Publications by authors named "Haiyang Wang"

375 Publications

Determinant Factors and Regulatory Systems for Anthocyanin Biosynthesis in Rice Apiculi and Stigmas.

Rice (N Y) 2021 Apr 21;14(1):37. Epub 2021 Apr 21.

Institute of Crop Sciences, Chinese Academy of Agriculture Sciences/National Key Facility for Crop Gene Resources and Genetic Improvement, Beijing, 100081, China.

Anthocyanins cause purple, brown or red colors in various tissues of rice plants, but the specific determinant factors and regulatory systems for anthocyanin biosynthesis in almost all tissues remain largely unknown. In the present study, we mapped and isolated two complementary genes, OsC1 encoding a R2R3-MYB transcriptional factor and OsDFR encoding a dihydroflavonol 4-reductase, which are responsible for the purple coloration of apiculi and stigmas in indica cultivar Xieqingzao by the map-based cloning strategy. We also identified two tissue-specific pigmentation genes, OsPa for apiculi and OsPs for stigmas, by phylogenetic analysis of all anthocyanin biosynthesis-associated bHLH transcriptional factors in maize and rice, CRISPR/Cas9 knockout and transcriptional expression analysis. The OsC1, OsPa and OsPs proteins are all localized in the nucleus while the OsDFR protein is localized in the nucleus and cytoplasm, and the OsC1 and OsDFR genes are preferentially strongly expressed in both purple-colored tissues while the OsPa and OsPs genes are preferentially strongly expressed in apiculi and stigmas, respectively. OsC1 specifically interacts with OsPa or OsPs to activate OsDFR and other anthocyanin biosynthesis genes, resulting in purple-colored apiculi or stigmas. OsC1 itself does not produce color but can produce brown apiculi when functioning together with OsPa. Loss of function of OsDFR alone leads to brown apiculi and straw-white stigmas. Genotyping and phenotyping of a panel of 176 rice accessions revealed diverse genotypic combinations of OsC1, OsDFR, OsPa and OsPs that enable accurate prediction of their apiculus and stigma pigmentation phenotypes, thus validating the general applicability of the OsC1-OsDFR-OsPa and OsC1-OsDFR-OsPs models to natural populations. Our findings disclosed the biological functions of OsC1, OsPa and OsPs, and shed light on the specific regulatory systems of anthocyanin biosynthesis in apiculi and stigmas, a further step in understanding the regulatory network of anthocyanin biosynthesis in rice.
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http://dx.doi.org/10.1186/s12284-021-00480-1DOI Listing
April 2021

Acylation of Arenes with Aldehydes through Dual C-H Activations by Merging Photocatalysis and Palladium Catalysis.

Org Lett 2021 Apr 19. Epub 2021 Apr 19.

Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Provincial Center for Research & Development of Natural Products, School of Chemical Science and Technology, Yunnan University, Kunming 650091, China.

An acylation of arenes with aldehydes through dual C-H activations at room temperature is reported. The acylation was initiated by phenanthraquinone-catalyzed hydrogen atom transfer from aldehyde under visible light irradiation. The aldehyde-derived acyl radical merged with palladium-catalyzed activation of arenes to afford the cross coupling products.
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http://dx.doi.org/10.1021/acs.orglett.1c01184DOI Listing
April 2021

HOTAIRM1 Promotes Malignant Progression of Transformed Fibroblasts in Glioma Stem-Like Cells Remodeled Microenvironment Regulating miR-133b-3p/TGFβ Axis.

Front Oncol 2021 19;11:603128. Epub 2021 Mar 19.

Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Recent studies have reported that cancer associated fibroblasts (CAFs) and glioma stem-like cells (GSCs) played active roles in glioma progression in tumor microenvironment (TME). Long non-coding RNAs (lncRNAs) have been found to be closely associated with glioma development in recent years, however, their molecular regulatory mechanisms on CAFs in GSCs remodeled TME kept largely unelucidated. Our study found that GSCs could induce malignant transformation of fibroblasts (t-FBs) based on dual-color fluorescence tracing orthotopic model. Associated with poor prognosis, Lnc HOXA transcript antisense RNA, myeloid-specific 1 (HOTAIRM1) was highly expressed in high-grade gliomas and t-FBs. Depleting HOTAIRM1 inhibited the proliferation, invasion, migration, and even tumorigenicity of t-FB. Conversely, overexpression of HOTAIRM1 promoted malignancy phenotype of t-FB. Mechanistically, HOTAIRM1 directly bound with miR-133b-3p, and negatively regulated the latter. MiR-133b-3p partly decreased the promotion effect of HOTAIRM1 on t-FBs. Furthermore, transforming growth factor-β (TGFβ) was verified to be a direct target of miR-133b-3p. HOTAIRM1 can modulate TGFβ competing with miR-133b-3p. Collectively, HOTAIRM1/miR-133b-3p/TGFβ axis was involved in modulating t-FBs malignancy in TME remodeled by GSCs, which had the potential to serve as a target against gliomas.
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http://dx.doi.org/10.3389/fonc.2021.603128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017308PMC
March 2021

Proteomic Profiling of Lysine Acetylation Indicates Mitochondrial Dysfunction in the Hippocampus of Gut Microbiota-Absent Mice.

Front Mol Neurosci 2021 11;14:594332. Epub 2021 Mar 11.

The Ministry of Education, Key Laboratory of Laboratory Medical Diagnostics, The College of Laboratory Medicine, Chongqing Medical University, Chongqing, China.

Major depressive disorder (MDD) is a leading cause of disability around the world and contributes greatly to the global burden of disease. Mounting evidence suggests that gut microbiota dysbiosis may be involved in the pathophysiology of MDD through the microbiota-gut-brain axis. Recent research suggests that epigenetic modifications might relate to depression. However, our knowledge of the role of epigenetics in host-microbe interactions remains limited. In the present study, we used a combination of affinity enrichment and high-resolution liquid chromatography tandem mass spectrometry analysis to identify hippocampal acetylated proteins in germ-free and specific pathogen-free mice. In total, 986 lysine acetylation sites in 543 proteins were identified, of which 747 sites in 427 proteins were quantified. Motif analysis identified several conserved sequences surrounding the acetylation sites, including DKac, DKac, KacY, KacD, and DKac. Gene ontology annotations revealed that these differentially expressed acetylated proteins were involved in multiple biological functions and were mainly located in mitochondria. In addition, pathway enrichment analysis demonstrated that oxidative phosphorylation and the tricarboxylic acid cycle II (eukaryotic), both of which are exclusively localized to the mitochondria, were the primarily disturbed functions. Taken together, this study indicates that lysine acetylation alterations may play a pivotal role in mitochondrial dysfunction and may be a mechanism by which gut microbiota regulate brain function and behavioral phenotypes.
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http://dx.doi.org/10.3389/fnmol.2021.594332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991600PMC
March 2021

Prolonged chronic social defeat stress promotes less resilience and higher uniformity in depression-like behaviors in adult male mice.

Biochem Biophys Res Commun 2021 May 22;553:107-113. Epub 2021 Mar 22.

NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases & Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, 400016, Chongqing, China. Electronic address:

Chronic social defeat stress (CSDS) is widely applied to study of depression in rodents. 10-day CSDS was a most commonly employed paradigm but with high resilience ratio (∼30%), producing potential variation in depression-like behavioral symptoms. Whether prolonged period (21 days) of CSDS would promote less resilience and reduce behavioral variability remains unknown. We applied 10-day and 21-day CSDS paradigms to induce mouse model of depression and compared their resilience ratio and behavioral phenotypes. Mice under 21-day CSDS had significantly lower resilience ratio and greater changes in behavioral indicators relative to mice under 10-day CSDS. Behavioral indicators from 21-day CSDS paradigm had higher correlations and better prediction for susceptibility which indicating higher uniformity in behavioral phenotypes. Furthermore, a subset of behavioral indicators in 21-day CSDS had high prediction efficacy and should be first applied to screen susceptibility of CSDS. Thus, our study demonstrates that 21-day CSDS is a more robust paradigm inducing reliable depression-like behaviors relative to 10-day CSDS, and should be preferentially used in rodent studies of depression.
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http://dx.doi.org/10.1016/j.bbrc.2021.03.058DOI Listing
May 2021

Preparation of bioactive and antibacterial PMMA-based bone cement by modification with quaternary ammonium and alkoxysilane.

J Biomater Appl 2021 Mar 24:8853282211004413. Epub 2021 Mar 24.

Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Kitakyushu, Japan.

Bone cement based on poly(methyl methacrylate) (PMMA) powder and methyl methacrylate (MMA) liquid is a very popular biomaterial used for the fixation of artificial joints. However, there is a risk of this cement loosening from bone because of a lack of bone-bonding bioactivity. Apatite formation in the body environment is a prerequisite for cement bioactivity. Additionally, suppression of infection during implantation is required for bone cements to be successfully introduced into the human body. In this study, we modified PMMA cement with γ-methacryloxypropyltrimetoxysilane and calcium acetate to introduce bioactive properties and 2-(-butylamino)ethyl methacrylate (TBAEMA) to provide antibacterial properties. The long-term antibacterial activity is attributed to the copolymerization of TBAEMA and MMA. As the TBAEMA content increased, the setting time increased and the compressive strength decreased. After soaking in simulated body fluid, an apatite layer was detected within 7 days, irrespective of the TBAEMA content. The cement showed better antibacterial activity against Gram-negative than Gram-positive bacteria; however, of the Gram-positive bacteria investigated, was more susceptible than .
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http://dx.doi.org/10.1177/08853282211004413DOI Listing
March 2021

Stimulated Brillouin scattering in high-birefringence elliptical-core AsSe-PMMA microfibers.

Opt Lett 2021 Mar;46(5):945-948

In this Letter, we design and fabricate elliptical-core (ECORE) chalcogenide-polymethyl methacrylate (-PMMA) microfibers to explore the birefringence impact on stimulated Brillouin scattering. Numerical simulations based on the finite-element method and elastodynamic equation are utilized to calculate the phase and group birefringence and Brillouin gain spectra of the fundamental mode in three ECORE -PMMA microfibers at different core diameters. Experimentally measured and numerically calculated results show that as the core diameter of the minor axis of an ECORE microfiber with a ratio of 1.108 is reduced from 1.50 µm to 0.87 µm, a high group birefringence of ∼10 to ∼10 and a large Brillouin frequency shift difference of ∼6 to ∼30 are achieved, while the Brillouin gain spectra are broadened significantly from ∼70 to ∼140. The high-birefringence ECORE -PMMA microfiber is important for Brillouin sensing due to the tailorable high birefringence and ultrahigh nonlinearity.
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http://dx.doi.org/10.1364/OL.418137DOI Listing
March 2021

ZmSPL10/14/26 are required for epidermal hair cell fate specification on maize leaf.

New Phytol 2021 05 24;230(4):1533-1549. Epub 2021 Mar 24.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou, 510642, China.

The epidermal hair and stomata are two types of specialized structures on the surface of plant leaves. On mature maize leaves, stomatal complexes and three types of hairs are distributed in a stereotyped pattern on the adaxial epidermis. However, the spatiotemporal relationship between epidermal hair and stomata development and the regulatory mechanisms governing their formation in maize remain largely unknown. Here, we report that three homologous ZmSPL transcription factors, ZmSPL10, ZmSPL14 and ZmSPL26, act in concert to promote epidermal hair fate on maize leaf. Cytological analyses revealed that Zmspl10/14/26 triple mutants are completely glabrous, but possess ectopic stomatal files. Strikingly, the precursor cells for prickle and bicellular hairs are transdifferentiated into ectopic stomatal complexes in the Zmspl10/14/26 mutants. Molecular analyses demonstrated that ZmSPL10/14/26 bind directly to the promoter of a WUSCHEL-related homeobox gene, ZmWOX3A, and upregulate its expression in the hair precursor cells. Moreover, several auxin-related genes are downregulated in the Zmspl10/14/26 triple mutants. Our results suggest that ZmSPL10/14/26 play a key role in promoting epidermal hair fate on maize leaves, possibly through regulating ZmWOX3A and auxin-related gene expression, and that the fates of epidermal hairs and stomata are switchable.
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http://dx.doi.org/10.1111/nph.17293DOI Listing
May 2021

Nicardipine sensitizes temozolomide by inhibiting autophagy and promoting cell apoptosis in glioma stem cells.

Aging (Albany NY) 2021 02 17;13(5):6820-6831. Epub 2021 Feb 17.

Department of Neurosurgery, Second Affiliated Hospital of Soochow University, Suzhou, China.

Glioblastoma multiforme (GBM) is the most invasive malignant central nervous system tumor with poor prognosis. Nicardipine, a dihydropyridine calcium channel antagonist, has been used as an adjuvant to enhance sensitivity to chemotherapeutic drugs. However, whether glioma stem cells (GSCs) can be sensitized to chemotherapy via combined treatment with temozolomide (TMZ) and nicardipine is unclear. In this study, surgical specimen derived GSCs SU4 and SU5 were applied to explore the sensitization effect of nicardipine on temozolomide against GSCs, and further explore the relevant molecular mechanisms. Our results showed that nicardipine can enhance the toxic effect of temozolomide against GSCs, promote apoptosis of GSCs, and inhibit autophagy of GSCs. The relevant mechanisms were related to activation of mTOR, and selective inhibition of mTOR by rapamycin could weaken the sensitization of nicardipine to temozolomide, which suggest that nicardipine can be applied as an adjuvant to inhibit autophagy in GSCs, and enhance apoptosis-promoting effect of temozolomide in GSCs as well. Nicardipine can inhibit autophagy by activating expression of mTOR, thus play tumor inhibition roles both and . Repurposing of nicardipine can help to improving therapeutic effect of TMZ against GBM, which deserves further clinical investigations.
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http://dx.doi.org/10.18632/aging.202539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993688PMC
February 2021

Elucidating the dominant mechanisms in burn rate increase of thermite nanolaminates incorporating nanoparticle inclusions.

Nanotechnology 2021 Feb 16. Epub 2021 Feb 16.

LAAS-CNRS, Toulouse, Occitanie, FRANCE.

It was experimentally found that silica and gold particles can modify the combustion properties of nanothermites but the exact role of the thermal properties of these additives on the propagating combustion front relative to other potential contributions remains unknown. Gold and silica particles of different sizes and volume loadings were added into aluminum/copper oxide thermites. Their effects on the flame front dynamics were investigated experimentally using microscopic dynamic imaging techniques and theoretically via a reaction model coupling mass and heat diffusion processes. A detailed theoretical analysis of the local temperature and thermal gradients at the vicinity of these two additives shows that highly conductive inclusions do not accelerate the combustion front while poor conductive inclusions result in the distortion of the flame front (corrugation), and therefore produce high thermal gradients (up to 1010 K.m-1) at the inclusion/host material interface. This results in an overall slowing down of the combustion front. These theoretical findings contradict the experimental observations in which a net increase of the flame front velocity was found when Au and SiO2 particles are added into the thermite. This leads to the conclusion that the faster burn rate observed experimentally cannot be fully associated with thermal effects only, but rather on chemical (catalytic) and/or mechanical mechanisms: formation of highly-stressed zones around the inclusion promoting the reactant mixing. One additional experiment in which physical SiO2 particles were replaced by voids (filled with Ar during experiment) to cancel the potential mechanical effects while preserving the thermal inhomogeneity in the thermite structure confirms the hypothesis that instead of pure thermal conduction, it is the mechanical mechanisms dominating the propagation velocity in our particular Al/CuO multilayered films.
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http://dx.doi.org/10.1088/1361-6528/abe6c8DOI Listing
February 2021

A Simulated Dosimetric Study of Contribution to Radiotherapy Accuracy by Fractional Image Guidance Protocol of Halcyon System.

Front Oncol 2020 25;10:543147. Epub 2021 Jan 25.

Laboratory Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China.

Purpose: Frequency of conventional kV-image guidance is sometimes sacrificed to reduce concomitant risk, leaving deviations of unguided fractions unknown. MV-imaging and treatment dose can be collectively optimized on Halcyon, where fractional MVCBCT provides complete anatomic records for course-wide dose reconstruction. By retrospective dose accumulation, this work simulated the impact of imaging frequency on patient treatment dose on the platform of Halcyon.

Methods: Four hundred and sixteen MVCBCT image sets from 16 patients of various tumor sites treated with radiotherapy on Halcyon were retrospectively selected. After applying the image-guided couch shifts of the clinical records, deformable image registration was performed using Velocity software, to deform the planning CTs to the corresponding MVCBCTs, generating pseudo CTs representing the actual anatomies on the treatment day. Fractional treatment dose was reconstructed on pseudo CTs for accumulation, representing the actual patient dose (D). To simulate weekly image guidance, fractional dose was reconstructed and accumulated by incorporating 1 CBCT-guided corrections and 4 laser-guided setups of each week (D). Limited by partially imaged volumes and different organs-at-risk of various sites, only target dose-volume parameters were evaluated across all patients.

Results: GTV_D98%, CTV_D98%, PTV_D90%, PTV_D95%, PGTV_D90%, and PGTV_D95% were evaluated, where Dx% means the minimal dose received by x% volume. Pairwise comparisons were made between plan dose and D, D and D respectively. PGTV_D of accumulated D were significantly lower than those of accumulated D by up to 32.90% of prescription dose, suggesting that weekly-guidance may result in unacceptable under dose to the target. The broad distribution of fractional differences between D and D suggested unreliable patient positioning based on aligning surface markers to laser beams, as a popular approach broadly used on conventional Linac systems. Slight target under-dose was observed on daily reconstructed results compared with planned dose, which provided quantitative data to guide clinical decisions such as the necessity of adaptive radiotherapy.

Conclusion: Fractional image guided radiotherapy on Halcyon provides more reliable treatment accuracy than using sacrificed imaging frequency, which also provides complete anatomic records for deformable dose reconstruction supporting more informed clinical decisions.
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http://dx.doi.org/10.3389/fonc.2020.543147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871016PMC
January 2021

Chronic D-ribose and D-mannose overload induce depressive/anxiety-like behavior and spatial memory impairment in mice.

Transl Psychiatry 2021 Feb 2;11(1):90. Epub 2021 Feb 2.

Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China.

The effects of different forms of monosaccharides on the brain remain unclear, though neuropsychiatric disorders undergo changes in glucose metabolism. This study assessed cell viability responses to five commonly consumed monosaccharides-D-ribose (RIB), D-glucose, D-mannose (MAN), D-xylose and L-arabinose-in cultured neuro-2a cells. Markedly decreased cell viability was observed in cells treated with RIB and MAN. We then showed that high-dose administration of RIB induced depressive- and anxiety-like behavior as well as spatial memory impairment in mice, while high-dose administration of MAN induced anxiety-like behavior and spatial memory impairment only. Moreover, significant pathological changes were observed in the hippocampus of high-dose RIB-treated mice by hematoxylin-eosin staining. Association analysis of the metabolome and transcriptome suggested that the anxiety-like behavior and spatial memory impairment induced by RIB and MAN may be attributed to the changes in four metabolites and 81 genes in the hippocampus, which is involved in amino acid metabolism and serotonin transport. In addition, combined with previous genome-wide association studies on depression, a correlation was found between the levels of Tnni3k and Tbx1 in the hippocampus and RIB induced depressive-like behavior. Finally, metabolite-gene network, qRT-PCR and western blot analysis showed that the insulin-POMC-MEK-TCF7L2 and MAPK-CREB-GRIN2A-CaMKII signaling pathways were respectively associated with RIB and MAN induced depressive/anxiety-like behavior and spatial memory impairment. Our findings clarified our understanding of the biological mechanisms underlying RIB and MAN induced depressive/anxiety-like behavior and spatial memory impairment in mice and highlighted the deleterious effects of high-dose RIB and MAN as long-term energy sources.
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http://dx.doi.org/10.1038/s41398-020-01126-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854712PMC
February 2021

Overlap of burnout-depression symptoms among Chinese neurology graduate students in a national cross-sectional study.

BMC Med Educ 2021 Feb 2;21(1):83. Epub 2021 Feb 2.

School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, China.

Background: The overlap of burnout and depression is a phenomenon that can effectively reflect the psychological state of a group. However, whether burnout is a type of depression is still debated in current research. The high incidence of burnout and depressive symptoms among medical students indicates that it is urgent to provide appropriate health services for them. However, the proportion of burnout and depression in the overlapping symptoms experienced by medical students, and the characteristics of the relative influencing factors, remain unclear. Therefore, we addressed these issues for neurology graduate students in China.

Methods: Using data from a cross-sectional survey of Chinese neurology graduate students, a diagnostic model was established according to their burnout and/or depression symptoms. Burnout was assessed by using the Maslach Burnout Inventory. Depression symptoms were assessed with a two-item depression screening tool for primary care evaluation of mental disorders. Univariate analyses with chi-squared tests were conducted to assess associations between variables. Multinomial logistic regression models were used to analyze the effects of multiple factors on dependent variables. The factors included demographic information and three medical-study related problems.

Results: In total, 32.2% of surveyed students evidenced overlapping burnout and depression symptoms. Students with depressive symptoms tended to be included in the burnout students' category. In the regression model, being unmarried, having children, and career choice regret were related to students who had only burnout, while the students with overlapping symptoms were affected by more factors such as family income, the consideration of dropping out once.

Conclusions: The symptoms and related factors of burnout and depression among Chinese neurology postgraduates have obvious overlap and show a significant trend. The occurrence of depressive symptoms among medical students is closely related to whether they are burned out. Students with only burnout were common, but students with only depressive symptoms were uncommon. Finally, burnout may be a pre-depression state.
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http://dx.doi.org/10.1186/s12909-021-02511-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851928PMC
February 2021

Regulation of Gut Microbiota Disrupts the Glucocorticoid Receptor Pathway and Inflammation-related Pathways in the Mouse Hippocampus.

Exp Neurobiol 2021 Feb;30(1):59-72

NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.

An increasing number of studies have recently indicated the important effects of gut microbes on various functions of the central nervous system. However, the underlying mechanisms by which gut microbiota regulate brain functions and behavioral phenotypes remain largely unknown. We therefore used isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic analysis to obtain proteomic profiles of the hippocampus in germ-free (GF), colonized GF, and specific pathogen-free (SPF) mice. We then integrated the resulting proteomic data with previously reported mRNA microarray data, to further explore the effects of gut microbes on host brain functions. We identified that 61 proteins were upregulated and 242 proteins were downregulated in GF mice compared with SPF mice. Of these, 124 proteins were significantly restored following gut microbiota colonization. Bioinformatic analysis of these significant proteins indicated that the glucocorticoid receptor signaling pathway and inflammation-related pathways were the most enriched disrupted pathways. This study provides new insights into the pathological mechanisms of gut microbiota-regulated diseases.
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http://dx.doi.org/10.5607/en20055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926043PMC
February 2021

Alteration of lipids and amino acids in plasma distinguish schizophrenia patients from controls: A targeted metabolomics study.

Psychiatry Clin Neurosci 2021 Apr 5;75(4):138-144. Epub 2021 Feb 5.

NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Background: Schizophrenia (SCZ) is a serious psychiatric disorder. Metabolite disturbance is an important pathogenic factor in schizophrenic patients. In this study, we aim to identify plasma lipid and amino acid biomarkers for SCZ using targeted metabolomics.

Methods: Plasma from 76 SCZ patients and 50 matched controls were analyzed using the LC/MS-based multiple reaction monitoring (MRM) metabolomics approach. A total of 182 targeted metabolites, including 22 amino acids and 160 lipids or lipid-related metabolites were observed. We used binary logistic regression analysis to determine whether the lipid and amino acid biomarkers could discriminate SCZ patients from controls. The area under the curve (AUC) from receiver operation characteristic (ROC) curve analysis was conducted to evaluate the diagnostic performance of the biomarkers panel.

Results: We identified 19 significantly differentially expressed metabolites between the SCZ patients and the controls (false discovery rate < 0.05), including one amino acid and 18 lipids or lipid-related metabolites. The binary logistic regression-selected panel showed good diagnostic performance in the drug-naïve group (AUC = 0.936) and all SCZ patients (AUC = 0.948), especially in the drug-treated group (AUC = 0.963).

Conclusions: Plasma lipids and amino acids showed significant dysregulation in SCZ, which could effectively discriminate SCZ patients from controls. The LC/MS/MS-based approach provides reliable data for the objective diagnosis of SCZ.
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http://dx.doi.org/10.1111/pcn.13194DOI Listing
April 2021

Differential DNA Methylation Profiles in Patients with Temporal Lobe Epilepsy and Hippocampal Sclerosis ILAE Type I.

J Mol Neurosci 2021 Jan 5. Epub 2021 Jan 5.

Department of Neurosurgery of the First Affiliate Hospital, Harbin Medical University, Harbin, China.

Hippocampal sclerosis (HS) is one of the most prevalent pathological types of temporal lobe epilepsy (TLE), and it significantly affects patient prognoses. The methylation of DNA plays an important role in the development of epilepsy. However, few studies have focused on HS subtypes to determine DNA methylation profiles in TLE. This study aimed to determine the pathogenesis of TLE from an epigenetic perspective in patients with TLE-HS type I (TLE-HSTI) and TLE without HS (TLE-nHS) using whole-genome bisulfite sequencing (WGBS). We defined 1171 hypermethylated and 2537 hypomethylated regions and found 632 differentially methylated genes (DMG) in the promoter region that were primarily involved in the regulation of various aspects of epilepsy development. Twelve DMG overlapped with differentially expressed genes (DEG) in the promoter region, and RT-qPCR findings revealed significant overexpression of the SBNO2, CBX3, RASAL3, and TMBIM4 genes in TLE-HSTI. We present the first systematic analysis of methylation profiles of TLE-HSTI and TLE-nHS from an epigenetic perspective using WGBS. Overall, our preliminary data highlight the underlying mechanism of TLE-HSTI, providing a new perspective for guiding treatment of TLE.
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http://dx.doi.org/10.1007/s12031-020-01780-9DOI Listing
January 2021

Integrative single-cell transcriptome analysis reveals a subpopulation of fibroblasts associated with favorable prognosis of liver cancer patients.

Transl Oncol 2021 Jan 6;14(1):100981. Epub 2020 Dec 6.

Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing 100850, China; South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou 510005, China. Electronic address:

Single-cell transcriptome analysis has provided detailed insights into the ecosystem of liver cancer. However, the changes of the cellular and molecular components of liver tumors in comparison with normal livers have not been described at single-cell level. Here, we performed an integrative single-cell analysis of both normal livers and liver cancers. Principal component analysis was firstly performed to delineate the cell lineages in liver tissues. Differential gene expression within major cell types were then analyzed between tumor and normal samples, thus resolved the cell type-specific molecular alterations in liver cancer development. Moreover, a comparison between liver cancer derived versus normal liver derived cell components revealed that two subpopulations of fibroblasts were exclusively expanded in liver cancer tissues. By further defining subpopulation-specific gene signatures, characterizing their spatial distribution in tumor tissues and investigating their clinical significance, we found that the SPARCL1 positive fibroblasts, representing a group of tumor vessel associated fibroblasts, were related to reduced vascular invasion and prolonged survival of liver cancer patients. Through establishing an in-vitro endothelial-to-mesenchymal transition model, we verified the conversion of the fetal liver sinusoidal endothelial cells into the fibroblast-like cells, demonstrating a possible endothelial cell origination of the SPARCL1 positive fibroblasts. Our study provides new insights into the cell atlas alteration, especially the expanded fibroblasts in liver cancers.
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http://dx.doi.org/10.1016/j.tranon.2020.100981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719961PMC
January 2021

Silicon Nanoparticles for the Reactivity and Energetic Density Enhancement of Energetic-Biocidal Mesoparticle Composites.

ACS Appl Mater Interfaces 2021 Jan 29;13(1):458-467. Epub 2020 Dec 29.

University of California, Riverside, California 92521, United States.

Biocidal nanothermite composites show great potential in combating biological warfare threats because of their high-energy-release rates and rapid biocidal agent release. Despite their high reactivity and combustion performance, these composites suffer from low-energy density because of the voids formed due to inefficient packing of fuel and oxidizer particles. In this study, we explore the potential of plasma-synthesized ultrafine Si nanoparticles (nSi, ∼5 nm) as an energetic filler fuel to increase the energy density of Al/Ca(IO) energetic-biocidal composites by filling in the voids in the microstructure. Microscopic and elemental analyses show the partial filling of mesoparticle voids by nSi, resulting in an estimated energy density enhancement of ∼21%. In addition, constant-volume combustion cell results show that nSi addition leads to a ∼2-3-fold increase in reactivity and combustion performance, as compared to Al/Ca(IO) mesoparticles. Oxidation timescale analyses suggest that nSi addition can promote initiation due to faster oxygen transport through the oxide shell of Si nanoparticles. At nSi loadings higher than ∼8%, however, slower burning characteristics of nSi and sintering effects lead to an overall degradation of combustion behavior of the composites.
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http://dx.doi.org/10.1021/acsami.0c17159DOI Listing
January 2021

Light Regulation of Stomatal Development and Patterning: Shifting the Paradigm from to Grasses.

Plant Commun 2020 Mar 13;1(2):100030. Epub 2020 Feb 13.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou 510642, China.

The stomatal pores of plant leaves control gas exchange with the environment. Stomatal development is prevised regulated by both internal genetic programs and environmental cues. Among various environmental factors, light regulation of stomata formation has been extensively studied in . In this review, we summarize recent advances in the genetic control of stomata development and its regulation by light. We also present a comparative analysis of the conserved and diverged stomatal regulatory networks between and cereal grasses. Lastly, we provide our perspectives on manipulation of the stomata density on plant leaves for the purpose of breeding crops that are better adapted to the adverse environment and high-density planting conditions.
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http://dx.doi.org/10.1016/j.xplc.2020.100030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747992PMC
March 2020

Outcomes of Aspirex®S thrombectomy system combined with catheter-directed thrombolysis for treating bilateral lower extremity deep venous thrombosis.

J Vasc Surg Venous Lymphat Disord 2021 Feb 2. Epub 2021 Feb 2.

Department of Abdominal Wall, Hernia and Vascular Surgery, 2nd Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address:

Background: Pharmacomechanical catheter-directed thrombolysis (PCDT) is rarely reported in treating bilateral lower extremity deep venous thrombosis (LEDVT). This study was aimed to investigate the safety, patency, and mid-term outcomes of the Aspirex®S thrombectomy system combined with catheter-directed thrombolysis (CDT) in treating symptomatic bilateral LEDVT.

Patients And Methods: The clinical data of 45 consecutive patients with acute or subacute bilateral LEDVT (60.00% male; mean age, 53.8 ± 16.5 years) who received endovascular treatment with PCDT between January 2015 and June 2019 were retrospectively analyzed in this study. The clinical efficacy of thrombolysis (≥50% thrombolysis), complications, primary patency, valvular function, and cumulative prevalence of post-thrombotic syndrome (PTS) were retrospectively analyzed.

Results: PCDT was performed in all 45 patients successfully. No serious procedure-related complication or death was observed. The average urokinase dosage was 4.1 ± 1.5 million IU, and the average thrombolysis time was 5.3 ± 1.3 days. The mean length of hospital stay was 9.9 ± 2.5 days. The primary patency was 100% after lysis. The clinical efficacy of thrombolysis was 86.7% (39/45). Deep venous thrombosis recurrence was observed in six (13.3%) patients within 12 months after discharge. The primary patency at 1-, 3-, 6-, 9-, and 12-month follow-up was 97.8%, 93.3%, 88.9%, 82.2%, and 73.3%, respectively. The cumulative prevalence of PTS was 24.4% (11/45) throughout the follow-up period, whereas the prevalence of moderate and severe PTS was only 6.7% (3/45).

Conclusions: PCDT for treating bilateral LEDVT is feasible, effective, and safe.
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http://dx.doi.org/10.1016/j.jvsv.2020.11.025DOI Listing
February 2021

Transcriptional and post-transcriptional regulation of heading date in rice.

New Phytol 2021 05 14;230(3):943-956. Epub 2021 Feb 14.

State Key Laboratory for Crop Genetics and Germplasm Enhancement, Jiangsu Plant Gene Engineering Research Center, Nanjing Agricultural University, Nanjing, 210095, China.

Rice is a facultative short day (SD) plant. In addition to serving as a model plant for molecular genetic studies of monocots, rice is a staple crop for about half of the world's population. Heading date is a critical agronomic trait, and many genes controlling heading date have been cloned over the last 2 decades. The mechanism of flowering in rice from recognition of day length by leaves to floral activation in the shoot apical meristem has been extensively studied. In this review, we summarise current progress on transcriptional and post-transcriptional regulation of heading date in rice, with emphasis on post-translational modifications of key regulators, including Heading date 1 (Hd1), Early heading date 1 (Ehd1), Grain number, plant height, and heading date7 (Ghd7). The contribution of heading date genes to heterosis and the expansion of rice cultivation areas from low-latitude to high-latitude regions are also discussed. To overcome the limitations of diverse genetic backgrounds used in heading date studies and to gain a clearer understanding of flowering in rice, we propose a systematic collection of genetic resources in a common genetic background. Strategies in breeding adapted cultivars by rational design are also discussed.
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http://dx.doi.org/10.1111/nph.17158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048436PMC
May 2021

A semi-covalent molecularly imprinted fluorescent sensor for highly specific recognition and optosensing of bisphenol A.

Anal Methods 2021 01 15;13(1):133-140. Epub 2020 Dec 15.

Key Laboratory of Food Processing Technology and Quality Control in Shandong Province, College of Food Science and Engineering, Shandong Agricultural University, Tai'an, Shandong 271018, P. R. China.

A novel mesoporous fluorescent molecularly imprinted sensor for selective detection of bisphenol A (BPA) in food materials was fabricated via a semi-covalent imprinting method. The imprinting precursor that served as an alternative template molecule for BPA was prepared via thermally reversible isocyanate bonding, which effectively improved the imprinting efficiency for the molecularly imprinted sensor. Carbon dots (CDs) were embedded in mesoporous silica as signal recognition elements that exhibited quenching upon BPA binding. Subsequently, through the sol-gel process, the molecularly imprinted layer was coated on the CDs silica layer and provided specific recognition sites for BPA. The composite of CDs embedded in the mesoporous molecularly imprinted polymer (CDs@MIP) was characterized with scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, Brunauer-Emmett-Teller measurements and thermogravimetric analysis. The mechanism of carbon dots quenching and the high selectivity of CDs@MIP towards BPA were explored. The linear response range of the sensor was from 0.025 mg L to 2 mg L with a limit of detection of 0.016 mg L. The method was successfully applied for the determination of food samples and recoveries ranged from 92.5% to 101.1%. The BPA contents in actual samples were determined using high performance liquid chromatography and the proposed sensor, showing no significant difference between the two methods.
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http://dx.doi.org/10.1039/d0ay01822hDOI Listing
January 2021

Prognostic comparison of transoral laser microsurgery for early glottic cancer with or without anterior commissure involvement: A meta-analysis.

Am J Otolaryngol 2021 Mar-Apr;42(2):102787. Epub 2020 Dec 9.

Department of Otolaryngology Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, China. Electronic address:

Objectives: Transoral laser microsurgery (TLM) has gradually gained approval in the treatment of early glottic cancer. However, the oncological outcomes of TLM for glottic cancer with anterior commissure (AC) involvement are still a controversial topic. We aimed to systematically review the literature on glottic cancer (Tis-T2) with patients who received TLM as first choice therapy and to evaluate several prognostic outcomes in patients with or without AC involvement.

Methods: A systematic literature retrieval was conducted in PubMed, Medline (Ovid) and Web of Science. Risk ratio (RR) between AC involvement (AC+) or without AC involvement (AC-) was assessed and 95% confidence interval(95%CI) was calculated, which was performed on RevMan 5.3.

Results: A total of 20 literatures were included when comparing the local recurrence (LR) rate of patients with or without AC involvement, and the results suggested LR matters in group AC+ over group AC- (RR = 2.39, 95%CI = 1.99-2.86, p < 0.00001). The 5-year overall survival(5yOS) rate included 10 studies, and there was no significant difference between AC+ and AC- (RR = 0.98, 95%CI = 0.93-1.02, p = 0.35). The laryngeal preservation rate (LPR) of AC+ was lower than that of AC- (RR = 0.97, 95%CI = 0.94-1.00, p = 0.04).

Conclusion: The results indicate that the prognosis of early glottic cancer with AC involvement is more likely to have higher local recurrence and lower LPR but no statistical difference in 5yOS rate.
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http://dx.doi.org/10.1016/j.amjoto.2020.102787DOI Listing
December 2020

Promotional effect of Mn-doping on the catalytic performance of NiO sheets for the selective oxidation of styrene.

J Colloid Interface Sci 2021 Mar 24;585:61-71. Epub 2020 Nov 24.

School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, Jiangsu 225002, China.

The direct oxidation of styrene into high-value chemicals under mild reaction conditions remains a great challenge in both academia and industry. Herein, we report a successful electronic structure modulation of intrinsic NiO sheets via Mn-doping towards the oxidation of styrene. By doping NiO with only a small content of Mn (Mn/Ni atomic ratio of 0.030), a 75.0% yield of STO can be achieved under the optimized reaction conditions, which is 2.13 times higher than that of the pure NiO. In addition, the catalyst exhibits robust stability and good recycling performance. The performance enhancement originates from the synergistic effect regarding the abundant Ni(II) species, the rich oxygen vacancy sites and the large amount of surface redox centers. This work provides new findings of the elemental-doping-induced multifunctionality in designing powerful catalysts for the efficient and selective oxidation of styrene and beyond.
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http://dx.doi.org/10.1016/j.jcis.2020.11.069DOI Listing
March 2021

Transcriptional activation and phosphorylation of OsCNGC9 confer enhanced chilling tolerance in rice.

Mol Plant 2021 02 2;14(2):315-329. Epub 2020 Dec 2.

National Key Facility for Crop Gene Resources and Genetic Improvement, Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, Beijing 100081, China.

Low temperature is a major environmental factor that limits plant growth and productivity. Although transient elevation of cytoplasmic calcium has long been recognized as a critical signal for plant cold tolerance, the calcium channels responsible for this process have remained largely elusive. Here we report that OsCNGC9, a cyclic nucleotide-gated channel, positively regulates chilling tolerance by mediating cytoplasmic calcium elevation in rice (Oryza sativa). We showed that the loss-of-function mutant of OsCNGC9 is defective in cold-induced calcium influx and more sensitive to prolonged cold treatment, whereas OsCNGC9 overexpression confers enhanced cold tolerance. Mechanistically, we demonstrated that in response to chilling stress, OsSAPK8, a homolog of Arabidopsis thaliana OST1, phosphorylates and activates OsCNGC9 to trigger Ca influx. Moreover, we found that the transcription of OsCNGC9 is activated by a rice dehydration-responsive element-binding transcription factor, OsDREB1A. Taken together, our results suggest that OsCNGC9 enhances chilling tolerance in rice through regulating cold-induced calcium influx and cytoplasmic calcium elevation.
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http://dx.doi.org/10.1016/j.molp.2020.11.022DOI Listing
February 2021

Auxin response factors (ARFs) differentially regulate rice antiviral immune response against rice dwarf virus.

PLoS Pathog 2020 12 2;16(12):e1009118. Epub 2020 Dec 2.

The State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.

There are 25 auxin response factors (ARFs) in the rice genome, which play critical roles in regulating myriad aspects of plant development, but their role (s) in host antiviral immune defense and the underneath mechanism remain largely unknown. By using the rice-rice dwarf virus (RDV) model system, here we report that auxin signaling enhances rice defense against RDV infection. In turn, RDV infection triggers increased auxin biosynthesis and accumulation in rice, and that treatment with exogenous auxin reduces OsIAA10 protein level, thereby unleashing a group of OsIAA10-interacting OsARFs to mediate downstream antiviral responses. Strikingly, our genetic data showed that loss-of-function mutants of osarf12 or osarf16 exhibit reduced resistance whereas osarf11 mutants display enhanced resistance to RDV. In turn, OsARF12 activates the down-stream OsWRKY13 expression through direct binding to its promoter, loss-of-function mutants of oswrky13 exhibit reduced resistance. These results demonstrated that OsARF 11, 12 and 16 differentially regulate rice antiviral defense. Together with our previous discovery that the viral P2 protein stabilizes OsIAA10 protein via thwarting its interaction with OsTIR1 to enhance viral infection and pathogenesis, our results reveal a novel auxin-IAA10-ARFs-mediated signaling mechanism employed by rice and RDV for defense and counter defense responses.
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http://dx.doi.org/10.1371/journal.ppat.1009118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735678PMC
December 2020

[Treatment efficacy of electronic endoscope-guided botulinum toxin injection in adductor spasmodic dysphonia patients].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2020 Nov;34(11):1019-1023

Department of Otolaryngology Head and Neck Surgery,West China Hospital,Sichuan University,Chengdu,610041,China.

To investigate the treatment efficacy of electronic endoscope-Guided botulinum toxin injection in Adductor Spasmodic Dysphonia Patients. Clinical characteristics of forty- three cases were retrospectively analyzed. The disease were diagnosed with adductor spasmodic dysphonia and graded according to the severity of the disease by experienced voice specialist. All the cases were treated by electronic endoscope-guided botulinum toxin type A injection in bilateral thyroarytenoid muscles. All the subjects underwent stroboscopic laryngoscope examination and filled in the Voice Handicap Index-10(VHI-10). They also filled in the VAS score of Voice related symptoms by self evaluation and other evaluation . One month Later, the patients and someone they lived with filled in the VAS score of Voice related symptoms again. After the first injection, the voice-related symptoms of 35 patients improved to varying degrees..All The average onset time of drug was(2.33±1.86) days. The duration of curative effect ranged from 1 to 6 months, the average duration was(2.42±1.65) months. After injection, no one had serious or persistent adverse reactions. There were significant differences in the total score of VHI-10, physiology(P) and function(F) dimensions in VHI-10 of moderate and severe SD patients before and after injection(<0.05) in all patients. For moderate cases, no significant change in speech articulation(>0.05), overall evaluation of voice quality and any other subprojects are statistically significant(<0.05) in the VAS score of Voice related symptoms; For severe cases, the degree of squeezing and effort during vocalization are no statistically significant(>0.05), overall evaluation of voice quality and any other subitems are statistically significant(<0.05) in the VAS score of Voice related symptoms. In the absence of LEMG, electronic endoscope-guided botulinum toxin injection in adductor spasmodic dysphonia patients can significantly improve the voice quality and quality of life of adductive SD patients. The method is simple to operate, less traumatic, safe and effective, and easy to carry out outpatients service.
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http://dx.doi.org/10.13201/j.issn.2096-7993.2020.11.014DOI Listing
November 2020

Human decellularized adipose matrix derived hydrogel assists mesenchymal stem cells delivery and accelerates chronic wound healing.

J Biomed Mater Res A 2020 Nov 30. Epub 2020 Nov 30.

Department of Plastic and Reconstructive Surgery, The First Medical, Chinese PLA General Hospital Centre, Beijing, China.

Biological scaffolds based stem cell delivery methods have emerged as a promising approach for tissue repair and regeneration. Here we developed a hydrogel biological scaffold from human decellularized adipose matrix (hDAM) for human adipose-derived stem cells (hASCs) delivery to accelerate chronic wound healing. The hDAM hydrogel was prepared by pepsin mediated digestion and pH controlled neutralization. The morphology, survival, proliferation, and angiogenic paracrine activity of hASCs cultured in the hydrogel were assessed. Moreover, the therapeutic efficacy of the hASCs-hydrogel composite for impaired wound healing was evaluated by using a full-thickness wound model on diabetic mouse. The developed hDAM hydrogel was a thermosensitive hydrogel, presented the biochemical complexity of native extracellular matrix and formed a porous nanofiber structure after gelation. The hydrogel can support hASCs adhesion, survival, and proliferation. Compared to standard culture condition, hASCs cultured in the hydrogel exhibited enhanced paracrine activity with increased secretion of hepatocyte growth factor. In the diabetic mice model with excisional full-thickness skin wounds, mice treated with the hASCs-hydrogel composite displayed accelerated wound closure and increased neovascularization. Our results suggested that the developed hDAM hydrogel can provide a favorable microenvironment for hASCs with augmented regeneration potential to accelerate chronic wound healing.
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http://dx.doi.org/10.1002/jbm.a.37133DOI Listing
November 2020

DHD4, a CONSTANS-like family transcription factor, delays heading date by affecting the formation of the FAC complex in rice.

Mol Plant 2021 02 24;14(2):330-343. Epub 2020 Nov 24.

National Key Facility for Crop Gene Resources and Genetic Improvement, Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, Beijing 100081, China. Electronic address:

Heading date (or flowering time) is one of the most important agronomic traits in rice, influencing its regional adaptability and crop yield. Many major-effect genes for rice heading date have been identified, but in practice they are difficult to be used for rice molecular breeding because of their dramatic effects on heading date. Genes with minor effects on heading date, which are more desirable for fine-tuning flowering time without significant yield penalty, were seldom reported. In this study, we identified a new minor-effect heading date repressor, Delayed Heading Date 4 (DHD4). The dhd4 mutant shows a slightly earlier flowering phenotype without a notable yield penalty compared with wild-type plants under natural long-day conditions. DHD4 encodes a CONSTANS-like transcription factor localized in the nucleus. Molecular, biochemical, and genetic assays show that DHD4 can compete with 14-3-3 to interact with OsFD1, thus affecting the formation of the Hd3a-14-3-3-OsFD1 tri-protein FAC complex, resulting in reduced expression of OsMADS14 and OsMADS15, and ultimately delaying flowering. Taken together, these results shed new light on the regulation of flowering time in rice and provide a promising target for fine-tuning flowering time to improve the regional adaptability of rice.
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http://dx.doi.org/10.1016/j.molp.2020.11.013DOI Listing
February 2021

Clinical evaluation of vitamin D status and its relationship with disease activity and changes of intestinal immune function in patients with Crohn's disease in the Chinese population.

Scand J Gastroenterol 2021 Jan 18;56(1):20-29. Epub 2020 Nov 18.

Department of Gastroenterology, First Affliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, P.R. China.

Background: High prevalence of vitamin D deficiency has been found among Crohn's disease (CD) patients. Vitamin D probably participates in the pathogenesis of CD, but this idea remains controversial. This study was to investigate the levels of vitamin D in CD patients and analyze the relationship between vitamin D and intestinal inflammation.

Methods: Vitamin D levels were measured by chemiluminescence immunoassay in 198 CD patients (96 in active, 102 in remission) and 100 healthy controls. The correlation between vitamin D levels and clinical parameters was analysed. The expression of intestinal tight junction (TJ) proteins in CD patients was measured by immunofluorescence staining. Treg and Th17 percentages in the peripheral blood were determined by flow cytometry.

Results: CD patients exhibited significantly lower 25(OH)D levels than healthy controls, especially in active CD patients. Serum 25(OH)D levels in CD patients were negatively correlated with the CD activity index (CDAI), the simple endoscopic score for CD (SES-CD), and inflammatory markers, including erythrocyte sedimentation rate (ESR), platelet (PLT) count and faecal calprotectin (FC) levels. Moreover, in patients with vitamin D deficiency, the expression of TJ proteins (Occludin, claudin-1, ZO-1 and JAM-1) in the intestinal mucosa was reduced, and Treg cells in the peripheral blood were decreased, while Th17 cells were increased compared to those with vitamin D sufficiency and controls.

Conclusions: Vitamin D deficiency in CD patients is common. Vitamin D is associated with disease activity and intestinal inflammation, which may affect the Treg/Th17 balance and the expression of gut TJ proteins.
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http://dx.doi.org/10.1080/00365521.2020.1844793DOI Listing
January 2021