Publications by authors named "Kun Chen"

972 Publications

lncRNA-GM targets Foxo1 to promote T cell-mediated autoimmunity.

Sci Adv 2022 Aug 5;8(31):eabn9181. Epub 2022 Aug 5.

Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.

RNA-RBP interaction is important in immune regulation and implicated in various immune disorders. The differentiation of proinflammatory T cell subset T17 and its balance with regulatory T cell (T) generation is closely related to autoimmune pathogenesis. The roles of RNA-RBP interaction in regulation of T17/T differentiation and autoinflammation remain in need of further investigation. Here we report that lncRNA-GM polarizes T17 differentiation but inhibits iT differentiation by reducing activity of Foxo1, a transcriptional factor that is important in inhibiting T17 differentiation but promoting T generation. -deficient mice were protected from experimental autoimmune encephalomyelitis. Mechanistically, lncRNA-GM directly binds to cytoplasmic Foxo1, thus inhibiting its activity through blocking dephosphorylation of Foxo1 by phosphatase PP2A to promote transcription. The human homolog of lncRNA-GM (AK026392.1) also polarizes human T17 differentiation. Our study provides mechanistic insight into the interaction of lncRNA and transcriptional factor in determining T cell subset differentiation during T cell-mediated autoimmune diseases.
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http://dx.doi.org/10.1126/sciadv.abn9181DOI Listing
August 2022

Clinical Investigations of CAR-T Cell Therapy for Solid Tumors.

Front Immunol 2022 18;13:896685. Epub 2022 Jul 18.

Clinical Cancer Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Cell therapy is a distinguished targeted immunotherapy with great potential to treat solid tumors in the new era of cancer treatment. Cell therapy products include genetically engineered cell products and non-genetically engineered cell products. Several recent cell therapies, especially chimeric antigen receptor (CAR)-T cell therapies, have been approved as novel treatment strategies for cancer. Many clinical trials on cell therapies, in the form of cell therapy alone or in combination with other treatments, in solid tumors, have been conducted or ongoing. However, there are still challenges since adverse events and the limited efficacy of cell therapies have also been observed. Here, we concisely summarize the clinical milestones of the conducted and ongoing clinical trials of cell therapy, introduce the evolution of CARs, discuss the challenges and limitations of these therapeutic modalities taking CAR-T as the main focus, and analyze the disparities in the regulatory policies in different countries.
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http://dx.doi.org/10.3389/fimmu.2022.896685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339623PMC
August 2022

Activation of GPR81 Aggravates Remote Organ Injury During Hepatic Ischemia-Reperfusion Injury.

Transplant Proc 2022 Jul 25. Epub 2022 Jul 25.

Department of Pathophysiology, Basic Medical College, Chongqing Medical University, Chongqing, China; Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing, China. Electronic address:

Hepatic ischemia-reperfusion injury (HIRI) is a serious situation with high morbidity and mortality, which is usually accompanied with hyperlactatemia due to impaired lactate clearance in liver. G-protein-coupled receptor 81 (GPR81) has recently been identified as the bioactive receptor of lactate. GPR81 is profoundly involved in the modulation of metabolism and inflammation, but its significance in HIRI remains unclear. The present study investigated the potential roles of GPR81 in HIRI by using the GPR81 agonist 3-chloro-5-hydroxybenzoic acid (CHBA). The results indicated that treatment with CHBA had no obvious effects on HIRI-induced histologic abnormalities and elevation of serum aspartate aminotransferase, alanine aminotransferase. However, CHBA significantly upregulated the serum level of tumor necrosis factor alpha and interleukin-6 in mice with HIRI. Administration of CHBA also exacerbated HIRI-induced histologic lesions in lung, increased the level of myeloperoxidase in lung tissue and the protein concentration in bronchoalveolar lavage fluid. In addition, the serum levels of brain natriuretic peptide and creatinine also increased in CHBA-treated mice. The results indicate that activation of GPR81 might aggravate HIRI-induced remote organ injury and result in serious outcomes.
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http://dx.doi.org/10.1016/j.transproceed.2022.04.024DOI Listing
July 2022

Flexible coding scheme for robotic arm control driven by motor imagery decoding.

J Neural Eng 2022 Jul 27. Epub 2022 Jul 27.

School of Information Engineering, Wuhan University of Technology, No.122,Luoshi Road, Hongshan District, Wuhan, Hubei, 430070, CHINA.

Objective: Brain computer interface (BCI) technology is a new way of information exchange, which can effectively convert physiological signals into control instructions of machines. Due to its spontaneity and device-independence, motor imagery (MI) electroencephalography (EEG) signal is used as a common BCI signal source to achieve direct control of external devices. However, the generalization ability of current classification model of MI tasks is still limited. Moreover, the real time prototype is far from established in practice.

Approach: In order to solve these problems, this paper proposed an optimized neural network architecture based on our previous work. Firstly, the artifact components in MI-EEG signal are removed by using the threshold and threshold function related to the artifact removal evaluation index, and then the data is augmented by the empirical mode decomposition (EMD) algorithm. Furthermore, ensemble learning (EL) method and fine-tuning strategy in transfer learning (TL) are used to optimize the classification model. Finally, combined with the flexible binary encoding strategy, the EEG signal recognition results are mapped to the control commands of the robotic arm, which realizes the multiple degree of freedom control of the robotic arm.

Main Results: The results show that EMD has an obvious data amount enhancement effect on small dataset, and the EL and TL can improve intra-subject and inter-subject model evaluation performance, respectively. The use of binary coding method realizes the expansion of control instructions, i.e., four kinds of MI-EEG signals are used to complete the control of 7 degrees of freedom of the robotic arm.

Significance: Our work not only improves the classification accuracy of subject and the generality of classification model, but also extends the BCI control instruction set.
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http://dx.doi.org/10.1088/1741-2552/ac84a9DOI Listing
July 2022

Source/Drain Trimming Process to Improve Gate-All-Around Nanosheet Transistors Switching Performance and Enable More Stacks of Nanosheets.

Micromachines (Basel) 2022 Jul 8;13(7). Epub 2022 Jul 8.

Primarius Technologies Co., Ltd., Shanghai 201306, China.

A new S/D trimming process was proposed to significantly reduce the parasitic RC of gate-all-around (GAA) nanosheet transistors (NS-FETs) while retaining the channel stress from epitaxy S/D stressors at most. With optimized S/D trimming, the 7-stage ring oscillator (RO) gained up to 27.8% improvement of delay with the same power consumption, for a 3-layer stacked GAA NS-FETs. Furthermore, the proposed S/D trimming technology could enable more than 4-layer vertical stacking of nanosheets for GAA technology extension beyond 3 nm CMOS technology.
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http://dx.doi.org/10.3390/mi13071080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321815PMC
July 2022

Study on the Effect of NTO on the Performance of HMX-Based Aluminized Cast-PBX.

Materials (Basel) 2022 Jul 9;15(14). Epub 2022 Jul 9.

School of Materials Science and Engineering, Beijing Institute of Technology, Zhongguancun South Street 5, Beijing 100081, China.

3-Nitro-1,2,4-triazol-5-one (NTO) is an explosive with broad application prospects. To study the effect of NTO content on the properties of HMX-based cast-PBX (polymer bonded explosive), five different HMX/NTO-based cast-PBXs were prepared and characterized by experiments and simulations. The results show that the addition of NTO is beneficial to reduce the mechanical sensitivity of cast-PBX, but will reduce the energy level of cast-PBX. We then found that with the increase in NTO content, cast-PBX showed a trend of first increasing and then decreasing in terms of mechanical properties, specific heat capacity (Cp) and thermal conductivity (λ). In addition, we found that the Gurney energy () of N30 is 2.31 kJ/g. Finally, the increase in NTO content greatly improves the thermal safety performance of the cast-PBXs, and numerical simulation of slow cook-off can be used as one reliable method to obtain the ignition location, ignition temperature and the transient temperature distribution.
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http://dx.doi.org/10.3390/ma15144808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322992PMC
July 2022

Role of PsnWRKY70 in Regulatory Network Response to Infection with (Fr.) Keissl in .

Int J Mol Sci 2022 Jul 7;23(14). Epub 2022 Jul 7.

State Key Laboratory of Tree Genetics and Breeding, Northeast Forestry University, 26 Hexing Road, Harbin 150040, China.

WRKY is an important complex family of transcription factors involved in plant immune responses. Among them, plays an important role in the process of the plant defense response to the invasion of pathogens. However, the defense mechanism of is not clear in . In this study, we showed that -overexpression lines (OE) had fewer leaf blight symptoms than -repressing lines (RE). activated MAP kinase cascade genes (, , ), calcium channel proteins-related genes (, , ), and calcium-dependent protein kinases genes (, , , ). Furthermore, 129 genes of putative genome-wide direct targets (DTGs) were identified by using transcriptome (RNA-seq) and DNA affinity purification sequencing (DAP-seq). directly binds to the promoters of homologous genes and LRR domain proteins to promote the expression of , , , and , LRR domain proteins , , , , etc. Our study suggests that enhances the resistance of in poplar by activating genes in both pathogen-associated molecular pattern-triggered immunity (PTI) and effector-triggered immunity (ETI).
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http://dx.doi.org/10.3390/ijms23147537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9324512PMC
July 2022

Principal Amalgamation Analysis for Microbiome Data.

Genes (Basel) 2022 Jun 24;13(7). Epub 2022 Jun 24.

Department of Statistics, University of Connecticut, Storrs, CT 06269, USA.

In recent years microbiome studies have become increasingly prevalent and large-scale. Through high-throughput sequencing technologies and well-established analytical pipelines, relative abundance data of operational taxonomic units and their associated taxonomic structures are routinely produced. Since such data can be extremely sparse and high dimensional, there is often a genuine need for dimension reduction to facilitate data visualization and downstream statistical analysis. We propose (PAA), a novel amalgamation-based and taxonomy-guided dimension reduction paradigm for microbiome data. Our approach aims to aggregate the compositions into a smaller number of , guided by the available taxonomic structure, by minimizing a properly measured loss of information. The choice of the loss function is flexible and can be based on familiar diversity indices for preserving either within-sample or between-sample diversity in the data. To enable scalable computation, we develop a hierarchical PAA algorithm to trace the entire trajectory of successive simple amalgamations. Visualization tools including dendrogram, scree plot, and ordination plot are developed. The effectiveness of PAA is demonstrated using gut microbiome data from a preterm infant study and an HIV infection study.
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http://dx.doi.org/10.3390/genes13071139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318429PMC
June 2022

Exposure to amitriptyline induces persistent gut damages and dysbiosis of the gut microbiota in zebrafish (Danio rerio).

Comp Biochem Physiol C Toxicol Pharmacol 2022 Jul 21;260:109417. Epub 2022 Jul 21.

Institute of Environmental Health and Ecological Security, School of the Environment and Safety Engineering, Jiangsu University, Zhenjiang 212013, China; Jiangsu Collaborative Innovation Center of Technology and Material of Water Treatment, Suzhou University of Science and Technology, Suzhou 215009, China. Electronic address:

Amitriptyline (AMI), the most commonly prescribed tricyclic antidepressant, is widely detected in water environments. Exposure to AMI may lead to diverse adverse effects on aquatic organisms, but little is known about the effect of short-term exposure to AMI on the gut microbiota of aquatic organisms and their recovery characteristics. In the present study, adult zebrafish (Danio rerio) were exposed to AMI (0, 2.5, 10, and 40 μg/L) for seven days, and then allowed to recover in AMI-free culture water for 21 days. The exposure caused gut damages in all the AMI treated groups of zebrafish, which became more severe after recovery compared to the control group. AMI exposure also disturbed the microbiota of zebrafish guts and rearing water even after the 21-day recovery period. Furthermore, AMI exposure affected microbes involved in the substance and energy metabolic functions in zebrafish guts and tended to increase the abundance of microbial genera associated with opportunistic pathogens. In addition, the microbial predicted metabolic functions in AMI-exposed guts of zebrafish were significantly altered after the 21-day recovery period, explaining the persistent effects of short-term exposure to AMI. The results of this study suggest that acute exposure to AMI may have persistent impacts on the gut histomorphology and the gut microbiota in aquatic organisms.
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http://dx.doi.org/10.1016/j.cbpc.2022.109417DOI Listing
July 2022

Long-term exposure to residential surrounding greenness and incidence of diabetes: A prospective cohort study.

Environ Pollut 2022 Jul 20;310:119821. Epub 2022 Jul 20.

Department of Epidemiology and Biostatistics at School of Public Health and National Clinical Research Center for Child Health of the Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China. Electronic address:

Exposure to residential greenness might affect population health through increasing physical activity and social engagement, improving mental health, and reducing harmful environmental exposure. However, evidence on the association of greenness with risk of diabetes is still controversial. In this study, we recruited a total of 22,535 participants aged ≥18 years from Yinzhou District, Ningbo, Zhejiang Province, China to investigate the associations between residential greenness and risk of diabetes incidence. Residential greenness was estimated using Normalized Difference Vegetation Index (NDVI), Enhanced Vegetation Index (EVI), and Vegetation Continuous Field (VCF). We also calculated cumulative average NDVI, EVI and VCF values, and changes in NDVI, EVI and VCF during the follow-up period. We used Cox proportional hazards models controlling for demographic characteristics, lifestyles, individual socioeconomic status, history of diseases and particulate matter with an aerodynamic diameter ≤2.5 μm (PM) to examine hazard ratios (HRs) and 95% confidence intervals (95% CIs) and assessed physical activity, body mass index (BMI) or PM as potential mediators. During 84,992.64 person-years of follow-up, a total of 1,154 incident cases of diabetes occurred. In multivariable models, living in the highest quartile of cumulative average NDVI, EVI and VCF within 250-m buffer was associated with 57% (HR = 0.43, 95% CI: 0.36, 0.52), 62% (HR = 0.38, 95% CI: 0.32, 0.45), and 55% (HR = 0.45, 95% CI: 0.38, 0.54) reduction in diabetes risk compared with the lowest quartile, respectively. Results remained similar for NDVI, EVI, and VCF within 500-m and 1000-m buffers. Stratified analyses showed stronger association for residential greenness and diabetes among older people. The association between greenness and diabetes did not appear to be mediated by physical activity, PM or BMI. Our findings suggested that higher residential greenness was significantly associated with lower risk of diabetes.
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http://dx.doi.org/10.1016/j.envpol.2022.119821DOI Listing
July 2022

A Two-Stream Graph Convolutional Network Based on Brain Connectivity for Anesthetized States Analysis.

IEEE Trans Neural Syst Rehabil Eng 2022 28;30:2077-2087. Epub 2022 Jul 28.

Investigating neural mechanisms of anesthesia process and developing efficient anesthetized state detection methods are especially on high demand for clinical consciousness monitoring. Traditional anesthesia monitoring methods are not involved with the topological changes between electrodes covering the prefrontal-parietal cortices, by investigating electrocorticography (ECoG). To fill this gap, a framework based on the two-stream graph convolutional network (GCN) was proposed, i.e., one stream for extracting topological structure features, and the other one for extracting node features. The two-stream graph convolutional network includes GCN Model 1 and GCN Model 2. For GCN Model 1, brain connectivity networks were constructed by using phase lag index (PLI), representing different structure features. A common adjacency matrix was founded through the dual-graph method, the structure features were expressed on nodes. Therefore, the traditional spectral graph convolutional network can be directly applied on the graphs with changing topological structures. On the other hand, the average of the absolute signal amplitudes was calculated as node features, then a fully connected matrix was constructed as the adjacency matrix of these node features, as the input of GCN Model 2. This method learns features of both topological structure and nodes of the graph, and uses a dual-graph approach to enhance the focus on topological structure features. Based on the ECoG signals of monkeys, results show that this method which can distinguish awake state, moderate sedation and deep sedation achieved an accuracy of 92.75% in group-level experiments and mean accuracy of 93.50% in subject-level experiments. Our work verifies the excellence of the graph convolutional network in anesthesia monitoring, the high recognition accuracy also shows that the brain network may carry neurological markers associated with anesthesia.
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http://dx.doi.org/10.1109/TNSRE.2022.3193103DOI Listing
August 2022

[Synovial chondromatosis of left hip joint misdiagnosed as pigmented villonodular synovitis:a case report].

Zhongguo Gu Shang 2022 Jul;35(7):675-7

Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Xianyang 712046, Shaanxi, China.

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http://dx.doi.org/10.12200/j.issn.1003-0034.2022.07.015DOI Listing
July 2022

Effectiveness of automated alerting system compared to usual care for the management of sepsis.

NPJ Digit Med 2022 Jul 19;5(1):101. Epub 2022 Jul 19.

Department of Emergency Medicine, Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

There is a large body of evidence showing that delayed initiation of sepsis bundle is associated with adverse clinical outcomes in patients with sepsis. However, it is controversial whether electronic automated alerts can help improve clinical outcomes of sepsis. Electronic databases are searched from inception to December 2021 for comparative effectiveness studies comparing automated alerts versus usual care for the management of sepsis. A total of 36 studies are eligible for analysis, including 6 randomized controlled trials and 30 non-randomized studies. There is significant heterogeneity in these studies concerning the study setting, design, and alerting methods. The Bayesian meta-analysis by using pooled effects of non-randomized studies as priors shows a beneficial effect of the alerting system (relative risk [RR]: 0.71; 95% credible interval: 0.62 to 0.81) in reducing mortality. The automated alerting system shows less beneficial effects in the intensive care unit (RR: 0.90; 95% CI: 0.73-1.11) than that in the emergency department (RR: 0.68; 95% CI: 0.51-0.90) and ward (RR: 0.71; 95% CI: 0.61-0.82). Furthermore, machine learning-based prediction methods can reduce mortality by a larger magnitude (RR: 0.56; 95% CI: 0.39-0.80) than rule-based methods (RR: 0.73; 95% CI: 0.63-0.85). The study shows a statistically significant beneficial effect of using the automated alerting system in the management of sepsis. Interestingly, machine learning monitoring systems coupled with better early interventions show promise, especially for patients outside of the intensive care unit.
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http://dx.doi.org/10.1038/s41746-022-00650-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296632PMC
July 2022

RNA-binding protein ZCCHC4 promotes human cancer chemoresistance by disrupting DNA-damage-induced apoptosis.

Signal Transduct Target Ther 2022 07 20;7(1):240. Epub 2022 Jul 20.

National Key Laboratory of Medical Immunology, Institute of Immunology, Second Military Medical University, 200433, Shanghai, China.

RNA-binding proteins (RBPs) play important roles in cancer development and treatment. However, the tumor-promoting RBPs and their partners, which may potentially serve as the cancer therapeutic targets, need to be further identified. Here, we report that zinc finger CCHC domain-containing protein 4 (ZCCHC4) is of aberrantly high expression in multiple human cancer tissues and is associated with poor prognosis and chemoresistance in patients of hepatocellular carcinoma (HCC), pancreatic cancer and colon cancer. ZCCHC4 promotes chemoresistance of HCC cells to DNA-damage agent (DDA) both in vitro and in vivo. HCC cell deficiency of ZCCHC4 reduces tumor growth in vivo and intratumoral interference of ZCCHC4 expression obviously enhances the DDA-induced antitumor effect. Mechanistically, ZCCHC4 inhibits DNA-damage-induced apoptosis in HCC cells by interacting with a new long noncoding RNA (lncRNA) AL133467.2 to hamper its pro-apoptotic function. Also, ZCCHC4 blocks the interaction between AL133467.2 and γH2AX upon DDA treatment to inhibit apoptotic signaling and promote chemoresistance to DDAs. Knockout of ZCCHC4 promotes AL133467.2 and γH2AX interaction for enhancing chemosensitivity in HCC cells. Together, our study identifies ZCCHC4 as a new predictor of cancer poor prognosis and a potential target for improving chemotherapy effects, providing mechanistic insights to the roles of RBPs and their partners in cancer progression and chemoresistance.
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http://dx.doi.org/10.1038/s41392-022-01033-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296561PMC
July 2022

A resource for assessing dynamic binary choices in the adult brain using EEG and mouse-tracking.

Sci Data 2022 07 16;9(1):416. Epub 2022 Jul 16.

Centre for Cognitive and Brain Sciences, University of Macau, Taipa, Macau SAR, China.

We present a dataset combining high-density Electroencephalography (HD-EEG, 128-channels) and mouse-tracking intended as a resource for examining the dynamic decision process of semantics and preference choices in the human brain. The dataset includes resting-state and task-related (food preference choices and semantic judgments) EEG acquired from 31 individuals (ages: 18-33). Along with the dataset, we also provided the preliminary microstate analysis of resting-state EEG and the ERPs, topomap, and time-frequency maps of the task-related EEG. We believe that the simultaneous mouse-tracking and EEG recording would crack the core components of binary choices and further index the temporal dynamics of decision making and response hesitation. This publicly available dataset could support the development of neural signal processing methods in motor EEG, thus advancing research in both the decision neuroscience and brain-computer interface (BCI) applications.
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http://dx.doi.org/10.1038/s41597-022-01538-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9288455PMC
July 2022

APRIL and BAFF play a key role in differentiating vitreoretinal lymphoma from uveitis.

Clin Chim Acta 2022 Jul 9;535:1-6. Epub 2022 Jul 9.

Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, China.

Background: Early diagnosis of vitreoretinal lymphoma (VRL) is critical for the successful treatment of this rare intraocular malignancy. However, fast and reliable diagnosis of VRL in patients presenting with intermediate or posterior non-infectious uveitis remains a challenge. A proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF) are vital factors in the pathophysiology, diagnosis, and prognosis of primary central nervous system lymphoma (PCNSL) and systemic autoimmune diseases. However, their utility as biomarkers for the diagnosis of VRL and uveitis remains unclear.

Methods: In this retrospective study, we analyzed APRIL and BAFF levels in the aqueous humor (AH) of 43 eyes of 40 patients, including 23 eyes of 20 patients with VRL, eight eyes of eight patients with uveitis, and 12 eyes of 12 patients with other ocular diseases (OODs). Additionally, we measured their levels after induction of chemotherapy in five eyes of five patients with VRL.

Results: AH levels of APRIL reliably distinguished VRL from uveitis, with a specificity of 78.3% and sensitivity of 75%. BAFF also showed similar potential. Serial AH analysis of patients with VRL during chemotherapy demonstrated a corresponding decline in AH levels of APRIL and BAFF.

Conclusion: This study extends the spectrum of valuable diagnostic biomarkers for VRL and uveitis. In patients with uveitis, the assessment of AH APRIL may help accelerate the diagnosis of VRL. Moreover, our results underline the important role of APRIL and BAFF in therapeutic monitoring of VRL.
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http://dx.doi.org/10.1016/j.cca.2022.06.014DOI Listing
July 2022

Sequentially co-immobilized PET and MHET hydrolases via Spy chemistry in calcium phosphate nanocrystals present high-performance PET degradation.

J Hazard Mater 2022 Jul 3;438:129517. Epub 2022 Jul 3.

Department of Biochemical Engineering, School of Chemical Engineering and Technology and Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China. Electronic address:

Accumulation of polyethylene terephthalate (PET) has brought an enormous threat to the ecosystem. The recently reported PET hydrolase (DuraPETase) and MHET hydrolase (MHETase) can synergistically catalyze the complete PET degradation. Hence, this work was designed to develop a bienzymatic cascade catalysis by co-immobilizing the two enzymes for PET biodegradation. DuraPETase and MHETase were sequentially co-immobilized in calcium phosphate nanocrystals (CaP) through SpyTag/SpyCatcher system. MHETase-SpyCatcher was first embedded inside the nanocrystals via biomimetic mineralization, and DuraPETase-SpyTag was then conjugated on the outlayer (~1.5 µm). The bienzyme compartmentalization facilitated DuraPETase interaction with the solid substrate, and the layered structures of the nanocrystals protected the enzymes, thus enhancing their stability. The high specific surface area of the nanocrystals and the proximity effects from the bienzymatic cascade were beneficial to the improved enzyme activity. Experimental data and molecular dynamics simulations revealed the activation effect of Ca on DuraPETase. Taken together, the final results indicate that the PET degradation efficiency of [email protected] increased by 6.1 and 1.5 times over the free bienzyme system within 10 d at 40 °C and 50 °C, with weight losses at 32.2% and 50.3%, respectively. The bienzymatic cascade with [email protected] can completely degrade PET, contributing to the recycling of PET.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129517DOI Listing
July 2022

Chiral Non-Fullerene Acceptor Enriched Bulk Heterojunctions Enable High-Performance Near-Infrared Circularly Polarized Light Detection.

Small 2022 Aug 9;18(31):e2202941. Epub 2022 Jul 9.

CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology, Beijing, 100190, China.

Organic photodetectors that can sensitively convert near-infrared (NIR) circularly polarized light (CPL) into modulable electrical signals have promising applications in spectroscopy, imaging, and communications. However, the preparation of chiral NIR organic photodetectors with simultaneously high dissymmetry factor, responsivity, detectivity, and response speed is challenging. Here, direct CPL detectors based on the bulk heterojunctions (BHJs) of chiral BTP-4Cl non-fullerene acceptor with dilute achiral PM6 donor are constructed, which successfully address these issues. The chiral acceptor-enriched BHJs with a donor/acceptor ratio of 1/10 achieve an optimal trade-off between chiroptical properties and optoelectronic performance. The supramolecular chirality from the acceptor aggregates provides the BHJs with a true absorption dissymmetry factor (g ) of ±0.02 at 830 nm, the highest value among NIR-sensitive detectors, which endows the photodetector with a photocurrent dissymmetry factor (g ) of ±0.03. Impressively, the photodetector demonstrates an external quantum efficiency as high as 60%, a responsivity of 0.4 A W , a detectivity of 3 × 10 Jones (based on noise current), and a fast response speed on the microsecond scale with the -3 dB bandwidth over 7000 Hz in the NIR region. This study exhibits a promising strategy for building high-performing direct NIR CPL detectors by introducing supramolecular chirality into BHJs.
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http://dx.doi.org/10.1002/smll.202202941DOI Listing
August 2022

Macroporous Hydrogel for High-Performance Atmospheric Water Harvesting.

ACS Appl Mater Interfaces 2022 Jul 8;14(28):32433-32443. Epub 2022 Jul 8.

College of Medicine and Biological Information Engineering, Northeastern University, Shenyang 110169, China.

Simple, low-cost, and high-performance atmospheric water harvesting (AWH) still remains challenging in the context of global water shortage. Here, we present a simple and low-cost macroporous hydrogel for high-performance AWH to address this challenge. We employed an innovative strategy of pore foaming and vacuum drying to rationally fabricate a macroporous hydrogel. The hydrogel is endowed with a macroporous structure and a high specific surface area, enabling sufficient contact of the inner sorbent with outside air and high-performance AWH. The experiments demonstrate that macroporous hydrogels can achieve high-performance AWH with a broad range of sorption humidity [relative humidity (RH) from 100% to even lower than 20%], high water sorption capacity (highest 433.72% of hydrogel's own weight at ∼98% RH, 25 °C within 60 h), rapid vapor capturing (the sorption efficiency is as high as 0.32 g g h in the first 3 h at 90% RH, 25 °C), unique durability, low desorption temperature (∼50 °C, lowest), and high water-releasing rate (release 99.38% of the sorbed water under 500 W m light for 6 h). The results show that this macroporous hydrogel can sorb water more than 193.46% of its own weight overnight (13 h) at a RH of ∼90%, 25 °C and release as high as 99.38% of the sorbed water via the photothermal effect. It is estimated that the daily water yield can reach up to approximately 2.56 kg kg day in real outdoor conditions, enabling daily minimum water consumption of an adult. Our simple, affordable, and easy-to-scale-up macroporous hydrogel can not only unleash the unlimited possibilities for large-scale and high-performance AWH but also offer promising opportunities for functional materials, soft matter, flexible electronics, tissue engineering, and biomedical applications.
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http://dx.doi.org/10.1021/acsami.2c04228DOI Listing
July 2022

Neuropathy-associated Fars2 deficiency affects neuronal development and potentiates neuronal apoptosis by impairing mitochondrial function.

Cell Biosci 2022 Jul 6;12(1):103. Epub 2022 Jul 6.

Department of Anatomy, Histology and Embryology and K.K. Leung Brain Research Centre, School of Basic Medicine, Air Force Medical University, Xi'an, Shaanxi, People's Republic of China.

Background: Neurodegenerative diseases encompass an extensive and heterogeneous group of nervous system disorders which are characterized by progressive degeneration and death of neurons. Many lines of evidence suggest the participation of mitochondria dysfunction in these diseases. Mitochondrial phenylalanyl-tRNA synthetase, encoded by FARS2, catalyzes the transfer of phenylalanine to its cognate tRNA for protein synthesis. As a member of mt-aaRSs genes, FARS2 missense homozygous mutation c.424G > T (p.D142Y) found in a Chinese consanguineous family first built the relationship between pure hereditary spastic paraplegia (HSP) and FARS2 gene. More FARS2 variations were subsequently found to cause heterogeneous group of neurologic disorders presenting three main phenotypic manifestations: infantile-onset epileptic mitochondrial encephalopathy, later-onset spastic paraplegia and juvenile onset refractory epilepsy. Studies showed that aminoacylation activity is frequently disrupt in cases with FARS2 mutations, indicating a loss-of-function mechanism. However, the underlying pathogenesis of neuropathy-associated Fars2 deficiency is still largely unknown.

Results: Early gestation lethality of global Fars2 knockout mice was observed prior to neurogenesis. The conditional Fars2 knockout-mouse model delayed lethality to late-gestation, resulting in a thinner cortex and an enlarged ventricle which is consist with the MRI results revealing cortical atrophy and reduced cerebral white matter volume in FARS2-deficient patients. Delayed development of neurite outgrowth followed by neuronal apoptosis was confirmed in Fars2-knockdown mouse primary cultured neurons. Zebrafish, in which fars2 was knocked down, exhibited aberrant motor neuron function including reduced locomotor capacity which well restored the spastic paraplegia phenotype of FARS2-deficient patients. Altered mitochondrial protein synthesis and reduced levels of oxidative phosphorylation complexes were detected in Fars2-deficient samples. And thus, reduced ATP, total NAD levels and mitochondrial membrane potential, together with increased ROS production, revealed mitochondrial dysfunction both in vitro and in vivo. Dctn3 is a potential downstream molecule in responds to Fars2 deficient in neurons, which may provide some evidence for the development of pathogenesis study and therapeutic schedule.

Conclusions: The Fars2 deficiency genetic models developed in this study cover the typical clinical manifestations in FARS2 patients, and help clarify how neuropathy-associated Fars2 deficiency, by damaging the mitochondrial respiratory chain and impairing mitochondrial function, affects neuronal development and potentiates neuronal cell apoptosis.
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http://dx.doi.org/10.1186/s13578-022-00838-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258231PMC
July 2022

Neuropathy-associated Fars2 deficiency affects neuronal development and potentiates neuronal apoptosis by impairing mitochondrial function.

Cell Biosci 2022 Jul 6;12(1):103. Epub 2022 Jul 6.

Department of Anatomy, Histology and Embryology and K.K. Leung Brain Research Centre, School of Basic Medicine, Air Force Medical University, Xi'an, Shaanxi, People's Republic of China.

Background: Neurodegenerative diseases encompass an extensive and heterogeneous group of nervous system disorders which are characterized by progressive degeneration and death of neurons. Many lines of evidence suggest the participation of mitochondria dysfunction in these diseases. Mitochondrial phenylalanyl-tRNA synthetase, encoded by FARS2, catalyzes the transfer of phenylalanine to its cognate tRNA for protein synthesis. As a member of mt-aaRSs genes, FARS2 missense homozygous mutation c.424G > T (p.D142Y) found in a Chinese consanguineous family first built the relationship between pure hereditary spastic paraplegia (HSP) and FARS2 gene. More FARS2 variations were subsequently found to cause heterogeneous group of neurologic disorders presenting three main phenotypic manifestations: infantile-onset epileptic mitochondrial encephalopathy, later-onset spastic paraplegia and juvenile onset refractory epilepsy. Studies showed that aminoacylation activity is frequently disrupt in cases with FARS2 mutations, indicating a loss-of-function mechanism. However, the underlying pathogenesis of neuropathy-associated Fars2 deficiency is still largely unknown.

Results: Early gestation lethality of global Fars2 knockout mice was observed prior to neurogenesis. The conditional Fars2 knockout-mouse model delayed lethality to late-gestation, resulting in a thinner cortex and an enlarged ventricle which is consist with the MRI results revealing cortical atrophy and reduced cerebral white matter volume in FARS2-deficient patients. Delayed development of neurite outgrowth followed by neuronal apoptosis was confirmed in Fars2-knockdown mouse primary cultured neurons. Zebrafish, in which fars2 was knocked down, exhibited aberrant motor neuron function including reduced locomotor capacity which well restored the spastic paraplegia phenotype of FARS2-deficient patients. Altered mitochondrial protein synthesis and reduced levels of oxidative phosphorylation complexes were detected in Fars2-deficient samples. And thus, reduced ATP, total NAD levels and mitochondrial membrane potential, together with increased ROS production, revealed mitochondrial dysfunction both in vitro and in vivo. Dctn3 is a potential downstream molecule in responds to Fars2 deficient in neurons, which may provide some evidence for the development of pathogenesis study and therapeutic schedule.

Conclusions: The Fars2 deficiency genetic models developed in this study cover the typical clinical manifestations in FARS2 patients, and help clarify how neuropathy-associated Fars2 deficiency, by damaging the mitochondrial respiratory chain and impairing mitochondrial function, affects neuronal development and potentiates neuronal cell apoptosis.
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http://dx.doi.org/10.1186/s13578-022-00838-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258231PMC
July 2022

Combined treatment with Rg1 and adipose-derived stem cells alleviates DSS-induced colitis in a mouse model.

Stem Cell Res Ther 2022 06 21;13(1):272. Epub 2022 Jun 21.

Colorectal Disease Center of Nanjing Hospital of Chinese Medicine, Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210022, China.

Background: Inflammatory bowel diseases, consisting of Crohn's disease and ulcerative colitis constitute chronic inflammatory conditions that may compromise the whole gastrointestinal tract as well as the colonic mucosa. Currently, there are no curative interventions for IBD, and all available treatments have side effects that limit their use. Adipose-derived stem cell (ADSC) treatment is a prospective treatment option for IBD. Previous findings indicated that ginsenoside (Rg1) dampened inflammatory diseases like colitis by inhibiting the binding of LPS to TLR4 on macrophages and restoring the Th17/Treg ratio. The purpose of this work was to investigate whether Rg1 can increase the influence of ADSC in a mouse model of colitis triggered by dextran sulfate sodium (DSS).

Methods: ADSC was intravenously inoculated into mice with DSS-triggered colitis, while Rg1 was delivered via oral gavage. Colon inflammation was assessed via body weight, colon length along with H&E staining. Serum cytokine levels were measured using ELISA. Besides, flow cytometry was adopted to determine the percentage, as well as FMI of immune cells in the spleen. The effects of simultaneous Rg1 and ADSC treatment on TLR4-MyD88 signaling were assessed via immunofluorescence.

Results: Rg1 and ADSC effectively alleviated the impacts of colon inflammation, weight loss, and colon length reduction along with histological score. Treatment with Rg1 and ADSC reduced serum levels of the proinflammatory cytokines, IL-1β, TNF-α, IL-6, IL-4, and IL-17A and upregulated the level of immunosuppressive cytokine, IL-10. Compared with ADSC or Rg1 alone, combined treatment with Rg1 and ADSC significantly improved the structure of microbial community. Additionally, treatment with Rg1 plus ADSC selectively elevated the level of splenic regulatory T (Treg) cells and downregulated the proportion of T helper type 17 (Th17) cells, indicating restoration of intestinal homeostasis. Besides, we established that the combination of ADSC + Rg1 restored immunological balance more effectively than either ADSC or Rg1 alone, illustrating that Rg1's modulatory function on the gut microbiota may boost the impact of ADSCs in restoration of the immune balance. ADSC combined with Rg1 might downregulate the expression of TLR4 and MyD88, thereby suppressing TLR4-MyD8 signaling. The immunofluorescence results also suggested that co-therapy with Rg-1 and ADSC may optimize treatment strategies of IBD.

Conclusions: Here, we find that the combination of Rg1 and ADSC alleviates DSS-induced colitis in a mouse model more efficiently than ADSC alone, indicating that Rg1 enhances the effect of ADSC against colitis.
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http://dx.doi.org/10.1186/s13287-022-02940-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210677PMC
June 2022

The landscape of isoform switches in sepsis: a multicenter cohort study.

Sci Rep 2022 Jun 17;12(1):10276. Epub 2022 Jun 17.

Department of Emergency Medicine, Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No 3, East Qingchun Road, Hangzhou, 310016, Zhejiang, China.

Sepsis is caused by an uncontrolled inflammatory response, whose underlying mechanisms are not fully understood. It is well known that the majority of human genes can be expressed as alternative isoforms. While isoform switching is implicated in many diseases and is particularly prominent in cancer, it has never been reported in the context of sepsis. Patients presented to the emergency department of three tertiary care hospitals from January 2020 to December 2020 were enrolled. Clinical variables and genome-wide transcriptome of peripheral blood mononuclear cells (PBMC) were obtained. Isoform switching analysis were performed to identify significant isoform switches and relevant biological consequences. A total of 48 subjects with sepsis, involving 42 survivors and 6 non-survivors, admitted to the emergency department of three tertiary care hospitals were enrolled in this study. PBMCs were extracted for RNA sequencing (RNA-seq). Patients (n = 4) with mild stroke or acute coronary syndrome without infection were enrolled in this study as controls. The most frequent functional changes resulting from isoform switching were changes affecting the open reading frame, protein domains and intron retention. Many genes without differences in gene expression showed significant isoform switching. Many genes with significant isoform switches ([Formula: see text]> 0.1) were associated with higher mortality risk, including PIGS, CASP3, LITAF, HBB and RUVBL2. The study for the first time described the landscape of isoform switching in sepsis, including differentially expressed isoform fractions between patients with and without sepsis and survivors and nonsurvivors. The biological consequences of isoform switching, including protein domain loss, signal peptide gain, and intron retention, were identified.
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http://dx.doi.org/10.1038/s41598-022-14231-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205547PMC
June 2022

A Novel Pseudogene Methylation Signature to Predict Temozolomide Outcome in Non-G-CIMP Glioblastomas.

J Oncol 2022 6;2022:6345160. Epub 2022 Jun 6.

School of Aerospace Medicine, Air Force Medical University, Xi'an, China.

Objective: Alterations in the methylation state of pseudogenes may serve as clinically useful biomarkers of glioblastomas (GBMs) that do not have glioma-CpG island methylator phenotype (G-CIMP).

Methods: Non-G-CIMP GBM datasets were included for evaluation, and a RISK-score signature was determined from the methylation state of pseudogene loci. Both bioinformatic and experimental analyses were performed for biological validation.

Results: By integrating clinical information with DNA methylation microarray data, we screened a panel of eight CpGs from discovery cohorts of non-G-CIMP GBMs. Each CpG could accurately and independently predict the prognosis of patients under a treatment regime that combined radiotherapy (RT) and temozolomide (TMZ). The 8-CpG signature appeared to show opposite prognostic correlations between patients treated with RT/TMZ and those treated with RT monotherapy. The analyses further indicated that this signature had predictive value for TMZ efficacy because different survival benefits between RT/TMZ and RT therapies were observed in each risk subgroup. The incorporation of other risk factors, such as age and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, with our pseudogene methylation signature could provide precise risk classification. In vitro experimental data revealed that two locus-specific pseudogenes (ZNF767P and CLEC4GP1) may modulate TMZ resistance via distinct mechanisms in GBM cells.

Conclusion: The biologically and clinically relevant RISK-score signature, based on pseudogene methylation loci, may offer information for predicting TMZ responses of non-G-CIMP GBMs, that is independent from, but complementary to, MGMT-based approaches.
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http://dx.doi.org/10.1155/2022/6345160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9194959PMC
June 2022

Computerized-Assisted Scoliosis Diagnosis Based on Faster R-CNN and ResNet for the Classification of Spine X-Ray Images.

Comput Math Methods Med 2022 6;2022:3796202. Epub 2022 Jun 6.

Department of Medical Examination Center, Huaqiao University Affiliated Strait Hospital, Quanzhou, Fujian 362000, China.

In order to reduce the subjectivity of preoperative diagnosis and achieve accurate and rapid classification of idiopathic scoliosis and thereby improving the standardization and automation of spinal surgery diagnosis, we implement the Faster R-CNN and ResNet to classify patient spine images. In this paper, the images are based on spine X-ray imaging obtained by our radiology department. We compared the results with the orthopedic surgeon's measurement results for verification and analysis and finally presented the grading results for performance evaluation. The final experimental results can meet the clinical needs, and a fast and robust deep learning-based scoliosis diagnosis algorithm for scoliosis can be achieved without manual intervention using the X-ray scans. This can give rise to a computerized-assisted scoliosis diagnosis based on X-ray imaging, which has strong potential in clinical utility applied to the field of orthopedics.
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http://dx.doi.org/10.1155/2022/3796202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9192275PMC
June 2022

The "Hand as Foot" teaching method in the carpal tunnel and the ankle tunnel.

Asian J Surg 2022 Jun 12. Epub 2022 Jun 12.

Inner Mongolia Medical University, Department of Orthopedics, Affiliated Hospital of Inner Mongolia Medical University, Huhehot North Street, Inner Mongolia 010050, China.

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http://dx.doi.org/10.1016/j.asjsur.2022.05.093DOI Listing
June 2022

Impacts of cetylpyridinium chloride on the behavior and brain neurotransmitter levels of juvenile and adult zebrafish (Danio rerio).

Comp Biochem Physiol C Toxicol Pharmacol 2022 Sep 11;259:109393. Epub 2022 Jun 11.

Institute of Environmental Health and Ecological Security, School of the Environment and Safety Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, China; Jiangsu Collaborative Innovation Center of Technology and Material of Water Treatment, Suzhou University of Science and Technology, Suzhou 215009, China. Electronic address:

Cetylpyridinium chloride (CPC) is a cationic surfactant that has been widely used as an antibacterial ingredient in pharmaceutical and personal care products. Due to its high residue in surface waters, there is increasing concern over the potential risk of CPC to aquatic ecosystems. However, knowledge of its impacts on fish is still limited. Therefore, this study exposed juvenile and adult zebrafish to CPC (0, 10, and 40 μg/L) for four days. Subsequently, changes in their behavioral traits and brain levels of several neurotransmitters were investigated. The behavioral assay showed that CPC exposure significantly decreased the locomotor activity and social interaction of zebrafish at both life stages, and juveniles were more sensitive to CPC exposure than adults. In the control groups, the brain neurotransmitters concentrations increased with age in zebrafish. However, CPC exposure tended to increase the brain neurotransmitter levels of juveniles but decreased their levels in adults. Correlation analysis revealed that the brain monoamine neurotransmitters and their turnover might play important roles in the life stage-dependent behavioral response to CPC. In particular, the DOPAC/DA ratio was significantly associated with CPC-induced hypoactivity and reduced social interactions in juveniles but not adults. Our findings demonstrated that CPC exposure could cause abnormal behavior in juvenile and adult zebrafish and disturb their brain neurotransmitters, even at environmentally relevant concentrations, and thus highlighted the necessity for further assessing its potential risks to aquatic ecosystems.
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http://dx.doi.org/10.1016/j.cbpc.2022.109393DOI Listing
September 2022

BpEIN3.1 represses leaf senescence by inhibiting synthesis of ethylene and abscisic acid in Betula platyphylla.

Plant Sci 2022 Aug 25;321:111330. Epub 2022 May 25.

State Key Laboratory of Tree Genetics and Breeding, Northeast Forestry University, Harbin 150040, China. Electronic address:

Leaf senescence and abscission play crucial role in annual plant adapting to seasonal alteration and climate changes by shortening life cycle and development process in response to abiotic and/or biotic stressors underlying phytohormones and environmental signals. Ethylene and abscisic acid are the major phytohormones that promotes leaf senescence, involving various transcription factors, such as EIN3 (ethylene-insensitive 3) and EIL (ethylene-insensitive 3-like) gene family, controlling leaf senescence through metabolite biosynthesis and signal transduction pathways. However, the roles of EIN3 regulating leaf senescence responding to environmental changes in perennial plant, especially forestry tree, remain unclear. In this study, we found that BpEIN3.1 from a subordinated to EIL3 subclade, is a transcription repressor and regulated light-dependent premature leaf senescence in birch (Betula platyphylla). BpEIN3.1 might inhibits the transcription of BpATPS1 by binding to its promoter. Shading suppressed premature leaf senescence in birch ein3.1 mutant line. Ethylene and abscisic acid biosynthesis were also reduced. In addition, abscisic acid positively regulated the expression of BpEIN3.1. This was demonstrated by the hormone-response element analysis of BpEIN3.1 promoter and its gene expression after the hormone treatments. Moreover, our results showed that abscisic acid is also involved in maintaining homeostasis. The molecular mechanism of leaf senescence provides a possibility to increasing wood production by delaying of leaf senescence.
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http://dx.doi.org/10.1016/j.plantsci.2022.111330DOI Listing
August 2022

Pigment of (A. St.-Hil.) Flowers: Separation, Extraction, Purification and Antioxidant Activity.

Molecules 2022 May 31;27(11). Epub 2022 May 31.

Precise Genome Engineering Center, School of Life Sciences, Guangzhou University, Guangzhou 510006, China.

In this work, the extraction procedure of a natural pigment from the flower of (A. St.-Hil.) was optimized by response surface methodology. It is the first time that the extraction of the flower pigment of (FPCS) has been reported, along with an evaluation of its stability and biological activity under various conditions, and an exploration of its potential use as a food additive and in medicine. Specifically, the effects of ethanol concentration, solid-liquid ratio, temperature and time on the extraction rate of FPCS were determined using a Box-Behnken design. The optimum extraction conditions for FPCS were 75% ethanol with a solid-liquid ratio of 1:75 mg/mL) at 66 °C for 39 min. The purification of FPCS using different macroporous resins showed that D101 performed best when the initial mass concentration of the injection solution was 1.50 mg/mL, resulting in a three-fold increase in color value. The yield of dry flowers was 9.75% of fresh petals and the FPCS extraction efficiency was 43.2%. The effects of light, solubility, pH, temperature, sweeteners, edible acids, redox agents, preservatives and metal ions on FPCS were also investigated. Furthermore, the characteristics of FPCS were determined by spectrophotometry at a specific wavelength using the Lambert-Beer law to correlate the mass of FPCS with its absorbance value. An acute toxicological test performed according to Horne's method showed that FPCS is a non-toxic extract and thus may be used as a food additive or in other ingestible forms. Finally, western blotting showed that FPCS prevents lipopolysaccharide-induced hippocampal oxidative stress in mice. The study suggests that FPCS may function as an antioxidant with applications in the food, cosmetics and polymer industries.
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http://dx.doi.org/10.3390/molecules27113555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9182074PMC
May 2022

Healing of ExcisionAl wounds on Lower legs by Secondary intention (HEALS) cohort study. Part 2: feasibility data from a multicentre prospective observational cohort study to inform a future randomized controlled trial.

Clin Exp Dermatol 2022 Jun 3. Epub 2022 Jun 3.

Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.

Background: Compression therapy is considered beneficial for postsurgical lower leg wound healing by secondary intention; however, there is a lack of supportive evidence. To plan a randomized controlled trial (RCT), suitable data are needed.

Aim: To determine the feasibility of recruitment and estimate recruitment rate; to understand the standard postoperative wound management pathway; to determine uptake of optional additional clinic visits for healing confirmation; and to explore patient acceptability of compression bandaging and plan a future RCT.

Methods: Participant recruitment was performed from secondary care dermatology clinics, during a period of 22 months. Inclusion criteria were age ≥ 18 years, planned excision of keratinocyte cancer on the lower leg with healing by secondary intention and an ankle-brachial pressure index of ≥ 0.8. Exclusion criteria were planned primary closure/graft or flap; inability to receive, comply with or tolerate high compression; planned compression; or suspected melanoma. Patients were followed up weekly (maximum 6 months) in secondary care clinics and/or by telephone. Information was collected on healthcare resource use, unplanned compression, wound healing and an optional clinic visit to confirm healing.

Results: This study recruited 58 patients from 9 secondary care dermatology clinics over 22 months. Mean recruitment/centre/month was 0.8 (range 0.1-2.3). Four centres had dedicated Research Nurse support. The analysis population (n = 53) had weekly follow-up assessments. Standard care clinical contacts were: general practitioner (7 visits; 1.2%), community nurse (169; 28.5%), practice nurse visits (189; 31.8%) and dermatology clinic visits (138; 23.2%). Participants whose wounds healed (34 of 45; 75.6%) attended an optional clinic visit.

Conclusion: Data were obtained to inform a future RCT. Recruitment rates were found to be higher in centres with dedicated research support. People would be willing to take part in a trial and attend a confirmation of healing visit.
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http://dx.doi.org/10.1111/ced.15283DOI Listing
June 2022
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