, including the interconnection between photosynthesis and ABA/GA biosynthesis/signaling. Our findings suggested that OsLEC1 acts as not only a central regulator of seed maturation but also an inhibitor of embryo greening during rice seed development. This study would provide new understanding for the OsLEC1 regulatory mechanisms on photosynthesis in the monocot seed development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpls.2022.887980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128838PMC
May 2022

Bidirectional relations between depression symptoms and chronic kidney disease.

J Affect Disord 2022 08 21;311:224-230. Epub 2022 May 21.

Division of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology; Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou 510515, China. Electronic address:

Background: Depression and chronic kidney disease (CKD) often coexist. However, both the relations of depression with CKD development and CKD with depression risk were still elusive. We aimed to investigate the bidirectional relations between renal function and depression in a cohort of young and middle-aged adults.

Methods: Using data from the Coronary Artery Risk Development in Young Adults study, the analysis of depressive symptoms and incident CKD (analysis 1) was performed in 3,731 participants without CKD, and the analysis of renal function and incident depression (analysis 2) was performed in 2,994 participants without depression. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale (-CES-D), and depression was defined as CES-D scores ≥16 or self-reported history of depression or antidepressant medication use. CKD was defined as estimated glomerular filtration rate <60 ml/min/1.73 m or urinary albumin to creatinine ratio ≥30 mg/g.

Results: In analysis 1, 485 participants developed incident CKD during 61,202 person-years of follow-up, and CES-D scores (≥16 vs. <16; adjusted HR, 1.28; 95% CI, 1.04 to 1.59) were significant positive associated with incident CKD. In analysis 2, 1,029 participants developed incident depression during 42,927 person-years of follow-up, and CKD was significantly associated with a 36% increased risk of incident depression compared to non-CKD (HR, 1.36; 95% CI, 1.05 to 1.76).

Limitations: Depressive symptoms were only assessed using CES-D score, which is not the gold standard for the clinical diagnosis of depression.

Conclusions: This prospective cohort study monitored over 20 years indicated a bidirectional association between depression and CKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jad.2022.05.104DOI Listing
August 2022

Domestic physical activity and new-onset hypertension: A nationwide cohort study in China.

Am J Med 2022 May 15. Epub 2022 May 15.

Division of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory; Guangdong Provincial Clinical Research Center for Kidney Disease, Guangzhou, China; Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China; Institute of Biomedicine, Anhui Medical University, Hefei 230032, China. Electronic address:

Background: The association between domestic physical activity and the risk of hypertension remains uncertain. We aimed to evaluate the prospective relation of domestic physical activity and new-onset hypertension among Chinese males and females.

Methods: A total of 9254 adults who were free of hypertension at baseline were enrolled from the China Health and Nutrition Survey (CHNS). Data on domestic physical activity were obtained by using self-reported questionnaires, and calculated as metabolic equivalent task (MET)-hours/week. MET-hours/week may account for both intensity and time spent on activities. The study outcome was new-onset hypertension, defined as systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg or diagnosed by physician or under antihypertensive treatment during the follow-up.

Results: During a median of 8.0 years (81,996 person-years) of follow-up, a total of 2892 participants developed hypertension. Overall, there were reversed J-shaped associations between the domestic physical activity and new-onset hypertension in both males and females (both P values for nonlinearity<0.001). Consistently, when domestic physical activity was assessed as categories (<10, 10-<20, 20-<30, 30-<40, 40-<50, 50-<60, 60-<70, 70-<80, 80-<90, 90-<100, ≥100 MET-hours/week), compared with those with domestic physical activity <10 MET-hours/week, the lower and similar risks of new-onset hypertension were found in participants with domestic physical activity 30-<90 MET-hours/week in both males and females.

Conclusion: Moderate domestic physical activity was associated with a lower risk of new-onset hypertension among both males and females.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjmed.2022.04.023DOI Listing
May 2022

Structural insights into Ras regulation by SIN1.

Proc Natl Acad Sci U S A 2022 05 6;119(19):e2119990119. Epub 2022 May 6.

School of Public Health, Zhejiang University School of Medicine, Hangzhou, 310058, China.

Over the years it has been established that SIN1, a key component of mTORC2, could interact with Ras family small GTPases through its Ras-binding domain (RBD). The physical association of Ras and SIN1/mTORC2 could potentially affect both mTORC2 and Ras-ERK pathways. To decipher the precise molecular mechanism of this interaction, we determined the high-resolution structures of HRas/KRas-SIN1 RBD complexes, showing the detailed interaction interface. Mutation of critical interface residues abolished Ras-SIN1 interaction and in SIN1 knockout cells we demonstrated that Ras-SIN1 association promotes SGK1 activity but inhibits insulin-induced ERK activation. With structural comparison and competition fluorescence resonance energy transfer (FRET) assays we showed that HRas-SIN1 RBD association is much weaker than HRas-Raf1 RBD but is slightly stronger than HRas-PI3K RBD interaction, providing a possible explanation for the different outcome of insulin or EGF stimulation. We also found that SIN1 isoform lacking the PH domain binds stronger to Ras than other longer isoforms and the PH domain appears to have an inhibitory effect on Ras-SIN1 binding. In addition, we uncovered a Ras dimerization interface that could be critical for Ras oligomerization. Our results advance our understanding of Ras-SIN1 association and crosstalk between growth factor-stimulated pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2119990119DOI Listing
May 2022

Correction to: Dysregulation of miR-202-3p Affects Migration and Invasion of Endometrial Stromal Cells in Endometriosis via Targeting ROCK1.

Reprod Sci 2022 Jun;29(6):1963-1964

Reproductive Medicine Center, Zhongnan Hospital, Wuhan University, No.169 East Lake Road, Wuhan, 430071, Hubei, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s43032-022-00950-xDOI Listing
June 2022

Folate intake and incident chronic kidney disease: a 30-y follow-up study from young adulthood to midlife.

Am J Clin Nutr 2022 Apr 23. Epub 2022 Apr 23.

Division of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510515, China.

Background: The relation of long-term dietary folate intake with incident chronic kidney disease (CKD) remains uncertain.

Objective: We aimed to investigate the association between dietary folate intake and incident CKD in a 30-y follow-up study from young adulthood to midlife.

Methods: A total of 4038 American adults aged 18-30 years and without reduced estimated glomerular filtration rate (eGFR) were enrolled in 1985-1986 and monitored until 2015-2016 in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Diet was assessed by a validated dietary-history questionnaire at baseline, in 1992-1993, and in 2005-2006. The primary outcome was incident CKD, defined as an eGFR <60mL/min per 1.73 m2 or urinary albumin to creatinine ratio (ACR) ≥30mg/g. The secondary outcomes included: (1) incident decreased eGFR, defined as an eGFR <60mL/min/1.73 m2, and (2) incident albuminuria, defined as an ACR ≥30mg/g.

Results: During the follow-up, 642 (15.9%) participants developed CKD. Overall, there was a significant L-shaped relation of dietary folate with incident CKD after adjustment for potential confounders. Compared with the lowest quintile of total folate intake, the multivariable-adjusted hazard ratios (95%CI) in quintile 2-5 were 0.69(0.56, 0.85), 0.35(0.27, 0.45), 0.34(0.26, 0.45), and 0.39(0.30, 0.51), respectively. Similar results were found for the secondary outcomes. Moreover, the L-shaped association was confirmed in a subset of the cohort (n=1462) with serum folate measured at baseline, and in 1992 and 2000.

Conclusions: Higher folate intake in young adulthood was longitudinally associated with a lower incidence of CKD later in life. Additional studies are warranted to establish the causal inference.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajcn/nqac109DOI Listing
April 2022

Practical Security of High-Dimensional Quantum Key Distribution with Intensity Modulator Extinction.

Entropy (Basel) 2022 Mar 26;24(4). Epub 2022 Mar 26.

Henan Key Laboratory of Quantum Information and Cryptography, SSF IEU, Zhengzhou 450001, China.

Quantum key distribution (QKD) has attracted much attention due to its unconditional security. High-dimensional quantum key distribution (HD-QKD) is a brand-new type of QKD protocol that has many excellent advantages. Nonetheless, practical imperfections in realistic devices that are not considered in the theoretical security proof may have an impact on the practical security of realistic HD-QKD systems. In this paper, we research the influence of a realistic intensity modulator on the practical security of HD-QKD systems with the decoy-state method and finite-key effects. We demonstrate that there is a certain impact in the secret key rate and the transmission distance when taking practical factors into security analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/e24040460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9026895PMC
March 2022

Structural Changes during the Conversion Reaction of Tungsten Oxide Electrodes with Tailored, Mesoscale Porosity.

ACS Nano 2022 Mar 31. Epub 2022 Mar 31.

Pritzker School of Molecular Engineering, University of Chicago, 5640 South Ellis Avenue, Chicago, Illinois 60637, United States.

In-plane tungsten oxide nanostructures, including hexagonally patterned cylinders and holes in a matrix, were fabricated sequential infiltration synthesis (SIS) on self-assembled block copolymer templates. Using the tailored morphology and porosity of these model electrodes with grazing incidence small-angle X-ray scattering, the intrinsic structural change of nanoscale active materials during the conversion reaction of WO + 6Li ↔ W + 3LiO was investigated at controlled electrochemical conditions. Reversible electrode volume expansion and contraction was observed during lithiation and delithiation cycles, respectively. The potential where the electrode's thickness expansion started was ∼1.6 V, which is close to the thermodynamically expected one for the conversion reaction of WO with lithium (1.65 V). The temporal evolution of the electrode volume at constant electrode potentials revealed high overpotential for bulk lithiation and slow conversion reaction kinetics, despite the tailored porosity of the SIS electrodes. Oxide cylinders showed a smaller overall electrode thickness change, likely due to unconstrained lateral volume change, as compared to a matrix with holes. On the other hand, better connectivity and guided volume change of the latter electrode morphology provided improved cycling stability. In addition, heterogeneity in an electrode, from internal pores and density gradients, was found to aggravate the fragmentation of the electrode during the conversion reaction. Insights into oxide conversion reaction kinetics and the relationship between electrode mesostructure and cycling behavior obtained from this study can help guide the more rational design of conversion electrodes for high-performing batteries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.1c08599DOI Listing
March 2022

Use of Digital Whiteboard to Engage Undergraduates in Online Studies of Instructor-Generated Biological Diagrams.

J Microbiol Biol Educ 2022 Apr 31;23(1). Epub 2022 Jan 31.

Department of Natural Sciences, School of Health and Natural Sciences, Mercy College, Dobbs Ferry, New York, USA.

The development of critical thinking skills is one of the core values of higher education. As an important aspect of visual literacy in the core competencies of undergraduate biology teaching, diagram learning activities have been shown to facilitate students' gains in understanding biology concepts and improving critical thinking skills. To address a need to scaffold students' learning processes of the higher-order cognitive skills in Bloom's Taxonomy via diagram, we have developed an instructional tool using diagrams for online and in-person classes. This teaching and learning tool utilizes a digital canvas created in Microsoft Whiteboard. A diagram of a certain complexity is designed and created by the instructor to model the critical thinking linked to the taught content. Students can work simultaneously to fill in the blanks of the diagram using provided terms and phrases that are derived from lecture slides and aligned with course learning objectives. A moderator, either a peer leader or the instructor, can use this online whiteboard to observe and advise students for their study activities and engage students in discussions in real-time. This customized teaching tool may be particularly useful for introductory biology courses to train first-year students and sophomores to learn biological concepts and mechanisms. More importantly, it helps students comprehend and learn the critical thinking skills embedded in the provided diagrams to prepare them to conduct more complex diagram activities and generate their own diagrams.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/jmbe.00195-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8943568PMC
April 2022

Inverse Association Between Variety of Proteins With Appropriate Quantity From Different Food Sources and New-Onset Hypertension.

Hypertension 2022 05 10;79(5):1017-1027. Epub 2022 Mar 10.

National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Division of Nephrology, Nanfang Hospital, Southern Medical University, China (C.Z., Q.W., Z.Y., M.L., Z.Z., Y.Z., H.L., P.H., Q.L., C.L., X.Q.).

The relationships of the variety and quantity of different sources of dietary proteins with hypertension remain uncertain. We aimed to investigate associations between the variety and quantity of proteins intake from 8 major food sources and new-onset hypertension among 12 177 participants from the China Health and Nutrition Survey. Dietary intake was measured by 3 consecutive 24-hour dietary recalls combined with a household food inventory. The variety score of protein sources was defined as the number of protein sources consumed at the appropriate level, accounting for types and quantity of proteins. New-onset hypertension was defined as systolic blood pressure ≥140 mm Hg and diastolic blood pressure ≥90 mm Hg, or physician-diagnosed hypertension or receiving antihypertensive treatment, during the follow-up. During a median follow-up of 6.1 years, there were U-shaped associations of percentages energy from total, unprocessed or processed red meat-derived, whole grain-derived, and poultry-derived proteins with new-onset hypertension; an reverse J-shaped association of fish-derived protein with new-onset hypertension; L-shaped associations of eggs-derived and legumes-derived proteins with new-onset hypertension; and an reverse L-shaped association of refined grain-derived protein with new-onset hypertension (all values for nonlinearity <0.001). That is, for each protein, there is a window of consumption (appropriate level) where the risk of hypertension is lower. Moreover, a significantly lower risk of new-onset hypertension was found in those with higher variety score of protein sources (per score increment, hazard ratio, 0.74 [95% CI, 0.72-0.76]). In summary, there was an inverse association between the variety of proteins with appropriate quantity from different food sources and new-onset hypertension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.18222DOI Listing
May 2022

Signaling Dynamics of TSHR-Specific CAR-T Cells Revealed by FRET-Based Biosensors.

Front Cell Dev Biol 2022 17;10:845319. Epub 2022 Feb 17.

Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China.

Although most patients with thyroid cancers have good prognosis and long-term survival, some patients are refractory to traditional therapeutic approaches and face a high risk of mortality. CAR-T therapy provides an attractive strategy to treat these patients. Considering the limited expression in thyroid tissues, thyroid-stimulating hormone receptor (TSHR) has been considered as a promising candidate as CAR-T target. However, it is still a challenge to find the optimal CAR design for the treatment of thyroid cancers. Dynamic signaling cascade is initiated by CAR molecules during CAR-T cell activation. The development of FRET-based biosensors enables us to detect the signaling dynamics of key kinases during CAR-T cell activation with high spatiotemporal resolution. Here using the ZAP70 and ERK biosensors, we visualized the dynamics of ZAP70 and ERK activities in TSHR-specific CAR-T cells upon antigen stimulation. We first constructed several TSHR-targeting CARs for the treatment of advanced thyroid cancers. The TSHR CAR-T cells with CD28 or 4-1BB co-stimulatory signaling domains exhibited potent cytotoxicity . By FRET imaging, we observed rapid increase of ZAP70 and ERK activities in TSHR CAR-T cells upon target cell binding. Even though CD28-based CAR-T cells had similar ZAP70 activation dynamics as 4-1BB-based CAR-T cells, they displayed slightly enhanced ERK activation, which may contribute to their faster anti-tumor kinetics . These results demonstrated the efficacy of TSHR CAR-T cells to treat advanced thyroid cancers. Our study indicated the potential of applying FRET biosensors to optimize the design of CAR for effective CAR-T therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2022.845319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8893275PMC
February 2022

Asperosaponin VI protects mice from sepsis by regulating Hippo and Rho signaling pathway.

Phytomedicine 2022 Feb 18;99:154010. Epub 2022 Feb 18.

SMU-KI United Medical Inflammatory Center, Guangdong Provincial Key Laboratory of Shock and Microcirculation, School of Pharmaceutical Sciences, Southern Medical University, No. 1023-1063, Shatai South Road, Baiyun District, Guangzhou 510515, China. Electronic address:

Objective: To explore the novel protective effect of Asperosaponin VI (AVI) on sepsis and its potential mechanism.

Methods: In in vitro experiments, bone marrow mononuclear cells and THP-1-derived cells were used to evaluate the viability of AVI treatment. Besides, the quantitative real-time PCR and Western blot were adopted to explore the protective effect of AVI on LPS-induced inflammation. For in vivo work, the effect of AVI on mice was evaluated by using both CLP-induced and the LPS-induced sepsis mice model. The fluctuation of anal temperature and the behavior of mice were recorded after surgery. Further, the content of bacteria in peritoneal lavage fluid was detected, as well as the levels of ALT, AST, LD and LDH in serum with ELISA. H&E staining and real-time PCR were used to evaluate the histopathology of liver, spleen and lung. Finally, relevant signaling pathways were detected by Western blot, real-time PCR and immunohistochemistry.

Results: AVI inhibited the expression of inflammatory factors in both CLP-induced and LPS-induced sepsis mice models, and reduced the number of bacteria in abdominal lavage fluid. The preventive treatment with AVI alleviated sepsis-induced organ injuries, reduced inflammatory responses, which was through inhibiting Hippo and Rho signaling pathway.

Conclusions: This study indicated that AVI effectively protected mice from sepsis by down-regulating the activation of Hippo signaling and Rho family, and reducing inflammation and organ damage. However, conventional treatment was using antibiotics, and its mechanism was different with AVI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phymed.2022.154010DOI Listing
February 2022

Identification of New ATG8s-Binding Proteins with Canonical LC3-Interacting Region in Autophagosomes of Barley Callus.

Plant Cell Physiol 2022 Feb 3. Epub 2022 Feb 3.

Autophagy is essential to maintain cellular homeostasis for normal cell growth and development. In selective autophagy, ATG8 plays a crucial role in cargo target recognition by binding to various adaptors and receptors with the ATG8-interacting motif, also known as the LC3-interacting region (LIR). However, the process of autophagy in the callus, as a proliferating cell type, is largely unknown. In this study, we overexpressed green fluorescent protein (GFP)-ATG8a and GFP-ATG8b transgenic barley callus and checked their autophagic activities. We identified five new ATG8 candidate interactors containing the canonical LIR motif by using immunoprecipitation coupled with mass spectrometry: RPP3, COPE, NCLN, RAE1, and CTSL. The binding activities between these candidate interactors and ATG8 were further demonstrated in the punctate structure. Notably, RPP3 was colocalized in ATG8-labeled autophagosomes under tunicamycin-induced ER stress. GST pull-down assays showed that the interaction between RPP3 and ATG8 could be prevented by mutating the LIRs region of RPP3 or the LIR docking site (LDS) of ATG8, suggesting that RPP3 directly interacted with ATG8 in an LIR-dependent manner via the LDS. Our findings would provide the basis for further investigations on novel receptors and functions of autophagy in plants, especially in the physiological state of cell de-differentiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/pcp/pcac015DOI Listing
February 2022

Application of Logistic Regression and Decision Tree Models in the Prediction of Activities of Daily Living in Patients with Stroke.

Neural Plast 2022 28;2022:9662630. Epub 2022 Jan 28.

Department of Rehabilitation, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, China.

An improvement in the activities of daily living (ADLs) is significantly related to the quality of life and prognoses of patients with stroke. However, the factors predicting significant improvement in ADL (SI-ADL) have not yet been clarified. Therefore, we sought to identify the key factors affecting SI-ADL in patients with stroke after rehabilitation therapy using both logistic regression modeling and decision tree modeling. We retrospectively collected and analyzed the clinical data of 190 patients with stroke who underwent rehabilitation therapy at our hospital between January 2020 and July 2020. General and rehabilitation therapy data were extracted, and the Barthel index (BI) score was used for outcome assessment. We defined SI-ADL as an improvement in the BI score by 15 points or more during hospitalization. Logistic regression and decision tree models were established to explore the SI-ADL predictors. We then used receiver operating characteristic (ROC) curves to compare the logistic regression and decision tree models. Univariate analysis revealed that compared with the non-SI-ADL group, the SI-ADL group showed a significantly shorter course of stroke, longer hospital stay, and higher rate of receiving occupational and speech therapies (all < 0.05). Binary logistic regression analysis revealed the course of stroke at admission (odds ratio (OR) = 0.986, 95%confidence interval (CI) = 0.979-0.993; < 0.001) and the length of hospital stay (OR = 1.030, 95%CI = 1.013-1.047;  =0.001) as the independent predictors of SI-ADL. ROC comparisons revealed no significant differences in the areas under the curves for the logistic regression and decision tree models (0.808 0.831; = 0.977, = 0.329). Both models identified the course of disease at admission and the length of hospital stay as key factors affecting SI-ADL. Early initiation of rehabilitation therapy is of immense importance for improving the ADLs in patients with stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2022/9662630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8816537PMC
March 2022

Predicted fat mass and lean mass in relation to all-cause and cause-specific mortality.

J Cachexia Sarcopenia Muscle 2022 Apr 23;13(2):1064-1075. Epub 2022 Jan 23.

Division of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China.

Background: Studies on the prospective association of body composition with mortality in US general populations are limited. We aimed to examine this association by utilizing data from the National Health and Nutrition Examination Survey (NHANES), a representative sample of US adults, linked with data from the National Death Index.

Methods: We analysed data of NHANES 1988-1994 and 1999-2014, with 55 818 participants [50.6% female, baseline mean age: 45.0 years (SE, 0.2)]. Predicted fat mass and lean mass were calculated using the validated sex-specific anthropometric prediction equations developed by the NHANES based on individual age, race, height, weight, and waist circumference. Body composition and other covariates were measured at only one time point. Multivariable Cox regression was used to investigate the associations of predicted fat mass and lean mass with overall and cause-specific mortality, adjusting for potential confounders. Interactions between age and body composition on mortality were examined with likelihood ratio testing.

Results: Mean predicted fat mass was 24.1 kg [95% confidence interval (CI): 23.9-24.3) for male participants and 29.9 kg (95% CI: 29.6-30.1) for female participants, while mean predicted lean mass was 59.3 kg (95% CI: 59.1-59.5) for male participants and 41.7 kg (95% CI: 41.5-41.8) for female participants. During a median period of 9.7 years from the survey, 10 408 deaths occurred. When predicted fat and lean mass were both included in the model, predicted fat mass showed a U-shaped association with all-cause mortality, with significantly higher risk at two ends: Quintile 1 (HR, 1.17; 95% CI: 1.05-1.31), Quintile 2 (HR, 1.14; 95% CI: 1.04-1.26) and Quintile 5 (HR, 1.37; 95% CI: 1.12-1.68) compared with Quintile 3. In contrast, predicted lean mass showed a L-shaped association with all-cause mortality, with higher mortality in those with lower lean mass: Quintile 1 (HR, 1.64; 95% CI: 1.46-1.83) and Quintile 2 (HR, 1.29; 95% CI: 1.18-1.42) compared with Quintile 3. Similar results were found for cardiovascular, cancer, and respiratory cause-specific mortality. Age was a significant modifier: There was a monotonic positive association of predicted fat mass with mortality in younger participants (<60 years), but an approximate J-shaped association in older participants (≥60 years) (P interaction <0.001); there was a stronger inverse association between predicted lean mass and mortality in older participants (≥60) compared with those <60 years (P interaction <0.001).

Conclusions: In this US general population, predicted fat mass and lean mass were independent predictors for overall and cause-specific mortality. Age was a significant modifier on the associations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcsm.12921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8978015PMC
April 2022

Association of waist-calf circumference ratio with incident cognitive impairment in older adults.

Am J Clin Nutr 2022 Apr;115(4):1005-1012

Division of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China.

Background: The longitudinal relation of central fat and muscle mass with cognitive function remains unclear.

Objectives: We aimed to evaluate the relation of anthropometric measures, including BMI, waist circumference (WC), calf circumference (CC), and waist-calf circumference ratio (WCR), with incident cognitive impairment in older adults.

Methods: A total of 3312 participants aged ≥65 y (mean: 81.8 y) who were free of cognitive impairment [the Chinese version of the Mini-Mental State Examination (MMSE) scores ≥24 points] in the Chinese Longitudinal Healthy Longevity Survey were included. The primary outcome was incident cognitive impairment, defined as MMSE scores <24 points at the exit visit. Secondary outcomes were incident cognitive decline, defined as a reduction of MMSE scores ≥3 points at the exit visit, and incident decline in different cognitive domains, defined as a reduction of MMSE scores in the domain ≥15% at the exit visit.

Results: During a median follow-up duration of 3.6 y, 565 (17.1%) participants developed incident cognitive impairment. Overall, with mutual adjustments, higher WC [≥89 cm (fourth quartile) compared with <75 cm (first quartile); adjusted HR: 1.56; 95% CI: 1.19, 2.04] and higher WCR [≥2.9 (fourth quartile) compared with <2.4 (first quartile); adjusted HR: 1.96; 95% CI: 1.52, 2.52] were significantly associated with a higher risk of cognitive impairment, and higher CC [≥34 cm (fourth quartile) compared with <28 cm (first quartile); adjusted HR: 0.44; 95% CI: 0.33, 0.59] was associated with a lower hazard of cognitive impairment. Similar results were found for the secondary outcomes. However, BMI was not significantly associated with the study outcomes.

Conclusions: High WC and low CC were significantly associated with higher incident cognitive impairment in older adults. Moreover, WCR had a relatively stronger association with cognitive impairment compared with each circumference, suggesting maintaining both higher lean mass and lower central fat in older adults for the prevention of cognitive impairment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajcn/nqac011DOI Listing
April 2022

U-shaped association between dietary copper intake and new-onset hypertension.

Clin Nutr 2022 02 31;41(2):536-542. Epub 2021 Dec 31.

Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangdong Provincial Clinical Research Center for Kidney Disease, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 510515, China. Electronic address:

Aims: To investigate the relationship of dietary copper intake with new-onset hypertension among Chinese adults.

Methods: A total of 12,245 participants who were free of hypertension at baseline from the China Health and Nutrition Survey (CHNS) were included. Dietary intake was measured by 3 consecutive 24-h dietary recalls combined with a household food inventory. New-onset hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg or diagnosed by a physician or under antihypertensive treatment during the follow-up.

Results: During a median follow-up of 6.1 years, 4304 participants developed new-onset hypertension. Overall, the associations between dietary copper intake and new-onset hypertension followed a U-shape (P for nonlinearity <0.001). The risk of new-onset hypertension significantly decreased with the increment of dietary copper intake (per SD increment: HR, 0.71; 95% CI, 0.57-0.88) in participants with copper intake <1.57 mg/day, and increased with the increment of dietary copper intake (per SD increment: HR, 1.09; 95% CI: 1.07-1.12) in participants with copper intake ≥1.57 mg/day.

Conclusions: There was a U-shaped association between dietary copper intake and new-onset hypertension in general Chinese adults, with an inflection point at about 1.57 mg/day. Our results emphasized the importance of maintaining optimal copper intake levels for the primary prevention of hypertension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clnu.2021.12.037DOI Listing
February 2022

Variety and quantity of dietary protein intake from different sources and risk of new-onset diabetes: a Nationwide Cohort Study in China.

BMC Med 2022 01 13;20(1). Epub 2022 Jan 13.

National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.

Background: The relation of the variety and quantity of different sources of dietary proteins intake and diabetes remains uncertain. We aimed to investigate the associations between the variety and quantity of proteins intake from eight major food sources and new-onset diabetes, using data from the China Health and Nutrition Survey (CHNS).

Methods: 16,260 participants without diabetes at baseline from CHNS were included. Dietary intake was measured by three consecutive 24-h dietary recalls combined with a household food inventory. The variety score of protein sources was defined as the number of protein sources consumed at the appropriate level, accounting for both types and quantity of proteins. New-onset diabetes was defined as self-reported physician-diagnosed diabetes or fasting glucose ≥7.0mmol/L or glycated hemoglobin ≥6.5% during the follow-up.

Results: During a median follow-up of 9.0 years, 1100 (6.8%) subjects developed diabetes. Overall, there were U-shaped associations of percentages energy from total protein, whole grain-derived and poultry-derived proteins with new-onset diabetes; J-shaped associations of unprocessed or processed red meat-derived proteins with new-onset diabetes; a reverse J-shaped association of the fish-derived protein with new-onset diabetes; L-shaped associations of egg-derived and legume-derived proteins with new-onset diabetes; and a reverse L-shaped association of the refined grain-derived protein with new-onset diabetes (all P values for nonlinearity<0.001). Moreover, a significantly lower risk of new-onset diabetes was found in those with a higher variety score of protein sources (per score increment; HR, 0.69; 95%CI, 0.65-0.72).

Conclusions: There was an inverse association between the variety of proteins with appropriate quantity from different food sources and new-onset diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12916-021-02199-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8756636PMC
January 2022

An Ovine Model of Awake Veno-Arterial Extracorporeal Membrane Oxygenation.

Front Vet Sci 2021 23;8:809487. Epub 2021 Dec 23.

Department of Cardiopulmonary Bypass, State Key Laboratory of Cardiovascular Medicine, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

Large animal models are developed to help understand physiology and explore clinical translational significance in the continuous development of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) technology. The purpose of this study was to investigate the establishment methods and management strategies in an ovine model of VA-ECMO. Seven sheep underwent VA-ECMO support for 7 days by cannulation the right jugular vein and artery. The animals were transferred into the monitoring cages after surgery and were kept awake after anesthesia recovery. The hydraulic parameters of ECMO, basic hemodynamics, mental state, and fed state of sheep were observed in real time. Blood gas analysis and activated clotting time (ACT) were tested every 6 h, while the complete blood count, blood chemistry, and coagulation tests were monitored every day. Sheep were euthanized after 7 days. Necropsy was performed and the main organs were removed for histopathological evaluation. Five sheep survived and successfully weaned from ECMO. Two sheep died within 24-48 h of ECMO support. One animal died of fungal pneumonia caused by reflux aspiration, and the other died of hemorrhagic shock caused by bleeding at the left jugular artery cannulation site used for hemodynamic monitoring. During the experiment, the hemodynamics of the five sheep were stable. The animals stayed awake and freely ate hay and feed pellets and drank water. With no need for additional nutrition support or transfusion, the hemoglobin concentration and platelet count were in the normal reference range. The ECMO flow remained stable and the oxygenation performance of the oxygenator was satisfactory. No major adverse pathological injury occurred. The perioperative management strategies and animal care are the key points of the VA-ECMO model in conscious sheep. This model could be a platform for further research of disease animal models, pathophysiology exploration, and new equipment verification.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fvets.2021.809487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8735256PMC
December 2021

Tuning the ignition of CAR: optimizing the affinity of scFv to improve CAR-T therapy.

Cell Mol Life Sci 2021 Dec 29;79(1):14. Epub 2021 Dec 29.

Bone Marrow Transplantation Center of the First Affiliated Hospital & Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

How single-chain variable fragments (scFvs) affect the functions of chimeric antigen receptors (CARs) has not been well studied. Here, the components of CAR with an emphasis on scFv were described, and then several methods to measure scFv affinity were discussed. Next, scFv optimization studies for CD19, CD38, HER2, GD2 or EGFR were overviewed, showing that tuning the affinity of scFv could alleviate the on-target/off-tumor toxicity. The affinities of scFvs for different antigens were also summarized to designate a relatively optimal working range for CAR design. Last, a synthetic biology approach utilizing a low-affinity synthetic Notch (synNotch) receptor to achieve ultrasensitivity of antigen-density discrimination and murine models to assay the on-target/off-tumor toxicity of CARs were highlighted. Thus, this review provides preliminary guidelines of choosing the right scFvs for CARs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00018-021-04089-xDOI Listing
December 2021

TGF-β1 induces epithelial-to-mesenchymal transition in chronic rhinosinusitis with nasal polyps through microRNA-182.

Asian Pac J Allergy Immunol 2021 Dec 26. Epub 2021 Dec 26.

The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine, University of Chinese Academy of Sciences, Shanghai, China.

Background: Epithelial-to-mesenchymal transition (EMT) in nasal epithelial cells is involved in tissue remodeling of chronic rhinosinusitis with nasal polyps (CRSwNP). Our study investigated the molecular mechanisms that microRNA-182 (miR-182) regulated EMT in eosinophilic (Eos) and non-eosinophilic (non-Eos) CRSwNP.

Objective: To investigate the mechanism by which miR-182 regulates EMT in human nasal epithelial cells (hNEPCs).

Methods: The expression of EMT markers (E-cadherin, N-cadherin and vimentin), transforming growth factor (TGF)-β1, and miR-182 were determined by western blotting and reverse transcription-quantitative PCR (RT-qPCR). Fluorescence in situ hybridization (FISH) was used to detect the miR-182 localization. Additionally, EMT markers expression and cell morphology changes were checked upon treatment with TGF-β1, or TGF-β1 with miR-182 inhibitor, or miR-182 mimics, or miR-182 inhibitor alone in hNEPCs.

Results: In both Eos CRSwNP and non-Eos CRSwNP, the expression levels of E-cadherin were downregulated while the expression levels of N-cadherin, vimentin, TGF-β1 and miR-182 were significantly upregulated compared with control nasal tissues. Additionally, more significant changes in these EMT markers were observed in the Eos-CRSwNP when compared with the non-Eos CRSwNP. Invitro hNEPCs model, TGF-β1 upregulated miR-182 expression and promoted EMT in hNEPCs, indicated by changes in cell morphology and EMT markers expression. Furthermore, these upregulations were reversed by miR-182 inhibitor.

Conclusions: This study showed that miR-182-induced EMT in response to TGF-β1 might promote nasal polypogenesis in both Eos CRSwNP and non-Eos CRSwNP, thus providing potential targets for the future development of novel therapeutic approaches for the management of CRSwNP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12932/AP-040921-1224DOI Listing
December 2021

Cas9-Cleavage Sequences in Size-Reduced Plasmids Enhance Nonviral Genome Targeting of CARs in Primary Human T Cells.

Small Methods 2021 07 19;5(7):e2100071. Epub 2021 May 19.

Department of Cell Biology and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.

T cell genome editing holds great promise to advance a range of immunotherapies but is encumbered by the dependence on difficult-to-produce and expensive viral vectors. Here, small double-stranded plasmid DNA modified to mediate high-efficiency homologous recombination is designed. The resulting chimeric antigen receptor (CAR)-T cells display a similar phenotype, transcriptional profile, and in vivo potency to CAR-T cells generated using adeno-associated viral vector. This method should simplify and accelerate the use of precision engineering to produce edited T cells for research and clinical purposes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/smtd.202100071DOI Listing
July 2021

Decellularized tracheal scaffolds in tracheal reconstruction: An evaluation of different techniques.

J Appl Biomater Funct Mater 2021 Jan-Dec;19:22808000211064948

Department of Orthopedic Surgery, Zhejiang Provincial People's Hospital, Hangzhou, China.

In humans, the trachea is a conduit for ventilation connecting the throat and lungs. However, certain congenital or acquired diseases may cause long-term tracheal defects that require replacement. Tissue engineering is considered a promising method to reconstruct long-segment tracheal lesions and restore the structure and function of the trachea. Decellularization technology retains the natural structure of the trachea, has good biocompatibility and mechanical properties, and is currently a hotspot in tissue engineering studies. This article lists various recent representative protocols for the generation of decellularized tracheal scaffolds (DTSs), as well as their validity and limitations. Based on the advancements in decellularization methods, we discussed the impact and importance of mechanical properties, revascularization, recellularization, and biocompatibility in the production and implantation of DTS. This review provides a basis for future research on DTS and its application in clinical therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/22808000211064948DOI Listing
December 2021

Cytotoxic tau released from lung microvascular endothelial cells upon infection with Pseudomonas aeruginosa promotes neuronal tauopathy.

J Biol Chem 2022 01 8;298(1):101482. Epub 2021 Dec 8.

Department of Physiology and Cell Biology, University of South Alabama, Mobile, Alabama, USA; Center for Lung Biology, University of South Alabama, Mobile, Alabama, USA. Electronic address:

Patients who recover from nosocomial pneumonia oftentimes exhibit long-lasting cognitive impairment comparable with what is observed in Alzheimer's disease patients. We previously hypothesized that the lung endothelium contributes to infection-related neurocognitive dysfunction, because bacteria-exposed endothelial cells release a form(s) of cytotoxic tau that is sufficient to impair long-term potentiation in the hippocampus. However, the full-length lung and endothelial tau isoform(s) have yet to be resolved and it remains unclear whether the infection-induced endothelial cytotoxic tau triggers neuronal tau aggregation. Here, we demonstrate that lung endothelial cells express a big tau isoform and three additional tau isoforms that are similar to neuronal tau, each containing four microtubule-binding repeat domains, and that tau is expressed in lung capillaries in vivo. To test whether infection elicits endothelial tau capable of causing transmissible tau aggregation, the cells were infected with Pseudomonas aeruginosa. The infection-induced tau released from endothelium into the medium-induced neuronal tau aggregation in reporter cells, including reporter cells that express either the four microtubule-binding repeat domains or the full-length tau. Infection-induced release of pathological tau variant(s) from endothelium, and the ability of the endothelial-derived tau to cause neuronal tau aggregation, was abolished in tau knockout cells. After bacterial lung infection, brain homogenates from WT mice, but not from tau knockout mice, initiated tau aggregation. Thus, we conclude that bacterial pneumonia initiates the release of lung endothelial-derived cytotoxic tau, which is capable of propagating a neuronal tauopathy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbc.2021.101482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718960PMC
January 2022

Corrigendum to 'Dietary carbohydrate intake and new-onset diabetes: A Nationwide Cohort Study in China' [Metab Clin Exp 123 (2021) 154865].

Metabolism 2022 Feb 23;127:154940. Epub 2021 Nov 23.

National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Institute of Biomedicine, Anhui Medical University, Hefei 230032, China. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.metabol.2021.154940DOI Listing
February 2022

Quantity and variety of food groups consumption and the risk of diabetes in adults: A prospective cohort study.

Clin Nutr 2021 12 11;40(12):5710-5717. Epub 2021 Oct 11.

Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 510515, China. Electronic address:

Background: Evidence remains inconsistent regarding the association between quantity of food groups and diabetes, and remains scarce regarding the relation of dietary diversity with diabetes.

Objective: We aimed to evaluate the prospective relation of variety and quantity of 12 major food groups with new-onset diabetes.

Methods: A total of 16,117 participants who were free of diabetes at baseline from China Health and Nutrition Survey were included. Dietary intake and variety score were measured by three consecutive 24-h dietary recalls combined with a household food inventory in each survey round. The study outcome was new-onset diabetes, defined as self-reported physician-diagnosed diabetes during the follow-up period. Cox proportional hazards models and restricted cubic spline analysis were used to estimate hazard ratios (HR) and dose-response relation, respectively.

Results: During a median follow-up duration of 9.0 years, a total of 1088 (6.7%) participants developed new-onset diabetes. Overall, there was a significant inverse association between dietary variety score and the risk of new-onset diabetes (per one point increment; HR, 0.85; 95% CI, 0.80-0.90). In addition, there were U-shaped associations of refined grains, whole grains, nuts, red meat, poultry, processed meat, dairy products, and aquatic products intake with diabetes, and L-shaped associations of legumes, vegetables, fruits, and eggs intake with diabetes (all P values for nonlinearity <0.001).

Conclusion: Our results suggested that greater variety of food groups consumption was associated with significantly lower risk of new-onset diabetes. Furthermore, when the quantity of food groups intakes was relatively low, there was a negative correlation between the quantity of each different food group consumption and diabetes risk; however, when intake exceeded certain thresholds, the risks of new-onset diabetes increased or reached a plateau.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clnu.2021.10.003DOI Listing
December 2021
-->