Publications by authors named "Zhe Li"

1,429 Publications

  • Page 1 of 1

Relationship between molecular properties and degradation mechanisms of organic solar cells based on bis-adducts of phenyl-C butyric acid methyl ester.

J Mater Chem C Mater 2022 May 25;10(20):7875-7885. Epub 2022 Apr 25.

Department of Physics and Centre for Plastic Electronics, Imperial College London London SW7 2AZ UK

Environmental stability remains a major challenge for the commercialisation of organic solar cells and degradation pathways remain poorly understood. Designing materials for improved device stability requires an understanding of the relationship between the properties of the donor or acceptor molecule and different degradation mechanisms. Here we study the correlations between various molecular parameters of the fullerene derivative bis-PCBM and the degradation rate of polymer:bis-PCBM organic solar cells, based on the same carbazole--benzothiadiazole polymer, in aerobic and anaerobic conditions. We compare eight high purity bis-PCBM isomers with different electronic, chemical and packing properties along with PCBM and the mixture of bis isomers. In the case of aerobic photodegradation, we find that device degradation rate is positively correlated to the LUMO energy of the bis-PCBM isomer and to the degree of crystallinity of the isomer, while the correlation of degradation with driving force for epoxide formation is unclear. These results support the idea that in these samples, aerobic photodegradation proceeds superoxide formation by the photogenerated polaron on the fullerene, followed by further chemical reaction. In the absence of air, photodegradation rate is correlated with molecular structure, supporting the mechanism of microstructural degradation fullerene dimerization. The approach and findings presented here show how control of specific molecular parameters through chemical design can serve as a strategy to enhance stability of organic solar cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1tc05768eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134990PMC
May 2022

Characterization of Nematicidal Activity and Nematode-Toxic Metabolites of a Soilborne Isolate.

Pathogens 2022 Jun 20;11(6). Epub 2022 Jun 20.

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China.

The increasing prevalence of crop-threatening root-knot nematodes (RKNs) has stimulated extensive research to discover effective nematicides. A highly focused strategy for accomplishing this is the development of biocontrol agents by a variety of soilborne microorganisms, as different bacterial metabolites have demonstrated promising nematicidal activities. In this study, we characterized the nematicidal and suppressive activity of a bacterial isolate against the agriculturally important RKN and the model nematode , and the main -toxic metabolite of the strain. After a preliminary screening of 22 bacterial isolates with a corrected mortality (CM) of whole-cell culture greater than 50% against from different RKN-incident soils in China, a total of 14 isolates with CM of the supernatant of culture suspension (SCS) higher than 50% against both and were rescreened. An isolate with the highest CM of 86.1% and 95.0% for and , respectively, was further identified as the species via morphological examination, physiological and biochemical assays and alignment analysis of 16S rRNA gene sequences. The SCS of this strain, namely, MB756, exhibited synchronous killing activity along with significant detrimental effects on the growth, brood size, and locomotion of . The effects of heat treatment, pH, inoculations, and protease K proteolysis on the CM of MB756 SCS were evaluated. A major -toxic substance in the MB756 SCS was assayed and identified using thin-layer chromatography, column chromatography and high-performance liquid chromatography with a mass spectrometer, and it was preliminarily identified as 2-ethylhexan-1-ol, with a molecular formula of CHO and a molecular weight of 130.3 Da.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pathogens11060708DOI Listing
June 2022

The Impact of Enhancing Diet Quality or Dietary Supplementation of Flavor and Multi-Enzymes on Primiparous Lactating Sows.

Animals (Basel) 2022 Jun 8;12(12). Epub 2022 Jun 8.

Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, 211 Huimin Road, Wenjiang District, Chengdu 611130, China.

This study was aimed to explore how a high-quality diet or a flavor plus multi-enzyme diet affects the feed intake, nutrient digestibility and antioxidation capacity of lactating sows and the growth of their progeny. Thirty primiparous sows were randomly assigned to three treatments from d 2 of lactation until weaning (d 21): control (CON), with a basal diet; high quality (HQ), with 200 kcal/kg higher net energy than CON; or the CON diet supplemented with 500 mg/kg flavor and 100 mg/kg multi-enzymes (F + E). Sows fed with the HQ or F + E diets improved piglets' live weight ( < 0.05) and average daily weight gain ( < 0.10), litter weight gain ( < 0.10) and piglet growth to milk yield ratio ( < 0.10). Compared with CON, the HQ and F + E groups increased the digestibility of ether extract, ash, neutral detergent fiber, crude fiber and phosphorus ( < 0.10), and the HQ group also increased dry matter, gross energy, crude protein, acid detergent fiber and energy intake ( < 0.05). Compared with CON, the F + E group decreased serum urea nitrogen and aspartate aminotransferase ( < 0.05) and enhanced superoxide dismutase, catalase and glutathione peroxidase, but it decreased malondialdehyde in milk supernatant ( < 0.05).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ani12121493DOI Listing
June 2022

Fast and specific enrichment and quantification of cancer-related exosomes by DNA-nanoweight-assisted centrifugation.

Anal Chem 2022 Jun 22. Epub 2022 Jun 22.

Department of Biomedical Engineering, College of Engineering and Applied Sciences, Nanjing University, Nanjing, Jiangsu 210023, People's Republic of China.

Exosomes are nanoscale membrane vesicles actively released by cells and play an important role in the diagnosis of cancer-related diseases. However, it is challenging to efficiently enrich exosomes from extracellular fluids. In this work, we used DNA nanostructures as "nanoweights" during centrifugation to facilitate the enrichment of cancerous exosomes in human serum. Two different DNA tetrahedral nanostructures (DTNs), each carrying a specific aptamer for exosome biomarker recognition, were incubated with clinical samples simultaneously. One DTN triggered the cross-linking of multiple target exosomes and, therefore, enabled low-speed and fast centrifugation for enrichment. The other DTN further narrowed down the target exosome subtype and initiated a hybridization chain reaction (HCR) for sensitive signal amplification. The method enabled the detection of 1.8 × 10 MCF-7-derived exosomes per microliter and 5.6 × 10 HepG2-derived exosomes per microliter, with 1000-fold higher sensitivity than conventional ELISA and 10-fold higher sensitivity than some recently reported fluorescence assays. Besides, the dual-aptamer system simultaneously recognized multiple surface proteins, eliminating the interference risk from free proteins. Thus, this easy-to-operate method can enrich exosomes with excellent specificity and sensitivity and therefore will be appealing in biomedical research and clinical diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.analchem.2c01872DOI Listing
June 2022

DNA-catalysed alternative RNA splicing.

Chem Commun (Camb) 2022 Jun 21. Epub 2022 Jun 21.

State Key Laboratory of Coordination Chemistry, Department of Biomedical Engineering, College of Engineering and Applied Sciences, Chemistry and Biomedicine Innovation Center (ChemBIC), Jiangsu Key Laboratory of Artificial Functional Materials, Nanjing University, Nanjing, Jiangsu, 210023, China.

We report DNA-catalysed alternative RNA splicing . Using modular DNA catalysts with RNA endonuclease and RNA ligase activities, we show that DNA can modulate RNA structure and activity. Furthermore, we illustrate that such DNA-catalysed reactions can yield, from a common precursor, different splicing isoforms with distinct functions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d2cc00812bDOI Listing
June 2022

Development of a multivariable clinical prediction model for liposomal doxorubicin-induced cardiotoxicity in adult breast cancer patients: a retrospective multicenter study.

Ann Transl Med 2022 May;10(10):605

Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

Background: The clinical use of anthracyclines is limited by the risk of cardiotoxicity. So, we aim to develop a clinical prediction model for liposomal doxorubicin-induced cardiotoxicity in adult breast cancer patients.

Methods: We designed a multicenter retrospective cohort study. A total of 257 hospitalized breast cancer patients treated with doxorubicin liposomes were finally enrolled in the study, including 58 patients from Beijing Friendship Hospital and 199 from Beijing Cancer Hospital. In all, 32 cases developed cardiotoxicity, including 4 at the Beijing Friendship Hospital and 28 at the Beijing Cancer Hospital. The study involved breast cancer patients with no pre-existing heart disease, whose clinical data were collected from their medical records. All patients underwent electrocardiogram (ECG) and/or left ventricular ejection fraction (LVEF) measurements prior to treatment with doxorubicin liposomes. Patients were clinically assessed after each cycle of treatment, and ECG and/or LVEF measurements were performed at least once after treatment. Liposomal doxorubicin-induced cardiotoxicity was defined when one of the following three conditions was met: (I) a reduction in LVEF of at least 5% from the baseline and the absolute value was less than 55%, accompanied by congestive heart failure (CHF) symptoms or signs; (II) a reduction in LVEF of at least 10% to an absolute value of less than 55%, without CHF symptoms or signs; (III) the definite diagnosis of CHF. Variables associated with cardiotoxicity were identified by univariate and multivariate logistic regression, and the consistency and differentiation of the final model were evaluated.

Results: In our final model, age [odds ratio (OR): 5.626, 95% confidence interval (CI): 2.321 to 13.639], cancer metastasis (OR: 3.873, 95% CI: 1.220 to 12.299), paclitaxel (OR: 3.601, 95% CI: 1.010 to 12.843), and hypertension (OR: 2.435, 95% CI: 1.046 to 5.671) were significantly associated with cardiotoxicity. The final model was tested for Hosmer-Lemeshow goodness-of-fit, the χ was 2.696 and the P value was 0.747, and the resultant predictive model had an area under the receiver operating characteristic (ROC; AUC) curve of 0.781.

Conclusions: This study established a risk prediction model for liposomal doxorubicin-induced cardiotoxicity in breast cancer patients and performed a stratified risk scores.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-22-1935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201141PMC
May 2022

Influences of fresh and frozen embryo transfer on neonatal birthweight and the expression of imprinted genes PEG10 /L3MBTL1 in placenta.

Reprod Biol 2022 Jun 14;22(3):100665. Epub 2022 Jun 14.

The Third Affiliated Hospital of Zhengzhou University, China. Electronic address:

To investigate the influences of fresh embryo transfer (ET) and frozen embryo transfer (FET) on neonatal birthweight and the expression of imprinted genes PEG10 and L3MBTL1 in the placenta after in vitro fertilization-embryo transfer (IVF-ET), we analyzed the neonatal birthweight between fresh ET and FET transfer cycles. Then, we collected placentas delivered by fresh ET and FET, and real-time quantitative PCR, Western blotting and immunohistochemistry were used to detect the expression of PEG10 and L3MBTL1. The mean neonatal birthweight of fresh ET was lower than that of FET(3348.48 ± 521.05 vs. 3450.34 ± 524.13, P < 0.001). The risks of low birthweight (LBW) and small-for-gestational age (SGA) were lower after FET (3.9 % vs. 5.4 %; 7.2 % vs. 10.3 %), with adjusted rate ratios of 0.74 (95 % CI, 0.59-0.93; P = 0.003) and 0.70 (95 % CI, 0.59-0.84; P < 0.001), respectively. FET resulted in higher frequencies of macrosomia and large-for-gestational age (LGA) (14.2 % vs. 10.3; 11.0 % vs. 7.1 %) than fresh ET, with adjusted rate ratios of 1.45 (95 % CI, 1.26-1.68; P < 0.001) and 1.62 (95 % CI, 1.37-1.91; P < 0.001), respectively. We also observed PEG10 mRNA and protein expression levels in placentas delivered by fresh ET and FET were significantly different, but there were no significant differences in L3MBTL1 between the two groups. Fresh ET may affect the expression of the imprinted gene PEG10 in the placenta and adverse to placental implantation and development, resulting to increasing incidences of LBW and SGA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.repbio.2022.100665DOI Listing
June 2022

Identifying influential spreaders by gravity model considering multi-characteristics of nodes.

Authors:
Zhe Li Xinyu Huang

Sci Rep 2022 Jun 14;12(1):9879. Epub 2022 Jun 14.

Software College, Northeastern University of China, Shenyang, 110819, People's Republic of China.

How to identify influential spreaders in complex networks is a topic of general interest in the field of network science. Therefore, it wins an increasing attention and many influential spreaders identification methods have been proposed so far. A significant number of experiments indicate that depending on a single characteristic of nodes to reliably identify influential spreaders is inadequate. As a result, a series of methods integrating multi-characteristics of nodes have been proposed. In this paper, we propose a gravity model that effectively integrates multi-characteristics of nodes. The number of neighbors, the influence of neighbors, the location of nodes, and the path information between nodes are all taken into consideration in our model. Compared with well-known state-of-the-art methods, empirical analyses of the Susceptible-Infected-Recovered (SIR) spreading dynamics on ten real networks suggest that our model generally performs best. Furthermore, the empirical results suggest that even if our model only considers the second-order neighborhood of nodes, it still performs very competitively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-022-14005-3DOI Listing
June 2022

Prediction of high-flow nasal cannula outcomes at the early phase using the modified respiratory rate oxygenation index.

BMC Pulm Med 2022 Jun 13;22(1):227. Epub 2022 Jun 13.

Department of Critical Care Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.

Background: This study was designed to explore the early predictive value of the respiratory rate oxygenation (ROX) index modified by PaO (mROX) in high-flow nasal cannula (HFNC) therapy in patients with acute hypoxemia respiratory failure (AHRF).

Method: Seventy-five patients with AHRF treated with HFNC were retrospectively reviewed. Respiratory parameters at baseline and 2 h after HFNC initiation were analyzed. The predictive value of the ROX (ratio of pulse oximetry/FIO to respiratory rate) and mROX (ratio of arterial oxygen /FIO to respiratory rate) indices with two variations by adding heart rate to each index (ROX-HR and mROX-HR) was evaluated.

Results: HFNC therapy failed in 24 patients, who had significantly higher intensive care unit (ICU) mortality and longer ICU stay. Both the ROX and mROX indices at 2 h after HFNC initiation can predict the risk of intubation after HFNC. Two hours after HFNC initiation, the mROX index had a higher area under the receiver operating characteristic curve (AUROC) for predicting HFNC success than the ROX index. Besides, baseline mROX index of greater than 7.1 showed a specificity of 100% for HFNC success.

Conclusion: The mROX index may be a suitable predictor of HFNC therapy outcomes at the early phase in patients with AHRF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12890-022-02017-8DOI Listing
June 2022

Uncertainty index and stock volatility prediction: evidence from international markets.

Financ Innov 2022 8;8(1):57. Epub 2022 Jun 8.

Business School, Nanjing Normal University, Nanjing, China.

This study investigates the predictability of a fixed uncertainty index (UI) for realized variances (volatility) in the international stock markets from a high-frequency perspective. We construct a composite UI based on the scaled principal component analysis (s-PCA) method and demonstrate that it exhibits significant in- and out-of-sample predictabilities for realized variances in global stock markets. This predictive power is more powerful than those of two commonly employed competing methods, namely, PCA and the partial least squares (PLS) methods. The result is robust in several checks. Further, we explain that s-PCA outperforms other dimension-reduction methods since it can effectively increase the impacts of strong predictors and decrease those of weak factors. The implications of this research are significant for investors who allocate assets globally.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40854-022-00361-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9173841PMC
June 2022

[Effects and molecular mechanism of histone methyltransferase enhancer of zeste homolog 2 on regulating sepsis-induced T cell dysfunction].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2022 Apr;34(4):357-361

Department of Emergency Medicine and Critical Care, East Hospital, Tongji University, Shanghai 200120, China.

Objective: To investigate the effect and mechanism of histone methyltransferase enhancer of zeste homolog 2 (EZH2) on sepsis-induced T cell dysfunction.

Methods: Twenty-four male C57BL/6 mice were divided into three groups randomly: sham operated group, sepsis model group [cecum ligation and puncture (CLP)+dimethyl sulfoxide (DMSO) group] and EZH2 selective inhibitor treated group (CLP+GSK126 group), with 8 mice in each group. Sepsis murine model was reproduced by CLP. CLP+DMSO group and CLP+GSK126 group were treated with DMSO or GSK126 (10 mg/kg) respectively right after surgery through intraperitoneal injection. The mice were sacrificed 24 hours after operation, and the mesenteric lymph nodes were collected. The expression of EZH2, apoptosis rates, cell proliferation marker ki-67 antigen positive T lymphocytes (ki-67 cell), interferon-γ positive T lymphocytes (IFN-γ cell), programmed death receptor-1 positive T lymphocytes (PD-1 cell) and programmed death-ligand 1 positive T lymphocytes (PD-L1 cell) were determined by flow cytometry.

Results: Compared with sham operated group, the expression of EZH2 in T lymphocytes was up-regulated on mesenteric lymph nodes of CLP+DMSO group. Compared with CLP+DMSO group, the ratio of CD3 T lymphocytes in CLP+GSK126 group was up-regulated (0.70±0.02 vs. 0.50±0.07, P < 0.01), indicating that the EZH2 inhibitor could increase the number of T lymphocytes in lymph nodes of septic mice; the ratio of ki-67 cells in CD4 and CD8 T lymphocytes in CLP+GSK126 group was increased (CD4: 0.74±0.05 vs. 0.63±0.04, CD8: 0.82±0.06 vs. 0.70±0.04, both P < 0.05), indicating that the EZH2 inhibitor could increase the ratio of T lymphocytes with high proliferative activity in lymph nodes of septic mice. However, no significant difference was found on both CD4 and CD8 T lymphocytes apoptosis rates in the mesenteric lymph nodes of mice between CLP+GSK126 group and CLP+DMSO group [CD4: (21.53±2.87)% vs. (20.48±3.21)%, CD8: (8.34±1.02)% vs. (7.71±1.38)%, both P > 0.05], indicating that no extra T lymphocytes apoptosis was induced by EZH2 inhibitor. Compared with CLP+DMSO group, the ratios of IFN-γ CD4 and IFN-γ CD8 T lymphocytes were increased in CLP+GSK126 group (IFN-γ CD4: 0.31±0.11 vs. 0.14±0.06, IFN-γ CD8: 0.30±0.10 vs. 0.13±0.06, both P < 0.05), suggesting that secretion of IFN-γ in lymph nodes by sepsis T lymphocytes was augmented after EZH2 inhibitor administration. Furthermore, compared with CLP+DMSO group, the ratio of PD-1 cell in CD8 T lymphocyte was down-regulated in CLP+GSK126 group (0.092±0.006 vs. 0.135±0.004, P < 0.01), suggesting that EZH2 inhibitor restrained the PD-1 expression on sepsis lymphoid node CD8 T lymphocytes, however, it had no significant effect on PD-L1 cells.

Conclusions: EZH2, regulates sepsis-induced T lymphocyte dysfunction, possibly through modulating the expression of PD-1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3760/cma.j.cn121430-20210906-01323DOI Listing
April 2022

Quantitative Morphology of Polder Landscape Based on SOM Identification Model: Case Study of Typical Polders in the South of Yangtze River.

Comput Intell Neurosci 2022 29;2022:1362272. Epub 2022 May 29.

School of Architecture, Southeast University, Nanjing, Jiangsu 210096, China.

Landscape morphology is a significant area of landscape architecture research. One of the scientific and technological issues in recent landscape morphology research is the use of quantitative analysis technology driven by morphology indexes and computational models to describe, compare, and analyze form features. This article focuses on the form features of the polder landscape, based on existing theoretical and practical achievements in landscape morphology. First, we choose five landscape morphology indexes based on the morphological constituent units of the landscape (elongation, rectangular compactness, concavity, ellipse compactness, and fractal dimension). Then, using the self-organizing map (SOM), we create an identification model for clustering the types of constituent units. The experimental results show that the identification model can classify polder morphology and analyze the distribution of units using typical polders in the Yangtze River's south bank as study cases. This article presents a technical approach to polder landscape morphology classification as well as a reference and developable quantitative analysis method for landscape morphology research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2022/1362272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168159PMC
June 2022

BHI-Net: Brain-Heart Interaction-Based Deep Architectures for Epileptic Seizures and Firing Location Detection.

IEEE Trans Neural Syst Rehabil Eng 2022 15;30:1576-1588. Epub 2022 Jun 15.

Automatic detection of epileptic seizures is still a challenging problem due to the intolerance of EEG. Introducing ECG can help with EEG for detecting seizures. However, the existing methods depended on fusing either the extracted features or the classification results of EEG-only and ECG-only with ignoring the interaction between them, so the detection rate did not improve much. Also, all EEG channels were considered in a complex manner. Moreover, the detection of epilepsy firing location, which is an important issue for diagnosing epilepsy, is not considered before. Therefore, we propose a new method based on the brain-heart interaction (BHI) for detecting the seizure onset and its firing location in the brain with lower complexity and better performance. BHI allows us to study the nonlinear coupling and variation of phase-synchronization between brain regions and heart activity, which are effective for distinguishing seizures. In our method, the EEG channels are mapped into two surrogate channels to reduce the computational complexity. Moreover, the firing location detector is triggered only once the seizure is detected to save the system's power. Evaluation using different proposed classification networks based on the TUSZ, the largest available EEG/ECG dataset with 315 subjects and 7 seizure types, showed that our BHI method improves the sensitivity by 48% with only 4 false alarms/24h compared to using only EEG. Moreover, it outperforms the performance of the average human detector based on the quantitative EEG tools by achieving a sensitivity of 68.2% with 11.9 false alarms/ 24h and a latency of 11.94 sec.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TNSRE.2022.3181151DOI Listing
June 2022

Three Gorges Dam: friend or foe of riverine greenhouse gases?

Natl Sci Rev 2022 Jun 28;9(6):nwac013. Epub 2022 Jan 28.

School of Engineering, The University of Edinburgh, Edinburgh EH9 3JL, UK.

Dams are often regarded as greenhouse gas (GHG) emitters. However, our study indicated that the world's largest dam, the Three Gorges Dam (TGD), has caused significant drops in annual average emissions of CO, CH and NO over 4300 km along the Yangtze River, accompanied by remarkable reductions in the annual export of CO (79%), CH (50%) and NO (9%) to the sea. Since the commencement of its operation in 2003, the TGD has altered the carbonate equilibrium in the reservoir area, enhanced methanogenesis in the upstream, and restrained methanogenesis and denitrification via modifying anoxic habitats through long-distance scouring in the downstream. These findings suggest that 'large-dam effects' are far beyond our previous understanding spatiotemporally, which highlights the fundamental importance of whole-system budgeting of GHGs under the profound impacts of huge dams.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nsr/nwac013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9166553PMC
June 2022

Oral methotrexate at doses 15-25 mg/week is non-inferior to parenteral regarding efficacy and safety in the treatment of rheumatoid arthritis: a systematic review and meta-analysis.

Clin Rheumatol 2022 Jun 7. Epub 2022 Jun 7.

School of Ethnic Medicine, State Ethnic Affairs Commission & Ministry of Education, Key Laboratory of Chemistry in Ethnic Medicinal Resources, Yunnan Minzu University, Kunming, 650500, Yunnan, People's Republic of China.

Objective: The most optimal route of methotrexate (MTX) administration for the treatment of rheumatoid arthritis (RA) has not yet been established. Our aim was to compare the efficacy, safety, and bioavailability profiles of oral MTX with parenteral MTX in adult patients with RA.

Methods: PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, and ClinicalKey were searched for published randomized trials through December 30, 2021. Random-effects models were used to assess pooled odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (95% CIs). This review was registered in PROSPERO (number CRD42022297810).

Results: Of 705 identified trials, 6 met the criteria and were included in our meta-analysis (644 subjects). Compared to parenteral MTX, oral MTX yielded no significant differences in response rates of 20% (OR: 0.68; 95% CI: 0.40-1.75), 50% (OR: 0.75; 95% CI: 0.44-1.28), and 70% (OR: 0.75; 95% CI: 0.51-1.09) improvement according to American College of Rheumatology criteria (ACR20/50/70 response), and no increased relative risk of any adverse event (OR: 1.20; 95% CI: 0.49-2.93). Furthermore, parenteral MTX showed a significant advantage in the value of AUC (MD: - 536.36; 95% CI: - 1054.22 to - 18.50), but not in C (MD: - 12.86; 95% CI: - 84.30 to 58.58) and T (MD: - 0.31; 95% CI: - 0.70 to 0.08) compared with oral MTX.

Conclusion: Oral MTX at doses of 15-25 mg/week in active RA is not inferior to parenteral regarding efficacy and safety. This supports the initial therapy with oral MTX.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10067-022-06221-zDOI Listing
June 2022

An interfacial floating tumbler with a penetrable structure and Janus wettability inspired by .

Mater Horiz 2022 Jun 6. Epub 2022 Jun 6.

School of Materials Science and Engineering, Nankai University, Tianjin, 300350, P. R. China.

Designing advanced interfacial materials is decisive to the improvement of multiphase systems. Inspired by the superior floatability of , here we present a superhydrophobic/hydrophilic 3D Janus floater with a water managing ability. Its self-regulated floatation mechanism, as well as its water removal logic, should provide insight into the development of multifunctional interfacial carriers in the fields of micro-devices, solar evaporation,
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d2mh00361aDOI Listing
June 2022

Structural Modifications of Nimodipine Lead to Novel PDE1 Inhibitors with Anti-pulmonary Fibrosis Effects.

J Med Chem 2022 Jun 6;65(12):8444-8455. Epub 2022 Jun 6.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.

Our previous research demonstrated that phosphodiesterase-1 (PDE1) could work as a potential target against idiopathic pulmonary fibrosis. Nimodipine, a calcium antagonist commonly used to improve hypertension, was reported to have inhibition against PDE1. Herein, a series of nimodipine analogues were discovered as novel selective and potent PDE1 inhibitors after structural modifications. Compound exhibited excellent inhibitory activity against PDE1C (IC = 10 nM), high selectivity over other PDEs except for PDE4, and weak calcium channel antagonistic activity. Administration of compound exhibited remarkable therapeutic effects in a rat model of pulmonary fibrosis induced by bleomycin and prevented myofibroblast differentiation induced by TGF-β1. The expressions of PDE1B and PDE1C were found to be increased and concentrated in the focus of fibrosis. Compound increased the levels of 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP) in the lungs of rats with pulmonary fibrosis, supporting the fact that the anti-fibrosis effects of were through the regulation of cAMP and cGMP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jmedchem.2c00458DOI Listing
June 2022

Can Daytime Transcranial Direct Current Stimulation Treatment Change the Sleep Electroencephalogram Complexity of REM Sleep in Depressed Patients? A Double-Blinded, Randomized, Placebo-Controlled Trial.

Front Psychiatry 2022 18;13:851908. Epub 2022 May 18.

Sleep Center, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Study Objectives: The purpose of this study was to determine the effects of daytime transcranial direct current stimulation (tDCS) on sleep electroencephalogram (EEG) in patients with depression.

Methods: The study was a double-blinded, randomized, controlled clinical trial. A total of 37 patients diagnosed with a major depression were recruited; 19 patients (13 females and 6 males mean age 44.79 ± 15.25 years) received tDCS active stimulation and 18 patients (9 females and 9 males; mean age 43.61 ± 11.89 years) received sham stimulation. Ten sessions of daytime tDCS were administered with the anode over F3 and the cathode over F4. Each session delivered a 2 mA current for 30 min per 10 working days. Hamilton-24 and Montgomery scales were used to assess the severity of depression, and polysomnography (PSG) was used to assess sleep structure and EEG complexity. Eight intrinsic mode functions (IMFs) were computed from each EEG signal in a channel. The sample entropy of the cumulative sum of the IMFs were computed to acquire high-dimensional multi-scale complexity information of EEG signals.

Results: The complexity of Rapid Eye Movement (REM) EEG signals significantly decreased intrinsic multi-scale entropy (iMSE) (1.732 ± 0.057 vs. 1.605 ± 0.046, = 0.0004 in the case of the C4 channel, IMF 1:4 and scale 7) after tDCS active stimulation. The complexity of the REM EEG signals significantly increased iMSE (1.464 ± 0.101 vs. 1.611 ± 0.085, = 0.001 for C4 channel, IMF 1:4 and scale 7) after tDCS sham stimulation. There was no significant difference in the Hamilton-24 ( = 0.988), Montgomery scale score ( = 0.726), and sleep structure (N1% = 0.383; N2% = 0.716; N3% = 0.772) between the two groups after treatment.

Conclusion: Daytime tDCS changed the complexity of sleep in the REM stage, and presented as decreased intrinsic multi-scale entropy, while no changes in sleep structure occurred. This finding indicated that daytime tDCS may be an effective method to improve sleep quality in depressed patients. Trial registration This trial has been registered at the ClinicalTrials.gov (protocol ID: TCHIRB-10409114, in progress).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyt.2022.851908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157570PMC
May 2022

Electronic Metal-Support Interactions Between CuO and ZnO for CuO/ZnO Catalysts With Enhanced CO Oxidation Activity.

Front Chem 2022 13;10:912550. Epub 2022 May 13.

Key Laboratory of Catalysis and Energy Materials Chemistry of Ministry of Education & Hubei Key Laboratory of Catalysis and Materials Science, South-Central Minzu University, Wuhan, China.

Metal-support interaction has been one of the main topics of research on supported catalysts all the time. However, many other factors including the particle size, shape and chemical composition can have significant influences on the catalytic performance when considering the role of metal-support interaction. Herein, we have designed a series of CuO/ZnO catalysts as examples to quantitatively investigate how the metal-support interaction influences the catalytic performance. The electronic metal-support interactions between CuO and ZnO were regulated successfully without altering the structure of CuO/ZnO catalyst. Due to the lower work function of ZnO, electrons would transfer from ZnO to CuO, which is favorable for the formation of higher active Cu species. Combined experimental and theoretical calculations revealed that electron-rich interface result from interaction was favorable for the adsorption of oxygen and CO oxidation reaction. Such strategy represents a new direction to boost the catalytic activity of supported catalysts in various applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fchem.2022.912550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9136224PMC
May 2022

Research on the Error of Global Positioning System Based on Time Series Analysis.

Sensors (Basel) 2022 May 10;22(10). Epub 2022 May 10.

School of Information and Control Engineering, Xi'an University of Architecture and Technology, Xi'an 710055, China.

Due to the poor dynamic positioning precision of the Global Positioning System (GPS), Time Series Analysis (TSA) and Kalman filter technology are used to construct the positioning error of GPS. According to the statistical characteristics of the autocorrelation function and partial autocorrelation function of sample data, the Autoregressive (AR) model which is based on a Kalman filter is determined, and the error model of GPS is combined with a Kalman filter to eliminate the random error in GPS dynamic positioning data. The least square method is used for model parameter estimation and adaptability tests, and the experimental results show that the absolute value of the maximum error of longitude and latitude, the mean square error of longitude and latitude and average absolute error of longitude and latitude are all reduced, and the dynamic positioning precision after correction has been significantly improved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s22103614DOI Listing
May 2022

Alkaline Stress Induces Different Physiological, Hormonal and Gene Expression Responses in Diploid and Autotetraploid Rice.

Int J Mol Sci 2022 May 16;23(10). Epub 2022 May 16.

Faculty of Agronomy, Jilin Agricultural University, Changchun 130000, China.

Saline-alkaline stress is a critical abiotic stress that negatively affects plants' growth and development. Considerably higher enhancements in plant tolerance to saline-alkaline stress have often been observed in polyploid plants compared to their diploid relatives, the underlying mechanism of which remains elusive. In this study, we explored the variations in morphological and physiological characteristics, phytohormones, and genome-wide gene expression between an autotetraploid rice and its diploid relative in response to alkaline stress. It was observed that the polyploidization in the autotetraploid rice imparted a higher level of alkaline tolerance than in its diploid relative. An eclectic array of physiological parameters commonly used for abiotic stress, such as proline, soluble sugars, and malondialdehyde, together with the activities of some selected antioxidant enzymes, was analyzed at five time points in the first 24 h following the alkaline stress treatment between the diploid and autotetraploid rice. Phytohormones, such as abscisic acid and indole-3-acetic acid were also comparatively evaluated between the two types of rice with different ploidy levels under alkaline stress. Transcriptomic analysis revealed that gene expression patterns were altered in accordance with the variations in the cellular levels of phytohormones between diploid and autotetraploid plants upon alkaline stress. In particular, the expression of genes related to peroxide and transcription factors was substantially upregulated in autotetraploid plants compared to diploid plants in response to the alkaline stress treatment. In essence, diploid and autotetraploid rice plants exhibited differential gene expression patterns in response to the alkaline stress, which may shed more light on the mechanism underpinning the ameliorated plant tolerance to alkaline stress following genome duplication.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms23105561DOI Listing
May 2022

Combination of Chitosan, Tea Polyphenols, and Nisin on the Bacterial Inhibition and Quality Maintenance of Plant-Based Meat.

Foods 2022 May 23;11(10). Epub 2022 May 23.

College of Grain Science and Technology, Shenyang Normal University, Shenyang 110034, China.

Plant-based meat products have gained attention in the food industry and with consumers. Plant-based meat products primarily comprise plant proteins and are rich in nutrients. However, the products are highly susceptible to bacterial contamination during storage. Biological preservatives are easily degradable alternatives to chemical preservatives and can preserve different kinds of food. In order to investigate the preservation properties of chitosan (CS), tea polyphenols (TPs), and nisin treatments on plant-based meats, the sensory evaluation, color difference, pH, TBARS, and the total plate count of , , and , indicators of the biological preservative-treated plant-based meat, were determined in this study. The experiment involved blank control- and biological preservative-treated samples. We found that the total microbial count exceeded the national standard provisions in the control samples stored for 14 days. The colors, tissue structures, and flavors of plant-based meat have gradually deteriorated, with the sensory score dropping from 90 to 52. The sample had a loose tissue structure and an obvious sour taste. However, the shelf life of the plant-based meat samples treated with different combinations of the biological preservatives increased compared to the shelf life of the control samples. After 56 d of storage, 1% chitosan, 2.5% tea polyphenols, and 0.04% nisin sensory reduction to 56, the total number of colonies and were 4.91 and 2.95 lg CFU/g, approaching the national standard threshold; was 2 lg CFU/g, reaching the national standard threshold. Thus, the samples treated with 1% chitosan, 2.5% tea polyphenols, and 0.04% nisin had the longest shelf life (56 days) among all experimental groups. Hence, this study reveals that a combination of biological preservatives may be a non-toxic alternative for the efficient preservation of plant-based meat products.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/foods11101524DOI Listing
May 2022

Aptamer-based photonic crystals enable ultra-trace detection of staphylococcal enterotoxin B without labels.

Food Chem 2022 Oct 20;391:133271. Epub 2022 May 20.

Tianjin Key Laboratory of Risk Assessment and Control Technology for Environment and Food Safety, Tianjin Institute of Environmental and Operational Medicine, Tianjin 300050, PR China. Electronic address:

Staphylococcal enterotoxin B (SEB) is one of the most common serotypes in staphylococcal food-poisoning cases. A rapid, sensitive, and simple method for SEB detection is crucial for public health. A photonic crystal (PC) sensing material for label-free detection of ultra-trace SEB was proposed in this study. Gold nanoparticle-doped silica microspheres were stacked to form an opal PC through self-assembly, and SEB aptamers, as the recognition element, were modified onto the PC. When the target protein of SEB came in contact with the PC sensing material, the reflection peak intensity of PCs decreased accordingly. The detection range was 1 × 10 to 1 ng mL, and the detection limit was 0.103 × 10 ng mL. Furthermore, the PC sensing material had great specificity and accuracy, which can be used for real sample monitoring. This PC sensing material achieved ultra-sensitive detection, which did not involve complicated preparation processes and reporter labelling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.foodchem.2022.133271DOI Listing
October 2022

Prognostic Value of Modified Model for End-Stage Liver Disease Scores in Patients With Significant Tricuspid Regurgitation.

Eur Heart J Qual Care Clin Outcomes 2022 May 24. Epub 2022 May 24.

Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Aims: Tricuspid regurgitation (TR) may cause damage to liver and kidney function. The Model for End-Stage Liver Disease excluding international normalized ratio (MELD-XI) and the model with albumin replacing international normalized ratio (MELD-Albumin) scores, which include both liver and kidney function indexes, may predict mortality in patients with TR. The study aimed to analyze the prognostic value of MELD-XI and MELD-Albumin scores in patients with significant TR.

Methods And Results: A total of 1825 patients with at least moderate pure native TR from the China Valvular Heart Disease study between April and June 2018, were included in this analysis. The primary outcome was all-cause death within 2 years. Of 1825 patients, 165 (9.0%) died during follow-up. Restricted cubic splines revealed that hazard ratio for death increased monotonically with greater modified MELD scores. The MELD-XI and MELD-Albumin scores, as continuous variables or categorized using thresholds determined by maximally selected rank statistics, were independently associated with 2-year mortality (all adjusted P<0.001). Both scores provided incremental value over prognostic model without hepatorenal indexes (MELD-XI score: net reclassification index [95% confidence interval], 0.237 [0.138-0.323]; MELD-Albumin score: net reclassification index [95% confidence interval], 0.220 [0.122-0.302]). Results were similar in clinically meaningful subgroups, including but not limited to patients under medical treatment and with normal left ventricular ejection fraction. Models including modified MELD scores were established for prognostic evaluation of significant TR.

Conclusion: Both MELD-XI and MELD-Albumin scores provided incremental prognostic information, and could play important roles in risk assessment in patients with significant TR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ehjqcco/qcac027DOI Listing
May 2022

Computer simulation and design of DNA-nanoprobe for fluorescence imaging DNA repair enzyme in living cells.

Biosens Bioelectron 2022 Sep 10;211:114360. Epub 2022 May 10.

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China. Electronic address:

In situ imaging of DNA repair enzymes in living cells gives important insights to diagnosis and explore the formation of various diseases. Fluorescent probes have become a powerful and widely used technique for their high sensitivity and real-time capabilities, but empirical design and optimization of the corresponding probes can be blind and time-consuming. Herein, we report a strategy combining experimental studies with molecular simulation techniques for the rapid and rational design of sensitive fluorescent DNA probes for a representative DNA repair enzyme human apurinic/apyrimidinic endonuclease 1 (APE1). Extended-system Adaptive Biasing Force (eABF) was applied to study the interaction mechanism between DNA probes with respect to the enzyme, based on which a novel sensitive DNA probe was designed efficiently and economically. Product inhibition effect which significantly limited the sensitivity of existing probes was eliminated by decreasing the key interactions between DNA probe products and enzyme. Experimental mechanism studies showed the existence of intramolecular hairpin structure in DNA probes is important for the recognition of APE1 and elimination of product inhibition, which is in consistent with the simulations. The obtained fluorescent DNA nanoprobe (Nanoprobe N) showed a high sensitivity for APE1 with the detection limit as low as 0.5 U/L (∼0.018 pM), and the Nanoprobe N could effectively respond to the variation of APE1 within cells and distinguish cancer cells from normal cells. This work not only demonstrated the effectiveness of molecular simulations in probe design, but also provided a reliable platform for accurate imaging of APE1 and effectors screening at single-cell level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bios.2022.114360DOI Listing
September 2022

The characteristics and influencing factors of dissolved methane concentrations in Chongqing's central urban area in the Three Gorges Reservoir, China.

Environ Sci Pollut Res Int 2022 May 24. Epub 2022 May 24.

Key Laboratory of Reservoir Aquatic Environment, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 400714, China.

Methane (CH) emissions from reservoirs have received widespread attention. The central urban area of Chongqing in the Three Gorges Reservoir area was selected as the study area in 2020. The temporal and spatial distribution of dissolved CH concentration and flux, key generation pathways, and influencing factors have been studied. The dissolved CH concentration in low-water-level period and impoundment period varied from 0.037~0.12 μmol·L and 0.11~0.23 μmol·L, with the average values of (0.066 ± 0.0067) μmol·L and (0.13 ± 0.034) μmol·L. The CH flux was (0.941 ± 0.217) μmol·m·h in low-water-level period and (1.915 ± 0.204) μmol·m·h in impoundment period. CH was produced by CO reduction and acetic acid fermentation, accounting for 17.95% and 82.05% of the total CH production, respectively. The dissolved CH concentration was significantly positively correlated with DO and NO-N, and it is opposite with dissolved inorganic carbon. The dissolved CH concentration in this study area is affected by water environment (33.42%), inorganic nitrogen (29.60%), organic carbon (23.88%), and inorganic carbon (13.10%), and anthropogenic influences promoted dissolved CH concentration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-022-20822-wDOI Listing
May 2022

Correlation Study between Rural Human Settlement Health Factors: A Case Study of Xiangxi, China.

Comput Intell Neurosci 2022 12;2022:2484850. Epub 2022 May 12.

Department of Architecture, School of Architecture and Art, Central South University, Changsha 410075, China.

With the emergence of the Industry 4.0 era in China, more refined methods are being proposed for healthy living requirements for human settlements. Since the rural human settlements in China are relatively backward, this study aimed to investigate the influencing factors of human health. First, through field surveys and questionnaires conducted with villagers in Xiangxi's traditional villages in Hunan Province, we analyzed the factors affecting human health qualitatively and quantitatively using the SPSS software. We identified three main dimensions affecting human health in rural human settlements including human behavioral activities, physical environment, and natural environment. Then, we used correlation analysis and multiple linear regression analysis methods to analyze the correlation between environmental factors and human health. The results showed that human activities, building physical environment, and natural environment are significantly correlated with human health. Among them, human behavior has the strongest correlation with health. This research contributes to creating healthy human settlements and guiding the creation of a healthy environment in rural China.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2022/2484850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9119787PMC
May 2022

Mental state, biological rhythm and social support among healthcare workers during the early stages of the COVID-19 epidemic in Wuhan.

Heliyon 2022 May 14:e09439. Epub 2022 May 14.

Mental Health Center, West China Hospital, Sichuan University, No. 28 Dianxin South Road, Chengdu, China.

Background: The COVID-19 pandemic has put the mental health of healthcare workers at risk. However, the potential psychosocial factors underlying mental health problems, such as depression and anxiety, require further investigation. The present study aimed to explore the factors that influence the mental state of healthcare workers.

Methods: A total of 276 healthcare workers completed a set of online self-report questionnaires from February 2 to 5, 2020, in the following order: general information related to the COVID-19 outbreak, Biological Rhythms Interview of Assessment in Neuropsychiatry, Beck Depression Inventory-II, Beck Anxiety Inventory, and Social Support Rating Scale.

Results: Our study revealed that both social support and age moderated the ability of biological rhythm disturbance to exacerbate depression (R = 0.47; effect size f = 0.85). Higher levels of social support buffered the amplification of depression associated with increased biological rhythm disturbance in all age groups, and especially in younger individuals (mean age = 26.57, = 0.04). Depressive symptoms were predicted by both social and sleeping rhythms, whereas anxiety symptoms were predicted only by social rhythm. Married individuals had lower biological rhythm disturbance ratings and higher social support ratings. Females also reported higher ratings in social support.

Conclusions: Our study suggests that biological rhythm intervention along with social support can reduce the negative effect of biological rhythm disturbance on mood disorders, especially in younger people. We also provide evidence for the ability of social support to buffer stress in a major health crisis and demonstrate the effects of marital status and sex, which provide a different perspective for studying mental crisis management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.heliyon.2022.e09439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9107281PMC
May 2022

MiR-26b-5p in small extracellular vesicles derived from dying tumor cells after irradiation enhances the metastasis promoting microenvironment in esophageal squamous cell carcinoma.

Cancer Lett 2022 Aug 17;541:215746. Epub 2022 May 17.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, China. Electronic address:

Radiation therapy is effective in achieving local control in esophageal squamous cell carcinoma; however, changes in the tumor microenvironment induced by radiation can also promote metastasis. Dying tumor cells play vital roles in promoting the survival of living tumor cells; however, few studies have investigated the effects of dying tumor cells on the tumor microenvironment. Since myeloid-derived suppressor cells (MDSCs) and macrophages constitute the pre-metastatic niche (PMN), we used a 4-nitroquinoline-1-oxide induced in situ tumor model to investigate the effects of irradiation on MDSCs and macrophages in esophageal squamous cell carcinoma (ESCC). When primary tumor sites were irradiated, we observed an increase in MDSCs in the spleen and the deposition of PMN components in lung and liver. Enhanced MDSC accumulation and function were induced by small extracellular vesicles (sEVs) isolated from irradiated tumor-bearing mice. The MDSC induction function of sEVs after irradiation was reaffirmed using sEVs derived from ESCC cell lines. The irradiation-induced upregulation of miR-26b-5p in sEVs enhanced MDSC expansion and activation by targeting phosphatase and tensin homolog. Our results first elucidated a mechanism by which dying tumor cells enhanced the deposition of PMN components and potentiated MDSCs in ESCC after irradiation. sEVs played a vital role in mediating signals between the primary tumor and the microenvironment to form a metastasis-promoting microenvironment after irradiation. Furthermore, miR-26b-5p or PI3K/AKT signaling pathway inhibitors should be evaluated in clinical trials in combination with radiotherapy as a strategy to improve outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.canlet.2022.215746DOI Listing
August 2022

T Cell Defects: New Insights Into the Primary Resistance Factor to CD19/CD22 Cocktail CAR T-Cell Immunotherapy in Diffuse Large B-Cell Lymphoma.

Front Immunol 2022 27;13:873789. Epub 2022 Apr 27.

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Despite impressive progress, a significant portion of patients still experience primary or secondary resistance to chimeric antigen receptor (CAR) T-cell immunotherapy for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). The mechanism of primary resistance involves T-cell extrinsic and intrinsic dysfunction. In the present study, a total of 135 patients of DLBCL treated with murine CD19/CD22 cocktail CAR T-therapy were assessed retrospectively. Based on four criteria (maximal expansion of the transgene/CAR-positive T-cell levels post-infusion [C], initial persistence of the transgene by the CAR transgene level at +3 months [T], CD19+ B-cell levels [B-cell recovery], and the initial response to CAR T-cell therapy), 48 patients were included in the research and divided into two groups (a T-normal group [n=22] and a T-defect [n=26] group). According to univariate and multivariate regression analyses, higher lactate dehydrogenase (LDH) levels before leukapheresis (hazard ratio (HR) = 1.922; = 0.045) and lower cytokine release syndrome (CRS) grade after CAR T-cell infusion (HR = 0.150; = 0.026) were independent risk factors of T-cell dysfunction. Moreover, using whole-exon sequencing, we found that germline variants in 47 genes were significantly enriched in the T-defect group compared to the T-normal group (96% vs. 41%; p<0.0001), these genes consisted of CAR structure genes (n=3), T-cell signal 1 to signal 3 genes (n=13), T cell immune regulation- and checkpoint-related genes (n=9), cytokine- and chemokine-related genes (n=13), and T-cell metabolism-related genes (n=9). Heterozygous germline mutations had the highest intergroup differences (26.9% vs. 0%; =0.008). Compound heterozygous variants, referred to as pathogenic and risk factors according to the ClinVar database, were enriched in the T-defect group (3 of 26). In summary, the clinical characteristics and T-cell immunodeficiency genetic features may help explain the underlying mechanism of treatment primary resistance and provide novel insights into CAR T-cell immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2022.873789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9094425PMC
May 2022
-->