Abstract
Flexible covalent organic frameworks (COFs) have been studied for applications containing sorption, selective separation, and catalysis. How to correlate the microscopic structure with ...flexibility in COFs is a great challenge. Herein, we visually track the flexible deformation behaviors of single COF-300 and COF-300-AR particles in response to solvent vapour guests with dark-field microscopy (DFM) in an in operando manner. COF-300-AR with freely-rotating C-N single bonds are synthesized by the reduction of imine-based COF-300 consisting of rigid C=N double bonds without changing topological structure and crystallinity. Unexpectedly, we observe that the flexible deformation of COF-300 is extremely higher than that of COF-300-AR despite it bears many C-N single bonds, clearly illustrating the apparent flexibility decrease of COF-300 after reduction. The high spatiotemporal resolution of DFM enables the finding of inter-particle variations of the flexibility among COF-300 crystals. Experimental characterizations by variable-temperature X-ray diffraction and infrared spectroscopy as well as theoretical calculations demonstrate that the flexible deformation of COF-300 is ascribed to the pedal motion around rigid C=N double bonds. These observations provide new insights into COF flexibility.
Obesity is a chronic metabolic disease caused by genetic and environmental factors that has become a serious global health problem. There is evidence that gut microbiota is closely related to the ...occurrence and development of obesity. Erchen Decoction (ECD), a traditional Chinese medicine, has been widely used for clinical treatment and basic research of obesity and related metabolic diseases in recent years. It can significantly improve insulin resistance (IR) and lipid metabolism disorders. However, there is no microbiological study on its metabolic regulation. In this study, we investigated the effects of ECD on obesity, especially lipid metabolism and the composition and function of gut microbiota in Zucker diabetic fatty (ZDF) rats, and explored the correlation between the biomarkers of gut microbiota and metabolite and host phenotype. The results showed that ECD could reduce body weight, improve IR and lipid metabolism, and reduce the concentration of free fatty acids (FFA) released from white adipose tissue (WAT) due to excessive lipolysis by interfering with the insulin receptor substrate 1 (IRS1)/protein kinase B (AKT)/protein kinase A (PKA)/hormone-sensitive triglyceride lipase (HSL) signaling pathway in ZDF rats. Additionally, ECD gradually adjusted the overall structure of changed gut microbiota, reversed the relative abundance of six genera, and changed the function of gut microbiota by reducing the content of propionic acid, a metabolite of gut microbiota, in ZDF rats. A potentially close relationship between biomarkers, especially
Prevotella
,
Blautia
, and
Holdemania
, propionic acid and host phenotypes were demonstrated through correlation analysis. The results suggested that the beneficial effects of ECD on obesity, especially lipid metabolism disorders, are related to the regulation of gut microbiota in ZDF rats. This provides a basis for further research on the mechanism and clinical application of ECD to improve obesity via gut microbiota.
With the help of robot technology, intelligent rehabilitation of patients with lower limb motor dysfunction caused by stroke can be realized. A key factor constraining the clinical application of ...rehabilitation robots is how to realize pattern recognition of human movement intentions by using the surface electromyography (sEMG) sensors to ensure unhindered human-robot interaction.
A multilayer CNN-LSTM prediction network incorporating the self-attention mechanism (SAM) is proposed, in this paper, which can extract and learn the periodic and trend characteristics of the sEMG signals, and realize the accurate autoregressive prediction of the human motion information. Firstly, the multilayer CNN-LSTM network utilizes the CNN layer for initial feature extraction of data, and the LSTM network is used to improve the enhancement of the historical time-series features. Then, the SAM is used to improve the global feature extraction performance and parallel computation speed of the network.
In comparison with existing test is carried out using actual data from five healthy subjects as well as a clinical hemiplegic patient to verify the superiority and practicality of the proposed algorithm. The results show that most of the model's prediction
> 0.9 for different motion states of healthy subjects; in the experiments oriented to the motion characteristics of patient subjects, the angle prediction results of
> 0.99 for the untrained data on the affected side, which proves that our proposed model also has a better effect on the angle prediction of the affected side.
The main contribution of this paper is to realize continuous motion estimation of ankle joint for healthy and hemiplegic individuals under non-ideal conditions (weak sEMG signals, muscle fatigue, high muscle tension, etc.), which improves the pattern recognition accuracy and robustness of the sEMG sensor-based system.
Background and Purpose:
Neurodegenerative diseases are associated with metabolic disturbances. Pyruvate dehydrogenase E1 component subunit alpha (PDHA1) is an essential component in the process of ...glucose metabolism, and its deficiency exists in various diseases such as Alzheimer’s disease (AD), epilepsy, Leigh’s syndrome, and diabetes-associated cognitive decline. However, the exact role of PDHA1 deficiency in neurodegenerative diseases remains to be elucidated. In this study, we explored the effect of PDHA1 deficiency on cognitive function and its molecular mechanism.
Methods:
A hippocampus-specific
Pdha1
knockout (
Pdha1
–/–
) mouse model was established, and behavioral tests were used to evaluate the cognitive function of mice. Transmission electron microscopy (TEM) was performed to observe the morphological changes of the hippocampus. The lactate level in the hippocampus was measured. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to explore the possible mechanism of the effect of PDHA1 on cognition.
Results:
Pdha1
knockout damaged the spatial memory of mice and led to the ultrastructural disorder of hippocampal neurons. Lactate accumulation and abnormal lactate transport occurred in
Pdha1
–/–
mice, and the cyclic AMP-protein kinase A-cAMP response element-binding protein (cAMP/PKA/CREB) pathway was inhibited.
Conclusion:
Lactate accumulation caused by PDHA1 deficiency in the hippocampus may impair cognitive function by inhibiting the cAMP/PKA/CREB pathway.
Bipolar disorder (BD) is a distinctly heterogeneous and multifactorial disorder with a high individual and social burden. Immune pathway dysregulation is an important pathophysiological feature of ...BD. Recent studies have suggested a potential role for T lymphocytes in the pathogenesis of BD. Therefore, greater insight into T lymphocytes' functioning in patients with BD is essential. In this narrative review, we describe the presence of an imbalance in the ratio and altered function of T lymphocyte subsets in BD patients, mainly in T helper (Th) 1, Th2, Th17 cells and regulatory T cells, and alterations in hormones, intracellular signaling, and microbiomes may be potential causes. Abnormal T cell presence explains the elevated rates of comorbid inflammatory illnesses in the BD population. We also update the findings on T cell-targeting drugs as potentially immunomodulatory therapeutic agents for BD disease in addition to classical mood stabilizers (lithium, valproic acid). In conclusion, an imbalance in T lymphocyte subpopulation ratios and altered function may be involved in the development of BD, and maintaining T cell immune homeostasis may provide an overall therapeutic benefit.
•DENV-2 was the dominant epidemic serotype in mainland China during 2015–2020.•Ten new intra-serotype recombinants were identified by analyzing 291 complete genomes of naturally circulating ...DENV.•Large-span substitution of gene fragments (eight genomic regions) were detected for the first time.•A total of seven sites under positive selection were revealed in DENV-1, DENV-2 and DENV-3.
Immune pressure can select for escape mutants that can become epidemiologically relevant. Thus, surveillance of recombinants and positively selected mutants of the dengue virus (DENV) are vital for preventing and controlling the dengue fever outbreak. However, little is known about recombinants and positively selected mutants of circulating DENV strains in mainland China. In this study, those variants with recombination and adaptive evolutionary sites of circulating DENV strains were identified during 2015–2020. Phylogenetic analysis showed that the DENV-2 was the dominant epidemic serotype, and the dengue epidemic in China was closely related to the imported virus from Southeast Asian countries. Recombination analysis based on 291 complete genomes of naturally circulating DENV identified 10 new intra-serotype recombinant variants. Two or three recombination regions in a single dengue isolate were also observed. The breakpoints of recombinants were distributed in different regions of the genome. In particular, two recombinant strains (strain DENV-4/China/YN/15DGR394 (2015) and XLLM10666) with extremely large exchange fragments were detected. This large-scale gene fragment exchange (eight genomic regions) of strain DENV-4/China/YN/15DGR394 (2015) with substitutions at both the 5′ and 3′ ends of the genome, had never been described before. Moreover, selection pressure analyses revealed seven positive selection sites located in regions encoding the NS1, NS3 and NS5 proteins. Overall, this study is the first to report ten specific intra-serotype recombinants and seven positive selection sites of Chinese epidemic strains of DENV, which highlight their significance for DENV surveillance and effective control.
To investigate the GSDMD, CASP1, CASP4 and CASP5 expression in peripheral blood mononuclear cells of non-small cell lung cancer patients and analyze their clinical significance.
71 non-small cell ...lung cancer patients were selected as the study group and 50 healthy individuals as the control group. The GSDMD, CASP1, CASP4 and CASP5 expression in peripheral blood mononuclear cells of the two groups were detected by real-time fluorescence quantitative PCR. The GSDMD, CASP1, CASP4, CASP5 expression and their relationship with the clinical characteristics of the patients were analyzed.
Compared with the control group, the GSDMD, CASP4 and CASP5 expression in PBMCs of lung cancer patients was significantly higher(P < 0.05). Lymph node metastasis had significant difference with the CASP4 and GSDMD expression (P < 0.05); tumor volume had significant difference with CASP1 and CASP5 expression (P < 0.05). The areas under predictive ROC curve of the GSDMD, CASP1, CASP4, and CASP5 mRNA expression were 0.629(P < 0.05), 0.574(p > 0.05), 0.701(P < 0.05) and 0.628(P < 0.05), the sensitivity values were 84.5%, 67.6% 43.7%, and 84.3%;the specificity values were 42%, 52%, 84% and 64%, respectively.
GSDMD, CASP1, CASP4 and CASP5 gene expression are highly increased in PBMCs of non-small cell lung cancer patients and their expression are closely related to the clinical characteristics of patients. The early enhanced pyroptosis-related gene expression may be potential molecular markers for early diagnosis of non-small cell lung cancer.
For patients with functional motor disorders of the lower limbs due to brain damage or accidental injury, restoring the ability to stand and walk plays an important role in clinical rehabilitation. ...Lower limb exoskeleton robots generally require patients to convert themselves to a standing position for use, while being a wearable device with limited movement distance.
This paper proposes a reconfigurable behavioral assistive robot that integrates the functions of an exoskeleton robot and an assistive standing wheelchair through a novel mechanism. The new mechanism is based on a four-bar linkage, and through simple and stable conformal transformations, the robot can switch between exoskeleton state, sit-to-stand support state, and wheelchair state. This enables the robot to achieve the functions of assisted walking, assisted standing up, supported standing and wheelchair mobility, respectively, thereby meeting the daily activity needs of sit-to-stand transitions and gait training. The configuration transformation module controls seamless switching between different configurations through an industrial computer. Experimental protocols have been developed for wearable testing of robotic prototypes not only for healthy subjects but also for simulated hemiplegic patients.
The experimental results indicate that the gait tracking effect during robot-assisted walking is satisfactory, and there are no sudden speed changes during the assisted standing up process, providing smooth support to the wearer. Meanwhile, the activation of the main force-generating muscles of the legs and the plantar pressure decreases significantly in healthy subjects and simulated hemiplegic patients wearing the robot for assisted walking and assisted standing-up compared to the situation when the robot is not worn.
These experimental findings demonstrate that the reconfigurable behavioral assistive robot prototype of this study is effective, reducing the muscular burden on the wearer during walking and standing up, and provide effective support for the subject's body. The experimental results objectively and comprehensively showcase the effectiveness and potential of the reconfigurable behavioral assistive robot in the realms of behavioral assistance and rehabilitation training.
Cervical cancer continues to be a concern, and the prognosis of locally advanced cervical cancer remains poor.
was previously identified as a potential oncogene and regulator of tumor apoptosis. In ...this study, we aim to further elucidate the underlying mechanisms of
gene in the regulation of cervical cancer apoptosis. First, we identify
as an upregulated gene in
-silenced cervical cancer cells, and inhibition of
reverses
knockdown-induced apoptosis. Further study reveals that
regulates cell apoptosis in a mitochondrial-dependent manner with a redistribution of mitochondrial membrane potential and intracellular Ca
levels. However, the analysis of the STRING database and our experimental results show that
has little effect on cervical cancer progression and survival. Further mechanistic study demonstrates that
and
silencing inhibits apoptosis by activating p53. Meanwhile, the knockdown of
enhances the chemosensitivity of cervical cancer cells by strengthening paclitaxel-induced apoptosis. Based on the above results, the IMPA2/AIFM2/p53 pathway may be a new molecular mechanism for paclitaxel treatment of cervical cancer and an effective strategy to enhance the sensitivity of cervical cancer cells to paclitaxel. Our findings display a novel function of
in regulating cell apoptosis and paclitaxel resistance mediated by a disturbance of
and
expression, potentially making it a novel therapeutic target for cervical cancer treatment.
A 58-year-old male was admitted to our hospital due to lasting fever, progressive lymphadenopathy and bicytopenia, with a previously histological diagnosis of follicular lymphoma grade 3a with ...Epstein–Barr virus-encoded RNA positive one month ago. A second biopsy of axillary lymph node revealed concurrent diffuse large B-cell lymphoma with Epstein–Barr virus-encoded RNA positive. Another diagnosis of hemophagocytic lymphohistiocytosis secondary to Epstein–Barr virus positive diffuse large B-cell lymphoma was further concluded by clinical manifestation, laboratory test and atypical lymphocytes in peripheral-blood smear. After a pulse of steroid pre-phase treatment, the patient’s clinical condition deteriorated and died in two weeks. The presence of Epstein–Barr virus infection in patients with follicular lymphoma is associated with more aggressive clinical course and increased risk of high-grade transformation. Hemophagocytic lymphohistiocytosis in response to Epstein–Barr virus infection or lymphoma remains fatal. Early diagnosis and initiation of treatment may improve the outcome.
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