169 results on '"Kong X."'
Search Results
2. Nuclear magnetic resonance spectroscopy with single spin sensitivity
- Author
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Mueller, C, Kong, X, Cai, J-M, Melentijevic, K, Stacey, A, Markham, M, Twitchen, D, Isoya, J, Pezzagna, S, Meijer, J, Du, JF, Plenio, MB, Naydenov, B, McGuinness, LP, Jelezko, F, Mueller, C, Kong, X, Cai, J-M, Melentijevic, K, Stacey, A, Markham, M, Twitchen, D, Isoya, J, Pezzagna, S, Meijer, J, Du, JF, Plenio, MB, Naydenov, B, McGuinness, LP, and Jelezko, F
- Abstract
Nuclear magnetic resonance spectroscopy and magnetic resonance imaging at the ultimate sensitivity limit of single molecules or single nuclear spins requires fundamentally new detection strategies. The strong coupling regime, when interaction between sensor and sample spins dominates all other interactions, is one such strategy. In this regime, classically forbidden detection of completely unpolarized nuclei is allowed, going beyond statistical fluctuations in magnetization. Here we realize strong coupling between an atomic (nitrogen-vacancy) sensor and sample nuclei to perform nuclear magnetic resonance on four (29)Si spins. We exploit the field gradient created by the diamond atomic sensor, in concert with compressed sensing, to realize imaging protocols, enabling individual nuclei to be located with Angstrom precision. The achieved signal-to-noise ratio under ambient conditions allows single nuclear spin sensitivity to be achieved within seconds.
- Published
- 2014
3. Inhibition of synapse assembly in mammalian muscle in vivo by RNA interference
- Author
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Kong, X. C., Barzaghi, P., and Ruegg, M. A.
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- 2004
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4. Aegilops tauschii draft genome sequence reveals a gene repertoire for wheat adaptation
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Jia, J., Zhao, S., Kong, X., Liu, Y., Zhao, G., He, W., Appels, R., Pfeifer, M., Tao, Y., Zhang, X., Jing, R., Zhang, C., Ma, Y., Gao, L., Gao, C., Spannagl, M., Mayer, K.F.X., Li, D., Pan, S., Zheng, F., Hu, Q., Xia, X., Li, J., Liang, Q., Chen, J., Wicker, T., Gou, C., Kuang, H., He, G., Luo, Y., Keller, B., Xia, Q., Lu, P., Wang, J., Zou, H., Zhang, R., Xu, J., Gao, J., Middleton, C., Quan, Z., Liu, G., Yang, H., Liu, X., He, Z., Mao, L., Jia, J., Zhao, S., Kong, X., Liu, Y., Zhao, G., He, W., Appels, R., Pfeifer, M., Tao, Y., Zhang, X., Jing, R., Zhang, C., Ma, Y., Gao, L., Gao, C., Spannagl, M., Mayer, K.F.X., Li, D., Pan, S., Zheng, F., Hu, Q., Xia, X., Li, J., Liang, Q., Chen, J., Wicker, T., Gou, C., Kuang, H., He, G., Luo, Y., Keller, B., Xia, Q., Lu, P., Wang, J., Zou, H., Zhang, R., Xu, J., Gao, J., Middleton, C., Quan, Z., Liu, G., Yang, H., Liu, X., He, Z., and Mao, L.
- Abstract
About 8,000 years ago in the Fertile Crescent, a spontaneous hybridization of the wild diploid grass Aegilops tauschii (2n = 14; DD) with the cultivated tetraploid wheat Triticum turgidum (2n = 4x = 28; AABB) resulted in hexaploid wheat (T. aestivum; 2n = 6x = 42; AABBDD). Wheat has since become a primary staple crop worldwide as a result of its enhanced adaptability to a wide range of climates and improved grain quality for the production of baker's flour. Here we describe sequencing the Ae. tauschii genome and obtaining a roughly 90-fold depth of short reads from libraries with various insert sizes, to gain a better understanding of this genetically complex plant. The assembled scaffolds represented 83.4% of the genome, of which 65.9% comprised transposable elements. We generated comprehensive RNA-Seq data and used it to identify 43,150 protein-coding genes, of which 30,697 (71.1%) were uniquely anchored to chromosomes with an integrated high-density genetic map. Whole-genome analysis revealed gene family expansion in Ae. tauschii of agronomically relevant gene families that were associated with disease resistance, abiotic stress tolerance and grain quality. This draft genome sequence provides insight into the environmental adaptation of bread wheat and can aid in defining the large and complicated genomes of wheat species.
- Published
- 2013
5. ERRATUM: Inhibition of respiratory syncytial virus infection with intranasal siRNA nanoparticles targeting the viral NS1 gene
- Author
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Zhang, W, Yang, H, Kong, X, Mohapatra, S, Juan-Vergara, H San, Hellermann, G, Behera, S, Singam, R, Lockey, R F, and Mohapatra, S S
- Abstract
Author(s): W Zhang; H Yang; X Kong; S Mohapatra; H San Juan-Vergara; G Hellermann; S Behera; R Singam; R F Lockey; S S Mohapatra Nat. Med. 11, 56-62 (2005) The [...]
- Published
- 2005
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6. Automatic tiling method for mosaic ceramic art images based on subpixel edge fitting localization and collaborative operation of multiple manipulators.
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Dong G, You R, Xu X, Kong X, Wu N, Chen X, Feng H, and Wang Z
- Abstract
Mosaic ceramics are not limited to use solely as building materials, they also possess artistic value. Artists can create images by arranging and combining mosaic ceramics, resulting in a perfect fusion of large-scale public art for external walls and ceramic materials. However, the current approach for artists to create mosaic ceramic exterior wall art images involves manual laying and assembling of individual mosaic ceramics. This manual process suffers from issues such as low efficiency, eye fatigue, selection errors, and the risk of high-altitude operations. These challenges significantly impact the quality and efficiency of creating mosaic ceramic exterior wall art image images. To address these problems, this paper proposes an automatic mosaic ceramic art image stitching method based on subpixel edge fitting positioning and collaborative operation of multiple robotic arms. Additionally, a new U + I type conveying method is designed for efficient and space-saving transportation of mosaic ceramics. Experimental results demonstrate a high success rate of recognition, absorption, and placement of multi-color mosaic ceramics using this method reaching 95.45%, with a positioning error within 0.5 mm. The method can also adapt to varying levels of light intensity or noise interference. This approach effectively enhances the quality and efficiency of creating mosaic ceramic exterior wall art images and promotes the development of mosaic ceramic exterior wall public art creation., (© 2024. The Author(s).)
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- 2024
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7. Exploring the activation potential of heme for 2,4-dichlorophenol, 2,4,6-trichlorophenol, and pentachlorophenol.
- Author
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Lan W, Meng Y, Kong X, Wang X, and Nie C
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- Water Pollutants, Chemical chemistry, Water Purification methods, Catalysis, Chlorophenols chemistry, Pentachlorophenol chemistry, Heme chemistry
- Abstract
The presence of chlorophenols in water poses a significant threat to human health and the environment. In response to this issue, a study was undertaken to evaluate the catalytic capabilities of chlorinated Heme towards common chlorophenols present in water, such as 2,4-dichlorophenol, 2,4,6-trichlorophenol, and pentachlorophenol. The study employed the B3LYP method, a sophisticated computational technique within density functional theory, to investigate the molecular interactions and transformations involved. It scrutinized structural parameters, Wiberg Bond Indices, which offer insights into the strength and nature of chemical bonds, along with spectroscopic data including infrared vibrational spectra, ultraviolet-visible absorption spectra, and molecular fluorescence spectra. Furthermore, the research analyzed molecular binding energies and orbital energy levels before and after the formation of complexes between Heme and the targeted chlorophenols. The findings indicate that Heme displays a notable activation characteristic towards these chlorophenols. This suggests that Heme could act as an effective catalyst in the degradation of chlorophenols in water, presenting a novel approach to water purification. The theoretical insights derived from this study are invaluable, potentially guiding the development of more efficient catalytic systems for treating chlorophenol-contaminated water, thereby reducing the environmental and health risks associated with these hazardous compounds., (© 2024. The Author(s).)
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- 2024
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8. Sleeve gastrectomy ameliorates renal injury in obesity-combined hyperuricemic nephropathy mice by modulating the AMPK/Nrf2/ABCG2 pathway.
- Author
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Song K, Kong X, Zhang Z, Xian Y, He M, Zhang Y, Liao X, Huang Z, Kang A, Xiao D, and Ren Y
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- Animals, Mice, Male, Signal Transduction, Kidney Diseases metabolism, Kidney Diseases etiology, Kidney Diseases pathology, Disease Models, Animal, Kidney metabolism, Kidney pathology, Humans, Mice, Inbred C57BL, ATP Binding Cassette Transporter, Subfamily G, Member 2 metabolism, ATP Binding Cassette Transporter, Subfamily G, Member 2 genetics, NF-E2-Related Factor 2 metabolism, NF-E2-Related Factor 2 genetics, Hyperuricemia metabolism, AMP-Activated Protein Kinases metabolism, Obesity metabolism, Obesity complications, Obesity surgery, Gastrectomy methods
- Abstract
Hyperuricemic nephropathy (HN) is renal injury caused by hyperuricemia (HUA). While sleeve gastrectomy (SG) has shown promise in improving renal injury in patients with obesity-related HN, the mechanisms are not fully understood. This study induced an obesity-combined HN model in male ob/ob mice and measured serum uric acid (SUA), creatinine, and other biochemical indicators 6 weeks post-surgery. Renal histological changes were evaluated through staining techniques, and the study also assessed renal adenosine monophosphate-activated protein kinase (AMPK) and nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation levels and urate transporter ABCG2 expression. In vitro experiments involved Nrf2 knockdown in AMPK-activated HK-2 cells and ChIP to confirm Nrf2 binding to the ABCG2 promoter. Results showed that SG reduced SUA levels, serum creatinine, and blood urea nitrogen, increased p-AMPK, p-Nrf2 protein, and ABCG2 expression, and alleviated renal fibrosis and inflammation. In vitro, Nrf2 knockdown down-regulated ABCG2 expression, and ChIP confirmed Nrf2's role in ABCG2 transcription. The study suggests that SG may improve renal injury in HN mice by modulating the AMPK/Nrf2 pathway and upregulating ABCG2 transcription., (© 2024. The Author(s).)
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- 2024
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9. Low-threshold distributed feedback laser based on holographic polymer dispersed liquid crystals through the oriented organic semiconductor films.
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Liu L, Liu M, Wang Q, Hu H, Zhang F, and Kong X
- Abstract
A specific optimized configuration for low threshold organic semiconductor laser based on a holographic polymer dispersed liquid crystal (HPDLC) transmission grating was demonstrated. Here the organic semiconductor films and phase separated liquid crystal (LC) molecules were oriented along the direction of the HPDLC grating grooves. The influence of the organic semiconductor chain orientation and the excitation polarization on the optical properties of the materials has been investigated. Especially, when polymer chain orientation, LC molecules and pump light polarization are consistent with the direction of the grating grooves, the performance of the outgoing laser is greatly improved. Up to 9.78% conversion efficiency with a threshold lower to 0.12 μJ/pulse can be obtained, indicating their potential for high-performance organic optoelectronics., (© 2024. The Author(s).)
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- 2024
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10. Quantitative evaluation of acid flow behavior in fractures and optimization of design parameters based on acid wormhole filtration losses.
- Author
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Yang S, Zheng K, Zhang J, Dai N, Wang L, Wang Z, Wang H, and Kong X
- Abstract
The technique of matrix acidification or acid fracturing is commonly utilized to establish communication with natural fractures during reservoir reconstruction. However, this process often encounters limitations due to filtration, which restricts the expansion of the primary acid-etching fracture. To address this issue, a computational model has been developed to simulate the expansion of an acid-etching wormhole by considering various factors such as formation process, injection duration, pressure build-up, and time-varying acid percolation rate. By analyzing the pumping displacement of acid-etching wormholes, this model provides valuable insights into the time-dependent quantities of acid percolation. It has been revealed that the filtration rate of acid-etching wormholes is strongly influenced by pumping displacement, viscosity, and concentration of the acid fluid used in stimulation as well as physical properties of the reservoir itself. Notably, viscosity plays a significant role in determining the effectiveness of acid fracturing especially in low-viscosity conditions. Acid concentration within 15% to 20% exhibits maximum impact on successful acid fracturing while concentrations below 15% or above 20% show no obvious effect. Furthermore, it was found that pumping displacement has a major influence on effective fracturing. However, beyond a certain threshold (> 5.0 m
3 /min), increased pumping displacement leads to slower etching distance for acids used in construction purposes. The simulation also provides real-time distribution analysis for acidity levels within eroded fractures during matrix-acidification processes and quantifies extent of chemical reactions between acids and rocks within these fractures thereby facilitating optimization efforts for design parameters related to matrix-acidification., (© 2024. The Author(s).)- Published
- 2024
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11. A real-world study of foreign body aspiration in children with 4227 cases in Western China.
- Author
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Wang Q, Kong X, Wang G, Dai J, Li Y, Wu C, Pan Z, He L, and Li H
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- Humans, China epidemiology, Male, Female, Infant, Child, Preschool, Child, Respiratory Aspiration epidemiology, Adolescent, Foreign Bodies epidemiology, Bronchoscopy methods
- Abstract
The early diagnosis and treatment of foreign body aspiration (FBA) can significantly improve the overall prognosis of children. There are significant differences in the epidemiology and clinical characteristics of FBA in different regions. Therefore, we conducted a real-world study in the western region of China with over 4000 patients. The aim of this study was to improve the understanding of FBA in terms of its types, the specific months of its occurrence, and the distribution of primary caregiver characteristics in western China. We collected the clinical and epidemiological data of children who were diagnosed with FBA in our hospital over the past 20 years through a big data centre. We matched the data of healthy children who underwent routine physical examinations at the paediatric health clinic during the same period to analyse the differences in the data of actual guardians. A total of 4227 patients from five provinces were included in this study. Foreign bodies were removed by rigid bronchoscopy in 99.4% (4202/4227) of patients, with a median age of 19 months and a median surgical duration 16 min. January was the most common month of onset for 1725 patients, followed by February, with 1027 patients. The most common types of foreign objects were melon peanuts, seeds and walnuts, accounting for 47.2%, 15.3%, and 10.2%, respectively. In the FBA group, the proportion of grandparents who were primary caregivers was 70.33% (2973/4227), which was significantly greater than the 63.05% in the healthy group (2665/4227) (P < 0.01). FBA most commonly occurs in January and February. More than 60% of FBAs occur between the ages of 1 and 2 years, and the incidence of FBA may be greater in children who are cared for by grandparents. A rigid bronchoscope can be used to remove most aspirated foreign bodies in a median of 16 min., (© 2024. The Author(s).)
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- 2024
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12. Resistance to pyrethroids and the relationship between adult resistance and knockdown resistance (kdr) mutations in Aedes albopictus in dengue surveillance areas of Guizhou Province, China.
- Author
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Zhang Y, Wang D, Shi W, Zhou J, Xiang Y, Guan Y, Kong X, Liang W, and Hu Y
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- Animals, China epidemiology, Mosquito Vectors genetics, Mosquito Vectors drug effects, Mosquito Vectors virology, Larva drug effects, Larva genetics, Larva virology, Voltage-Gated Sodium Channels genetics, Mosquito Control methods, Nitriles pharmacology, Pyrethrins pharmacology, Aedes genetics, Aedes drug effects, Aedes virology, Insecticide Resistance genetics, Dengue transmission, Dengue genetics, Mutation, Insecticides pharmacology
- Abstract
The Ae. albopictus mosquito has gained global attention due to its ability to transmit viruses, including the dengue and zika. Mosquito control is the only effective way to manage dengue fever, as no effective treatments or vaccines are available. Insecticides are highly effective in controlling mosquito densities, which reduces the chances of virus transmission. However, Ae. albopictus has developed resistance to pyrethroids in several provinces in China. Pyrethroids target the voltage-gated sodium channel gene (VGSC), and mutations in this gene may result in knockdown resistance (kdr). Correlation studies between resistance and mutations can assist viruses in managing Ae. albopictus, which has not been studied in Guizhou province. Nine field populations of Ae. albopictus at the larval stage were collected from Guizhou Province in 2022 and reared to F1 to F2 generations. Resistance bioassays were conducted against permethrin, beta-cypermethrin, and deltamethrin for both larvae and adults of Ae. albopictus. Kdr mutations were characterized by PCR and sequencing. Additionally, the correlation between the kdr allele and pyrethroid resistance was analyzed. All nine populations of Ae. albopictus larvae and adults were found to be resistant to three pyrethroid insecticides. One kdr mutant allele at codon 1016, one at 1532 and three at 1534 were identified with frequencies of 13.86% (V1016G), 0.53% (I1532T), 58.02% (F1534S), 11.69% (F1534C), 0.06% (F1534L) and 0.99% (F1534P), respectively. Both V1016G and F1534S mutation mosquitoes were found in all populations. The kdr mutation F1534S was positively correlated with three pyrethroid resistance phenotypes (OR > 1, P < 0.05), V1016G with deltamethrin and beta-cypermethrin resistance (OR > 1, P < 0.05) and F1534C only with beta-cypermethrin resistance (OR > 1, P < 0.05). Current susceptibility status of wild populations of Ae. albopictus to insecticides and a higher frequency of kdr mutations from dengue-monitored areas in Guizhou Province are reported in this paper. Outcomes of this study can serve as data support for further research and development of effective insecticidal interventions against Ae. albopictus populations in Guizhou Province., (© 2024. The Author(s).)
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- 2024
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13. Outcomes from a new modified single needle laparoscopic percutaneous extraperitoneal closure and cut off for pediatric inguinal hernia.
- Author
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Zeng D, Pu C, Guo C, and Kong X
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- Humans, Male, Female, Child, Preschool, Retrospective Studies, Child, Infant, Treatment Outcome, Recurrence, Postoperative Complications etiology, Postoperative Complications epidemiology, Suture Techniques instrumentation, Needles, Hernia, Inguinal surgery, Laparoscopy methods, Laparoscopy adverse effects, Herniorrhaphy methods, Herniorrhaphy instrumentation, Herniorrhaphy adverse effects
- Abstract
Inguinal hernia is a prevalent surgical condition in pediatric patients. Despite the efficacy of current treatment modalities, a certain recurrence rate still persists. Hence, our objective in this study is to introduce an innovative surgical technique designed to minimize surgical complications. We conducted a retrospective analysis on 809 pediatric cases that underwent laparoscopic repair with our innovative technique for inguinal hernia from June 2020 to June 2022. Demographic information, perioperative details, and postoperative follow-up outcomes were thoroughly assessed. All surgeries were conducted laparoscopically under general anesthesia. The procedure commenced by encircling the hernia sac with two sutures under laparoscopic guidance. Subsequently, the sac was exteriorized from the body using the two sutures, followed by ligation and excision of the hernia sac. The research findings demonstrate that the duration of unilateral and bilateral procedures was recorded as 15.9 ± 4.8 and 21.7 ± 3.9 min, respectively. Incision infection occurred in 7 patients (0.87%), and Male Complicated Inguinal Hernia (MCIH) was observed in 2 patients (0.23%). Notably, there were no occurrences of iatrogenic cryptorchidism, testicular atrophy, or recurrence (0%) during the follow-up period. In conclusion, our novel modification shows a notable reduction in postoperative recurrence rates and alleviates the impact of the procedure on the positioning of the testis or uterus. This modified technique is both safe and valuable, thus warranting broader adoption and promotion., (© 2024. The Author(s).)
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- 2024
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14. A comparative study on the dose-effect of low-dose radiation based on microdosimetric analysis and single-cell sequencing technology.
- Author
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Wang Y, Gao J, Tang B, Mo W, Gao H, Guo J, Kong X, Zhang W, Yin Y, Jiao Y, and Sun L
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- Humans, Monte Carlo Method, Radiometry methods, Cell Line, Gamma Rays adverse effects, Single-Cell Analysis methods, Dose-Response Relationship, Radiation
- Abstract
The biological mechanisms triggered by low-dose exposure still need to be explored in depth. In this study, the potential mechanisms of low-dose radiation when irradiating the BEAS-2B cell lines with a Cs-137 gamma-ray source were investigated through simulations and experiments. Monolayer cell population models were constructed for simulating and analyzing distributions of nucleus-specific energy within cell populations combined with the Monte Carlo method and microdosimetric analysis. Furthermore, the 10 × Genomics single-cell sequencing technology was employed to capture the heterogeneity of individual cell responses to low-dose radiation in the same irradiated sample. The numerical uncertainties can be found both in the specific energy distribution in microdosimetry and in differential gene expressions in radiation cytogenetics. Subsequently, the distribution of nucleus-specific energy was compared with the distribution of differential gene expressions to guide the selection of differential genes bioinformatics analysis. Dose inhomogeneity is pronounced at low doses, where an increase in dose corresponds to a decrease in the dispersion of cellular-specific energy distribution. Multiple screening of differential genes by microdosimetric features and statistical analysis indicate a number of potential pathways induced by low-dose exposure. It also provides a novel perspective on the selection of sensitive biomarkers that respond to low-dose radiation., (© 2024. The Author(s).)
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- 2024
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15. Effect of plateletcrit and methylenetetrahydrofolate reductase (MTHFR) C677T genotypes on folic acid efficacy in stroke prevention.
- Author
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Shi Y, Zhang Z, Wang B, Wang Y, Kong X, Sun Y, Li A, Cui Y, Zhang Y, Li J, Huo Y, and Huang H
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- Humans, Male, Female, Middle Aged, Aged, Hypertension genetics, Platelet Activation genetics, Platelet Activation drug effects, China epidemiology, Blood Platelets metabolism, Blood Platelets drug effects, Platelet Count, Adult, Methylenetetrahydrofolate Reductase (NADPH2) genetics, Folic Acid administration & dosage, Folic Acid genetics, Stroke genetics, Stroke prevention & control, Genotype
- Abstract
Previous studies have shown that low platelet count combined with high plasma total homocysteine (tHcy) increased stroke risk and can be lowered by 73% with folic acid. However, the combined role of other platelet activation parameters and the methylenetetrahydrofolate reductase (MTHFR) C677T genotypes on stroke risk and folic acid treatment benefit remain to be examined. This study aimed to investigate if platelet activation parameters and MTHFR genotypes jointly impact folic acid treatment efficacy in first stroke prevention. Data were derived from the China Stroke Primary Prevention Trial. This study includes a total of 11,185 adult hypertensive patients with relevant platelet activation parameters and MTHFR genotype data. When simultaneously considering both platelet activation parameters (plateletcrit, platelet count, mean platelet volume, platelet distribution width) and MTHFR genotypes, patients with both low plateletcrit (Q1) and the TT genotype had the highest stroke incidence rate (5.6%) in the enalapril group. This subgroup significantly benefited from folic acid treatment, with a 66% reduction in first stroke (HR: 0.34; 95% CI: 0.14-0.82; p = 0.016). Consistently, the subgroup with low plateletcrit (Q1) and the CC/CT genotype also benefited from folic acid treatment (HR: 0.40; 95% CI: 0.23-0.70; p = 0.001). In Chinese hypertensive adults, low plateletcrit can identify those who may greatly benefit from folic acid treatment, in particular, those with the TT genotype, a subpopulation known to have the highest stroke risk., (© 2024. The Author(s).)
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- 2024
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16. Research on the impact of ESG performance on carbon emissions from the perspective of green credit.
- Author
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Kong X, Li Z, and Lei X
- Abstract
Utilizing panel data from 30 Chinese provinces, this research examines the non-linear relationship between regional environmental, social, and governance (ESG) performance and carbon emissions (CE) from the viewpoint of green credit. The study reveals a single threshold effect between ESG performance and CE, with green credit acting as the threshold variable. When the amount of green credit in a region exceeds the threshold, the growth rate of CE in that region begins to decline with higher ESG scores. Furthermore, green credit acts as a catalyst, playing a negative moderating role between ESG performance and CE, validated by both threshold regression and fixed effects models on panel data. Green credit indirectly influences carbon emissions by supporting green innovation, thus facilitating the transition to a greener economic development framework. Lastly, regional disparities are found in the moderating influence of green credit between ESG performance and CE. In regions with high ESG performance, the moderating impact of green credit is smaller, while in regions with low ESG performance, the effect is more significant. The research findings offer theoretical backing for policymakers regarding the efficacy of ESG in achieving carbon neutrality objectives, and offer valuable strategic recommendations for the diversified formulation of green credit strategies on both national and provincial scales. Regional heterogeneity test results provide valuable support for formulating policies that encourage green credit in provinces with low ESG performance., (© 2024. The Author(s).)
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- 2024
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17. Mrgprb2-mediated mast cell activation exacerbates Modic changes by regulating immune niches.
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Ji Z, Li J, Tao S, Li H, Kong X, Huang B, Feng Z, Wei X, Zheng Z, Chen J, Chen B, Liu J, and Zhao F
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- Animals, Female, Humans, Male, Mice, Middle Aged, Disease Models, Animal, Intervertebral Disc Degeneration pathology, Intervertebral Disc Degeneration metabolism, Intervertebral Disc Degeneration immunology, Intervertebral Disc Degeneration genetics, Signal Transduction, Mast Cells immunology, Mast Cells metabolism, Mice, Knockout
- Abstract
Modic changes are radiographic features associated with microfracture, low-virulence organism infection and chronic inflammation with inflammatory cell infiltration in the vertebral endplate region. Mast cells, as innate immune cells similar to macrophages, are present in painful degenerated intervertebral discs. However, the involvement and mechanisms of mast cells in the development of Modic changes remain unclear. Herein, we found increased mast cell infiltration in samples from patients with Modic changes and in mouse models of Modic changes. To clarify the role of mast cells in the progression of Modic changes, we used mast cell-deficient (KIT
W-SH/W-SH ) mice to construct a model of Modic changes and found that the severity of Modic changes in KITW-SH/W-SH mice was significantly lower than that in WT mice. These findings were further supported by the use of a mast cell-specific activator (compound 48/80) and a stabilizer (cromolyn). Furthermore, we found that mast cells were not activated via the classic IgE pathway in the Modic change models and that Mrgprb2 is the specific receptor for mast cell activation reported in recent studies. Then, we utilized Mrgprb2 knockout mice to demonstrate that Mrgprb2 knockout inhibited mast cell activation and thus reduced the degree of Modic changes. Transcriptomic sequencing revealed aberrant PI3K-AKT and MAPK pathway activation in the Mrgprb2-deficient mast cells. Additionally, Mrgpbrb2-activated mast cells regulate immune niches by recruiting macrophages, promoting M1 polarization and reducing M2 polarization, thereby promoting the progression of Modic changes. These findings suggest that mast cells may serve as a novel therapeutic target for addressing Modic changes., (© 2024. The Author(s).)- Published
- 2024
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18. Author Correction: Inhibition of acetylation of histones 3 and 4 attenuates aortic valve calcification.
- Author
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Gu J, Lu Y, Deng M, Qiu M, Tian Y, Ji Y, Zong P, Shao Y, Zheng R, Zhou B, Kong X, and Sun W
- Published
- 2024
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19. RIPK3 signaling and its role in regulated cell death and diseases.
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Zhou Y, Xiang Y, Liu S, Li C, Dong J, Kong X, Ji X, Cheng X, and Zhang L
- Abstract
Receptor-interacting protein kinase 3 (RIPK3), a member of the receptor-interacting protein kinase (RIPK) family with serine/threonine protein kinase activity, interacts with RIPK1 to generate necrosomes, which trigger caspase-independent programmed necrosis. As a vital component of necrosomes, RIPK3 plays an indispensable role in necroptosis, which is crucial for human life and health. In addition, RIPK3 participates in the pathological process of several infections, aseptic inflammatory diseases, and tumors (including tumor-promoting and -suppressive activities) by regulating autophagy, cell proliferation, and the metabolism and production of chemokines/cytokines. This review summarizes the recent research progress of the regulators of the RIPK3 signaling pathway and discusses the potential role of RIPK3/necroptosis in the aetiopathogenesis of various diseases. An in-depth understanding of the mechanisms and functions of RIPK3 may facilitate the development of novel therapeutic strategies., (© 2024. The Author(s).)
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- 2024
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20. Comparison of arterial stiffness indices measured by pulse wave velocity and pulse wave analysis for predicting cardiovascular and all-cause mortality in a Chinese population.
- Author
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Yue X, Chen L, Shi Y, Suo Y, Liao S, Cheang I, Gao R, Zhu X, Zhou Y, Yao W, Sheng Y, Kong X, Li X, and Zhang H
- Subjects
- Humans, Ankle Brachial Index, Pulse Wave Analysis, Proportional Hazards Models, Risk Factors, Cardiovascular Diseases epidemiology, Vascular Stiffness
- Abstract
Arterial stiffness measured by pulse wave velocity and pulse wave analysis has been widely studied in different populations in terms of its correlation with cardiovascular events and all-cause mortality. It remains unknown which arterial stiffness index is better for risk stratification in the general population. We included 4129 participants from Gaoyou County, Jiangsu Province, China, with a median follow-up of 11 years. The primary endpoint was cardiovascular mortality, and the secondary endpoint was all-cause mortality. Harrell's C-index, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) based on the Cox proportional hazards regression model were evaluated to assess predictive discrimination and accuracy. The associations between the 4 indices and cardiovascular mortality remained significant after adjusting for the Framingham Risk Score (FRS) and/or associated risk factors. Considering reclassification based on the newly integrated models (FRS model combined with the 4 indices), NRI for cardiovascular mortality showed that haPWV and baPWV had more significant improvement in reclassification compared with C1 and C2 [NRI with 95% CI: haPWV 0.410 (0.293, 0.523); baPWV 0.447 (0.330, 0.553); C1 0.312 (0.182, 0.454); C2 0.328 (0.159, 0.463); all P < 0.05]. This study showed that pulse wave velocity (haPWV and baPWV) provides better discrimination of long-term risk than arterial elasticity indices (C1 and C2) in the general population., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)
- Published
- 2024
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21. LncRNA PRBC induces autophagy to promote breast cancer progression through modulating PABPC1-mediated mRNA stabilization.
- Author
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Liang Y, Chen B, Xu F, Long L, Ye F, Wang Y, Luo D, Li Y, Zhao W, Wang L, Jin Y, Wang L, Kong X, Su P, and Yang Q
- Subjects
- Female, Humans, Autophagy genetics, Cell Line, Tumor, Cell Proliferation, Gene Expression Regulation, Neoplastic, MicroRNAs genetics, RNA, Messenger genetics, RNA-Binding Proteins genetics, Breast Neoplasms metabolism, Breast Neoplasms pathology, Poly(A)-Binding Protein I genetics, Poly(A)-Binding Protein I metabolism, RNA, Long Noncoding genetics, RNA, Long Noncoding metabolism
- Abstract
Breast cancer is one of the major malignant tumors among women worldwide. Long noncoding RNAs (lncRNAs) have been documented as significant modulators in the development and progression of various cancers; however, the contribution of lncRNAs to breast cancer remains largely unknown. In this study, we found a novel lncRNA (NONHSAT137675) whose expression was significantly increased in the breast cancer tissues. We named the novel lncRNA as lncRNA PRBC (PABPC1-related lncRNA in breast cancer) and identified it as a key lncRNA associated with breast cancer progression and prognosis. Functional analysis displayed that lncRNA PRBC could promote autophagy and progression of breast cancer. Mechanistically, we verified that lncRNA PRBC physically interacted with PABPC1 through RIP assay, and PABPC1 overexpression could reverse the inhibiting effect of lncRNA PRBC knockdown on the malignant behaviors in breast cancer cells. Knockdown of lncRNA PRBC interfered the translocation of PABPC1 from nucleus to cytoplasm as indicated by western blot and IF assays. Significantly, the cytoplasmic location of PABPC1 was required for the interaction between PABPC1 and AGO2, which could be enhanced by lncRNA PRBC overexpression, leading to strengthened recruitment of mRNA to RNA-induced silencing complex (RISC) and thus reinforcing the inhibition efficiency of miRNAs. In general, lncRNA PRBC played a critical role in malignant progression of breast cancer by inducing the cytoplasmic translocation of PABPC1 to further regulate the function of downstream miRNAs. This study provides novel insight on the molecular mechanism of breast cancer progression, and lncRNA PRBC might be a promising therapeutic target and prognostic predictor for breast cancer., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2024
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22. Bioinformatics-based analysis of the relationship between disulfidptosis and prognosis and treatment response in pancreatic cancer.
- Author
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Xiong Y, Kong X, Mei H, Wang J, and Zhou S
- Subjects
- Humans, Prognosis, Immunotherapy, Nomograms, Computational Biology, Tumor Microenvironment, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms genetics
- Abstract
Tumor formation is closely associated with disulfidptosis, a new form of cell death induced by disulfide stress-induced. The exact mechanism of action of disulfidptosis in pancreatic cancer (PCa) is not clear. This study analyzed the impact of disulfidptosis-related genes (DRGs) on the prognosis of PCa and identified clusters of DRGs, and based on this, a risk score (RS) signature was developed to assess the impact of RS on the prognosis, immune and chemotherapeutic response of PCa patients. Based on transcriptomic data and clinical information from PCa tissue and normal pancreatic tissue samples obtained from the TCGA and GTEx databases, differentially expressed and differentially surviving DRGs in PCa were identified from among 15 DRGs. Two DRGs clusters were identified by consensus clustering by merging the PCa samples in the GSE183795 dataset. Analysis of DRGs clusters about the PCa tumor microenvironment and differential analysis to obtain differential genes between the two DRG clusters. Patients were then randomized into the training and testing sets, and a prognostic prediction signature associated with disulfidptosis was constructed in the training set. Then all samples were divided into high-disulfidptosis-risk (HDR) and low-disulfidptosis-risk (LDR) subgroups based on the RS calculated from the signature. The predictive efficacy of the signature was assessed by survival analysis, nomograms, correlation analysis of clinicopathological characteristics, and the receiver operating characteristic (ROC) curves. To assess differences between different risk subgroups in immune cell infiltration, expression of immune checkpoint molecules, somatic gene mutations, and effectiveness of immunotherapy and chemotherapy. The GSE57495 dataset was used as external validation, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of DRGs. A total of 12 DRGs with differential expression and prognosis in PCa were identified, based on which a risk-prognosis signature containing five differentially expressed genes (DEGs) was developed. The signature was a good predictor and an independent risk factor. The nomogram and calibration curve shows the signature's excellent clinical applicability. Functional enrichment analysis showed that RS was associated with tumor and immune-related pathways. RS was strongly associated with the tumor microenvironment, and analysis of response to immunotherapy and chemotherapy suggests that the signature can be used to assess the sensitivity of treatments. External validation further demonstrated the model's efficacy in predicting the prognosis of PCa patients, with RT-qPCR and immunohistochemical maps visualizing the expression of each gene in PCa cell lines and the tissue. Our study is the first to apply the subtyping model of disulfidptosis to PCa and construct a signature based on the disulfidptosis subtype, which can provide an accurate assessment of prognosis, immunotherapy, and chemotherapy response in PCa patients, providing new targets and directions for the prognosis and treatment of PCa., (© 2023. The Author(s).)
- Published
- 2023
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23. MRI can help differentiate Ménière's disease from other menieriform diseases.
- Author
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Li J, Li L, Jin X, Hu N, Kong X, Wang L, Li X, Dou W, Sun L, Li C, and Gong R
- Subjects
- Humans, Gadolinium, Vertigo, Magnetic Resonance Imaging methods, Meniere Disease diagnostic imaging, Endolymphatic Hydrops diagnosis, Vestibule, Labyrinth, Neuroma, Acoustic, Migraine Disorders diagnosis
- Abstract
It is difficult to distinguish other pathologies mimicking Ménière's disease (MD) clinically. This study aims to investigate the differences of imaging findings and features between MD and other menieriform diseases via intravenous gadolinium-enhanced magnetic resonance imaging (MRI). 426 patients with menieriform symptoms, including MD, vestibular migraine (VM), and vestibular schwannoma (VS), underwent 3D-FLAIR and 3D-T2WI MRI 6 h after the intravenous gadolinium injection. MR images were analyzed for inner ear morphology, perilymphatic enhancement (PE), EH and other abnormalities. EH was observed at a higher rate in MD patients (85.71%) than patients with other menieriform diseases (VM group = 14.75%, VS group = 37.50%). The prevalence of unilateral EH as well as both cochlear and vestibular EH showed significant differences between MD and VM groups. The prevalence of cochlear EH (I and II) and vestibular EH (II and III) was different between MD and VM groups. The prevalence of PE was higher in MD than VM group. The degrees of cochlear and vestibular hydrops were higher in the definite than probable MD group (P < 0.05). Using these imaging features, MRI can be used to help differentiate MD from other menieriform diseases., (© 2023. The Author(s).)
- Published
- 2023
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24. Shape memory polymer with programmable recovery onset.
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Ni C, Chen D, Yin Y, Wen X, Chen X, Yang C, Chen G, Sun Z, Wen J, Jiao Y, Wang C, Wang N, Kong X, Deng S, Shen Y, Xiao R, Jin X, Li J, Kong X, Zhao Q, and Xie T
- Abstract
Stimulus-responsive shape-shifting polymers
1-3 have shown unique promise in emerging applications, including soft robotics4-7 , medical devices8 , aerospace structures9 and flexible electronics10 . Their externally triggered shape-shifting behaviour offers on-demand controllability essential for many device applications. Ironically, accessing external triggers (for example, heating or light) under realistic scenarios has become the greatest bottleneck in demanding applications such as implantable medical devices8 . Certain shape-shifting polymers rely on naturally present stimuli (for example, human body temperature for implantable devices)8 as triggers. Although they forgo the need for external stimulation, the ability to control recovery onset is also lost. Naturally triggered, yet actively controllable, shape-shifting behaviour is highly desirable but these two attributes are conflicting. Here we achieved this goal with a four-dimensional printable shape memory hydrogel that operates via phase separation, with its shape-shifting kinetics dominated by internal mass diffusion rather than by heat transport used for common shape memory polymers8-11 . This hydrogel can undergo shape transformation at natural ambient temperature, critically with a recovery onset delay. This delay is programmable by altering the degree of phase separation during device programming, which offers a unique mechanism for shape-shifting control. Our naturally triggered shape memory polymer with a tunable recovery onset markedly lowers the barrier for device implementation., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2023
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25. Multi-attribute fuzzy pattern decision making based on information systems.
- Author
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Sun Z and Kong X
- Abstract
This paper introduces an innovative approach aimed at enhancing multi-attribute decision-making through the utilization of fuzzy pattern recognition, with a specific emphasis on engaging decision-makers more effectively. The methodology establishes a multi-attribute fuzzy pattern recognition model within a hybrid information system framework. It categorizes attributes into natural and abstract groups, standardizes them, and employs membership functions to transform them into degrees of membership. This adaptable approach permits the derivation of various decision criteria from the hybrid system. Subsequently, a testing set is generated from this system, and a suitable fuzzy operator is selected. The optimal solution is determined by assessing the similarity between the standard and testing sets. To underscore its effectiveness, a practical example is provided. Crucially, in the realm of multi-attribute decision-making, our method simplifies the process by reducing computational steps in contrast to the conventional TOPSIS model, while maintaining consistent outcomes. This streamlines the decision-making process and reduces complexity. We also demonstrate its applicability in multi-objective decision-making through a case study evaluating exemplary educators, thereby highlighting its adaptability and effectiveness. This method exhibits significant promise for enhancing multi-attribute decision-making and offers practical applications., (© 2023. Springer Nature Limited.)
- Published
- 2023
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26. Reconfigurable integrated structures with functions of Fabry-Perot antenna and wideband liquid absorber for radar system stealth.
- Author
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Zou Y, Kong X, Cao Z, Zhang X, and Zhao Y
- Abstract
This paper proposes a functionally reconfigurable integrated structure of a Fabry-Perot (FP) antenna and wideband liquid absorber. First, a two-layer partial reflecting surface (PRS) has been designed. Then, a patch antenna is used to act as the source antenna. By combining the source antenna with the PRS, an FP antenna has been designed. What's more, taking full advantage of the reflective properties of PRS, a liquid broadband absorber is then designed. Last, the integrated structure with two functions has been realized. It can be used as the FP antenna or the liquid absorber through the extraction and injection of ethanol. In this way, it is effective to switch between stealth and detection states which can be used in different electromagnetic environments. The PRS is elaborately tailored to serve as both a component of the FP antenna and the metal ground of the broadband liquid absorber. Then the integrated structure is realized by combining the FP antenna with the liquid absorber. The PRS is composed of patches on the top layer of the substrate and the square loop on the bottom. The liquid absorber is composed of a 3-D printed container, 45% ethanol layer and the PRS is used to serve as the metal ground. The formula of Mie resonance theory has been extended and used to design the liquid absorber. The gain of the antenna is 19.7 dBi when the ethanol is extracted. When the ethanol is injected, a wideband liquid absorber is achieved. The absorption band (S
11 < - 10 dB) ranges from 4 to 18 GHz. The absorption bandwidth is over 133%. The monostatic RCS reduction bands of the structure with ethanol range from 4 to 18 GHz and the average RCS reduction is 28.4 dBsm. The measured and simulated results are in good agreement., (© 2023. Springer Nature Limited.)- Published
- 2023
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27. The efficacy and safety of low-intensity extracorporeal shock wave treatment combined with or without medications in Chronic prostatitis/chronic pelvic pain syndrome: a systematic review and meta-analysis.
- Author
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Kong X, Hu W, Dong Z, Tian J, Wang Y, Jin C, Liang C, Hao Z, and Wang Z
- Subjects
- Male, Humans, Chronic Disease, Pelvic Pain therapy, Databases, Factual, Prostatitis drug therapy, Prostatic Neoplasms, Chronic Pain therapy
- Abstract
Background: We performed this systematic review and meta-analysis to investigate the efficacy and safety of Li-ESWT combined with or without medications for patients with Chronic prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS)., Methods: A comprehensive search was conducted of PUBMED, Cochrane Library, and Web of Science databases from inception to February 2022 for randomized controlled trials (RCTs) assessing the efficacy and safety of Li-ESWT with or without the combination of medications compared with the control group. The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), Visual Analogue Scale/Score (VAS), International Index of Erectile Function (IIEF), and International prostate symptom score (IPSS) were used to assess the improvements of symptoms in CP/CPPS patients., Results: 651 patients from 12 randomized controlled studies were included in this study. The total NIH-CPSI scores, pain domain scores, and quality of life (QOL) scores were significantly lower in the Li-ESWT group than those in the control group at the termination of treatment, and 1, 4, 12, and 24 weeks after treatment. And these scores were significantly reduced in the Li-ESWT group than in baselines. In the subgroup analysis, reductions of these scores lasted longer and were greater in Li-ESWT combined with medications than in Li-ESWT alone. In the Li-ESWT group, the VAS score; IIEF score; and IPSS score were significant improvements than those in control group at the termination of treatment, and 1, 4, and 12 weeks after treatment; 4, 12, and 24 weeks after treatment; and 1, 4, and 12 weeks after treatment, respectively., Conclusions: Li-ESWT is a safe, non-invasive, and effective option for patients with CP/CPPS, whether combined with medications or not, should be recommended for widespread use in clinical practice., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2023
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28. GRAPE: A multi-modal dataset of longitudinal follow-up visual field and fundus images for glaucoma management.
- Author
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Huang X, Kong X, Shen Z, Ouyang J, Li Y, Jin K, and Ye J
- Subjects
- Humans, Artificial Intelligence, Cross-Sectional Studies, Follow-Up Studies, Visual Fields, Glaucoma diagnostic imaging, Vitis
- Abstract
As one of the leading causes of irreversible blindness worldwide, glaucoma is characterized by structural damage and functional loss. Glaucoma patients often have a long follow-up and prognosis prediction is an important part in treatment. However, existing public glaucoma datasets are almost cross-sectional, concentrating on segmentation on optic disc (OD) and glaucoma diagnosis. With the development of artificial intelligence (AI), the deep learning model can already provide accurate prediction of future visual field (VF) and its progression with the support of longitudinal datasets. Here, we proposed a public longitudinal glaucoma real-world appraisal progression ensemble (GRAPE) dataset. The GRAPE dataset contains 1115 follow-up records from 263 eyes, with VFs, fundus images, OCT measurements and clinical information, and OD segmentation and VF progression are annotated. Two baseline models demonstrated the feasibility in prediction of VF and its progression. This dataset will advance AI research in glaucoma management., (© 2023. Springer Nature Limited.)
- Published
- 2023
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29. Clinicopathological characteristics of HER2-low breast cancer: a retrospective study.
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Yang M, Sun J, Liu L, Kong X, Lin D, Zhou H, and Gao J
- Subjects
- Humans, Female, Retrospective Studies, Receptor, ErbB-2 metabolism, Prognosis, Receptors, Progesterone metabolism, Breast Neoplasms pathology
- Abstract
Human Epidermal Growth Factor Receptor-2 (HER2)-negative breast cancers (BCs) contain HER2-low and HER2-zero ones. HER2-low breast cancer has been receiving wide-spread concerns as the marvelous effect of novel anti-HER2 antibody-drug conjugates, however, the characteristic remains unknown. Our aim was to explore the differences of clinicopathological indicators and survival outcomes between HER2-low and HER2-0 breast cancers. We retrospectively analyzed 501 invasive breast cancer patients with complete data on HER2 status from 2017 to 2021 in our single center, of whom 415 HER2 negative patients were included for subsequent analysis. Each cohort was further divided into hormone receptor (HR) positive and HR negative subgroup. Clinicopathological factors and survival outcomes were collected and compared between HER2-low BCs and HER2-0 BCs. HER2-low BCs was obviously higher in HR positive BCs, with 277 (90.5%) HER2-low HR positive patients, 29 (9.5%) HER2-low HR negative patients, 68 (62.4%) HER2-0 HR positive patients and 41 (37.6%) HER2-0 HR negative patients (P < 0.001). Significant differences between HER2-low BCs and Her2-0 BCs were observed in lymph node ratio (LNR) (mean rank, 215 vs. 188 P = 0.014), estrogen receptor (ER)expression (90.5% vs. 62.4% P < 0.001), progesterone receptor (PR) expression (84.3% vs. 56.9% P < 0.001), Ki-67 expression (46.4% vs. 61.5% P < 0.001), androgen receptor (AR) expression (68% vs. 50.5% P < 0.001), adjuvant chemotherapy (69% vs. 79.8% P = 0.03). HER2-low BCs had lower histological grade than HER2-0 BCs, with grade I-II (68.7% vs. 43.1%) and grade III (22.2% vs. 43.1%) P < 0.01. No statistical differences were detected between the two groups for DFS and DDFS. Our results demonstrated that HR and AR status was closely related to HER2-low breast cancers. Further exploration about survival prognosis of HER2-low breast cancer is badly needed., (© 2023. The Author(s).)
- Published
- 2023
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30. Identification of cuproptosis-related lncRNA for predicting prognosis and immunotherapeutic response in cervical cancer.
- Author
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Kong X, Xiong Y, Xue M, He J, Lu Q, Chen M, and Li L
- Subjects
- Humans, Female, Reproducibility of Results, Prognosis, Immunotherapy, Apoptosis, Copper, Frizzled Receptors, Uterine Cervical Neoplasms genetics, Uterine Cervical Neoplasms therapy, RNA, Long Noncoding genetics
- Abstract
Patients diagnosed with advanced cervical cancer (CC) have poor prognosis after primary treatment, and there is a lack of biomarkers for predicting patients with an increased risk of recurrence of CC. Cuproptosis is reported to play a role in tumorigenesis and progression. However, the clinical impacts of cuproptosis-related lncRNAs (CRLs) in CC remain largely unclear. Our study attempted to identify new potential biomarkers to predict prognosis and response to immunotherapy with the aim of improving this situation. The transcriptome data, MAF files, and clinical information for CC cases were obtained from the cancer genome atlas, and Pearson correlation analysis was utilized to identify CRLs. In total, 304 eligible patients with CC were randomly assigned to training and test groups. LASSO regression and multivariate Cox regression were performed to construct a cervical cancer prognostic signature based on cuproptosis-related lncRNAs. Afterwards, we generated Kaplan-Meier curves, receiver operating characteristic curves and nomograms to verify the ability to predict prognosis of patients with CC. Genes for assessing differential expression among risk subgroups were also evaluated by functional enrichment analysis. Immune cell infiltration and the tumour mutation burden were analysed to explore the underlying mechanisms of the signature. Furthermore, the potential value of the prognostic signature to predict response to immunotherapy and sensitivity to chemotherapy drugs was examined. In our study, a risk signature containing eight cuproptosis-related lncRNAs (AL441992.1, SOX21-AS1, AC011468.3, AC012306.2, FZD4-DT, AP001922.5, RUSC1-AS1, AP001453.2) to predict the survival outcome of CC patients was developed, and the reliability of the risk signature was appraised. Cox regression analyses indicated that the comprehensive risk score is an independent prognostic factor. Moreover, significant differences were found in progression-free survival, immune cell infiltration, therapeutic response to immune checkpoint inhibitors, and IC50 for chemotherapeutic agents between risk subgroups, suggesting that our model can be well employed to assess the clinical efficacy of immunotherapy and chemotherapy. Based on our 8-CRLs risk signature, we were able to independently assess the outcome and response to immunotherapy of CC patients, and this signature might benefit clinical decision-making for individualized treatment., (© 2023. The Author(s).)
- Published
- 2023
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31. Genome editing of a rice CDP-DAG synthase confers multipathogen resistance.
- Author
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Sha G, Sun P, Kong X, Han X, Sun Q, Fouillen L, Zhao J, Li Y, Yang L, Wang Y, Gong Q, Zhou Y, Zhou W, Jain R, Gao J, Huang R, Chen X, Zheng L, Zhang W, Qin Z, Zhou Q, Zeng Q, Xie K, Xu J, Chiu TY, Guo L, Mortimer JC, Boutté Y, Li Q, Kang Z, Ronald PC, and Li G
- Subjects
- Genome, Plant genetics, Phosphatidylinositols metabolism, Alleles, Phosphatidylinositol 4,5-Diphosphate metabolism, Disease Resistance genetics, Gene Editing methods, Oryza enzymology, Oryza genetics, Oryza microbiology, Plant Breeding methods, Plant Diseases genetics, Plant Diseases microbiology, Diacylglycerol Cholinephosphotransferase genetics, Diacylglycerol Cholinephosphotransferase metabolism
- Abstract
The discovery and application of genome editing introduced a new era of plant breeding by giving researchers efficient tools for the precise engineering of crop genomes
1 . Here we demonstrate the power of genome editing for engineering broad-spectrum disease resistance in rice (Oryza sativa). We first isolated a lesion mimic mutant (LMM) from a mutagenized rice population. We then demonstrated that a 29-base-pair deletion in a gene we named RESISTANCE TO BLAST1 (RBL1) caused broad-spectrum disease resistance and showed that this mutation caused an approximately 20-fold reduction in yield. RBL1 encodes a cytidine diphosphate diacylglycerol synthase that is required for phospholipid biosynthesis2 . Mutation of RBL1 results in reduced levels of phosphatidylinositol and its derivative phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2 ). In rice, PtdIns(4,5)P2 is enriched in cellular structures that are specifically associated with effector secretion and fungal infection, suggesting that it has a role as a disease-susceptibility factor3 . By using targeted genome editing, we obtained an allele of RBL1, named RBL1Δ12 , which confers broad-spectrum disease resistance but does not decrease yield in a model rice variety, as assessed in small-scale field trials. Our study has demonstrated the benefits of editing an LMM gene, a strategy relevant to diverse LMM genes and crops., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2023
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32. Intact regulation of G1/S transition renders esophageal squamous cell carcinoma sensitive to PI3Kα inhibitors.
- Author
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Zhang X, Wang Y, Zhang X, Shen Y, Yang K, Ma Q, Qiao Y, Shi J, Wang Y, Xu L, Yang B, Ge G, Hu L, Kong X, Yang C, Chen Y, Ding J, and Meng L
- Subjects
- Humans, Cell Proliferation, Phosphorylation, Phosphoinositide-3 Kinase Inhibitors therapeutic use, Phosphatidylinositol 3-Kinases metabolism, Esophageal Squamous Cell Carcinoma metabolism, Esophageal Neoplasms metabolism
- Abstract
Phosphatidylinositol 3-kinase alpha (PI3Kα) inhibitors are currently evaluated for the therapy of esophageal squamous cell carcinoma (ESCC). It is of great importance to identify potential biomarkers to predict or monitor the efficacy of PI3Kα inhibitors in an aim to improve the clinical responsive rate in ESCC. Here, ESCC PDXs with CCND1 amplification were found to be more sensitive to CYH33, a novel PI3Kα-selective inhibitor currently in clinical trials for the treatment of advanced solid tumors including ESCC. Elevated level of cyclin D1, p21 and Rb was found in CYH33-sensitive ESCC cells compared to those in resistant cells. CYH33 significantly arrested sensitive cells but not resistant cells at G1 phase, which was associated with accumulation of p21 and suppression of Rb phosphorylation by CDK4/6 and CDK2. Hypo-phosphorylation of Rb attenuated the transcriptional activation of SKP2 by E2F1, which in turn hindered SKP2-mediated degradation of p21 and reinforced accumulation of p21. Moreover, CDK4/6 inhibitors sensitized resistant ESCC cells and PDXs to CYH33. These findings provided mechanistic rationale to evaluate PI3Kα inhibitors in ESCC patients harboring amplified CCND1 and the combined regimen with CDK4/6 inhibitors in ESCC with proficient Rb., (© 2023. The Author(s).)
- Published
- 2023
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33. Research on SPDTRS-PNN based intelligent assistant diagnosis for breast cancer.
- Author
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Kong X, Zhou M, Bian K, Lai W, Hu F, Dai R, and Yan J
- Subjects
- Humans, Female, Neural Networks, Computer, Algorithms, Machine Learning, Probability, Nuclear Proteins, Cell Adhesion Molecules, Breast Neoplasms diagnosis
- Abstract
Breast cancer is the second dangerous cancer in the world. Breast cancer data often contains more redundant information. Redundant information makes the breast cancer auxiliary diagnosis less accurate and time consuming. Dimension reduction algorithm combined with machine learning can solve these problems well. This paper proposes the single parameter decision theoretic rough set (SPDTRS) combined with the probability neural network (PNN) model for breast cancer diagnosis. We find that when the parameter value of SPDTRS is 2.5 and the SPREAD value is 0.75, the number of 30 attributes of the original breast cancer data dropped to 12, the accuracy of the SPDTRS-PNN model training set is 99.25%, the accuracy of the test set is 97.04%, and the test time is 0.093 s. The experimental results show that the SPDTRS-PNN model can improve the ac-curacy of breast cancer recognition, reduce the time required for diagnosis., (© 2023. The Author(s).)
- Published
- 2023
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34. Screening and identification of key biomarkers of depression using bioinformatics.
- Author
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Kong X, Wang C, Wu Q, Wang Z, Han Y, Teng J, and Qi X
- Subjects
- Humans, Depression, Gene Expression Regulation, Neoplastic, Biomarkers metabolism, Protein Interaction Maps genetics, Computational Biology, Biomarkers, Tumor genetics, Gene Expression Profiling, Depressive Disorder, Major genetics
- Abstract
We aimed to identify the molecular biomarkers of MDD disease progression to uncover potential mechanisms of major depressive disorder (MDD). In this study, three microarray data sets, GSE44593, GSE12654, and GSE54563, were cited from the Gene Expression Omnibus database for performance evaluation. To perform molecular functional enrichment analyses, differentially expressed genes (DEGs) were identified, and a protein-protein interaction network was configured using the Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape. To assess multi-purpose functions and pathways, such as signal transduction, plasma membrane, protein binding, and cancer pathways, a total of 220 DEGs, including 143 upregulated and 77 downregulated genes, were selected. Additionally, six central genes were observed, including electron transport system variant transcription factor 6, FMS-related receptor tyrosine kinase 3, carnosine synthetase 1, solute carrier family 22 member 13, prostaglandin endoperoxide synthetase 2, and protein serine kinase H1, which had a significant impact on cell proliferation, extracellular exosome, protein binding, and hypoxia-inducible factor 1 signaling pathway. This study enhances our understanding of the molecular mechanism of the occurrence and progression of MDD and provides candidate targets for its diagnosis and treatment., (© 2023. The Author(s).)
- Published
- 2023
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35. Outcomes of combined phacoemulsification, anterior vitrectomy, and sclerectomy in nanophthalmic eyes with glaucoma.
- Author
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Fan X, Wang J, Sheng Q, Zhai R, and Kong X
- Subjects
- Humans, Vitrectomy, Retrospective Studies, Intraocular Pressure, Treatment Outcome, Phacoemulsification methods, Sclerostomy, Trabeculectomy methods, Glaucoma surgery, Microphthalmos complications, Microphthalmos surgery, Glaucoma, Angle-Closure surgery
- Abstract
Objectives: To compare the long-term efficacy and safety of combined phacoemulsification, anterior vitrectomy, and sclerectomy (triple procedure surgery, TS); combined phacoemulsification and anterior vitrectomy (double procedure surgery, DS); and filtering surgery (FS) in nanophthalmos with angle-closure glaucoma (NACG)., Methods: Retrospective cohort study. Forty patients (44 eyes) diagnosed with NACG who underwent TS, DS, and FS were included. All eyes in the TS group and seven (47%) eyes in the DS group also underwent goniosynechialysis during the surgery. The main outcome measures (intraocular pressure [IOP], best-corrected visual acuity, complications, and second surgeries) were recorded at the early- (within 1 week) and late-stage (>3 months) follow-up., Results: The late-stage IOP was significantly lower in the TS (mean ± standard deviation: 13.29 ± 2.49 mm Hg) than in the DS (19.69 ± 6.97 mm Hg) and FS groups (27.57 ± 12.26 mm Hg, p < 0.001). More visual improvements were observed in the TS and DS groups than in the FS group at late-stage follow-up (p = 0.04). The complication rates in the TS, DS, and FS groups were 26%, 33%, and 70%, respectively (p = 0.046); the second surgery rates were 0%, 33%, and 60%, respectively (p < 0.001). In total, one, three, and six severe complications were observed in the TS, DS, and FS groups, respectively. The mean follow-up durations in the TS, DS, and FS groups were 18.89, 20.02, and 25.75 months, respectively., Conclusions: NACG management remains challenging. TS presented relatively good clinical efficacy and safety with better postoperative IOP outcomes, lower complications, and second surgery rates among the three groups in eyes with NACG., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)
- Published
- 2023
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36. A novel long noncoding RNA SP100-AS1 induces radioresistance of colorectal cancer via sponging miR-622 and stabilizing ATG3.
- Author
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Zhou Y, Shao Y, Hu W, Zhang J, Shi Y, Kong X, and Jiang J
- Subjects
- Humans, Cell Line, Tumor, Transcription Factors metabolism, Cell Proliferation genetics, Gene Expression Regulation, Neoplastic, Cell Movement genetics, Autoantigens, Antigens, Nuclear genetics, Autophagy-Related Proteins metabolism, Ubiquitin-Conjugating Enzymes metabolism, RNA, Long Noncoding genetics, RNA, Long Noncoding metabolism, MicroRNAs genetics, MicroRNAs metabolism, Colorectal Neoplasms genetics, Colorectal Neoplasms radiotherapy, Colorectal Neoplasms metabolism
- Abstract
Although radiotherapy is an essential modality in the treatment of colorectal cancer (CRC), the incidence of radioresistance remains high clinically. Long noncoding RNAs (lncRNAs) reportedly play critical roles in CRC radioresistance by regulating genes or proteins at the transcriptional or post-translational levels. This study aimed to identify novel lncRNAs involved in radioresistance. We found that SP100-AS1 (lncRNA targeting antisense sequence of SP100 gene) was upregulated in radioresistant CRC patient tissues using RNA-seq analysis. Importantly, knockdown of SP100-AS1 significantly reduced radioresistance, cell proliferation, and tumor formation in vitro and in vivo. Mechanistically, mass spectrometry and bioinformatics analyses were used to identify the interacting proteins and microRNAs of SP100-AS1, respectively. Moreover, SP100-AS1 was found to interact with and stabilize ATG3 protein through the ubiquitination-dependent proteasome pathway. In addition, it could serve as a sponge for miR-622, which targeted ATG3 mRNA and affected autophagic activity. Thus, lncRNA SP100-AS1 could act as a radioresistance factor in CRC patients via RNA sponging and protein stabilizing mechanisms. In conclusion, the present study indicates that SP100-AS1/miR-622/ATG3 axis contributes to radioresistance and autophagic activity in CRC patients, suggesting it has huge prospects as a therapeutic target for improving CRC response to radiation therapy., (© 2022. The Author(s).)
- Published
- 2023
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37. Self-extracted corn-stalk cellulose/epoxy resin composites.
- Author
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Lou C, Jiang S, Yan A, Zhou Y, Liu Y, Zhang Y, and Kong X
- Subjects
- Zea mays, Tensile Strength, Thermogravimetry, Epoxy Resins, Cellulose
- Abstract
In order to make full use of crop waste stalk, corn-stalk cellulose (CSC) was extracted by acid-base method and used as modifier of epoxy resin (E51) to prepare the self-extracted corn-stalk cellulose/epoxy resin composites (CSCEC). Differential scanning calorimeter (DSC), thermogravimetry (TG) analysis, dynamic mechanical analysis (DMA), morphology analysis by scanning electron microscope (SEM), the mechanical properties by electronic universal testing machine and impact testing machine were used for characterization and analysis. The experimental results showed that when the CSC content was 20 wt%, the impact strength of the composite was 2.50 kJ/m
2 , which was 127.2% higher than that of pure epoxy resin. When the CSC content was 20 wt%, the Tg of epoxy resin obtained by DMA was the lowest, 167.4 °C, which decreased by 11.3 °C compared with that of pure epoxy resin. The SEM result showed that the fracture surface of the composite became obviously rough and had of obvious folds, which was a ductile fracture. These results indicated that the addition of CSC could toughen the epoxy resin., (© 2022. The Author(s).)- Published
- 2022
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38. Thermal property evaluation of a 2.5D integration method with device level microchannel direct cooling for a high-power GaN HEMT device.
- Author
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Lian T, Xia Y, Wang Z, Yang X, Fu Z, Kong X, Lin S, and Ma S
- Abstract
Gallium nitride high electron mobility transistor (GaN HEMT) devices have become critical components in the manufacturing of high-performance radio frequency (RF) or power electronic modules due to their superior characteristics, such as high electron saturation speeds and high power densities. However, the high heat characteristics of GaN HEMTs make device level cooling a critical problem to solve since performance degradation or even failure may occur under high temperatures. In this paper, we proposed a 2.5D integration method with device-level microchannel direct cooling for a high-power GaN HEMT device. To demonstrate this technological concept, a multigate GaN HEMT device featuring a gate length/width/source drain spacing of 0.5 μm/300 μm/6 μm that underwent in-house backside thinning and metallization was used as the test vehicle. A high-resistivity silicon (HR Si) interposer embedded with four-layer microchannels was designed, having widths/pitches of 30 μm/30 μm at the top microchannel. The high-power GaN HEMT device was soldered on a Si interposer embedded with open microchannels for heat dissipation. A pair of GSG Pad chips was soldered simultaneously to display the capacity for the heterogeneous integration of other chip types. Thermal property evaluation was conducted with experiments and simulations. The test results showed that the maximum surface temperature of the GaN HEMT device decreased to 93.8 °C when it experienced a heat dissipation density of 32 kW/cm
2 in the gate finger area and an average heat dissipation density of 5 kW/cm2 was found in the active area with the DI water coolant at a flow rate of 3 mL/min. To our knowledge, among recently reported works, this finding was the best cooling capacity of heterogeneously integrated microchannels for GaN HEMT devices. In addition, this technology was scalable regarding the numbers of gate fingers or GaN HEMT devices., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s) 2022.)- Published
- 2022
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39. Effect of different revascularization times on intermediate-risk non-ST-elevation acute coronary syndrome.
- Author
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Kong X, Yin J, Chen H, Wu J, Yu X, Zhou N, and Ma L
- Subjects
- Humans, Registries, Risk Assessment, Risk Factors, Acute Coronary Syndrome diagnosis, Acute Coronary Syndrome surgery, Myocardial Infarction diagnosis, Myocardial Infarction surgery, Myocardial Revascularization
- Abstract
Non-ST-elevation acute coronary syndrome (NSTE-ACS) is a specific type of acute coronary syndrome. We applied the Thrombolysis in Myocardial Infarction (TIMI) score for risk stratification of patient prognosis. There was uncertainty about the routine revascularization time in patients with intermediate-risk NSTE-ACS. A total of 2835 patients with intermediate-risk NSTE-ACS (TIMI score 3-4) included in the China Acute Myocardial Infarction Registry from November 2014 to January 2017 were analyzed according to the time window from symptom onset to revascularization: within 24 h, Group I (814/28.7%); within 24 to 48 h, Group II (526/18.6%); within 48 to 72 h, Group III (403/14.2%); and after 72 h, Group IV (1092/38.5%). Risk factors, management and in-hospital outcomes were analyzed in the four groups. The results of the chi-square test showed that there was a significant difference in the incidence of in-hospital major adverse cardiovascular events (MACEs) when revascularization was completed within 48 h than when it was completed after 48 h (P < 0.05). The results of revascularization within 48 h were similar, and the incidence of in-hospital MACEs was lower than when revascularization was completed after 48 h. The incidence of in-hospital MACEs among patients who underwent revascularization within 48 h is lower than that of patients who underwent revascularization after 48 h., (© 2022. The Author(s).)
- Published
- 2022
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40. Community lung health service design for COPD patients in China by the Breathe Well group.
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Pang H, Pan Z, Adams R, Duncan E, Chi C, Kong X, Adab P, Cheng KK, Cooper BG, Correia-de-Sousa J, Dickens AP, Enocson A, Farley A, Gale N, Jolly K, Jowett S, Maglakelidze M, Maghlakelidze T, Martins S, Sitch A, Stavrik K, Stelmach R, Turner A, Williams S, and Jordan RE
- Subjects
- Focus Groups, Humans, Lung, Surveys and Questionnaires, General Practitioners, Pulmonary Disease, Chronic Obstructive psychology, Pulmonary Disease, Chronic Obstructive therapy
- Abstract
COPD is increasingly common in China but is poorly understood by patients, medications are not used as prescribed and there is no access to recommended non-pharmacological treatment. We explored COPD patients' and general practitioners' (GPs) knowledge of COPD, views on its management and the acceptability of a flexible lung health service (LHS) offering health education, exercise, self-management, smoking cessation and mental health support. Using a convergent mixed methods design, data were collected from patients and GPs using focus groups (FGs) in four Chinese cities, questionnaires were also used to collect data from patients. FGs were audio-recorded and transcribed. Quantitative data were analysed descriptively, thematic framework analysis was used for the qualitative data. Two-hundred fifty-one patients completed the questionnaire; 39 patients and 30 GPs participated in ten separate FGs. Three overarching themes were identified: patients' lack of knowledge/understanding of COPD, current management of COPD not meeting patients' needs and LHS design, which was well received by patients and GPs. Participants wanted COPD education, TaiChi, psychological support and WeChat for social support. 39% of survey responders did not know what to do when their breathing worsened and 24% did not know how to use their inhalers. 36% of survey respondents requested guided relaxation. Overall, participants did not fully understand the implications of COPD and current treatment was sub-optimal. There was support for developing a culturally appropriate intervention meeting Chinese patients' needs, health beliefs, and local healthcare delivery. Further research should explore the feasibility of such a service., (© 2022. The Author(s).)
- Published
- 2022
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41. A Ctnnb1 enhancer regulates neocortical neurogenesis by controlling the abundance of intermediate progenitors.
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Wang J, Wang A, Tian K, Hua X, Zhang B, Zheng Y, Kong X, Li W, Xu L, Wang J, Li Z, Liu Y, and Zhou Y
- Abstract
β-catenin-dependent canonical Wnt signaling plays a plethora of roles in neocortex (Ncx) development, but its function in regulating the abundance of intermediate progenitors (IPs) is elusive. Here we identified neCtnnb1, an evolutionarily conserved cis-regulatory element with typical enhancer features in developing Ncx. neCtnnb1 locates 55 kilobase upstream of and spatially close to the promoter of Ctnnb1, the gene encoding β-catenin. CRISPR/Cas9-mediated activation or interference of the neCtnnb1 locus enhanced or inhibited transcription of Ctnnb1. neCtnnb1 drove transcription predominantly in the subventricular zone of developing Ncx. Knock-out of neCtnnb1 in mice resulted in compromised expression of Ctnnb1 and the Wnt reporter in developing Ncx. Importantly, knock-out of neCtnnb1 lead to reduced production and transit-amplification of IPs, which subsequently generated fewer upper-layer Ncx projection neurons (PNs). In contrast, enhancing the canonical Wnt signaling by stabilizing β-catenin in neCtnnb1-active cells promoted the production of IPs and upper-layer Ncx PNs. ASH2L was identified as the key trans-acting factor that associates with neCtnnb1 and Ctnnb1's promoter to maintain Ctnnb1's transcription in both mouse and human Ncx progenitors. These findings advance understanding of transcriptional regulation of Ctnnb1, and provide insights into mechanisms underlying Ncx expansion during development., (© 2022. The Author(s).)
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- 2022
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42. Mitigating risks from hydraulic fracturing-induced seismicity in unconventional reservoirs: case study.
- Author
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Hui G, Chen Z, Wang P, Gu F, Kong X, and Zhang W
- Subjects
- Canada, Geology, Risk, Water Wells, Hydraulic Fracking
- Abstract
The recent remarkable increase in induced seismicity in Western Canada has been largely attributed to hydraulic fracturing in unconventional reservoirs. The nucleation of large magnitude events has been demonstrated to be closely linked to site-specific geological and operational factors. A mitigation strategy of fracturing-induced seismicity concerning both factors has not been well investigated. In this paper, a comprehensive investigation of risk mitigations from induced seismicity is conducted based on the formation overpressure, distance to Precambrian basement, proximity to faults, fracturing job size and safe hydraulic fracture-fault distance. It is found that the middle-south region near Crooked Lake is an optimal region for fracturing operations with low formation pressure, a great distance to the basement and relatively fewer pre-existing faults. A field case study suggests that fracturing operations of three new horizontal wells are successful with low magnitude induced events and with high production performance, demonstrating the applicability of a comprehensive approach of seismicity risk mitigations. Such an approach can be applied to other field cases to mitigate the potential fracturing-induced seismicity in unconventional reservoirs., (© 2022. The Author(s).)
- Published
- 2022
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43. Control methodology of synchronous lifting for the dual forging manipulator at clamping condition.
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Zhai F, He Z, Zhao Y, Yang L, and Kong X
- Abstract
Asynchronous coupling force of dual forging manipulator frequently results in poor forging and even equipment failure. In this paper, a synchronous control strategy in dual forging manipulator systems (DFMS) is proposed to stabilize its operation. Kinematic model of the hanging system and finite element model of the forgings are established to investigate the relationships of tension, forging deformation and deformation rate. The rigid-flexible coupling model of DFMS is further established and simulated concerning hydraulics, mechanics and controls. A correction based on the independent feedback state difference is concerned, simulated results show good agreements with experimental data, validating the dead zone compensation algorithm of the proportional valve. Moreover, by the control strategy, the vertical synchronous error of the pincers end is rather small as ± 0.125 mm. The methodology presented in this paper represents a fundamental step towards the cooperation of DFMS and the press to realize collaborative operations., (© 2022. The Author(s).)
- Published
- 2022
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44. Machine learning prediction of antiviral-HPV protein interactions for anti-HPV pharmacotherapy.
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Lin HH, Zhang QR, Kong X, Zhang L, Zhang Y, Tang Y, and Xu H
- Subjects
- Antiviral Agents administration & dosage, Area Under Curve, Bayes Theorem, Humans, Papillomaviridae isolation & purification, Papillomavirus Infections metabolism, Papillomavirus Infections virology, Algorithms, Antiviral Agents metabolism, Drug Discovery, Machine Learning, Papillomaviridae drug effects, Papillomavirus Infections drug therapy, Viral Proteins metabolism
- Abstract
Persistent infection with high-risk types Human Papillomavirus could cause diseases including cervical cancers and oropharyngeal cancers. Nonetheless, so far there is no effective pharmacotherapy for treating the infection from high-risk HPV types, and hence it remains to be a severe threat to the health of female. Based on drug repositioning strategy, we trained and benchmarked multiple machine learning models so as to predict potential effective antiviral drugs for HPV infection in this work. Through optimizing models, measuring models' predictive performance using 182 pairs of antiviral-target interaction dataset which were all approved by the United States Food and Drug Administration, and benchmarking different models' predictive performance, we identified the optimized Support Vector Machine and K-Nearest Neighbor classifier with high precision score were the best two predictors (0.80 and 0.85 respectively) amongst classifiers of Support Vector Machine, Random forest, Adaboost, Naïve Bayes, K-Nearest Neighbors, and Logistic regression classifier. We applied these two predictors together and successfully predicted 57 pairs of antiviral-HPV protein interactions from 864 pairs of antiviral-HPV protein associations. Our work provided good drug candidates for anti-HPV drug discovery. So far as we know, we are the first one to conduct such HPV-oriented computational drug repositioning study., (© 2021. The Author(s).)
- Published
- 2021
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45. Competitive endogenous RNA network and pathway-based analysis of LncRNA single-nucleotide polymorphism in myasthenia gravis.
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Wang T, Xu S, Zhang H, Lu X, Li S, Liu L, Kong X, Gao H, Wang X, Ning S, Wang J, and Wang L
- Subjects
- Humans, Myasthenia Gravis genetics, Myasthenia Gravis metabolism, Risk Factors, Biomarkers, Tumor biosynthesis, Biomarkers, Tumor genetics, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Polymorphism, Single Nucleotide, RNA, Long Noncoding biosynthesis, RNA, Long Noncoding genetics
- Abstract
Myasthenia gravis (MG) is a complex neurological autoimmune disease with a pathogenetic mechanism that has yet to be elucidated. Emerging evidence has revealed that genes, non-coding RNAs and genetic variants play significant roles in the pathogenesis of MG. However, the molecular mechanisms of single nucleotide polymorphisms (SNPs) located on lncRNAs could disturb lncRNA-mediated ceRNA regulatory functions still unclear in MG. In this study, we collated 276 experimentally confirmed MG risk genes and 192 MG risk miRNAs. We then constructed a lncRNA-mediated ceRNA network for MG based on multi-step computational strategies. Next, we systematically integrated risk pathways and identified candidate SNPs in lncRNAs for MG based on data acquired from public databases. In addition, we constructed a pathway-based lncRNA-SNP mediated network (LSPN) that contained 128 lncRNAs targeting 8 MG risk pathways. By analyzing network, we propose a latent mechanism for how the "lncRNA-SNP-mRNA-pathway" axis affects the pathogenesis of MG. Moreover, 25 lncRNAs and 51 SNPs on lncRNAs were extracted from the "lncRNA-SNP-mRNA-pathway" axis. Finally, functional analyses demonstrated lncRNA-SNPs mediated ceRNA regulation pairs associated with MG participated in the MAPK signaling pathway. In summary, we constructed MG-specific lncRNA-SNPs mediated ceRNA regulatory networks based on pathway in the present study, which was helpful to elucidate the roles of lncRNA-SNPs in the pathogenesis of MG and provide novel insights into mechanism of lncRNA-SNPs as potential genetic risk biomarkers of MG., (© 2021. The Author(s).)
- Published
- 2021
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46. Author Correction: Genetic analysis by targeted next-generation sequencing and novel variation identification of maple syrup urine disease in Chinese Han population.
- Author
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Fang X, Zhu X, Feng Y, Bai Y, Zhao X, Liu N, and Kong X
- Published
- 2021
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47. METTL3 improves cardiomyocyte proliferation upon myocardial infarction via upregulating miR-17-3p in a DGCR8-dependent manner.
- Author
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Zhao K, Yang C, Zhang J, Sun W, Zhou B, Kong X, and Shi J
- Abstract
Myocardial infarction (MI), one of the most severe types of heart attack, exerts a strong negative effect on heart muscle by causing a massive and rapid loss of cardiomyocytes. However, the existing therapies do little to improve cardiac regeneration. Due to the role of methyltransferase-like 3 (METTL3) in the physiological proliferation of cardiomyocytes, we aimed to determine whether METTL3 could also promote cardiomyocyte proliferation under pathological conditions and to elucidate the underlying mechanism. The effects of METTL3 on cardiomyocyte proliferation and apoptosis were investigated in an in vivo rat model of MI and in an in vitro model of neonatal rat cardiomyocytes (NRCMs) exposed to hypoxia. We found that METTL3 expression was downregulated in hypoxia-exposed NRCMs and MI-induced rats. Furthermore, METTL3 pretreatment enhanced cardiomyocyte proliferation and inhibited cardiomyocyte apoptosis under hypoxic or MI conditions, and silencing METTL3 had the opposite effects. Additionally, METTL3 overexpression upregulated miR-17-3p expression. The miR-17-3p agomir mimicked the pro-proliferative and antiapoptotic effects of METTL3 in hypoxia-exposed cells or rats with MI, while the miR-17-3p antagomir blocked these effects. Additionally, pretreatment with the RNA-binding protein DGCR8 also hampered the protective role of METTL3 in hypoxia-exposed cells. Overall, the current study indicated that METTL3 could improve cardiomyocyte proliferation and subsequently ameliorate MI in rats by upregulating proliferation-related miR-17-3p in a DGCR8-dependent pri-miRNA-processing manner., (© 2021. The Author(s).)
- Published
- 2021
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48. Genetic analysis by targeted next-generation sequencing and novel variation identification of maple syrup urine disease in Chinese Han population.
- Author
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Fang X, Zhu X, Feng Y, Bai Y, Zhao X, Liu N, and Kong X
- Subjects
- 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) metabolism, Amino Acids, Branched-Chain metabolism, Asian People genetics, Computer Simulation, DNA Mutational Analysis, Female, Genetic Testing, High-Throughput Nucleotide Sequencing, Humans, Infant, Infant, Newborn, Male, Maple Syrup Urine Disease diagnosis, Models, Molecular, Mutation, Missense, Pedigree, Protein Structure, Tertiary genetics, Retrospective Studies, 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) genetics, Maple Syrup Urine Disease genetics
- Abstract
Maple syrup urine disease (MSUD) is a rare autosomal recessive disorder that affects the degradation of branched chain amino acids (BCAAs). Only a few cases of MSUD have been documented in Mainland China. In this report, 8 patients (4 females and 4 males) with MSUD from 8 unrelated Chinese Han families were diagnosed at the age of 6 days to 4 months. All the coding regions and exon/intron boundaries of BCKDHA, BCDKHB, DBT and DLD genes were analyzed by targeted NGS in the 8 MSUD pedigrees. Targeted NGS revealed 2 pedigrees with MSUD Ia, 5 pedigrees with Ib, 1 pedigree with MSUD II. Totally, 13 variants were detected, including 2 variants (p.Ala216Val and p.Gly281Arg) in BCKDHA gene, 10 variants (p.Gly95Ala, p.Ser171Pro, p.Phe175Leu, p.Arg183Trp, p.Lys222Thr, p.Arg285Ter, p.Arg111Ter, p.S184Pfs*46, p.Arg170Cys, p.I160Ffs*25) in BCKDHB gene, 1 variant (p.Arg431Ter) in DBT gene. In addition, 4 previously unidentified variants (p.Gly281Arg in BCKDHA gene, p.Ser171Pro, p.Gly95Ala and p.Lys222Thr in BCKDHB gene) were identified. NGS plus Sanger sequencing detection is effective and accurate for gene diagnosis. Computational structural modeling indicated that these novel variations probably affect structural stability and considered as likely pathogenic variants., (© 2021. The Author(s).)
- Published
- 2021
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49. Spatial allocation of anthropogenic carbon dioxide emission statistics data fusing multi-source data based on Bayesian network.
- Author
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Tao J and Kong X
- Abstract
A gridded social-economic data is essential for geoscience analysis and multidisciplinary application. Spatial allocation of carbon dioxide statistics data is an important issue in the context of global climate change, which involves the carbon emissions accounting and decomposition of responsibility for carbon emission reductions. In this research a new spatial allocation method for non-point source anthropogenic carbon dioxide emissions (ACDE) fusing multi-source data using Bayesian Network (BN) was introduced. In addition to common-used DMSP (Defense Meteorological Satellite Program), PD (population density) and GDP (Gross Domestic Production) data, the land cover and vegetation data was imported into the model as prior knowledge to optimize the model fitting. The prior knowledge here was based on the understanding that ACDE was dominated by human activities and has strong correlations with land cover and vegetation conditions. A 1 km gridded ACDE map integrated emissions form point-source and non-point source was generated and validated. The model predicts ACDE with high accuracies and great improvement can be observed when fusing land cover and vegetation as prior knowledge. The model can achieve successful statistics data downscaling on national scale provided adequate sample data are available, offering a novel method for ACDE accounting in China., (© 2021. The Author(s).)
- Published
- 2021
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50. Interaction between genetic predisposition, smoking, and dementia risk: a population-based cohort study.
- Author
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Zhang N, Ranson JM, Zheng ZJ, Hannon E, Zhou Z, Kong X, Llewellyn DJ, King DA, and Huang J
- Subjects
- Adult, Aged, Alleles, Dementia diagnosis, Female, Genotype, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Population Surveillance, Risk Assessment, Risk Factors, Tobacco Smoking adverse effects, Dementia epidemiology, Dementia etiology, Disease Susceptibility, Genetic Predisposition to Disease, Smoking adverse effects
- Abstract
We evaluated whether the association between cigarette smoking and dementia risk is modified by genetic predisposition including apolipoprotein E (APOE) genotype and polygenic risk (excluding the APOE region). We included 193,198 UK Biobank participants aged 60-73 years without dementia at baseline. Of non-APOE-ε4 carriers, 0.89% (95% CI 0.73-1.08%) current smokers developed dementia compared with 0.49% (95% CI 0.44-0.55%) of never smokers (adjusted HR 1.78; 95% CI 1.39-2.29). In contrast, of one APOE-ε4 allele carriers, 1.69% (95% CI 1.31-2.12%) current smokers developed dementia compared with 1.40% (95% CI 1.25-1.55%) of never smokers (adjusted HR 1.06; 95% CI 0.77-1.45); of two APOE-ε4 alleles carriers, 4.90% (95% CI 2.92-7.61%) current smokers developed dementia compared with 3.87% (95% CI 3.11-4.74%) of never smokers (adjusted HR 0.94; 95% CI 0.49-1.79). Of participants with high polygenic risk, 1.77% (95% CI 1.35-2.27%) current smokers developed dementia compared with 1.05% (95% CI 0.91-1.21%) of never smokers (adjusted HR 1.63; 95% CI 1.16-2.28). A significant interaction was found between APOE genotype and smoking status (P = 0.002) while no significant interaction was identified between polygenic risk and smoking status (P = 0.25). APOE genotype but not polygenic risk modified the effect of smoking on dementia risk.
- Published
- 2021
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