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1.
Neural Regen Res ; 18(1): 162-169, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35799537

RESUMO

We previously prepared nerve growth factor poly-lactide co-glycolid sustained-release microspheres to treat rat sciatic nerve injury using the small gap sleeve technique. Multiple growth factors play a synergistic role in promoting the repair of peripheral nerve injury; as a result, in this study, we added basic fibroblast growth factors to the microspheres to further promote nerve regeneration. First, in an in vitro biomimetic microenvironment, we developed and used a drug screening biomimetic microfluidic chip to screen the optimal combination of nerve growth factor/basic fibroblast growth factor to promote the regeneration of Schwann cells. We found that 22.56 ng/mL nerve growth factor combined with 4.29 ng/mL basic fibroblast growth factor exhibited optimal effects on the proliferation of primary rat Schwann cells. The successfully prepared nerve growth factor-basic fibroblast growth factor-poly-lactide-co-glycolid sustained-release microspheres were used to treat rat sciatic nerve transection injury using the small gap sleeve bridge technique. Compared with epithelium sutures and small gap sleeve bridging alone, the small gap sleeve bridging technique combined with drug-free sustained-release microspheres has a stronger effect on rat sciatic nerve transfection injury repair at the structural and functional level.

2.
Bioact Mater ; 20: 42-52, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35633873

RESUMO

Soft tissue integration is one major difficulty in the wide applications of metal materials in soft tissue-related areas. The inevitable inflammatory response and subsequent fibrous reaction toward the metal implant is one key response for metal implant-soft tissue integration. It is of great importance to modulate this inflammatory-fibrous response, which is mainly mediated by the multidirectional interaction between fibroblasts and macrophages. In this study, macrophages are induced to generate M1 and M2 macrophage immune microenvironments. Their cytokine profiles have been proven to have potentially multi-regulatory effects on fibroblasts. The multi-reparative effects of soft tissue cells (human gingival fibroblasts) cultured on metal material (titanium alloy disks) in M1 and M2 immune microenvironments are then dissected. Fibroblasts in the M1 immune microenvironment tend to aggravate the inflammatory response in a pro-inflammatory positive feedback loop, while M2 immune microenvironment enhances multiple functions of fibroblasts in soft tissue integration, including soft tissue regeneration, cell adhesion on materials, and contraction to immobilize soft tissue. Enlighted by the close interaction between macrophages and fibroblasts, we propose the concept of an "inflammatory-fibrous complex" to disclose possible methods of precisely and effectively modulating inflammatory and fibrous responses, thus advancing the development of metal soft tissue materials.

3.
Neural Regen Res ; 18(2): 396-403, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35900436

RESUMO

After spinal cord injury (SCI), a fibroblast- and microglia-mediated fibrotic scar is formed in the lesion core, and a glial scar is formed around the fibrotic scar as a result of the activation and proliferation of astrocytes. Simultaneously, a large number of neurons are lost in the injured area. Regulating the dense glial scar and replenishing neurons in the injured area are essential for SCI repair. Polypyrimidine tract binding protein (PTB), known as an RNA-binding protein, plays a key role in neurogenesis. Here, we utilized short hairpin RNAs (shRNAs) and antisense oligonucleotides (ASOs) to knock down PTB expression. We found that reactive spinal astrocytes from mice were directly reprogrammed into motoneuron-like cells by PTB downregulation in vitro. In a mouse model of compression-induced SCI, adeno-associated viral shRNA-mediated PTB knockdown replenished motoneuron-like cells around the injured area. Basso Mouse Scale scores and forced swim, inclined plate, cold allodynia, and hot plate tests showed that PTB knockdown promoted motor function recovery in mice but did not improve sensory perception after SCI. Furthermore, ASO-mediated PTB knockdown improved motor function restoration by not only replenishing motoneuron-like cells around the injured area but also by modestly reducing the density of the glial scar without disrupting its overall structure. Together, these findings suggest that PTB knockdown may be a promising therapeutic strategy to promote motor function recovery during spinal cord repair.

4.
Poult Sci ; 101(9): 102034, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35926351

RESUMO

Fatty liver hemorrhagic syndrome (FLHS) is a chronic hepatic disease which occurs when there is a disorder in lipid metabolism. FLHS is often observed in caged laying hens and characterized by a decrease in egg production and dramatic increase of mortality. Salidroside (SDS) is an herbal drug which has shown numerous pharmacological activities, such as protecting mitochondrial function, attenuating cell apoptosis and inflammation, and promoting antioxidant defense system. We aimed to determine the therapeutic effects of SDS on FLHS in laying hens and investigate the underlying mechanisms through which SDS operates these functions. We constructed oleic acid (OA)-induced fatty liver model in vitro and high-fat diet-induced FLHS of laying hens in vivo. The results indicated that SDS inhibited OA-induced lipid accumulation in chicken primary hepatocytes, increased hepatocyte activity, elevated the mRNA expression of proliferation related genes PCNA, CDK2, and cyclinD1 and increased the protein levels of PCNA and CDK2 (P < 0.05), as well as decreased the cleavage levels of Caspase-9, Caspase-8, and Caspase-3 and apoptosis in hepatocytes (P < 0.05). Moreover, SDS promoted the phosphorylation levels of PDK1, AKT, and Gsk3-ß, while inhibited the PI3K inhibitor (P < 0.05). Additionally, we found that high-fat diet-induced FLHS hens had heavier body weight, liver weight, and abdominal fat weight, and severe steatosis in histology, compared with the control group (Con). However, hens fed with SDS maintained lighter body weight, liver weight, and abdominal fat weight, as well as normal liver without hepatic steatosis. In addition, high-fat diet-induced FLHS hens had high levels of serum total cholesterol (TC), triglyceride (TG), alanine transaminase (ALT), and aspartate aminotransferase (AST) compared to the Con group, however, in the Model+SDS group, the levels of TC, TG, ALT, and AST decreased significantly, whereas the level of superoxide dismutase (SOD) increased significantly (P < 0.05). We also found that SDS significantly decreased the mRNA expression abundance of PPARγ, SCD, and FAS in the liver, as well as increased levels of PPARα and MTTP, and decreased the mRNA expression of TNF-α, IL-1ß, IL-6, and IL-8 in the Model+SDS group (P < 0.05). In summary, this study showed that 0.3 mg/mL SDS attenuated ROS generation, inhibited lipid accumulation and hepatocyte apoptosis, and promoted hepatocyte proliferation by targeting the PI3K/AKT/Gsk3-ß pathway in OA-induced fatty liver model in vitro, and 20 mg/kg SDS alleviated high-fat-diet-induced hepatic steatosis, oxidative stress, and inflammatory response in laying hens in vivo.

5.
Cytokine ; 158: 155982, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35932499

RESUMO

Innate immune cells are of broad interest in a variety of diseases. These cells include neutrophils, macrophages, dendritic cells and mast cells, etc. Innate immune cells are often mentioned in inflammatory diseases as the first line of defense against pathogens' invasion. As chronic obstructive pulmonary disease and periodontitis are inflammatory diseases, innate immune cells play an important role in the development of both diseases. COPD and periodontitis are common epidemic diseases with a very high prevalence, thus affecting a large number of people and also reducing the quality of life of patients. In addition, epidemiological studies suggested a link between the two, creating a co-morbid burden, but the mechanism of the link is yet to be explained. This article discusses the possible mechanism of the link between the two diseases in terms of innate immune cells and discusses possible future targeted therapies that could alleviate the burden on patients.

6.
Biochem Biophys Res Commun ; 624: 40-46, 2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35932578

RESUMO

Diabetic nephropathy (DN) is one of the most important complications of diabetes mellitus (DM) and has become the second cause of end-stage renal disease (ESRD). This study intends to investigate the molecular mechanism of increased mitochondrial fission in podocytes under the effect of high glucose (HG), and to preliminarily study the role of mitochondrial fission factor (MFF)-mediated mitochondrial fission in podocyte injury of DN. In vitro studies, we found that HG induced increased mitochondrial fission and podocyte damage. At the same time MFF mRNA and protein levels was increased, suggesting that MFF was transcriptional upregulated under HG conditions. Consistent with this, in vivo studies found that mitochondrial fission was also significantly increased in podocytes of diabetic nephropathy mice, and MFF expression was up-regulated. Therefore, our study proves that mitochondrial fission increases in podocytes under DM both in vitro and in vivo, and the up-regulation of MFF expression may be one of the reasons for the increase of mitochondrial fission. After inhibiting the expression of MFF, the survival rate of podocytes was significantly decreased under HG conditions, suggesting that MFF may play a protective role in podocyte injury in DN.

7.
Jpn J Clin Oncol ; 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35946332

RESUMO

BACKGROUND: Pain is one of the most common concomitant symptoms among cancer patients. Pharmacologic agents are regarded as a cornerstone of cancer pain management. 'Dose titration' with short-acting morphine is widely accepted. Such a titration method is very complicated. The analgesic background establishment is often delayed. Titration based on sustained-release opioids is also recommended, but the onset of analgesic effect requires hours, whereas the rescue analgesia is always needed. This study evaluated the optimized morphine titration scheme with a simultaneous combination of sustained-release morphine and subcutaneous morphine. METHODS: In a multicenter, 7-day, randomized controlled study, patients with moderate to severe cancer pain were assigned to receive either sustained-release morphine and subcutaneous morphine simultaneously (rapid titration) or only subcutaneous morphine to dose titration. The primary outcome was the safety and the number of times of rescue therapy as needed in the first 24 h. RESULTS: A total of 108 patients with moderate to severe cancer pain were included in the study. The number of times of rescue analgesics in the first 24 h significantly reduced in the rapid titration group (0.4 ± 0.48 vs. 2.3 ± 0.78, P = 0.000). No differences in the intensity of opioid-related symptoms were found between the two groups. CONCLUSIONS: Rapid titration is safe and efficient, which could significantly decrease rescue analgesics in the first 24 h and achieve better analgesic efficacy for cancer pain patients.

8.
Front Neurosci ; 16: 934471, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35937865

RESUMO

Background: Cerebral blood flow (CBF) alterations are involved in the onset and progression of Alzheimer's disease (AD) and can be a potential biomarker. However, CBF measured by single-delay arterial spin labeling (ASL) for discrimination of mild cognitive impairment (MCI, an early stage of AD) was lack of accuracy. Multi-delay ASL can not only provide CBF quantification but also provide arterial transit time (ATT). Unfortunately, the technique was scarcely applied to the diagnosis of AD. Here, we detected the utility of ASL with 1-delay and 7-delay in ten regions of interest (ROIs) to identify MCI and AD. Materials and Methods: Pseudocontinuous ASL (pCASL) MRI was acquired on a 3T GE scanner in adults from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) Study of AD cohort, including 26 normal cognition (NC), 37 MCI, and 39 AD. Receiver operating characteristic (ROC) analyses with 1-delay and 7-delay ASL were performed for the identification of MCI and AD. The DeLong test was used to compare ROC curves. Results: For CBF of 1-delay or 7-delay the AUCs showed moderate-high performance for the AD/NC and AD/MCI comparisons (AUC = 0.83∼0.96) (p < 0.001). CBF of 1-delay performed poorly in MCI/NC comparison (AUC = 0.69) (p < 0.001), but CBF of 7-delay fared well with an AUC of 0.79 (p < 0.001). The combination of CBF and ATT of 7-delay showed higher performance for AD/NC, AD/MCI, and MCI/NC comparisons with AUCs of 0.96, 0.89, and 0.89, respectively (p < 0.001). Furthermore, combination of CBF, ATT, sex, age, APOE ε4, and education improved further the accuracy (p < 0.001). In subgroups analyses, there were no significant differences in CBF of 7-delay ASL for identification of AD or MCI between age subgroups (p > 0.05). Conclusion: The combination of CBF and ATT with 7-delay ASL showed higher performance for identification of MCI than CBF of 1-delay, when adding to sex, age, APOE ε4 carrier status, and education years, the diagnostic performance was further increased, presenting a potential imaging biomarker in early AD.

9.
Phytochemistry ; : 113365, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35940425

RESUMO

Capsaicin widely exists in the Capsicum genus (e.g., hot peppers) and is commonly used as a food additive or medicinal material. In this work, microbial transformation of capsaicin was performed based on the three cultivated human intestinal fungi. Fourteen metabolites were obtained, and their chemical structures were elucidated by spectroscopic data analysis, including 13 compounds with undescribed structures. Hydroxylation, lactylation, succinylation, citric acylation, and acetylation were observed for these microbial metabolites derived from capsaicin, which indicated diverse catalytic characteristics of human intestinal fungi. In an in vitro bioassay, four metabolites and capsaicin inhibited the activity of lysine-specific demethylase 1 (LSD1) with a more than 70% inhibitory rate at 10 µM. In particular, 9,5'-dihydroxycapsaicin displayed the strongest inhibitory effect with an IC50 of 1.52 µM. Therefore, capsaicin analogs displayed potential application as LSD1 inhibitors against the invasion and migration of cancer cells.

10.
Int Urol Nephrol ; 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35941302

RESUMO

PURPOSE: Acute kidney injury (AKI) induced by renal ischaemia/reperfusion (I/R) during renal transplantation has been reported to be linked to the regulation of SIRT2, one of the members of SIRTUINS family. Current work is attempted to explore the influence and mechanism of SIRT7 in renal cell apoptosis controlled by miR-152-3p during renal I/R injury. METHODS: Three databases were used to select the miRNAs regulating the expression of SIRT7. Overexpression and inhibition of miR-152-3p and Luciferase assay were employed to certify the modulation of miR-152-3p to SIRT7 in cells. RT-qPCR assay was used to measure the mRNA levels. Western blot assay was employed to determine the expression of proteins. TUNEL assay and Flow Cytometry were conducted to analyze cell apoptosis. RESULTS: SIRT7 expression decreased in tissues of AKI patients and rats underwent renal I/R, which was associated with enhanced impairment of renal function. SIRT7 downregulation was attributed to the direct inhibition by miR-152-3p due to binding and inhibiting its seed sequence in 3'-UTR of SIRT7 mRNA. Consequently, the upregulation of miR-152-3p led to an inhibition of SIRT7 expression, an increase in expression of extrinsic apoptosis molecules containing FOXO3a, Bim, and caspase3, and apoptotic renal cells; while miR-152-3p inhibition abolished these phenotypes. CONCLUSION: SIRT7 downregulation by miR-152-3p is a leading cause of renal cell apoptosis and functional impairment induced by renal I/R. Inhibition of miR-152-3p to restore SIRT7 expression can be a promising strategy against renal I/R injury.

11.
Cell Biosci ; 12(1): 125, 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35941702

RESUMO

BACKGROUND: Alternative splicing (AS) of genes has been found to affect gene stability, and its abnormal regulation can lead to tumorigenesis. CELF2 is a vital splicing factor to participate in mRNA alternative splicing. Its downregulation has been confirmed to promote the occurrence and development of pancreatic cancer (PC). However, the regulatory role and mechanisms in PC has not been elucidated. RESULTS: CELF2 was downregulated in PC tissues, which affected tumor TNM stage and tumor size, and low expression of CELF2 indicated a poor prognosis of PC. In vivo and in vitro experiments showed that abnormal expression of CELF2 affected the stemness, apoptosis, and proliferation of PC cells. Furthmore, we also found that CELF2 was targeted by ALKBH5 for m6A modification, leading to CELF2 degradation by YTHDF2. Bioinformatic analysis of AS model based on the TCGA database indicated that CELF2 could target CD44 to form different spliceosomes, thereby affecting the biological behavior of PC cells. The conversion of CD44s to CD44V is the key to tumorigenesis. Transcriptomic analysis was conducted to reveal the mechanism of CELF2-mediated CD44 AS in PC. We found that CELF2-mediated splicing of CD44 led to changes in the level of endoplasmic reticulum stress, further regulating the endoplasmic reticulum-associated degradation (ERAD) signaling pathway, thereby affecting apoptosis and cell stemness. In addition, ERAD signaling pathway inhibitor, EerI, could effectively reverse the effect of CD44 on tumors. CONCLUSIONS: This study indicates that N6-methyladenosine-mediated CELF2 promotes AS of CD44, affecting the ERAD pathway and regulating the biological behavior of PC cells. CELF2 is expected to be a new target for targeted-drug development.

12.
Plast Reconstr Surg ; 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35943963

RESUMO

BACKGROUND: Complications including infection and wound dehiscence are major concerns for direct-to-implant (DTI) breast reconstruction. However, the risk factors associated with severe complications and implant salvage remain unclear. METHODS: Retrospective study of all patients undergoing unilateral DTI breast reconstruction from 2014 through 2019. The risk factors associated with complications and prosthesis explantation were identified using multivariate logistic regression modeling and interaction analyses. RESULTS: Among 1027 patients enrolled, 90 experienced severe complications, 41of which underwent prosthesis explantation, while 49 were successfully salvaged. Multivariate analysis demonstrated that patients with larger implant size (p=0.003), use of bovine mesh (p<0.001), adjuvant radiotherapy (p=0.047), low plasma albumin (p=0.013), and elevated blood glucose (p=0.006) were significantly more likely to suffer complications. Adjuvant radiation (OR: 7.44; 95%CI, 1.49-37.18; p = 0.014) and obesity (OR, 4.17; 95%CI, 1.17-14.88; p = 0.028) had significantly lower rates of implant salvage as well as surgical site infection (SSI) and wound dehiscence, while mastectomy skin flap necrosis was not associated with device explanation. There were no differences in complication and explantation rates between nipple-sparing and skin-sparing mastectomies. However, the combined impact of SSI and wound dehiscence added over fourteen-fold higher risk of prosthesis explantation (95%CI, 9.97-19.53). CONCLUSION: Success in direct-to-implant breast reconstruction is multifactorial. Larger implant size, adjuvant radiation therapy, diabetes, and malnutrition demonstrate increased risk of complications in the DTI approach. Surgical site infections and wound dehiscence should be treated aggressively, but the combination of both complications portends poor salvage rates.

13.
Biomater Adv ; 138: 212868, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35913250

RESUMO

The radical treatment of neurological impairments remains a major clinical challenge. Stem cells with high neural differentiation ability delivered by electroconductive hydrogel scaffolds have demonstrated promising applications in neural tissue regeneration. However, there are still challenges in designing bioactive scaffolds with good biocompatibility, appropriate electrical conductivity, and neurogenic niche. Herein, a three-dimensional (3D) electroconductive gelatin methacryloyl-multi-walled carbon nanotube/cobalt (GelMA-MWCNTs/Co) hydrogel scaffold was fabricated by incorporating MWCNTs/Co composites into a GelMA hydrogel matrix. The surface morphology, pore size, elastic modulus, swelling ratio, and conductivity of the hydrogels were measured. GelMA-MWCNTs/Co exhibited higher electrical conductivity than GelMA-MWCNTs. Live/dead and CCK8 assays demonstrated the good biocompatibility of the hydrogel for stem cells from apical papilla (SCAP) growth and differentiation. The cells encapsulated in the GelMA-MWCNTs and GelMA-MWCNTs/Co hydrogel scaffolds exhibited significant neuronal cell-like changes and a notable level of neuronal-specific marker expression after the electrical stimulation (ES) for 7 days, compared to that in the hydrogels without ES. Notably, the neurite spreading and Tuj1 fluorescent intensity of the SCAP in the electrically conductive GelMA-MWCNTs/Co hydrogel were more prominent compared to those of the other two groups. In addition, the 3D conductive hydrogel scaffolds advanced the neural differentiation of SCAP to an earlier time point. Considering these aspects, the novel electroconductive GelMA-MWCNTs/Co hydrogel synergized with ES greatly promotes SCAP neuronal differentiation.


Assuntos
Hidrogéis , Nanotubos de Carbono , Gelatina/farmacologia , Metacrilatos , Células-Tronco
14.
Front Plant Sci ; 13: 872054, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35909727

RESUMO

The use of alternative transcription start or termination sites (aTSS or aTTS) as well as alternative splicing (AS) produce diverse transcript isoforms, playing indispensable roles in the plant development and environmental adaptations. Despite the advances in the finding of the genome-wide alternatively spliced genes in strawberry, it remains unexplored how AS responds to the developmental cues and what relevance do these outcomes have to the gene function. In this study, we have systematically investigated the transcriptome complexity using long-read Oxford Nanopore Technologies along the four successive developmental stages. The full-length cDNA sequencing results unraveled thousands of previously unexplored transcript isoforms raised from aTSS, aTTS, and AS. The relative contributions of these three processes to the complexity of strawberry fruit transcripts were compared. The aTSS and aTTS were more abundant than the AS. Differentially expressed transcripts unraveled the key transitional role of the white fruit stage. Isoform switches of transcripts from 757 genes were observed. They were associated with protein-coding potential change and domain gain or loss as the main consequences. Those genes with switched isoforms take part in the key processes of maturation in the late stages. A case study using yeast two hybrid analysis supported the functional divergence of the two isoforms of the B-box protein 22. Our results provided a new comprehensive overview of the dynamic transcriptomic landscape during strawberry fruit development and maturation.

15.
Front Plant Sci ; 13: 860742, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35909741

RESUMO

Aquaporins (AQPs) constitute a highly diverse family of channel proteins that transport water and neutral solutes. AQPs play crucial roles in plant development and stress responses. However, the characterization and biological functions of RsAQPs in radish (Raphanus sativus L.) remain elusive. In this study, 61 non-redundant members of AQP-encoding genes were identified from the radish genome database and located on nine chromosomes. Radish AQPs (RsAQPs) were divided into four subfamilies, including 21 plasma membrane intrinsic proteins (PIPs), 19 tonoplast intrinsic proteins (TIPs), 16 NOD-like intrinsic proteins (NIPs), and 5 small basic intrinsic proteins (SIPs), through phylogenetic analysis. All RsAQPs contained highly conserved motifs (motifs 1 and 4) and transmembrane regions, indicating the potential transmembrane transport function of RsAQPs. Tissue- and stage-specific expression patterns of AQP gene analysis based on RNA-seq data revealed that the expression levels of PIPs were generally higher than TIPs, NIPs, and SIPs in radish. In addition, quantitative real-time polymerase chain reaction (qRT-PCR) revealed that seven selected RsPIPs, according to our previous transcriptome data (e.g., RsPIP1-3, 1-6, 2-1, 2-6, 2-10, 2-13, and 2-14), exhibited significant upregulation in roots of salt-tolerant radish genotype. In particular, the transcriptional levels of RsPIP2-6 dramatically increased after 6 h of 150 mM NaCl treatment during the taproot thickening stage. Additionally, overexpression of RsPIP2-6 could enhance salt tolerance by Agrobacterium rhizogenes-mediated transgenic radish hairy roots, which exhibited the mitigatory effects of plant growth reduction, leaf relative water content (RWC) reduction and alleviation of O2- in cells, as shown by nitro blue tetrazolium (NBT) staining, under salt stress. These findings are helpful for deeply dissecting the biological function of RsAQPs on the salt stress response, facilitating practical application and genetic improvement of abiotic stress resistance in radish.

16.
Front Pharmacol ; 13: 801337, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910360

RESUMO

Acute respiratory distress syndrome (ARDS), a devastating complication of numerous conditions, is often associated with high mortality. It is well known that endothelial cell (EC) damage and inflammation are vital processes in the pathogenesis of ARDS. Nevertheless, the mechanisms of EC damage are largely unknown. In the present study, we investigated the role of pyroptosis in the initiation of ARDS and demonstrated that endothelial pyroptosis might play a pivotal role in the pathophysiology of ARDS. Metformin, an antidiabetic drug, exhibited a protective effect in lipopolysaccharide (LPS)-induced lung injury, and we hypothesized that metformin alleviated LPS-induced lung injury via inhibiting ECs pyroptosis. In vivo, male ICR mice were intratracheally injected with LPS, and metformin was previously administered intraperitoneally. Morphological properties of lung tissues were detected. We showed that metformin inhibited NLRP3 inflammasome activation and NLRP3-stimulated pyroptosis induction, as shown by decreased levels of cleaved caspase-1, N-terminal fragment of GSDMD, and protein contents of IL-1ß in lung tissues of mice exposed to LPS. LPS-induced expression of vascular adhesion molecules was also reduced after the treatment with metformin. In vitro, exposure of pulmonary ECs to LPS resulted in increased expression of NLRP3 and pyroptosis-associated indicators. By inhibiting the expression of NLRP3 with NLRP3 inhibitor MCC950, pyroptosis-related markers and vascular adhesion molecules were ameliorated. Moreover, metformin treatment significantly inhibited the NF-κB signaling pathway and increased the expression of sirtuin 1 (SIRT1) both in LPS-stimulated lung tissues and pulmonary ECs. Administration of the selective SIRT1 inhibitor nicotinamide significantly reversed the protective effect of metformin against endothelial pyroptosis and lung injury in LPS-treated ECs and LPS-induced acute lung injury (ALI). Thus, these findings demonstrated that metformin alleviated LPS-induced ALI by inhibiting NF-κB-NLRP3-mediated ECs pyroptosis, possibly by upregulating the expression of SIRT1.

17.
Front Microbiol ; 13: 927139, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910660

RESUMO

To successfully survive and reproduce, all species constantly modify the structure and expression of their genomes to cope with changing environmental conditions including ultraviolet (UV) radiation. Thus, knowledge of species adaptation to environmental changes is a central theme of evolutionary studies which could have important implication for disease management and social-ecological sustainability in the future but is generally insufficient. Here, we investigated the evolution of UV adaptation in organisms by population genetic analysis of sequence structure, physiochemistry, transcription, and fitness variation in the radiation-sensitive 4 (RAD4) gene of the Irish potato famine pathogen Phytophthora infestans sampled from various altitudes. We found that RAD4 is a key gene determining the resistance of the pathogen to UV stress as indicated by strong phenotype-genotype-geography associations and upregulated transcription after UV exposure. We also found conserved evolution in the RAD4 gene. Only five nucleotide haplotypes corresponding to three protein isoforms generated by point mutations were detected in the 140 sequences analyzed and the mutations were constrained to the N-terminal domain of the protein. Physiochemical changes associated with non-synonymous mutations generate severe fitness penalty to mutants, which are purged out by natural selection, leading to the conserved evolution observed in the gene.

18.
Front Psychol ; 13: 865877, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911016

RESUMO

Professionalism and popularity are two important external identity cues of the review party. Previous studies have mostly focused on the content of the reviewers' comments. However, few studies have explored the potential impact of the review party's cues on consumers' adoption willingness and consumption behavior. This study mainly examined the neural mechanisms of how the differences in the two identity cues of the review party affect consumers while adopting the comments. The current study employed an event-related potential (ERP) experiment, in which the participants were asked to make a personal choice quickly based on the review party's identity cues after seeing the target product. A 2-level professionalism (low vs. high) x 2-level popularity (low vs. high) experiment design was used to test the impact of the review party's professionalism and popularity on consumers' intentions to adopt the review. The behavioral data reveal that the two identity cues of the review party impact the adoption rate, and the review party's popularity has an impact on the reaction time. The ERP data indicate that the review party's popularity affects the perceived risk (the N2 component, which is a high-risk signal) and the two identity cues of the review party affect the evaluation and classification process [the later positive potential (LPP) component]. These results indicate that when the review party has a high degree of professionalism, its popularity has less influence on consumers' review adoption intention. On the contrary, when the level of professionalism is low, high popularity will promote consumers' review adoption intention. Compared to professionalism, popularity is a higher risk cue for consumers.

19.
Open J Stat ; 12(1)2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911620

RESUMO

Generalized Linear Mixed Model (GLMM) has been widely used in small area estimation for health indicators. Bayesian estimation is usually used to construct statistical intervals, however, its computational intensity is a big challenge for large complex surveys. Frequentist approaches, such as bootstrapping, and Monte Carlo (MC) simulation, are also applied but not evaluated in terms of the interval magnitude, width, and the computational time consumed. The 2013 Florida Behavioral Risk Factor Surveillance System data was used as a case study. County-level estimated prevalence of three health-related outcomes was obtained through a GLMM; and their 95% confidence intervals (CIs) were generated from bootstrapping and MC simulation. The intervals were compared to 95% credential intervals through a hierarchial Bayesian model. The results showed that 95% CIs for county-level estimates of each outcome by using MC simulation were similar to the 95% credible intervals generated by Bayesian estimation and were the most computationally efficient. It could be a viable option for constructing statistical intervals for small area estimation in public health practice.

20.
Nature ; 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35914677

RESUMO

Digital logic circuits are based on complementary pairs of n- and p-type field effect transistors (FETs) via complementary metal oxide semiconductor (CMOS) technology. In three dimensional (3D or bulk) semiconductors, substitutional doping of acceptor or donor impurities is used to achieve p- and n-type FETs. However, the controllable p-type doping of low-dimensional semiconductors such as two-dimensional transition metal dichalcogenides (2D TMDs) has proved to be challenging. Although it is possible to achieve high quality, low resistance n-type van der Waals (vdW) contacts on 2D TMDs1-5, obtaining p-type devices from evaporating high work function metals onto 2D TMDs has not been realised so far. Here we report high-performance p-type devices on single and few-layered molybdenum disulphide (MoS2) and tungsten diselenide (WSe2) based on industry-compatible electron beam evaporation of high work function metals such as Pd and Pt. Using atomic resolution imaging and spectroscopy, we demonstrate near ideal vdW interfaces without chemical interactions between the 2D TMDs and 3D metals. Electronic transport measurements reveal that the Fermi level is unpinned and p-type FETs based on vdW contacts exhibit low contact resistance of 3.3 kΩ·µm, high mobility values of ~ 190 cm2-V-1s-1 at room temperature with saturation currents in excess of > 10-5 Amperes per micron (A-µm-1) and on/off ratio of 107. We also demonstrate an ultra-thin photovoltaic cell based on n- and p-type vdW contacts with an open circuit voltage of 0.6 V and power conversion efficiency of 0.82%.

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