Publications by authors named "Bing Liu"

1,768 Publications

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Systematic screening reveals synergistic interactions that overcome MAPK inhibitor resistance in cancer cells.

Cancer Biol Med 2021 Jun 9. Epub 2021 Jun 9.

Department of Cell Biology, Basic Medical College, Army Medical University (Third Military Medical University), Chongqing 400038, China.

Objective: Effective adjuvant therapeutic strategies are urgently needed to overcome MAPK inhibitor (MAPKi) resistance, which is one of the most common forms of resistance that has emerged in many types of cancers. Here, we aimed to systematically identify the genetic interactions underlying MAPKi resistance, and to further investigate the mechanisms that produce the genetic interactions that generate synergistic MAPKi resistance.

Methods: We conducted a comprehensive pair-wise sgRNA-based high-throughput screening assay to identify synergistic interactions that sensitized cancer cells to MAPKi, and validated 3 genetic combinations through competitive growth, cell viability, and spheroid formation assays. We next conducted Kaplan-Meier survival analysis based on The Cancer Genome Atlas database and conducted immunohistochemistry to determine the clinical relevance of these synergistic combinations. We also investigated the MAPKi resistance mechanisms of these validated synergistic combinations by using co-immunoprecipitation, Western blot, qRT-PCR, and immunofluorescence assays.

Results: We constructed a systematic interaction network of MAPKi resistance and identified 3 novel synergistic combinations that effectively targeted MAPKi resistance ( + + , and + ). We next analyzed their clinical relevance and the mechanisms by which they sensitized cancer cells to MAPKi exposure. Specifically, we discovered a novel protein complex, HDGF-LGR5, that adaptively responded to MAPKi to enhance cancer cell stemness, which was up- or downregulated by the inhibitors of ITGB3 + JNK or ITGB3 + IGF1R.

Conclusions: Pair-wise sgRNA library screening provided systematic insights into elucidating MAPKi resistance in cancer cells. ITGB3- + IGF1R-targeting drugs (cilengitide + linsitinib) could be used as an effective therapy for suppressing the adaptive formation of the HDGF-LGR5 protein complex, which enhanced cancer stemness during MAPKi stress.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0560DOI Listing
June 2021

[Regulation of RNA Binding Protein Mbnl1 on Development of Mouse Embryonic Hematopoietic Stem Cells].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Jun;29(3):924-930

School of Medicine, Jinan University, Guangzhou 510000, Guangdong Province, China,E-mail:

Objective: To analyze the dynamic molecular expression characteristics of single cell RNA binding proteins (RBPs) in the development of mouse embryonic hematopoitic stem cells (HSCs), and obtain the functional research target RNA splicing factor--Mbnl1, to clarify the function of Mbnl1 involved in regulating mouse embryonic HSC development.

Methods: Bioinformatics was used to analyze the single-cell transcriptome data of mouse embryos during HSC development, and the single-cell RBP dynamic molecular expression maps in HSC development was obtained. Mbnl1 was obtained by combining differential analysis and literature research screening. The Mbnl1-knockout mouse model was constructed by the CRISPER/Cas9 technology. Aorta-gonad-mesonephros (AGM) and yolk sac (YS) tissue in two genotype embryos of Mbnl1 and Mbnl1 at E11.5 were digested into single cells, and then a methylcellulose semi-solid culture system was used to perform an in vitro CFU-C of hematopoietic cells. The number and type of hematopoietic cell colonies in the two hematopoietic tissues in Mbnl1-knockout mice after 7 days were calculated. Furthermore, the whole AGM tissue cells of E11.5 Mbnl1 and Mbnl1 donor mice were transplanted via tail vein injection respectively, and the function of HSC in AGM region of mice after Mbnl1 knockout was evaluated through the chimerism rate of peripheral blood in recipient mice at 4w and 8w and the kinetic experiment of hematopoietic system reconstruction.

Results: The in vitro CFU-C experiment of hematopoietic cells preliminarily indicated that there was no significant difference in the number of cell colonies in AGM region and YS transformed by the two genotypes of Mbnl1 and Mbnl1 at E11.5, which suggested that HPC function in AGM and YS tissues had no abnormality after Mbnl1 knockout. Single cell transplantation in AGM region vin tail vein showed no significant difference in the hematopoietic reconstruction chimeric rate between Mbnl1 and Mbnl1 mice, suggesting that there was no abnormality in HSC function in AGM tissues after Mbnl1 knockout.

Conclusion: Through functional experiments in vivo and in vitro, it has been confirmed that knockout of the RNA splicing factor--Mbnl1 does not affect the development of HSPC in AGM region of mouse embryo.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.03.043DOI Listing
June 2021

Evaluation of eyestrain with vertical electrooculogram.

Comput Methods Programs Biomed 2021 May 25;208:106171. Epub 2021 May 25.

Ophthalmology Department, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.

Background And Objective: Eyestrain has been increasingly severe in our lives and works as the progress of computers and smartphones. Evaluating eyestrain helps to prevent and relieve eyestrain. Our study aimed to evaluate eyestrain by analyzing vertical electrooculogram (VEOG).

Methods: 21 young subjects were asked to watch a video on the computer for a totally 120 minutes each, during which the VEOG signal was acquired using only three electrodes, and the questionnaire was answered every 30 minutes. The VEOG signal was divided into four 30-minute phases, from which VEOG signal power probability (VEOGSPP) features and blink features were extracted. The blink features include the changes of blink number (BN), group blinks number (GBN) and ratio (GBR), mean blink amplitude (Mean_BA) and duration (Mean_BD), mean blink duration at 50% (Mean_BD50), mean closing duration (Mean_CD) and opening duration (Mean_OD), mean opening duration at early 50% (Mean_ODE50) and late 50% (Mean_ODL50), mean blink maximum rising slope (Mean_BMRS) and falling slope (Mean_BMFS).

Results: The results showed that the VEOGSPP in the high-frequency band (0.8-6.3Hz), BN, GBN, and GBR significantly increased while the VEOGSPP in the low-frequency band (0.1-0.4Hz), Mean_BA, Mean_OD, and Mean_ODL50 significantly decreased with eyestrain (P<0.05).

Conclusions: In conclusion, eyestrain induced by watching videos for a long time could be well evaluated by analyzing the VEOG signal.
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http://dx.doi.org/10.1016/j.cmpb.2021.106171DOI Listing
May 2021

Estrogen/ER in anti-tumor immunity regulation to tumor cell and tumor microenvironment.

Cancer Cell Int 2021 Jun 7;21(1):295. Epub 2021 Jun 7.

Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, #88 Jiefang Road, Hangzhou, 310009, Zhejiang, People's Republic of China.

As the essential sexual hormone, estrogen and its receptor has been proved to participate in the regulation of autoimmunity diseases and anti-tumor immunity. The adjustment of tumor immunity is related to the interaction between cancer cells, immune cells and tumor microenvironment, all of which is considered as the potential target in estrogen-induced immune system regulation. However, the specific mechanism of estrogen-induced immunity is poorly understood. Typically, estrogen causes the nuclear localization of estrogen/estrogen receptor complex and alternates the transcription pattern of target genes, leading to the reprogramming of tumor cells and differentiation of immune cells. However, the estrogen-induced non-canonical signal pathway activation is also crucial to the rapid function of estrogen, such as NF-κB, MAPK-ERK, and β-catenin pathway activation, which has not been totally illuminated. So, the investigation of estrogen modulatory mechanisms in these two manners is vital for the tumor immunity and can provide the potential for endocrine hormone targeted cancer immunotherapy. Here, this review summarized the estrogen-induced canonical and non-canonical signal transduction pathway and aimed to focus on the relationship among estrogen and cancer immunity as well as immune-related tumor microenvironment regulation. Results from these preclinical researches elucidated that the estrogen-target therapy has the application prospect of cancer immunotherapy, which requires the further translational research of these treatment strategies.
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http://dx.doi.org/10.1186/s12935-021-02003-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182917PMC
June 2021

3D IFPN: Improved Feature Pyramid Network for Automatic Segmentation of Gastric Tumor.

Front Oncol 2021 20;11:618496. Epub 2021 May 20.

School of Biomedical Engineering, Shenzhen University, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, Shenzhen, China.

Automatic segmentation of gastric tumor not only provides image-guided clinical diagnosis but also assists radiologists to read images and improve the diagnostic accuracy. However, due to the inhomogeneous intensity distribution of gastric tumors in CT scans, the ambiguous/missing boundaries, and the highly variable shapes of gastric tumors, it is quite challenging to develop an automatic solution. This study designs a novel 3D improved feature pyramidal network (3D IFPN) to automatically segment gastric tumors in computed tomography (CT) images. To meet the challenges of this extremely difficult task, the proposed 3D IFPN makes full use of the complementary information within the low and high layers of deep convolutional neural networks, which is equipped with three types of feature enhancement modules: 3D adaptive spatial feature fusion (ASFF) module, single-level feature refinement (SLFR) module, and multi-level feature refinement (MLFR) module. The 3D ASFF module adaptively suppresses the feature inconsistency in different levels and hence obtains the multi-level features with high feature invariance. Then, the SLFR module combines the adaptive features and previous multi-level features at each level to generate the multi-level refined features by skip connection and attention mechanism. The MLFR module adaptively recalibrates the channel-wise and spatial-wise responses by adding the attention operation, which improves the prediction capability of the network. Furthermore, a stage-wise deep supervision (SDS) mechanism and a hybrid loss function are also embedded to enhance the feature learning ability of the network. CT volumes dataset collected in three Chinese medical centers was used to evaluate the segmentation performance of the proposed 3D IFPN model. Experimental results indicate that our method outperforms state-of-the-art segmentation networks in gastric tumor segmentation. Moreover, to explore the generalization for other segmentation tasks, we also extend the proposed network to liver tumor segmentation in CT images of the MICCAI 2017 Liver Tumor Segmentation Challenge.
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http://dx.doi.org/10.3389/fonc.2021.618496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173118PMC
May 2021

Diagnostic performance of corrected FFR metrics to predict hemodynamically significant coronary artery stenosis.

Eur Radiol 2021 Jun 2. Epub 2021 Jun 2.

Department of Radiology, Xijing Hospital, Fourth Military Medical University, 127# Changle West Road, Xi'an, 710032, China.

Objectives: To determine the diagnostic performance of the fractional flow reserve (FFR) derived from coronary computed tomography angiography (CCTA) (FFR) difference across the lesion (ΔFFR) or the vessel (ΔFFR) and the gradient of FFR for the identification of hemodynamically significant coronary stenosis.

Methods: From June 2016 to December 2018, 73 patients suspected of having coronary artery disease who underwent CCTA followed invasive coronary angiography (ICA) within 1 month were retrospectively included. ΔFFR, ΔFFR, and FFR gradient were calculated. Performance characteristics of different corrected FFR metrics in detecting ischemic stenosis were analyzed. Impacts of coronary calcification and lesion length on the corrected FFR metrics were also analyzed.

Results: The diagnostic sensitivities, specificities, and accuracies of 94.4%, 88.7%, and 91.0% with ΔFFR, 57.1%, 72.3%, and 65.2% with ΔFFR, and 50.0%, 85.1%, and 68.5% with FFR gradient, respectively, were detected. There was higher specificity, accuracy, and area under the curve (AUC) for ΔFFR compared with CCTA (p < 0.05 for all). The specificity and AUC of FFR gradient and ΔFFR were significantly higher than CCTA (p < 0.05 for all). Coronary calcification showed no impact on corrected FFR metrics. ΔFFR for lesion length ratio (LLR) < 1/10 was significantly lower than that for LLR 1/10 to 3/10 and LLR > 3/10.

Conclusions: ΔFFR was significantly correlated with the hemodynamically significant coronary artery stenosis. ΔFFR had the potential to be immediately used in real-world practice to discriminate ischemic coronary artery stenosis.

Key Points: • The difference of FFR across the lesion or the vessel and the gradient of FFR was related to the hemodynamically significant coronary artery stenosis. • The difference of FFR across the lesion showed the best diagnostic performance in detecting the hemodynamically significant coronary artery stenosis. • Coronary calcification showed no impact on corrected FFR metrics, while lesion length related to the difference of FFR across the lesion.
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http://dx.doi.org/10.1007/s00330-021-08064-9DOI Listing
June 2021

Characterization of the Key Aroma-Active Compounds in Yongchuan Douchi (Fermented Soybean) by Application of the Sensomics Approach.

Molecules 2021 May 20;26(10). Epub 2021 May 20.

Beijing Key Laboratory of Flavor Chemistry, Beijing Technology and Business University, Beijing 100048, China.

Yongchuan douchi is a traditional fermented soya bean product which is popular in Chinese dishes due to its unique flavor. In this study, the key aroma-active compounds of Yongchuan douchi were characterized by the combined gas chromatography-olfactometry (GC-O) and gas chromatography-mass spectrometry (GC-MS) with sensory evaluation. In total, 49 aroma compounds were sniffed and identified, and 20 of them with high flavor dilution factors (FD) and odor activity values (OAVs) greater than one were screened by applied aroma extract dilution analysis (AEDA) and quantitated analysis. Finally, aroma recombination and omission experiments were performed and 10 aroma-active compounds were thought to have contributed significantly including 2,3-butanedione (butter, cheese), dimethyl trisulfide (garlic-like), acetic acid (pungent sour), acetylpyrazine (popcorn-like), 3-methylvaleric acid (sweaty), 4-methylvaleric acid (sweaty), 2-mehoxyphenol (smoky), maltol (caramel), γ-nonanolactone (coconut-like), eugenol (woody) and phenylacetic acid (flora). In addition, sensory evaluation showed that the flavor profile of Yongchuan douchi mainly consisted of sauce-like, sour, nutty, smoky, caramel and fruity notes.
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http://dx.doi.org/10.3390/molecules26103048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161213PMC
May 2021

Individual and Combined Effects of Booting and Flowering High-Temperature Stress on Rice Biomass Accumulation.

Plants (Basel) 2021 May 20;10(5). Epub 2021 May 20.

National Engineering and Technology Center for Information Agriculture, Nanjing Agricultural University, Nanjing 210095, China.

Extreme temperature events as a consequence of global climate change result in a significant decline in rice production. A two-year phytotron experiment was conducted using three temperature levels and two heating durations to compare the effects of heat stress at booting, flowering, and combined (booting + flowering) stages on the production of photosynthates and yield formation. The results showed that high temperature had a significant negative effect on mean net assimilation rate (MNAR), harvest index (HI), and grain yield per plant (YPP), and a significant positive effect under treatment T on mean leaf area index (MLAI) and duration of photosynthesis (DOP), and no significant effect on biomass per plant at maturity (BPP), except at the flowering stage. Negative linear relationships between heat degree days (HDD) and MNAR, HI, and YPP were observed. Conversely, HDD showed positive linear relationships with MLAI and DOP. In addition, BPP also showed a positive relationship with HDD, except at flowering, for both cultivars and Wuyunjing-24 at combined stages. The variation of YPP in both cultivars was mainly attributed to HI compared to BPP. However, for biomass, from the first day of high-temperature treatment to maturity (BPP), the main change was caused by MNAR followed by DOP and then MLAI. The projected alleviation effects of multiple heat stress at combined stages compared to single-stage heat stress would help to understand and evaluate rice yield formation and screening of heat-tolerant rice cultivars under current scenarios of high temperature during the rice-growing season.
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http://dx.doi.org/10.3390/plants10051021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160744PMC
May 2021

A novel Apigenin derivative suppresses renal cell carcinoma via directly inhibiting wild-type and mutant MET.

Biochem Pharmacol 2021 May 24;190:114620. Epub 2021 May 24.

Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China. Electronic address:

MET, the receptor of hepatocyte growth factor (HGF), is a driving factor in renal cell carcinoma (RCC) and also a proven drug target for cancer treatment. To improve the activity and to investigate the mechanisms of action of Apigenin (APG), novel derivatives of APG with improved properties were synthesized and their activities against Caki-1 human renal cancer cell line were evaluated. It was found that compound 15e exhibited excellent potency against the growth of multiple RCC cell lines including Caki-1, Caki-2 and ACHN and is superior to APG and Crizotinib. Subsequent investigations demonstrated that compound 15e can inhibit Caki-1 cell proliferation, migration and invasion. Mechanistically, 15e directly targeted the MET kinase domain, decreased its auto-phosphorylation at Y1234/Y1235 and inhibited its kinase activity and downstream signaling. Importantly, 15e had inhibitory activity against mutant MET V1238I and Y1248H which were resistant to approved MET inhibitors Cabozantinib, Crizotinib or Capmatinib. In vivo tumor graft study confirmed that 15e repressed RCC growth through inhibition of MET activation. These results indicate that compound 15e has the potential to be developed as a treatment for RCC, and especially against drug-resistant MET mutations.
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http://dx.doi.org/10.1016/j.bcp.2021.114620DOI Listing
May 2021

Influence of socioeconomic development on river water quality: a case study of two river basins in China.

Environ Sci Pollut Res Int 2021 May 26. Epub 2021 May 26.

State Key Laboratory of Hydraulics and Mountain River Engineering, Sichuan University, Chengdu, 610065, China.

Social and economic development processes require large amounts of natural resources and in some cases seriously deteriorate river water quality. Since the reform and expansion era began, China has vigorously pursued socioeconomic development but neglected environmental protection. However, in recent years, improvements in environmental awareness and the implementation of environmental protection measures have led to a balanced relationship between economic development and the environment. In this study, the Yangtze River Basin and the Yellow River Basin were selected as research areas. We used a combination of canonical correlation analysis (CCA) and a distance-based influence assessment method to quantitatively assess the influence of socioeconomic development on river water quality. The results revealed a strong correlation between socioeconomic development and river water quality. The degree of influence of socioeconomic development on water quality varied not only temporally but also spatially due to differences in socioeconomic development and hydrometeorology in the two basins in North and South China. The average degree of influence in the Yangtze River Basin was between 0.22 and 0.27, and that in the Yellow River Basin was between 0.2 and 0.36. Moreover, the degree of influence in the Yangtze River Basin in the wet season was greater than that in the dry season, whereas the opposite pattern was observed in the Yellow River Basin. The degree of influence in both basins gradually declined after 2011, indicating that the coupling and coordination between socioeconomic development and environmental protection have continuously improved and that the water quality has gradually improved. By analysing the influences of various socioeconomic indicators on water quality, we found that the main factors that influence water quality are per capita GDP and urbanization rate in the Yangtze River Basin and urbanization rate in the Yellow River Basin. The results provide a basis for future sustainable development in the Yangtze River Basin and the Yellow River Basin.
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http://dx.doi.org/10.1007/s11356-021-14338-yDOI Listing
May 2021

Two new sesquiterpenes from and inhibitory mechanism on murine haemangioendothelioma (EOMA) cell lines.

Nat Prod Res 2021 May 27:1-7. Epub 2021 May 27.

Department of Neurology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, P. R. China.

is a kind of medicinal and edible plant which is widely distributed. In this study, two new sesquiterpenes and along with three known compounds - were isolated from by the methods of column chromatography. The structures of the two novel compounds were constructed on the basis of HR-MS and NMR spectra. Cytotoxicities of and were assayed on EOMA cell lines and exhibited no inhibitory effect while elicited moderate inhibitory effect on EOMA cells with IC value of 26.5 μM. Western Blot assay indicated that could suppress EOMA cell proliferation by inducing apoptosis through Bax/caspase-3 pathway.
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http://dx.doi.org/10.1080/14786419.2021.1931186DOI Listing
May 2021

Long non-coding RNA H19 as a diagnostic marker in peripheral blood of patients with sepsis.

Am J Transl Res 2021 15;13(4):2923-2930. Epub 2021 Apr 15.

Department of Clinical Laboratory, Weihai Hosptial of Traditional Chinese Medicine Weihai 264200, Shandong, China.

Objective: To evaluate the diagnostic and prognostic value of circulating long non-coding RNA H19 (H19) in sepsis.

Methods: A total of 104 septic patients admitted to our hospital from June 2018 to April 2019 were enrolled as the disease group, and another 92 healthy individuals were selected as the control group. The relative expression of H19 in peripheral blood was quantified by quantitative real-time polymerase chain reaction, and the diagnostic value in sepsis was assessed by receiver operating characteristic curve analysis. Pearson correlation coefficient was used to analyze the correlation between H19 and other inflammatory markers.

Results: Compared with the control group, the expression of peripheral blood H19 in the disease group was significantly down-regulated. The area under the curve (AUC) of H19 for diagnosing sepsis was 0.849. The expression of H19 in the survival group was significantly up-regulated compared with that in the death group, and the AUC in the survival group was 0.865. The relative expression of H19 was negatively correlated with PCT, CRP, IL-6, TNF-α, CK-MB, and cTnI. Multivariate logistic regression showed that patients with high lactic acid, coagulation dysfunction, high levels of PCT, CRP, IL-6, TNF-α, CK-MB, and cTnI, but low H19 expression had an increased risk of sepsis.

Conclusion: Peripheral blood H19 may be used for early diagnosis, clinical assessment, and prognosis of sepsis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129366PMC
April 2021

Glomerulopathic Light Chain-Mesangial Cell Interactions: Sortilin-Related Receptor (SORL1) and Signaling.

Kidney Int Rep 2021 May 13;6(5):1379-1396. Epub 2021 Mar 13.

Department of Pathology, College of Medicine, University of South Alabama, Mobile, Alabama, USA.

Introduction: Deciphering the intricacies of the interactions of glomerulopathic Ig light chains with mesangial cells is key to delineate signaling events responsible for the mesangial pathologic alterations that ensue.

Methods: Human mesangial cells, caveolin 1 (CAV1), wild type (WT) ,and knockout (KO), were incubated with glomerulopathic light chains purified from the urine of patients with light chain-associated (AL) amyloidosis or light chain deposition disease. Associated signaling events induced by surface interactions of glomerulopathic light chains with caveolins and other membrane proteins, as well as the effect of epigallocatechin-3-gallate (EGCG) on the capacity of mesangial cells to intracellularly process AL light chains were investigated using a variety of techniques, including chemical crosslinking with mass spectroscopy, immunofluorescence, and ultrastructural immunolabeling.

Results: Crosslinking experiments provide evidence suggesting that sortilin-related receptor (SORL1), a transmembrane sorting receptor that regulates cellular trafficking of proteins, is a component of the receptor on mesangial cells for glomerulopathic light chains. Colocalization of glomerulopathic light chains with SORL1 in caveolae and also in lysosomes when light chain internalization occurred, was documented using double immunofluorescence and immunogold labeling ultrastructural techniques. It was found that EGCG directly blocks c-Fos cytoplasmic to nuclei signal translocation after interactions of AL light chains with mesangial cells, resulting in a decrease in amyloid formation.

Conclusion: Our findings document for the first time a role for SORL1 linked to glomerular pathology and signaling events that take place when certain monoclonal light chains interact with mesangial cells. This finding may lead to novel therapies for treating renal injury caused by glomerulopathic light chains.
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http://dx.doi.org/10.1016/j.ekir.2021.02.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116754PMC
May 2021

[Observation of acupoint application of gel plaster on insomnia].

Zhongguo Zhen Jiu 2021 May;41(5):505-9

Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing 100700, China; Department of TCM, Tsinghua University Hospital, Beijing 100084.

Objective: To observe the effect of acupoint application of gel plaster on quality of sleep and life in patients with insomnia.

Methods: A total of 63 patients with insomnia were randomized into a gel plaster group (32 cases, 1 case dropped off) and a placebo plaster group (31 cases). Acupoint application of gel plaster was applied at Yintang (GV 29) and Yongquan (KI 1) in the gel plaster group, placebo plaster was applied at the same acupoints in the placebo plaster group. The treatment was given from bedtime to early moming of the next day, 5 days were as one course, with 2-day interval, totally 4 courses were required in the both groups. Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS) and Flinders fatigue scale were used to evaluate the sleep quality and fatigue level of the patients in the both groups before and after treatment and at 2 weeks of follow-up. The variations of insomnia TCM syndrome score and the 36-item short-form health survey (SF-36) score before and after treatment were observed.

Results: Compared before treatment, the scores of PSQI, ESS and FFS after treatment and at follow-up were decreased in the both groups (<0.01), and the variations of PSQI total scores and ESS scores in the gel plaster group were larger than those in the placebo plaster group (<0.05). Compared before treatment, the insomnia TCM syndrome scores were decreased (<0.01), the scores of physiological function, physiological role, general health, role emotion, mental health of SF-36 were improved after treatment in the both groups (<0.05), and the social function score after treatment in the gel plaster group was superior to that in the placebo plaster group (<0.05).

Conclusion: Acupoint application of gel plaster can effectively improve the quality of sleep and life in patients with insomnia.
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http://dx.doi.org/10.13703/j.0255-2930.20200423-0005DOI Listing
May 2021

Modeling impacts of climate change on the potential distribution of six endemic baobab species in Madagascar.

Plant Divers 2021 Apr 18;43(2):117-124. Epub 2020 Jul 18.

Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan, Hubei, 430074, PR China.

Madagascar, a globally renowned biodiversity hotspot characterized by high rates of endemism, is one of the few remaining refugia for many plants and animal species. However, global climate change has greatly affected the natural ecosystem and endemic species living in Madagascar, and will likely continue to influence species distribution in the future. Madagascar is home to six endemic baobab ( spp., Bombacoideae [Malvaceae]) species (, , , , , ), which are remarkable and endangered plants. This study aimed to model the current distribution of suitable habitat for each baobab species endemic to Madagascar and determine the effect that climate change will have on suitable baobab habitat by the years 2050 and 2070. The distribution was modeled using MaxEnt based on locality information of 245 occurrence sites of six species from both online database and our own field work. A total of seven climatic variables were used for the modeling process. The present distribution of all six Madagascar's baobabs was largely influenced by temperature-related factors. Although both expansion and contraction of suitable habitat are predicted for all species, loss of original suitable habitat is predicted to be extensive. For the most widespread Madagascar baobab, , more than 40% of its original habitat is predicted to be lost because of climate change. Based on these findings, we recommend that areas predicted to contract in response to climate change should be designated key protection regions for baobab conservation.
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http://dx.doi.org/10.1016/j.pld.2020.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103343PMC
April 2021

L-Proline: An Effective Agent for Frozen and Post-thawed Donkey Semen Storage.

J Equine Vet Sci 2021 Jun 3;101:103393. Epub 2021 Feb 3.

National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing, China. Electronic address:

The aim of this study was to evaluate the effects of L-proline on the extender quality of frozen and post-thawed jackass semen. Jackass (n = 6) semen samples were collected and cryopreserved in gradient concentrations (0-80 mM) of L-proline in extenders; post-thawed semen samples were cultured in L-proline medium for 10 hours at 37°C. For cryopreservation experiment I, the motile parameters, mitochondrial membrane potential (MMP), and plasma membrane, acrosome, and chromatin structure integrities of post-thawed semen were assessed. For culture experiment II, additional ROS contents were analyzed after incubation. For the fertility trial, jennies (n = 135) were divided into group I (30 mM L-proline in cryopreservation extender), group II (40 mM L-proline in culture medium), and the control. Pregnancy was diagnosed using an ultrasound scanner 30 days after ovulation. The results of experiment I showed that, motile parameters and acrosome and chromatin structure integrities of groups I and 40 mM were significantly higher than the control (P < .05). MMP of group I was significantly higher than the control and 40 mM groups (P < .05). In experiment II, after 4 hours of incubation, motile parameters, MMP, and DNA integrity in group II were significantly higher than the control (P < .05). Additionally, 40 and 80 mM L-proline in culture medium significantly reduced ROS accumulation after 4 and 10 hours of incubation (P < .05). Pregnancy rates of the control and groups I and II were 28.85%, 40%, and 36.84%, respectively. In conclusion, the extenders containing 30 to 40 mM L-proline improved both qualities of frozen and post-thawed semen, and it will be a beneficial agent for donkey frozen spermatozoa or post-thawed semen storage.
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http://dx.doi.org/10.1016/j.jevs.2021.103393DOI Listing
June 2021

Gut microbiota mediated the protective effects of tuna oil on collagen-induced arthritis in mice.

Food Funct 2021 Jun;12(12):5387-5398

State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, China. and School of Marine Science, Ningbo University, Ningbo, China.

Rheumatoid arthritis is emerging as a chronic autoimmune disease worldwide. In this study, the beneficial effects of tuna oil (TO) on collagen-induced arthritis (CIA) mice were investigated. Dietary administration of TO relieved arthritis severity and joint bone erosion, and ameliorated systemic inflammation. Furthermore, TO treatments regulated the phosphorylation of nuclear factor-kappa B (NF-κB) and Wnt1/β-catenin signaling pathways in the joint, enhanced osteoblastogenesis biomarkers and suppressed osteoclastogenesis biomarkers, and subsequently re-balanced bone remodeling. Moreover, the impaired intestinal epithelial barrier was repaired after TO treatments, along with gut microbiota modulation. By employing fecal microbiota transplantation, we clarified that the beneficial effects of TO in CIA alleviation were mediated by the modulated gut microbiota. These results indicated that gut microbiota mediated the protective effects of tuna oil on collagen-induced arthritis in mice.
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http://dx.doi.org/10.1039/d1fo00709bDOI Listing
June 2021

Absolute Neutrophil Count in the Peripheral Blood Predicts Prognosis in Lung Cancer Patients Treated with Anlotinib.

Cancer Manag Res 2021 3;13:3619-3627. Epub 2021 May 3.

Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

Purpose: Anlotinib is a multi-targeted tyrosine kinase inhibitor that inhibits tumor angiogenesis and cell proliferation. It is widely used as a third-line therapy for lung cancer. However, reliable prognostic biomarkers for predicting the efficacy of anlotinib are lacking. We conducted a retrospective study to investigate the prognostic value of serological inflammatory biomarkers in anlotinib treatment.

Patients And Methods: Patients with advanced lung cancer treated with anlotinib monotherapy were enrolled. Cox regression was conducted to analyze the significant factors related to progression-free survival (PFS) and overall survival (OS). The objective response rate (ORR) was compared based on the median cut-off value of the significant inflammation index. Meanwhile, we created survival curves to compare the two groups and performed receiver operating characteristic curve analysis to assess the predictive ability of the inflammation index.

Results: Among a total of 71 patients, the median PFS was 5.5 months and the median OS was 9.5 months. The ORR and disease control rate were 16.9% and 84.5%, respectively. According to univariate and multivariate analyses, absolute neutrophil count (ANC) was the only indicator associated with both PFS (hazard ratio [HR] =1.095, 95% confidence interval [CI] 1.030-1.163, P=0.003) and OS (HR=1.057, 95% CI 1.003-1.113, P=0.037). In the group with ANC ≥4.58, the ORR was relatively lower (8.1% vs 26.5%, P=0.057), but not statistically significant; PFS and OS were relatively shorter (median PFS 5.0 [95% CI 4.4-9.6] vs 7.0 months [95% CI 4.4-5.7], P=0.024 and median OS 7.3 [95% CI 4.7-10.0] vs 17.6 months [95% CI 12.3-22.9], P < 0.001). ANC had a relatively high discriminatory ability to predict 10-month survival, with an area under the curve of 0.729, sensitivity of 82.5%, and specificity of 67.7%.

Conclusion: Elevated pre-treatment ANC was associated with a poor prognosis. Patients with lower peripheral blood levels of ANC might benefit from anlotinib.
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http://dx.doi.org/10.2147/CMAR.S307368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106457PMC
May 2021

Voiding and Storage Domain-Specific Symptom Score Outcomes After Prostate Artery Embolization for Lower Urinary Tract Symptoms and Urinary Retention.

Urology 2021 May 4. Epub 2021 May 4.

Yale University School of Medicine, New Haven, CT. Electronic address:

Objective: To characterize voiding and storage symptom domain-specific outcomes after prostate artery embolization (PAE) to treat lower urinary tract symptoms (LUTS) or urinary retention caused by benign prostatic hyperplasia (BPH).

Methods: Two hundred forty patients (age = 74.5 ± 8.6 years) underwent PAE between May 2013 and March 2020 at a single center for LUTS (n = 161) or urinary retention (n = 79). Total International Prostate Symptom Score (IPSS-t), voiding domain score (IPSS-v), storage domain score (IPSS-s), and Quality of Life score (QoL) were obtained pre-PAE for LUTS patients (IPSS-t = 21.7 ± 6.2, IPSS-v = 11.9 ± 4.3, IPSS-s = 9.6 ± 3.1, QoL = 4.5 ± 1.2), and post-PAE through 36 months (mean = 22.9 ± 15.2 months) for LUTS and retention patients. Mean relative changes in IPSS-t, IPSS-v, IPSS-s, and QoL were calculated for LUTS patients. Mean voiding or storage component scores were calculated for retention patients.

Results: For evaluable LUTS patients (n = 147), IPSS-t showed sustained substantial improvement through 36 months (6.3 ± 4.2-8.6 ± 7.6), as did QoL (1.1 ± 1.1-1.8 ± 1.5). One month after PAE, improvements in IPSS-v (69% ± 29%) were greater than in IPSS-s (46% ± 33%; P < .000001), and remained so through 36 months (68% ± 31% vs 53% ± 28%, P = .004). Among evaluable retention patients (n = 75), 84% passed voiding trials. Both IPSS-t (6.0 ± 3.9-8.2 ± 6.7) and QoL (0.9 ± 1.2-1.5 ± 1.6) remained low through 36 months. One month after PAE, mean IPSS-v component score (0.9 ± 1.3) was lower than mean IPSS-s component score (1.7 ± 1.4; P = .003) and remained so through 24 months (0.9 ± 1.2 vs 1.3 ± 1.1, P = .02), with similar trend at 36 months (0.7 ± 1.1 vs 1.1 ± 1.1, P = .07).

Conclusions: PAE effectively treated BPH-related LUTS and retention. IPSS-v improved more than IPSS-s in LUTS patients, and remained lower in LUTS and retention patients through 36 months.
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http://dx.doi.org/10.1016/j.urology.2021.02.046DOI Listing
May 2021

The role of the potential field on occurrence and flow of octane in quartz nanopores.

Phys Chem Chem Phys 2021 May;23(19):11507-11514

College of Science, China University of Petroleum (East China), Qingdao 266580, P. R. China.

Occurrence and flow of hydrocarbons in nanopores are two important issues in the effective exploitation of shale oil reservoirs. In this study, molecular dynamics simulations are employed to investigate the mechanisms about occurrence and flow of octane in slit-shaped quartz nanopores. We show that the occurrence state of octane and, therefore, its flow behavior are profoundly affected by the potential field from quartz walls and adsorption layers if the nanopore width w becomes less than 50 Å. Two main adsorption layers are always formed, adjacent to the walls and independent of w, due to two potential wells generated by the attractive potentials of the walls. Each pair of symmetrical adsorption layers, each of which can be considered as a solid-like surface, forms a confined environment similar to a nano-slit. The attractive potentials from them are found to be the cause for the formation of the adsorption layers between them. The obvious bulk phase of octane is formed in the pore of w = 50 Å due to the wide zero potential barrier induced by the innermost two adsorption layers. The nonlinear dependence of flow rate on pressure gradient shows that Darcy's law fails to describe the flow in the nanopore. The non-Darcy behavior mainly arises from adsorption effects from the walls and the adsorption layers, slippage between octane and walls and between adjacent two adsorption layers, and the molecular exchange between adsorption layers. A modified microscopic model is established to predict the dependence of flow rate on potential field, pressure gradient and w, which is in a good agreement with our simulation results and verified by the dodecane flow through the nanopore. Our work can be of great importance for revealing the mechanisms of occurrence and transport and guiding the estimation and exploitation of shale oil resources.
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http://dx.doi.org/10.1039/d1cp00891aDOI Listing
May 2021

Inspecting the nonbonding and antibonding orbitals in a surface-supported metal-organic framework.

Chem Commun (Camb) 2021 May;57(37):4580-4583

Beijing National Laboratory for Condensed Matter Physics and Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China. and Songshan Lake Materials Laboratory, Dongguan, Guangdong 523808, China.

By using low-temperature scanning tunnelling microscopy and spectroscopy, ligand field theory and density functional theory calculations, we revealed the spatial distribution and energy separation of the nonbonding and antibonding orbitals associated with the top-Ni atoms in a surface-supported Ni-TPyP metal-organic framework with dinuclear coordination centres.
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http://dx.doi.org/10.1039/d1cc00506eDOI Listing
May 2021

Potential role for EZH2 in promotion of asthma through suppression of miR-34b transcription by inhibition of FOXO3.

Lab Invest 2021 May 3. Epub 2021 May 3.

Pediatric Intensive Care Unit, Linyi People's Hospital, Linyi, P. R. China.

Highly expressed enhancer of zeste homolog 2 (EZH2) has been associated with many kinds of cancers and other diseases, while its functional role in asthma is largely unknown. In our study, we investigated the molecular mechanism of EZH2 in the development of asthma. An ovalbumin-induced mouse asthma model was established, followed by injection of short hairpin RNA (sh)-EZH2, overexpression-B-cell translocation gene 2 (oe-BTG2), microRNA (miR)-34b agomir as well as their corresponding controls. Next, primary bronchial epithelial cells were isolated and cultured, followed by treatment of oe-FOXO3, miR-34b inhibitor, sh-EZH2, oe-BTG2, and corresponding controls. The effects of EZH2 on inflammation were evaluated by determining levels of inflammatory factors interleukin (IL)-4, IL-5, IL-13, IL-17, and protein levels of transforming growth factor β, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinases-1. The interactions between EZH2 and forkhead box O3 (FOXO3), between FOXO3 and miR-34b promoter, and between miR-34b and BTG2 were analyzed by conducting dual-luciferase reporter and chromatin immunoprecipitation assays. Notably, EZH2 and BTG2 were significantly overexpressed, while FOXO3 and miR-34b were obviously underexpressed in asthma. EZH2 silencing led to inhibited inflammation though upregulation of FOXO3, which could bind to the miR-34b promoter and facilitate its expression. In turn, miR-34b reduced BTG2 expression by targeting its 3'untranslated region. Our study provides evidence that EZH2 promotes asthma progression by regulating the FOXO3-miR-34b-BTG2 axis.
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http://dx.doi.org/10.1038/s41374-021-00585-7DOI Listing
May 2021

Differential metabolic network construction for personalized medicine: Study of type 2 diabetes mellitus patients' response to gliclazide-modified-release-treated.

J Biomed Inform 2021 Jun 29;118:103796. Epub 2021 Apr 29.

Department of Respiratory Medicine, the Second Hospital of Dalian Medical University, Dalian, 116023, China. Electronic address:

Individual variation in genetic and environmental factors can cause the differences in metabolic phenotypes, which may have an effect on drug responses of patients. Deep exploration of patients' responses to therapeutic agents is a crucial and urgent event in the personalized treatment study. Using machine learning methods for the discovery of suitability evaluation biomarkers can provide deep insight into the mechanism of disease therapy and facilitate the development of personalized medicine. To find important metabolic network signals for the prediction of patients' drug responses, a novel method referred to as differential metabolic network construction (DMNC) was proposed. In DMNC, concentration changes in metabolite ratios between different pathological states are measured to construct differential metabolic networks, which can be used to advance clinical decision-making. In this study, DMNC was applied to characterize type 2 diabetes mellitus (T2DM) patients' responses against gliclazide modified-release (MR) therapy. Two T2DM metabolomics datasets from different batches of subjects treated by gliclazide MR were analyzed in depth. A network biomarker was defined to assess the patients' suitability for gliclazide MR. It can be effective in the prediction of significant responders from nonsignificant responders, achieving area under the curve values of 0.893 and 1.000 for the discovery and validation sets, respectively. Compared with the metabolites selected by the other methods, the network biomarker selected by DMNC was more stable and precise to reflect the metabolic responses in patients to gliclazide MR therapy, thereby contributing for the personalized medicine of T2DM patients. The better performance of DMNC validated its potential for the identification of network biomarkers to characterize the responses against therapeutic treatments and provide valuable information for personalized medicine.
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http://dx.doi.org/10.1016/j.jbi.2021.103796DOI Listing
June 2021

Integrative transcriptomic analysis of developing hematopoietic stem cells in human and mouse at single-cell resolution.

Biochem Biophys Res Commun 2021 Jun 27;558:161-167. Epub 2021 Apr 27.

Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, Guangdong, 510632, China. Electronic address:

Current understanding of hematopoietic stem cell (HSC) development comes from mouse models is considered to be evolutionarily conserved in human. However, the cross-species comparison of the transcriptomic profiles of developmental HSCs at single-cell level is still lacking. Here, we performed integrative transcriptomic analysis of a series of key cell populations during HSC development in human and mouse, including HSC-primed hemogenic endothelial cells and pre-HSCs in mid-gestational aorta-gonad-mesonephros (AGM) region, and mature HSCs in fetal liver and adult bone marrow. We demonstrated the general similarity of transcriptomic characteristics between corresponding cell populations of the two species. Of note, one of the previously transcriptomically defined hematopoietic stem progenitor cell (HSPC) populations with certain arterial characteristics in AGM region of human embryos showed close transcriptomic similarity to pre-HSCs in mouse embryos. On the other hand, the other two HSPC populations in human AGM region displayed molecular similarity with fetal liver HSPCs, suggesting the maturation in AGM before HSCs colonizing the fetal liver in human, which was different to that in mouse. Finally, we re-clustered cells based on the integrated dataset and illustrated the evolutionarily conserved molecular signatures of major cell populations. Our results revealed transcriptomic conservation of critical cell populations and molecular characteristics during HSC development between human and mouse, providing a resource and theoretic basis for future studies on mammalian HSC development and regeneration by using mouse models.
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http://dx.doi.org/10.1016/j.bbrc.2021.04.058DOI Listing
June 2021

Systemic Expression, Purification, and Initial Structural Characterization of Bacteriophage T4 Proteins Without Known Structure Homologs.

Front Microbiol 2021 13;12:674415. Epub 2021 Apr 13.

BioBank, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Bacteriophage T4 of is one of the most studied phages. Research into it has led to numerous contributions to phage biology and biochemistry. Coding about 300 gene products, this double-stranded DNA virus is the best-understood model in phage study and modern genomics and proteomics. Ranging from viral RNA polymerase, commonly found in phages, to thymidylate synthase, whose mRNA requires eukaryotic-like self-splicing, its gene products provide a pool of fine examples for phage research. However, there are still up to 130 gene products that remain poorly characterized despite being one of the most-studied model phages. With the recent advancement of cryo-electron microscopy, we have a glimpse of the virion and the structural proteins that present in the final assembly. Unfortunately, proteins participating in other stages of phage development are absent. Here, we report our systemic analysis on 22 of these structurally uncharacterized proteins, of which none has a known homologous structure due to the low sequence homology to published structures and does not belong to the category of viral structural protein. Using NMR spectroscopy and cryo-EM, we provided a set of preliminary structural information for some of these proteins including NMR backbone assignment for Cef. Our findings pave the way for structural determination for the phage proteins, whose sequences are mainly conserved among phages. While this work provides the foundation for structural determinations of proteins like Gp57B, Cef, Y04L, and Mrh, other studies would also benefit from the high yield expression of these proteins.
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http://dx.doi.org/10.3389/fmicb.2021.674415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076793PMC
April 2021

The Impact of Pine Wood Nematode Infection on the Host Fungal Community.

Microorganisms 2021 Apr 22;9(5). Epub 2021 Apr 22.

Collaborative Innovation Center of Sustainable Forestry in Southern China, College of Forestry, Nanjing Forestry University, Nanjing 210037, China.

Pine wilt disease (PWD), caused by pinewood nematode (PWN) , is globally one of the most destructive diseases of pine forests, especially in China. However, little is known about the effect of PWD on the host microbiome. In this study, the fungal community and functional structures in the needles, roots, and soil of and around naturally infected by PWN were investigated by using high-throughput sequencing coupled with the functional prediction (FUNGuild). The results showed that fungal richness, diversity, and evenness in the needles of diseased trees were significantly lower than those of healthy ones ( < 0.05), whereas no differences were found in the roots and soil. Principal coordinate analysis (PCoA) showed that the fungal community and functional structures significantly differed only in the needles of diseased and healthy trees, but not in the soil and roots. Functionally, the saprotrophs had a higher abundance in the needles of diseased trees, whereas symbiotrophs abundance was higher in the needles of healthy trees (linear discriminant analysis (LDA) > 2.0, < 0.05). These results indicated that PWN infection primarily affected the fungal community and functional structures in the needles of . , but not the roots and soil.
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http://dx.doi.org/10.3390/microorganisms9050896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146488PMC
April 2021

A Hypomorphic Mutant of PHD Domain Protein Male Meiocytes Death 1.

Genes (Basel) 2021 Apr 1;12(4). Epub 2021 Apr 1.

Unit HortiCell, Department of Plants and Crops, Faculty of Bioscience Engineering, Ghent University, 9000 Ghent, Belgium.

Meiosis drives reciprocal genetic exchanges and produces gametes with halved chromosome number, which is important for the genetic diversity, plant viability, and ploidy consistency of flowering plants. Alterations in chromosome dynamics and/or cytokinesis during meiosis may lead to meiotic restitution and the formation of unreduced microspores. In this study, we isolated an mutant (), which produces a small subpopulation of diploid or polyploid pollen grains. Cytological analysis revealed that produces dyads, triads, and monads indicative of male meiotic restitution. Both homologous chromosomes and sister chromatids in are separated normally, but chromosome condensation at metaphase I is slightly affected. The mutant displayed incomplete meiotic cytokinesis. Supportively, immunostaining of the microtubular cytoskeleton showed that the spindle organization at anaphase II and mini-phragmoplast formation at telophase II are aberrant. The causative mutation in was mapped to chromosome 1 at the chromatin regulator (/) locus. contains a C-to-T transition at the third exon of / at the genomic position 2168 bp from the start codon, which causes an amino acid change G618D that locates in the conserved PHD-finger domain of histone binding proteins. The F1 progenies of crossing with knockout / mutant exhibited same meiotic defects and similar meiotic restitution rate as . Taken together, we here report a hypomorphic / allele that typically shows defects in microtubule organization and cytokinesis.
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http://dx.doi.org/10.3390/genes12040516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066392PMC
April 2021

Isolation and modification of nano-scale cellulose from organosolv-treated birch through the synergistic activity of LPMO and endoglucanases.

Int J Biol Macromol 2021 Apr 24;183:101-109. Epub 2021 Apr 24.

Department of Materials and Environmental Chemistry, Stockholm University, 10691 Stockholm, Sweden. Electronic address:

Nanocellulose isolation from lignocellulose is a tedious and expensive process with high energy and harsh chemical requirements, primarily due to the recalcitrance of the substrate, which otherwise would have been cost-effective due to its abundance. Replacing the chemical steps with biocatalytic processes offers opportunities to solve this bottleneck to a certain extent due to the enzymes substrate specificity and mild reaction chemistry. In this work, we demonstrate the isolation of sulphate-free nanocellulose from organosolv pretreated birch biomass using different glycosyl-hydrolases, along with accessory oxidative enzymes including a lytic polysaccharide monooxygenase (LPMO). The suggested process produced colloidal nanocellulose suspensions (ζ-potential -19.4 mV) with particles of 7-20 nm diameter, high carboxylate content and improved thermostability (T = 301 °C, T = 337 °C). Nanocelluloses were subjected to post-modification using LPMOs of different regioselectivity. The sample from chemical route was the least favorable for LPMO to enhance the carboxylate content, while that from the C1-specific LPMO treatment showed the highest increase in carboxylate content.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.04.136DOI Listing
April 2021

Selectivity and Targeting of G-Quadruplex Binders Activated by Adaptive Binding and Controlled by Chemical Kinetics.

Angew Chem Int Ed Engl 2021 Apr 25. Epub 2021 Apr 25.

MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, State Key Laboratory of Oncology in South China, Sun Yat-Sen University, No. 135, Xingang Xi Road, 510275, Guangzhou, China.

G-quadruplexes (G4s) are prevalent in oncogenes and are potential antitumor drug targets. However, binding selectivity of compounds to G4s still faces challenges. Herein, we report a platinum(II) complex (Pt1), whose affinity to G4-DNA is activated by adaptive binding and selectivity controlled by binding kinetics. The resolved structure of Pt1/VEGF-G4 (a promoter G4) shows that Pt1 matches 3'-G-tetrad of VEGF-G4 through Cl -dissociation and loop rearrangement of VEGF-G4. Binding rate constants are determined by coordination bond breakage/formation, correlating fully with affinities. The selective rate-determining binding step, Cl -dissociation upon G4-binding, is 2-3 orders of magnitude higher than dsDNA. Pt1 potently targets G4 in living cells, effectively represses VEGF expression, and inhibits vascular growth in zebrafish. We show adaptive G4-binding activation and controlled by kinetics, providing a complementary design principle for compounds targeting G4 or similar biomolecules.
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http://dx.doi.org/10.1002/anie.202104624DOI Listing
April 2021

OCT3/4 enhances tumor immune response by upregulating the TET1-dependent NRF2/MDM2 axis in bladder cancer.

Genomics 2021 Apr 22;113(4):2122-2133. Epub 2021 Apr 22.

Department of General Surgery, the Fourth Affiliated Hospital of China Medical University, Shenyang 110000, PR China. Electronic address:

This study aimed to investigate the function of OCT3/4 on tumor immune escape in bladder cancer. Initially, the expression of OCT3/4, TET1, NRF2 and MDM2 was quantified in tumor tissues and cells, followed by gain- or loss-of-function studies to define their roles in cell migration, invasion and apoptosis and tumorigenicity in nude mice. Bladder cancer presented with abundant expression levels of OCT3/4, TET1, NRF2 and MDM2. We found that OCT3/4 promoted TET1 expression via binding to its promoter and that TET1 recruited MLL protein to NRF2 promoter and upregulated its expression, while NRF2 enhanced MDM2 expression. Upregulated MDM2 accelerated tumor immune escape in bladder cancer in mice. OCT3/4 knockdown suppressed the cell migration and invasion while inducing apoptosis, and consequently prevented tumor growth and immune escape in mice. Collectively, OCT3/4 may promote the progression of tumor immune escape in bladder cancer through acting as a promoter of the TET1/NRF2/MDM2 axis.
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http://dx.doi.org/10.1016/j.ygeno.2021.04.033DOI Listing
April 2021