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1.
Chin Med J (Engl) ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34483253

RESUMO

BACKGROUND: A deep learning model (DLM) that enables non-invasive hypokalemia screening from an electrocardiogram (ECG) may improve the detection of this life-threatening condition. This study aimed to develop and evaluate the performance of a DLM for the detection of hypokalemia from the ECGs of emergency patients. METHODS: We used a total of 9908 ECG data from emergency patients who were admitted at the Second Affiliated Hospital of Nanchang University, Jiangxi, China, from September 2017 to October 2020. The DLM was trained using 12 ECG leads (lead I, II, III, aVR, aVL, aVF, and V1-6) to detect patients with serum potassium concentrations <3.5 mmol/L and was validated using retrospective data from the Jiangling branch of the Second Affiliated Hospital of Nanchang University. The blood draw was completed within 10 min before and after the ECG examination, and there was no new or ongoing infusion during this period. RESULTS: We used 6904 ECGs and 1726 ECGs as development and internal validation data sets, respectively. In addition, 1278 ECGs from the Jiangling branch of the Second Affiliated Hospital of Nanchang University were used as external validation data sets. Using 12 ECG leads (leads I, II, III, aVR, aVL, aVF, and V1-6), the area under the receiver operating characteristic curve (AUC) of the DLM was 0.80 (95% confidence interval [CI]: 0.77-0.82) for the internal validation data set. Using an optimal operating point yielded a sensitivity of 71.4% and a specificity of 77.1%. Using the same 12 ECG leads, the external validation data set resulted in an AUC for the DLM of 0.77 (95% CI: 0.75-0.79). Using an optimal operating point yielded a sensitivity of 70.0% and a specificity of 69.1%. CONCLUSIONS: In this study, using 12 ECG leads, a DLM detected hypokalemia in emergency patients with an AUC of 0.77 to 0.80. Artificial intelligence could be used to analyze an ECG to quickly screen for hypokalemia.

2.
PLoS One ; 16(9): e0256922, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34469486

RESUMO

The democratization of AI tools for content generation, combined with unrestricted access to mass media for all (e.g. through microblogging and social media), makes it increasingly hard for people to distinguish fact from fiction. This raises the question of how individual opinions evolve in such a networked environment without grounding in a known reality. The dominant approach to studying this problem uses simple models from the social sciences on how individuals change their opinions when exposed to their social neighborhood, and applies them on large social networks. We propose a novel model that incorporates two known social phenomena: (i) Biased Assimilation: the tendency of individuals to adopt other opinions if they are similar to their own; (ii) Backfire Effect: the fact that an opposite opinion may further entrench people in their stances, making their opinions more extreme instead of moderating them. To the best of our knowledge, this is the first DeGroot-type opinion formation model that captures the Backfire Effect. A thorough theoretical and empirical analysis of the proposed model reveals intuitive conditions for polarization and consensus to exist, as well as the properties of the resulting opinions.

3.
Mediators Inflamm ; 2021: 5573594, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34531703

RESUMO

Background: Abnormal endometrial repair after injury results in the formation of intrauterine adhesions (IUA) and a thin endometrium, which are key causes for implantation failure and infertility. Stem cell transplantation offers a potential alternative for some cases of severe Asherman's syndrome that cannot be treated with surgery or hormonal therapy. Umbilical cord-derived mesenchymal stem cells (UCMSCs) have been reported to repair the damaged endometrium. However, there is no report on the effects of UCMSCs previously seeded on human acellular amniotic matrix (AAM) on endometrial injury. Methods: Absolute ethanol was injected into rat uteri to damage the endometrium. UCMSCs previously seeded on AAM were surgically transplanted. Using a variety of methods, the treatment response was assessed by endometrial thickness, endometrial biomarker expression, endometrial receptivity, cell proliferation, and inflammatory factors. Results: Endometrial thickness was markedly improved after UCMSC-AAM transplantation. The expression of endometrial biomarkers, namely, vimentin, cytokeratin, and integrin ß3, in treated rats increased compared with untreated rats. In the UCMSC-AAM group, the VEGF expression decreased, whereas that of MMP9 increased compared with the injury group. Moreover, in the AAM group, the MMP9 expression increased. The expression of proinflammatory factors (IL-2, TNFα, and IFN-γ) in the UCMSC-AAM group decreased compared with the untreated group, whereas the expression of anti-inflammatory factors (IL-4, IL-10) increased significantly. Conclusions: UCMSC transplantation using AAM as the carrier can be applied to treat endometrial injury in rats. The successful preparation of lyophilized AAM provides the possibility of secondary infectious disease screening and amniotic matrix quality detection, followed by retrospective analysis. The UCMSC-AAM complex may promote the better application of UCMSCs on the treatment of injured endometrium.

4.
Aging (Albany NY) ; 13(undefined)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34534105

RESUMO

BACKGROUND: Hepatitis B virus (HBV) variants in the preS region have been associated with hepatocellular carcinoma (HCC). However, the effect of the preS variants on HCC prognosis remains largely unknown. We aimed to identify the preS variants that reliably predict postoperative prognosis in HCC. METHODS: RNA-seq data of 203 HCC patients retrieved from public database were screened for the preS variants related to HCC prognosis. The variants in the sera and tumors were then validated in our prospective cohort enrolling 103 HBV-associated HCC patients. RESULTS: By analyzing prognosis-related gene sets in the RNA-seq data, 12 HBV preS variants were associated with HCC recurrence. Of those, G40C and C147T in the sera predicted an unfavorable recurrence-free survival in our cohort (hazard ratio [HR]=2.18, 95% confidence interval [CI]=1.37-3.47, p=0.001 for G40C; HR=1.84, 95% CI=1.15-2.92, p=0.012 for C147T). G40C and C147T were significantly associated with microscopic vascular invasion, larger tumor size, and abnormal liver function. Multivariate Cox regression analysis showed that G40C significantly increased the risk of HCC recurrence in patients with postoperative antiviral treatment. The HCC prognosis-prediction model consisting of α-fetoprotein and G40C in the sera achieved the best performance (sensitivity=0.80, specificity=0.70, and area under the curve=0.79). Functional analysis indicated that these two variants were associated with cell proliferation, chromosome instability, carcinogenesis, metastasis, and anticancer drug resistance. CONCLUSIONS: G40C and C147T are serological biomarkers for HCC prognosis and the prognostic model consisting of serological α-fetoprotein and G40C achieved the best performance in predicting postoperative prognosis.

5.
Chemosphere ; 287(Pt 2): 132172, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34509006

RESUMO

The increasing presence of microplastics in marine environment is a critical issue and the plastic-metal contamination has received much attention. However, conventional methods for heavy metal determination are time-consuming, need sample pretreatments, require a strict operation environment, or have high limits of detection. In this study, heavy metals contaminated microplastics samples collected from a remote coral island were quantified and analyzed by using Laser-Induced Breakdown Spectroscopy (LIBS). The characters of the trace metals in microplastics were used to determine the sources of the contaminants, and the potential origins of the metals were demonstrated from the statistical analysis. LIBS is a facile and non-destructive trace analysis technique and the strategy led to rapid and multi-metals detection of individual samples. Heavy metals such as copper (Cu), lead (Pb), iron (Fe), cadmium (Cd), zinc (Zn), manganese (Mn), chromium (Cr) were detected and quantified in the individual microplastics samples. The findings showed that LIBS is a promising strategy for the characterization of microplastics and for the analysis of the source of heavy metals contaminants present in the microplastics particles.

6.
J Pharmacol Exp Ther ; 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465632

RESUMO

Acute respiratory distress syndrome (ARDS), a common and fatal clinical condition, is characterized by the destruction of epithelium and augmented permeability of the alveolar-capillary barrier. Resolvin conjugates in tissue regeneration (RCTR1) is an endogenous lipid mediator derived from DHA, exerting pro-resolution effects in the process of inflammation. In our research, we evaluated the role of RCTR1 in alveolar fluid clearance (AFC) in Lipopolysaccharide-induced ARDS/ALI rat model. Rats were injected with RCTR1 (5 µg/kg) via caudal veins 8h after LPS (14 mg/kg) treatment, then AFC was estimated after 1h of ventilation. Primary type II alveolar epithelial cells (AEC II) were incubated with LPS (1 ug/ml) with or without RCTR1 (10 nM) for 8 h. Our results showed that RCTR1 significantly enhanced the survival rate, promoted the AFC, and alleviated LPS-induced ARDS/ALI in vivo. Furthermore, RCTR1 remarkably elevated the protein expression of sodium channels and Na, K-ATPase, and the activity of Na, K-ATPase in vivo and in vitro. Additionally, RCTR1 also decreased Nedd4-2 level via up-regulating P-Akt expression. Besides, inhibitors of ALX, cAMP, and PI3K (BOC-2, KH-7, and LY294002) notably inhibited the effects of RCTR1 on AFC. In summary, RCTR1 enhances the protein levels of sodium channels and Na, K-ATPase, and the Na, K-ATPase activity to improve AFC in ALI through ALX/cAMP/PI3K/Nedd4-2 pathway, suggesting that RCTR1 may become a therapeutic drug for ARDS/ALI. Significance Statement 1.RCTR1, an endogenous lipid mediator, enhanced the rate of AFC to accelerate the resolution of inflammation in the LPS-induced murine lung injury model. 2. RCTR1 up-regulates the expression of ENaC and Na, K-ATPase in vivo and in vitro to accelerate the AFC. 3. The efficacy of RCTR1 on the ENaC and Na, K-ATPase level was in an ALX/cAMP/PI3K/Nedd4-2-dependent.

7.
Cancer Med ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34472719

RESUMO

BACKGROUND: Anthracycline-based chemotherapy (ABC) is one of the standard therapies against breast cancer. However, few guidelines are currently available to optimize the use of ABC. Therefore, the present analysis aimed at determining the profile and treatment patterns of ABC and the association of clinicopathological characteristics with ABC selection. METHODS: We retrospectively analyzed the data of a nation-wide multicenter epidemiological study, which collected the medical records of breast cancer patients receiving chemotherapy in different settings from seven geographic regions in China (NCT03047889). RESULTS: In total, 3393 patients were included, with 2917 treated with ABC. Among them, 553 (89.8%), 2165 (81.7%), and 814 (25.7%) were subjected to ABC as neoadjuvant, adjuvant, and advanced chemotherapy, respectively. The most frequently used regimens were anthracycline-taxane-based combinations for neo- and adjuvant chemotherapy, along with taxanes and oral fluorouracils for the palliative stages. In the overall cohort, patients aged < 40 or 40-65 (p < 0.001), in premenopause (p < 0.001), without comorbidities (p = 0.016), with invasive ductal carcinoma (p= 0.001), high lymph node involvement (p < 0.001), in the pTNM stage II, III, or IV versus stage I (p < 0.001), subjected to mastectomy (p < 0.001) or subjected to sentinel lymph node biopsy combined with axillary lymph node dissection (p = 0.044), or with a decreased disease-free survival (p < 0.001) were more likely to be recommended to ABC. CONCLUSION: Taken together, ABC remained the mainstay of breast cancer treatment, especially in neo and adjuvant therapy. ABC was mainly used as a combination therapy, and the correlation between influencing factors and ABC choice varied during different settings, indicating the preference and different perspectives of medication considered by medical oncologists regarding the use ABC in China.

8.
Genome Med ; 13(1): 146, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493320

RESUMO

BACKGROUND: Epstein-Barr virus (EBV)-associated gastric carcinomas (EBVaGCs) present unique molecular signatures, but the tumorigenesis of EBVaGCs and the role EBV plays during this process remain poorly understood. METHODS: We applied whole-exome sequencing, EBV genome sequencing, and whole-genome bisulfite sequencing to multiple samples (n = 123) derived from the same patients (n = 25), which covered saliva samples and different histological stages from morphologically normal epithelial tissues to dysplasia and EBVaGCs. We compared the genomic landscape between EBVaGCs and their precursor lesions and traced the clonal evolution for each patient. We also analyzed genome sequences of EBV from samples of different histological types. Finally, the key molecular events promoting the tumor evolution were demonstrated by MTT, IC50, and colony formation assay in vitro experiments and in vivo xenograft experiments. RESULTS: Our analysis revealed increasing mutational burden and EBV load from normal tissues and low-grade dysplasia (LD) to high-grade dysplasia (HD) and EBVaGCs, and oncogenic amplifications occurred late in EBVaGCs. Interestingly, within each patient, EBVaGCs and HDs were monoclonal and harbored single-strain-originated EBV, but saliva or normal tissues/LDs had different EBV strains from that in EBVaGCs. Compared with precursor lesions, tumor cells showed incremental methylation in promotor regions, whereas EBV presented consistent hypermethylation. Dominant alterations targeting the PI3K-Akt and Wnt pathways were found in EBV-infected cells. The combinational inhibition of these two pathways in EBV-positive tumor cells confirmed their synergistic function. CONCLUSIONS: We portrayed the (epi) genomic evolution process of EBVaGCs, revealed the extensive genomic diversity of EBV between tumors and normal tissue sites, and demonstrated the synergistic activation of the PI3K and Wnt pathways in EBVaGCs, offering a new potential treatment strategy for this disease.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34503922

RESUMO

BACKGROUND: To explore the development of central nervous system (CNS) symptoms and clinical application in predicting the clinical outcomes of SARS-COV-2 patients. METHODS: A retrospective cohort study was performed on the hospitalized patients with SARS-COV-2 recruited from four hospitals in Hubei Province, China from 18 January to 10 March 2020. The patients with CNS symptoms were determined. Data regarding clinical symptoms and laboratory tests were collected from medical records. RESULTS: Of 1268 patients studied, 162 (12.8%) had CNS symptoms, manifested as unconsciousness (71, 5.6%), coma (69, 5.4%), dysphoria (50, 3.9%), somnolence (34, 2.7%) and convulsion (3, 0.2%), which were observed at median of 14 (interquartile range 9-18) days after symptom onset and significantly associated with older age (OR = 5.71, 95% confidence interval [CI] 2.78-11.73), male (OR = 1.73, 95% CI 1.22-2.47) and preexisting hypertension (OR = 1.78, 95% CI 1.23-2.57). The presence of CNS symptoms could be predicted by abnormal laboratory tests across various clinical stages, including by lymphocyte counts of <0.93 × 109/L, LDH≥435 U/L and IL-6≥28.83 pg/L at 0-10 days post disease; by lymphocyte count<0.86 × 109/L, IL-2R ≥ 949 U/L, LDH≥382 U/L and WBC≥8.06 × 109/L at 11-20 days post disease. More patients with CNS symptoms developed fatal outcome compared with patients without CNS symptoms (HR = 33.96, 95% CI 20.87-55.16). CONCLUSION: Neurological symptoms of COVID-19 were related to increased odds of developing poor prognosis and even fatal infection.

10.
Mol Cancer Ther ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518296

RESUMO

A hallmark of pancreatic ductal adenocarcinoma (PDAC) is the presence of a dense, desmoplastic stroma and the consequent altered interactions between cancer cells and their surrounding tumor microenvironment (TME) that promote disease progression, metastasis, and chemoresistance. We have previously shown that IL-6 secreted from pancreatic stellate cells (PSCs) stimulates the activation of STAT3 signaling in tumor cells, an established mechanism of therapeutic resistance in PDAC. We have now identified the tumor cell-derived cytokine interleukin-1α (IL-1α) as an upstream mediator of IL-6 release from PSCs that is involved in STAT3 activation within the TME. Herein, we show that IL-1α is overexpressed in both murine and human PDAC tumors and engages with its cognate receptor IL-1R1 which is strongly expressed on stromal cells. Further, we show that IL-1R1 inhibition using anakinra (recombinant IL-1 receptor antagonist) significantly reduces stromal-derived IL-6, thereby suppressing IL-6-dependent STAT3 activation in human PDAC cell lines. Anakinra treatment results in significant reduction in IL-6 and activated STAT3 levels in pancreatic tumors from Ptf1aCre/+;LSL-KrasG12D/+; Tgfbr2flox/flox (PKT) mice. Additionally, the combination of anakinra with cytotoxic chemotherapy significantly extends overall survival compared with vehicle treatment or anakinra monotherapy in this aggressive genetic mouse model of PDAC. These data highlight the importance of IL-1 in mediating tumor-stromal IL-6/STAT3 crosstalk in the TME and provide preclinical rationale for targeting IL-1 signaling as a therapeutic strategy in PDAC.

11.
Eur J Endocrinol ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34519671

RESUMO

BACKGROUND: Obesity is associated with impaired immune function and chronic low-grade inflammation. Metabolic surgery is one of the most effective therapies for treating obesity and related metabolic disorders. We aimed to explore the pathophysiological roles of peripheral DCs and T lymphocytes in metabolic surgery. METHOD: In this observational cohort study, a total of 106 individuals, including obese participants with or without T2DM, overweight subjects and normal controls, were recruited. All obese participants underwent laparoscopic sleeve gastrectomy surgery and returned for evaluation of the clinical indicators after surgery. We evaluated the frequencies of circulating DCs subsets (mDCs and pDCs), the pro-inflammatory (Th1 and Th17) and antiinflammatory (Th2 and Treg) T cell subsets by flow cytometry. RESULTS: Compared with the normal controls, the frequencies of mDCs, Th1 and Th17 cells increased, while Treg and Th2 cells decreased in the obese participants. The frequency of mDCs and Th1 cells consistently declined after surgery compared with baseline in the obese patients and were restored to the levels observed in the normal controls after surgery. Moreover, the frequency of Treg cells was increased at 6 months after surgery in the obese patients with T2DM, and Th17 cells declined at 6 months after surgery in the severely obese patients without T2DM. CONCLUSION: This study indicates that metabolic surgery can effectively improve imbalanced immune cells in peripheral blood and restore the proportion of immune cells to a normal range during a 12-month follow-up.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34520665

RESUMO

Active targeted therapy for bowel cancer using untethered microrobots has attracted extensive attention. However, traditional microrobots face challenges, such as issues of mobility, biocompatibility, drug loading, sustained-release capabilities, and targeting accuracy. Here, we propose an untethered triple-configurational magnetic robot (TCMR) that is composed of three geometrically nested parts: actuation and guarding, anchoring and seeding, and drug release part. A targeting magnetic driving system actuates the TCMR along the predetermined trajectory to the target position. The pH-sensitive actuation and guarding part formed by electrodeposition is degraded in the intestinal environment and separates from the two other parts. A majority of magnetic nanoparticles encapsulated in this part are retrieved. The anchoring and seeding part anchors the lesion area and seeds the drug release part in the gaps of intestinal villi by hydrolysis. Ultimately, the drug release part containing the therapeutic completes the sustained release to prolong the duration of the therapeutic agent. Cytotoxicity and therapeutic tests reveal that TCMRs are biocompatible and suitable for targeted therapy and have good therapeutic performance. The newly designed TCMR will provide new ideas for targeted therapy, thus expanding the application scope of robotics technology in the biomedical field.

13.
J Fluoresc ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34524573

RESUMO

A chemical sensor that can induce near-infrared red-shifted response represents a promising strategy for the design and development of anion probes. In this work, novel CH-controlled colorimetric probe 3 based on anthracene carboximide was developed for near-infrared detection of cyanide. Probe 3 consisted of CHCN binding site to anthracene carboximide fluorophore, and showed a significant visual change from yellow-green (535 nm) to deep violet (825 nm) with a larger redshift (≈ 290 nm) and fluorescence quenching at 480 nm and 520 nm upon interacting with cyanide. Job curves determined 1:1 binding stoichiometry of probe 3 with cyanide. Additonally, probe 3 detected cyanide ion conveniently in aqueous solution and could be reused after trifluoroacetic acid treatment. Colorimetric test paper was used to detect cyanide in aqueous solutions. The C-H deprotonation sensing mechanism was confirmed by 1H NMR titration. The near-infrared detection of cyanide by CH-controlled probes was founded for the first time.

14.
Environ Pollut ; 290: 118008, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34479157

RESUMO

Individuals with metabolic disorders exhibit enhanced susceptibility to the cardiovascular health effects of particulate air pollution, but the underlying mechanisms are not yet understood. We aim to assess whether changes in proinflammatory lipid signals are associated with fine particulate matter (PM2.5) exposure in individuals with and without prediabetes. A longitudinal panel study was conducted in Beijing, China, and included 120 participants followed up over 589 clinical visits from August 2013 to February 2015. We measured 12 lipids derived from arachidonic acid pathways in blood samples of the participants via targeted lipidomic analyses. Ambient PM2.5 concentrations were continuously monitored at a station for associations with the lipids. Among the 120 participants, 110 (mean [SD] age at recruitment, 56.5 [4.2] years; 31 prediabetics) who visited the clinic at least twice over the follow-up period were assigned exposure values of the outdoor residential PM2.5 concentrations during the 1-14 days preceding each clinical visit. With an interquartile range increase in the 1-day-lag PM2.5 exposure (64.0 µg/m3), the prediabetic group had consistently greater increases in the concentration of arachidonate metabolites derived from the cytochrome P450 (CYP450) pathway (5,6-DHET, 15.8% [95% CI, 3.5-29.7%]; 8,9-DHET, 9.7% [95% CI, 0.6-19.6%]; 11,12-DHET, 8.3% [95% CI, 1.9-15.1%]; 14,15-DHET, 7.4% [95% CI, 0.9-14.4%]; and 20-HETE, 8.9% [95% CI, 1.0-17.5%]), compared with the healthy group. Among CYP450-derived lipids, 14,15-DHET and 20-HETE significantly mediated 8% and 8% of the PM2.5-associated increase in white blood cells, 10% and 13% of that in neutrophils, and 20% and 23% of that in monocytes, respectively, in the prediabetic group. In conclusion, proinflammatory lipid signals from CYP450 pathways triggered the health effects of particulate air pollution in individuals with prediabetes, suggesting that targeting lipid metabolism has therapeutic potential to attenuate or prevent the cardiovascular effects of air pollution in susceptible populations.

15.
Sens Actuators B Chem ; : 130706, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34493903

RESUMO

The lateral flow immunoassay (LFIA) has played a crucial role in early diagnosis during the current COVID-19 pandemic owing to its simplicity, speed and affordability for coronavirus antibody detection. However, the sensitivity of the commercially available LFIAs needs to be improved to better prevent the spread of the infection. Here, we developed an ultra-sensitive surface-enhanced Raman scattering-based lateral flow immunoassay (SERS-based LFIA) strip for simultaneous detection of anti-SARS-CoV-2 IgM and IgG by using gap-enhanced Raman nanotags (GERTs). The GERTs with a 1 nm gap between the core and shell were used to produce the "hot spots", which provided about 30-fold enhancement as compared to conventional nanotags. The COVID-19 recombinant antigens were conjugated on GERTs surfaces and replaced the traditional colloidal gold for the Raman sensitive detection of human IgM and IgG. The LODs of IgM and IgG were found to be 1 ng/mL and 0.1 ng/mL (about 100 times decrease was observed as compared to commercially available LFIA strips), respectively. Moreover, under the condition of common nano-surface antigen, precise SERS signals proved the unreliability of quantitation because of the interference effect of IgM on IgG.

16.
PLoS Pathog ; 17(9): e1009930, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496007

RESUMO

Fatty acid-derived acyl chains of phospholipids and lipoproteins are central to bacterial membrane fluidity and lipoprotein function. Though it can incorporate exogenous unsaturated fatty acids (UFA), Staphylococcus aureus synthesizes branched chain fatty acids (BCFA), not UFA, to modulate or increase membrane fluidity. However, both endogenous BCFA and exogenous UFA can be attached to bacterial lipoproteins. Furthermore, S. aureus membrane lipid content varies based upon the amount of exogenous lipid in the environment. Thus far, the relevance of acyl chain diversity within the S. aureus cell envelope is limited to the observation that attachment of UFA to lipoproteins enhances cytokine secretion by cell lines in a TLR2-dependent manner. Here, we leveraged a BCFA auxotroph of S. aureus and determined that driving UFA incorporation disrupted infection dynamics and increased cytokine production in the liver during systemic infection of mice. In contrast, infection of TLR2-deficient mice restored inflammatory cytokines and bacterial burden to wildtype levels, linking the shift in acyl chain composition toward UFA to detrimental immune activation in vivo. In in vitro studies, bacterial lipoproteins isolated from UFA-supplemented cultures were resistant to lipase-mediated ester hydrolysis and exhibited heightened TLR2-dependent innate cell activation, whereas lipoproteins with BCFA esters were completely inactivated after lipase treatment. These results suggest that de novo synthesis of BCFA reduces lipoprotein-mediated TLR2 activation and improves lipase-mediated hydrolysis making it an important determinant of innate immunity. Overall, this study highlights the potential relevance of cell envelope acyl chain repertoire in infection dynamics of bacterial pathogens.

17.
Cancer Lett ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34480971

RESUMO

Endometrial cancer represents one of the most common gynecological tumors in the world. Advanced and relapsed patients rely on drug therapy. Therefore, it is extremely important to seek more effective targeted drugs. This study found that esculetin has an anti-tumor effect on endometrial cancer through cellular proliferation and apoptosis. At the same time, its anti-tumor effect has also been verified in human endometrial cancer xenograft models in nude mice. Western blot results showed that BCLXL, XIAP, and pAKT protein expression level were down-regulated. A pulldown experiment and LC-MS/MS analysis technology revealed that esculetin targets the hnRNPA1 protein. Cellular proliferation experiments following si-hnRNPA1 transfection verified the tumor-promoting effect of hnRNPA1 in endometrial cancer cells. Nuclear and cytoplasmic separation experiment demonstrated esculetin affecting the export of the hnRNPA1/mRNA complex from the nucleus into the cytoplasm. Thus, esculetin targets hnRNPA1, thereby downregulates BCLXL and XIAP mRNA transcription and translation, resulting in apoptosis and an arrest in proliferation.

18.
Artigo em Inglês | MEDLINE | ID: mdl-34482459

RESUMO

Uniformly dispersed Pd nanoparticles on certain supports exhibit exceptional catalytic performance toward various environmental applications. In this work, ultrafine Pd nanoparticles anchored on CeO2 nanorods were synthesized via an absorption-in situ reduction method. The activity of the CeO2/Pd nanocomposites was systematically investigated toward reduction of 4-nitrophenol (4-NP) and organic dyes including methyl blue, rhodamine B, methyl orange, and Congo red. The results indicated that the CeO2/Pd nanocomposites with different weight ratios of Pd nanoparticles (10.23 wt%, 11.01 wt%, and 14.27 wt%) can almost completely reduce 4-NP with a rate constant of 3.31×10-1, 3.22×10-1, and 2.23×10-1 min-1. Besides, the 10.23 wt% CeO2/Pd nanocomposites exhibit remarkable enhanced catalytic activity toward reduction of organic dyes. The catalysts display ideal stability after being used for three times for the reduction of 4-NP. We believe that our strategy demonstrated here offers insights into the design and fabrication of novel Pd-based nanocomposites for various heterogeneous catalysis applications.

19.
Clin Ther ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34482960

RESUMO

PURPOSE: Gastric emptying time is one of limiting factors that determines the pharmacokinetic properties of drugs administered by mouth. Despite the high prevalence of obesity worldwide, modifications in gastric emptying time have not been systematically addressed in this set of patients. The current analysis aims to quantitatively address obesity-related changes in gastric emptying time of solids, semisolids, and liquids compared with lean individuals, highlighting the relevant pharmacokinetic implications of oral drug absorption in patients with obesity. METHODS: We searched the Cochrane Library, PubMed, Web of Science, and Embase for all relevant articles published until November 1, 2020. Differences in gastrointestinal variables in relation to gastric emptying between obese and lean individuals were quantified by weighted mean difference (WMD) and ratio of means (RoM). Robustness of the analyses was evaluated by subgroup analysis and publication bias test. FINDINGS: A total of 17 studies with 906 participants were included. The gastric half-emptying time of solids (WMD, -10.4 minutes; P = 0.001; RoM, 0.90; P = 0.01) and liquids (WMD, -6.14 minutes; P < 0.001; RoM, 0.83, P = 0.03) was significantly shorter in individuals with obesity compared with lean individuals. These findings were confirmed by the subgroup analyses and publication bias tests. IMPLICATIONS: Our pooled analysis systemically quantifies the differences in gastric half-emptying time between individuals with obesity and lean individuals, facilitating better understanding and prediction of drug absorption in individuals with obesity through physiologically based pharmacokinetic approaches. Obesity is associated with a faster transit of both solids and liquids through the stomach.

20.
Chem Commun (Camb) ; 57(71): 8981-8984, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34486627

RESUMO

All-inorganic CsPbI3 halide perovskite has become a hot research topic for applications in next-generation optoelectronic devices. However, the main limitations are the high-temperature synthesis and poor phase stability. In this study, we demonstrate a unique solution-phase strategy for the low-temperature preparation of black-phase CsPbI3 by in situ electrochemistry. By controllable adjustment of the electrochemical growth process, annealing-free black-phase CsPbI3 can be synthesized. The black-phase CsPbI3 showed high-purity red photoluminescence at approximately 690 nm with ultra-high environmental stability for up to 11 days at a high relative humidity of 70%. The underlying mechanisms of the formation of the highly stable black-phase CsPbI3 at room temperature have been discussed in this study. The results provide a new platform for the large scale, low-temperature, and convenient synthesis of black-phase CsPbI3 perovskite.

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