Publications by authors named "Qiang Zhang"

3,540 Publications

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Emerging open microfluidics for cell manipulation.

Chem Soc Rev 2021 May;50(9):5333-5348

Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing, 100084, China.

Cell manipulation is the foundation of biochemical studies, which demands user-friendly, multifunctional and precise tools. Based on flow confinement principles, open microfluidics can control the movement of microscale liquid in open space. Every position of the circuit is accessible to external instruments, making it possible to perform precise treatment and analysis of cells at arbitrary target positions especially at the single-cell/sub-cell level. Benefiting from its unique superiority, various manipulations including patterned cell culture, 3D tissue modelling, localized chemical stimulation, online cellular factor analysis, single cell sampling, partial cell treatment, and subcellular free radical attack can be easily realized. In this tutorial review, we summarize two basic ideas to design open microfluidics: open microfluidic networks and probes. The principles of mainstream open microfluidic methods are explained, and their recent important applications are introduced. Challenges and developing trends of open microfluidics are also discussed.
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http://dx.doi.org/10.1039/d0cs01516dDOI Listing
May 2021

Absence of long-range magnetic order in lithium-containing honeycombs in the Li-Cr-Sb(Te)-O phases.

J Phys Condens Matter 2021 May 10. Epub 2021 May 10.

Department of Physics, The University of Texas at El Paso, 500 W University Ave, El Paso, El Paso, Texas, 79968, UNITED STATES.

Li$_3$((LiCr)(Te/Sb))O$_{6}$ compounds where Cr atoms along with Li and Te or Sb are part of a honeycomb and are studied using magnetic susceptibility, specific heat, X-ray photoelectron spectroscopy and neutron diffraction. The oxides stoichiometries as determined from the neutron diffraction studies are Li$_{4.47}$Cr$_{0.53}$TeO$_6$ and Li$_{3.88}$Cr$_{1.12}$SbO$_6$ with a stable oxidation state of +3 for Cr. Both the compounds crystallize in space group $C2/m$ with intermixing of cations at the $4g$ sites leaving the $2a$ sites preferentially for Te or Sb. Again, the Li+ ions alone predominantly occur in the interlayer sites. Both the compounds show a broad anomaly in specific heat at 8 K, which is robust against 8 T. A corresponding anomaly is absent in the magnetic susceptibility but recovers from its derivative, $d\chi (T)/dT$. We ascertain the magnetic anomaly temperatures ($T_a$) of \lcto\ and \lcso\ as 5.9 K and 6.7 K respectively from specific heat. Although the physical properties indicated a low temperature anomaly, neutron diffraction data did not reveal a magnetic signal or a structural anomaly down to 1.5 K. This rules out a conventional long-range ordered magnetic ground state in either compounds. Combining the results from specific heat, neutron diffraction and electron paramagnetic resonance, we put forth a scenario of depleted honeycomb lattice of Cr$^{3+}$ with predominant short-range magnetic correlations as the magnetic ground states of the title compounds.
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http://dx.doi.org/10.1088/1361-648X/abff90DOI Listing
May 2021

The Traditional Uses, Phytochemistry and Pharmacology of (Thunb.) Nakai, a Chinese Herb With Potential for Development: Review.

Front Pharmacol 2021 22;12:652926. Epub 2021 Apr 22.

College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

(Thunb.) Nakai is a folk medicine with a long history in China, which has been applied to treat sore throat, abscess, even tumor and so on. Meanwhile, it is also used as tea in some areas. At present, more than 200 chemical compounds have been isolated and identified from it, such as, sesquiterpenes, flavonoids, phenolic acids, coumarins and so on. Pharmacological studies have already confirmed that the extracts of have many effects, such as antibacterial, antiviral, anti-inflammatory, anti-tumor, and anti-thrombocytopenia, especially the effects of anti-tumor and anti-thrombocytopenia are confirmed in clinic. Therefore, this paper systematically summarized the traditional uses, botany, phytochemistry, pharmacology, and toxicity of , in order to provide a beneficial reference of its further research.
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http://dx.doi.org/10.3389/fphar.2021.652926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100461PMC
April 2021

A novel through-the-scope twin clip for the closure of gastrointestinal wounds: the first experimental survival study in pigs (with videos).

Gastrointest Endosc 2021 May 6. Epub 2021 May 6.

Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.

Background And Aims: We developed a through-the-scope twin clip (TTS-TC) for closing gastrointestinal wounds. The objective of this study was to evaluate the efficacy and safety of the TTS-TC in gastrointestinal wound closure.

Methods: Gastrointestinal nonperforating and perforating wounds (≥2.5 cm) were created in live pigs. TTS-TCs were used to convert the large wounds into small wounds. The remaining small wounds were closed using conventional through-the-scope clips (TTSC). The follow-up period was 1 month. Location and size of the wound, time of wound closure, intraoperative and postoperative adverse events and the conditions of wound healing were investigated.

Results: Thirteen wounds were created in 5 live pigs, including 2 gastric nonperforating and 3 perforating wounds, and 5 large intestinal nonperforating and 3 perforating wounds. The average long and short diameters of the wounds was 4.1 (0.9) cm, 3.4 (0.7) cm, respectively. All wounds were successfully closed using the TTS-TCs combined with TTSCs. The total average time for wound closure was 9.2 (5.3) minutes, and the average time for using the TTS-TCs was 3.9 (4.7) minutes. During the 1-month follow-up period, no bleeding, perforation, or death occurred, all the wounds healed with scar formation, and all the TTS-TCs detached spontaneously.

Conclusions: The TTS-TC was successfully used to close large-sized gastrointestinal wounds. The TTS-TC is a promising tool for large-size wound closure under flexible endoscopy.
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http://dx.doi.org/10.1016/j.gie.2021.04.027DOI Listing
May 2021

A Scale for Predicting the Outcomes of Patients with Epilepsy: A Study of 141 Cases.

Int J Gen Med 2021 28;14:1565-1574. Epub 2021 Apr 28.

Department of Neurology, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China.

Objective: This study aimed to identify the factors relevant for developing a scale to estimate the prognosis of patients with epilepsy.

Methods: This study followed 141 patients with newly or previously diagnosed epilepsy for between four and nine years. The patients were divided into three groups on the basis of their outcomes during the follow-up period: patients that were seizure-free without anti-epileptic drugs (AEDs) (group A, n = 48), patients with pharmacoresponsive epilepsy (group B, n = 52), and patients with pharmacoresistant epilepsy (group C, n = 41). The predictors of the prognosis of epilepsy were determined using logistic regression models and optimum subsets regression, and a scale for estimating the prognosis of epilepsy (SEPE) was developed.

Results: The SEPE was able to distinguish between better and worse outcomes for the three groups. A score ≤3 on the SEPE predicted that a patient would become seizure-free without the use of AEDs, with a specificity of 67% and a sensitivity of 50%. A score ≤4 on the SEPE predicted that a patient may have a positive outcome; scores in this range were assigned to 97.9% of patients that were seizure-free without the use of AEDs and 65% of patients with pharmacoresponsive epilepsy, with a specificity of 80%, a sensitivity of 81%. Scores ≥6 on the SEPE predicted a poor outcome.

Conclusion: Of the patients with a SEPE score ≤3, some were able to become seizure-free without the use of AEDs, while for other patients, it may be possible that AED use can be discontinued. Patients with a SEPE score ≤4 have the potential to achieve long-term remission. Patients with a SEPE score ≥6 are more likely to have pharmacoresistant epilepsy.
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http://dx.doi.org/10.2147/IJGM.S302735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089470PMC
April 2021

Fiber optic hydrogen sensor based on a Fabry-Perot interferometer with a fiber Bragg grating and a nanofilm.

Lab Chip 2021 May;21(9):1752-1758

Shenzhen Key Laboratory of Photonic Devices and Sensing Systems for Internet of Things, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China. and Guangdong and Hong Kong Joint Research Centre for Optical Fibre Sensors, Shenzhen University, Shenzhen 518060, China.

Hydrogen is widely used in industrial production and clinical medicine, and as fuel. Hydrogen becomes explosive when the hydrogen-air mixture ranges from 4 to 76 vol%; thus, a rapid hydrogen concentration measurement is particularly important in practical applications. We present a novel fiber optic hydrogen sensor with fast response fabricated from a graphene-Au-Pd sandwich nanofilm and an ultrashort fiber Bragg grating. The response time is only 4.3 s at a 3.5 vol% hydrogen concentration. When the measured hydrogen concentration was increased from 0 to 4.5 vol%, the optical resonance dip in the sensor near 1550 nm shifted by 290 pm. In addition, the sensor has an insertion loss of only -2.22 dB, a spectral contrast of 10.8 dB, and a spectral finesse of 5. Such a flexible, fast-response sensor is expected to be used in the development of hydrogen sensors with low power consumption.
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http://dx.doi.org/10.1039/d1lc00012hDOI Listing
May 2021

Interrogation of gender disparity uncovers androgen receptor as the transcriptional activator for oncogenic miR-125b in gastric cancer.

Cell Death Dis 2021 May 4;12(5):441. Epub 2021 May 4.

Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China.

There is a male preponderance in gastric cancer (GC), which suggests a role of androgen and androgen receptor (AR). However, the mechanism of AR signaling in GC especially in female patients remains obscure. We sought to identify the AR signaling pathway that might be related to prognosis and examine the potential clinical utility of the AR antagonist for treatment. Deep learning and gene set enrichment analysis was used to identify potential critical factors associated with gender bias in GC (n = 1390). Gene expression profile analysis was performed to screen differentially expressed genes associated with AR expression in the Tianjin discovery set (n = 90) and TCGA validation set (n = 341). Predictors of survival were identified via lasso regression analyses and validated in the expanded Tianjin cohort (n = 373). In vitro and in vivo experiments were established to determine the drug effect. The GC gender bias was attributable to sex chromosome abnormalities and AR signaling dysregulation. The candidates for AR-related gene sets were screened, and AR combined with miR-125b was associated with poor prognosis, particularly among female patients. AR was confirmed to directly regulate miR-125b expression. AR-miR-125b signaling pathway inhibited apoptosis and promoted proliferation. AR antagonist, bicalutamide, exerted anti-tumor activities and induced apoptosis both in vitro and in vivo, using GC cell lines and female patient-derived xenograft (PDX) model. We have shed light on gender differences by revealing a hormone-regulated oncogenic signaling pathway in GC. Our preclinical studies suggest that AR is a potential therapeutic target for this deadly cancer type, especially in female patients.
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http://dx.doi.org/10.1038/s41419-021-03727-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096848PMC
May 2021

Qki regulates myelinogenesis through Srebp2-dependent cholesterol biosynthesis.

Elife 2021 May 4;10. Epub 2021 May 4.

Department of Cancer Biology, MD Anderson Cancer Center, Houston, United States.

Myelination depends on timely, precise control of oligodendrocyte differentiation and myelinogenesis. Cholesterol is the most abundant component of myelin and essential for myelin membrane assembly in the central nervous system. However, the underlying mechanisms of precise control of cholesterol biosynthesis in oligodendrocytes remain elusive. In the present study, we found that Qki depletion in neural stem cells or oligodendrocyte precursor cells in neonatal mice resulted in impaired cholesterol biosynthesis and defective myelinogenesis without compromising their differentiation into AspaGstpi myelinating oligodendrocytes. Mechanistically, Qki-5 functions as a co-activator of Srebp2 to control transcription of the genes involved in cholesterol biosynthesis in oligodendrocytes. Consequently, Qki depletion led to substantially reduced concentration of the cholesterol in mouse brain, impairing proper myelin assembly. Our study demonstrated that Qki-Srebp2-controlled cholesterol biosynthesis is indispensable for myelinogenesis and highlights a novel function of Qki as a transcriptional co-activator beyond its canonical function as an RNA-binding protein.
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http://dx.doi.org/10.7554/eLife.60467DOI Listing
May 2021

Genetic network and gene set enrichment analyses identify MND1 as potential diagnostic and therapeutic target gene for lung adenocarcinoma.

Sci Rep 2021 May 3;11(1):9430. Epub 2021 May 3.

Department of Respiratory Medicine, The Second Affiliated Hospital of Jilin University, Changchun, 130041, China.

This study aimed to characterize the key survival-specific genes for lung adenocarcinoma (LUAD) using machine-based learning approaches. Gene expression profiles were download from gene expression omnibus to analyze differentially expressed genes (DEGs) in LUAD tissues versus healthy lung tissue and to construct protein-protein interaction (PPI) networks. Using high-dimensional datasets of cancer specimens from clinical patients in the cancer genome atlas, gene set enrichment analysis was employed to assess the independent effect of meiotic nuclear divisions 1 (MND1) expression on survival status, and univariate and multivariate Cox regression analyses were applied to determine the associations of clinic-pathologic characteristics and MND1 expression with overall survival (OS). A set of 495 DEGs (145 upregulated and 350 downregulated) was detected, including 63 hub genes with ≥ 10 nodes in the PPI network. Among them, MND1 was participated in several important pathways by connecting with other genes via 17 nodes in lung cancer, and more frequently expressed in LUAD patients with advancing stage (OR = 1.68 for stage III vs. stage I). Univariate and multivariate Cox analyses demonstrated that the expression level of MND1 was significantly and negatively correlated with OS. Therefore, MND1 is a promising diagnostic and therapeutic target for LUAD.
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http://dx.doi.org/10.1038/s41598-021-88948-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093199PMC
May 2021

Homocysteine restrains hippocampal neurogenesis in focal ischemic rat brain by inhibiting DNA methylation.

Neurochem Int 2021 May 1;147:105065. Epub 2021 May 1.

Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin, 300070, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin Medical University, Tianjin, 300070, China. Electronic address:

Ischemic stroke represents a major cause of mortality worldwide. An elevated level of homocysteine (Hcy) is recognized as a powerful risk factor of ischemic stroke. We previously reported that Hcy induces cytotoxicity and proliferation inhibition in neural stem cells (NSCs) derived from the neonatal rat hippocampus in vitro. However, the toxic potential of Hcy on NSCs and its underlying mechanisms are not entirely clear in ischemic brain. Since DNA methylation is critical for establishing the diverse cell fates in the central nervous system, we hypothesized that negative effect of Hcy (an intermediate in the one-carbon metabolism) on neurogenesis might be link to DNA methylation in ischemic stroke. In our study, the rats in Hcy intervention group were intraperitoneally injected with 2% Hcy solution (5 mL/kg/d) for 7 consecutive days before MCAO surgery until they were sacrificed. Our study indicated that Hcy inhibited NSCs self-renewal capacity, which was exhibited by lowering the number of DCX/BrdU and NeuN/BrdU in ischemic brain hippocampus. A reduction in the activity of the DNA methyltransferases (DNMTs), total methylation level and the number of 5mC/NeuN and DCX/5mC cells was observed in Hcy-treated ischemic brains. Additionally, Hcy also induced an increase in S-adenosylhomocysteine (SAH), and a decrease in the ratio of S-adenosylmethionine (SAM) to SAH. These results suggest that the alterations in DNA methylation may be an important mechanism by which Hcy inhibits neurogenesis after stroke. Hcy-induced DNA hypomethylation may be mainly caused by a reduction in the DNMT activity which is regulated by the concentrations of SAM and SAH. Maintaining normal DNA methylation by lowering Hcy level may possess therapeutic potential for promoting neurological recovery and reconstruction after stroke.
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http://dx.doi.org/10.1016/j.neuint.2021.105065DOI Listing
May 2021

Can Aqueous Zinc-Air Batteries Work at Sub-Zero Temperatures?

Angew Chem Int Ed Engl 2021 May 3. Epub 2021 May 3.

Tsinghua University, Department of Chemical Engineering, Gongwu Building 308B, 100084, Beijing, CHINA.

Efficient energy storage at low temperatures starves for competent battery techniques. Herein, inherent advantages of zinc-air batteries on low-temperature electrochemical energy storage are discovered. The electrode reactions are resistive against low temperatures to render feasible working zinc-air batteries under sub-zero temperatures. The relatively reduced ionic conductivity of electrolyte is identified as the main limiting factor, which can be addressed by employing a CsOH-based electrolyte through regulating the solvation structures. Accordingly, 500 cycles with a stable voltage gap of 0.8 V at 5.0 mA cm-2 is achieved at -10oC. This work reveals the promising potential of zinc-air batteries for low-temperature electrochemical energy storage and inspires advanced battery systems under extreme working conditions.
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http://dx.doi.org/10.1002/anie.202104171DOI Listing
May 2021

Bioactive skin-mimicking hydrogel band-aids for diabetic wound healing and infectious skin incision treatment.

Bioact Mater 2021 Nov 17;6(11):3962-3975. Epub 2021 Apr 17.

School of Chemistry, Xi'an Jiaotong University, Xi'an, 710049, China.

The treatment of diabetic chronic wounds remains a global challenge due to the up-regulated inflammation response, oxidant stress, and persistent infection during healing process. Developing wound dressing materials with ideal biocompatibility, adequate mechanical strength, considerable under-water adhesion, sufficient anti-inflammation, antioxidant, and antibacterial properties is on-demand for clinical applications. In this study, we developed a bioactive skin-mimicking hydrogel band-aid through the combination of tannic acid (TA) and imidazolidinyl urea reinforced polyurethane (PMI) (TAP hydrogel) and explored its potentials in various medical applications, including hemostasis, normal skin incision, full-thickness skin wounds, and bacterial-infection skin incision on diabetic mice. TA was loaded into PMI hydrogel network to enhance the mechanical properties of TAP hydrogels through multiple non-covalent interactions (break strength: 0.28-0.64 MPa; elongation at break: 650-930%), which could resist the local stress and maintain the structural integrity of wound dressings during applications. Moreover, owing to the promising moisture-resistant adhesiveness and organ hemostasis, outstanding anti-inflammation, antibacterial, and antioxidant properties, TAP hydrogels could efficiently promote the recovery of skin incision and defects on diabetic mice. To further simulate the practical situation and explore the potential in clinical application, we also verified the treatment efficiency of TAP hydrogel in -infected skin incision model on diabetic mice.
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http://dx.doi.org/10.1016/j.bioactmat.2021.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079829PMC
November 2021

The Establishment of New Thresholds for PLND-Validated Clinical Nomograms to Predict Non-Regional Lymph Node Metastases: Using Ga-PSMA PET/CT as References.

Front Oncol 2021 15;11:658669. Epub 2021 Apr 15.

Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Purpose: PLND (pelvic lymph node dissection)-validated nomograms are widely accepted clinical tools to determine the necessity of PLND by predicting the metastasis of lymph nodes (LNMs) in pelvic region. However, these nomograms are in lacking of a threshold to predict the metastasis of extrareolar lymph nodes beyond pelvic region, which is not suitable for PLND. The aim of this study is to evaluate a threshold can be set for current clinical PLND-validated nomograms to predict extrareolar LN metastases beyond pelvic region in high-risk prostate cancer patients, by using Ga-PSMA PET/CT as a reference to determine LN metastases (LNMs).

Experimental Design: We performed a retrospective analysis of 57 high-risk treatment-naïve PC patients in a large tertiary care hospital in China who underwent Ga-PSMA-617 PET/CT imaging. LNMs was detected by Ga-PSMA-617 PET/CT and further determined by imaging follow-up after anti-androgen therapy. The pattern of LN metastatic spread of PC patients were evaluated and analyzed. The impact of Ga-PSMA PET/CT on clinical decisions based on three clinical PLND-validated nomograms (Briganti, Memorial Sloan Kettering Cancer Center, Winter) were evaluated by a multidisciplinary prostate cancer therapy team. The diagnostic performance and the threshold of these nomograms in predicting extrareolar LNMs metastasis were evaluated receiver operating characteristic (ROC) curve analysis.

Results: LNMs were observed in 49.1% of the patients by Ga-PSMA PET/CT, among which 65.5% of LNMs were pelvic-regional and 34.5% of LNMs were observed in extrareolar sites (52.1% of these were located above the diaphragm). The Briganti, MSKCC and Winter nomograms showed that 70.2%-71.9% of the patients in this study need to receive ePLND according to the EAU and NCCN guidelines. The LN staging information obtained from Ga-PSMA PET/CT would have led to changes of planned management in 70.2% of these patients, including therapy modality changes in 21.1% of the patients, which were mainly due to newly detected non-regional LNMs. The thresholds of nomograms to predict non-regional LNMs were between 64% and 75%. The PC patients with a score >64% in Briganti nomogram, a score >75% in MSKCC nomogram and a score >67% in Winter nomogram were more likely to have non-regional LNMs. The AUCs (Area under curves) of the clinical nomograms (Briganti, MSKCC and Winter) in predicting non-regional LNMs were 0.816, 0.830 and 0.793, respectively.

Conclusions: By using Ga-PSMA PET/CT as reference of LNM, the PLND-validated clinical nomograms can not only predict regional LNMs, but also predict non-regional LNMs. The additional information from Ga-PSMA PET/CT may provide added benefit to nomograms-based clinical decision-making in more than two-thirds of patients for reducing unnecessary PLND. We focused on that a threshold can be set for current clinical PLND-validated nomograms to predict extrareolar LN metastases with an AUC accuracy of about 80% after optimizing the simple nomograms which may help to improve the efficiency for PC therapy significantly in clinical practice.
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http://dx.doi.org/10.3389/fonc.2021.658669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082014PMC
April 2021

Bayesian toxicokinetic modeling of cadmium exposure in Chinese population.

J Hazard Mater 2021 Jul 19;413:125465. Epub 2021 Feb 19.

School of Public Health/Key Laboratory of Public Health Safety, Ministry of Education, Department of Nutrition and food science, Fudan University, Shanghai 200032, China. Electronic address:

Cadmium (Cd) is a toxic heavy metal widely present in the environment. Estimating its internal levels for a given external exposure using toxicokinetic (TK) models is key to the human health risk assessment of Cd. In this study, existing Cd TK models were adapted to develop a one-compartment TK model and a multi-compartment physiologically based toxicokinetic (PBTK) model by estimating the characteristics of Cd kinetics based on Cd exposure data from 814 Chinese residents. Both models not only considered the effect of gender difference on Cd kinetics, but also described the model parameters in terms of distributions to reflect individual variability. For both models, the posterior distributions of sensitive parameters were estimated using the Markov chain-Monte Carlo method (MCMC) and the approximate Bayesian computation-MCMC algorithm (ABC-MCMC). Validation with the test dataset showed 1.4-22.5% improvement in the root mean square error (RMSE) over the original models. After a systematic literature search, the optimized models showed acceptable prediction on other Chinese datasets. The study provides a method for parameter optimization of TK models under different exposure environment, and the validated models can serve as new quantitative assessment tools for the risk assessment of Cd in the Chinese population.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125465DOI Listing
July 2021

Bortezomib Inhibits Hypoxia-Induced Proliferation by Suppressing Caveolin-1/SOCE/[Ca] Signaling Axis in Human PASMCs.

Biomed Res Int 2021 8;2021:5551504. Epub 2021 Apr 8.

Department of Image Diagnoses, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China 010059.

Background: Previous studies have demonstrated the ubiquitin-proteasome inhibitor bortezomib (BTZ) can effectively alleviate hypoxia-induced pulmonary hypertension (HPH) by suppressing the intracellular calcium homeostasis in pulmonary arterial smooth muscle cells (PASMCs). Further evaluation showed that the antiproliferation roles of BTZ are mainly mediated by inhibition of the intracellular calcium homeostasis. Caveolin-1 belongs to one of the key regulators of the intracellular calcium homeostasis in PASMCs, which can regulate the store-operated calcium entry (SOCE). However, the effects of BTZ on Caveolin-1 remain unclear.

Methods: Primarily cultured human PASMCs were used as the cell model. CCK-8 assay was performed to assess the PASMCs proliferation. Western blotting and real-time qPCR were used to detect the mRNA and protein expressions. Fura-2-based fluorescence imaging experiments were used to determine the intracellular calcium concentration ([Ca]). The protein synthesis inhibitor cycloheximide (CHX) was utilized to determine the protein degradation process.

Results: Firstly, in cultured human PASMCs, treatment of BTZ for 24 or 60 hours significantly downregulates Caveolin-1 at both mRNA and protein levels. Secondly, in the presence CHX, BTZ treatment also leads to downregulated protein expression and fastened protein degradation of Caveolin-1, indicating that BTZ can promote the Caveolin-1 protein degradation, other than the BTZ on Caveolin-1 mRNA transcription. Then, BTZ significantly attenuates the hypoxia-elevated baseline [Ca], SOCE, and cell proliferation.

Conclusion: We firstly observed that the ubiquitin-proteasome inhibitor BTZ can inhibit the Caveolin-1 expression at both mRNA transcription and protein degradation processes, providing new mechanistic basis of BTZ on PASMC proliferation.
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http://dx.doi.org/10.1155/2021/5551504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049800PMC
April 2021

Electrolyte Structure of Lithium Polysulfides with Anti-Reductive Solvent Shells for Practical Lithium-Sulfur Batteries.

Angew Chem Int Ed Engl 2021 Apr 29. Epub 2021 Apr 29.

Tsinghua University, Department of Chemical Engineering, Gongwu Building 308B, 100084, Beijing, CHINA.

Lithium-sulfur (Li-S) battery is regarded as a promising secondary battery. However, constant parasitic reactions between Li anode and soluble polysulfide (PS) intermediates significantly deteriorate the working Li anode. The rational design to inhibit the parasitic reactions is plagued by the inability to understand and regulate the electrolyte structure of PSs. Herein, the electrolyte structure of PSs with anti-reductive solvent shells was unveiled by molecular dynamics simulations and nuclear magnetic resonance. The reduction resistance of the solvent shell is proved to be a key reason in decreasing the reactivity of PSs against Li. With isopropyl ether (DIPE) as a cosolvent, DIPE molecules tend to distribute in the outer solvent shell due to poor solvating power. Furthermore, DIPE is more stable than conventional ether solvents against Li metal. The reactivity of PSs is suppressed by encapsulating PSs into anti-reductive solvent shells. Consequently, the cycling performance of working Li-S batteries was significantly improved and a pouch cell of 300 Wh kg-1 was demonstrated. The fundamental understanding in this work provides an unprecedented ground to understand the electrolyte structure of PSs and the rational electrolyte design in Li-S batteries.
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http://dx.doi.org/10.1002/anie.202103470DOI Listing
April 2021

Immune activation during brain infection in African infants with frequent cytomegalovirus co-infection.

iScience 2021 Apr 23;24(4):102351. Epub 2021 Mar 23.

Center for Neural Engineering, Pennsylvania State University, State College, PA 16801, USA.

Inflammation during neonatal brain infections leads to significant secondary sequelae such as hydrocephalus, which often follows neonatal sepsis in the developing world. In 100 African hydrocephalic infants we identified the biological pathways that account for this response. The dominant bacterial pathogen was a species, with frequent cytomegalovirus co-infection. A proteogenomic strategy was employed to confirm host immune response to and to define the interplay within the host immune response network. Immune activation emphasized neuroinflammation, oxidative stress reaction, and extracellular matrix organization. The innate immune system response included neutrophil activity, signaling via IL-4, IL-12, IL-13, interferon, and Jak/STAT pathways. Platelet-activating factors and factors involved with microbe recognition such as Class I MHC antigen-presenting complex were also increased. Evidence suggests that dysregulated neuroinflammation propagates inflammatory hydrocephalus, and these pathways are potential targets for adjunctive treatments to reduce the hazards of neuroinflammation and risk of hydrocephalus following neonatal sepsis.
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http://dx.doi.org/10.1016/j.isci.2021.102351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065213PMC
April 2021

Cationic Glycopolymers with Aggregation-Induced Emission for the Killing, Imaging, and Detection of Bacteria.

Biomacromolecules 2021 May 28;22(5):2224-2232. Epub 2021 Apr 28.

Key Laboratory of New Membrane Materials, Ministry of Industry and Information Technology, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, P. R. China.

Cationic glycopolymers with structures similar to those of typical poly(ionic liquid)s (PILs) were synthesized the quaternization reaction of poly(4-vinyl pyridine) with halogen-functionalized d-mannose and tetraphenylethylene units. Such postpolymerization modification provided PILs with aggregation-induced emission effect as well as specific carbohydrate-protein recognition with lectins such as concanavalin A. The interactions between cationic glycopolymers and different microorganisms, including Gram-positive and Gram-negative , were used for the killing, imaging, and detection of bacteria. Besides, these sugar-containing PILs showed a relatively low hemolysis rate due to the presence of saccharide units, which may have potential application in the field of biomaterials.
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http://dx.doi.org/10.1021/acs.biomac.1c00298DOI Listing
May 2021

A photostable reaction-based A-A-A type two-photon fluorescent probe for rapid detection and imaging of sulfur dioxide.

J Mater Chem B 2021 Apr;9(16):3554-3562

Laboratory of Functionalized Molecular Solids, Ministry of Education, Anhui Key Laboratory of Chemo/Biosensing, Laboratory of Biosensing and Bioimaging (LOBAB), College of Chemistry and Materials Science, Anhui Normal University, Wuhu 241002, P. R. China.

In this study, a novel reaction-based A-A-A (acceptor-acceptor-acceptor) type two-photon fluorescent probe, BTC, is prepared using the benzothiadiazole (BTD) scaffold as the two-photon fluorophore and electron-accepting centre. Two β-chlorovinyl aldehyde moieties are symmetrically connected to both ends of the BTD scaffold and act as reaction groups to recognize SO2 and quenching groups to make the dis-activated probe stay at off-state due to their weak electron-withdrawing effect. In the presence of SO2 derivatives, the aldehyde groups are consumed through aldehyde addition, resulting in the activation of intramolecular charge transfer (ICT) processes and therefore recovering the fluorescence of the probe. The designed probe shows excellent two-photon properties including large two-photon absorption cross-sections (TPA) of 91 GM and photostability. Beyond these, the BTC probe exhibits a fast response to SO2 within 30 s, high specificity without foreign interference and a broad detection range from 500 nM to 120 μM with a detection limit of 190 nM. The designed fluorescent probe is further applied to the two-photon imaging of exogenous and endogenous SO2 derivatives under different physiological processes in HeLa cells and zebrafish with satisfactory results. We believe that the proposed design strategy can be extended to fabricate versatile BTD-based two-photon fluorescent probes through molecular engineering for further applications in bioassays and two-photon imaging.
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http://dx.doi.org/10.1039/d1tb00433fDOI Listing
April 2021

A shapeable, ultra-stretchable rubber strain sensor based on carbon nanotubes and Ag flakes via melt-mixing process.

J Mater Chem B 2021 Apr 24;9(16):3502-3508. Epub 2021 Mar 24.

MicroNano System Research Center, College of Information and Computer & Key Laboratory of Advanced Transducers and Intelligent Control System of Ministry of Education and Shanxi Province, Taiyuan University of Technology, Taiyuan, 030024, China.

Promoting the detection range, durability, and shapeable manufacturing of flexible strain sensors is essential to broaden their applications. Therefore, in this study, styrene ethylene butylene styrene (SEBS) rubber as a flexible material and a melt-mixing molding method are adopted to design an ultra-flexible strain sensor. Carbon nanotubes (CNTs) are added to form a conductive network, and the effect of Ag flakes on improving the sensor performance is studied. The experiment results exhibit good strain-resistance dependent characteristics of the obtained sensor, which demonstrates an excellent sensing range of about 540% with a gauge factor (GF) of 5.197. The good hydrophobicity (water contact angle ≈120.4°), repeatable characteristics at different rates, strain-dependence and long-term recycling of the sensor are demonstrated as well. Finally, the fabricated round bracelet sensor is applied to detect different cross-sections, the movement of human joints, balloon inflation, bottle cap sealing and numerous other aspects.
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http://dx.doi.org/10.1039/d1tb00199jDOI Listing
April 2021

To Reveal the Importance of the Crystallization Sequence on Micro-Morphological Structures of All-Crystalline Polymer Blends by Investigation.

ACS Appl Mater Interfaces 2021 Apr 28. Epub 2021 Apr 28.

State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, China.

In crystalline/crystalline polymer blend systems, complex competition and coupling of crystallization and morphology usually happen due to the different crystal nucleation and growth processes of polymers, making the morphology and crystallization behavior difficult to control. Herein, we probe the crystallization sequence during the film formation process (crystallize simultaneously, component A crystallizes prior to B or inverse) to illustrate the micro-morphology evolution process in poly(3-hexylthiophene) (P3HT) and poly[[,-bis(2-octyldodecyl)-napthalene-1,4,5,8-bis(dicarboximide)-2,6-diyl]- alt-5, 5'-(2,2'-bithiophene)] (N2200) blend using UV-vis absorption spectra and two-dimensional grazing incidence X-ray diffraction (2D GIXRD). When P3HT and N2200 crystallize simultaneously, a large-sized morphology structure is formed. When strengthening the solution aggregation of P3HT by increasing the solvent-polymer interaction, P3HT crystallizes prior to N2200. A P3HT-based micro-morphology structure is obtained. As the molecular weight of N2200 increases to a critical value (72.0 kDa), the crystallization of N2200 dominates the film formation process. A N2200-based micro-morphology is formed guided by N2200 domains. The results confirm that the crystallization sequence is one of the most important factors to determine the micro-morphology structure in all-crystalline polymer blends.
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http://dx.doi.org/10.1021/acsami.1c02984DOI Listing
April 2021

OsMORF9 is necessary for chloroplast development and seedling survival in rice.

Plant Sci 2021 Jun 7;307:110907. Epub 2021 Apr 7.

State Key Lab of Rice Biology, China National Rice Research Institute, Hangzhou, 310006, China. Electronic address:

Chloroplasts are closely associated with the growth and development of higher plants. Accumulating evidence has revealed that the multiple organellar RNA editing factors (MORF) family of proteins influences plastidic and mitochondrial development through post-transcriptional regulation. However, the role of MORFs in regulating the development of chloroplasts in rice is still unclear. The OsMORF9 gene belongs to a small family of 7 genes in rice and is highly expressed in young leaves. We used the CRISPR/Cas9 system to mutate OsMORF9. The resulting knockout lines osmorf9-1 and osmorf9-2 exhibited an albino seedling lethal phenotype. Besides, the expression of many plastid-encoded genes involved in photosynthesis, the biogenesis of plastidic ribosomes and the editing and splicing of specific plastidic RNA molecules were severely affected in these two OsMORF9 mutants. Furthermore, yeast two-hybrid analysis revealed that OsMORF9 could interact with OsSLA4 and DUA1 which are members of the pentatricopeptide repeat (PPR) family of proteins. Analysis of subcellular localization of OsMORF9 also suggested that it might function in chloroplasts. The findings from the present study demonstrated the critical role of OsMORF9 in the biogenesis of chloroplast ribosomes, chloroplast development and seedling survival. This therefore provides new insights on the function of MORF proteins in rice.
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http://dx.doi.org/10.1016/j.plantsci.2021.110907DOI Listing
June 2021

Falsely high rebound tonometry.

J AAPOS 2021 Apr 23. Epub 2021 Apr 23.

Pediatric Ophthalmology and Ocular Genetics, Wills Eye Hospital, Philadelphia, Pennsylvania; Department of Ophthalmology, Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address:

Background: Rebound tonometry (RBT) can be used to measure intraocular pressure (IOP) in children unable to tolerate measurement with applanation tonometry (AT) while awake. RBT readings are often 2-3 mm Hg higher than AT. We have experienced children with a repeatedly higher difference between RBT and AT measurements (≥6 mm Hg). The purpose of this study was to identify demographic and ocular characteristics that contribute to this artifactuous discrepancy.

Methods: The medical records of pediatric patients with IOP measured by RBT followed by AT within 6 months without intervening surgery or change in medical management were retrospectively reviewed to identify potential predictors of greater difference between RBT and AT readings.

Results: A total of 123 eyes of 65 patients were included. In patients with normal IOP (≤24 mm Hg), 18.5% had a ≥6 mm Hg difference between RBT and AT, with RBT being higher. Risk factors for this included presence of persistent fetal vasculature (PFV), increased corneal diameter, and higher initial RBT value (>20). In patients with elevated IOP (>24 mm Hg), 77% had ≥6 mm Hg difference, with larger corneal diameter being the sole predictor. Eyes were less likely to have significant RBT-AT difference if there was corneal opacity or iris abnormalities in eyes with elevated IOP (>24 mm Hg).

Conclusions: In some children, RBT readings are ≥ 6 mm Hg higher than AT readings. Caution should be taken when interpreting RBT values in patients with PFV, increased corneal diameter, and higher initial RBT values.
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http://dx.doi.org/10.1016/j.jaapos.2020.11.017DOI Listing
April 2021

Endothelial ether lipids link the vasculature to blood pressure, behavior, and neurodegeneration.

J Lipid Res 2021 Apr 21:100079. Epub 2021 Apr 21.

Division of Endocrinology, Metabolism & Lipid Research, Department of Medicine, Washington University, St. Louis, MO 63110, USA; Departments of Cell Biology & Physiology, Washington University, St. Louis, MO 63110, USA. Electronic address:

Vascular disease contributes to neurodegeneration, which is associated with decreased blood pressure in older humans. Plasmalogens, ether phospholipids produced by peroxisomes, are decreased in Alzheimer's disease, Parkinson's disease and other neurodegenerative disorders. However, the mechanistic links between ether phospholipids, blood pressure, and neurodegeneration are not fully understood. Here, we show that endothelium-derived ether phospholipids affect blood pressure, behavior, and neurodegeneration in mice. In young adult mice, inducible endothelial-specific disruption of PexRAP, a peroxisomal enzyme required for ether lipid synthesis, unexpectedly decreased circulating plasmalogens. PexRAP Endothelial KnockOut (PEKO) mice responded normally to hindlimb ischemia but had lower blood pressure and increased plasma renin activity. In PEKO as compared to control mice, tyrosine hydroxylase was decreased in the locus coeruleus, which maintains blood pressure and arousal. PEKO mice moved less, slept more, and had impaired attention to and recall of environmental events as well as mild spatial memory deficits. In PEKO hippocampus, gliosis was increased and a plasmalogen associated with memory was decreased. Despite lower blood pressure, PEKO mice had generally normal homotopic functional connectivity by optical neuroimaging of the cerebral cortex. Decreased GSK3 phosphorylation, a marker of neurodegeneration, was detected in PEKO cerebral cortex. In a co-culture system, PexRAP knockdown in brain endothelial cells decreased GSK3 phosphorylation in co-cultured astrocytes that was rescued by incubation with the ether lipid alkylglycerol. Taken together, our findings suggest that endothelium-derived ether lipids mediate several biological processes and may also confer neuroprotection in mice.
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http://dx.doi.org/10.1016/j.jlr.2021.100079DOI Listing
April 2021

Effect of Methionine on the Thermal Degradation of -(1-Deoxy-d-fructos-1-yl)-methionine Affecting Browning Formation.

J Agric Food Chem 2021 May 23;69(17):5167-5177. Epub 2021 Apr 23.

Department of Food Science, Rutgers University, 65 Dudley Road, New Brunswick, New Jersey 08901, United States.

The effect of additional dl-methionine (Met) on the thermal degradation of a methionine-glucose-derived Amadori rearrangement product (MG-ARP) was investigated under different reaction conditions. The resulting color formation and changes in the concentrations of MG-ARP, Met, and α-dicarbonyl compounds were investigated. Additional Met did not affect the degradation rate of MG-ARP but got involved in subsequent reactions and resulted in a decrease in the contents of C-α-dicarbonyl compounds. During MG-ARP degradation, the formation of glyoxal (GO) and methylglyoxal (MGO) was facilitated by additional Met, through retro-aldolization reaction of C-α-dicarbonyl compounds. This effect of Met addition was dependent on the reaction temperature, and the consistent conclusion could be made in a buffer system. The improvement of GO and MGO formation as color precursors caused by the additional Met contributed to the acceleration of browning formation.
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http://dx.doi.org/10.1021/acs.jafc.1c02023DOI Listing
May 2021

Sensitivities of Ozone Air Pollution in the Beijing-Tianjin-Hebei Area to Local and Upwind Precursor Emissions Using Adjoint Modeling.

Environ Sci Technol 2021 05 23;55(9):5752-5762. Epub 2021 Apr 23.

Department of Mechanical Engineering, University of Colorado Boulder, Boulder, Colorado 80309, United States.

Effective mitigation of surface ozone pollution entails detailed knowledge of the contributing precursors' sources. We use the GEOS-Chem adjoint model to analyze the precursors contributing to surface ozone in the Beijing-Tianjin-Hebei area (BTH) of China on days of different ozone pollution severities in June 2019. We find that BTH ozone on heavily polluted days is sensitive to local emissions, as well as to precursors emitted from the provinces south of BTH (Shandong, Henan, and Jiangsu, collectively the SHJ area). Heavy ozone pollution in BTH can be mitigated effectively by reducing NO (from industrial processes and transportation), ≥C alkenes (from on-road gasoline vehicles and industrial processes), and xylenes (from paint use) emitted from both BTH and SHJ, as well as by reducing CO (from industrial processes, transportation, and power generation) and ≥C alkanes (from industrial processes, paint and solvent use, and on-road gasoline vehicles) emissions from SHJ. In addition, reduction of NO, xylene, and ≥C alkene emissions within BTH would effectively decrease the number of BTH ozone-exceedance days. Our analysis pinpoint the key areas and activities for locally and regionally coordinated emission control efforts to improve surface ozone air quality in BTH.
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http://dx.doi.org/10.1021/acs.est.1c00131DOI Listing
May 2021

Quantitative imaging of intracellular nanoparticle exposure enables prediction of nanotherapeutic efficacy.

Nat Commun 2021 04 22;12(1):2385. Epub 2021 Apr 22.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.

Nanoparticle internalisation is crucial for the precise delivery of drug/genes to its intracellular targets. Conventional quantification strategies can provide the overall profiling of nanoparticle biodistribution, but fail to unambiguously differentiate the intracellularly bioavailable particles from those in tumour intravascular and extracellular microenvironment. Herein, we develop a binary ratiometric nanoreporter (BiRN) that can specifically convert subtle pH variations involved in the endocytic events into digitised signal output, enabling the accurately quantifying of cellular internalisation without introducing extracellular contributions. Using BiRN technology, we find only 10.7-28.2% of accumulated nanoparticles are internalised into intracellular compartments with high heterogeneity within and between different tumour types. We demonstrate the therapeutic responses of nanomedicines are successfully predicted based on intracellular nanoparticle exposure rather than the overall accumulation in tumour mass. This nonlinear optical nanotechnology offers a valuable imaging tool to evaluate the tumour targeting of new nanomedicines and stratify patients for personalised cancer therapy.
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http://dx.doi.org/10.1038/s41467-021-22678-zDOI Listing
April 2021

RNA interference of Argonaute-1 delays ovarian development in the oriental fruit fly, Bactrocera dorsalis (Hendel).

Pest Manag Sci 2021 Apr 21. Epub 2021 Apr 21.

Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing, China.

Background: With the development of rapid resistance, new modes of action for pesticides are needed for insect control, such as RNAi-based biopesticides targeting essential genes. To explore the function of Argonaute-1 (Ago-1) and potential miRNAs in ovarian development of Bactrocera dorsalis, an important agricultural pest, and to develop a novel control strategy for the pest, BdAgo-1 was first identified in B. dorsalis.

Results: Spatiotemporal expression analysis indicated that BdAgo-1 had a relatively high transcriptional level in the ovarian tissues of adult female B. dorsalis during the sexual maturation period. RNA interference (RNAi) experiment showed that BdAgo-1 knockdown significantly decreased the expression levels of ovarian development-related genes and delayed ovarian development. Although RNAi-mediated silencing of Ago-1 led to a reduced ovary surface area, a subsequent oviposition assay revealed that the influence was minimal over a longer time period. Small RNA libraries were constructed and sequenced from different ovarian developmental stages of B. dorsalis adults. Among 161 identified miRNAs, 84 miRNAs were differentially expressed during the three developmental stages of the B. dorsalis ovary. BdAgo-1 silencing caused significant down-regulation of seven differentially expressed miRNAs (DEMs) showing relatively high expression levels (>1000 TPM (Transcripts per kilobase of exon model per million mapped reads)). The expression patterns of these seven core DEMs and their putative target genes were analyzed in the ovaries of B. dorsalis.

Conclusion: The results indicate that Ago-1 and Ago-1-dependent miRNAs are indispensable for normal ovarian development in B. dorsalis and help identify miRNA targets useful for control of this pest.
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http://dx.doi.org/10.1002/ps.6419DOI Listing
April 2021

Exploring the Complexity of Death-Censored Kidney Allograft Failure.

J Am Soc Nephrol 2021 Apr 21. Epub 2021 Apr 21.

Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Berlin, Germany.

Background: Few studies have thoroughly investigated the causes of kidney graft loss (GL), despite its importance.

Methods: A novel approach assigns each persistent and relevant decline in renal function over the lifetime of a renal allograft to a standardized category, hypothesizing that singular or multiple events finally lead to GL. An adjudication committee of three physicians retrospectively evaluated indication biopsies, laboratory testing, and medical history of all 303 GLs among all 1642 recipients of transplants between January 1, 1997 and December 31, 2017 at a large university hospital to assign primary and/or secondary causes of GL.

Results: In 51.2% of the patients, more than one cause contributed to GL. The most frequent primary or secondary causes leading to graft failure were intercurrent medical events in 36.3% of graft failures followed by T cell-mediated rejection (TCMR) in 34% and antibody-mediated rejection (ABMR) in 30.7%. In 77.9%, a primary cause could be attributed to GL, of which ABMR was most frequent (21.5%). Many causes for GL were identified, and predominant causes for GL varied over time.

Conclusions: GL is often multifactorial and more complex than previously thought.
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http://dx.doi.org/10.1681/ASN.2020081215DOI Listing
April 2021