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Some special manufacturing fields such as aerospace may encounter mixed production of multiple research and development projects and multiple batch production projects. Under these special production conditions resource conflicts are more severe, resulting in uncertain operating times that are difficult to predict. In addition, a single project may have tens of thousands of supporting products, making it difficult to effectively control the total construction process. To address these challenges this paper proposes new methods. A model, EMA-DCPM (dynamic critical path method) incorporating attention mechanisms in Enterprise Resource Planning and Mechanical Engineering Society) has been proposed. This model predicts product job time through machine learning methods and discovers the predictive advantage of the attention mechanism through data comparison. The CPM control algorithm was improved to enhance its robustness and an efficient modeling method, "5+X" was proposed. This new method is suitable for mixed line planning management in sophisticated manufacturing projects and has value for practical applications.
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With the accelerating pace of population aging in China and the implementation of the smart city pilot policy, whether the middle-aged and elderly population can integrate and adapt to this "smart" society has become an urgent problem that needs to be solved. In this context, exploring the impact of smart city pilot policies on the social adaptation health and mental health of middle-aged and elderly people has become a top priority for China to implement a national strategy to actively respond to population aging. Thus, based on panel data from the China Health and Retirement Longitudinal Study (CHARLS) for the years 2011, 2013, and 2015, this study employs the difference-in-differences (DID) method to investigate whether the smart city pilot policy can improve the social adaptive health and mental health of middle-aged and elderly people and to explore in depth the mechanism of its influence. The study finds that compared with non-pilot cities, the social adaptive health and mental health of middle-aged and elderly people in smart cities improve by 0.6% and 2.2%, respectively. The mechanism effect study shows that the smart city pilot policy can improve the mental health of the middle-aged and the elderly through the use of Information and Communication Technology (ICT) and the enhancement of human capital. Furthermore, for the social adaptive health of middle-aged and elderly individuals, the smart city pilot policy can only make improvements through the enhancement of human capital. Heterogeneity analysis shows that the effect of smart city pilot policies on social adaptive health is more pronounced in the middle-aged group than in the elderly group.
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The various mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pose a substantial challenge in mitigating the viral infectivity. The identification of novel host factors influencing SARS-CoV-2 replication holds potential for discovering new targets for broad-spectrum antiviral drugs that can combat future viral mutations. In this study, potential host factors regulated by SARS-CoV-2 infection were screened through different high-throughput sequencing techniques and further identified in cells. Subsequent analysis and experiments showed that the reduction of m6A modification level on ACTN4 (Alpha-actinin-4) mRNA leads to a decrease in mRNA stability and translation efficiency, ultimately inhibiting ACTN4 expression. In addition, ACTN4 was demonstrated to target nsp12 for binding and characterized as a competitor for SARS-CoV-2 RNA and the RNA-dependent RNA polymerase complex, thereby impeding viral replication. Furthermore, two ACTN4 agonists, YS-49 and demethyl-coclaurine, were found to dose-dependently inhibit SARS-CoV-2 infection in both Huh7 cells and K18-hACE2 transgenic mice. Collectively, this study unveils the pivotal role of ACTN4 in SARS-CoV-2 infection, offering novel insights into the intricate interplay between the virus and host cells, and reveals two potential candidates for future anti-SARS-CoV-2 drug development.
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Actinina , Antivirales , Tratamiento Farmacológico de COVID-19 , SARS-CoV-2 , Replicación Viral , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/genética , Humanos , Animales , Antivirales/farmacología , Actinina/genética , Actinina/metabolismo , Ratones , Replicación Viral/efectos de los fármacos , Replicación Viral/genética , COVID-19/virología , COVID-19/genética , COVID-19/metabolismo , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/metabolismo , Ratones Transgénicos , Enzima Convertidora de Angiotensina 2/genética , Enzima Convertidora de Angiotensina 2/metabolismo , ARN Polimerasa Dependiente de ARN de Coronavirus/genética , ARN Viral/genéticaRESUMEN
Mitochondrial DNA replication is initiated by the transcription of mitochondrial RNA polymerase (mtRNAP), as mitochondria lack a dedicated primase. However, the mechanism determining the switch between continuous transcription and premature termination to generate RNA primers for mitochondrial DNA (mtDNA) replication remains unclear. The pentatricopeptide repeat domain of mtRNAP exhibits exoribonuclease activity, which is required for the initiation of mtDNA replication in Drosophila. In this review, we explain how this exonuclease activity contributes to primer synthesis in strand-coupled mtDNA replication, and discuss how its regulation might co-ordinate mtDNA replication and transcription in both Drosophila and mammals.
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Replicación del ADN , ADN Mitocondrial , Mitocondrias , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Animales , Mitocondrias/metabolismo , Mitocondrias/genética , Humanos , ARN Polimerasas Dirigidas por ADN/metabolismo , Transcripción Genética , Drosophila/genética , Drosophila/metabolismo , Exorribonucleasas/metabolismo , Exorribonucleasas/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismoRESUMEN
In this study, we investigated the role of LINC00520 in colorectal cancer (CRC) progression. We analyzed LINC00520 expression in 15 pairs of CRC tissues and adjacent tissues using qRT-PCR, revealing significantly elevated levels in CRC tissues and cell lines. Lentivirus-mediated up/down-regulation of LINC00520 in CRC cell lines demonstrated that increased LINC00520 expression enhanced cell invasiveness, as confirmed by transwell and wound healing assays. Bioinformatics analysis identified a regulatory axis involving LINC00520, microRNA-195-3p, and NAT2. Luciferase assays confirmed direct binding between LINC00520 and microRNA-195-3p, as well as microRNA-195-3p and NAT2. Overexpression of NAT2 reversed the inhibitory effects on invasion and migration induced by LINC00520 silencing. This suggests that LINC00520, highly expressed in CRC tissues, may modulate tumor biological functions through the microRNA-195-3p/NAT2 axis. Our findings provide insights into the mechanism underlying CRC progression, highlighting the potential of LINC00520 as a therapeutic target.
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Arilamina N-Acetiltransferasa , Movimiento Celular , Neoplasias Colorrectales , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , MicroARNs , ARN Largo no Codificante , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Línea Celular Tumoral , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Arilamina N-Acetiltransferasa/genética , Arilamina N-Acetiltransferasa/metabolismo , Movimiento Celular/genética , Invasividad Neoplásica/genética , Proliferación Celular/genéticaRESUMEN
BACKGROUND: Previous studies implied that local M2 polarization of macrophage promoted mucosal edema and exacerbated TH2 type inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific pathogenic role of M2 macrophages and the intrinsic regulators in the development of CRS remains elusive. OBJECTIVE: We sought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP. METHODS: Real-time reverse transcription-quantitative PCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5-knockout mice were used to establish a nasal polyp model with TH2 inflammation and to investigate the effects of SIRT5 in macrophage on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages. RESULTS: Clinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophage markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5-deficient mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages by promoting glutaminolysis. CONCLUSIONS: SIRT5 plays a crucial role in promoting the development of CRSwNP by supporting alternative polarization of macrophages, thus providing a potential target for CRSwNP interventions.
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Macrófagos , Ratones Noqueados , Pólipos Nasales , Rinitis , Sinusitis , Sirtuinas , Animales , Sinusitis/inmunología , Sinusitis/patología , Sinusitis/genética , Humanos , Enfermedad Crónica , Macrófagos/inmunología , Macrófagos/metabolismo , Sirtuinas/genética , Sirtuinas/metabolismo , Ratones , Rinitis/inmunología , Rinitis/patología , Rinitis/genética , Pólipos Nasales/inmunología , Pólipos Nasales/patología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Eosinofilia/inmunología , Activación de Macrófagos/inmunología , Activación de Macrófagos/genética , Ratones Endogámicos C57BL , Eosinófilos/inmunología , Células Th2/inmunología , RinosinusitisRESUMEN
Increasing evidences suggest that the methyltransferase NSUN2 catalyzes 5-methylcytosine (m5C) modifications on viral RNAs, which are essential for the replication of various viruses. Despite the function of m5C deposition is well characterized, other potential roles of NSUN2 in regulating viral replication remain largely unknown. In this study, the m5C modified residues catalyzed by NSUN2 on enterovirus 71 (EV71) RNAs were mapped. NSUN2, along with m5C modifications, played multiple roles during the EV71 life cycle. Functional m5C modified nucleotides increased the translational efficiency and stability of EV71 RNAs. Additionally, NSUN2 was found to target the viral protein VP1 for binding and promote its stability by inhibiting the ubiquitination. Furthermore, both viral replication and pathogenicity in mice were largely attenuated when functional m5C residues were mutated. Taken together, this study characterizes distinct pathways mediated by NSUN2 in regulating EV71 replication, and highlights the importance of its catalyzed m5C modifications on EV71 RNAs for the viral replication and pathogenicity.
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Enterovirus Humano A , Infecciones por Enterovirus , Metiltransferasas , ARN Viral , Replicación Viral , Animales , Ratones , Enterovirus Humano A/genética , Enterovirus Humano A/fisiología , Infecciones por Enterovirus/virología , Metiltransferasas/genética , Metiltransferasas/metabolismo , ARN Viral/genética , ARN Viral/metabolismo , UbiquitinaciónRESUMEN
Objective: We compared the effects of early and delayed rehabilitation on the function of patients after rotator cuff repair by meta-analysis to find effective interventions to promote the recovery of shoulder function. Methods: This meta-analysis was registered in PROSPERO (CRD42023466122). We manually searched the randomized controlled trials (RCTs) in the Cochrane Library, Pubmed, Cochrane Library, EMBASE, the China National Knowledge Infrastructure (CNKI), the China VIP Database (VIP), and the Wanfang Database to evaluate the effect of early and delayed rehabilitation after arthroscopic shoulder cuff surgery on the recovery of shoulder joint function. Review Manager 5.3 software was used to analyze the extracted data. Then, the PEDro scale was employed to appraise the methodological quality of the included research. Results: This research comprised nine RCTs and 830 patients with rotator cuff injuries. According to the findings of the meta-analysis, there was no discernible difference between the early rehabilitation group and the delayed rehabilitation group at six and twelve months after the surgery in terms of the VAS score, SST score, follow-up rotator cuff healing rate, and the rotator cuff retear rate at the final follow-up. There was no difference in the ASES score between the early and delayed rehabilitation groups six months after the operation. However, although the ASES score in the early rehabilitation group differed significantly from that in the delayed rehabilitation group twelve months after the operation, according to the analysis of the minimal clinically important difference (MCID), the results have no clinical significance. Conclusions: The improvement in shoulder function following arthroscopic rotator cuff surgery does not differ clinically between early and delayed rehabilitation. When implementing rehabilitation following rotator cuff repair, it is essential to consider the paradoxes surrounding shoulder range of motion and tendon anatomic healing. A program that allows for flexible progression based on the patient's ability to meet predetermined clinical goals or criteria may be a better option.
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Artroscopía , Recuperación de la Función , Lesiones del Manguito de los Rotadores , Humanos , Artroscopía/rehabilitación , Lesiones del Manguito de los Rotadores/cirugía , Lesiones del Manguito de los Rotadores/rehabilitación , Manguito de los Rotadores/cirugía , Rango del Movimiento Articular , Factores de Tiempo , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
The integration of HPV DNA into human chromosomes plays a pivotal role in the onset of papillomavirus-related cancers. HPV DNA integration often occurs by linearizing the viral DNA in the E1/E2 region, resulting in the loss of a critical viral early polyadenylation signal (PAS), which is essential for the polyadenylation of the E6E7 bicistronic transcripts and for the expression of the viral E6 and E7 oncogenes. Here, we provide compelling evidence that, despite the presence of numerous integrated viral DNA copies, virus-host fusion transcripts originate from only a single integrated HPV DNA in HPV16 and HPV18 cervical cancers and cervical cancer-derived cell lines. The host genomic elements neighboring the integrated HPV DNA are critical for the efficient expression of the viral oncogenes that leads to clonal cell expansion. The fusion RNAs that are produced use a host RNA polyadenylation signal downstream of the integration site, and almost all involve splicing to host sequences. In cell culture, siRNAs specifically targeting the host portion of the virus-host fusion transcripts effectively silenced viral E6 and E7 expression. This, in turn, inhibited cell growth and promoted cell senescence in HPV16+ CaSki and HPV18+ HeLa cells. Showing that HPV E6 and E7 expression from a single integration site is instrumental in clonal cell expansion sheds new light on the mechanisms of HPV-induced carcinogenesis and could be used for the development of precision medicine tailored to combat HPV-related malignancies. IMPORTANCE: Persistent oncogenic HPV infections lead to viral DNA integration into the human genome and the development of cervical, anogenital, and oropharyngeal cancers. The expression of the viral E6 and E7 oncogenes plays a key role in cell transformation and tumorigenesis. However, how E6 and E7 could be expressed from the integrated viral DNA which often lacks a viral polyadenylation signal in the cancer cells remains unknown. By analyzing the integrated HPV DNA sites and expressed HPV RNAs in cervical cancer tissues and cell lines, we show that HPV oncogenes are expressed from only one of multiple chromosomal HPV DNA integrated copies. A host polyadenylation signal downstream of the integrated viral DNA is used for polyadenylation and stabilization of the virus-host chimeric RNAs, making the oncogenic transcripts targetable by siRNAs. This observation provides further understanding of the tumorigenic mechanism of HPV integration and suggests possible therapeutic strategies for the development of precision medicine for HPV cancers.
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ADN Viral , Proteínas Oncogénicas Virales , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Integración Viral , Humanos , Femenino , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/genética , Integración Viral/genética , Proteínas Oncogénicas Virales/genética , Proteínas Oncogénicas Virales/metabolismo , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/genética , ADN Viral/genética , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Línea Celular Tumoral , Oncogenes/genética , PoliadenilaciónRESUMEN
The quantum battery (QB) makes use of quantum effects to store and supply energy, which may outperform its classical counterpart. However, there are two challenges in this field. One is that the environment-induced decoherence causes the energy loss and aging of the QB, the other is that the decreasing of the charger-QB coupling strength with increasing their distance makes the charging of the QB become inefficient. Here, we propose a QB scheme to realize a remote charging via coupling the QB and the charger to a rectangular hollow metal waveguide. It is found that an ideal charging is realized as long as two bound states are formed in the energy spectrum of the total system consisting of the QB, the charger, and the electromagnetic environment in the waveguide. Using the constructive role of the decoherence, our QB is immune to the aging. Additionally, without resorting to the direct charger-QB interaction, our scheme works in a way of long-range and wireless-like charging. Effectively overcoming the two challenges, our result supplies an insightful guideline to the practical realization of the QB by reservoir engineering.
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ETHNOPHARMACOLOGICAL RELEVANCE: Baoyuan Decoction (BYD) was initially recorded in the classic of "Bo Ai Xin Jian" in the Ming dynasty. It is traditionally used for treating weakness and cowardice, and deficiency of vital energy. In researches related to anti-fatigue effects, the reciprocal regulation of AMPK and circadian clocks likely plays an important role in anti-fatigue mechanism, while it has not yet been revealed. Therefore, we elucidated the anti-fatigue mechanism of BYD through AMPK/CRY2/PER1 pathway. AIM OF THE STUDY: To investigate the effect and mechanism of BYD in reducing fatigue, using pharmacodynamics, network pharmacology and transcriptomics through the AMPK/CRY2/PER1 signaling pathway. MATERIALS AND METHODS: Firstly, the chemical constituents of BYD were qualitatively identified by UHPLC-Q-Exactive Orbitrap/MS, establishing a comprehensive strategy with an in-house library, Xcalibur software and Pubchem combined. Secondly, a Na2SO3-induced fatigue model and 2,2'-Azobis (2-methylpropionamidine) dihydrochloride (AAPH)-induced oxidative stress model were developed to evaluate the anti-fatigue and anti-oxidant activities of BYD using AB zebrafish. The anti-inflammatory activity of BYD was evaluated using CuSO4-induced and tail cutting-induced Tg (lyz: dsRed) transgenic zebrafish inflammation models. Then, target screening was performed by Swiss ADME, GeneCards, OMIM and DrugBank databases, the network was constructed using Cytoscape 3.9.0. Transcriptome and network pharmacology technology were used to investigate the related signaling pathways and potential mechanisms after treatment with BYD, which were verified by real-time quantitative PCR (RT-qPCR). RESULTS: In total, 114 compounds from the water extract of BYD were identified as major compounds. Na2SO3-induced fatigue model and AAPH-induced oxidative stress model indicated that BYD has significant anti-fatigue and antioxidant effects. Meanwhile, BYD showed significant anti-inflammatory effects on CuSO4-induced and tail cutting-induced zebrafish inflammation models. The KEGG result of network pharmacology showed that the anti-fatigue function of BYD was mainly effected through AMPK signaling pathway. Besides, transcriptome analysis indicated that the circadian rhythm, AMPK and IL-17 signaling pathways were recommended as the main pathways related to the anti-fatigue effect of BYD. The RT-qPCR results showed that compared with a model control group, the treatment of BYD significantly elevated the expression mRNA of AMPK, CRY2 and PER1. CONCLUSION: Herein, we identified 114 chemical constituents of BYD, performed zebrafish activity validation, while demonstrated that BYD can relieve fatigue by AMPK/CRY2/PER1 signaling pathway through network pharmacology and transcriptome.
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Proteínas Quinasas Activadas por AMP , Amidinas , Medicamentos Herbarios Chinos , Animales , Pez Cebra , Estrés Oxidativo , Fatiga/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Inflamación/tratamiento farmacológico , Antioxidantes , Transducción de Señal , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéuticoRESUMEN
Purpose: This research aims to study and compare the effects of moderate-intensity continuous exercise and accumulated exercise with different number of bouts on common carotid arterial stiffness and hemodynamic variables. Methods: Thirty healthy male adults were recruited to complete four trials in a randomized crossover design: no-exercise (CON); continuous exercise (CE, 30-min cycling); accumulated exercise including two or three bouts with 10-min rest intervals (AE15, 2 × 15-min cycling; AE10, 3 × 10-min cycling). The intensity in all the exercise trials was set at 45%-55% heart rate reserve. Blood pressure, right common carotid artery center-line velocity, and arterial inner diameter waveforms were measured at baseline and immediately after exercise (0 min), 10 min, and 20 min. Results: 1) The arterial stiffness index and pressure-strain elastic modulus of the CE and AE15 groups increased significantly at 0 min, arterial diameters decreased in AE15 and AE10, and all indicators recovered at 10 min. 2) The mean blood flow rate and carotid artery center-line velocity increased in all trials at 0 min, and only the mean blood flow rate of AE10 did not recover at 10 min. 3) At 0 min, the blood pressure in all trials was found to be increased, and the wall shear stress and oscillatory shear index of AE10 were different from those in CE and AE15. At 20 min, the blood pressure of AE10 significantly decreased, and the dynamic resistance, pulsatility index, and peripheral resistance of CE partially recovered. Conclusion: There is no significant difference in the acute effects of continuous exercise and accumulated exercise on the arterial stiffness and diameter of the carotid artery. Compared with continuous exercise, accumulated exercise with an increased number of bouts is more effective in increasing cerebral blood supply and blood pressure regulation, and its oscillatory shear index recovers faster. However, the improvement of blood flow resistance in continuous exercise was better than that in accumulated exercise.
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Histone modifications function in both cellular and viral gene expression. However, the roles of acetyltransferases and histone acetylation in parvoviral infection remain poorly understood. In the current study, we found the histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), promoted the replication and transcription of parvovirus minute virus of canines (MVC). Notably, the expression of host acetyltransferases KAT5, GTF3C4, and KAT2A was increased in MVC infection, as well as H4 acetylation (H4K12ac). KAT5 is not only responsible for H4K12ac but also crucial for viral replication and transcription. The viral nonstructural protein NS1 interacted with KAT5 and enhanced its expression. Further study showed that Y44 in KAT5, which may be tyrosine-phosphorylated, is indispensable for NS1-mediated enhancement of KAT5 and efficient MVC replication. The data demonstrated that NS1 interacted with KAT5, which resulted in an enhanced H4K12ac level to promote viral replication and transcription, implying the epigenetic addition of H4K12ac in viral chromatin-like structure by KAT5 is vital for MVC replication.IMPORTANCEParvoviral genomes are chromatinized with host histones. Therefore, histone acetylation and related acetyltransferases are required for the virus to modify histones and open densely packed chromatin structures. This study illustrated that histone acetylation status is important for MVC replication and transcription and revealed a novel mechanism that the viral nonstructural protein NS1 hijacks the host acetyltransferase KAT5 to enhance histone acetylation of H4K12ac, which relies on a potential tyrosine phosphorylation site, Y44 in KAT5. Other parvoviruses share a similar genome organization and coding potential and may adapt a similar strategy for efficient viral replication and transcription.
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Lisina Acetiltransferasa 5 , Infecciones por Parvoviridae , Animales , Perros , Acetilación , Acetiltransferasas/metabolismo , Cromatina , Histona Acetiltransferasas/genética , Histona Acetiltransferasas/metabolismo , Histonas/genética , Histonas/metabolismo , Infecciones por Parvoviridae/metabolismo , Infecciones por Parvoviridae/veterinaria , Infecciones por Parvoviridae/virología , Tirosina/metabolismo , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/metabolismo , Línea Celular , Enfermedades de los Perros/metabolismo , Enfermedades de los Perros/virología , Lisina Acetiltransferasa 5/metabolismoRESUMEN
Eukaryotic five-methylcytosine (m5C) is an important regulator of viral RNA splicing, stability, and translation. However, its role in HBV replication remains largely unknown. In this study, functional m5C sites are identified in hepatitis B virus (HBV) mRNA. The m5C modification at nt 1291 is not only indispensable for Aly/REF export factor (ALYREF) recognition to promote viral mRNA export and HBx translation but also for the inhibition of RIG-I binding to suppress interferon-ß (IFN-ß) production. Moreover, NOP2/Sun RNA methyltransferase 2 (NSUN2) catalyzes the addition of m5C to HBV mRNA and is transcriptionally downregulated by the viral protein HBx, which suppresses the binding of EGR1 to the NSUN2 promoter. Additionally, NSUN2 expression correlates with m5C modification of type I IFN mRNA in host cells, thus, positively regulating IFN expression. Hence, the delicate regulation of NSUN2 expression induces m5C modification of HBV mRNA while decreasing the levels of m5C in host IFN mRNA, making it a vital component of the HBV life cycle. These findings provide new molecular insights into the mechanism of HBV-mediated IFN inhibition and may inform the development of new IFN-α based therapies.
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Virus de la Hepatitis B , Replicación Viral , Virus de la Hepatitis B/genética , Replicación Viral/genética , Antivirales/farmacología , ARN Mensajero/genética , Epigénesis GenéticaRESUMEN
BACKGROUND: Sedentary behavior is widespread among older adults and accelerates the decline of motor function. Nevertheless, there is insufficient evidence concerning the effectiveness of regular exercise in enhancing the same in sedentary older adults. OBJECTIVE: To compare the effects of 24 weeks of aerobic and combined aerobic-resistance exercise on the motor function of sedentary older adults. METHODS: Sixty healthy sedentary older (65-80 years) were randomly enrolled. Participants were randomly divided into 3 groups (1:1:1): aerobic exercise group (AEG), combined aerobic-resistance exercise group (CEG), and health education group (HEG). The training group underwent a five-day-a-week regimen, with each session lasting for 40 minutes (including 10 min warm-up and cool-down). HEG received only monthly health lectures. We assessed lower limb muscle strength (30-second sit-to-stand ability), single-dual task gait, static and dynamic balance functions at baseline and after 24 weeks of intervention using per-protocol analysis. RESULTS: Among 60 elderly healthy who were randomized (mean age 70.59 ± 3.31 years; 28 women (46%)), 42 (70%) completed the evaluation after 24 weeks. Both the aerobic exercise and combined aerobic-resistance exercise groups exhibited improved 30-second sit-to-stand ability, static balance in closed-eye standing mode, and dynamic balance (P< 0.05). However, there were no statistically significant changes in the single-task gait parameters of stride length, stride width, and stride speed (P> 0.05). Additionally, compared to the aerobic exercise group, the combined exercise group showed an increase in dual-task gait speed and medial and lateral dynamic stability indices (P< 0.05). CONCLUSION: Both the aerobic exercise and combined aerobic-resistance exercise programs are effective in enhancing lower limb muscle strength, dynamic balance, and static balance while standing with eyes closed in sedentary older adults. Furthermore, the combined aerobic-resistance exercise program is more effective in improving dual-task gait speed as well as medial and lateral dynamic balance.
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Entrenamiento de Fuerza , Humanos , Femenino , Anciano , Entrenamiento de Fuerza/métodos , Equilibrio Postural/fisiología , Ejercicio Físico/fisiología , Terapia por Ejercicio/métodos , Marcha/fisiologíaRESUMEN
In the application of driverless technology, current traffic sign recognition methods are susceptible to the influence of ambient light interference, target size changes and complex backgrounds, resulting in reduced recognition accuracy. To address these challenges, this study introduces an optimisation algorithm called ETSR-YOLO, which is based on the YOLOv5s algorithm. First, this study improves the path aggregation network (PANet) of YOLOv5s to enhance multi-scale feature fusion by generating an additional high-resolution feature layer to improve the recognition of YOLOv5s for small-sized objects. Second, the study introduces two improved C3 modules that aim to suppress background noise interference and enhance the feature extraction capabilities of the network. Finally, the study uses the Wise-IoU (WIoU) function in the post-processing stage to improve the learning ability and robustness of the algorithm to different samples. The experimental results show that ETSR-YOLO improves mAP@0.5 by 6.6% on the Tsinghua-Tencent 100K (TT100K) dataset and by 1.9% on the CSUST Chinese Traffic Sign Detection Benchmark 2021 (CCTSDB2021) dataset. In the experiments conducted on the embedded computing platform, ETSR-YOLO demonstrates a short average inference time, thereby affirming its capability to deliver dependable traffic sign detection for intelligent vehicles operating in real-world traffic scenes. The source code and test results of the models used in this study are available at https://github.com/cbrook16/ETSR-YOLO.
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Subgenomic flaviviral RNAs (sfRNAs) are produced during flavivirus infections in both arthropod and vertebrate cells. They are undegraded products originating from the viral 3' untranslated region (3' UTR), a result of the action of the host 5'-3' exoribonuclease, Xrn1, when it encounters specific RNA structures known as Xrn1-resistant RNAs (xrRNAs) within the viral 3' UTR. Dengue viruses generate three to four distinct species of sfRNAs through the presence of two xrRNAs and two dumbbell structures (DBs). The tertiary structures of xrRNAs have been characterized to form a ringlike structure around the 5' end of the viral RNA, effectively inhibiting the activity of Xrn1. The most important role of DENV sfRNAs is to inhibit host antiviral responses by interacting with viral and host proteins, thereby influencing viral pathogenicity, replicative fitness, epidemiological fitness, and transmission. In this review, we aimed to summarize the biogenesis, structures, and functions of DENV sfRNAs, exploring their implications for viral interference.
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Virus del Dengue , Dengue , Flavivirus , Humanos , Flavivirus/genética , Virus del Dengue/genética , Virus del Dengue/metabolismo , ARN Subgenómico , Regiones no Traducidas 3' , Conformación de Ácido Nucleico , ARN Viral/metabolismo , Dengue/genéticaRESUMEN
The biological clock system is an intrinsic timekeeping device that integrates internal physiology and external cues. Maintaining a healthy biological clock system is crucial for life. Disruptions to the body's internal clock can lead to disturbances in the sleep-wake cycle and abnormalities in hormone regulation, blood pressure, heart rate, and other vital processes. Long-term disturbances have been linked to the development of various common major diseases, including cardiovascular diseases, metabolic disorders, tumors, neuropsychiatric conditions, and so on. External factors, such as the diurnal rhythm of light, have a significant impact on the body's internal clock. Additionally, as an important non-photic zeitgeber, exercise can regulate the body's internal rhythms to a certain extent, making it possible to become a non-drug intervention for preventing and treating circadian rhythm disorders. This comprehensive review encompasses behavioral, physiological, and molecular perspectives to provide a deeper understanding of how exercise influences circadian rhythms and its association with related diseases.
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Recent studies have highlighted the critical roles of long non-coding RNAs (lncRNAs) in various biological processes, including but not limited to dosage compensation, epigenetic regulation, cell cycle regulation, and cell differentiation regulation. Consequently, lncRNAs have emerged as a central focus in genetic studies. The identification of the subcellular localization of lncRNAs is essential for gaining insights into crucial information about lncRNA interaction partners, post- or co-transcriptional regulatory modifications, and external stimuli that directly impact the function of lncRNA. Computational methods have emerged as a promising avenue for predicting the subcellular localization of lncRNAs. However, there is a need for additional enhancement in the performance of current methods when dealing with unbalanced data sets. To address this challenge, we propose a novel ensemble deep learning framework, termed lncLocator-imb, for predicting the subcellular localization of lncRNAs. To fully exploit lncRNA sequence information, lncLocator-imb integrates two base classifiers, including convolutional neural networks (CNN) and gated recurrent units (GRU). Additionally, it incorporates two distinct types of features, including the physicochemical pattern feature and the distributed representation of nucleic acids feature. To address the problem of poor performance exhibited by models when confronted with unbalanced data sets, we utilize the label-distribution-aware margin (LDAM) loss function during the training process. Compared with traditional machine learning models and currently available predictors, lncLocator-imb demonstrates more robust category imbalance tolerance. Our study proposes an ensemble deep learning framework for predicting the subcellular localization of lncRNAs. Additionally, a novel approach is presented for the management of different features and the resolution of unbalanced data sets. The proposed framework exhibits the potential to serve as a significant resource for various sequence-based prediction tasks, providing a versatile tool that can be utilized by professionals in the fields of bioinformatics and genetics.
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AIM: To elucidate the association between gut microbiota, short-chain fatty acids (SCFAs), and glucolipid metabolism in women with large for gestational age (LGA) infants. METHODS AND RESULTS: A single-center, observational prospective cohort study was performed at a tertiary hospital in Wenzhou, China. Normal pregnant women were divided into LGA group and appropriate for gestational age (AGA) group according to the neonatal birth weight. Fecal samples were collected from each subject before delivery for the analysis of gut microbiota composition (GMC) and SCFAs. Blood samples were obtained at 24-28 weeks of gestation age to measure fasting blood glucose and fasting insulin levels, as well as just before delivery to assess serum triglycerides, total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein. The GMC exhibited differences at various taxonomic levels. Within the Firmicutes phylum, genus Lactobacillus, genus Clostridium, species Lactobacillus agil, and species Lactobacillus salivarius were enriched in the LGA group. Microbispora at genus level, Microbispora rosea at species level belonging to the Actinobacteria phylum, Neisseriales at order level, Bartonellaceae at family level, Paracoccus aminovorans, and Methylobacterium at genus level from the Proteobacteria phylum were more abundant in the LGA group. In contrast, within the Bacteroidetes phylum, Prevotella at genus level and Parabacteroides distasonis at species level were enriched in the AGA group. Although there were few differences observed in SCFA levels and most glucolipid metabolism indicators between the two groups, the serum HDL level was significantly lower in the LGA group compared to the AGA group. No significant relevance among GMC, SCFAs, and glucolipid metabolism indicators was found in the LGA group or in the AGA group. CONCLUSIONS: Multiple different taxa, especially phylum Firmicutes, genus Prevotella, and genus Clostridium, might play an important role in excessive fetal growth, and LGA might be associated with the lower serum HDL level.