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1.
BMC Public Health ; 23(1): 242, 2023 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-36737734

RESUMO

BACKGROUND: Gallbladder disease (GBD) can increase the risk of cardiovascular disease (CVD). However, GBD has rarely been reported in the less developed, rural areas of Xinjiang. This study aimed to determine the prevalence of GBD and incidence of CVD in a prospective cohort study in rural Xinjiang. Moreover, the study aimed to explore the association between GBD and CVD within this cohort. METHODS: The study cohort included 11,444 Uyghur adults in Xinjiang, 3rd division, from the 51st Mission. Study groups were classified according to whether GBD was present or absent at baseline. The occurrence of CVD was the end event. Demographic, anthropometric, and biochemical data were recorded, and the incidence of CVD in the GBD and non-GBD groups analysed. Cox proportional hazards regression models were used to assess the association between GBD and CVD and factors associated with their incidence. Several subgroup analyses were performed to assess CVD incidence in different subgroups. The interaction between GBD and cardiometabolic risk factors, and subsequent risk of developing CVD, was evaluated. RESULTS: Prevalence of GBD in the study cohort was 10.29%. After a median follow-up of 4.92 years, the cumulative incidence of CVD in the study cohort was 10.49%, 8.43% in males and 12.65% in females. CVD incidence was higher in the GBD group (34.04% vs. 7.78%, HR = 4.96, 95% CI: 4.40-5.59). After multivariate adjustment, the risk of CVD remained higher in the GBD group (HR = 2.89, 95% CI: 2.54-3.29). Subgroup analyses showed male sex, smoking, alcohol consumption, lack of exercise, and abnormal renal function were all associated with increased risk of CVD. Moreover, the risk of CVD was markedly higher in GBD combined with cardiometabolic risk factors (hypertension, T2DM, dyslipidaemia, overweight, and abdominal obesity), than in cardiometabolic risk factors alone and this was higher in the GBD group than in the non-GBD group regardless of whether cardiometabolic risk factors were combined. CONCLUSION: GBD is an important independent risk factor for CVD development. Awareness of these associations will raise concerns among clinicians about the risk of cardiovascular disease in patients with GBD.

2.
J Econ Entomol ; 2023 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-36738303

RESUMO

We investigated the accumulation of energy substances, dynamics of flight muscle development, changes in energy substances accumulation, and flight muscle structure after flight activities in female adults of the green lacewing Chrysoperla sinica (Tjeder), a common natural enemy of various insect pests in China. Virgin individuals were chosen at 24, 72, and 120 h after eclosion for energy substance determination and flight muscle observation in this study. Individuals with strong flight ability at 72 h after eclosion were selected for tethered flight assays, followed by detection of energy substances, and flight muscle observation. The results showed that virgin female adults had the highest fat content 72 h after eclosion. Sarcomere length and myofibril diameter changed significantly with age, with the lowest at 24 h after eclosion. With an increase in flight distance, the fat and glycogen contents, sarcomere length, and volume fraction of the transverse tubular system (T-system) decreased and myofibril diameters increased. The volume fraction of the mitochondria did not significantly change, but the structure of the mitochondrial membrane was destroyed, inclusions were reduced, and cavities appeared. The reserves of energy substances, especially lipids, are closely related to the flight ability of C. sinica. The observational results of both flight muscle structure and morphology of mitochondria build a strong relationship with flight behavior. This research should help reveal the regulatory mechanism of flight activity of C. sinica.

3.
Zhongguo Zhong Yao Za Zhi ; 48(1): 13-21, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-36725253

RESUMO

Rheumatoid arthritis(RA) is a chronic degenerative joint disease characterized by inflammation. Due to the complex causes, no specific therapy is available. Non-steroidal anti-inflammatory agents and corticosteroids are often used(long-term, oral/injection) to interfere with related pathways for reducing inflammatory response and delaying the progression of RA, which, however, induce many side effects. Microneedle, an emerging transdermal drug delivery system, is painless and less invasive and improves drug permeability. Thus, it is widely used in the treatment of RA and is expected to be a new strategy in clinical treatment. This paper summarized the application of microneedles in the treatment of RA, providing a reference for the development of new microneedles and the expansion of its clinical application.


Assuntos
Artrite Reumatoide , Sistemas de Liberação de Medicamentos , Humanos , Administração Cutânea , Preparações Farmacêuticas , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Agulhas
5.
J Agric Food Chem ; 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36734836

RESUMO

Rapid identification and quantitative simultaneous analysis for multiple pesticide in real samples based on surface-enhanced Raman spectroscopy (SERS) is still a challenge because of sample complexity, reproducibility, and stability of SERS substrate. With use of colloidal silver nanoparticles loaded three-dimensional (3D) silica photonic microspheres (SPMs) array as the analytical platform, a SERS-based array assay for multiple pesticides was developed in this work. The silver nanoparticles were fixed into the gaps formed by the self-assembled nanospheres of the 3D SPMs to produce "hot spots", on which the Raman enhanced effect was up to 9.86 × 107 and the maximum electric field enhancement effect reached to 9.75 times, ensuring the target pesticides on the surface of the SERS-substrate integrated SPM can be detected sensitively. Using 2,4-dichlorophenoxyacetic acid (2,4-D), glyphosate, and imidacloprid as the testing pesticides, the label-free and high-throughput SERS assay for simultaneous detection of the pesticides was established, giving good linear detection ranges (0.1-204.8 µg/mL for 2,4-D, 0.3-247.9 µg/mL for glyphosate, and 0.2-204.8 µg/mL for imidacloprid) and low detection limits (3.03 ng/mL for 2,4-D, 3.14 ng/mL for glyphosate, and 8.82 ng/mL for imidacloprid). The spiked recovery rates in the real samples were measured in the range of 82-112%, which was consistent with that of the classical standard methods. The label-free 3D SERS array analytical platform provides a powerful tool for high-throughput and low-cost screening of multiple pesticide residues in real samples.

6.
Chin Med J (Engl) ; 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36728571

RESUMO

BACKGROUND: Sepsis is a serious disease caused by infection. Aminophylline has anti-asthma and anti-inflammatory effects. We aimed to explore the safety and effect of aminophylline in sepsis. METHODS: We conducted a clinical randomized controlled trial involving 100 patients diagnosed with sepsis within 48 h after intensive care unit (ICU) admission in two sites. All patients were randomized in a 1:1 ratio to receive standard therapy with or without aminophylline. The primary clinical outcome was all-cause mortality at 28 days. RESULTS: From September 27, 2018 to February 12, 2020, we screened 277 septic patients and eventually enrolled 100 patients, with 50 assigned to the aminophylline group and 50 to the usual-care group. At 28 days, 7 of 50 patients (14.0%) in the aminophylline group had died, compared with 16 of 50 (32.0%) in the usual-care group (P = 0.032). Cox regression showed that the aminophylline group had a lower hazard of death (hazard ratio = 0.312, 95% confidence interval: 0.129-0.753). Compared with the usual-care group, patients in the aminophylline group had a longer survival time (P = 0.039 by the log-rank test). The effects of aminophylline on vasopressor dose, oxygenation index, and sequential organ failure assessment score were time-dependent with treatment. There were no significant differences in total hospitalization days, ICU hospitalization days, and rates of serious adverse events (all P > 0.05). No adverse events were observed in the trial. CONCLUSIONS: Aminophylline as an adjunct therapy could significantly reduce the risk of death and prolong the survival time of patients with sepsis. TRIAL REGISTRATION: ChiCTR.org.cn, ChiCTR1800019173.

7.
Pest Manag Sci ; 2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36730167

RESUMO

BACKGROUND: Fruit flies are important economic pests of fruit, vegetables, and nuts over the world. In this study, a permanent ecological trap, which was created by ovicidal effect of phytogenic hydrogen cyanide (HCN) liberated from passion fruits due to oviposition by fruit flies and can be used in the pest management, were determined. RESULTS: Observation of fruit fly eggs in Passiflora within the passion fruit cultivation region in southern China, from Aug 2019 to Oct 2020 showed that the exotic Passiflora attracted the native fruit flies to oviposit, but the eggs could not hatch. Using classical staging to categorize embryonic development and fumigation assays, we show that oviposition by fruit fly on passion fruits, release HCN from the cyanogenic mesocarp. Exposure of the eggs to HCN causes arrest of embryonic development and finally the death of eggs. CONCLUSION: Our results reveal that the life cycle of fruit fly in Passiflora is interrupted at the egg stage. Consequently, we predict that this ecological trap may be permanent. Extensive cultivation of the Passiflora vine as a dead-end trap crop may be an effective avenue to reduce populations of fruit fly pests. This article is protected by copyright. All rights reserved.

8.
Micromachines (Basel) ; 14(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36677188

RESUMO

To improve the response-ability of the energy harvester to multidirectional wind, this paper proposes a wind energy harvester to scavenge wind-induced vibration energy. The harvester comprises a cylindrical beam instead of conventional thin rectangular cantilevers, a bluff body (square prism or circle cylinder), and a piezoelectric tube bonded to the bottom side of the beam for energy conversion. Benefiting from the symmetry of the cylindrical structure, this harvester can respond to airflow from every direction of the two-dimensional plane. The performance of the harvester under a wind speed range of 1.5-8 m/s has been tested. The results demonstrate that the proposed harvester can respond to the wind from all directions of the two-dimensional plane. It provides a direction for the future in-depth study of multidirectional wind energy harvesting.

9.
Scand J Gastroenterol ; : 1-8, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36651020

RESUMO

BACKGROUND: To analyze the diversity in endoscopic manifestations of Meckel's diverticulum (MD) in adults by using balloon-assisted enteroscopy (BAE) and supply more information on the application of BAE. METHODS: A retrospective study was carried out on adult patients diagnosed with MD by BAE in two tertiary general hospitals in China, from May 2007 to September 2021. The patients were divided into a small bowel bleeding (SBB) group and a control group according to their main symptoms. Clinical charts and endoscopic images were reviewed, analyzed, and summarized. RESULTS: Single diverticulum in the ileum and double-lumen sign were observed in all patients. The SBB group consisted of 51 patients, among which 35 cases of ulcerative lesions, 9 cases of erosive lesions, 9 cases of active bleeding/blood clots, and 4 cases of lumps inside the diverticulum were observed respectively. Majority of ulcerative lesions were inside the diverticulum (23/35). A circumferential stricture inside the diverticulum was discovered in 11 cases, and ulcerative lesions tended to occur at this structure (10/11). In the control group consisting of 15 patients, 1 case of erosive lesions at the orifice edge was observed. The percentage of patients with MD-associated ulcerative lesions was significantly higher in the SBB group than that in the control group (p < 0.001). CONCLUSIONS: The endoscopic manifestations of MD in adults are extraordinarily complex and connected with the patients' primary symptoms. The internal features of MD should be regarded as crucial observational objectives in adult patients.

11.
Chemosphere ; 317: 137913, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36682640

RESUMO

Amino antioxidants (AAOs), a suite of emerging organic contaminants, have been widely used in numerous industrial and commercial products to inhibit oxidation and corrosion. Recently, their environmental ubiquity, health risks, bioaccumulative and toxic potential have led to mounting public concern. This review summarizes the current state of knowledge on the production and usage, environmental occurrence, bioavailability, human exposure, and aquatic toxicity of representative AAOs, and provides suggestions for future research directions. Previous studies have revealed widespread distribution of many AAOs in various environmental matrixes, including air, water, sediment, dust, and biota. In addition to parent compounds, their degradation products, such as 2-anilino-5-(1,3-dimethylbutylamino)-1,4-benzoquinone (6PPD-Q) and 4-nitrodiphenylamine (4-NO2-DPA), have also been detected at high levels in multiple compartments. Dust ingestion and air inhalation are the two most well-investigated routes for human exposure to AAOs and their transformation products, while studies on other pathways (e.g., skin contact and dietary intake) still remain extremely limited. Moreover, AAO burdens in human tissue have been poorly documented. Toxicological data have shown that a few AAOs may cause teratogenic, developmental, reproductive, endocrinic, neuronic, and genetic toxicity to aquatic organisms, and the toxic capacities of degradation products differ from their precursors. Future studies should focus on elucidating AAO exposure for humans and associated health risks. Additionally, more attention should be given to AAO transformation products (particularly those quinoid derivatives possessing substantial affinity with DNA) and to the effects of complex mixtures of these chemicals.

12.
Inorg Chem ; 62(2): 739-747, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36598509

RESUMO

A new donor-acceptor biradical complex, TpCum,MeZn(SQ-VD) (TpCum,MeZn+ = zinc(II) hydro-tris(3-cumenyl-5-methylpyrazolyl)borate complex cation; SQ = orthosemiquinone; VD = oxoverdazyl), which is a ground-state analogue of a charge-separated excited state, has been synthesized and structurally characterized. The magnetic exchange interaction between the S = 1/2 SQ and the S = 1/2 VD within the SQ-VD biradical ligand is observed to be ferromagnetic, with JSQ-VD = +77 cm-1 (H = -2JSQ-VDŜSQ·ŜVD) determined from an analysis of the variable-temperature magnetic susceptibility data. The pairwise biradical exchange interaction in TpCum,MeZn(SQ-VD) can be compared with that of the related donor-acceptor biradical complex TpCum,MeZn(SQ-NN) (NN = nitronyl nitroxide, S = 1/2), where JSQ-NN ≅ +550 cm-1. This represents a dramatic reduction in the biradical exchange by a factor of ∼7, despite the isolobal nature of the VD and NN acceptor radical SOMOs. Computations assessing the magnitude of the exchange were performed using a broken-symmetry density functional theory (DFT) approach. These computations are in good agreement with those computed at the CASSCF NEVPT2 level, which also reveals an S = 1 triplet ground state as observed in the magnetic susceptibility measurements. A combination of electronic absorption spectroscopy and CASSCF computations has been used to elucidate the electronic origin of the large difference in the magnitude of the biradical exchange coupling between TpCum,MeZn(SQ-VD) and TpCum,MeZn(SQ-NN). A Valence Bond Configuration Interaction (VBCI) model was previously employed to highlight the importance of mixing an SQSOMO → NNLUMO charge transfer configuration into the electronic ground state to facilitate the stabilization of the high-spin triplet (S = 1) ground state in TpCum,MeZn(SQ-NN). Here, CASSCF computations confirm the importance of mixing the pendant radical (e.g., VD, NN) LUMO (VDLUMO and NNLUMO) with the SOMO of the SQ radical (SQSOMO) for stabilizing the triplet, in addition to spin polarization and charge transfer contributions to the exchange. An important electronic structure difference between TpCum,MeZn(SQ-VD) and TpCum,MeZn(SQ-NN), which leads to their different exchange couplings, is the reduced admixture of excited states that promote ferromagnetic exchange into the TpCum,MeZn(SQ-VD) ground state, and the intrinsically weaker mixing between the VDLUMO and the SQSOMO compared to that observed for TpCum,MeZn(SQ-NN), where this orbital mixing is significant. The results of this comparative study contribute to a greater understanding of biradical exchange interactions, which are important to our understanding of excited-state singlet-triplet energy gaps, electron delocalization, and the generation of electron spin polarization in both the ground and excited states of (bpy)Pt(CAT-radical) complexes.

13.
Signal Transduct Target Ther ; 8(1): 14, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36617552

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Identification of the underlying mechanism of HCC progression and exploration of new therapeutic drugs are urgently needed. Here, a compound library consisting of 419 FDA-approved drugs was taken to screen potential anticancer drugs. A series of functional assays showed that desloratadine, an antiallergic drug, can repress proliferation in HCC cell lines, cell-derived xenograft (CDX), patient-derived organoid (PDO) and patient-derived xenograft (PDX) models. N-myristoyl transferase 1 (NMT1) was identified as a target protein of desloratadine by drug affinity responsive target stability (DARTS) and surface plasmon resonance (SPR) assays. Upregulation of NMT1 expression enhanced but NMT1 knockdown suppressed tumor growth in vitro and in vivo. Metabolic labeling and mass spectrometry analyses revealed that Visinin-like protein 3 (VILIP3) was a new substrate of NMT1 in protein N-myristoylation modification, and high NMT1 or VILIP3 expression was associated with advanced stages and poor survival in HCC. Mechanistically, desloratadine binds to Asn-246 in NMT1 and inhibits its enzymatic activity, disrupting the NMT1-mediated myristoylation of the VILIP3 protein and subsequent NFκB/Bcl-2 signaling. Conclusively, this study demonstrates that desloratadine may be a novel anticancer drug and that NMT1-mediated myristoylation contributes to HCC progression and is a potential biomarker and therapeutic target in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Ácido Mirístico/metabolismo , Processamento de Proteína Pós-Traducional
14.
Adv Healthc Mater ; : e2202590, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36716702

RESUMO

mRNA-based therapy has emerged as the most promising nucleic acid therapy in the fight against COVID-19. However, a safe and efficacious systemic delivery remains a challenge for mRNA therapy. Lipid nanoparticles (LNPs) are currently widely used in mRNA delivery vehicles. Here, series of ionizable LNPs are rationally designed. YK009-LNP is an optimal delivery platform to carry mRNA. YK009-LNP exhibited higher mRNA delivery efficiency, a more favorable biodistribution pattern, and better safety than the approved MC3-LNP. In addition, mRNA encoding SARS-CoV-2 Omicron receptor binding domain protein was synthesized, and intramuscular administration of mice with YK009-LNP-Omicron mRNA induced a robust immune response and immune protective effect. Our study provides a novel mRNA delivery vehicle with more powerful delivery efficiency and better safety than the approved LNPs. This article is protected by copyright. All rights reserved.

15.
Artigo em Inglês | MEDLINE | ID: mdl-36718115

RESUMO

The residues of organophosphorus pesticides (OPs) have drawn worldwide increasing attention because of their potential fatal effects on human health and ecological systems. It is of great significance to develop an efficient and portable method for in-field detection of OPs. Herein, a novel core-shell nanocomposite of prussian blue@Fe-covalent organic framework@Au (PB@Fe-COF@Au) was constructed. Fe2+ and Fe3+ in PB nanoparticle (PBNP) cores, Fe-porphyrin in COF shells, and AuNPs grown on shells all acted as peroxidase-like catalytic active sites, enabling PB@Fe-COF@Au to possess triplet peroxidase-like activity. A colorimetric, affordable, sensitive, and selective strategy was designed to detect OPs. Compared with previous reports, this sensor realized a wider linear range for chlorpyrifos of 10-800 ng mL-1 with a relatively lower detection limit of 0.61 ng mL-1, which was attributed to the overlapping triple catalytic sites of PB@Fe-COF@Au and triple response sites to OPs. The assay was successfully employed to detect chlorpyrifos in food and environmental samples. Moreover, to meet the demand of in-field detection for OPs, a spherical hydrogel method based on PB@Fe-COF@Au with visual, portable, and equipment-free features was fabricated. This work provides a new pathway to design and apply effective nanozymes for on-site monitoring of pesticides.

16.
J Clin Invest ; 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36719747

RESUMO

Myeloproliferative neoplasms (MPNs) are characterized by the activated JAK2-STAT pathway. Pleckstrin-2 (Plek2) is a downstream target of the JAK2-STAT pathway and overexpressed in patients with MPNs. We previously revealed that Plek2 plays critical roles in the pathogenesis of JAK2 mutated MPNs. The non-essential roles of Plek2 under physiologic conditions makes it an ideal target for MPN therapy. Here we identified first-in-class Plek2 inhibitors through an in silico high-throughput screening and cell-based assays followed by the synthesis of analogs. The Plek2 specific small molecule inhibitors showed potent inhibitory effects on cell proliferation. Mechanistically, Plek2 interacts with and enhances the activity of Akt through the recruitment of downstream effector proteins. The Plek2 signaling complex also includes Hsp72 that protects Akt from degradation. These functions were blocked by Plek2 inhibitors via their direct binding to Plek2 DEP domain. The role of Plek2 in activating the Akt signaling was further confirmed in vivo using a hematopoietic specific Pten knockout mouse model. We next tested Plek2 inhibitors alone or in combination with an Akt inhibitor in various MPN mouse models, which showed significant therapeutic efficacies similar to the genetic depletion of Plek2. The Plek2 inhibitor was also effective in reducing proliferation of CD34 positive cells from MPN patients. Our studies reveal a Plek2-Akt complex that drives cell proliferation and can be targeted by a new class of anti-proliferative compounds for MPN therapy.

17.
J Agric Food Chem ; 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36705580

RESUMO

Bemisia tabaci has developed high resistance to many insecticides and causes substantial agricultural and economic losses annually. The insecticide resistance of whitefly has been widely reported in previous studies; however, the underlying mechanism remains little known. In this study, we cloned two P450 genes: CYP6DW3 and CYP6DW5v1; these genes were markedly overexpressed in imidacloprid-resistant whitefly populations compared with susceptible populations, and knockdown of these genes decreased the imidacloprid resistance of whitefly. Moreover, heterologous expression of whitefly P450 genes in SF9 cells and metabolic studies showed that the CYP6DW3 protein could metabolize 14.11% imidacloprid and produced imidacloprid-urea in vitro. Collectively, the expression levels of CYP6DW3 and CYP6DW5v1 are positively correlated with imidacloprid resistance in B. tabaci. Our study further reveals that cytochrome P450 enzymes affect the physiological activities related to resistance in insects, which helps scholars more deeply understand the resistance mechanism, and contributes to the development of integrated pest management framework.

18.
Artigo em Inglês | MEDLINE | ID: mdl-36705635

RESUMO

Antiferroelectric thin-film capacitors with ultralow remanent polarization and fast discharge speed have attracted extensive attention for energy storage applications. A multilayer heterostructure is considered to be an efficient approach to enhance the breakdown strength and improve the functionality. Here, we report a high-performance multilayer heterostructure (PbZrO3/PbTiO3)n with a maximum recoverable energy storage density of 36.4 J/cm3 due to its high electric breakdown strength (2.9 MV/cm) through the heterostructure strategy. The positive effect of interfacial blockage and the negative effect of local strain defects competitively affect the breakdown strength, showing an inflection point at n = 3. The atomic-scale characterizations reveal the underlying microstructure mechanism of the interplay between the heterointerface dislocations and the decreased energy storage performance. This work offers the potential of well-designed multilayers with high energy storage performance through heterostructure engineering.

19.
BMC Med Res Methodol ; 23(1): 2, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36597042

RESUMO

BACKGROUND: Due to the high cost and high failure rate of Phase III trials where a classical group sequential design (GSD) is usually used, seamless Phase II/III designs are more and more popular to improve trial efficiency. A potential attraction of Phase II/III design is to allow a randomized proof-of-concept stage prior to committing to the full cost of a Phase III trial. Population selection during the trial allows a trial to adapt and focus investment where it is most likely to provide patient benefit. Previous methods have been developed for this problem when there is a single primary endpoint and two possible populations. METHODS: To find the population that potentially benefits with one or two primary endpoints (e.g., progression free survival (PFS), overall survival (OS)), we propose a gated group sequential design for a seamless Phase II/III trial design with adaptive population selection. RESULTS: The investigated design controls the familywise error rate and allows multiple interim analyses to enable early stopping for efficacy or futility. Simulations and an illustrative example suggest that the proposed gated group sequential design has more power and requires less time and resources compared to the group sequential design and adaptive design. CONCLUSIONS: Combining the group sequential design and adaptive design, the gated group sequential design has more power and higher efficiency while controlling for the familywise error rate. It has the potential to save drug development cost and more quickly fulfill unmet medical needs.


Assuntos
Projetos de Pesquisa , Humanos
20.
Mol Biol Rep ; 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36609753

RESUMO

Recently, researches have revealed the key roles of the cytoskeleton in the occurrence and development of multiple diseases, suggesting that targeting the cytoskeleton is a viable approach for treating numerous refractory diseases. The cytoskeleton is a highly structured and complex network composed of actin filaments, microtubules, and intermediate filaments. In normal cells, these three cytoskeleton components are highly integrated and coordinated. However, the cytoskeleton undergoes drastic remodeling in cytoskeleton-related diseases, causing changes in cell polarity, affecting the cell cycle, leading to senescent diseases, and influencing cell migration to accelerate cancer metastasis. Additionally, mutations or abnormalities in cytoskeletal proteins and their related proteins are closely associated with several congenital diseases. Therefore, this review summarizes the roles of the cytoskeleton in cytoskeleton-related diseases as well as its potential roles in disease treatment to provide insights regarding the physiological functions and pathological roles of the cytoskeleton.

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