Publications by authors named "Xiaoyi Li"

184 Publications

An effective approach to develop targetable and responsive fluorescent probes for imaging of organelles based on cresyl violet scaffold.

Biosens Bioelectron 2022 Mar 31;200:113929. Epub 2021 Dec 31.

Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

Fluorescent probes combined with confocal microscopy are recognized as a powerful tool for imaging living cells and even organelles due to their high sensitivity and resolution. However, many of analyte-activatable and organelle-targetable fluorescent probes are developed via tedious attempts, and a relatively predictable method to design such probes is still lacking. Herein, we put forward an effective synthetic strategy to construct both targetable and responsive probes for organelles based on the cresyl violet scaffold. The approach allows access to a variety of organelle-targeting fluorescent probes for an analyte of interest via introducing the corresponding targeting and recognition groups to the 5- and 9-positions of cresyl violet, respectively. The potency of the approach is exemplified by its application to develop four cresyl violet-based fluorophores with different organelle-targeting groups, and a mitochondrion-targeting ratiometric probe capable of imaging Pd in living cells.
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http://dx.doi.org/10.1016/j.bios.2021.113929DOI Listing
March 2022

Single-cell RNA sequencing reveals a pro-invasive cancer-associated fibroblast subgroup associated with poor clinical outcomes in patients with gastric cancer.

Theranostics 2022 1;12(2):620-638. Epub 2022 Jan 1.

Center for Bioinformatics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.

The protumor activities of cancer-associated fibroblasts (CAFs) suggest that they are potential therapeutic targets for the treatment of cancer. The mechanism of CAF heterogeneity in gastric cancer (GC) remains unclear and has slowed translational advances in targeting CAFs. Therefore, a comprehensive understanding of the classification, function, activation stage, and spatial distribution of the CAF subsets in GC is urgently needed. In this study, the characteristics of the CAF subsets and the dynamic communication among the tumor microenvironment (TME) components regulated by the CAF subsets were analyzed by performing single-cell RNA sequencing of eight pairs of GC and adjacent mucosal (AM) samples. The spatial distribution of the CAF subsets in different Lauren subtypes of GC, as well as the neighborhood relations between these CAF subsets and the protumor immune cell subsets were evaluated by performing multistaining registration. Tumor epithelial cells exhibited significant intratumor and intertumor variabilities, while CAFs mainly exhibited intratumor variability. Moreover, we identified four CAF subsets with different properties in GC. These four CAF subsets shared similar properties with their resident fibroblast counterparts in the adjacent mucosa but also exhibited enhanced protumor activities. Additionally, two CAF subsets, inflammatory CAFs (iCAFs) and extracellular matrix CAFs (eCAFs), communicated with adjacent immune cell subsets in the GC TME. iCAFs interacted with T cells by secreting interleukin (IL)-6 and C-X-C motif chemokine ligand 12 (CXCL12), while eCAFs correlated with M2 macrophages via the expression of periostin (POSTN). eCAFs, which function as a pro-invasive CAF subset, decreased the overall survival time of patients with GC. iCAFs and eCAFs not only exhibited enhanced pro-invasive activities but also mobilized the surrounding immune cells to construct a tumor-favorable microenvironment. Therefore, inhibiting their activation restrains the GC 'seed' and simultaneously improves the 'GC' soil, suggesting that it represents a promising therapeutic strategy for the treatment of GC.
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http://dx.doi.org/10.7150/thno.60540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8692898PMC
January 2022

Long noncoding RNA PVT1 promotes breast cancer proliferation and metastasis by binding miR-128-3p and UPF1.

Breast Cancer Res 2021 Dec 18;23(1):115. Epub 2021 Dec 18.

Department of Medical Laboratory, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, 26 Shengli St., Jiangan District, Wuhan, 430014, China.

Background: Mounting evidence supports that long noncoding RNAs (lncRNAs) have critical roles during cancer initiation and progression. In this study, we report that the plasmacytoma variant translocation 1 (PVT1) lncRNA is involved in breast cancer progression.

Methods: qRT-PCR and western blot were performed to detect the gene and protein expression. Colony formation would healing and transwell assays were used to detect cell function. Dual-luciferase reporter assay and RNA pull-down experiments were used to examine the mechanisms interaction between molecules. Orthotopic mouse models were established to evaluate the influence of PVT1 on tumor growth and metastasis in vivo.

Results: PVT1 is significant upregulated in breast cancer patients' plasma and cell lines. PVT1 promotes breast cancer cell proliferation and metastasis both in vitro and in vivo. Mechanistically, PVT1 upregulates FOXQ1 via miR-128-3p and promotes epithelial-mesenchymal transition. In addition, PVT1 binds to the UPF1 protein, thereby inducing epithelial-mesenchymal transition, proliferation and metastasis in breast cancer cells.

Conclusion: PVT1 may act as an oncogene in breast cancer through binding miR-128-3p and UPF1 and represents a potential target for BC therapeutic development.
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http://dx.doi.org/10.1186/s13058-021-01491-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8684126PMC
December 2021

Excess Heritability Contribution of Alcohol Consumption Variants in the "Missing Heritability" of Type 2 Diabetes Mellitus.

Int J Mol Sci 2021 Nov 15;22(22). Epub 2021 Nov 15.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China.

We aim to compare the relative heritability contributed by variants of behavior-related environmental phenotypes and elucidate the role of these factors in the conundrum of "missing heritability" of type 2 diabetes. Methods: We used Linkage-Disequilibrium Adjusted Kinships (LDAK) and LDAK-Thin models to calculate the relative heritability of each variant and compare the relative heritability for each phenotype. Biological analysis was carried out for the phenotype whose variants made a significant contribution. Potential hub genes were prioritized based on topological parameters of the protein-protein interaction network. We included 16 behavior-related phenotypes and 2607 valid variants. In the LDAK model, we found the variants of alcohol consumption and caffeine intake were identified as contributing higher relative heritability than that of the random variants. Compared with the relative expected heritability contributed by the variants associated with type 2 diabetes, the relative expected heritability contributed by the variants associated with these two phenotypes was higher. In the LDAK-Thin model, the relative heritability of variants of 11 phenotypes was statistically higher than random variants. Biological function analysis showed the same distributions among type 2 diabetes and alcohol consumption. We eventually screened out 31 hub genes interacting intensively, four of which were validated and showed the upregulated expression pattern in blood samples seen in type 2 diabetes cases. Conclusion: We found that alcohol consumption contributed higher relative heritability. Hub genes may influence the onset of type 2 diabetes by a mediating effect or a pleiotropic effect. Our results provide new insight to reveal the role of behavior-related factors in the conundrum of "missing heritability" of type 2 diabetes.
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http://dx.doi.org/10.3390/ijms222212318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623960PMC
November 2021

Improvement of stability and reduction of energy consumption for Ti-based MnO electrode by Ce and carbon black co-incorporation in electrochemical degradation of ammonia nitrogen.

Water Sci Technol 2021 Nov;84(9):2278-2287

Collaborative Innovation Center for Vessel Pollution Monitoring and Control, Dalian Maritime University, Dalian 116026, China E-mail:

Ti-based electrode coated with MnO catalytic layer has presented superior electrochemical activity for degradation of organic pollution in wastewater, however, the industrial application of Ti-based MnO electrode is limited by the poor stability of the electrode. In this study, the novel Ti-based MnO electrodes co-incorporated with rare earth (Ce) and conductive carbon black (C) were prepared by spraying-calcination method. The Ti/Ce:MnO-C electrode, with uniform and integrated surface and enhanced Mn(IV) content by C and Ce co-incorporation, could completely remove ammonia nitrogen (NH-N) with N as the main product. The cell potential and energy consumption of Ti/Ce:MnO-C electrode during the electrochemical process was significantly reduced compared with Ti/MnO electrode, which mainly originated from the enhanced electrochemical activity and reduced charge transfer resistance by Ce and C co-incorporation. The accelerated lifetime tests in sulfuric acid showed that the actual service lifetime of Ti/Ce:MnO-C was ca. 25 times that of Ti/MnO, which demonstrated the significantly promoted stability of MnO-based electrode by Ce and C co-incorporation.
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http://dx.doi.org/10.2166/wst.2021.421DOI Listing
November 2021

Recent Progress in Self-Powered Sensors Based on Triboelectric Nanogenerators.

Sensors (Basel) 2021 Oct 27;21(21). Epub 2021 Oct 27.

School of Materials Science and Engineering, Ocean University of China, Qingdao 266100, China.

The emergence of the Internet of Things (IoT) has subverted people's lives, causing the rapid development of sensor technologies. However, traditional sensor energy sources, like batteries, suffer from the pollution problem and the limited lifetime for powering widely implemented electronics or sensors. Therefore, it is essential to obtain self-powered sensors integrated with renewable energy harvesters. The triboelectric nanogenerator (TENG), which can convert the surrounding mechanical energy into electrical energy based on the surface triboelectrification effect, was born of this background. This paper systematically introduces the working principle of the TENG-based self-powered sensor, including the triboelectrification effect, Maxwell's displacement current, and quantitative analysis method. Meanwhile, this paper also reviews the recent application of TENG in different fields and summarizes the future development and current problems of TENG. We believe that there will be a rise of TENG-based self-powered sensors in the future.
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http://dx.doi.org/10.3390/s21217129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587673PMC
October 2021

Identification and Mapping of HBsAg Loss-Related B-Cell Linear Epitopes in Chronic HBV Patients by Peptide Array.

Front Immunol 2021 15;12:767000. Epub 2021 Oct 15.

State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Identification of immunogenic targets against hepatitis B virus (HBV)-encoded proteins will provide crucial advances in developing potential antibody therapies. In this study, 63 treatment-naïve patients with chronic HBV infection and 46 patients who achieved hepatitis B surface antigen loss (sAg loss) following antiviral treatment were recruited. Moreover, six patients who transitioned from the hepatitis B e antigen-positive chronic infection phase (eAgCInf) to the hepatitis phase (eAgCHep) were enrolled from real-life clinical practice. Additionally, telbivudine-treated eAgCHep patients and relapsers or responders from an off-treatment cohort were longitudinally studied. The frequencies and function of B cells were assessed by flow cytometry. We devised a peptide array composed of 15-mer overlapping peptides of HBV-encoded surface (S), core (C), and polymerase (P) proteins and performed a screening on B-cell linear epitopes with sera. Naïve B cells and plasmablasts were increased, whereas total memory, activated memory (AM), and atypical memory (AtM) B cells were reduced in sAg patients compared with sAg patients. Importantly, longitudinal observations found that AtM B cells were associated with successful treatment withdrawal. Interestingly, we identified six S-specific dominant epitopes (S33, S34, S45, S76, S78, and S89) and one C-specific dominant epitope (C37) that reacted with the majority of sera from sAg patients. Of note, more B-cell linear epitopes were detected in CHep patients with alanine aminotransferase (ALT) flares than in nonflare CInf patients, and five B-cell linear epitopes (S4, S5, S10, S11, and S68) were overwhelmingly recognized by ALT flare patients. The recognition rates of epitopes on C and P proteins were significantly increased in CHep patients relative to CInf patients. Strikingly, a statistically significant elevation in the number of positive epitopes was observed when ALT nonflare patients shifted into the flare phase. Moreover, S76 identified at baseline was confirmed to be associated with a complete response after 48 weeks of telbivudine therapy. Taken together, we identified several functional cure-related B-cell linear epitopes of chronic HBV infection, and these epitopes may serve as vaccine candidates to elicit neutralizing antibodies to treat HBV infection.
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http://dx.doi.org/10.3389/fimmu.2021.767000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554339PMC
October 2021

Left ventricular and atrial remodelling in hypertensive patients using thresholds from international guidelines and EMINCA data.

Eur Heart J Cardiovasc Imaging 2021 Oct 29. Epub 2021 Oct 29.

The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, 107 Wenhuaxi Road, Jinan 250012, China.

Aims: To investigate differences in the prevalence of left ventricular (LV) and left atrial (LA) remodelling in hypertensive patients using various thresholds defined by international guidelines and data from the Echocardiographic Measurements in Normal Chinese Adults (EMINCA) study and different indexation methods.

Methods And Results: LV mass (LVM), relative ventricular wall thickness, and LA volume (LAV) were measured using 2D echocardiography in 612 healthy volunteers selected from the EMINCA study population and 306 adult Chinese patients with hypertension who were age- and gender-matched using propensity score-matched analysis. LVM and LAV values were indexed to body surface area (BSA), height2.7, height1.7, and height2 recommended by guidelines or investigators. Using a previously reported method, LV geometry was divided into normal geometry, concentric remodelling, eccentric hypertrophy, and concentric hypertrophy. The prevalence of LV hypertrophy (LVH) and LV geometric patterns in hypertensive patients were compared using different thresholds and indexation methods. Echocardiographic thresholds from guidelines and healthy volunteers exhibited notable differences, particularly for LAV indexed to height2 and for LVM indexed to height1.7, which resulted in a significantly lower prevalence of LA dilatation and LVH in healthy volunteers. The total proportion of abnormal LV geometric patterns was significantly lower with thresholds from healthy volunteers than from guidelines when LVM was indexed to BSA, height1.7, and height2,7.

Conclusion: Using current echocardiographic thresholds and indexing methods recommended by guidelines may lead to significant misdiagnosis of LA dilatation, and abnormal LV geometry in Chinese patients with hypertension, and thresholds based on ethnic-specific normal echocardiographic reference values and an accurate indexing algorithm are warranted.
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http://dx.doi.org/10.1093/ehjci/jeab216DOI Listing
October 2021

FeP encapsulated in carbon nanowalls decorated with well-dispersed FeC nanodots for efficient hydrogen evolution and oxygen reduction reactions.

Nanoscale 2021 Nov 4;13(42):17920-17928. Epub 2021 Nov 4.

School of Materials Science and Engineering, International S&T Cooperation Foundation of Shaanxi Province, Xi'an Key Laboratory of Green Manufacture of Ceramic Materials, Key Laboratory of Auxiliary Chemistry and Technology for Chemical Industry, Ministry of Education, Shaanxi University of Science and Technology, Xi'an, 710021, China.

The development of cost-effective, high-efficiency bifunctional electrocatalysts as alternatives to the state-of-the-art Pt-based materials toward the hydrogen evolution reaction (HER) and oxygen reduction reaction (ORR) is of great significance but still challenging. Herein, an advanced bifunctional electrocatalyst is presented, composed of FeP encapsulated in carbon nanowalls decorated with well-dispersed FeC nanodots (denoted as [email protected]/CNTs), which is achieved by a novel "inside-out" gas-solid reaction protocol. When functioning as a cathodic catalyst for water splitting, the [email protected]/CNT catalyst needs an ultralow overpotential of 83 mV to deliver a current density of 10 mA cm, shows a small Tafel slope of 53 mV dec and ensures long-term stability for over 200 h in an alkaline electrolyte. Notably, the [email protected]/CNT catalyst exhibits an extremely impressive ORR performance with an onset potential () of 1.060 V and a half-wave potential () of 0.930 V, excellent stability (≈94% activity retention after 36 000 s), and a strong methanol resistance ability, even far outperforming commercial Pt/C ( = 0.955 V, = 0.825 V, ≈75% activity retention after less than 3500 s). Such outstanding HER and ORR performances are mainly ascribed to the improved corrosion resistance of the unique [email protected] core-shell structures, the abundant catalytically active sites of ultrasmall FeC nanodots incorporated in carbon nanowalls, and the good electrical conductivity of 2D graphitic carbon nanotubes used as a support.
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http://dx.doi.org/10.1039/d1nr03380hDOI Listing
November 2021

β-galactosidase GALA from with high transgalactosylation activity.

Bioengineered 2021 12;12(1):8908-8919

Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China.

β-galactosidase catalyzes lactose hydrolysis and transfers reactions to produce prebiotics such as galacto-oligosaccharides (GOS) with potential applications in the food industry and pharmaceuticals. However, there is still a need for improved transgalactosylation activity of β-galactosidases and reaction conditions of GOS production in order to maximize GOS output and reduce production costs. In this study, a β-galactosidase gene, , from was expressed in , which not only hydrolyzed lactose but also had strong transgalactosylation activity to produce GOS. Response surface methodology was adopted to investigate the effects of temperature, enzyme concentration, pH, initial lactose concentration, and reaction time on the production of GOS and optimize the reaction conditions for GOS. The optimal pH for the enzyme was 6.0 and remained stable under neutral and basic conditions. Meanwhile, GALA showed most activity at 50°C and retained considerable activity at a lower temperature 30-40°C, indicating this enzyme could work under mild conditions. The enzyme concentration and temperature were found to be the critical parameters affecting the transgalactosylation activity. Response surface methodology showed that the optimal enzyme concentration, initial lactose concentration, temperature, pH, and reaction time were 3.03 U/mL, 500 g/L, 30°C, 5.08, and 4 h, respectively. Under such conditions, the maximum yield of GOS was 252.8 g/L, accounting for approximately 50.56% of the total sugar. This yield can be considered relatively high compared to those obtained from other sources of β-galactosidases, implying a great potential for GALA in the industrial production and application of GOS.
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http://dx.doi.org/10.1080/21655979.2021.1988370DOI Listing
December 2021

Access to Chiral Chromenones through Organocatalyzed Mannich/Annulation Sequence.

Org Lett 2021 10 4;23(20):8007-8012. Epub 2021 Oct 4.

School of Pharmaceutical Sciences and Chongqing Key Laboratory of Natural Drug Research, Chongqing University, Chongqing 401331, P. R. China.

Herein we report an efficient and practical method to access chiral chromenones bearing one α-amino stereogenic center in the β position of the carbonyl group. The quinine-derived squaramide could efficiently promote Mannich/cycloketalization/dehydration tandem reactions between 1-(2-hydroxyaryl)-1,3-diketones and functionalized imines generated , providing a wide range of chiral chromenones with propargylamine or α-amino ester moieties with good results (54 examples, up to 98% ee).
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http://dx.doi.org/10.1021/acs.orglett.1c03010DOI Listing
October 2021

Removal of elemental mercury from flue gas using the magnetic attapulgite by Mn-Cu oxides modification.

Environ Sci Pollut Res Int 2021 Oct 2. Epub 2021 Oct 2.

School of Resource and Environmental Sciences, Wuhan University, Wuhan, Hubei, 430079, People's Republic of China.

Mercury pollution has become one of the most concerned environmental issues in the world because of its high toxicity, non-degradability, and bioaccumulation. Attapulgite adsorbents modified by magnetic manganese-copper (MnCu-MATP) were fabricated by co-precipitation and ultrasonic impregnation method, aiming at removing Hg from coal-fired flue gas. BET, SEM, XRD, VSM, and XPS were used to systematically explore the physical and chemical properties of the adsorbents, the effects of manganese and copper additions, reaction temperature, and various components in the flue gas on the efficiency of Hg removal were investigated. MnCu-MATP exhibited the optimal properties, and excessive copper loadings led to the aggregation of the active components. The efficiency of mercury removal can be effectively improved by NO and HCl regardless of the absence and presence of O, because the NO, NO, NO, and Cl* produced during the reaction can promote the adsorption and oxidation of Hg. SO and HO inhibited the oxidation of Hg because of the competitive adsorption at the active sites, while a large amount of sulfite and sulfate were formed to block the pores. However, the introduction of copper caused the sample to obtain SO resistance, which resulted in a mercury removal efficiency of 84.3% even under 1500 ppm SO. In addition, after 5 cycles of adsorption and regeneration, MnCu-MATP can still maintain excellent Hg removal ability. The fabricated adsorbent can save the actual production cost and effectively improve the mercury removal efficiency in sulfur-containing flue gas.
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http://dx.doi.org/10.1007/s11356-021-16777-zDOI Listing
October 2021

Measurement of talc in flour by the prompt-gamma ray neutron activation analysis method.

Appl Radiat Isot 2021 Dec 10;178:109932. Epub 2021 Sep 10.

College of Physics, Jilin University, Changchun, 130012, China.

Prompt gamma-ray neutron activation analysis method (PGNAA) was used to measure the talc content in flour. Neutron activation prompt gamma spectrum measured by NaI(Tl) detector has complex components, poor energy resolution, and high Compton plateau, how to obtain accurate element content from the prompt γ spectrum is one of the core problems of PGNAA. To reduce the systematic uncertainty caused by the variation of the neutron energy spectrum and γ self-absorption in different samples, the spectral decomposition method based on library least-squares was improved. As a result, the average relative deviation between the calculated values from measured spectra and the theoretical values based on the known composition was reduced from 6.1% to 0.3%. The relative uncertainty of 30 measurements on the same sample was reduced from 4.8% to 3.0%. The detection time can be reduced to 1 min, which meets the requirement of on-line measurement for talc in flour.
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http://dx.doi.org/10.1016/j.apradiso.2021.109932DOI Listing
December 2021

ATP-binding cassette transporter subfamily C members 2, 3 and cadherin protein are susceptibility-determining factors in Bombyx mori for multiple Bacillus thuringiensis Cry1 toxins.

Insect Biochem Mol Biol 2021 12 22;139:103649. Epub 2021 Sep 22.

Institute of Agrobiological Sciences, NARO, 1-2 Ohwashi, Tsukuba, Ibaraki 305-8634, Japan. Electronic address:

Field-evolved resistance of insect pests to Bacillus thuringiensis (Bt) toxins (Cry toxins) is a threat to the efficacy of Bt-based bio-insecticides and transgenic crops. Recent reports have suggested that ATP-binding cassette transporter subfamily C2 (ABCC2) and cadherin-like receptor play important roles in conferring susceptibility to Cry1 toxins. However, the receptors involved in Bt susceptibility in each insect remain unclear. To determine the receptors that are involved in the susceptibility of Bombyx mori to Cry1 toxins (1Ab, 1Ac and 1Fa), we conducted diet overlay bioassay using B. mori strains disrupted with one or two receptor (s) among BmABCC2, BmABCC3, and cadherin-like receptor (BtR175) generated by transcription activator-like effector nuclease (TALEN)-mediated gene editing. The single-knockout strains for BmABCC2 showed resistance to Cry1Ab and Cry1Ac, whereas only strains with double knockout of BmABCC2 and BmABCC3 exhibited high resistance to Cry1Fa. Progeny populations generated from the crossing of heterozygotes for BtR175 knockout allele included 25% theoretical homozygotes for the BtR175 knockout allele and they showed resistance to Cry1Ab and Cry1Ac. Then, through a cell swelling assay using Sf9 cells ectopically expressing the receptor, we analyzed the mechanisms underlying the different contributions of BmABCC2, BmABCC3, and BtR175 to larval susceptibility. The receptor activity of BmABCC2 for Cry1Ab and Cry1Ac was far higher than that of BmABCC3, and BtR175 synergistically enhanced the receptor activity of BmABCC2. This result well explained the important involvement of BmABCC2 and BtR175 in the larval susceptibility to Cry1A toxins. By contrast, the receptor activities of BmABCC2 and BmABCC3 for Cry1Fa were observed at a similar level and synergistic effect of BtR175 was small. This finding explains the equal importance of BmABCC2 and BmABCC3 and very small contribution of BtR175 on larval susceptibility to Cry1Fa. Thus, we demonstrated the different importance of BmABCC2, BmABCC3, and BtR175 to various Cry1 toxins as susceptibility-determining factors in B. mori larvae and the underlying basis for the observed differences. Furthermore, a weak correlation was indicated between the binding affinity and receptor activities of BmABCC2 and BmABCC3 to Cry1 toxins.
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http://dx.doi.org/10.1016/j.ibmb.2021.103649DOI Listing
December 2021

Inducible and reversible inhibition of miRNA-mediated gene repression in vivo.

Elife 2021 08 31;10. Epub 2021 Aug 31.

Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, United States.

Although virtually all gene networks are predicted to be controlled by miRNAs, the contribution of this important layer of gene regulation to tissue homeostasis in adult animals remains unclear. Gain and loss-of-function experiments have provided key insights into the specific function of individual miRNAs, but effective genetic tools to study the functional consequences of global inhibition of miRNA activity in vivo are lacking. Here we report the generation and characterization of a genetically engineered mouse strain in which miRNA-mediated gene repression can be reversibly inhibited without affecting miRNA biogenesis or abundance. We demonstrate the usefulness of this strategy by investigating the consequences of acute inhibition of miRNA function in adult animals. We find that different tissues and organs respond differently to global loss of miRNA function. While miRNA-mediated gene repression is essential for the homeostasis of the heart and the skeletal muscle, it is largely dispensable in the majority of other organs. Even in tissues where it is not required for homeostasis, such as the intestine and hematopoietic system, miRNA activity can become essential during regeneration following acute injury. These data support a model where many metazoan tissues primarily rely on miRNA function to respond to potentially pathogenic events.
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http://dx.doi.org/10.7554/eLife.70948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476124PMC
August 2021

Palladium-Catalyzed Selective [2 + 2 + 2] Annulation of 2-(2-Enynyl)pyridines with Arynes.

J Org Chem 2021 Sep 11;86(17):12403-12411. Epub 2021 Aug 11.

School of Pharmaceutical Sciences and Chongqing Key Laboratory of Natural Drug Research, Chongqing University, Chongqing 401331, P.R. China.

The palladium-catalyzed chemo- and stereoselective [2 + 2 + 2] annulation reaction of 2-(2-enynyl)pyridines with arynes has been developed. A wide range of ()- or ()-isomers of 2-(2-enynyl)pyridines and arynes was tolerated, providing a spectrum of ()-phenanthrenylated 2-alkenylpyridines in good yield, together with the generation of a chiral axis between an alkene and a phenanthrene ring.
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http://dx.doi.org/10.1021/acs.joc.1c01393DOI Listing
September 2021

Pharmacokinetic and pharmacodynamic evaluation of the new prolonged-release leuprorelin acetate microspheres for injection compared with Enantone® in healthy Chinese male volunteers.

Expert Opin Drug Metab Toxicol 2021 Sep 10;17(9):1149-1156. Epub 2021 Aug 10.

First-in-Human Clinical Trial Wards in the National Institute of Clinical Drug Trials, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China.

Purpose: To compare the pharmacokinetics, pharmacodynamics and safety of the new prolonged-release leuprorelin acetate microspheres for injection (3.75 mg) with the reference product Enantone® (3.75 mg).

Method: 48 healthy male volunteers were enrolled and randomly received a single 3.75 mg dose of the test drug or Enantone®.

Results: There were no significant differences in C, AUC and AUC between the test group and reference group (P > 0.05). The 90% confidence intervals of the two groups were 87.49%~112.74%, 97.15%~154.25%, and 80.85%~109.01%, respectively. Twenty-eight days after administration, both groups reached 100.0% castration level; there was no difference in the time from administration to reaching castration level between the two groups (P > 0.05); However, the difference between the two groups in the duration of castration level was statistically significant (P < 0.05). There were no major or serious adverse events, and the severity was mild to moderate.

Conclusion: The pharmacokinetic characteristics of leuprorelin in two groups were consistent. The two groups exhibited similar inhibitory effects on testosterone and more subjects in the test group maintained a longer castration time than those in the reference group.
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http://dx.doi.org/10.1080/17425255.2021.1948534DOI Listing
September 2021

Baicalin Protects Vascular Tight Junctions in Piglets During Infection.

Front Vet Sci 2021 25;8:671936. Epub 2021 Jun 25.

Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM, United States.

() can cause Glässer's disease and severely affect swine industry worldwide. This study is an attempt to address the issue of the capability of to damage the vascular barrier and the effects of baicalin on vascular tight junctions (TJ) in order to investigate the interactions between the pathogen and the porcine vascular endothelium. Piglets were challenged with and treated with or without baicalin. The expressions of vascular TJ genes were examined using RT-PCR. The distribution patterns of TJ proteins were detected by immunofluorescence. The involved signaling pathways were determined by Western blot assays on related proteins. can downregulate TJ expression and disrupt the distribution of TJ proteins. Baicalin can alleviate the downregulation of vascular TJ mRNA, maintain the distribution, and prevent the abnormalities of TJ. These results provide ample evidence that baicalin has the capacity to protect vascular TJ damaged by through inhibiting PKC and MLCK/MLC pathway activation. As a result, baicalin is a promising candidate for application as a natural agent for the prevention and control of infection.
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http://dx.doi.org/10.3389/fvets.2021.671936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267157PMC
June 2021

High L-Carnitine Levels Impede Viral Control in Chronic Hepatitis B Virus Infection.

Front Immunol 2021 21;12:649197. Epub 2021 Jun 21.

State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Persistent antigen exposure during chronic hepatitis B infection leads to exhausted immune responses, thus impeding viral control. In recent years, immunometabolism opens new therapeutic possibilities for the modulation of immune responses. Herein, we investigated the immunomodulatory effect of L-carnitine (L-Cn) on immune cells in chronic HBV infection. In this study, 141 treatment-naïve patients with chronic HBV infection, 38 patients who achieved HBsAg loss following antiviral treatment, and 47 patients who suffered from HBV-related HCC from real-life clinical practice were recruited. The plasma L-Cn levels were measured by ELISA. RNA sequencing was conducted to define the transcriptional profiles of peripheral blood mononuclear cells after L-Cn stimulation. assays were performed to assess the effect of L-Cn on immune cells; the frequencies and function of immune cells were analyzed by flow cytometry. We found that compared with patients with HBsAg loss, patients with HBsAg positivity and patients who suffered from HBV-related HCC had higher levels of L-Cn, and the plasma levels of L-Cn in the HBeAg-positive chronic hepatitis patients who had elevated ALT were significantly higher than that of HBeAg-negative chronic infection and HBsAg loss groups. Moreover, a positive correlation between plasma levels of L-Cn and HBsAg levels was found. Additionally, RNA sequencing analysis demonstrated that L-Cn altered the transcriptional profiles related to immune response. assays revealed that L-Cn suppressed the proliferation of and IFN-γ production by CD4 and CD8 T cells. It also down-regulated the proliferation and IgG production of B cells. Notably, L-Cn enhanced IL-10 secretion from regulatory T cells and up-regulated the expression of inhibitory receptors on T cells. Moreover, a variant in (rs1799821) was confirmed to be associated with L-Cn levels as well as complete response in CHB patients following Peg-IFNα antiviral therapy. Taken together, the immunosuppressive properties of L-Cn may hinder the control of HBV in chronic HBV infection, implicating that L-Cn manipulation might influence the prognosis of patients with HBV infection.
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http://dx.doi.org/10.3389/fimmu.2021.649197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255973PMC
September 2021

Abscisic acid receptors are involves in the Jasmonate signaling in .

Plant Signal Behav 2021 10 5;16(10):1948243. Epub 2021 Jul 5.

Key Laboratory of Bio-Resources and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, China.

The phytohormones jasmonates (JAs) act as important molecules of elicitors for the chlorophyll degradation and anthocyanin biosynthesis. JAs do usually not act independently but integrate in complex networks linking to other hormonal signaling transduction. Here, the crosstalk was detected between the JAs (jasmonic acid) and abscisic acid (ABA) signaling pathways in the mediation of chlorophyll degradation and anthocyanin biosynthesis. In this study, we found that the ABA receptor mutants, (1124) and (112458) showed less level of chlorophyll and anthocyanin than the wild-type plants, while gain-of-function of transgenic lines inhibited chlorophyll degradation and enhanced anthocyanin accumulation after MeJA treatment. The amidohydrolases, including and and cytochrome P450 (), encoding JA-Ile catabolism were markedly depressed by ABA receptors. While transcripts of the enzymes for activation of anthocyanin biosynthesis pathway were analyzed, the results indicating that JA biosynthetic genes, including allene oxide synthase ( and were enhanced by the link of JAs and ABA receptors. Moreover, the ABA receptors are also involved in JAs signal transduction through the regulation of and transcripts. These findings elucidate a connection between a core component of the ABA signaling pathway and JA responses.
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http://dx.doi.org/10.1080/15592324.2021.1948243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8331031PMC
October 2021

Hepatocyte-derived L-carnitine restricts hepatitis B surface antigen loss through an immunosuppressive effect on germinal center-related immune cells.

J Infect Dis 2021 Jul 2. Epub 2021 Jul 2.

State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Background: The outcome of hepatitis B virus (HBV) infection is significantly affected by host immune response; herein, we aim to dissect the effect of L-carnitine (L-Cn) on germinal center (GC)-related immune cells and the influence on the prognosis of HBV infection.

Methods: In vitro and in vivo experiments were performed in patients with chronic HBV infection and a hydrodynamic injection mouse model.

Results: In vitro assays revealed that L-Cn significantly reduced GC-related immune responses and enhanced immunosuppressive profiles. Intriguingly, L-Cn released from lysed hepatocytes was associated with the degree of liver damage. Besides, the administration of L-Cn in an HBV mouse model resulted in delayed clearance of HBsAg in serum and decreased GC formation in the spleen. Notably, patients with HBsAg loss showed decreased plasma L-Cn levels, and longitudinal observations found that low baseline levels of L-Cn were associated with a favorable treatment response in chronic hepatitis B patients.

Conclusions: The suppressive effect of hepatocyte-derived L-Cn on GC-related immune cells may contribute to the inability of HBsAg clearance in chronic HBV infection, indicating that L-Cn might serve as a potential therapeutic target for the treatment of HBV infection.
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http://dx.doi.org/10.1093/infdis/jiab344DOI Listing
July 2021

Covalent Interaction between High Hydrostatic Pressure-Pretreated Rice Bran Protein Hydrolysates and Ferulic Acid: Focus on Antioxidant Activities and Emulsifying Properties.

J Agric Food Chem 2021 Jul 2;69(27):7777-7785. Epub 2021 Jul 2.

College of Food Science, Northeast Agricultural University, Harbin 150030, China.

Rice bran protein hydrolysates (RBPH) pretreated with high hydrostatic pressure (HHP) covalently interacted with ferulic acid (FA) (0.5 to 2.5 mg/mL) under alkaline conditions. The structural and functional properties of the conjugates were investigated. The results revealed that the FA binding equivalent on RBPH increased from 6.03 to 207.64 nmol/mg. FTIR spectral analysis indicated that the content of α-helix increased, whereas the contents of β-sheet, β-turn, and random coil decreased. The surface hydrophobicity () of RBPH increased, the fluorescence intensity decreased, and the tertiary structure changed because of covalent interactions between RBPH and FA. The emulsifying activity index of RBPH-FA (1.5 mg/mL) was 35.10% higher than that of the control, whereas FA concentrations higher than 1.5 mg/mL had a negative effect on emulsifying properties. RBPH-FA (2.5 mg/mL) exhibited the strongest antioxidant activity. This study provides a new reference for the application of RBPH-FA conjugates in food processing.
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http://dx.doi.org/10.1021/acs.jafc.1c01949DOI Listing
July 2021

Corrigendum: Characterizing Adult Cochlear Supporting Cell Transcriptional Diversity Using Single-Cell RNA-Seq: Validation in the Adult Mouse and Translational Implications for the Adult Human Cochlea.

Front Mol Neurosci 2021 3;14:699859. Epub 2021 Jun 3.

Laboratory of Cochlear Development, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD, United States.

[This corrects the article DOI: 10.3389/fnmol.2020.00013.].
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http://dx.doi.org/10.3389/fnmol.2021.699859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209547PMC
June 2021

The response of tartary buckwheat and 19 bZIP genes to abscisic acid (ABA).

Mol Biol Rep 2021 May 7;48(5):4341-4350. Epub 2021 Jun 7.

Key Laboratory of Bio-Resources and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610065, China.

Tartary buckwheat is a kind of plant which can be used as medicine as well as edible. Abscisic acid (ABA) signaling plays an important role in the response of plants such as tartary buckwheat to drought and other stress. However, there are not many studies on tartary buckwheat by ABA treatment. In this study, the germination, root length, stoma, and anthocyanin accumulation of tartary buckwheat were all significantly affected by ABA. ABA signaling is important for plants to respond to drought and other stresses, the bZIP gene family is an important member of the ABA signaling pathway. Through the analysis of the origin relationship between tartary buckwheat bZIP family and its related species, 19 bZIP genes in tartary buckwheat were found to be relatively conserved, which laid a foundation for further study of bZIP family. The qRT-PCR results showed that most of the group members were induced by ABA treatment, including 0, 15, 30, 50, 70 µM ABA and 0, 0.5, 2, 4, 8, 16, 24 h ABA treatment. These results suggested that ABA could affect the growth and development of tartary buckwheat, and FtbZIPs might have different functions in the response of tartary buckwheat to drought. This study will be helpful to further analyze the genetic breeding and economic value of tartary buckwheat resistance.
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http://dx.doi.org/10.1007/s11033-021-06449-zDOI Listing
May 2021

Correction: Assembly of fluorinated chromanones enantioselective tandem reaction.

Chem Commun (Camb) 2021 Jun;57(47):5842-5843

School of Pharmaceutical Sciences and Chongqing Key Laboratory of Natural Drug Research, Chongqing University, Chongqing 401331, P. R. China.

Correction for 'Assembly of fluorinated chromanones via enantioselective tandem reaction' by Mengxue Lu et al., Chem. Commun., 2021, 57, 4722-4725, DOI: 10.1039/D1CC01187A.
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http://dx.doi.org/10.1039/d1cc90194jDOI Listing
June 2021

Assembly of fluorinated chromanones enantioselective tandem reaction.

Chem Commun (Camb) 2021 May;57(38):4722-4725

School of Pharmaceutical Sciences and Chongqing Key Laboratory of Natural Drug Research, Chongqing University, Chongqing 401331, P. R. China.

The enantioselective synthesis of fluorinated tricyclic chromanones with multiple vicinal stereogenic centers has been realized for the first time, through the tandem reaction between 2-fluorinated 1-(2-hydroxyaryl)-1,3-diketones and α,β-unsaturated aldehydes. In the presence of chiral amine, the organo-tandem reaction including catalytic Michael addition/cycloketalization/hemiacetalization and acylation sequence provided a wide range of fluorinated tricyclic chromanones with excellent outcomes (>30 examples, up to >99% ee and >19 : 1 d.r.). A plausible catalytic cycle and transition state are also provided for this tandem reaction to rationalize the observed sense of asymmetric induction.
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http://dx.doi.org/10.1039/d1cc01187aDOI Listing
May 2021

An RFC4/Notch1 signaling feedback loop promotes NSCLC metastasis and stemness.

Nat Commun 2021 05 11;12(1):2693. Epub 2021 May 11.

Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.

Notch signaling represents a key mechanism mediating cancer metastasis and stemness. To understand how Notch signaling is overactivated to couple tumor metastasis and self-renewal in NSCLC cells, we performed the current study and showed that RFC4, a DNA replication factor amplified in more than 40% of NSCLC tissues, directly binds to the Notch1 intracellular domain (NICD1) to competitively abrogate CDK8/FBXW7-mediated degradation of NICD1. Moreover, RFC4 is a functional transcriptional target gene of Notch1 signaling, forming a positive feedback loop between high RFC4 and NICD1 levels and sustained overactivation of Notch signaling, which not only leads to NSCLC tumorigenicity and metastasis but also confers NSCLC cell resistance to treatment with the clinically tested drug DAPT against NICD1 synthesis. Furthermore, together with our study, analysis of two public datasets involving more than 1500 NSCLC patients showed that RFC4 gene amplification, and high RFC4 and NICD1 levels were tightly correlated with NSCLC metastasis, progression and poor patient prognosis. Therefore, our study characterizes the pivotal roles of the positive feedback loop between RFC4 and NICD1 in coupling NSCLC metastasis and stemness properties and suggests its therapeutic and diagnostic/prognostic potential for NSCLC therapy.
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http://dx.doi.org/10.1038/s41467-021-22971-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113560PMC
May 2021

A tumor-targeted near-infrared fluorescent probe for HNO and its application to the real-time monitoring of HNO release .

Chem Commun (Camb) 2021 May;57(41):5063-5066

Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China. and University of Chinese Academy of Sciences, Beijing 100049, China.

Nitroxyl (HNO) is a promising regulator for cancer therapy. Here, we develop a tumor-targeted near-infrared fluorescent probe for HNO and utilize it in the real-time imaging of HNO release in vivo.
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http://dx.doi.org/10.1039/d1cc01462eDOI Listing
May 2021

Structural, Functional, and Molecular Imaging of Autism Spectrum Disorder.

Neurosci Bull 2021 Jul 29;37(7):1051-1071. Epub 2021 Mar 29.

Department of Nuclear Medicine and Medical PET Center, The Second Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder associated with both genetic and environmental risks. Neuroimaging approaches have been widely employed to parse the neurophysiological mechanisms underlying ASD, and provide critical insights into the anatomical, functional, and neurochemical changes. We reviewed recent advances in neuroimaging studies that focused on ASD by using magnetic resonance imaging (MRI), positron emission tomography (PET), or single-positron emission tomography (SPECT). Longitudinal structural MRI has delineated an abnormal developmental trajectory of ASD that is associated with cascading neurobiological processes, and functional MRI has pointed to disrupted functional neural networks. Meanwhile, PET and SPECT imaging have revealed that metabolic and neurotransmitter abnormalities may contribute to shaping the aberrant neural circuits of ASD. Future large-scale, multi-center, multimodal investigations are essential to elucidate the neurophysiological underpinnings of ASD, and facilitate the development of novel diagnostic biomarkers and better-targeted therapy.
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http://dx.doi.org/10.1007/s12264-021-00673-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275699PMC
July 2021
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