Assuntos
Fosfatidilinositol 3-Quinases , Transdução de Sinais , Fosforilação , Transporte Ativo do Núcleo Celular , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Proteína ran de Ligação ao GTP/genética , Proteína ran de Ligação ao GTP/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
Fluorescence in situ hybridization (FISH) allows researchers to visualize the spatial position and quantity of nucleic acids in fixed samples. Recently, considerable progress has been made in developing oligonucleotide (oligo)-based FISH methods that have enabled researchers to study the three-dimensional organization of the genome at super-resolution and visualize the spatial patterns of gene expression for thousands of genes in individual cells. However, there are few existing computational tools to support the bioinformatics workflows necessary to carry out these experiments using oligo FISH probes. Here, we introduce paint server and homology optimization pipeline (PaintSHOP), an interactive platform for the design of oligo FISH experiments. PaintSHOP enables researchers to identify probes for their experimental targets efficiently, to incorporate additional necessary sequences such as primer pairs and to easily generate files documenting library design. PaintSHOP democratizes and standardizes the process of designing complex probe sets for the oligo FISH community.
Assuntos
Coloração Cromossômica/métodos , Biologia Computacional/métodos , Genoma Humano , Hibridização in Situ Fluorescente/métodos , Sondas de Oligonucleotídeos/química , Sequências Repetitivas de Ácido Nucleico , Transcriptoma , HumanosRESUMO
QiXueShuFu Decoction (QXSFD) modified from the Bazhen Decoction which was originally from the classic Ming Dynasty is a traditional folk formula that boosts the body's immune system. However, its ambiguous chemical components limited its quality control evaluation. In this study, ultra-performance liquid chromatography (UPLC) fingerprint combined with multivariate analysis was used to evaluate the quality of 15 batches of QXSFD, and UPLC quadrupole-orbitrap mass spectrometry was used to further examine the chemical components in QXSFD, after which representative compounds from each disassembled prescription were selected for comparison. Fifteen batches of samples had 33 common peaks in which 11 differential components could be used as a reference for subsequent quality control. One hundred forty-three components were identified from QXSFD. Saponins were mainly derived from the monarch, terpenes from the minister, and polysaccharides and glycosides from the assistant. In addition, quantitative assay revealed that the content of ferulic acid, chlorogenic acid, 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside and 3,6'-disinapoyl sucrose in the whole prescription were higher than the contents of each disassembled prescription. This is the first comprehensive quality report on the chemical components of QXSFD, which is important for pharmacodynamic material basis and quality control.
Assuntos
Medicamentos de Ervas Chinesas , Saponinas , Medicamentos de Ervas Chinesas/análise , Cromatografia Líquida de Alta Pressão/métodos , Glicosídeos , Saponinas/análise , Espectrometria de Massa com Cromatografia LíquidaRESUMO
Acne is a long-lasting inflammatory skin condition that impacts the sebaceous units of the hair follicles, affecting around 85-90% of the population. Due to the potential for permanent facial scarring and negative social consequences, as well as the limitations of conventional medications like drug resistance and difficulties following treatment plans, it's crucial to investigate non-pharmacological options for treating acne, among which radiofrequency(RF) shows distinct superiority. To assess the impact of RF in the management of acne vulgaris, we conducted a thorough examination of scientific literature (including clinical trials and scientific reviews) through electronic databases like MEDLINE and PubMed. Our analysis indicates that RF could be a viable substitute for acne treatment due to its notable effectiveness and minimal adverse effects.
Assuntos
Acne Vulgar , Humanos , Acne Vulgar/radioterapia , Acne Vulgar/tratamento farmacológico , Pele , Cicatriz/radioterapia , Folículo Piloso , Resultado do TratamentoRESUMO
PURPOSE: This split-face randomized study compared the efficacy and safety between 1064-nm picosecond laser with fractionated microlens array (MLA) and 1565-nm nonablative fractional laser to treat enlarged pores. METHODS: Participants with enlarged facial pores were enrolled and underwent three consecutive sessions at 2-week intervals with either a 1064-nm picosecond laser with MLA or a 1565-nm nonablative fractional laser. Images were captured at each visit. Objective (pore number) and subjective assessments, including patient self-evaluations and quartile improvement scales, were used to evaluate the treatment efficacy. The pain levels and adverse effects were recorded at each subsequent visit. RESULTS: The participants were 3 men and 22 women with enlarged facial pores. At the initial and 2-month checkups after the last treatment, the pore numbers were significantly decreased bilaterally for both lasers. The respective quartile improvement scale scores for the 1064-nm picosecond and 1565-nm fractional lasers were 2.22 ± 1.06 and 2.14 ± 1.11, while those for patient self-assessment were 3.72 ± 0.74 and 3.68 ± 0.75. The pore number, quartile improvement scale score, and patients' self-assessments did not differ significantly between the two lasers. Treatment with the 1064-nm picosecond laser better reduced pain compared with the 1565-nm nonablative fractional laser (4.11 ± 1.33 vs. 4.83 ± 1.17). The occurrence of pigmentation did not differ significantly between the lasers. CONCLUSION: Both the 1064-nm picosecond laser with MLA and the 1565-nm nonablative fractional laser are viable options for treating enlarged pores, and showed comparable respective efficacies; however, the former was less likely to cause hyperpigmentation and was better tolerated.
Assuntos
Hiperpigmentação , Lasers de Estado Sólido , Masculino , Humanos , Feminino , Satisfação do Paciente , Lasers de Estado Sólido/uso terapêutico , Resultado do Tratamento , Hiperpigmentação/etiologia , Dor/etiologiaRESUMO
In the rosid species Arabidopsis thaliana, the AP2-type AP2 transcription factor (TF) is required for specifying the sepals and petals identities and confers a major A-function to antagonize the C-function in the outer floral whorls. In the asterid species Petunia, the AP2-type ROB TFs are required for perianth and pistil development, as well as repressing the B-function together with TOE-type TF BEN. In Long-homostyle (LH) Fagopyrum esculentum, VIGS-silencing showed that FaesAP2 is mainly involved in controlling filament and style length, but FaesTOE is mainly involved in regulating filament length and pollen grain development. Both FaesAP2 (AP2-type) and FaesTOE (TOE-type) are redundantly involved in style and/or filament length determination instead of perianth development. However, neither FaesAP2 nor FaesTOE could directly repress the B and/or C class genes in common buckwheat. Moreover, the FaesAP1_2 silenced flower showed tepal numbers, and filament length decreased obviously. Interestingly, yeast one-hybrid (Y1H) and dual-luciferase reporter (DR) further suggested that FaesTOE directly up-regulates FaesAP1_2 to be involved in filament length determination in LH common buckwheat. Moreover, the knockdown of FaesTOE expression could result in expression down-regulation of the directly target FaesAP1_2 in the FaesTOE-silenced LH plants. Our findings uncover a stamen development pathway in common buckwheat and offer deeper insight into the functional evolution of AP2 orthologs in the early-diverging core eudicots.
Assuntos
Fagopyrum , Flores , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Fagopyrum/genética , Fagopyrum/crescimento & desenvolvimento , Fagopyrum/metabolismo , Flores/genética , Flores/crescimento & desenvolvimento , Flores/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação para Cima/genéticaRESUMO
According to our recent studies on hydrophobicity, this work is aimed at understanding the dependence of hydrophobic interactions on the shape of a solute's surface. It has been observed that dissolved solutes primarily affect the structure of interfacial water, which refers to the top layer of water at the interface between the solute and water. As solutes aggregate in a solution, hydrophobic interactions become closely related to the transition of water molecules from the interfacial region to the bulk water. It is inferred that hydrophobic interactions may depend on the shape of the solute surface. To enhance the strength of hydrophobic interactions, the solutes tend to aggregate, thereby minimizing their surface area-to-volume ratio. This also suggests that hydrophobic interactions may exhibit directional characteristics. Moreover, this phenomenon can be supported by calculated potential mean forces (PMFs) using molecular dynamics (MD) simulations, where different surfaces, such as convex, flat, or concave, are associated with a sphere. Furthermore, this concept can be extended to comprehend the molecular packing parameter, commonly utilized in studying the self-assembly behavior of amphiphilic molecules in aqueous solutions.
RESUMO
External interfaces, such as the air-water and solid-liquid interfaces, are ubiquitous in nature. Hydrophobic interactions are considered the fundamental driving force in many physical and chemical processes occurring in aqueous solutions. It is important to understand the effects of external interfaces on hydrophobic interactions. According to the structural studies on liquid water and the air-water interface, the external interface primarily affects the structure of the topmost water layer (interfacial water). Therefore, an external interface may affect hydrophobic interactions. The effects of interfaces on hydrophobicity are related not only to surface molecular polarity but also to the geometric characteristics of the external interface, such as shape and surface roughness. This study is devoted to understanding the effects of a smooth interface on hydrophobicity. Due to hydrophobic interactions, the solutes tend to accumulate at external interfaces to maximize the hydrogen bonding of water. Additionally, these can be demonstrated by the calculated potential mean forces (PMFs) using molecular dynamic (MD) simulations.
RESUMO
Ion channels exhibit strong selectivity for specific ions over others under electrochemical potentials, such as KcsA for K+ over Na+. Based on the thermodynamic analysis, this study is focused on exploring the mechanism of ion selectivity in nanopores. It is well known that ions must lose part of their hydration layer to enter the channel. Therefore, the ion selectivity of a channel is due to the rearrangement of water molecules when entering the nanopore, which may be related to the hydrophobic interactions between ions and channels. In our recent works on hydrophobic interactions, with reference to the critical radius of solute (Rc), it was divided into initial and hydrophobic solvation processes. Additionally, the different dissolved behaviors of solutes in water are expected in various processes, such as dispersed and accumulated distributions in water. Correspondingly, as the ion approaches the nanopore, there seems to exist the "repulsive" or "attractive" forces between them. In the initial process (
RESUMO
BACKGROUND: PROpel met its primary endpoint showing statistically significant improvement in radiographic progression-free survival with olaparib plus abiraterone versus placebo plus abiraterone in patients with first-line metastatic castration-resistant prostate cancer (mCRPC) unselected by homologous recombination repair mutation (HRRm) status, with benefit observed in all prespecified subgroups. Here we report the final prespecified overall survival analysis. METHODS: This was a randomised, double-blind, phase 3 trial done at 126 centres in 17 countries worldwide. Patients with mCRPC aged at least 18 years, Eastern Cooperative Oncology Group performance status 0-1, a life expectancy of at least 6 months, with no previous systemic treatment for mCRPC and unselected by HRRm status were randomly assigned (1:1) centrally by means of an interactive voice response system-interactive web response system to abiraterone acetate (orally, 1000 mg once daily) plus prednisone or prednisolone with either olaparib (orally, 300 mg twice daily) or placebo. The patients, the investigator, and study centre staff were masked to drug allocation. Stratification factors were site of metastases and previous docetaxel at metastatic hormone-sensitive cancer stage. Radiographic progression-free survival was the primary endpoint and overall survival was a key secondary endpoint with alpha-control (alpha-threshold at prespecified final analysis: 0·0377 [two-sided]), evaluated in the intention-to-treat population. Safety was evaluated in all patients who received at least one dose of a study drug. This study is registered with ClinicalTrials.gov, NCT03732820, and is completed and no longer recruiting. FINDINGS: Between Oct 31, 2018 and March 11, 2020, 1103 patients were screened, of whom 399 were randomly assigned to olaparib plus abiraterone and 397 to placebo plus abiraterone. Median follow-up for overall survival in patients with censored data was 36·6 months (IQR 34·1-40·3) for olaparib plus abiraterone and 36·5 months (33·8-40·3) for placebo plus abiraterone. Median overall survival was 42·1 months (95% CI 38·4-not reached) with olaparib plus abiraterone and 34·7 months (31·0-39·3) with placebo plus abiraterone (hazard ratio 0·81, 95% CI 0·67-1·00; p=0·054). The most common grade 3-4 adverse event was anaemia reported in 64 (16%) of 398 patients in the olaparib plus abiraterone and 13 (3%) of 396 patients in the placebo plus abiraterone group. Serious adverse events were reported in 161 (40%) in the olaparib plus abiraterone group and 126 (32%) in the placebo plus abiraterone group. One death in the placebo plus abiraterone group, from interstitial lung disease, was considered treatment related. INTERPRETATION: Overall survival was not significantly different between treatment groups at this final prespecified analysis. FUNDING: Supported by AstraZeneca and Merck Sharp & Dohme.
RESUMO
High-risk human papillomavirus (HPV) persistent infection is the major tumorigenesis factor for cervical cancer (CC). However, the incidence of HPV-negative CC is 5% to 30% with different HPV detection methods. High-risk HPV E6/E7 mRNA in situ hybridization (RISH) can detect HPV-driven tumors. Our study aimed to explore whether HPV typing-negative CC was caused by HPV infection. The tissues of CC patients with HPV typing results, collected from cervical biopsies, conization, or hysterectomies, were submitted to RISH using RNAscope chromogenicin. Immunohistochemistry was performed to evaluate the expression of p16INK4a and Ki-67. A total of 308 women with HPV typing results were enrolled, and 30 (9.74%) cases of HPV typing were negative. In HPV typing-negative CCs, 28/30 (93.3%) were positive for RISH, which contained 22/22 (100%) squamous cell carcinomas and 6/8 (75%) adenocarcinomas. RISH was positive in 278/278 (100%) HPV typing-positive CCs, which included 232/232 (100%) squamous cell carcinomas and 46/46 (100%) adenocarcinomas. Positive RISH in HPV typing-negative CC was significantly lower than in the HPV typing-positive group ( P =0.002, 95% confidence interval: 0.848-1.027). However, this significant difference only existed in adenocarcinoma. No significant differences were seen in the expression of p16INK4a and Ki-67 (all P >0.05). HPV typing may cause misdiagnosis in 9.74% of CC patients, and HPV E6/E7 mRNA can detect HPV in CC with HPV typing-negative patients. This approach could provide a novel option to accurately detect high-risk HPVs in cervical tumors and help to eliminate the percentage of misdiagnosed HPV-related cases.
Assuntos
Carcinoma de Células Escamosas , Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/patologia , Proteínas Oncogênicas Virais/genética , Antígeno Ki-67 , RNA Viral/genética , Inibidor p16 de Quinase Dependente de Ciclina , Carcinoma de Células Escamosas/diagnóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Papillomaviridae/genéticaRESUMO
Aspergillus fumigatus biofilm development results in enhanced pathogenicity and treatment resistance. Most contemporary antibiotics, however, are unable to eliminate biofilms. In recent years, with the application of new photosensitizers and the development of treatment, ALA-PDT (5-aminolevulinic acid photodynamic treatment) has achieved remarkable curative effect in the treatment of fungal infectious diseases; however, no research has been conducted on ALA-PDT against A. fumigatus. This study investigated the inhibitory effect of ALA-PDT at various 5-aminolevulinic acid concentrations and light doses on A. fumigatus planktonic and biofilms in vitro. We found that ALA-PDT may successfully inhibit the development of A. fumigatus biofilm and disintegrate mature biofilm. After ALA-PDT treatment, the adherence rate and vitality dramatically decreased, and the biofilm's structure was severely compromised. Our findings show for the first time that ALA-PDT may be used to prevent the formation of A. fumigatus biofilm and disturb the structure of mature biofilm, and that it could be employed as a therapeutic therapy for A. fumigatus superficial infection.
Assuntos
Aspergilose , Fotoquimioterapia , Ácido Aminolevulínico/farmacologia , Aspergillus fumigatus , BiofilmesRESUMO
Aristolochic acid (AA) as an emerging contaminant in herbal medicines or crops has been well-recognized for causing nephropathy since 1990s. Over the last decade, mounting evidence has linked AA to liver injury; however, the underlying mechanism is poorly elucidated. MicroRNAs respond to environmental stress and mediate multiple biological processes, thus showing biomarker potentials prognostically or diagnostically. In the present study, we investigated the role of miRNAs in AA-induced hepatotoxicity, specifically in regulating NQO1, the key enzyme responsible for AA bioactivation. In silico analysis showed that hsa-miR-766-3p and hsa-miR-671-5p were significantly associated with AAI exposure as well as NQO1 induction. A 28-day rat experiment of 20 mg/kg AA exposure demonstrated a 3-fold increase of NQO1 and an almost 50 % decrease of the homologous miR-671 that were accompanied with liver injury, which was consistent with in silico prediction. Further mechanistic investigation using Huh7 cells with IC50 of AAI at 146.5 µM showed both hsa-miR-766-3p and hsa-miR-671-5p were able to directly bind to and down-regulate NQO1 basal expression. In addition, both miRNAs were shown to suppress AAI-induced NQO1 upregulation in Huh7 cells at a cytotoxic concentration of 70 µM, and consequently alleviate AAI-induced cellular effects, including cytotoxicity and oxidative stress. Together, these data illustrate that miR-766-3p and miR-671-5p attenuate AAI-induced hepatotoxicity, and thus have monitoring and diagnostic potentials.
Assuntos
Ácidos Aristolóquicos , Doença Hepática Induzida por Substâncias e Drogas , MicroRNAs , NAD(P)H Desidrogenase (Quinona) , Animais , Ratos , Ácidos Aristolóquicos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/genética , MicroRNAs/genética , NAD(P)H Desidrogenase (Quinona)/genética , NAD(P)H Desidrogenase (Quinona)/metabolismo , HumanosRESUMO
Accurate, robust and drift-free global pose estimation is a fundamental problem for autonomous vehicles. In this work, we propose a global drift-free map-based localization method for estimating the global poses of autonomous vehicles that integrates visual-inertial odometry and global localization with respect to a pre-built map. In contrast to previous work on visual-inertial localization, the global pre-built map provides global information to eliminate drift and assists in obtaining the global pose. Additionally, in order to ensure the local odometry frame and the global map frame can be aligned accurately, we augment the transformation between these two frames into the state vector and use a global pose-graph optimization for online estimation. Extensive evaluations on public datasets and real-world experiments demonstrate the effectiveness of the proposed method. The proposed method can provide accurate global pose-estimation results in different scenarios. The experimental results are compared against the mainstream map-based localization method, revealing that the proposed approach is more accurate and consistent than other methods.
RESUMO
In the field of quadruped robots, the most classic motion control algorithm is based on model prediction control (MPC). However, this method poses challenges as it necessitates the precise construction of the robot's dynamics model, making it difficult to achieve agile movements similar to those of a biological dog. Due to these limitations, researchers are increasingly turning to model-free learning methods, which significantly reduce the difficulty of modeling and engineering debugging and simultaneously reduce real-time optimization computational burden. Inspired by the growth process of humans and animals, from learning to walk to fluent movements, this article proposes a hierarchical reinforcement learning framework for the motion controller to learn some higher-level tasks. First, some basic motion skills can be learned from motion data captured from a biological dog. Then, with these learned basic motion skills as a foundation, the quadruped robot can focus on learning higher-level tasks without starting from low-level kinematics, which saves redundant training time. By utilizing domain randomization techniques during the training process, the trained policy function can be directly transferred to a physical robot without modification, and the resulting controller can perform more biomimetic movements. By implementing the method proposed in this article, the agility and adaptability of the quadruped robot can be maximally utilized to achieve efficient operations in complex terrains.
Assuntos
Movimento (Física) , Robótica , Animais , Cães , Algoritmos , Aprendizado de Máquina , Modelos BiológicosRESUMO
The purpose of this study was to investigate the effect of glutamate and its ionotropic receptor agonists on the response to acute hypoxia in rat carotid body in vitro. Briefly, after SD rats were anesthetized and decapitated, the bilateral carotid bifurcations were rapidly isolated. Then bifurcation was placed into a recording chamber perfused with 95% O2-5% CO2 saturated Kreb's solution. The carotid body-sinus nerve complex was dissected, and the carotid sinus nerve discharge was recorded using a suction electrode. To detect the response of carotid body to acute hypoxia, the chamber was perfused with 5% O2-5% CO2-90% N2 saturated Kreb's solution for a period of 100 s at an interval of 15 min. To observe the effect of glutamate, ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor agonist AMPA or N-methyl-D-aspartate (NMDA) receptor agonist NMDA on the response to acute hypoxia in rat carotid body, the chamber was perfused with 5% O2-5% CO2-90% N2 saturated Kreb's solution containing the corresponding reagent. The results showed that glutamate (20 µmol/L), AMPA (5 µmol/L) or NMDA (10 µmol/L) inhibited the acute hypoxia-induced enhancement of carotid sinus nerve activity, and these inhibitory effects were dose-dependent. In summary, the activation of glutamate ionotropic receptors appears to exert an inhibitory effect on the response to acute hypoxia in carotid body of rats.
Assuntos
Corpo Carotídeo , Ácido Glutâmico , Ratos , Animais , Ácido Glutâmico/farmacologia , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/farmacologia , N-Metilaspartato/farmacologia , Ratos Sprague-Dawley , Dióxido de Carbono , Receptores de N-Metil-D-Aspartato , Receptores de AMPA , HipóxiaRESUMO
The purpose of the present study was to explore the role of carotid body metabotropic glutamate receptor 1 (mGluR1) in chronic intermittent hypoxia (CIH)-induced carotid body plasticity. Sprague Dawley (SD) rats were exposed to CIH (6%-21% O2, 4 min/cycle, 8 h/day) for 4 weeks. The blood pressure of rats was monitored non-invasively by tail-cuff method under consciousness. RT-qPCR was used to examine the mRNA expression level of mGluR1 in rat carotid body. Western blot was used to detect the protein expression level of mGluR1 in rat carotid body. The role of mGluR1 in CIH-induced carotid body sensory long-term facilitation (sLTF) was investigated by ex vivo carotid sinus nerve discharge recording, and the carotid body sLTF was evoked by a 10-episode of repetitive acute intermittent hypoxia (AIH: 1 min of 5% O2 interspersed with 5 min of 95% O2). The results showed that: 1) CIH increased the systolic blood pressure (P < 0.001), diastolic blood pressure (P < 0.005) and mean arterial blood pressure (P < 0.001) of rats; 2) CIH decreased the mRNA and protein levels of mGluR1 in the rat carotid body (P < 0.01); 3) 4 weeks of CIH induced carotid body sLTF significantly, exhibiting as an increasing baseline sensory activity during post-AIH, which was inhibited by application of an agonist of group I metabotropic glutamate receptors, (S)-3,5-dihydroxyphenylglycine (DHPG), during sLTF induction (P < 0.005). In summary, these results suggest that activation of mGluR1 inhibits CIH-induced carotid body plasticity in rats.
Assuntos
Corpo Carotídeo , Receptores de Glutamato Metabotrópico , Ratos , Animais , Corpo Carotídeo/metabolismo , Ratos Sprague-Dawley , Hipóxia , Receptores de Glutamato Metabotrópico/metabolismo , RNA Mensageiro/metabolismoRESUMO
The aim of the present study was to explore the role of group II and III metabotropic glutamate receptors (mGluRs) in carotid body plasticity induced by chronic intermittent hypoxia (CIH) in rats. Sprague Dawley (SD) rats were treated with CIH in Oxycycler A84 hypoxic chamber for 4 weeks, and the tail artery blood pressure was measured at the end of model preparation. RT-qPCR was performed to examine the mRNA expression levels of mGluR2/3/8 in rat carotid body. Carotid sinus nerve activity was detected by ex vivo carotid sinus nerve discharge recording technique, and acute intermittent hypoxia (AIH) was administered to induce carotid body sensory long-term facilitation (sLTF), in order to observe the role of group II and group III mGluRs in carotid body plasticity induced by CIH. The results showed that: 1) After 4 weeks of CIH exposure, the blood pressure of rats increased significantly; 2) CIH down-regulated the mRNA levels of mGluR2/3, and up-regulated the mRNA level of mGluR8 in the carotid body; 3) AIH induced sLTF in carotid body of CIH group. In the CIH group, activation of group II mGluRs had no effect on sLTF of carotid body, while activation of group III mGluRs completely inhibited sLTF. These results suggest that CIH increases blood pressure in rats, and group III mGluRs play an inhibitory role in CIH-induced carotid body plasticity in rats.
Assuntos
Corpo Carotídeo , Receptores de Glutamato Metabotrópico , Ratos , Animais , Corpo Carotídeo/metabolismo , Ratos Sprague-Dawley , Hipóxia , Receptores de Glutamato Metabotrópico/genética , Receptores de Glutamato Metabotrópico/metabolismo , RNA Mensageiro/metabolismoRESUMO
Chinese patent medicines(CPMs) are unique therapeutic drugs in China. Establishing and improving the evaluation criteria is an important measure to promote the high-quality development of CPMs. Based on the "evaluation criteria of high-grade CPMs with quality as the core index" established by our group in 2018, the "high-quality evaluation criteria for CPMs based on whole process control" was proposed in the present study in 2022. The scope of application and basic principles of the new criteria were clarified. A quality evaluation scoring table was established in the new criteria, including five parts: raw material selection, production process, quality control, efficacy evaluation, and brand building. The technical evaluation indexes involved have increased from 20% in the original criteria to 70% in the new criteria, and efficacy evaluation has been added in the new criteria. The subjective evaluation indicators account for a large proportion in the original criteria, which is prone to bias. The improved criteria overcome this shortcoming. It is expected that the new criteria as a basis can play a better role in the selection of high-quality products of CPMs, guide enterprises and institutions to participate actively in the evaluation and research of high-quality CPMs, and promote the high-quality development of CPMs.
Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos sem Prescrição , Clorobenzenos , ChinaRESUMO
Understanding the electroosmotic flow through a nanochannel is essential to the design of novel nanofluidic devices, ranging from desalination to nanometer water pumps. Nonetheless, the competition between cation and anion in electric fields inevitably leads to a limited pumping of water, and thus weakening their competition could be a new avenue for the fundamental control of water transport. In this work, through a series of molecular dynamics simulations, we find a surprising phenomenon in which under the drive of a traditional longitudinal electric field, an additional lateral electric field can significantly weaken the competitive transport of a cation and anion through a carbon nanotube, which spontaneously leads to a massive increase in electroosmotic water flux. Specifically, with the increase in the lateral electric field, the anion flux exhibits an almost linear reduction, and the cation flux is stable and can even be enhanced. As a result, the net water flux along the cation direction increases significantly. The key to this unexpected phenomenon lies in the size and mobility difference between the cation and anion. The anion is larger and has greater mobility and is thus more susceptible to the lateral electric field, which ultimately leads to the reduction of its flux. For different ion types and CNT lengths, we can observe similar electropumping phenomenon, where the friction force induced by the lateral electric field becomes nontrivial for long CNTs. Our results provide a new route to tune the competitive transport of cations and anions and should be useful for the design of novel electroosmotic pumps.