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1.
Opt Lett ; 49(11): 2861-2864, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824277

ABSTRACT

Inspired by the advanced integrated sensing and communication (ISAC), in this Letter, we explore the non-line-of-sight (NLoS) optical channels formed by reflections from the ground or objects to establish an integrated channel model for simultaneous communication and sensing. The integrated channel model can, on the one hand, perceive the changes in the surrounding environment and, on the other hand, determine whether these changes positively or negatively affect the quality of communication simultaneously. To validate the effectiveness of the proposed model, from sensing, we analyze the impact of various floor materials and visible light communication (VLC) users on the integrated channel; from communication, we characterize the influence of perceived environmental changes on communication performance by calculating throughput. Experimental results confirm the capability of the derived model, which can support the design and deployment of VL-based ISAC networks.

2.
Front Microbiol ; 15: 1358137, 2024.
Article in English | MEDLINE | ID: mdl-38562471

ABSTRACT

Introduction: Paphiopedilum barbigerum is currently the rarest and most endangered species of orchids in China and has significant ornamental value. The mature seeds of P. barbigerum are difficult to germinate owing to the absence of an endosperm and are highly dependent on mycorrhizal fungi for germination and subsequent development. However, little is known about the regulation mechanisms of symbiosis and symbiotic germination of P. barbigerum seeds. Methods: Herein, transcriptomics and proteomics were used to explore the changes in the P. barbigerum seeds after inoculation with (FQXY019 treatment group) or without (control group) Epulorhiza sp. FQXY019 at 90 days after germination. Results: Transcriptome sequencing revealed that a total of 10,961 differentially expressed genes (DEGs; 2,599 upregulated and 8,402 downregulated) were identified in the control and FQXY019 treatment groups. These DEGs were mainly involved in carbohydrate, fatty acid, and amino acid metabolism. Furthermore, the expression levels of candidate DEGs related to nodulin, Ca2+ signaling, and plant lectins were significantly affected in P. barbigerum in the FQXY019 treatment groups. Subsequently, tandem mass tag-based quantitative proteomics was performed to recognize the differentially expressed proteins (DEPs), and a total of 537 DEPs (220 upregulated and 317 downregulated) were identified that were enriched in processes including photosynthesis, photosynthesis-antenna proteins, and fatty acid biosynthesis and metabolism. Discussion: This study provides novel insight on the mechanisms underlying the in vitro seed germination and protocorm development of P. barbigerum by using a compatible fungal symbiont and will benefit the reintroduction and mycorrhizal symbiotic germination of endangered orchids.

3.
PhytoKeys ; 239: 267-273, 2024.
Article in English | MEDLINE | ID: mdl-38577245

ABSTRACT

Oxalisxishuiensis, a new species of Oxalidaceae from Danxia landforms of Xishui County, Guizhou, China, is described and illustrated. It is morphologically similar to O.wulingensis by the two lateral leaflets arranged at about 180° angle and oblong pink petals with lilac veins, but clearly differs from the latter by leaflets almost as long as wide, obliquely obcordate lateral leaflets, shorter peduncles, longer capsule (1.2-1.5 cm vs. 0.5-0.7 cm) and alveolate seeds.

4.
Genes (Basel) ; 15(4)2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38674422

ABSTRACT

Zelkova schneideriana Hand.-Mazz is a valuable ornamental tree and timber source, whose seedling breeding and large-scale cultivation are restricted by low seed germination and seedling rates. The regulatory mechanisms underlying seed germination and seedling establishment in Z. schneideriana remain unknown. This study conducted metabolomic and transcriptomic analyses of seed germination and seedling establishment in Z. schneideriana. Regular expression of genes and metabolite levels has been observed in plant hormone signal transduction, starch and sucrose metabolism, linoleic acid metabolism, and phenylpropanoid biosynthesis. The reduction in abscisic acid during seed germination may lead to seed release from dormancy. After the seed is released from dormancy, the metabolic levels of auxin, cytokinins, brassinolide, and various sugars are elevated, and they are consumed in large quantities during the seedling establishment stage. Linoleic acid metabolism is gradually activated during seedling establishment. Transcriptome analysis showed that a large number of genes in different metabolic pathways are upregulated during plant establishment, and material metabolism may be accelerated during seedling establishment. Genes regulating carbohydrate metabolism are altered during seed germination and seedling establishment, which may have altered the efficiency of carbohydrate utilization. In addition, the syntheses of lignin monomers and cellulose have different characteristics at different stages. These results provide new insights into the complex mechanisms underlying seed germination and seedling establishment in Z. schneideriana and other woody plants.


Subject(s)
Gene Expression Regulation, Plant , Germination , Seedlings , Seeds , Transcriptome , Germination/genetics , Seedlings/genetics , Seedlings/growth & development , Seedlings/metabolism , Seeds/genetics , Seeds/metabolism , Seeds/growth & development , Metabolomics/methods , Gene Expression Profiling/methods , Plant Growth Regulators/metabolism , Plant Growth Regulators/genetics
5.
Phytomedicine ; 128: 155516, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38547625

ABSTRACT

BACKGROUND: Recently, osteoblast pyroptosis has been proposed as a potential pathogenic mechanism underlying osteoporosis, although this remains to be confirmed. Luteolin (Lut), a flavonoid phytochemical, plays a critical role in the anti-osteoporosis effects of many traditional Chinese medicine prescriptions. However, its protective impact on osteoblasts in postmenopausal osteoporosis (PMOP) has not been elucidated. PURPOSE: This research aimed to determine the effect of Lut in ameliorating PMOP by alleviating osteoblast pyroptosis and sustaining osteogenesis. STUDY DESIGN: This research was designed to investigate the novel mechanism of Lut in alleviating PMOP both in cell and animal models. METHODS: Ovariectomy-induced PMOP models were established in mice with/without daily gavaged of 10 or 20 mg/kg body weight Lut. The impact of Lut on bone microstructure, metabolism and oxidative stress was evaluated with 0.104 mg/kg body weight Estradiol Valerate Tablets daily gavaged as positive control. Network pharmacological analysis and molecular docking were employed to investigate the mechanisms of Lut in PMOP treatment. Subsequently, the impacts of Lut on the PI3K/AKT axis, oxidative stress, mitochondria, and osteoblast pyroptosis were assessed. In vitro, cultured MC3T3-E1(14) cells were exposed to H2O2 with/without Lut to examine its effects on the PI3K/AKT signaling pathway, osteogenic differentiation, mitochondrial function, and osteoblast pyroptosis. RESULTS: Our findings demonstrated that 20 mg/kg Lut, similar to the positive control drug, effectively reduced systemic bone loss and oxidative stress, and enhanced bone metabolism induced by ovariectomy. Network pharmacological analysis and molecular docking indicated that the PI3K/AKT axis was a potential target, with oxidative stress response and nuclear membrane function being key mechanisms. Consequently, the effects of Lut on the PI3K/AKT axis and pyroptosis were investigated. In vivo data revealed that the PI3K/AKT axis was deactivated following ovariectomy, and Lut restored the phosphorylation of key proteins, thereby reactivating the axis. Additionally, Lut alleviated osteoblast pyroptosis and mitochondrial abnormalities induced by ovariectomy. In vitro, Lut intervention mitigated the inhibition of the PI3K/AKT axis and osteogenesis, as well as H2O2-induced pyroptosis. Furthermore, Lut attenuated ROS accumulation and mitochondrial dysfunction. The effects of Lut, including osteogenesis restoration, anti-pyroptosis, and mitochondrial maintenance, were all reversed with LY294002 (a PI3K/AKT pathway inhibitor). CONCLUSION: In summary, Lut could improve mitochondrial dysfunction, alleviate GSDME-mediated pyroptosis and maintain osteogenesis via activating the PI3K/AKT axis, offering a new therapeutic strategy for PMOP.


Subject(s)
Luteolin , Molecular Docking Simulation , Osteoblasts , Osteogenesis , Osteoporosis, Postmenopausal , Ovariectomy , Oxidative Stress , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Pyroptosis , Signal Transduction , Animals , Female , Pyroptosis/drug effects , Osteoporosis, Postmenopausal/drug therapy , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Mice , Osteoblasts/drug effects , Signal Transduction/drug effects , Oxidative Stress/drug effects , Luteolin/pharmacology , Osteogenesis/drug effects , Disease Models, Animal , Humans , Mice, Inbred C57BL , Mitochondria/drug effects , Mitochondria/metabolism , Network Pharmacology , Cell Line
6.
J Am Chem Soc ; 146(1): 319-329, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38129955

ABSTRACT

Tumor invasion and metastasis are the main causes of tumor progression and are the leading causes of death among cancer patients. In the present study, we propose a strategy to regulate cellular signaling with a tumor metastasis-relevant cytoskeleton-associated protein 4 (CKAP4) specific aptamer for the achievement of tumor metastasis inhibition. The designed aptamer could specifically bind to CKAP4 in the cell membranes and cytoplasm to block the internalization and recycling of α5ß1 integrin, resulting in the disruption of the fibronectin-dependent cell adhesion and the weakening of the cell traction force. Moreover, the aptamer is able to impede the interaction between CKAP4 and Dickkopf1 (DKK1) to further block the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, which subsequently reduces AKT phosphorylation and inhibits the reorganization of the actin cytoskeleton in cell migration. The synergetic function of the designed aptamer in inhibiting cancer cell adhesion and blocking the PI3K signaling pathway enables efficient tumor cell metastasis suppression. The aptamer with specific targeting ability in regulating cellular signaling paves the way for cancer treatment and further provides a guiding ideology for inhibiting tumor metastasis.


Subject(s)
Neoplasms , Proto-Oncogene Proteins c-akt , Humans , Proto-Oncogene Proteins c-akt/metabolism , Cell Line, Tumor , Phosphatidylinositol 3-Kinases/metabolism , Signal Transduction , Cell Membrane/metabolism , Cell Movement , Neoplasms/metabolism
7.
Adv Mater ; : e2306252, 2023 Dec 04.
Article in English | MEDLINE | ID: mdl-38048547

ABSTRACT

Promising advances in molecular medicine have promoted the urgent requirement for reliable and sensitive diagnostic tools. Electronic biosensing devices based on field-effect transistors (FETs) exhibit a wide range of benefits, including rapid and label-free detection, high sensitivity, easy operation, and capability of integration, possessing significant potential for application in disease screening and health monitoring. In this perspective, the tremendous efforts and achievements in the development of high-performance FET biosensors in the past decade are summarized, with emphasis on the interface engineering of FET-based electrical platforms for biomolecule identification. First, an overview of engineering strategies for interface modulation and recognition element design is discussed in detail. For a further step, the applications of FET-based electrical devices for in vitro detection and real-time monitoring in biological systems are comprehensively reviewed. Finally, the key opportunities and challenges of FET-based electronic devices in biosensing are discussed. It is anticipated that a comprehensive understanding of interface engineering strategies in FET biosensors will inspire additional techniques for developing highly sensitive, specific, and stable FET biosensors as well as emerging designs for next-generation biosensing electronics.

8.
Plant Signal Behav ; 18(1): 2293405, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-38104263

ABSTRACT

Similar to other orchid species, Paphiopedilum hirsutissimum (Lindl.ex Hook.) Stein, relies on nutrients provided by mycorrhizal fungus for seed germination and seedling development in the wild owing to a lack of endosperm in its seeds. Therefore, obtaining suitable and specialized fungi to enhance seed germination, seedling formation, and further development is considered a powerful tool for orchid seedling propagation, reintroduction, and species conservation. In this study, we investigated the diversity, abundance, and frequency of endophytic fungal strains in the root organs of P. hirsutissimum. One family and five genera of the fungi were isolated and identified through rDNA-ITS sequencing. The ability of isolated fungi to germinate in vitro from the seeds of this species was evaluated, and the development of P. hirsutissimum protocorm has been described. The findings showed that the treatments inoculated with endophytic fungal DYXY033 may successfully support the advanced developmental stage of seedlings up to stage 5. In addition, scanning electron microscopy (SEM) revealed that the mycelium of this strain began to invade from either end of the seeds up to the embryo, extending rapidly from the inside to the outside. Its lengthening resulted in the bursting of the seed coat to form protocorms, which developed into seedlings. The results showed that DYXY033 has a high degree of mycobiont specificity under in vitro symbiotic seed germination conditions and is a representative mycorrhizal fungus with ecological value for the species. In summary, this strain may particularly be significant for the protection of P. hirsutissimum species that are endangered in China. In the long run, it may also contribute to global efforts in reintroducing orchid species and in realizing in situ restorations of threatened orchid populations.


Subject(s)
Mycorrhizae , Orchidaceae , Seedlings , Germination , Seeds , Symbiosis , Orchidaceae/microbiology , China
9.
Front Plant Sci ; 14: 1261323, 2023.
Article in English | MEDLINE | ID: mdl-37965005

ABSTRACT

Grain sorghum is an exceptional source of dietary nutrition with outstanding economic values. Breeding of grain sorghum can be slowed down by the occurrence of genotype × environment interactions (GEI) causing biased estimation of yield performance in multi-environments and therefore complicates direct phenotypic selection of superior genotypes. Multi-environment trials by randomized complete block design with three replications were performed on 13 newly developed grain sorghum varieties at seven test locations across China for two years. Additive main effects and multiplicative interaction (AMMI) and genotype + genotype × environment (GGE) biplot models were adopted to uncover GEI patterns and effectively identify high-yielding genotypes with stable performance across environments. Yield (YLD), plant height (PH), days to maturity (DTM), thousand seed weight (TSW), and panicle length (PL) were measured. Statistical analysis showed that target traits were influenced by significant GEI effects (p < 0.001), that broad-sense heritability estimates for these traits varied from 0.40 to 0.94 within the medium to high range, that AMMI and GGE biplot models captured more than 66.3% of total variance suggesting sufficient applicability of both analytic models, and that two genotypes, G3 (Liaoza No.52) and G10 (Jinza 110), were identified as the superior varieties while one genotype, G11 (Jinza 111), was the locally adapted variety. G3 was the most stable variety with highest yielding potential and G10 was second to G3 in average yield and stability whereas G11 had best adaptation only in one test location. We recommend G3 and G10 for the production in Shenyang, Chaoyang, Jinzhou, Jinzhong, Yulin, and Pingliang, while G11 for Yili.

10.
J Nanobiotechnology ; 21(1): 412, 2023 Nov 07.
Article in English | MEDLINE | ID: mdl-37936120

ABSTRACT

The immune system is closely associated with the pathogenesis of polycystic ovary syndrome (PCOS). Macrophages are one of the important immune cell types in the ovarian proinflammatory microenvironment, and ameliorate the inflammatory status mainly through M2 phenotype polarization during PCOS. Current therapeutic approaches lack efficacy and immunomodulatory capacity, and a new therapeutic method is needed to prevent inflammation and alleviate PCOS. Here, octahedral nanoceria nanoparticles with powerful antioxidative ability were bonded to the anti-inflammatory drug resveratrol (CeO2@RSV), which demonstrates a crucial strategy that involves anti-inflammatory and antioxidative efficacy, thereby facilitating the proliferation of granulosa cells during PCOS. Notably, our nanoparticles were demonstrated to possess potent therapeutic efficacy via anti-inflammatory activities and effectively alleviated endocrine dysfunction, inflammation and ovarian injury in a dehydroepiandrosterone (DHEA)-induced PCOS mouse model. Collectively, this study revealed the tremendous potential of the newly developed nanoparticles in ameliorating the proinflammatory microenvironment and promoting the function of granulosa cells, representing the first attempt to treat PCOS by using CeO2@RSV nanoparticles and providing new insights in combating clinical PCOS.


Subject(s)
Nanocomposites , Polycystic Ovary Syndrome , Mice , Animals , Female , Humans , Polycystic Ovary Syndrome/chemically induced , Polycystic Ovary Syndrome/drug therapy , Polycystic Ovary Syndrome/metabolism , Inflammation/drug therapy , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Tumor Microenvironment
11.
Exploration (Beijing) ; 3(3): 20210027, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37933385

ABSTRACT

Nano-biosensors that are composed of recognition molecules and nanomaterials have been extensively utilized in disease diagnosis, health management, and environmental monitoring. As a type of nano-biosensors, molecular specificity field-effect transistor (FET) biosensors with signal amplification capability exhibit prominent advantages including fast response speed, ease of miniaturization, and integration, promising their high sensitivity for molecules detection and identification. With intrinsic characteristics of high stability and structural tunability, aptamer has become one of the most commonly applied biological recognition units in the FET sensing fields. This review summarizes the recent progress of FET biosensors based on aptamer functionalized nanomaterials in medical diagnosis and environmental monitoring. The structure, sensing principles, preparation methods, and functionalization strategies of aptamer modified FET biosensors were comprehensively summarized. The relationship between structure and sensing performance of FET biosensors was reviewed. Furthermore, the challenges and future perspectives of FET biosensors were also discussed, so as to provide support for the future development of efficient healthcare management and environmental monitoring devices.

12.
Int J Mol Sci ; 24(22)2023 Nov 14.
Article in English | MEDLINE | ID: mdl-38003509

ABSTRACT

Foxtail millet (Setaria italica (L.) P. Beauv) is an important food and forage crop that is well adapted to nutrient-poor soils. However, our understanding of how different LN-tolerant foxtail millet varieties adapt to long-term low nitrogen (LN) stress at the physiological and molecular levels remains limited. In this study, two foxtail millet varieties with contrasting LN tolerance properties were investigated through analyses of physiological parameters and transcriptomics. The physiological results indicate that JG20 (high tolerance to LN) exhibited superior biomass accumulation both in its shoots and roots, and higher nitrogen content, soluble sugar concentration, soluble protein concentration, zeatin concentration in shoot, and lower soluble sugar and soluble protein concentration in its roots compared to JG22 (sensitive to LN) under LN, this indicated that the LN-tolerant foxtail millet variety can allocate more functional substance to its shoots to sustain aboveground growth and maintain high root activity by utilizing low soluble sugar and protein under LN conditions. In the transcriptomics analysis, JG20 exhibited a greater number of differentially expressed genes (DEGs) compared to JG22 in both its shoots and roots in response to LN stress. These LN-responsive genes were enriched in glycolysis metabolism, photosynthesis, hormone metabolism, and nitrogen metabolism. Furthermore, in the shoots, the glutamine synthetase gene SiGS5, chlorophyll apoprotein of photosystem II gene SiPsbQ, ATP synthase subunit gene Sib, zeatin synthesis genes SiAHP1, and aldose 1-epimerase gene SiAEP, and, in the roots, the high-affinity nitrate transporter genes SiNRT2.3, SiNRT2.4, glutamate synthase gene SiGOGAT2, fructose-bisphosphate aldolase gene SiFBA5, were important genes involved in the LN tolerance of the foxtail millet variety. Hence, our study implies that the identified genes and metabolic pathways contribute valuable insights into the mechanisms underlying LN tolerance in foxtail millet.


Subject(s)
Setaria Plant , Setaria Plant/genetics , Setaria Plant/metabolism , Plant Proteins/metabolism , Transcriptome , Nitrogen/metabolism , Zeatin/metabolism , Sugars/metabolism , Stress, Physiological/genetics , Gene Expression Regulation, Plant
13.
Nat Commun ; 14(1): 6800, 2023 10 26.
Article in English | MEDLINE | ID: mdl-37884498

ABSTRACT

Microbial communication can drive coordinated functions through sensing, analyzing and processing signal information, playing critical roles in biomanufacturing and life evolution. However, it is still a great challenge to develop effective methods to construct a microbial communication system with coordinated behaviors. Here, we report an electron transfer triggered redox communication network consisting of three building blocks including signal router, optical verifier and bio-actuator for microbial metabolism regulation and coordination. In the redox communication network, the Fe3+/Fe2+ redox signal can be dynamically and reversibly transduced, channeling electrons directly and specifically into bio-actuator cells through iron oxidation pathway. The redox communication network drives gene expression of electron transfer proteins and simultaneously facilitates the critical reducing power regeneration in the bio-actuator, thus enabling regulation of microbial metabolism. In this way, the redox communication system efficiently promotes the biomanufacturing yield and CO2 fixation rate of bio-actuator. Furthermore, the results demonstrate that this redox communication strategy is applicable both in co-culture and microbial consortia. The proposed electron transfer triggered redox communication strategy in this work could provide an approach for reducing power regeneration and metabolic optimization and could offer insights into improving biomanufacturing efficiency.


Subject(s)
Iron , Microbial Consortia , Biocatalysis , Oxidation-Reduction , Electron Transport
14.
ACS Nano ; 17(21): 21626-21638, 2023 Nov 14.
Article in English | MEDLINE | ID: mdl-37878521

ABSTRACT

Immunotherapy including immune checkpoint inhibition has reinvigorated the current cancer treatment field. The development of efficient cancer immunotherapies depends on a thorough understanding of the status of immune checkpoints and how they interact. However, the distribution and spatial organization changes of immune checkpoints during their interactions at the single-molecule level remain difficult to directly visualize due to the lack of in situ imaging techniques with appropriate spatial and stoichiometric resolution. Herein, we report the direct visualization and quantification of the spatial distribution and organization of CD47 on the bladder tumor cell membrane and SIRPα on the macrophage membrane by using a single-molecule localization imaging technique called quantitative direct stochastic optical reconstruction microscopy (QdSTORM). Results showed that a portion of CD47 and SIRPα was present on cell membranes as heterogeneous clusters of varying sizes and densities prior to activation. Quantitative analyses of the reconstructed super-resolution images and theoretical simulation revealed that CD47 and SIRPα were reorganized into larger clusters upon binding to each other. Furthermore, we found that blocking the immune checkpoint interaction with small-molecule inhibitors or antibodies significantly impacted the spatial clustering behavior of CD47 on bladder tumor cells, demonstrating the promise of our QdSTORM strategy in elucidating the molecular mechanisms underlying immunotherapy. This work offers a promising strategy to advance our understanding of immune checkpoint state and interactions while also contributing to the fields including signal regulation and cancer therapy.


Subject(s)
Neoplasms , Urinary Bladder Neoplasms , Humans , Phagocytosis , CD47 Antigen/metabolism , Microscopy , Neoplasms/therapy , Immunotherapy/methods , Cell Membrane/metabolism
15.
Phytomedicine ; 120: 155025, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37639813

ABSTRACT

BACKGROUND: Huashi Baidu granule (HSBD) and Paxlovid (Nirmatrelvir-Ritonavir) are antiviral Chinese patent medicine and western medicine specially developed for treating coronavirus disease 2019 (COVID-19). Their efficacy and safety in treating COVID-19 are still under investigated. PURPOSE: To assess and compare the efficacy and safety of HSBD, Paxlovid, and the combination in treating high-risk patients infected with SARS-CoV-2 Omicron. STUDY DESIGN: The study was a prospective single-center, open-label, randomized, controlled clinical trial conducted from April 18 to June 5, 2022. (ClinicalTrial.gov registration number: ChiCTR2200059390) METHODS: 312 severe patients aged 18 years and older infected with SARS-CoV-2 Omicron from Shuguang Hospital in Shanghai were randomly allocated to HSBD monotherapy (orally 137 g twice daily for 7 days, n = 105), Paxlovid monotherapy (orally 300 mg of Nirmatrelvir plus 100 mg of Ritonavir every 12 h for 5 days, n = 103), or combination therapy (n = 104). The primary outcome was SARS-CoV-2 nucleic acid negative conversion within 7-day treatment. The secondary outcome included hospital discharging conditions, severe conversion of symptom, and adverse events. RESULTS: Of 312 participants, 85 (82%) of 104 in combination therapy, 71 (68%) of 105 in HSBD monotherapy, and 73 (71%) of 103 in Paxlovid monotherapy had a primary outcome event. The hazard ratios of primary outcome were 1.37 (95% CI 1.03 - 1.84, p = 0.012) for combination versus HSBD, 1.28 (0.98-1.69, p = 0.043) for combination versus Paxlovid, and 0.88 (0.66-1.18, p = 0.33) for HSBD versus Paxlovid. There was no statistical difference of efficacy between HSBD and Paxlovid, while combination therapy exhibited more effective than either alone. For secondary outcomes, the hospital discharging rates within 7 days exhibited the significant increase in combination therapy than in HSBD or Paxlovid monotherapy (71% (74/104) vs 55% (58/105) vs 52% (54/103), p < 0.05). The risk of severe conversion of symptom showed no statistical significance among three interventions (1% (1/104) vs 3% (3/105) vs 3% (3/103), p > 0.05). No severe adverse events occurred among combination therapy and monotherapies in the trial. CONCLUSION: For patients with severe COVID-19, HSBD exhibits similar efficacy to Paxlovid, while combination therapy is more likely to increase the curative efficacy of Omicron variant than monotherapies, with few serious adverse events.


Subject(s)
COVID-19 , Ritonavir , Humans , Ritonavir/adverse effects , Prospective Studies , COVID-19 Drug Treatment , SARS-CoV-2 , China , Antiviral Agents/adverse effects
16.
Angew Chem Int Ed Engl ; 62(30): e202304298, 2023 07 24.
Article in English | MEDLINE | ID: mdl-37218113

ABSTRACT

Mass pathogen screening is critical to preventing the outbreaks and spread of infectious diseases. The large-scale epidemic of COVID-19 and the rapid mutation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus have put forward new requirements for virus detection and identification techniques. Here, we report a CRISPR-based Amplification-free Viral RNA Electrical Detection platform (CAVRED) for the rapid detection and identification of SARS-CoV-2 variants. A series of CRISPR RNA assays were designed to amplify the CRISPR-Cas system's ability to discriminate between mutant and wild RNA genomes with a single-nucleotide difference. The identified viral RNA information was converted into readable electrical signals through field-effect transistor biosensors for the achievement of highly sensitive detection of single-base mutations. CAVRED can detect the SARS-CoV-2 virus genome as low as 1 cp µL-1 within 20 mins without amplification, and this value is comparable to the detection limit of real-time quantitative polymerase chain reaction. Based on the excellent RNA mutation detection ability, an 8-in-1 CAVRED array was constructed and realized the rapid identification of 40 simulated throat swab samples of SARS-CoV-2 variants with a 95.0 % accuracy. The advantages of accuracy, sensitivity, and fast speed of CAVRED promise its application in rapid and large-scale epidemic screening.


Subject(s)
COVID-19 , RNA, Viral , Humans , RNA, Viral/genetics , SARS-CoV-2/genetics , COVID-19/diagnosis , Nucleotides , CRISPR-Cas Systems/genetics , Nucleic Acid Amplification Techniques
17.
ACS Sens ; 8(5): 2096-2104, 2023 05 26.
Article in English | MEDLINE | ID: mdl-37195802

ABSTRACT

The large-scale pandemic and fast evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have triggered an urgent need for an efficient and sensitive on-site nucleic acid testing method with single-nucleotide polymorphism (SNP) identification capability. Here, we report a multiplexed electrical detection assay based on a paperclip-shaped nucleic acid probe (PNprobe) functionalized field-effect transistor (FET) biosensor for highly sensitive and specific detection and discrimination of SARS-CoV-2 variants. The three-stem structure of the PNprobe significantly amplifies the thermodynamic stability difference between variant RNAs that differ in a single-nucleotide mutation. With the assistance of combinatorial FET detection channels, the assay realizes simultaneously the detection and identification of key mutations of seven SARS-CoV-2 variants, including nucleotide substitutions and deletions at single-nucleotide resolution within 15 min. For 70 simulated throat swab samples, the multiplexed electrical detection assay shows an identification accuracy of 97.1% for the discrimination of SARS-CoV-2 variants. Our designed multiplexed electrical detection assay with SNP identification capability provides an efficient tool to achieve scalable pandemic screening.


Subject(s)
COVID-19 , Humans , COVID-19/diagnosis , Polymorphism, Single Nucleotide , SARS-CoV-2/genetics , Nucleic Acid Probes , Nucleotides
18.
Int J Mol Sci ; 24(8)2023 Apr 13.
Article in English | MEDLINE | ID: mdl-37108376

ABSTRACT

Early maturity is an important agronomic trait in most crops, because it can solve the problem of planting in stubble for multiple cropping as well as make full use of light and temperature resources in alpine regions, thereby avoiding damage from low temperatures in the early growth period and early frost damage in the late growth period to improve crop yield and quality. The expression of genes that determine flowering affects flowering time, which directly affects crop maturity and indirectly affects crop yield and quality. Therefore, it is important to analyze the regulatory network of flowering for the cultivation of early-maturing varieties. Foxtail millet (Setaria italica) is a reserve crop for future extreme weather and is also a model crop for functional gene research in C4 crops. However, there are few reports on the molecular mechanism regulating flowering in foxtail millet. A putative candidate gene, SiNF-YC2, was isolated based on quantitative trait loci (QTL) mapping analysis. Bioinformatics analysis showed that SiNF-YC2 has a conserved HAP5 domain, which indicates that it is a member of the NF-YC transcription factor family. The promoter of SiNF-YC2 contains light-response-, hormone-, and stress-resistance-related elements. The expression of SiNF-YC2 was sensitive to the photoperiod and was related to the regulation of biological rhythm. Expression also varied in different tissues and in response to drought and salt stress. In a yeast two-hybrid assay, SiNF-YC2 interacted with SiCO in the nucleus. Functional analysis suggested that SiNF-YC2 promotes flowering and improves resistance to salt stress.


Subject(s)
Setaria Plant , Setaria Plant/genetics , Setaria Plant/metabolism , Salt Tolerance/genetics , Quantitative Trait Loci , Phenotype , Transcription Factors/metabolism , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolism
20.
Anal Chem ; 2023 Jan 06.
Article in English | MEDLINE | ID: mdl-36607132

ABSTRACT

Portable point-of-care testing (POCT) is currently drawing enormous attention owing to its great potential for disease diagnosis and personal health management. Electrochemical biosensors, with the intrinsic advantages of cost-effectiveness, fast response, ease of miniaturization, and integration, are considered as one of the most promising candidates for POCT application. However, the clinical application of electrochemical biosensors-based POCT is hindered by the decreased detection sensitivity due to the low abundance of disease-relevant biomolecules in extremely complex biological samples. Herein, we construct a flexible electrochemical biosensor based on single-stranded DNA functionalized single-walled carbon nanotubes (ssDNA-SWNTs) for high sensitivity and stability detection of miRNA-21 in human urine to achieve bladder cancer (BCa) diagnosis and classification. The ssDNA-SWNT electrodes with a 2D interconnected network structure exhibit a high electrical conductivity, thus enabling the ultrasensitive detection of miRNA-21 with a detection limit of 3.0 fM. Additionally, the intrinsic flexibility of ssDNA-SWNT electrodes endows the biosensors with the capability to achieve high stability detection of miRNA-21 even under large bending deformations. In a cohort of 40 BCa patients at stages I-III and 44 negative control samples, the constructed ssDNA-SWNT biosensors could detect BCa with a 92.5% sensitivity, an 88.6% specificity, and classify the cancer stages with an overall accuracy of 81.0%. Additionally, the flexible ssDNA-SWNT biosensors could also be utilized for treatment efficiency assessment and cancer recurrence monitoring. Owing to their excellent sensitivity and stability, the designed flexible ssDNA-SWNT biosensors in this work propose a strategy to realize point-of-care detection of complex clinical samples to achieve personalized healthcare.

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