Publications by authors named "Xiaoqing Chen"

405 Publications

Enhancing cell membrane phase separation for inhibiting cancer metastasis with a stimuli-responsive DNA nanodevice.

Chem Sci 2022 Jun 2;13(21):6303-6308. Epub 2022 May 2.

School of Chemistry and Molecular Engineering, East China Normal University 200241 Shanghai China

Phase separation in cell membranes promotes the assembly of transmembrane receptors to initiate signal transduction in response to environmental cues. Many cellular behaviors are manipulated by promoting membrane phase separation through binding to multivalent extracellular ligands. However, available extracellular molecule tools that enable manipulating the clustering of transmembrane receptors in a controllable manner are rare. In the present study, we report a DNA nanodevice that enhances membrane phase separation through the clustering of dynamic lipid rafts. This DNA nanodevice is anchored in the lipid raft region of the cell membrane and initiated by ATP. In a tumor microenvironment, this device could be activated to form a long DNA duplex on the cell membrane, which not only enhances membrane phase separation, but also blocks the interaction between the transmembrane surface adhesion receptor and extracellular matrix, leading to reduced migration. We demonstrate that the ATP-activated DNA nanodevice could inhibit cancer cell migration both and . The concept of using DNA to regulate membrane phase separation provides new possibilities for manipulating versatile cell functions through rational design of functional DNA structures.
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http://dx.doi.org/10.1039/d2sc00371fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9159096PMC
June 2022

Innate immune responses against the fungal pathogen Candida auris.

Nat Commun 2022 Jun 21;13(1):3553. Epub 2022 Jun 21.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.

Candida auris is a multidrug-resistant human fungal pathogen responsible for nosocomial outbreaks worldwide. Although considerable progress has increased our understanding of the biological and clinical aspects of C. auris, its interaction with the host immune system is only now beginning to be investigated in-depth. Here, we compare the innate immune responses induced by C. auris BJCA001 and Candida albicans SC5314 in vitro and in vivo. Our results indicate that C. auris BJCA001 appears to be less immunoinflammatory than C. albicans SC5314, and this differential response correlates with structural features of the cell wall.
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http://dx.doi.org/10.1038/s41467-022-31201-xDOI Listing
June 2022

Identification of Differentially Expressed Genes and miRNAs for Ulcerative Colitis Using Bioinformatics Analysis.

Front Genet 2022 2;13:914384. Epub 2022 Jun 2.

Department of Rheumatology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.

Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine whose cause and underlying mechanisms are not fully understood. The aim of this study was to use bioinformatics analysis to identify differentially expressed genes (DEGs) with diagnostic and therapeutic potential in UC. Three UC datasets (GSE179285, GSE75214, GSE48958) were downloaded from the Gene Expression Omnibus (GEO) database. DEGs between normal and UC tissues were identified using the GEO2R online tool. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEGs were performed using Metascape. Protein-protein interaction network (PPI) analysis and visualization using STRING and Cytoscape. Finally, the miRNA gene regulatory network was constructed by Cytoscape to predict potential microRNAs (miRNAs) associated with DEGs. A total of 446 DEGs were identified, consisting of 309 upregulated genes and 137 downregulated genes. The enriched functions and pathways of the DEGs include extracellular matrix, regulation of cell adhesion, inflammatory response, response to cytokine, monocarboxylic acid metabolic process, response to toxic substance. The analysis of KEGG pathway indicates that the DEGs were significantly enriched in Complement and coagulation cascades, Amoebiasis, TNF signaling pathway, bile secretion, and Mineral absorption. Combining the results of the PPI network and CytoHubba, 9 hub genes including CXCL8, ICAM1, CXCR4, CD44, IL1B, MMP9, SPP1, TIMP1, and HIF1A were selected. Based on the DEG-miRNAs network construction, 7 miRNAs including miR-335-5p, mir-204-5p, miR-93-5p, miR106a-5p, miR-21-5p, miR-146a-5p, and miR-155-5p were identified as potential critical miRNAs. In summary, we identified DEGs that may be involved in the progression or occurrence of UC. A total of 446 DEGs,9 hub genes and 7 miRNAs were identified, which may be considered as biomarkers of UC. Further studies, however, are needed to elucidate the biological functions of these genes in UC.
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http://dx.doi.org/10.3389/fgene.2022.914384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201719PMC
June 2022

Neuroprotective alkamides from Achillea alpina L.

Chem Biodivers 2022 Jun 11. Epub 2022 Jun 11.

Capital Medical University, School of traditional Chinese medicine, XiTouTiao 10, YouAnMenWai, FengTai, 100069, Beijing, CHINA.

[ABSTRACT] Three new alkamides, achilleamide B-D (1-3) along with five known alkamides (4-8) were isolated from the aerial parts of Achillea alpina L. Structures were elucidated by spectroscopic analysis. Modified Mosher's method and electronic circular dichroism (ECD) calculations were introduced for the absolute configuration of 3. Neuroprotective effects of all the compounds were evaluated by 6-hydroxydopamine (6-OHDA)-induced cell death in human neuroblastoma SH-SY5Y cells, with concentration for 50% of maximal effect (EC50) values of 3.16-24.75 μM and the structure activity relationship was conducted.
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http://dx.doi.org/10.1002/cbdv.202200218DOI Listing
June 2022

Deficiency of Autism-Related Gene Dock4 Leads to Impaired Spatial Memory and Hippocampal Function in Mice at Late Middle Age.

Cell Mol Neurobiol 2022 May 30. Epub 2022 May 30.

JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, College of Pharmacy, Jinan University, Guangzhou, 510632, Guangdong, China.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that lasts lifelong and causes noticeably higher premature mortality. Although the core symptoms and other behavioral deficits of ASD can persist or be deteriorated from early development to old age, how aging affects the behaviors and brain anatomy in ASD is largely unknown. DOCK4 is an ASD risk gene highly expressed in the hippocampus, and Dock4 knockout (KO) mice display ASD-like behaviors in adulthood (4- to 6-month-old). In this study, we evaluated the behavioral and hippocampal pathological changes of late-middle-aged (15- to 17-month-old) Dock4 male KO mice. Aged Dock4 KO mice continuously showed similar social deficit, elevated anxiety, and disrupted object location memory as observed in the adulthood, when compared to their wild-type (WT) littermates. Notably, Dock4 KO mice displayed an age-related decline of hippocampal dependent spatial memory, showing decreased spatial memory in Barnes maze than their WT littermates at late middle age. Morphological analysis from WT and Dock4 KO littermates revealed that Dock4 deficiency led to decreased mature neurons and oligodendrocytes but increased astrocytes in the hippocampus of late-middle-aged mice. Together, we report that ASD-like behaviors mostly persist into late-middle age in Dock4 KO mice, with specific alterations of spatial memory and hippocampal anatomy by age, thus providing new evidence for understanding age differences in behavioral deficits of ASD.
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http://dx.doi.org/10.1007/s10571-022-01233-4DOI Listing
May 2022

Melatonin, an endogenous hormone, modulates Th17 cells via the reactive-oxygen species/TXNIP/HIF-1α axis to alleviate autoimmune uveitis.

J Neuroinflammation 2022 May 27;19(1):124. Epub 2022 May 27.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratoryof Ophthalmologyand VisualScience, Sun Yat-Sen University, Guangzhou, 510060, China.

Background: Melatonin, an indoleamine produced by the pineal gland, plays a pivotal role in maintaining circadian rhythm homeostasis. Recently, the strong antioxidant and anti-inflammatory properties of melatonin have attracted attention of researchers. We evaluated the therapeutic efficacy of melatonin in experimental autoimmune uveitis (EAU), which is a representative animal model of human autoimmune uveitis.

Methods: EAU was induced in mice via immunization with the peptide interphotoreceptor retinoid binding protein 1-20 (IRBP). Melatonin was then administered via intraperitoneal injection to induce protection against EAU. With EAU induction for 14 days, clinical and histopathological scores were graded to evaluate the disease progression. T lymphocytes accumulation and the expression of inflammatory cytokines in the retinas were assessed via flow cytometry and RT-PCR, respectively. T helper 1 (Th1), T helper 17 (Th17), and regulatory T (Treg) cells were detected via flow cytometry for both in vivo and in vitro experiments. Reactive-oxygen species (ROS) from CD4 + T cells was tested via flow cytometry. The expression of thioredoxin-interacting protein (TXNIP) and hypoxia-inducible factor 1 alpha (HIF-1α) proteins were quantified via western blot.

Results: Melatonin treatment resulted in notable attenuation of ocular inflammation in EAU mice, evidenced by decreasing optic disc edema, few signs of retinal vasculitis, and minimal retinal and choroidal infiltrates. Mechanistic studies revealed that melatonin restricted the proliferation of peripheral Th1 and Th17 cells by suppressing their transcription factors and potentiated Treg cells. In vitro studies corroborated that melatonin restrained the polarization of retina-specific T cells towards Th17 and Th1 cells in addition to enhancing the proportion of Treg cells. Pretreatment of retina-specific T cells with melatonin failed to induce EAU in naïve recipients. Furthermore, the ROS/ TXNIP/ HIF-1α pathway was shown to mediate the therapeutic effect of melatonin in EAU.

Conclusions: Melatonin regulates autoimmune T cells by restraining effector T cells and facilitating Treg generation, indicating that melatonin could be a hopeful treatment alternative for autoimmune uveitis.
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http://dx.doi.org/10.1186/s12974-022-02477-zDOI Listing
May 2022

Performance of PROPELLER FSE TWI in reducing metal artifacts of material porcelain fused to metal crown: a clinical preliminary study.

Sci Rep 2022 May 19;12(1):8442. Epub 2022 May 19.

Department of Radiology, The Second Hospital of Shanxi Medical University, NO.382 Wuyi Road, Taiyuan, 030001, Shanxi, China.

This study aimed to compare MRI quality between conventional fast spin echo T weighted imaging (FSE TWI) with periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) FSE TWI for patients with various porcelain fused to metal (PFM) crown and analyze the value of PROPELLER technique in reducing metal artifacts. Conventional FSE TWI and PROPELLER FSE TWI sequences for axial imaging of head were applied in participants with different PFM crowns: cobalt-chromium (Co-Cr) alloy, pure titanium (Ti), gold-palladium (Au-Pd) alloy. Two radiologists evaluated overall image quality of section in PFM using a 5-point scale qualitatively and measured the maximum artifact area and artifact signal-to-noise ratio (SNR) quantitatively. Fifty-nine participants were evaluated. The metal crown with the least artifacts and the optimum image quality shown in conventional FSE TWI and PROPELLER FSE TWI were in Au-Pd alloy, Ti, and Co-Cr alloy order. PROPELLER FSE TWI was superior to conventional FSE TWI in improving image quality and reducing artifact area for Co-Cr alloy (17.0 ± 0.2% smaller artifact area, p < 0.001) and Ti (11.6 ± 0.7% smaller artifact area, p = 0.005), but had similar performance compared to FSE TWI for Au-Pd alloy. The SNRs of the tongue and masseter muscle were significantly higher on PROPELLER FSE TWI compared with conventional FSE TWI (tongue: 29.76 ± 8.45 vs. 21.54 ± 9.31, p = 0.007; masseter muscle: 19.11 ± 8.24 vs. 15.26 ± 6.08, p = 0.016). Therefore, the different PFM crown generate varying degrees of metal artifacts in MRI, and the PROPELLER can effectively reduce metal artifacts especially in the PFM crown of Co-Cr alloy.
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http://dx.doi.org/10.1038/s41598-022-12402-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9120134PMC
May 2022

Comparison of different neonatal illness severity scores in predicting mortality risk of extremely low birth weight infants.

Zhejiang Da Xue Xue Bao Yi Xue Ban 2022 Feb;51(1):73-78

3. Department of Neonatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210036, China.

To compare different illness severity scores in predicting mortality risk of extremely low birth weight infants (ELBWI). From January 1st, 2019 to January 1st, 2020, all ELBWI admitted in the Children's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital and the First Affiliated Hospital of Nanjing Medical University were included in the study. ELBWI with admission age ≥1 h, gestational age ≥37 weeks and incomplete data required for scoring were excluded. The clinical data were collected, neonatal critical illness score (NCIS), score for neonatal acute physiology version Ⅱ (SNAP-Ⅱ), simplified version of the score for neonatal acute physiology perinatal extension (SNAPPE-Ⅱ), clinical risk index for babies (CRIB) and CRIB-Ⅱ were calculated. The scores of the fatal group and the survival group were compared, and the receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the above illness severity scores for the mortality risk of ELBWI. Pearson correlation analysis was used to analyze the correlation between illness scores and birth weight, illness scores and gestational age. A total of 192 ELBWI were finally included, of whom 114 cases survived (survival group) and 78 cases died (fatal group). There were significant differences in birth weight, gestational age and Apgar scores between fatal group and survival group (all <0.01). There were significant differences in NCIS, SNAP-Ⅱ, SNAPPE-Ⅱ, CRIB and CRIB-Ⅱ between fatal group and survival group (all <0.01). The CRIB had a relatively higher predictive value for the mortality risk. Its area under the ROC curve (AUC) was 0.787, the sensitivity was 0.678, the specificity was 0.804, and the Youden index was 0.482. The scores of NCIS, SNAP-Ⅱ, SNAPPE-Ⅱ, CRIB and CRIB-Ⅱ were significantly correlated with birth weight and gestational age (all <0.05). The correlation coefficients of CRIB-Ⅱ and CRIB with birth weight and gestational age were relatively large, and the correlations coefficients of NCIS with birth weight and gestational age were the smallest (0.191 and 0.244, respectively). Among these five illness severity scores, CRIB has better predictive value for the mortality risk in ELBWI. NCIS, which is widely used in China, has relatively lower sensitivity and specificity, and needs to be further revised.
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http://dx.doi.org/10.3724/zdxbyxb-2021-0217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9109766PMC
February 2022

Uniform nucleation and epitaxy of bilayer molybdenum disulfide on sapphire.

Nature 2022 05 4;605(7908):69-75. Epub 2022 May 4.

National Laboratory of Solid State Microstructures, School of Electronic Science and Engineering and Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing, China.

Two-dimensional transition-metal dichalcogenides (TMDs) are of interest for beyond-silicon electronics. It has been suggested that bilayer TMDs, which combine good electrostatic control, smaller bandgap and higher mobility than monolayers, could potentially provide improvements in the energy-delay product of transistors. However, despite advances in the growth of monolayer TMDs, the controlled epitaxial growth of multilayers remains a challenge. Here we report the uniform nucleation (>99%) of bilayer molybdenum disulfide (MoS) on c-plane sapphire. In particular, we engineer the atomic terrace height on c-plane sapphire to enable an edge-nucleation mechanism and the coalescence of MoS domains into continuous, centimetre-scale films. Fabricated field-effect transistor (FET) devices based on bilayer MoS channels show substantial improvements in mobility (up to 122.6 cm V s) and variation compared with FETs based on monolayer films. Furthermore, short-channel FETs exhibit an on-state current of 1.27 mA μm, which exceeds the 2028 roadmap target for high-performance FETs.
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http://dx.doi.org/10.1038/s41586-022-04523-5DOI Listing
May 2022

circDHTKD1 promotes lymphatic metastasis of bladder cancer by upregulating CXCL5.

Cell Death Discov 2022 May 3;8(1):243. Epub 2022 May 3.

Department of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing, Jiangsu, China.

Lymph node (LN) metastasis is associated with unfavorable prognosis of bladder cancer (BCa). Although lymphangiogenesis is functionally important in LN metastasis of tumors, the potential mechanism in BCa remains unclear. Here, we clarified a regulatory mechanism of circRNA-mediated lymphangiogenesis and LN metastasis in BCa based on next-generation sequencing data. We revealed that circDHTKD1 was positively associated with LN metastasis and significantly upregulated in BCa. By analyzing the co-expression patterns of circDHTKD1 and differentially expressed mRNAs, we identified that circDHTKD1 facilitated lymphangiogenesis by upregulating CXCL5. Mechanistically, circDHTKD1 directly interacted with miR-149-5p, and antagonized the repression of miR-149-5p on CXCL5. Furthermore, circDHTKD1-induced CXCL5 expression recruited and activated neutrophils, which participated in lymphangiogenesis by secreting VEGF-C. Our study supports circDHTKD1 as a promising diagnostic and therapeutic target for LN metastasis in BCa.
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http://dx.doi.org/10.1038/s41420-022-01037-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9065127PMC
May 2022

Penthorum chinense Pursh. extract attenuates non-alcholic fatty liver disease by regulating gut microbiota and bile acid metabolism in mice.

J Ethnopharmacol 2022 Aug 29;294:115333. Epub 2022 Apr 29.

Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, 100069, Beijing, China. Electronic address:

Ethnopharmacological Relevance: Penthorum chinense Pursh. (PCP) is commonly used as a Miao ethnomedicine and health food for liver protection in China. Gansukeli (WS3-B-2526-97) is made from the extract of PCP (PCPE) for the treatment of viral hepatitis. In recent years, PCPE has been reported in the treatment of non-alcoholic fatty liver disease (NAFLD), however its potential mechanism is not fully elucidated.

Aim Of The Study: To investigate the ameliorating effect of PCPE on high-fat diet (HFD)-induced NAFLD mice and demonstrate whether its protective effect is gut microbiota dependent and associated with bile acid (BA) metabolism.

Materials And Methods: The alleviating effect of PCPE on NAFLD was conducted on male C57BL/6J mice fed an HFD for 16 weeks, and this effect associated with gut microbiota dependent was demonstrated by pseudo-germfree mice treated with antibiotics and fecal microbiota transplantation (FMT). The composition of the gut microbiota in the cecum contents was analyzed by 16S rRNA sequencing, and the levels of BAs in liver and fecal samples were determined by UPLC/MS-MS.

Results: The results showed that administration of PCPE for 8 weeks could potently ameliorate HFD-induced NAFLD and alleviate dyslipidemia and insulin resistance. Moreover, PCPE treatment alleviated gut dysbiosis, especially reducing the relative abundance of bile salt hydrolase (BSH)-producing bacteria. Furthermore, PCPE significantly increased the levels of taurine-conjugated BAs in feces, such as tauro-β-muricholic acid (T-βMCA), tauroursodesoxycholic acid (TUDCA), and taurochenodeoxycholic acid (TCDCA), and increased hepatic chenodeoxycholic acid (CDCA). The protein and mRNA expression of farnesoid X receptor (FXR) and fibroblast growth factor 15 (FGF15) were decreased in intestine, increased taurine-conjugated BAs inhibited the intestinal signaling pathway, which was associated with increased genes expression of enzymes in the alternative BA synthesis pathway that reduced the levels of cholesterol. The increased CDCA produced via the alternative BA synthesis pathway promoted hepatic FXR activation and BA excretion.

Conclusion: Our study is the first time to demonstrate that PCPE could ameliorate NAFLD in HFD-induced mice by regulating the gut microbiota and BA metabolism, and from a novel perspective, to clarify the mechanism of PCPE in NAFLD.
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http://dx.doi.org/10.1016/j.jep.2022.115333DOI Listing
August 2022

Improved efficiency and stability of flexible perovskite solar cells by a new spacer cation additive.

RSC Adv 2021 Oct 14;11(53):33637-33645. Epub 2021 Oct 14.

College of Material Sciences and Engineering, Beijing University of Technology Beijing 100124 China.

Flexible perovskite solar cells (PSCs) have attracted tremendous attention due to their potential application in portable and wearable electronics. However, the photoelectric conversion efficiency (PCE) of flexible PSCs is still far lower than that of usual rigid PSCs. Moreover, the mechanical stability of flexible PSCs cannot meet the needs of commercial applications because of the cracking of perovskite grains caused by bending stress. Here, we introduced a spacer cation additive (2-(chloromethyl) pyridine hydrochloride, CPHC) within the perovskite organic precursor to improve the device PCE and its mechanical stability. We observed that the CPHC spacer cation additive could simultaneously facilitate the crystallization of perovskite and stitch the grain boundaries to improve the flexibility. Compared to the 17.64% PCE of the control devices, the target flexible PSCs achieved a more highly efficiency over 19% with an improved mechanical stability (87.2% of the initial PCE after the 1000 cycles with the bending radius = 6 mm). In addition, compared to methylammonium or formamidinium cation, due to the stronger hydrophobic and larger activation energy barrier for the ion migration of the CPHC spacer cation, the device retained over 80% of the initial PCE after 30 days storage in an ambient environment.
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http://dx.doi.org/10.1039/d1ra05399jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9042258PMC
October 2021

Distinct clinical and somatic mutational features of breast tumors with high-, low-, or non-expressing human epidermal growth factor receptor 2 status.

BMC Med 2022 04 29;20(1):142. Epub 2022 Apr 29.

Department of Breast Surgery, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, 510080, China.

Background: HER2-low breast cancers were reported to have distinct clinicopathological characteristics from HER2-zero; however, the difference in their genetic features remains unclear. This study investigated the clinical and molecular features of breast tumors according to HER2 status.

Methods: We analyzed the clinicopathological and genomic data of 523 Chinese women with breast cancer. Genomic data was generated by targeted next-generation sequencing (NGS) of breast tumor samples using a commercial 520 gene panel. The cohort was stratified according to HER2 status as HER2-zero (n = 90), HER2-low (n = 231), and HER2-positive (n = 202) according to their immunohistochemistry and fluorescence in situ hybridization results.

Results: HER2-low breast tumors were enriched with hormone receptor-positive tumors, and who had lower Ki67 expression levels. Genes were differentially mutated across HER2 subgroups. HER2-low tumors had significantly more mutations involved in PI3K-Akt signaling than HER2-positive (p < 0.001) and HER2-zero breast tumors (p < 0.01). HER2-zero tumors had more mutations in checkpoint factors (p < 0.01), Fanconi anemia (p < 0.05), and p53 signaling and cell cycle pathway (p < 0.05) compared to HER2-low breast tumors. Compared with HER2-zero tumors, HER2-low tumors had significantly lower pathological complete response rates after neoadjuvant therapy (15.9% vs. 37.5%, p = 0.042) and proportion of relapsed/progressed patients across follow-up time points (p = 0.031), but had comparable disease-free survival (p = 0.271).

Conclusion: Our results demonstrate the distinct clinical and molecular features and clinical outcomes of HER2-low breast tumors.
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http://dx.doi.org/10.1186/s12916-022-02346-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9052533PMC
April 2022

Chip-integrated van der Waals PN heterojunction photodetector with low dark current and high responsivity.

Light Sci Appl 2022 Apr 20;11(1):101. Epub 2022 Apr 20.

Key Laboratory of Light Field Manipulation and Information Acquisition, Ministry of Industry and Information Technology, and Shaanxi Key Laboratory of Optical Information Technology, School of Physical Science and Technology, Northwestern Polytechnical University, 710129, Xi'an, China.

Two-dimensional materials are attractive for constructing high-performance photonic chip-integrated photodetectors because of their remarkable electronic and optical properties and dangling-bond-free surfaces. However, the reported chip-integrated two-dimensional material photodetectors were mainly implemented with the configuration of metal-semiconductor-metal, suffering from high dark currents and low responsivities at high operation speed. Here, we report a van der Waals PN heterojunction photodetector, composed of p-type black phosphorous and n-type molybdenum telluride, integrated on a silicon nitride waveguide. The built-in electric field of the PN heterojunction significantly suppresses the dark current and improves the responsivity. Under a bias of 1 V pointing from n-type molybdenum telluride to p-type black phosphorous, the dark current is lower than 7 nA, which is more than two orders of magnitude lower than those reported in other waveguide-integrated black phosphorus photodetectors. An intrinsic responsivity up to 577 mA W is obtained. Remarkably, the van der Waals PN heterojunction is tunable by the electrostatic doping to further engineer its rectification and improve the photodetection, enabling an increased responsivity of 709 mA W. Besides, the heterojunction photodetector exhibits a response bandwidth of ~1.0 GHz and a uniform photodetection over a wide spectral range, as experimentally measured from 1500 to 1630 nm. The demonstrated chip-integrated van der Waals PN heterojunction photodetector with low dark current, high responsivity and fast response has great potentials to develop high-performance on-chip photodetectors for various photonic integrated circuits based on silicon, lithium niobate, polymer, etc.
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http://dx.doi.org/10.1038/s41377-022-00784-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021258PMC
April 2022

Electrically Tunable Second Harmonic Generation in Atomically Thin ReS.

ACS Nano 2022 Apr 15. Epub 2022 Apr 15.

Key Laboratory of Light Field Manipulation and Information Acquisition, Ministry of Industry and Information Technology, and Shaanxi Key Laboratory of Optical Information Technology, School of Physical Science and Technology, Northwestern Polytechnical University, Xi'an, 710129 China.

Electrical tuning of second-order nonlinearity in optical materials is attractive to strengthen and expand the functionalities of nonlinear optical technologies, though its implementation remains elusive. Here, we report the electrically tunable second-order nonlinearity in atomically thin ReS flakes benefiting from their distorted 1T crystal structure and interlayer charge transfer. Enabled by the efficient electrostatic control of the few-atomic-layer ReS, we show that second harmonic generation (SHG) can be induced in odd-number-layered ReS flakes which are centrosymmetric and thus without intrinsic SHG. Moreover, the SHG can be precisely modulated by the electric field, reversibly switching from almost zero to an amplitude more than 1 order of magnitude stronger than that of the monolayer MoS. For the even-number-layered ReS flakes with the intrinsic SHG, the external electric field could be leveraged to enhance the SHG. We further perform the first-principles calculations which suggest that the modification of in-plane second-order hyperpolarizability by the redistributed interlayer-transferring charges in the distorted 1T crystal structure underlies the electrically tunable SHG in ReS. With its active SHG tunability while using the facile electrostatic control, our work may further expand the nonlinear optoelectronic functions of two-dimensional materials for developing electrically controllable nonlinear optoelectronic devices.
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http://dx.doi.org/10.1021/acsnano.2c00514DOI Listing
April 2022

An effective and recyclable decolorization method for polysaccharides from Miquel by magnetic chitosan microspheres.

RSC Adv 2022 Jan 24;12(5):3147-3156. Epub 2022 Jan 24.

The First Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou 510405 Guangdong China

The purpose of this research was to develop an efficient and non-destructive method for decolorizing of polysaccharides extracted from Miquel by magnetic chitosan microspheres (MCM). The optimum decolorization parameters were achieved by response surface methodology as follows: the MCM amount was 8.0%, the adsorption temperature was 48 °C, the adsorption time was 82 min and the pH was 7. Under these optimal conditions, the %, %, and were 90.31 ± 0.12%, 95.40 ± 0.11% and 19.66 ± 0.49, respectively. MCM adsorption of pigment molecules was a spontaneous and endothermic process that could be fitted with the pseudo-second-order equation and the Freundlich equation. Besides, the adsorption mechanism could be controlled by multiple-diffusion steps, including film diffusion and intra-particle diffusion. Furthermore, MCM is a recyclable material. Adsorption with MCM is a promising method to remove pigment molecules of polysaccharide, it may replace the traditional decolorization method.
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http://dx.doi.org/10.1039/d1ra07758aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8979246PMC
January 2022

Distribution, sources, and ecological risk assessment of HCHs and DDTs in water from a typical coal mining subsidence area in Huainan, China.

Environ Sci Pollut Res Int 2022 Apr 12. Epub 2022 Apr 12.

Jiangsu Design Institute of Geology for Mineral Resources, Jiangsu, China.

Coal mining subsidence areas are a special and widespread ecosystem in China and many developing countries in the world. However, limited research has focused on HCHs and DDTs in coal mining subsidence areas. Investigating the concentration, distribution, and sources of HCHs and DDTs at the Yangzhuang coal mining subsidence area in Huainan, China, is the object of this study. Water samples from different depths were collected from this region to detect and analyze HCHs and DDTs using gas chromatography-mass spectrometry. The result showed that the concentrations of HCHs and DDTs increased with increasing water depth, and the average concentrations of HCHs and DDTs in the top (T-layer), middle (M-layer), and bottom (B-layer) layers were 152, 169, and 182 ng∙L, respectively. Spatial distribution of HCH and DDT concentrations in the study area revealed that the concentrations gradually decreased in the direction of water flow, and the highest concentration was observed at the entrance of the Nihe River. The T-layer was easily influenced by environmental and human activities, while the M-layer and B-layer were mainly influenced by sediment. Using principal component analysis and diagnostic ratios, we found that HCHs and DDTs in the study area mainly originated due to natural and human activities (such as pesticide use). Hexachlorocyclohexanes (HCHs) were mainly derived from lindane, and dichlorodiphenyltrichloroethanes (DDTs) mainly originated due to the recent agricultural use of dicofol; both of these are directly related to agricultural activities. Based on a comparison of reported concentrations of HCHs and DDTs in the rivers and lakes throughout China, we found that the overall ecological risk of HCHs and DDTs in the study area was elevated. The results are important for further understanding the transfer characteristics of HCHs and DDTs as well as the ecological health of the water in coal mining subsidence areas.
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http://dx.doi.org/10.1007/s11356-022-20087-3DOI Listing
April 2022

Hydroxychloroquine Alleviates EAU by Inhibiting Uveitogenic T Cells and Ameliorating Retinal Vascular Endothelial Cells Dysfunction.

Front Immunol 2022 25;13:859260. Epub 2022 Mar 25.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.

Purpose: Inflammation triggers the activation of CD4T cells and the breakdown of blood-retinal barrier, thus contributing to the pathology of experimental autoimmune uveitis (EAU). We explored the anti-inflammatory effect of hydroxychloroquine (HCQ) on EAU and the potential mechanisms active in T cells and retinal vascular endothelial cells (RVECs).

Methods: C57BL/6J mice were immunized with interphotoreceptor retinoid binding protein 1-20 (IRBP) to induce EAU and then treated with the vehicle or HCQ (100 mg/kg/day). On day 7, 14, 21, 30 and 60 after immunization, clinical scores were evaluated. On day 14, histopathological scores were assessed, and retinas, spleens, and lymph nodes were collected for quantitative polymerase chain reaction or flow cytometry analysis. RVEC dysfunction was induced by tumor necrosis factor α (TNF-α) stimulation. The expression of cytokines, chemokines, adhesion molecules, and lectin-like oxidized LDL receptor-1 (LOX-1)/nuclear factor κB (NF-κB) was measured in RVECs with or without HCQ.

Results: HCQ treatment protected mice from uveitis, evidenced by reduced expression of inflammatory factors, chemokines, and adhesion molecules in the retina. In systemic immune response, HCQ inhibited the activation of naïve CD4T cells and frequencies of T effector cells, and promoted T regulatory cells. HCQ decreased IRBP-specific T cell responses and proliferation of CD4T cells . Further studies established that TNF-α induced RVECs to express inflammatory cytokines, chemokines, and adhesion molecules, whereas HCQ alleviated the alterations the LOX-1/NF-κB pathways.

Conclusions: HCQ alleviates EAU by regulating the Teff/Treg balance and ameliorating RVECs dysfunction the LOX-1/NF-κB axis. HCQ may be a promising therapeutic candidate for uveitis.
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http://dx.doi.org/10.3389/fimmu.2022.859260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8989724PMC
April 2022

Non-invasive digital etching of van der Waals semiconductors.

Nat Commun 2022 Apr 5;13(1):1844. Epub 2022 Apr 5.

National Laboratory of Solid-State Microstructures and Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing, China.

The capability to finely tailor material thickness with simultaneous atomic precision and non-invasivity would be useful for constructing quantum platforms and post-Moore microelectronics. However, it remains challenging to attain synchronized controls over tailoring selectivity and precision. Here we report a protocol that allows for non-invasive and atomically digital etching of van der Waals transition-metal dichalcogenides through selective alloying via low-temperature thermal diffusion and subsequent wet etching. The mechanism of selective alloying between sacrifice metal atoms and defective or pristine dichalcogenides is analyzed with high-resolution scanning transmission electron microscopy. Also, the non-invasive nature and atomic level precision of our etching technique are corroborated by consistent spectral, crystallographic, and electrical characterization measurements. The low-temperature charge mobility of as-etched MoS reaches up to 1200 cm Vs, comparable to that of exfoliated pristine counterparts. The entire protocol represents a highly precise and non-invasive tailoring route for material manipulation.
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http://dx.doi.org/10.1038/s41467-022-29447-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983769PMC
April 2022

Metabonomics Study on Naotaifang Extract Alleviating Neuronal Apoptosis after Cerebral Ischemia-Reperfusion Injury.

Evid Based Complement Alternat Med 2022 14;2022:2112433. Epub 2022 Mar 14.

College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China.

Naotaifang extract (NTE) is a clinically effective traditional Chinese medicine compound for cerebral ischemia-reperfusion injury. Although NTE can achieve neuroprotective function through different mechanisms, the pharmacodynamic substances of NTE corresponding to these mechanisms have rarely been reported. Alleviating or inhibiting neuronal apoptosis is an important way to achieve neuroprotection. Accordingly, this study has evaluated the effects of NTE on alleviating neuronal apoptosis after cerebral ischemia-reperfusion injury from two levels of cells and tissues. Meanwhile, the serum pharmacochemistry of NTE was analyzed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) with the guidance of Chinmedomics. The results included three aspects: (1) NTE could significantly alleviate neuronal apoptosis caused by in vitro cellular models and in vivo animal models; (2) a total of 21 serum differential metabolites was discovered, including adenosine, inosine, ferulic acid, calycosin, salidroside, 6-gingerol, 2-methoxycinnamaldehyde, and so on; (3) the metabolic pathway regulated by NTE was mainly purine metabolism. From these results, it can be concluded that alleviating neuronal apoptosis by NTE after cerebral ischemia-reperfusion injury is one of the important mechanisms to achieve neuroprotection. The pharmacodynamic substances of NTE for alleviating neuronal apoptosis on the one hand are related to components directly absorbed into blood, such as ferulic acid, calycosin, salidroside, 6-gingerol, and 2-methoxycinnamaldehyde and on the other hand are also closely linked to its indirect regulation of purine metabolism in the body to produce adenosine and inosine. Therefore, our research not only identified the main pharmacodynamic substances of NTE that alleviated neuronal apoptosis but also provided a methodological reference for studying other neuroprotective effects of NTE.
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http://dx.doi.org/10.1155/2022/2112433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8938065PMC
March 2022

Identification and Integrated Analysis of the miRNA-mRNA Regulatory Network in Lens from an HO-Induced Zebrafish Cataract Model.

Curr Eye Res 2022 Jun 22;47(6):854-865. Epub 2022 Mar 22.

Department of Ophthalmology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.

Purpose: This study aimed to explore the regulatory mechanisms of age-related cataract (ARC) formation.

Methods: Cataracts in zebrafish were induced by injecting hydrogen peroxide into the fish anterior chamber. The mRNA and miRNA expression profiles of the lens from HO-injected and PBS-injected zebrafishes were detected by RNA sequencing. The LIMMA package was applied to identify differentially expressed genes (DEGs). Gene Ontology categories were enriched by the R "cluster Profiler" package and Kyoto Encyclopedia of Genes and Genomes pathway enrichment was performed based on hypergeometric distribution using the R "phyper" function. The protein-protein interaction network of DEGs was built the STRING. Target genes of differentially expressed miRNAs (DEmiRs) were predicted by miRanda. Furthermore, DEGs were selected as DEmiR targets and a DEmiR-DEG regulatory network was constructed Cytoscape.

Results: In total, 3689 DEGs (such as opn1mw4, LOC103908930, si:dkeyp-1h4.8, crispld1b, cyp1a, and gdpd3a) including 2478 upregulated and 1211 downregulated genes were identified. 177 DEmiRs (such as dre-miR-96-3p, dre-miR-182-5p, dre-miR-9-7-3p, and dre-miR-124-4-5p) including 108 upregulated and 69 downregulated miRNAs were detected. The DEGs are involved in cell death, DNA repair, and cell development-related pathways. A protein-protein interaction network including 79 node genes was constructed to explore the interactions of DEGs. Furthermore, a DEmiR-DEG regulatory network focusing on the DNA repair process was constructed, including 21 hub DEGs and 15 hub DEmiRs.

Conclusions: We identified several DEGs and constructed a miRNA-mRNA regulatory network related to the DNA repair process in a zebrafish cataract model. These genes participate in the oxidative stress response of lens epithelium cells and finally contribute to the formation of zebrafish cataracts. The hub DEGs and hub DEmiRs could be potential therapeutic targets for ARC.
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http://dx.doi.org/10.1080/02713683.2022.2050263DOI Listing
June 2022

Heterogenous and Low Expression of HER2 in Breast Cancer Overcome by DS-8201a in a Heavily Treated Patient: Case Report and Review of the Literature.

Clin Med Insights Oncol 2022 23;16:11795549211072880. Epub 2022 Feb 23.

Department of Breast Cancer, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Breast cancer is highly heterogenous with temporal and spatial heterogeneity making it necessary for rebiopsy. DS-8201a, a new potential therapy for human epidermal growth factor receptor 2 (HER2) low expression breast cancer, had been proved that it could overcome heterogenous HER2 expression in a preclinical setting. In January 2014, a 23-year-old woman was presented with a lump in the right breast with bone metastasis, diagnosed as infiltrating ductal carcinoma, estrogen receptor (ER)+, progesterone receptor (PR)+, HER2 immunohistochemistry (IHC) 2+, and fluorescence in situ hybridization negative. The patient received a series of therapies including surgery, radiotherapy, endocrine therapy, target therapy, and chemotherapy. The longest progression-free survival was 17 months after surgery. Biopsy of liver metastasis in February 2020 showed triple negative (HER2-, ER-, PR-), which was quite different from the initial diagnosis in 2014, so retesting was performed and the results showed ER-, PR+ by 10%, HER2 IHC score of 1+, indicating heterogeneity of HER2 expression. In May 2020, DS-8201a treatment was initiated and continued for 10 cycles until November 2020. Remarkable relief in symptoms was observed after the first dose. A reduction in the metastatic lesion size (liver and brain) and improved liver function was observed during the therapy. This case indicated the heterogeneity of breast cancer, and impressive efficacy of DS-8201a in a heavily treated patient with HER2-low and HER2 heterogeneity.
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http://dx.doi.org/10.1177/11795549211072880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8883389PMC
February 2022

A broad-spectrum nanobody targeting the C-terminus of the hepatitis B surface antigen for chronic hepatitis B infection therapy.

Antiviral Res 2022 03 17;199:105265. Epub 2022 Feb 17.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Science, Xiamen University, Xiamen, 361105, China.

Sustainable viral suppression with hepatitis B surface antigen (HBsAg) loss is the new treatment goal for chronic hepatitis B (CHB). The role of antibodies in therapies for persistent hepatitis B virus (HBV) infection has received constant attention. While immunotherapy holds great promise, challenges for the antibody-based prevention and control of HBV in CHB include broad HBV antigenic diversity and the need for long-term viral suppression. In this study, we identified a new anti-HBsAg nanobody (Nb), 125s, isolated from HBsAg-immunized alpaca and confirmed its excellent potency in HBsAg clearance and broad-spectrum therapeutic activity against three HBV subtypes in vivo. In addition, we characterized a novel epitope at the C-terminus of the HBsAg surface motif from amino acids 157 to 174. A 125s-based long-term passive immunization program was efficacious at HBsAg clearance and inducing cellular immune responses, offering a promising outlook for CHB immunotherapy.
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http://dx.doi.org/10.1016/j.antiviral.2022.105265DOI Listing
March 2022

A pilot study of the use of dynamic cfDNA from aqueous humor and vitreous fluid for the diagnosis and treatment monitoring of vitreoretinal lymphomas.

Haematologica 2022 Feb 10. Epub 2022 Feb 10.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou.

The diagnosis of vitreoretinal lymphoma (VRL), a rare subtype of primary central nervous system lymphoma (PCNSL), is challenging. We aimed to investigate the mutational landscape of VRL by sequencing circulating tumor DNA (ctDNA) from aqueous humor (AH) and/or vitreous fluid (VF), as well as the application of ctDNA sequencing to diagnosis and treatment monitoring. Baseline AH and/or VF specimens from 15 VRL patients underwent comprehensive genomic profiling using targeted next-generation sequencing. The molecular profiles of paired baseline AH and VF specimens were highly concordant, with comparable allele frequencies (AFs). However, the genetic alterations detected in cerebrospinal fluid (CSF) ctDNA only partially overlapped with those from simultaneously-collected AH/VF samples, with much lower AFs. Serial post-treatment AH or VF samples were available for five patients and their ctDNA AF changes displayed a similar trend as the changes in interleukin 10 (IL-10) levels; an indicator of treatment responses. A cohort of 23 PCNSL patients was included as a comparison group for the genetic landscape and evaluations of the efficacy of ibrutinib. More MYD88 mutations, but fewer IRF4 mutations and CDKN2A/B copy number losses were observed in the baseline samples of PCNSL than VRL patients. The objective response rate of ibrutinib treatment was much higher for PCNSL patients (64.7%, 11/17) than VRL (14.3%, 1/7) patients. In summary, we provided valuable clinical evidence that AH is a good source of tumor genomic information and can be substituted for VF. Moreover, molecular profiling of AH has clinical utility for the diagnosis of VRL and treatment monitoring.
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http://dx.doi.org/10.3324/haematol.2021.279908DOI Listing
February 2022

Framework Nucleic Acid-Based Spatial-Confinement Amplifier for miRNA Imaging in Living Cells.

Anal Chem 2022 02 2;94(6):2934-2941. Epub 2022 Feb 2.

College of Chemistry and Chemical Engineering, the Hunan Provincial Key Laboratory of Water Environment and Agriculture Product Safety, Central South University, Changsha 410083, Hunan, China.

Real-time monitoring of miRNAs in living cells is often appealed to signal amplifiers to tackle their low abundance challenges. However, the poor kinetics of amplifiers and potential interferences from the complex intracellular environment hamper its widespread applications . Herein, we report a framework nucleic acid (FNA)-based nonenzymatic spatial-confinement amplifier for rapid and reliable intracellular miRNA imaging. The amplifier consists of a localized catalytic hairpin assembly (L-CHA) reactor encapsulated in the inner cavity of an FNA (a 20 bp cube). The L-CHA reactor is certainly confined to the internal frame by integrating two probes (H1 and H2) of the L-CHA within a DNA strand and harnessing it to the opposite angles of the cube. We find that the stability of the amplifier is remarkably improved due to the protection of the FNA. More importantly, the spatial-confinement effect of the FNA can endow the confined L-CHA amplifier with enhanced local concentrations of reagents (5000-fold), thereby accelerating the reaction rate and improving the dynamic performance (up to 14.34-fold). With these advantages, the proposed amplifier can enable accurate and effective monitoring of miRNA expression levels in living cells and poses great potential in medical diagnostics and biomedical research.
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http://dx.doi.org/10.1021/acs.analchem.1c04866DOI Listing
February 2022

Fungal commensalism modulated by a dual-action phosphate transceptor.

Cell Rep 2022 01;38(4):110293

State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address:

Successful host colonization by fungi in fluctuating niches requires response and adaptation to multiple environmental stresses. However, our understanding about how fungal species thrive in the gastrointestinal (GI) ecosystem by combing multifaceted nutritional stress with respect to homeostatic host-commensal interactions is still in its infancy. Here, we discover that depletion of the phosphate transceptor Pho84 across multiple fungal species encountered a substantial cost in gastrointestinal colonization. Mechanistically, Pho84 enhances the gastrointestinal commensalism via a dual-action activity, coordinating both phosphate uptake and TOR activation by induction of the transcriptional regulator Try4 and downstream commensalism-related transcription. As such, Pho84 promotes Candida albicans commensalism, but this does not translate into enhanced pathogenicity. Thus, our study uncovers a specific nutrient-dependent dual-action regulatory pathway for Pho84 on fungal commensalism.
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http://dx.doi.org/10.1016/j.celrep.2021.110293DOI Listing
January 2022

Methazolamide Attenuates the Development of Diabetic Cardiomyopathy by Promoting β-Catenin Degradation in Type 1 Diabetic Mice.

Diabetes 2022 04;71(4):795-811

Key Laboratory of Molecular Target and Clinical Pharmacology and the State and NMPA Key Laboratory, School of Pharmaceutical Sciences and The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.

Methazolamide (MTZ), a carbonic anhydrase inhibitor, has been shown to inhibit cardiomyocyte hypertrophy and exert a hypoglycemic effect in patients with type 2 diabetes and diabetic db/db mice. However, whether MTZ has a cardioprotective effect in the setting of diabetic cardiomyopathy is not clear. We investigated the effects of MTZ in a mouse model of streptozotocin-induced type 1 diabetes mellitus (T1DM). Diabetic mice received MTZ by intragastric gavage (10, 25, or 50 mg/kg, daily for 16 weeks). In the diabetic group, MTZ significantly reduced both random and fasting blood glucose levels and improved glucose tolerance in a dose-dependent manner. MTZ ameliorated T1DM-induced changes in cardiac morphology and dysfunction. Mechanistic analysis revealed that MTZ blunted T1DM-induced enhanced expression of β-catenin. Similar results were observed in neonatal rat cardiomyocytes (NRCMs) and adult mouse cardiomyocytes treated with high glucose or Wnt3a (a β-catenin activator). There was no significant change in β-catenin mRNA levels in cardiac tissues or NRCMs. MTZ-mediated β-catenin downregulation was recovered by MG132, a proteasome inhibitor. Immunoprecipitation and immunofluorescence analyses showed augmentation of AXIN1-β-catenin interaction by MTZ in T1DM hearts and in NRCMs treated with Wnt3a; thus, MTZ may potentiate AXIN1-β-catenin linkage to increase β-catenin degradation. Overall, MTZ may alleviate cardiac hypertrophy by mediating AXIN1-β-catenin interaction to promote degradation and inhibition of β-catenin activity. These findings may help inform novel therapeutic strategy to prevent heart failure in patients with diabetes.
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http://dx.doi.org/10.2337/db21-0506DOI Listing
April 2022

A High-Performance In-Memory Photodetector Realized by Charge Storage in a van der Waals MISFET.

Adv Mater 2022 Mar 31;34(10):e2107734. Epub 2022 Jan 31.

Key Laboratory of Optoelectronics Technology, College of Microelectronics, Faculty of Information Technology, Beijing University of Technology, Beijing, 100124, China.

The emerging data-intensive applications in optoelectronics are driving innovation toward the fused integration of sensing, memory, and computing to break through the restrictions of the von Neumann architecture. However, the present photodetectors with only optoelectronic conversion functions cannot satisfy the growing demands of the multifunctions required in single devices. Here, a novel route for the integration of non-volatile memory into a photodetector is proposed, with a WSe /h-BN van der Waals heterostructure on a Si/SiO substrate to realize in-memory photodetection. This photodetector exhibits an ultrahigh readout photocurrent of 3.4 µA and photoresponsivity of 337.8 A W in the solar-blind wavelength region, together with an extended retention time of more than 10 years. Furthermore, the charge-storage-based non-volatile mechanism of h-BN/SiO is successfully proven through a novel analysis of in situ optoelectronic electron energy-loss spectroscopy. These results represent a leap forward to future applications and insightful mechanisms of in-memory photodetection.
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http://dx.doi.org/10.1002/adma.202107734DOI Listing
March 2022

Bone protein analysis via label-free quantitative proteomics in patients with periprosthetic joint infection.

J Proteomics 2022 02 6;252:104448. Epub 2021 Dec 6.

Department of Orthopedic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China. Electronic address:

Periprosthetic joint infection (PJI) is a catastrophic complication of arthroplasty. The treatment of PJI often requires multiple operations and long-term use of antibiotics, making PJI a substantial health and economic burden for patients. Therefore, there is an urgent need to elucidate the pathological mechanism of PJI to explore new therapeutic methods. This study aimed to explore proteomics changes in bone tissue around the prosthesis during PJI development, to explain the pathological mechanism and to provide new treatment ideas. Ten patients who underwent revision surgery at our institution were included: 5 patients with Staphylococcus aureus PJI and 5 patients with aseptic failure. The proteomics changes in bone tissues after PJI were investigated by label-free quantitative proteomics, and the pathways affected by the differential proteins were analyzed by GO annotation, GO enrichment analysis, KEGG enrichment analysis and protein-protein interaction network analysis. We identified 435 differentially expressed proteins (DEPs), with 213 upregulated and 222 downregulated proteins. Analysis revealed activation of immune-related pathways, such as complement and coagulation cascades, phagocytosis, and neutrophil activation, and inhibition of energy metabolism pathways represented by the TCA cycle. We also observed an altered balance between osteoblasts and osteoclasts during S. aureus PJI. We hope that these processes will reveal new treatment ideas. SIGNIFICANCE: PJI is a catastrophic complication of arthroplasty. When infection occurs, bacteria may invade periprosthetic bone tissue to escape immunity and cause damage. So far, only few studies focused on the changes of proteomics associated to PJI. This is the first study to describe the proteomics changes of periprosthetic bone tissue of patients with PJI. We found that the pathological process of S. aureus PJI mainly involves activation of the immune system, decreased energy metabolism, and an altered balance of osteoblasts and osteoclasts.
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http://dx.doi.org/10.1016/j.jprot.2021.104448DOI Listing
February 2022

The Calcium Channel Inhibitor Nimodipine Shapes the Uveitogenic T Cells and Protects Mice from Experimental Autoimmune Uveitis through the p38-MAPK Signaling Pathway.

J Immunol 2021 Nov 19. Epub 2021 Nov 19.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China

Autoimmune uveitis (AU) is a sight-threatening ocular inflammatory disorder, characterized by massive retinal vascular leakage and inflamed lesions with infiltration of the uveitogenic T cells in the retina and disorders of the T cell-related immune response in the system. Stimulation of TCRs can trigger calcium release and influx via Ca channels and then transmit signals from the surface to the nucleus, which are important for energy metabolism, proliferation, activation, and differentiation. Inhibition of Ca influx by pharmacological modulation of Ca channels may suppress T cell function, representing a novel anti-inflammatory strategy in the treatment of AU. This study investigated the effects of the l-type voltage-gated calcium channel blocker nimodipine in experimental AU (EAU). Nimodipine was found to not only decrease the clinical and histopathological inflammation score of EAU (C57BL/6J mice) but also dwindle the infiltration of uveitogenic CD4 T cells into the retina. Moreover, nimodipine decreased the effector T cells and increased the regulatory T cells in the immune system. In vitro, nimodipine reduced the effector T cell differentiation of the IRBP-specific CD4 T cells of EAU mice and LPS-stimulated PBMCs of uveitis patients. Meanwhile, nimodipine suppressed the energy metabolism, proliferation, activation, and Th1 cell differentiation of T cells. Further studies on RNA sequencing and molecular mechanisms have established that nimodipine alleviates EAU by regulating T cells response through the p38-MAPK pathway signaling. Taken together, our data reveal a novel therapeutic potential of the l-type Ca channels antagonist nimodipine in AU by regulating the balance of T cell subsets.
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http://dx.doi.org/10.4049/jimmunol.2100568DOI Listing
November 2021
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