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1.
Virulence ; 15(1): 2348252, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38712703

RESUMO

Heartland virus (HRTV), an emerging tick-borne pathogenic bunyavirus, has been a concern since 2012, with an increasing incidence, expanding geographical distribution, and high pathogenicity in the United States. Infection from HRTV results in fever, thrombocytopenia, and leucopenia in humans, and in some cases, symptoms can progress to severe outcomes, including haemorrhagic disease, multi-organ failure, and even death. Currently, no vaccines or antiviral drugs are available for treatment of the HRTV disease. Moreover, little is known about HRTV-host interactions, viral replication mechanisms, pathogenesis and virulence, further hampering the development of vaccines and antiviral interventions. Here, we aimed to provide a brief review of HRTV epidemiology, molecular biology, pathogenesis and virulence on the basis of published article data to better understand this virus and provide clues for further study.


Assuntos
Bunyaviridae , Replicação Viral , Humanos , Virulência , Animais , Infecções por Bunyaviridae/virologia , Thogotovirus/patogenicidade , Thogotovirus/genética , Thogotovirus/fisiologia , Estados Unidos/epidemiologia , Interações Hospedeiro-Patógeno
2.
Plant Dis ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698521

RESUMO

Fusarium pseudograminearum is an important plant pathogen that invades many crops (Zhang et al. 2018). Since it was first discovered in Australia in 1951, F. pseudograminearum has been reported in many countries and regions and caused huge economic losses (Burgess et al. 2001). In 2012, crown rot of wheat caused by F. pseudograminearum was discovered for the first time in Henan Province, China (Li et al. 2012). Wheat (Triticum aestivum L.) is one of the most important food crops in Xinjiang Uygur Autonomous Region (XUAR), with 1.07 million hectares cultivated in 2020. In June 2023, a survey of crown rot disease was carried out in winter wheat cv. Xindong 20 in Hotan area, XUAR, China (80.148907°E, 37.051474°N). About 5% of wheat plants showed symptoms of crown rot such as browning of the stem base and white head. The disease was observed in 85% of wheat fields. In order to identify the pathogens, 36 pieces of diseased stem basal tissue, 0.5 cm in length, were collected and sterilized with 75% alcohol for 30s and 5% NaOCl solution for 2 min, then rinsed three times with sterile water and placed on potato dextrose agar (PDA) medium at 25°C. A total of 27 isolates with consistent morphological characteristics were obtained using single-spore technique (Leslie and Summerell. 2006), and the isolation rate was 75%. The isolates grew rapidly on PDA, produced large numbers of fluffy white hyphae, and pink pigment accumulated in the medium. The isolates were grown on 2% mung bean flour medium and identified by morphological and molecular methods. Macroconidia were abundant, relatively slender, curved to almost straight, commonly two to seven septate, and averaged 22 to 72 × 1.8 to 4.9 µm. Microconidia were not observed. The morphological characters are consistent with Fusarium (Aoki and O'Donnell. 1999). Two isolates (LP-1 and LP-3) were selected for molecular identification. Primers EF1/EF2 (5'-ATGGGTAAGGARGACAAGAC-3'/5'-GGARGTACCAGTSATCATG-3') were used to amplify a portion of the EF-1α gene (O'Donnell et al. 1998). The two 696 bp PCR products were sequenced and submitted to GenBank. The EF-1α gene sequences (GenBank Accession No: PP062794 and PP062795) shared 99.9% identity (695/696) with published F.pseudograminearum sequences (e.g., OP105187, OP105184, OP105179, OP105173). The identification was further confirmed by F. pseudograminearum species-specific PCR primers Fp1-1/Fp1-2 (Aoki and O'Donnell. 1999). The expected PCR products of 518 bp were produced only in F. pseudograminearum. Pathogenicity tests of LP-1 and LP-3 isolates were performed on 7-day-old seedlings of winter wheat cv. Xindong 20 using the drip inoculation method with a 10-µl of a 106 macroconidia ml-1 suspension near the stem base (Xu et al. 2017). The experiment was repeated five times in a 20 to 25°C greenhouse. Control seedlings were treated with sterile water. After 4 weeks, wheat seedling death and crown browning occurred in the inoculated plants with over 90% incidence. No symptoms were observed in the control plants. The pathogen was reisolated from the inoculated plants by the method described above and identified by morphological and PCR amplification using F. pseudograminearum species-specific primers Fp1-1/Fp1-2. No F. pseudograminearum was isolated from the control plants, fulfilling Koch's postulates. To our knowledge, this is the first report of F. pseudograminearum causing crown rot of winter wheat in XUAR of China. Since F. pseudograminearum can cause great damage to wheat, one of the most important food crops in China, necessary measures should be taken to prevent the spread of F. pseudograminearum to other regions.

3.
Sci Total Environ ; 932: 172829, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38692332

RESUMO

Permafrost serves as a natural cold reservoir for viral communities. However, little is known about the viromes in deep permafrost soil, as most studies of permafrost were restricted to shallow areas. Here, permafrost soil samples of up to 100 m in depth were collected from two sites in the Tuotuo River permafrost area on the Tibetan Plateau. We investigated the viral composition in these permafrost soil samples and analyzed the relationship of viral composition and diversity along with depths. Our study revealed that greater permafrost thickness corresponds to higher diversity within the viral community. Bacteriophages were found to be the dominant viral communities, with "kill the winner" dynamics observed within the Siphoviridae and Myoviridae. The abundance and diversity of viral communities may follow a potential pattern along soil layers and depths, influenced by pH, trace elements, and permafrost thickness. Notably, strong correlations were discovered between the content of inorganic elements, including B, Mg, Cr, Bi, Ti, Na, Ni, and Cu, and the viral composition. Moreover, we discovered highly conserved sequences of giant viruses at depth of 10, 20, and 50 m in permafrost, which play a crucial role in evolutionary processes. These findings provide valuable insights into the viral community patterns from shallow to 100-m-depth in high-elevation permafrost, offering crucial data support for the formulation of strategies for permafrost thaw caused by climate change and anthropogenic activities.

4.
Virol Sin ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38599520

RESUMO

Infectious diseases caused by arboviruses are a public health concern in Pakistan. However, the studies on data prevalence and threats posed by arboviruses are limited. This study investigated the seroprevalence of arboviruses in a healthy population in Pakistan, including severe fever with thrombocytopenia syndrome virus (SFTSV), Crimean-Congo hemorrhagic fever virus (CCHFV), Tamdy virus (TAMV), and Karshi virus (KSIV) based on a newly established luciferase immunoprecipitation system (LIPS) assays, and Zika virus (ZIKV) by enzyme-linked immunosorbent assays (ELISA). Neutralizing activities against these arboviruses were further examined from the antibody positive samples. The results showed that the seroprevalence of SFTSV, CCHFV, TAMV, KSIV, and ZIKV was 17.37%, 7.58%, 4.41%, 1.10%, and 6.48%, respectively, and neutralizing to SFTSV (1.79%), CCHFV (2.62%), and ZIKV (0.69%) were identified, as well as to the SFTSV-related Guertu virus (GTV, 0.83%). Risk factors associated with the incidence of exposure and levels of antibody response were analyzed. Moreover, co-exposure to different arboviruses was demonstrated, as thirty-seven individuals were having antibodies against multiple viruses and thirteen showed neutralizing activity. Males, individuals aged ≤40 years, and outdoor workers had high risk of exposure to arboviruses. All these results reveal the substantial risks of infection with arboviruses in Pakistan, and indicate the threat from co-exposure to multiple arboviruses. The findings raise the need for further epidemiologic investigation in expanded regions and populations and the necessity to improve health surveillance in Pakistan.

5.
Antiviral Res ; 227: 105890, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38657838

RESUMO

Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic bunyavirus with a fatality rate of up to 40%. Currently, there are no licensed antiviral drugs for the treatment of CCHF; thus, the World Health Organization (WHO) listed the disease as a priority. A unique viral transcription initiation mechanism called "cap-snatching" is shared by influenza viruses and bunyaviruses. Thus, we tested whether baloxavir (an FDA-approved anti-influenza drug that targets the "cap-snatching" mechanism) could inhibit CCHFV infection. In cell culture, baloxavir acid effectively inhibited CCHFV infection and targeted CCHFV RNA transcription/replication. However, it has weak oral bioavailability. Baloxavir marboxil (the oral prodrug of baloxavir) failed to protect mice against a lethal dose challenge of CCHFV. To solve this problem, baloxavir sodium was synthesized owing to its enhanced aqueous solubility and pharmacokinetic properties. It consistently and significantly improved survival rates and decreased tissue viral loads. This study identified baloxavir sodium as a novel scaffold structure and mechanism of anti-CCHF compound, providing a promising new strategy for clinical treatment of CCHF after further optimization.

6.
FASEB J ; 38(7): e23584, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38568836

RESUMO

Cisplatin-induced acute kidney injury (AKI) is commonly seen in the clinical practice, and ferroptosis, a type of non-apoptotic cell death, plays a pivotal role in it. Previous studies suggested that protein arginine methyltransferase 4 (PRMT4) was incorporated in various bioprocesses, but its role in renal injuries has not been investigated. Our present study showed that PRMT4 was highly expressed in renal proximal tubular cells, and it was downregulated in cisplatin-induced AKI. Besides, genetic disruption of PRMT4 exacerbated, while its overexpression attenuated, cisplatin-induced redox injuries in renal proximal epithelia. Mechanistically, our work showed that PRMT4 interacted with NCOA4 to inhibit ferritinophagy, a type of selective autophagy favoring lipid peroxidation to accelerate ferroptosis. Taken together, our study demonstrated that PRMT4 interacted with NCOA4 to attenuate ferroptosis in cisplatin-induced AKI, suggesting that PRMT4 might present as a new therapeutic target for cisplatin-related nephropathy.


Assuntos
Injúria Renal Aguda , Cisplatino , Humanos , Cisplatino/efeitos adversos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/genética , Injúria Renal Aguda/metabolismo , Rim/metabolismo , Fatores de Transcrição/metabolismo , Autofagia , Coativadores de Receptor Nuclear/genética , Coativadores de Receptor Nuclear/metabolismo
7.
Mater Horiz ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38567423

RESUMO

Polymeric microspheres (PMs) have attracted great attention in the field of biomedicine in the last several decades due to their small particle size, special functionalities shown on the surface and high surface-to-volume ratio. However, how to fabricate PMs which can meet the clinical needs and transform laboratory achievements to industrial scale-up still remains a challenge. Therefore, advanced fabrication technologies are pursued. In this review, we summarize the technologies used to fabricate PMs, including emulsion-based methods, microfluidics, spray drying, coacervation, supercritical fluid and superhydrophobic surface-mediated method and their advantages and disadvantages. We also review the different structures, properties and functions of the PMs and their applications in the fields of drug delivery, cell encapsulation and expansion, scaffolds in tissue engineering, transcatheter arterial embolization and artificial cells. Moreover, we discuss existing challenges and future perspectives for advancing fabrication technologies and biomedical applications of PMs.

8.
Virol Sin ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38679334

RESUMO

Ticks are a major parasite on the Qinghǎi-Tibet Plateau, western China, and represent an economic burden to agriculture and animal husbandry. Despite research on tick-borne pathogens that threaten humans and animals, the viromes of dominant tick species remain unknown. In this study, we collected Dermacentor nuttalli ticks near Qinghǎi Lake and identified 13 viruses belonging to at least six families through metagenomic sequencing. Four viruses were of high abundance in pools, including Xinjiang tick-associated virus 1 (XJTAV1), and three novel viruses: Qinghǎi Lake virus 1, Qinghǎi Lake virus 2 (QHLV1, and QHLV2, unclassified), and Qinghǎi Lake virus 3 (QHLV3, genus Uukuvirus of family Phenuiviridae in order Bunyavirales), which lacks the M segment. The minimum infection rates of the four viruses among the tick groups were 8.2%, 49.5%, 6.2%, and 24.7%, respectively, suggesting the prevalence of these viruses in D. nuttalli ticks. A putative M segment of QHLV3 was identified from next-generation sequencing data and further characterized for its signal peptide cleavage site, N-glycosylation, and transmembrane region. Furthermore, we probed the L, M, and S segments of other viruses using the putative M segment sequence with sequencing data of other tick pools. By revealing the viromes of D. nuttalli ticks, this study enhances our understanding of tick-borne viral communities in highland regions. The putative M segment identified in a novel uukuvirus suggests that previously identified uukuviruses without M segments should have had the same genome organization as typical bunyaviruses. These results will facilitate virus discovery and our understanding of the phylogeny of tick-borne uukuviruses.

9.
Sci Rep ; 14(1): 9601, 2024 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671210

RESUMO

Detecting the water deficit status of vertical greenery plants rapidly and accurately is a significant challenge in the process of cultivating and planting greenery plants. Currently, the mainstream method involves utilizing a single target detection algorithm for this task. However, in complex real-world scenarios, the accuracy of detection is influenced by factors such as image quality and background environment. Therefore, we propose a multi-stage progressive detection method aimed at enhancing detection accuracy by gradually filtering, processing, and detecting images through a multi-stage architecture. Additionally, to reduce the additional computational load brought by multiple stages and improve overall detection efficiency, we introduce a Swin Transformer based on mobile windows and hierarchical representations for feature extraction, along with global feature modeling through a self-attention mechanism. The experimental results demonstrate that our multi-stage detection approach achieves high accuracy in vertical greenery plants detection tasks, with an average precision of 93.5%. This represents an improvement of 19.2%, 17.3%, 13.8%, and 9.2% compared to Mask R-CNN (74.3%), YOLOv7 (76.2%), DETR (79.7%), and Deformable DETR (84.3%), respectively.


Assuntos
Algoritmos , Água , Processamento de Imagem Assistida por Computador/métodos
10.
Artigo em Inglês | MEDLINE | ID: mdl-38600706

RESUMO

The inevitably positively and negatively charged defects on the SnO2/perovskite buried interface often lead to nonradiative recombination of carriers and unfavorable alignment of energy levels in perovskite solar cells (PSCs). Interface engineering is a reliable strategy to manage charged defects. Herein, the nicotinamide adenine dinucleotide (NAD) molecules with multiple active groups of ─P=O, ─P-O, and ─NH2 are introduced to bridge the SnO2/perovskite buried interface for achieving simultaneous elimination of positively and negatively charged defects. We demonstrate that the ─P=O and ─P-O groups in NAD not only fix the uncoordinated Pb2+ but also fill the oxygen vacancies (VO) on the SnO2 layer to eliminate positively charged defects. Meanwhile, ─NH2 groups form hydrogen bonds with PbI2 to reduce the number of negatively charged defects. In addition, the NAD biomolecules as a bridge induce high perovskite crystallization and accelerated electronic transfer along with favorable energy band alignment between SnO2 and perovskite. Finally, the PSCs with the ITO/SnO2/NAD/Cs0.15FA0.75MA0.1PbI3/Spiro-OMeTAD/Ag structure deliver an improvement in the power conversion efficiency from 20.49 to 23.18% with an excellent open-circuit voltage (Voc) of 1.175 V. This work demonstrates that interface engineering through multifunctional molecular bridges with various functional groups is an effective approach to improve the performance of PSCs by eliminating charged defects and simultaneously regulating energy level alignment.

11.
J Colloid Interface Sci ; 667: 543-552, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38657538

RESUMO

The electrocatalytic production of "green hydrogen", such as through the electrolysis of water or urea has been vigorously advocated to alleviate the energy crisis. However, their electrode reactions including oxygen evolution reaction (OER), urea oxidation reaction (UOR), and hydrogen evolution reaction (HER) all suffer from sluggish kinetics, which urgently need catalysts to accelerate the processes. Herein, we design and prepare an OER/UOR/HER trifunctional catalyst by transforming the homemade CoO nanorod into a two-dimensional (2D) ultrathin heterojunction nickel-iron-cobalt hybrid phosphides nanosheet (NiFeP/CoP) via a hydrothermal-phosphorization method. Consequently, a strong electronic interaction was found among the Ni2P/FeP4/CoP heterogeneous interfaces, which regulates the electronic structure. Besides the high mass transfer property of 2D nanosheet, Ni2P/FeP4/CoP displays improved OER/UOR/HER performance. At 10 mA cm-2, the OER overpotential reaches 274 mV in 1.0 M KOH, and the potential of UOR is only 1.389 V in 1.0 M KOH and 0.33 M urea. More strikingly, the two-electrode systems for electrolysis water and urea-assisted electrolysis water assembled by NiFeP/CoP could maintain long-term stability for 35 h and 12 h, respectively. This work may help to pave the way for upcoming research horizons of multifunctional electrocatalysts.

12.
Nat Commun ; 15(1): 1818, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443394

RESUMO

Control of CRISPR/Cas12a trans-cleavage is crucial for biosensor development. Here, we show that small circular DNA nanostructures which partially match guide RNA sequences only minimally activate Cas12a ribonucleoproteins. However, linearizing these structures restores activation. Building on this finding, an Autocatalytic Cas12a Circular DNA Amplification Reaction (AutoCAR) system is established which allows a single nucleic acid target to activate multiple ribonucleoproteins, and greatly increases the achievable reporter cleavage rates per target. A rate-equation-based model explains the observed near-exponential rate trends. Autocatalysis is also sustained with DNA nanostructures modified with fluorophore-quencher pairs achieving 1 aM level (<1 copy/µL) DNA detection (106 times improvement), without additional amplification, within 15 min, at room temperature. The detection range is tuneable, spanning 3 to 11 orders of magnitude. We demonstrate 1 aM level detection of SNP mutations in circulating tumor DNA from blood plasma, genomic DNA (H. Pylori) and RNA (SARS-CoV-2) without reverse transcription as well as colorimetric lateral flow tests of cancer mutations with ~100 aM sensitivity.


Assuntos
Helicobacter pylori , Nanoestruturas , DNA Circular/genética , RNA/genética , Sistemas CRISPR-Cas , RNA Guia de Sistemas CRISPR-Cas , DNA/genética , Ribonucleoproteínas
13.
Neuron ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38547869

RESUMO

Norepinephrine (NE) is an essential biogenic monoamine neurotransmitter. The first-generation NE sensor makes in vivo, real-time, cell-type-specific and region-specific NE detection possible, but its low NE sensitivity limits its utility. Here, we developed the second-generation GPCR-activation-based NE sensors (GRABNE2m and GRABNE2h) with a superior response and high sensitivity and selectivity to NE both in vitro and in vivo. Notably, these sensors can detect NE release triggered by either optogenetic or behavioral stimuli in freely moving mice, producing robust signals in the locus coeruleus and hypothalamus. With the development of a novel transgenic mouse line, we recorded both NE release and calcium dynamics with dual-color fiber photometry throughout the sleep-wake cycle; moreover, dual-color mesoscopic imaging revealed cell-type-specific spatiotemporal dynamics of NE and calcium during sensory processing and locomotion. Thus, these new GRABNE sensors are valuable tools for monitoring the precise spatiotemporal release of NE in vivo, providing new insights into the physiological and pathophysiological roles of NE.

14.
Virol Sin ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38521412

RESUMO

The high risk of SARS-CoV-2 infection and reinfection and the occurrence of post-acute pulmonary sequelae have highlighted the importance of understanding the mechanism underlying lung repair after injury. To address this concern, comparative and systematic analyses of SARS-CoV-2 infection in COVID-19 patients and animals were conducted. In the lungs of nine patients who died of COVID-19 and one recovered from COVID-19 but died of unrelated disease in early 2020, damage-related transient progenitor (DATP) cells expressing CK8 marker proliferated significantly. These CK8+ DATP cells were derived from bronchial CK5+ basal cells. However, they showed different cell fate toward differentiation into type I alveolar cells in the deceased and convalescent patients, respectively. By using a self-limiting hamster infection model mimicking the dynamic process of lung injury remodeling in mild COVID-19 patients, the accumulation and regression of CK8+ cell marker were found to be closely associated with the disease course. Finally, we examined the autopsied lungs of two patients who died of infection by the recent Omicron variant and found that they only exhibited mild pathological injury with no CK8+ cell proliferation. These results indicate a clear pulmonary cell remodeling route and suggest that CK8+ DATP cells play a primary role in mediating alveolar remodeling, highlighting their potential applications as diagnostic markers and therapeutic targets.

15.
BMC Geriatr ; 24(1): 222, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38439017

RESUMO

BACKGROUND: This study aimed to investigate the association of high-sensitivity C-reactive protein (hs-CRP) with incident frailty as well as its effects on pre-frailty progression and regression among middle-aged and older adults. METHODS: Based on the frailty index (FI) calculated with 41 items, 6890 eligible participants without frailty at baseline from China Health and Retirement Longitudinal Study (CHARLS) were categorized into health, pre-frailty, and frailty groups. Logistic regression models were used to estimate the longitudinal association between baseline hs-CRP and incident frailty. Furthermore, a series of genetic approaches were conducted to confirm the causal relationship between CRP and frailty, including Linkage disequilibrium score regression (LDSC), pleiotropic analysis, and Mendelian randomization (MR). Finally, we evaluated the association of hs-CRP with pre-frailty progression and regression. RESULTS: The risk of developing frailty was 1.18 times (95% CI: 1.03-1.34) higher in participants with high levels of hs-CRP at baseline than low levels of hs-CRP participants during the 3-year follow-up. MR analysis suggested that genetically determined hs-CRP was potentially positively associated with the risk of frailty (OR: 1.06, 95% CI: 1.03-1.08). Among 5241 participants with pre-frailty at baseline, we found pre-frailty participants with high levels of hs-CRP exhibit increased odds of progression to frailty (OR: 1.39, 95% CI: 1.09-1.79) and decreased odds of regression to health (OR: 0.84, 95% CI: 0.72-0.98) when compared with participants with low levels of hs-CRP. CONCLUSIONS: Our results suggest that reducing systemic inflammation is significant for developing strategies for frailty prevention and pre-frailty reversion in the middle-aged and elderly population.


Assuntos
Proteína C-Reativa , Fragilidade , Idoso , Humanos , Pessoa de Meia-Idade , Estudos Longitudinais , Proteína C-Reativa/genética , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Fragilidade/genética , Estudos de Coortes , Inflamação
16.
World J Clin Cases ; 12(6): 1063-1075, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38464932

RESUMO

BACKGROUND: Alzheimer's disease (AD) is a serious disease causing human dementia and social problems. The quality of life and prognosis of AD patients have attracted much attention. The role of chronic immune inflammation in the pathogenesis of AD is becoming more and more important. AIM: To study the relationship among cognitive dysfunction, abnormal cellular immune function, neuroimaging results and poor prognostic factors in patients. METHODS: A retrospective analysis of 62 hospitalized patients clinical diagnosed with AD who were admitted to our hospital from November 2015 to November 2020. Collect cognitive dysfunction performance characteristics, laboratory test data and neuroimaging data from medical records within 24 h of admission, including Mini Mental State Examination Scale score, drawing clock test, blood T lymphocyte subsets, and neutrophils and lymphocyte ratio (NLR), disturbance of consciousness, extrapyramidal symptoms, electroencephalogram (EEG) and head nucleus magnetic spectroscopy (MRS) and other data. Multivariate logistic regression analysis was used to determine independent prognostic factors. the modified Rankin scale (mRS) was used to determine whether the prognosis was good. The correlation between drug treatment and prognostic mRS score was tested by the rank sum test. RESULTS: Univariate analysis showed that abnormal cellular immune function, extrapyramidal symptoms, obvious disturbance of consciousness, abnormal EEG, increased NLR, abnormal MRS, and complicated pneumonia were related to the poor prognosis of AD patients. Multivariate logistic regression analysis showed that the decrease in the proportion of T lymphocytes in the blood after abnormal cellular immune function (odd ratio: 2.078, 95% confidence interval: 1.156-3.986, P < 0.05) was an independent risk factor for predicting the poor prognosis of AD. The number of days of donepezil treatment to improve cognitive function was negatively correlated with mRS score (r = 0.578, P < 0.05). CONCLUSION: The decrease in the proportion of T lymphocytes may have predictive value for the poor prognosis of AD. It is recommended that the proportion of T lymphocytes < 55% is used as the cut-off threshold for predicting the poor prognosis of AD. The early and continuous drug treatment is associated with a good prognosis.

17.
Nat Methods ; 21(4): 692-702, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38443508

RESUMO

The serotonergic system plays important roles in both physiological and pathological processes, and is a therapeutic target for many psychiatric disorders. Although several genetically encoded GFP-based serotonin (5-HT) sensors were recently developed, their sensitivities and spectral profiles are relatively limited. To overcome these limitations, we optimized green fluorescent G-protein-coupled receptor (GPCR)-activation-based 5-HT (GRAB5-HT) sensors and developed a red fluorescent GRAB5-HT sensor. These sensors exhibit excellent cell surface trafficking and high specificity, sensitivity and spatiotemporal resolution, making them suitable for monitoring 5-HT dynamics in vivo. Besides recording subcortical 5-HT release in freely moving mice, we observed both uniform and gradient 5-HT release in the mouse dorsal cortex with mesoscopic imaging. Finally, we performed dual-color imaging and observed seizure-induced waves of 5-HT release throughout the cortex following calcium and endocannabinoid waves. In summary, these 5-HT sensors can offer valuable insights regarding the serotonergic system in both health and disease.


Assuntos
Receptores Acoplados a Proteínas G , Serotonina , Humanos , Camundongos , Animais , Serotonina/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Córtex Cerebral/metabolismo
18.
Mol Biotechnol ; 66(5): 1000-1018, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38305844

RESUMO

Aptamers, as a kind of small-molecule nucleic acid, have attracted much attention since their discovery. Compared with biological reagents such as antibodies, aptamers have the advantages of small molecular weight, low immunogenicity, low cost, and easy modification. At present, aptamers are mainly used in disease biomarker discovery, disease diagnosis, treatment, and targeted drug delivery vectors. In the process of screening and optimizing aptamers, it is found that there are still many problems need to be solved such as the design of the library, optimization of screening conditions, the truncation of screened aptamer, and the stability and toxicity of the aptamer. In recent years, the incidence of liver-related diseases is increasing year by year and the treatment measures are relatively lacking, which has attracted the people's attention in the application of aptamers in liver diseases. This article mainly summarizes the research status of aptamers in disease diagnosis and treatment, especially focusing on the application of aptamers in liver diseases, showing the crucial significance of aptamers in the diagnosis and treatment of liver diseases, and the use of Discovery Studio software to find the binding target and sequence of aptamers, and explore their possible interaction sites.


Assuntos
Aptâmeros de Nucleotídeos , Hepatopatias , Técnica de Seleção de Aptâmeros , Humanos , Hepatopatias/terapia , Hepatopatias/genética , Hepatopatias/diagnóstico , Técnica de Seleção de Aptâmeros/métodos , Animais , Biomarcadores
19.
Virol Sin ; 39(2): 194-204, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38360150

RESUMO

Haemaphysalis longicornis ticks, commonly found in East Asia, can transmit various pathogenic viruses, including the severe fever with thrombocytopenia syndrome virus (SFTSV) that has caused febrile diseases among humans in Hubei Province. However, understanding of the viromes of H. longicornis was limited, and the prevalence of viruses among H. longicornis ticks in Hubei was not well clarified. This study investigates the viromes of both engorged (fed) and free (unfed) H. longicornis ticks across three mountainous regions in Hubei Province from 2019 to 2020. RNA-sequencing analysis identified viral sequences that were related to 39 reference viruses belonging to unclassified viruses and seven RNA viral families, namely Chuviridae, Nairoviridae, Orthomyxoviridae, Parvoviridae, Phenuiviridae, Rhabdoviridae, and Totiviridae. Viral abundance and diversity in these ticks were analysed, and phylogenetic characteristics of the Henan tick virus (HNTV), Dabieshan tick virus (DBSTV), Okutama tick virus (OKTV), and Jingmen tick virus (JMTV) were elucidated based on their full genomic sequences. Prevalence analysis demonstrated that DBSTV was the most common virus found in individual H. longicornis ticks (12.59%), followed by HNTV (0.35%), whereas JMTV and OKTV were not detected. These results improve our understanding of H. longicornis tick viromes in central China and highlight the role of tick feeding status and geography in shaping the viral community. The findings of new viral strains and their potential impact on public health raise the need to strengthen surveillance efforts for comprehensively assessing their spillover potentials.


Assuntos
Ixodidae , Filogenia , Viroma , Animais , Viroma/genética , China , Ixodidae/virologia , Genoma Viral , Vírus de RNA/genética , Vírus de RNA/isolamento & purificação , Vírus de RNA/classificação , Carrapatos/virologia , RNA Viral/genética , Análise de Sequência de RNA , Haemaphysalis longicornis
20.
Anal Sci ; 40(4): 701-707, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38316711

RESUMO

In this work, a novel zirconium phosphonate (ZrPR1R2) was prepared by decorating both the aminoethoxy- group (R1) and the carboxypropyl- group (R2) on the zirconium phosphate layers in order to manipulate further the immobilization of the peroxidase (POD), and an antioxidant biosensor with higher sensitivity was constructed by dropping the POD/ZrPR1R2 composite onto the glassy carbon electrode surface. The activity of the POD/ZrPR1R2 composite was detected by Uv-vis spectra. The direct electrochemical behavior, the electrocatalytic response to dissolved oxygen and hydrogen peroxide, as well as the ability to detect total antioxidant capacity in tea sample were investigated by the methods of cyclic voltammetry. The results indicated that the immobilization of POD in ZrPR1R2 nanosheets matrix enhanced the enzymatic activity, and achieved the fast and direct electron transfer between POD and glassy carbon electrode. Moreover, the POD/ZrPR1R2 composite modified electrode show the electrocatalytic response to hydrogen peroxide in the linear range of 8.8×10-8 to 8.8×10-7 mol L-1, with the detection limit of 3.3×10-8 mol L-1. Attributing to the sensitive response to dissolved oxygen, the total antioxidant capacity can be detected directly in the real tea water by this POD/ZrPR1R2 composite modified electrode.


Assuntos
Antioxidantes , Técnicas Biossensoriais , Peroxidase , Peróxido de Hidrogênio/análise , Zircônio , Carbono , Eletrodos , Peroxidases , Oxigênio , Chá , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos
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