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1.
Life Sci ; 286: 120039, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34637797

RESUMO

AIM: This study investigated the roles of bone morphogenetic protein-4 (BMP4) and ROS in diabetic endothelial dysfunction and explored whether Salvianolic acid B (Sal B) improved endothelial function by affecting BMP4-ROS in diabetic mice. MAIN METHODS: db/db mice were orally administrated with Sal B (10 mg/kg/day) for one week while db/m + mice were injected with adenoviral vectors delivering BMP4 (3 × 108 pfu) and then received one week-Sal B treatment. ROS levels were assayed by DHE staining. Protein expression and phosphorylation were evaluated by Western blot. Aortic rings were suspended in myograph for force measurement. Flow-mediated dilatations in the second-order mesenteric arteries were determined by pressure myograph. KEY FINDINGS: We first revealed the existence of a BMP4-ROS cycle in db/db mice, which stimulated p38 MAPK/JNK/caspase 3 and thus participated in endothelial dysfunction. One week-treatment or 24 h-incubation with Sal B disrupted the cycle, suppressed p38 MAPK/JNK/caspase 3 cascade, and improved endothelium-dependent relaxations (EDRs) in db/db mouse aortas. Importantly, in vivo Sal B treatment also improved flow-mediated dilatation in db/db mouse second order mesenteric arteries. Furthermore, in vivo BMP4 overexpression induced oxidative stress, stimulated p38 MAPK/JNK/caspase 3, and impaired EDRs in db/m + mouse aortas, which were all reversed by Sal B. SIGNIFICANCE: The present study demonstrates that Sal B ameliorates endothelial dysfunction through breaking the BMP4-ROS cycle and subsequently inhibiting p38 MAPK/JNK/caspase 3 in diabetic mice and provides evidence for the additional new mechanism underlying the benefit of Sal B against diabetic vasculopathy.

2.
Microvasc Res ; 139: 104263, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34655603

RESUMO

Cannabinoids are reported to regulate cardiovascular functions. Cannabinoid receptors 1 (CB1Rs) are widely expressed in both the neuronal system and vascular system, but the contribution of CB1Rs in vascular smooth muscle (CB1RSM) to cardiovascular functions is not clear yet. In this research, we analyzed the effects of CB1RSM on blood pressure, vasoconstriction, and vasodilation abilities by using conditionally CB1R knockout mice (CB1RSMKO). The results show no significant difference in basal blood pressure between the conscious CB1RSMKO and control mice, indicating that CB1RSM is not essential for basal blood pressure maintenance. The constriction of the CB1RSMKO mesenteric artery in vitro was not significantly altered compared with that of the control mice. In contrast, the relaxation to CB1R agonist 2-AG or WIN55212-2 was decreased in CB1RSMKO vessels, suggesting that activation of CB1RSM mediates the vasodilation effect of cannabinoids. Ischemia stroke mouse model was used to further identify the potential function of CB1RSM in pathological conditions, and the results showed that the infarct volume in CB1RSMKO mice is significantly increased compared with the control littermates. These results suggest that vascular CB1R may not play a central role in basal vascular health maintenance but is protective in ischemia states, such as stroke. The protection function may be mediated, at least partly, by the relaxation effect of CB1RSM-dependent activities of endocannabinoids.

3.
Front Neurosci ; 15: 703044, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34658758

RESUMO

The hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis caused by stress will inevitably disrupt the homeostasis of the neuroendocrine system and damage physiological functions. It has been demonstrated that electroacupuncture (EA) can modulate HPA axis hyperactivity during the perioperative period. As the initiating factor of the HPA axis, hypothalamic corticotrophin-releasing hormone (CRH) is the critical molecule affected by EA. However, the mechanism by which EA reduces CRH synthesis and secretion remains unclear. Activated N-methyl-D-aspartate receptor (NMDAR) has been linked to over-secretion of hypothalamic CRH induced by stress. To determine whether NMDAR is involved in EA regulating the over-expression of CRH, a surgical model of partial hepatectomy (HT) was established in our experiment. The effect of EA on hypothalamic NMDAR expression in HT mice was examined. Then, we investigated whether the extracellular regulated protein kinases (ERK)/cyclic adenosine monophosphate response element-binding protein (CREB) signaling pathway mediated by NMDAR was involved in EA regulating HPA axis hyperactivity. It was found that surgery enhanced the expression of hypothalamic CRH and caused HPA axis hyperactivity. Intriguingly, EA effectively suppressed the expression of CRH and decreased the activation of GluN2A (NMDAR subunit), ERK, and CREB in HT mice. GluN2A, ERK, and CREB antagonists had similar effects on normalizing the expression of CRH and HPA axis function compared with EA. Our findings suggested that surgery enhanced the activation of the hypothalamic GluN2A/ERK/CREB signaling pathway, thus promoting the synthesis and secretion of CRH. EA suppressed the phosphorylation of GluN2A, ERK, and CREB in mice that had undergone surgery, indicating that the GluN2A/ERK/CREB signaling pathway was involved in EA alleviating HPA axis hyperactivity.

4.
Nat Commun ; 12(1): 5875, 2021 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620854

RESUMO

The deglacial hydroclimate in South China remains a long-standing topic of debate due to the lack of reliable moisture proxies and inconsistent model simulations. A recent hydroclimate proxy suggests that South China became wet in cold stadials during the last deglaciation, with the intensification proposed to be contributed mostly by the East Asian summer monsoon (EASM). Here, based on a deglacial simulation in a state-of-the-art climate model that well reproduces the evolution of EASM, winter monsoon (EAWM) and the associated water isotopes in East Asia, we propose that the intensified hydroclimate in South China is also contributed heavily by the rainfall in autumn, during the transition between EASM and EAWM. The excessive rainfall in autumn results from the convergence between anomalous northerly wind due to amplified land-sea thermal contrast and anomalous southerly wind associated with the anticyclone over Western North Pacific, both of which are, in turn, forced by the slowdown of the Atlantic thermohaline circulation. Regardless the rainfall change, however, the modeled δ18Op remains largely unchanged in autumn. Our results provide new insights to East Asia monsoon associated with climate change in the North Atlantic.

5.
J Immunol ; 206(12): 2775-2783, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34602651

RESUMO

CD8+ T cells have conventionally been studied in relationship to pathogen or tumor clearance. Recent reports have identified novel functions of CXCR5+CD8+ T cells that can home to lymphoid follicles, a key site of antibody production. In this review we provide an in-depth analysis of conflicting reports regarding the impact of CXCR5+CD8+ T cells on antibody production and examine the data supporting a role for antibody-enhancement (B cell "helper") and antibody-downregulation (antibody-suppressor) by CXCR5+CD8+ T cell subsets. CXCR5+CD8+ T cell molecular phenotypes are associated with CD8-mediated effector functions including distinct subsets that regulate antibody responses. Co-inhibitory molecule PD-1, among others, distinguish CXCR5+CD8+ T cell subsets. We also provide the first in-depth review of human CXCR5+CD8+ T cells in the context of clinical outcomes and discuss the potential utility of monitoring the quantity of peripheral blood or tissue infiltrating CXCR5+CD8+ T cells as a prognostic tool in multiple disease states.

6.
Elife ; 102021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34633289

RESUMO

To assure complete tumor removal, frozen section analysis is the most common procedure for intraoperative pathological assessment of resected tumor margins. However, during one operation, multiple biopsies may be sent for examination, but only few of them are made into cryosections because of the complex preparation protocols and time-consuming pathological analysis, which potentially increases the risk of overlooking tumor involvement. Here, we propose a fluorescence-based pre-screening strategy that allows high-throughput, convenient, and fast gross assessment of resected tumor margins. A dual-activatable cationic fluorescent molecular rotor was developed to specifically illuminate live tumor cells' cytoplasm by emitting two different fluorescence signals in response to elevations in hypoxia-induced nitroreductase (a biochemical marker) and cytoplasmic viscosity (a biophysical marker), two characteristics of cancer cells. The ability of the fluorescent molecular rotor in detecting tumor cells was evaluated in mouse and human specimens of multiple tissues by comparing with hematoxylin and eosin staining. Importantly, the fluorescent molecular rotor achieved 100% specificity in discriminating lung and liver cancers from normal tissue, allowing pre-screening of the tumor-free surgical margins and promoting clinical decision. Altogether, this type of fluorescent molecular rotor and the proposed strategy may serve as a new option to facilitate intraoperative assessment of resected tumor margins.

7.
Appl Opt ; 60(25): 7686-7695, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34613238

RESUMO

Recovering targets through diffusers is an important topic as well as a general problem in optical imaging. The difficulty of recovering is increased due to the noise interference caused by an imperfect imaging environment. Existing approaches generally require a high-signal-to-noise-ratio (SNR) speckle pattern to recover the target, but still have limitations in de-noising or generalizability. Here, featuring information of high-SNR autocorrelation as a physical constraint, we propose a two-stage (de-noising and reconstructing) method to improve robustness based on data driving. Specifically, a two-stage convolutional neural network (CNN) called autocorrelation reconstruction (ACR) CNN is designed to de-noise and reconstruct targets from low-SNR speckle patterns. We experimentally demonstrate the robustness through various diffusers with different levels of noise, from simulative Gaussian noise to the detector and photon noise captured by the actual optical system. The de-noising stage improves the peak SNR from 20 to 38 dB in the system data, and the reconstructing stage, compared with the unconstrained method, successfully recovers targets hidden in unknown diffusers with the detector and photon noise. With the help of the physical constraint to optimize the learning process, our two-stage method is realized to improve generalizability and has potential in various fields such as imaging in low illumination.

8.
Acta Neurol Belg ; 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34661876

RESUMO

PURPOSE: There is growing evidence that autophagy-related gene 5 (ATG5) is involved in neural development, neuronal differentiation, and neurodegenerative diseases. The purpose of this study was to investigate the association between ATG5 gene single-nucleotide polymorphisms (SNPs) and Parkinson's disease (PD) in the Han population. METHODS: A case-control study was conducted in 120 PD patients and 100 healthy volunteers. MassArray platform was used to analyze polymorphisms in three different regions of ATG5 gene (rs510432, rs573775 and rs17587319). In the included subjects, 50 PD patients and 50 healthy volunteers were selected, and the plasma ATG5 concentration was detected by enzyme-linked immunosorbent assay (ELISA). The allele and genotype frequencies of SNPs were assessed using the SHEsis program. RESULTS: We found a significant correlation between rs17587319 and PD, and the subcomponent showed a high correlation between rs17587319 with cognitive impairment and age at onset in PD patients. At the same time, the total plasma ATG5 level of PD patients and the plasma ATG5 expression level of early-onset Parkinson's disease (EOPD) patients were significantly higher than the control group, while there was no significant difference of ATG5 expression between late-onset Parkinson's disease (LOPD) patients and the control group. CONCLUSION: These findings suggest that genetic variations in the ATG5 gene and low levels of the ATG5 protein are associated with susceptibility to PD and with cognitive impairment in PD patients. ATG5 could be a potential biomarker to assess the severity and prognosis of PD.

9.
Arch Biochem Biophys ; 711: 109024, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34487720

RESUMO

This study attempted to determine the effect of EphA2 on H2O2-treated lens epithelial cells (SRA01/04) and the underlying mechanisms. MTT assay and flow cytometry were performed to assess cell viability and cell apoptosis. Western blot was carried out to examine the levels of proteins associated with apoptosis and autophagy. Our results revealed that EphA2 significantly elevated the reduced cell viability, and inhibited the increased cell apoptosis in H2O2-treated SRA01/04 cells, along with the significant up-regulated Bcl-2 and down-regulated Cleaved-caspase-3 and Bax protein levels, but which were all abolished by Rapa (autophagy activator). We also found that EphA2 significantly suppressed cell autophagy in H2O2-treated SRA01/04 cells. Additionally, EphA2 significantly up-regulated the protein levels of p-Akt and p-mTOR in H2O2-treated SRA01/04 cells, and the inhibition of Akt by MK-2206 and inhibition of mTOR by Rapa both obviously reversed EphA2-mediated the inhibition of autophagy in H2O2-treated SRA01/04 cells. In summary, these data demonstrated that EphA2 inhibited the apoptosis of SRA01/04 cells by inhibiting autophagy via activating PI3K/Akt/mTOR pathway.

10.
Environ Pollut ; 290: 118000, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34482244

RESUMO

During three sampling periods in 2014, systematic investigations were conducted into contamination profiles of ten organophosphate flame retardants (OPFRs) in both suspended particulate phase and water phase in the Yellow River (Henan Area). This research shows that OPFRs exist at lower concentrations in the suspended phase than in the water phase. The median concentration of 10 OPFRs (∑10OPFRs) in the suspended particulate phase was 62.5 ng/g (fluctuating from ND to 6.17 × 103 ng/g, dw), while their median concentration in the water phase was 109 ng/L (fluctuating from 35.6 to 469 ng/L). Among the selected 10 OPFRs, triethylphosphate (TEP), tris(1-chloro-2-propyl) phosphate (TCPP), and tris(2-chloroethyl) phosphate (TCEP) were the predominant compounds in the water phase (occupying 91.6% of the ∑10OPFRs), while TCPP, TCEP, and tri-o-tolyl phosphate (o-TCP) were the most common in the suspended particulate phase, accounting for 90.1% of the ∑10OPFRs. Across the three sampling periods, there was no significant seasonable variation for OPFRs either in the water phase or in the suspended particulate phase, except for TCEP and TCPP in the water phase. Compared with research findings relating to concentrations of OPFRs around China and abroad, the OPFRs of the Yellow River (Henan Area) in the water phase were at a moderate level. Suspended particles (SS) had a very important impact on the transportation of OPFRs in the studied area, with about 83.9% of ∑10OPFRs inflow attributed to SS inflow and about 81.7% of ∑10OPFRs outflow attributed to SS outflow. The total annual inflow and outflow of OPFRs were 7.72 × 104 kg and 6.62 × 104 kg in the studied area, respectively.

11.
Br J Radiol ; : 20210682, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34478333

RESUMO

OBJECTIVE: To evaluate the correlation between elastic heterogeneity (EH) and lymphovascular invasion (LVI) in breast cancers and assess the clinical value of using EH to predict LVI pre-operatively. METHODS: This retrospective study consisted of 376 patients with breast cancers that had undergone shear wave elastography (SWE) with virtual touch tissue imaging quantification between June 2017 and June 2018. The EH was determined as the difference between the averaged three highest and three lowest shear wave value. Clinicalpathological parameters including histological type and grades, LVI, axillary lymph node status and molecular markers (estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 and Ki-67) were reviewed and recorded. Relationship EH and clinicalpathological parameters was investigated respectively. The diagnostic performance of EH in distinguishing LVI or not was analyzed. RESULTS: At multivariate regression analysis, only EH (p = 0.017) was positively correlated with LVI in all tumors. EH (p = 0.003) and Ki-67 (p = 0.025) were positively correlated with LVI in tumors ≤ 2 cm. None of clinicalpathological parameters were correlated with LVI in tumors > 2 cm (p > 0.05 for all). Using EH to predict LVI in tumors ≤ 2 cm, the sensitivity and negative predictive value were 93 and 89% respectively. CONCLUSION: EH has the potential to be served as an imaging biomarker to predict LVI in breast cancer especially for tumors ≤ 2 cm. ADVANCES IN KNOWLEDGE: There was no association between LVI and other most commonly used elastic features such as SWVmean and SWVmax. Elastic heterogeneity is an independent predictor of LVI, so it can provide additional prognostic information for routine preoperative breast cancer assessment.For tumors ≤ 2cm, using EH value higher than 1.36 m/s to predict LVI involvement, the sensitivity and negative predictive value can reach to 93% and 89%, respectively, suggesting that breast cancer with negative EH value was more likely to be absent of LVI.

12.
Biomed Res Int ; 2021: 5565973, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485516

RESUMO

Osteoclast, which mediates overactive bone resorption, is one of the key factors for bone destruction in rheumatoid arthritis (RA). Existing studies have shown that abnormal miR-143-3p expression was observed in both RA patients and arthritis animals, which can participate in osteoclast differentiation, and mitogen-activated protein kinase (MAPK) signaling pathway was closely related to osteoclast differentiation. The primary objective of the current study was to determine the role of miR-143-3p in the progression of osteoclast differentiation and its relationship with MAPK signaling pathways. The results showed that miR-143-3p inhibited osteoclast differentiation and decreased the levels of M-CSF and RANKL during osteoclast differentiation. miR-143-3p inhibited the expression of MAPK signaling proteins, which is ERK1/2 in the early stage and JNK in the later stage of osteoclast differentiation. It was also observed that MAPK inhibitors upregulated miR-143-3p expression in osteoclast differentiation. Taken together, our results suggested that miR-143-3p could inhibit the differentiation of osteoclast, which was related to inhibiting MAPK signaling pathways. This may provide a novel strategy for curing RA.

13.
J Neuroinflammation ; 18(1): 204, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34530841

RESUMO

BACKGROUND: Perioperative neurocognitive disorder (PND) is a long-term postoperative complication in elderly surgical patients. The underlying mechanism of PND is unclear, and no effective therapies are currently available. It is believed that neuroinflammation plays an important role in triggering PND. The secreted glycoprotein myeloid differentiation factor 2 (MD2) functions as an activator of the Toll-like receptor 4 (TLR4) inflammatory pathway, and α5GABAA receptors (α5GABAARs) are known to play a key role in regulating inflammation-induced cognitive deficits. Thus, in this study, we aimed to investigate the role of MD2 in PND and determine whether α5GABAARs are involved in the function of MD2. METHODS: Eighteen-month-old C57BL/6J mice were subjected to laparotomy under isoflurane anesthesia to induce PND. The Barnes maze was used to assess spatial reference learning and memory, and the expression of hippocampal MD2 was assayed by western blotting. MD2 expression was downregulated by bilateral injection of AAV-shMD2 into the hippocampus or tail vein injection of the synthetic MD2 degrading peptide Tat-CIRP-CMA (TCM) to evaluate the effect of MD2. Primary cultured neurons from brain tissue block containing cortices and hippocampus were treated with Tat-CIRP-CMA to investigate whether downregulating MD2 expression affected the expression of α5GABAARs. Electrophysiology was employed to measure tonic currents. For α5GABAARs intervention experiments, L-655,708 and L-838,417 were used to inhibit or activate α5GABAARs, respectively. RESULTS: Surgery under inhaled isoflurane anesthesia induced cognitive impairments and elevated the expression of MD2 in the hippocampus. Downregulation of MD2 expression by AAV-shMD2 or Tat-CIRP-CMA improved the spatial reference learning and memory in animals subjected to anesthesia and surgery. Furthermore, Tat-CIRP-CMA treatment decreased the expression of membrane α5GABAARs and tonic currents in CA1 pyramidal neurons in the hippocampus. Inhibition of α5GABAARs by L-655,708 alleviated cognitive impairments after anesthesia and surgery. More importantly, activation of α5GABAARs by L-838,417 abrogated the protective effects of Tat-CIRP-CMA against anesthesia and surgery-induced spatial reference learning and memory deficits. CONCLUSIONS: MD2 contributes to the occurrence of PND by regulating α5GABAARs in aged mice, and Tat-CIRP-CMA is a promising neuroprotectant against PND.

14.
J Musculoskelet Neuronal Interact ; 21(3): 397-400, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34465679

RESUMO

Miyoshi myopathy (MM) is a rare autosomal recessive disorder caused by dysferlin (DYSF) gene mutation. Miyoshi myopathy-inducing mutation sites in the DYSF gene have been discovered worldwide. In the present study, a patient with progressive lower extremity weakness is reported, for which MM was diagnosed according to clinical manifestations, muscle biopsy, and immunohistochemistry. In addition, the DYSF gene of the patient and his parents was sequenced and analyzed and two heterozygous mutations of the DYSF gene (c.4756C> T and c.5316dupC) were discovered. The first mutation correlated with MM while the second was a new mutation. The patient was diagnosed with a compound heterozygous mutation. The mutation site is a new member of pathogenic MM gene mutations.

15.
Int J Med Sci ; 18(15): 3437-3451, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522170

RESUMO

Aurora-A has attracted a great deal of interest as a potential therapeutic target for patients with CRC. However, the outcomes of inhibitors targeting Aurora-A are not as favorable as expected, and the basis behind the ineffectiveness remains unknown. Here, we found that signal transducer and activator of transcription 1 (STAT1) was highly expressed in colorectal cancer (CRC) xenograft mouse models that were resistant to alisertib, an Aurora-A inhibitor. Unexpectedly, we found that alisertib disrupted Aurora-A binding with ubiquitin-like with plant homeodomain and ring finger domain 1 (UHRF1), leading to UHRF1 mediated ubiquitination and degradation of DNA methyltransferase 1 (DNMT1), which in turn resulted in demethylation of CpG islands of STAT1 promoter and STAT1 overexpression. Simultaneous silencing Aurora-A and UHRF1 prevented STAT1 overexpression and effectively inhibited CRC growth. Hence, concomitant targeting Aurora-A and UHRF1 can be a promising therapeutic strategy for CRC.

16.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4117-4123, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467722

RESUMO

This study aims to explore the relationship of DNA methylation with the contents of the index components as well as the growth and development of Pogostemon cablin. The demethylation reagent 5-azacytidine(5-azaC) was used to treat the tissue culture seedlings of patchouliol-type P. cablin. High performance liquid chromatography was employed to evaluate the changes of DNA methy-lation in P. cablin, and GC-MS to detect the contents of index components in P.cablin. The agronomic characters of P.cablin were measured using the common methods. The results showcased that DNA methylation of P.cablin was significantly reduced by 5-azaC in a concentration-dependent manner. Thirty days after treatment with 5-azaC at different concentrations, the content of patchouli alcohol changed slightly; compared with that in the control group, the content of pogostone in 50 µmol·L~(-1) and 100 µmol·L~(-1) 5-azaC groups was significantly up-regulated. The 100 µmol·L~(-1) 5-azaC group had the largest differences in contents of pogostone and patchouli alcohol compared with the control group, followed by the 50 µmol·L~(-1) 5-azaC group. Ninety days after disinhibition, the content of pogostone in the treatment group was significantly increased and the content of patchouli alcohol was significantly decreased. In addition, 5-azaC significantly inhibited the growth and development of P.cablin in a dose-dependent manner. These results indicate that DNA methylation regulates the biosynthesis of the index components in patchouliol-type P.cablin and proper demethylation can directly promote the synthesis of pogostone and indirectly affect the accumulation of patchouli alcohol.


Assuntos
Pogostemon , Azacitidina , Metilação de DNA , Cromatografia Gasosa-Espectrometria de Massas , Óleos Voláteis , Pogostemon/genética
17.
Microb Biotechnol ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34473895

RESUMO

Polyhydroxyalkanoates (PHA) are a promising and sustainable alternative to the petroleum-based synthetic plastics. Regulation of PHA synthesis is receiving considerable importance as engineering the regulatory factors might help developing strains with improved PHA-producing abilities. PHA synthesis is dedicatedly regulated by a number of regulatory networks. They tightly control the PHA content, granule size and their distribution in cells. Most PHA-accumulating microorganisms have multiple regulatory networks that impart a combined effect on PHA metabolism. Among them, several factors ranging from global to specific regulators, have been identified and characterized till now. This review is an attempt to categorically summarize the diverse regulatory circuits that operate in some important PHA-producing microorganisms. However, in several organisms, the detailed mechanisms involved in the regulation of PHA synthesis is not well-explored and hence further research is needed. The information presented in this review might help researcher to identify the prevailing research gaps in PHA regulation.

18.
Clin Transl Med ; 11(9): e464, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34586738

RESUMO

Esophageal adenocarcinoma (EAC), a subtype of esophageal carcinoma, is a severe health problem associated with high death rate and poor prognosis. Immunotherapy has proven to be effective in many solid tumors, including EAC, but immune escape blocks its effectiveness. Thus, we explored the mechanisms and functional role of c-Myb in immune escape of EAC cells. Clinical EAC tissues were collected for determining the expression of c-Myb, speckled POZ protein (SPOP), and miR-145-5p. Functional assays were then performed to detect the interactions between c-Myb and SPOP as well as between SPOP and miR-145-5p. EAC cell invasion and migration were assessed. Next, T cells were sorted and cocultured with EAC cells with different treatments followed by detection of T-cell viability. In addition, a mouse model of EAC was constructed for relevant in vivo assays. c-Myb and miR-145-5p were highly expressed and SPOP had low expressions in EAC. c-Myb activated the transcription of miR-145-5p, which in turn targeted SPOP. Further, SPOP accelerated the ubiquitination of PD-L1 to enhance its expression. Overexpression of PD-L1 suppressed T-cell functions and promoted proliferative and migrative abilities of EAC cells to induce immune escape. The above findings were also confirmed in the ECA mouse model in vivo. Our findings uncovered that c-Myb can promote the immune escape of EAC cells by favoring the transcription of miR-145-5p and inhibiting SPOP-dependent ubiquitination and degradation of PD-L1, thus, presenting new target for EAC adjunct therapy.

19.
Adv Drug Deliv Rev ; 178: 113964, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34499982

RESUMO

Traditional herbal medicine (THM), an ancient science, is a gift from nature. For thousands of years, it has helped humans fight diseases and protect life, health, and reproduction. Nanomedicine, a newer discipline has evolved from exploitation of the unique nanoscale morphology and is widely used in diagnosis, imaging, drug delivery, and other biomedical fields. Although THM and nanomedicine differ greatly in time span and discipline dimensions, they are closely related and are even evolving toward integration and convergence. This review begins with the history and latest research progress of THM and nanomedicine, expounding their respective developmental trajectory. It then discusses the overlapping connectivity and relevance of the two fields, including nanoaggregates generated in herbal medicine decoctions, the application of nanotechnology in the delivery and treatment of natural active ingredients, and the influence of physiological regulatory capability of THM on the in vivo fate of nanoparticles. Finally, future development trends, challenges, and research directions are discussed.

20.
Environ Pollut ; 291: 118116, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34537597

RESUMO

Real-time river chloride prediction has received a lot of attention for its importance in chloride control and management. In this study, an artificial neural network model (i.e., multi-layer perceptron, MLP) and a statistical inference model (i.e., stepwise-cluster analysis, SCA) are developed for predicting chloride concentration in stream water. Then, an ensemble learning model based on MLP and SCA is proposed to further improve the modeling accuracy. A case study of hourly river chloride prediction in the Grand River, Canada is presented to demonstrate the model applicability. The results show that the proposed ensemble learning model, MLP-SCA, provides the best overall performance compared with its two ensemble members in terms of RMSE, MAPE, NSE, and R2 with values of 11.58 mg/L, 27.55%, 0.90, and 0.90, respectively. Moreover, MLP-SCA is more competent for predicting extremely high chloride concentration. The prediction of observed concentrations above 150 mg/L has RMSE and MAPE values of 9.88 mg/L and 4.40%, respectively. The outstanding performance of the proposed MLP-SCA, particularly in extreme value prediction, indicates that it can provide reliable chloride prediction using commonly available data (i.e., conductivity, water temperature, river flow rate, and rainfall). The high-frequency prediction of chloride concentration in the Grand River can supplement the existing water quality monitoring programs, and further support the real-time control and management of chloride in the watershed. MLP-SCA is the first ensemble learning model for river chloride prediction and can be extended to other river systems for water quality prediction.

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