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Context: Chronic nonspecific low back pain (CNLBP) is a common musculoskeletal disorder that seriously affects patients' quality of life (QoL). Clinicians have used Kinesio Taping (KT) in the treatment of CNLBP patients, but evidence is still lacking on the benefits of KT for CNLBP. Objective: The study aimed to perform a systematic review and meta-analysis of the currently published randomized controlled trails (RCTs) to determine KT's efficacy for CNLBP patients. Design: The research team performed a literature search using five major electronic databases-PubMed, Embase, Web of science, Cochrane Library, MEDLINE and OpenGrey-and included studies form inception to January 2018. The search used the keywords "kinesio tap*", "kinesio*", and "chronic low back pain (CLBP)" or "CNLBP". Setting: The study took place in the 942 Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army. Outcome Measures: The research team performed the meta-analysis using RevMan 5.3 software. The team selected studies that used pain intensity and disability as the primary outcome measures, and if the study used other outcomes, they had to be the secondary outcomes. Results: The systematic review included nine RCTs in the meta-analysis. KT can significantly reduce pain intensity between baseline and immediately postintervention (SMD = -0.47, 95% CI -0.93 to -0.02, P = .04) and between baseline and the short-term follow-up period (SMD = -0.67, 95% CI -0.44 to -0.20, P = .03). However, no significant differences existed between KT's ability to relieve other symptoms of CNLBP-disability, trunk flexion range of motion (ROM), change in status, fear of movement, isometric endurance of the trunk muscles, or extension-when compared to either sham taping or KT as an adjunct to physical therapy. Conclusions: KT can have immediate and short-term positive effects on reducing pain intensity, but existing evidence doesn't support KT's superiority to other interventions in improving functions for individuals with CNLBP.
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DNA-based analyses have become routine methods in soil microbial research, for their high throughput and resolution in characterizing microbial communities. Yet, concerns arise regarding the interference of relic DNA in estimates of viable bacterial community composition and individual taxa dynamics in soils that recovered from post-gamma irradiation. In this study, different soil samples with varying bacterial diversity but similar soil properties were randomly selected. We split each sample into two parts: one part was treated with propidium monoazide (PMA) before DNA extraction, PMA can bind to relic DNA and inhibit PCR amplification by chemical modification; DNA of the other part was extracted following the same process but without PMA pretreatment. Then, soil bacterial abundance was quantified by quantitative polymerase chain reaction, and bacterial community structure was examined by Illumina metabarcoding sequencing of 16S rRNA gene. The results showed that the higher bacterial richness and evenness were estimated when relic DNA was present. The variation trends of bacterial abundance, alpha diversity, and beta diversity remained the same, as reflected by the significant correlations between PMA-treated and -untreated samples (P < 0.05). Moreover, as the mean abundance increased, the reproducibility of detecting individual taxa dynamics between relic DNA present and absent treatments increased. These findings provide empirical evidence that a more even distribution of species abundance derived from relic DNA would result in the overestimation of richness in the total DNA pools and also have crucial implications for guiding proper application of high-throughput sequencing to estimate bacterial community diversity and taxonomic population dynamic. KEY POINTS: ⢠Relic DNA effects on the bacterial community in sterilized soils were assessed. ⢠More even species abundance distribution in relic DNA overestimates true richness. ⢠The reproducibility of individual taxa dynamics increased with their abundance.
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Stimulator of interferon genes (STING) orchestrates the production of proinflammatory cytokines in response to cytosolic double-stranded DNA; however, the pathophysiological significance and molecular mechanism underlying the folding and maturation of nascent STING protein at the endoplasmic reticulum (ER) remain unknown. Here we report that the SEL1L-HRD1 protein complex-the most conserved branch of ER-associated degradation (ERAD)-is a negative regulator of the STING innate immunity by ubiquitinating and targeting nascent STING protein for proteasomal degradation in the basal state. SEL1L or HRD1 deficiency in macrophages specifically amplifies STING signalling and immunity against viral infection and tumour growth. Mechanistically, nascent STING protein is a bona fide substrate of SEL1L-HRD1 in the basal state, uncoupled from ER stress or its sensor inositol-requiring enzyme 1α. Hence, our study not only establishes a key role of SEL1L-HRD1 ERAD in innate immunity by limiting the size of the activable STING pool, but identifies a regulatory mechanism and therapeutic approach to targeting STING.
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Degradação Associada com o Retículo Endoplasmático , Ubiquitina-Proteína Ligases , Ubiquitina-Proteína Ligases/metabolismo , Proteínas/metabolismo , Retículo Endoplasmático/metabolismo , Imunidade InataRESUMO
The hydrolysis acidification process is an economical and effective method, but its efficiency is still low in treating azo dye wastewater. It is therefore crucial to find more suitable and efficient means or techniques to further strengthen the process of treating azo dye wastewater by a hydrolytic acidification process. In this study, a hydrolytic acidification aerobic reactor was used to simulate the azo dye wastewater process. The change of wastewater quality during the reaction process was monitored, and the deep enhancement effect of single or composite biological intensification technology on the treatment of azo dye wastewater by the hydrolytic acidification process was also explored. Co-substrate strengthening and the addition of fructose co-substrate can significantly improve the efficiency of hydrolytic acidification. Compared with the experimental group without the addition of fructose, the decolorization ratio of wastewater was higher (93%) after adding fructose co-substrate. The immobilization technology was strengthened, and the immobilized functional bacteria DDMZ1 pellet was used to treat the simulated azo dye wastewater. The results showed that the composite technology experimental group with the additional fructose co-matrix had a better decolorization efficiency than the single immobilized bio-enhancement technology, with the highest decolorization ratio of 97%. As a composite biological intensification method, the fructose co-matrix composite with immobilized functional bacteria DDMZ1 technology can be applied to the treatment of azo dye wastewater.
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3-Hydroxypropionic acid (3-HP) is an important intermediate compound in the chemical industry. Green and environmentally friendly microbial synthesis methods are becoming increasingly popular in a range of industries. Compared to other chassis cells, Yarrowia lipolytica possesses advantages, such as high tolerance to organic acid and a sufficient precursor required to synthesize 3-HP. In this study, gene manipulations, including the overexpression of genes MCR-NCa, MCR-CCa, GAPNSm, ACC1 and ACSSeL641P and knocking out bypass genes MLS1 and CIT2, leading to the glyoxylate cycle, were performed to construct a recombinant strain. Based on this, the degradation pathway of 3-HP in Y. lipolytica was discovered, and relevant genes MMSDH and HPDH were knocked out. To our knowledge, this study is the first to produce 3-HP in Y. lipolytica. The yield of 3-HP in recombinant strain Po1f-NC-14 in shake flask fermentation reached 1.128 g·L-1, and the yield in fed-batch fermentation reached 16.23 g·L-1. These results are highly competitive compared to other yeast chassis cells. This study creates the foundation for the production of 3-HP in Y. lipolytica and also provides a reference for further research in the future.
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The allocation of executives' environmental attention (EEA) is of great significance in promoting the green upgrading of industrial structures and achieving corporate green transformation. Based on upper echelon theory and the attention-based view, we use panel data of Chinese manufacturing companies from 2015 to 2020 to construct a two-way fixed effects model to explore the impact mechanism of EEA on corporate green transformation performance (CGTP). Baseline regression shows that EEA significantly improves CGTP. The reliability of findings is verified by reducing time windows, replacing the independent variable, expanding the data source, and adding missing variables. In the heterogeneity analysis, the positive effect of EEA on CGTP is significant for eastern companies and does not differ in the property rights grouping. After propensity score matching, environmental attribute grouping shows that the positive effect of EEA on CGTP is more significant for non-heavy polluters. Extended research shows that government subsidies have a positive moderating effect, while female executives play only a symbolic role. Moreover, green innovation activities have positive partial mediating effects. Green innovation is the best way to address environmental pollution and achieve corporate green transformation. Our research provides implications for decision-makers to allocate their attention, and thereby achieve green development appropriately.
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Influenza is an infectious acute respiratory disease with complications and a high mortality rate; the effective medicines for influenza therapy are limited. "Huanglian" or Coptidis Rhizoma, Coptis chinensis Franch., Ranunculaceae, and "ganjiang" or Zingiberis Rhizoma, Zingiber officinale Roscoe, Zingiberaceae, combination is clinically used for treating respiratory diseases. HPLC was applied for the quantification of berberine hydrochloride (1.101 mg/ml) and 6-gingerol (38.41 µg/ml) in the H2O-soluble extract of the herbal formulation. In this study, the effect of "huanglian"- "ganjiang" extract on influenza virus H1N1-induced acute pulmonary inflammation was evaluated, in addition to the investigation of its anti-influenza mechanism in a mouse model. The analyzed herbal combination inhibited the expression of cytokine IL-6 and stimulated the expression of IL-2 in the serum of influenza virus-infected mice. Meanwhile, the herbal combination downregulated the gene and protein expression levels of TLR3, TLR7, MyD88, RIG-I, MAVS, TRAF3, and NF-κB p65, which are key targets of toll-like and RIG-I-like receptor signaling pathways in mice. In addition, the herbal combination could also promote the combination of intracellular autophagosomes and lysosomes in autophagosome-lysosome formation and improve impaired fusion of autophagosomes and lysosomes by influenza virus. This study suggested that the "huanglian"- "ganjiang" extract may be a candidate therapeutic strategy for the treatment of H1N1 influenza. Supplementary Information: The online version contains supplementary material available at 10.1007/s43450-023-00372-z.
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The structure of ligands has a significant influence on the separation properties of alkyl and aromatic phases in reversed-phase liquid chromatography. Compared with alkyl phases, the effect of stereoconfiguration of aromatic ligands on the retention and selectivity of stationary phases has rarely been addressed. To illustrate the issue, three terphenyl isomer-bonded stationary phases were prepared via the coupling chemistry of isocyanate with terphenyl amine isomers, 3,4-diphenylaniline, 2,4-diphenylaniline and 4-amino-p-terphenyl, respectively. The retention behaviors of stationary phases were assessed in terms of retention strength, selectivity, hydrophobic and π-π interaction by five kinds of solutes. It is found that the selectivity towards the solutes is slightly larger on the branched m-terphenyl-bonded phase (m-π3) than o-terphenyl-bonded phase (o-π3) but is significantly improved on the chain p-terphenyl-bonded phase (p-π3). The results can be interpreted by the ease self-adjustment of the conformation of the chain p-terphenyl ligand and the smaller steric effect of p-π3 towards the insertion of solutes into the ligand brushes. In addition, the p-π3 yields excellent selective separation towards aromatic solutes. These findings are of significance in the design of aromatic stationary phases.
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Cromatografia de Fase Reversa , Compostos de Terfenil , Ligantes , Interações Hidrofóbicas e Hidrofílicas , AminasRESUMO
OBJECTIVE: To evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with decitabine (Dec)-conditioning regimen in the treatment of myelodysplastic syndrome (MDS) and MDS transformed acute myeloid leukemia (MDS-AML). METHODS: The characteristics and efficacy data of 93 patients with MDS and MDS-AML who received allo-HSCT in our center from April 2013 to November 2021 were retrospectively analyzed. All patients were administered by myeloablative conditioning regimen containing Dec (25 mg/m2 /d×3 d). RESULTS: Among the 93 patients, 63 males and 30 females, were diagnosed as MDSï¼n ï¼77ï¼, MDS-AMLï¼n ï¼16ï¼. The incidence of I/II grade regimen-related toxicity (RRT) was 39.8%, and III grade RRT was only found in 1 patient (1%). Neutrophil engraftment was successful in 91 (97.8%) patients after a median neutrophil engraftment time of 14 (9-27) days; Successful platelet engraftment was achieved in 87 (93.5%) patients, with a median engraftment time of 18 (9-290) days. The incidence of acute graft versus host diseaseï¼aGVHDï¼ and grade III-IV aGVHD was 44.2% and 16.2%, respectively. The incidence of chronic graft versus host diseaseï¼cGVHDï¼ and moderate-to-severe cGVHD was 59.5% and 37.1%, respectively. Of the 93 patients, 54 (58%) developed posttransplant infections, among which lung infection (32.3%) and bloodstream infection (12.9%) were the most common. The median follow-up after transplantation was 45 (0.1-108) months. The 5-year overall survival (OS) rate, disease-free survival (DFS) rate, treatment-related mortality, and cumulative incidence of relapse were 72.7%, 68.4%, 25.1%, and 6.5%, respectively. And the 1-year graft-versus-host disease/relapse-free survival rate was 49.3%. The patients in different group of relative high-risk prognostic scoring or low-risk prognostic scoring, with or without poor-risk mutation(s), with mutations number ≥3 or <3 had similar 5-year OS rate (more than 70%). Multivariate analysis showed that the incidence of grade III-IV aGVHD was the independent risk factor affecting OSï¼P =0.008ï¼and DFS (P =0.019). CONCLUSION: Allo-HSCT with Dec-conditioning regimen is feasible and effective in the treatment of patients with MDS and MDS-AML, especially those in high prognostic risk and with poor-risk mutations.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Masculino , Feminino , Humanos , Decitabina , Estudos Retrospectivos , Transplante Homólogo/efeitos adversos , Condicionamento Pré-Transplante/efeitos adversos , Síndromes Mielodisplásicas/complicações , Leucemia Mieloide Aguda/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Crônica , Doença Enxerto-Hospedeiro/terapia , RecidivaRESUMO
OBJECTIVES: To investigate the role of fragile X mental retardation syndrome-related protein 1 (FXR1), an RNA binding protein, in the development of osteoarthritis (OA), to define its mechanism of action in cartilage, and to determine whether targeting FXR1 can prevent OA in mice. METHODS: Western blot analysis and quantitative polymerase chain reaction were performed using cartilage tissue from control and osteoarthritic mice. FXR1 expression was detected by immunofluorescence staining using cartilage tissue from mice. OA was induced by destabilising the medial meniscus in the mice. Infection of mouse chondrocytes with FXR1 lentivirus, as well as viral injection into the mouse knee joint cavity, resulted in high FXR1 protein expression. Chondrocyte apoptosis was detected by TUNEL assay and cell senescence was detected by SA-ß-gal staining assay. RESULTS: FXR1 expression was significantly reduced in cartilage and soft tissue from mice with OA compared with the controls. FXR1 overexpression reduced staphylococcal nuclease domain protein 1 (SND1) levels. Furthermore, FXR1 is able to inhibit apoptosis and senescence of chondrocytes via SND1 and hinder the development of OA in mice. CONCLUSIONS: FXR1 down-regulates SND1 expression, thereby alleviating osteoarthritic symptoms in mice. In summary, FXR1 may have a therapeutic approach to the treatment of OA.
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Primary cilia are microtubule-based organelles presenting on the surface of most postmitotic mammalian cells. As being signaling hubs and sensory organelles, primary cilia can respond to mechanical and chemical stimuli from the extracellular environment. Arl13b (ADP-ribosylation factor-like 13B), an atypical Arf/Arl family GTPase, was identified in genetic screening as a protein essential for maintaining the integrity of cilia and neural tubes. Previous studies on Arl13b have mostly focused on its role in the development of neural tubes, polycystic kidneys, and tumors, but no role in bone patterns was described. This study reported the essential roles of Arl13b in bone formation and osteogenic differentiation. Arl13b was highly expressed in bone tissues and osteoblasts, positively correlated with osteogenic activity during bone development. Furthermore, Arl13b was essential for primary cilium maintenance and Hedgehog signaling activation in osteoblasts. Arl13b knockdown in osteoblasts decreased the length of primary cilia and the upregulated levels of Gli1, Smo, and Ptch1 upon Smo agonist treatment. Additionally, Arl13b knockdown inhibited cell proliferation and migration. Moreover, Arl13b mediated osteogenesis and cell mechanosensation. Cyclic tension strain upregulated the Arl13b expression. Arl13b knockdown suppressed osteogenesis and mitigated cyclic tension strain-induced osteogenesis. These results suggest that Arl13b have important roles in bone formation and mechanosensation.
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Cellular mechanical properties are considered to be important factors affecting cell fate transitions, but the links between cellular mechanical properties and transition efficiency and chromatin structure remain elusive. Here, we predicted that mechanical strain treatment could induce signatures of cellular dedifferentiation and transdifferentiation, and we validated this prediction by showing that mechanical strain-treated mouse cumulus cells (CCs) exhibit significantly improved somatic cell nuclear transfer (SCNT) reprogramming efficiency. We found that the chromatin accessibility of CCs was globally increased by mechanical strain treatment and that this increase was partially mediated by the induction of the YAP-TEAD interaction. Moreover, using mechanical strain-treated CCs could prevent transcriptional dysregulation in SCNT embryos. Taken together, our study results demonstrated that modulating cell mechanical properties to regulate epigenetic status is a promising approach to facilitate cell fate transition.
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Cromatina , Técnicas de Transferência Nuclear , Animais , Camundongos , Cromatina/genética , Reprogramação Celular/genética , Embrião de Mamíferos , Desenvolvimento Embrionário/genéticaRESUMO
Regional wind speed prediction plays an important role in the development of wind power, which is usually recorded in the form of two orthogonal components, namely U-wind and V-wind. The regional wind speed has the characteristics of diverse variations, which are reflected in three aspects: (1) The spatially diverse variations of regional wind speed indicate that wind speed has different dynamic patterns at different positions; (2) The distinct variations between U-wind and V-wind denote that U-wind and V-wind at the same position exhibit different dynamic patterns; (3) The non-stationary variations of wind speed represent that the intermittent and chaotic nature of wind speed. In this paper, we propose a novel framework named Wind Dynamics Modeling Network (WDMNet) to model the diverse variations of regional wind speed and make accurate multi-step predictions. To jointly capture the spatially diverse variations and the distinct variations between U-wind and V-wind, WDMNet leverages a new neural block called Involution Gated Recurrent Unit Partial Differential Equation (Inv-GRU-PDE) as its key component. The block adopts involution to model spatially diverse variations and separately constructs hidden driven PDEs of U-wind and V-wind. The construction of PDEs in this block is achieved by a new Involution PDE (InvPDE) layers. Besides, a deep data-driven model is also introduced in Inv-GRU-PDE block as the complement to the constructed hidden PDEs for sufficiently modeling regional wind dynamics. Finally, to effectively capture the non-stationary variations of wind speed, WDMNet follows a time-variant structure for multi-step predictions. Comprehensive experiments have been conducted on two real-world datasets. Experimental results demonstrate the effectiveness and superiority of the proposed method over state-of-the-art techniques.
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VentoRESUMO
BACKGROUND: Evidence has indicated that the risk of gestational diabetes mellitus (GDM) was linked to PM2.5 exposure during pregnancy, but findings on susceptible exposure windows are inconsistent. Further, previous studies have not paid attention to B12 intake in the relationship between PM2.5 exposure and GDM. The study is aimed to identify the strength and exposure periods for associations of PM2.5 exposure with GDM, followed by exploring the potential interplay of gestational B12 levels and PM2.5 exposure on the risk of GDM. METHODS: The participants were recruited in a birth cohort between 2017 and 2018, and 1396 eligible pregnant women who completed a 75-g oral glucose tolerance test (OGTT) were included. Prenatal PM2.5 concentrations were estimated using an established spatiotemporal model. Logistic and linear regression analyses were used to test associations of gestational PM2.5 exposure with GDM and OGTT-glucose levels, respectively. The joint associations of gestational PM2.5 exposure and B12 level on GDM were examined under crossed exposure combinations of PM2.5 (high versus low) and B12 (insufficient versus sufficient). RESULTS: In the 1396 pregnant women, the median levels of PM2.5 exposure during the 12 weeks before pregnancy, the 1st trimester, and the 2nd trimesters were 59.33 µg/m3, 63.44 µg/m3, and 64.39 µg/m3, respectively. The risk of GDM was significantly associated with a 10 µg/m3 increase of PM2.5 during the 2nd trimester (RR = 1.44, 95 % CI: 1.01, 2.04). The percentage change in fasting glucose was also associated with PM2.5 exposure during the 2nd trimester. A higher risk of GDM was observed among women with high PM2.5 exposure and insufficient B12 levels than those with low PM2.5 and sufficient B12. CONCLUSION: The study supported higher PM2.5 exposure during the 2nd trimester is significantly associated with GDM risk. It first highlighted insufficient B12 status might enhance adverse effects of air pollution on GDM.
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Poluentes Atmosféricos , Poluição do Ar , Diabetes Gestacional , Gravidez , Feminino , Humanos , Diabetes Gestacional/induzido quimicamente , Diabetes Gestacional/epidemiologia , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Material Particulado/efeitos adversos , Material Particulado/análise , Vitamina B 12 , Exposição Materna/efeitos adversos , Poluição do Ar/análise , Glucose/análise , Vitaminas/análiseRESUMO
Prostate cancer remains a serious condition threatening the health of men. Due to the complicated nature of the tumour microenvironment (TME), conventional treatments face challenges including poor prognosis and tumour resistance, therefore new therapeutic strategies are urgently needed. Small interfering RNA (siRNA), a double-stranded non-coding RNA, regulates specific gene expression through RNA interference. Tumour-associated macrophages (TAMs) are a potential therapeutic target in cancer immunotherapy. Colony stimulating factor-1/colony stimulating factor-1 receptor (CSF-1/CSF-1R) signaling pathway plays a crucial role in the polarization of the immunosuppressive TAMs, M2 macrophages. Downregulation of CSF-1R is known to reprogram the immunosuppressive TAMs, M2 macrophages, to the immunostimulatory phenotype, M1 macrophages. Sialic acid is a ligand for Siglec-1 (CD169) which is overexpressed on M2 macrophages with little expression in other phenotypes. Therefore, a sialic acid-targeted cyclodextrin-based nanoparticle was developed to specifically deliver CSF-1R siRNA to M2 macrophages. The nanoparticles were studied in vitro using both human and mouse prostate cancer cell lines. Results show that the targeted nanoparticles achieved cell specific delivery to M2 macrophages via the sialic acid-CD169 axis. The expression of CSF-1R was significantly downregulated in M2 macrophages (29.64% for targeted vs 19.31% for non-targeted nanoparticles in THP-1-derived M2 macrophages and 38.94% for targeted vs 18.51% for non-targeted nanoparticles in RAW 264.7-derived M2 macrophages, n = 4, p < 0.01). The resulting reprograming of M2 macrophages to M1 enhanced the level of apoptosis in the prostate cancer cells in a Transwell model (49.17% for targeted vs 37.68% for non-targeted nanoparticles in PC-3 cells and 69.15% for targeted vs 44.73% for non-targeted nanoparticles in TRAMP C1 cells, n = 3, p < 0.01). Thus, this targeted cyclodextrin-based siRNA drug delivery system provides a potential strategy for prostate cancer immunotherapy.
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Ciclodextrinas , Nanopartículas , Neoplasias da Próstata , Animais , Humanos , Masculino , Camundongos , Fatores Estimuladores de Colônias , Imunoterapia/métodos , Ácido N-Acetilneuramínico , Nanopartículas/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/uso terapêutico , Microambiente Tumoral , Macrófagos Associados a Tumor , Receptor de Fator Estimulador de Colônias de Macrófagos/genéticaRESUMO
This study aims to investigate the causes of COVID-19 vaccine hesitancy among the Chinese population. The LDA model and content analysis were used to analyze the content of COVID-19 vaccine hesitancy expressed by the Chinese on Weibo from 2020 to 2022, the leading causes of vaccine hesitancy, and the changes in the reasons for vaccine hesitancy over time. The study found that when the Chinese expressed vaccine hesitancy, it usually involved themes such as information access (18.59%), vaccination services (13.91%), and physical illness (13.24%), and topics such as vaccination process (6.83%), allergic diseases (6.59%), and international news (6.43%). Constraints (35.48%), confidence (17.94%), and calculation (15.99%) are the leading causes of vaccine hesitancy on Weibo. These findings provide a comprehensive picture of how the Chinese express vaccine hesitancy in social media and the reasons and changes for vaccine hesitancy, which can help inspire public health experts, health organizations, or governments in various countries to improve the phenomenon of vaccine hesitancy.
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SARS-CoV-2 has continuously evolved as changes in the genetic code occur during replication of the genome, with some of the mutations leading to higher transmission among human beings. The spike aspartic acid-614 to glycine (D614G) substitution in the spike represents a "more transmissible form of SARS-CoV-2" and occurs in all SARS-CoV-2 mutants. However, the underlying mechanism of the D614G substitution in virus infectivity has remained unclear. In this paper, we adopt molecular simulations to study the contact processes of the D614G mutant and wild-type (WT) spikes with hACE2. The interaction areas with hACE2 for the two spikes are completely different by visualizing the whole binding processes. The D614G mutant spike moves towards the hACE2 faster than the WT spike. We have also found that the receptor-binding domain (RBD) and N-terminal domain (NTD) of the D614G mutant extend more outwards than those of the WT spike. By analyzing the distances between the spikes and hACE2, the changes of number of hydrogen bonds and interaction energy, we suggest that the increased infectivity of the D614G mutant is not possibly related to the binding strength, but to the binding velocity and conformational change of the mutant spike. This work reveals the impact of D614G substitution on the infectivity of the SARS-CoV-2, and hopefully could provide a rational explanation of interaction mechanisms for all the SARS-CoV-2 mutants.
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Recently, newly developed carbon-based nanomaterials known as carbon dots (CDs) have generated significant interest in nanomedicine. However, current knowledge regarding CD research in the biomedical field is still lacking. An overview of the most recent development of CDs in biomedical research is given in this review article. Several crucial CD applications, such as biosensing, bioimaging, cancer therapy, and antibacterial applications, are highlighted. Finally, CD-based biomedicine's challenges and future potential are also highlighted to enrich biomedical researchers' knowledge about the potential of CDs and the need for overcoming various technical obstacles.
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Nanoestruturas , Pontos Quânticos , Carbono , Sistemas de Liberação de Medicamentos , NanomedicinaRESUMO
Although metallacycle-based photosensitizers have attracted increasing attention in biomedicine, their clinical application has been hindered by their inherent dark toxicity and unsatisfactory phototherapeutic efficiency. Herein, we employ a π-expansion strategy for ruthenium acceptors to develop a series of Ru(ii) metallacycles (Ru1-Ru4), while simultaneously reducing dark toxicity and enhancing phototoxicity, thus obtaining a high phototoxicity index (PI). These metallacycles enable deep-tissue (â¼7 mm) fluorescence imaging and reactive oxygen species (ROS) production and exhibit remarkable anti-tumor activity even under hypoxic conditions. Notably, Ru4 has the lowest dark toxicity, highest ROS generation ability and an optimal PI (â¼146). Theoretical calculations verify that Ru4 exhibits the largest steric bulk and the lowest singlet-triplet energy gap (ΔE ST, 0.62 eV). In vivo studies confirm that Ru4 allows for effective and safe phototherapy against A549 tumors. This work thus is expected to open a new avenue for the design of high-performance metal-based photosensitizers for potential clinical applications.
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Background: In recent years, a large amount of clinical evidence and animal experiments have demonstrated the unique advantages of mineralocorticoid receptor antagonists (MRA) for treating chronic kidney disease (CKD). Aims: Accordingly, the present study aimed to systematically assess the second-generation selective MRAs eplerenone's safety and effectiveness for treating CKD. Methods: Four databases (PubMed, The Cochrane Library, Embase, and Web of Science) were searched for randomized controlled trials (RCT) correlated with eplerenone for treating CKD up to September 21, 2022. By complying with the inclusion and exclusion criteria, literature screening, and data extraction were conducted. Results: A total of 19 randomized controlled articles involving 4501 cases were covered. As suggested from the meta-analysis, significant differences were reported with the 24-h urine protein (MD = -42.23, 95% confidence interval [CI] = -76.72 to -7.73, P = 0.02), urinary albumin-creatinine ratio (UACR) (MD = -23.57, 95% CI = -29.28 to -17.86, P < 0.00001), the systolic blood pressure (SBP) (MD = -2.73, 95% CI = -4.86 to -0.59, P = 0.01), and eGFR (MD = -1.56, 95% CI = -2.78 to -0.34, P = 0.01) in the subgroup of eplerenone vs placebo. The subgroups of eplerenone vs placebo (MD = 0.13, 95% CI = 0.07 to 0.18, P < 0.00001) and eplerenone vs thiazide diuretic (MD = 0.18, 95% CI = 0.13 to 0.23, P < 0.00001) showed the significantly increased potassium levels. However, no statistical significance was reported between the eplerenone treatment groups and the control in the effect exerted by serum creatinine (MD=0.03, 95% CI = -0.01 to 0.07, P = 0.12) and diastolic blood pressure (DBP) (MD = 0.11, 95% CI = -0.41 to 0.63, P = 0.68). Furthermore, significant risks of hyperkalemia were reported in the eplerenone group (K+ ≥ 5.5 mmol/l, RR = 1.70, 95%CI = 1.35 to 2.13, P=<0.00001; K+≥6.0 mmol/l, RR = 1.61, 95% CIs = 1.06 to 2.44, P = 0.02), respectively. Conclusions: Eplerenone has beneficial effects on CKD by reducing urinary protein and the systolic blood pressure, but it also elevates the risk of hyperkalemia.
