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1.
Artigo em Inglês | MEDLINE | ID: mdl-34647135

RESUMO

Biofilms are heterogeneous structures composed of microorganisms and the surrounding extracellular polymeric substances (EPS) that protect the microbial cells from harsh environments. Saccharomyces boulardii is the first yeast classified as a probiotic strain with unique properties. However, tolerance of S. boulardii biofilms to harsh environments especially during production and in the gastrointestine remains unknown. In this study, S. boulardii cells were encapsulated in alginate microcapsules and subsequently cultured to form biofilms, and their survival and tolerance were evaluated. Microencapsulation provided S. boulardii a confined space that enhanced biofilm formation. The thick alginate shell and the mature biofilm improved the ability of S. boulardii to survive under harsh conditions. The exogenous encapsulation and the endogenous biofilm structure together enhanced the gastrointestinal tolerance and thermotolerance of S. boulardii. Besides, as the alginate shell became thinner with an increase in the subsequent culture duration, the EPS of S. boulardii biofilms exerted an important protective effect in resisting high temperatures. The encapsulated biofilm of S. boulardii after 24-h culture exhibited 60 × higher thermotolerance at 60 °C (10 min), while those after 6-h and 24-h culture showed 1000 × to 550,000 × higher thermotolerance at 120 °C (1 min) compared with the planktonic cells without encapsulation. The present study's findings suggest that a combination of encapsulation and biofilm mode efficiently enhanced gastrointestinal tolerance and thermotolerance of S. boulardii. KEY POINTS: • Encapsulated S. boulardii in biofilm mode showed enhanced tolerance. • Exogenous shell and endogenous biofilm provided dual protection to S. boulardii.

3.
Ann Med ; 53(1): 1722-1726, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34596490

RESUMO

OBJECTIVE: Low triiodothyronine syndrome (LT3S) is a common endocrine disease in preterm neonates. Various serious acute or chronic diseases result in LT3S. Few studies have investigated the causal relationship between perinatal factors and LT3S in preterm neonates with a gestational age (GA) of 28-35 weeks. The present study comprehensively analyzed the perinatal factors of LT3S in preterm neonates. METHODS: This was a retrospective study of neonates with and without LT3S from January 2018 to November 2019. Compared to 206 preterm neonates without LT3S, 158 neonates were diagnosed with LT3S, excluding neonates with congenital malformations, other endocrine diseases, genetic diseases and inherited metabolic diseases. RESULTS: Five perinatal risk factors for LT3S were confirmed using univariate and multivariate analyses: smaller gestational age, lower birth weight, respiratory distress syndrome (RDS), neonatal sepsis, and dopamine use. CONCLUSIONS: LT3S in preterm neonates was associated with multiple perinatal factors, including smaller gestational age, lower birth weight, RDS, sepsis, and dopamine use. Preterm neonates with a GA of 28-35 weeks who are exposed to a series of high-risk perinatal factors must be closely observed, diagnosed early and treated for primary diseases promptly to reduce the occurrence of LT3S and improve the outcomes.Key Message:Few studies have investigated the relationship between perinatal factors and Low triiodothyronine syndrome (LT3S) in preterm neonates with a gestational age (GA) of 28-35 weeks.LT3S was associated with multiple perinatal factors, including smaller gestational age, lower birth weight, respiratory distress syndrome (RDS), sepsis, and dopamine use.

4.
Nano Lett ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34644096

RESUMO

Memristor devices that exhibit high integration density, fast speed, and low power consumption are candidates for neuromorphic devices. Here, we demonstrate a filament-based memristor using p-type SnS as the resistive switching material, exhibiting superlative metrics such as a switching voltage ∼0.2 V, a switching speed faster than 1.5 ns, high endurance switching cycles, and an ultralarge on/off ratio of 108. The device exhibits a power consumption as low as ∼100 fJ per switch. Chip-level simulations of the memristor based on 32 × 32 high-density crossbar arrays with 50 nm feature size reveal on-chip learning accuracy of 87.76% (close to the ideal software accuracy 90%) for CIFAR-10 image classifications. The ultrafast and low energy switching of p-type SnS compared to n-type transition metal dichalcogenides is attributed to the presence of cation vacancies and van der Waals gap that lower the activation barrier for Ag ion migration.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34649425

RESUMO

Rational design of the sulfur cathode structure enables effective adsorption of polysulfides and accelerates the sulfur reduction reaction, which is of great significance to the practical application of lithium-sulfur batteries. Here, P-doped carbon foam (PCF) as a sulfur host for the lithium-sulfur battery cathode was successfully synthesized by a facile strategy. The tailored hierarchical pore structure combined with P doping not only facilitates Li+ diffusion but also enhances the adsorption and accelerates the catalytic conversion of lithium polysulfides, thus significantly improving lithium storage performance of the PCF/S cathode.

6.
mBio ; : e0212721, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34488445

RESUMO

Interferon (IFN) signaling is key to mucosal immunity in the gastrointestinal tract, but cellular regulatory elements that determine interferon gamma (IFN-γ)-mediated antimicrobial defense in intestinal epithelial cells are not fully understood. We report here that a long noncoding RNA (lncRNA), GenBank accession no. XR_001779380, was increased in abundance in murine intestinal epithelial cells following infection by Cryptosporidium, an important opportunistic pathogen in AIDS patients and a common cause of diarrhea in young children. Expression of XR_001779380 in infected intestinal epithelial cells was triggered by TLR4/NF-κB/Cdc42 signaling and epithelial-specific transcription factor Elf3. XR_001779380 primed epithelial cells for IFN-γ-mediated gene transcription through facilitating Stat1/Swi/Snf-associated chromatin remodeling. Interactions between XR_001779380 and Prdm1, which is expressed in neonatal but not adult intestinal epithelium, attenuated Stat1/Swi/Snf-associated chromatin remodeling induced by IFN-γ, contributing to suppression of IFN-γ-mediated epithelial defense in neonatal intestine. Our data demonstrate that XR_001779380 is an important regulator in IFN-γ-mediated gene transcription and age-associated intestinal epithelial antimicrobial defense. IMPORTANCE Epithelial cells along the mucosal surface provide the front line of defense against luminal pathogen infection in the gastrointestinal tract. These epithelial cells represent an integral component of a highly regulated communication network that can transmit essential signals to cells in the underlying intestinal mucosa that, in turn, serve as targets of mucosal immune mediators. LncRNAs are recently identified long noncoding transcripts that can regulate gene transcription through their interactions with other effect molecules. In this study, we demonstrated that lncRNA XR_001779380 was upregulated in murine intestinal epithelial cells following infection by a mucosal protozoan parasite Cryptosporidium. Expression of XR_001779380 in infected cells primed host epithelial cells for IFN-γ-mediated gene transcription, relevant to age-dependent intestinal antimicrobial defense. Our data provide new mechanistic insights into how intestinal epithelial cells orchestrate intestinal mucosal defense against microbial infection.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34469683

RESUMO

Conductive ionic hydrogel fibers and textiles with excellent mechanical properties and chemical stability are requested for flexible and wearable electronic devices, strain sensors, and even artificial skin. However, most of the reported hydrogel fibers are not suitable in complex environments, especially in alkaline solutions and organic solvents due to their poor chemical stability. Herein, we report ionic polyimide hydrogel fibers derived from an organosoluble polyimide salt that can be continuously and rapidly prepared via a facile wet spinning method. Thanks to their ion-rich property and robust skeletal structure, the obtained ionic polyimide hydrogel fibers showed an excellent conductivity of ∼21 mS/cm and outstanding mechanical properties with a tensile strength of 2.5 MPa and breaking elongation of 215%. Furthermore, the as-prepared fibers could be easily woven to form integral textiles, endowing them with good wearable properties. Accordingly, facile strain sensors assembled by polyimide hydrogel fibers show a linear response with high sensitivity and good cycling stability, which have great potential for applications in wearable and flexible strain sensors under diverse complex environments.

8.
J Surg Oncol ; 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34555187

RESUMO

OBJECTIVES: This study aimed to explore the effect of suturing upper mediastinum pleura on postoperative complications, surgery-related mortality, and hospital stay. METHODS: Four hundred and thirty-eight patients with esophageal cancer who underwent esophagectomy were identified. Patients were divided into two groups: those in the test group who received reconstruction of upper mediastinal pleura, those in the conventional group who did not. The incidence of postoperative complications, surgery-related mortality, and hospital stay were compared. To reduce the impact of confounding factors, a propensity score matching (PSM) method was performed. RESULTS: A total of 273 patients were treated with suturing upper mediastinal pleura and 165 were not. After PSM, compared with the conventional group, the incidence of atelectasis (7.2% vs. 1.4%, p = 0.035), anastomotic leakage (5.8% vs. 0.7%, p = 0.036), and delayed gastric emptying (10.8% vs. 3.6%, p = 0.034) were significantly lower in the test group. And suturing the upper mediastinal pleura could reduce the severity of leakage (p = 0.045), consistent with the results before PSM. Moreover, there were no significant differences in the incidence of other complications, postoperative hospital stay, and 30-day mortality (all p > 0.05). CONCLUSIONS: In this study, suturing the upper mediastinal pleura can reduce the incidence of atelectasis, anastomotic leakage, and delayed gastric emptying, and the severity of leakage, without increasing the incidence of other complications, surgery-related death, and postoperative hospital stay.

9.
J Am Chem Soc ; 143(37): 15073-15083, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34520194

RESUMO

Proteolysis targeting chimeras (PROTACs) represent a new class of promising therapeutic modalities. PROTACs hijack E3 ligases and the ubiquitin-proteasome system (UPS), leading to selective degradation of the target proteins. However, only a very limited number of E3 ligases have been leveraged to generate effective PROTACs. Herein, we report that the KEAP1 E3 ligase can be harnessed for targeted protein degradation utilizing a highly selective, noncovalent small-molecule KEAP1 binder. We generated a proof-of-concept PROTAC, MS83, by linking the KEAP1 ligand to a BRD4/3/2 binder. MS83 effectively reduces protein levels of BRD4 and BRD3, but not BRD2, in cells in a concentration-, time-, KEAP1- and UPS-dependent manner. Interestingly, MS83 degrades BRD4/3 more durably than the CRBN-recruiting PROTAC dBET1 in MDA-MB-468 cells and selectively degrades BRD4 short isoform over long isoform in MDA-MB-231 cells. It also displays improved antiproliferative activity than dBET1. Overall, our study expands the limited toolbox for targeted protein degradation.

10.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(3): 276-280, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34374240

RESUMO

Objective: To investigate the protective effects and mechanisms of the polysaccharide from Balanophora involucrata HK.f (BIH) on liver injury induced by D-galactose in rats. Methods: Sixty male SD rats were randomly divided into 5 groups: the control group (n=12), the D-gal group (n=12), the BIH-L treatment group (D-gal+50 mg/kg BIH, n=12), the BIH-M treatment group (D-gal+100 mg/kg BIH, n=12), and the BIH-H treatment group (D-gal+200 mg/kg BIH, n=12). The rats were injected into the back of the neck with D-gal of 100 mg/kg/d subcutaneously except for the control group. The BIH treatment group were divided into BIH-L group (50 mg/(kg·d)), BIH-M group (100 mg/(kg·d)), and BIH-H group (200 mg/(kg·d)), respectively. The rats in the BIH group were intragastrically administrated with the relative BIH solution, while the rats in the control and D-gal group were treated with saline solution for 42 days. The serum contents of ALT, AST and DBIL c were tested by automatic biochemical analyzer, the content of MDA was determined by thiobarbital acid method and the SOD activity was detected by xanthine oxidase method. Expressions of Caspase-3, Bax, and Bcl-2 in liver were measured by Western blot, and morphological changes by HE staining and immunohistochemistry. Results: The serum contents of ALT, AST and DBIL in the D-gal group were significantly increased compared with those in Con group (P<0.01) and were decreased in the BIH group as compared with the D-gal group (P<0.01). Cell apoptosis, the Caspase-3 and Bax levels, and the MDA content in the D-gal group were increased compared with those in the control group (P<0.01). And BIH treatment could attenuate these effects induced by D-gal. Meanwhile, the Bcl-2 level and SOD activity in the BIH group were increased compared with that in the D-gal group (P<0.05, 0.01). Conclusion: BIH can protective liver injury through reducing cell apoptosis and inhibiting oxidative stress.


Assuntos
Galactose , Fígado , Animais , Galactose/metabolismo , Galactose/toxicidade , Fígado/metabolismo , Masculino , Estresse Oxidativo , Polissacarídeos , Ratos , Ratos Sprague-Dawley
11.
J Int Med Res ; 49(8): 3000605211031438, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34369195

RESUMO

OBJECTIVE: This study was performed to analyze the risk factors associated with flexor pollicis longus (FPL) attrition or rupture after volar plating of distal radius fractures. METHODS: Three hundred thirty-eight patients with distal radius fractures were included in this retrospective study. Univariate analysis and multivariate logistic regression analysis were performed to predict risk factors. RESULTS: Univariate analysis showed that sex, volar tilt, the Soong grade, the plate-to-critical line distance (PCLD), the plate-to-volar rim distance (PVRD), and the time of plate removal were significantly associated with FPL attrition or rupture. Multivariate logistic regression analysis demonstrated that decreased volar tilt, Soong grade 2, PCLD of >2 mm, PVRD of <3 mm, and plate removal at ≥1 year were the risk factors significantly associated with FPL attrition or rupture. CONCLUSIONS: Reduced volar tilt, Soong grade 2, PCLD of >2 mm, and PVRD of <3 mm appear to be risk factors that are significantly associated with FPL attrition or rupture. The findings of this study also suggest that the risk of tendon rupture is lower if a Soong grade 2 plate is removed, the PCLD is >2 mm, the PVRD is <3 mm, or reduced volar tilt is achieved earlier (at <1 year).


Assuntos
Fraturas do Rádio , Placas Ósseas/efeitos adversos , Fixação Interna de Fraturas/efeitos adversos , Humanos , Fraturas do Rádio/cirurgia , Estudos Retrospectivos , Fatores de Risco , Ruptura
12.
Food Funct ; 12(18): 8635-8646, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34346464

RESUMO

Ulcerative colitis (UC) is a chronic lifetime disorder with a high incidence worldwide. A functional food-based method to prevent UC would be a good option for disease control. G. lemaneiformis oligosaccharides (GLOs) should have potent benefits for the gastrointestinal tract, based on in vitro fermentation assessed in our previous study. This study evaluated the therapeutic potential of GLOs in UC, as well as their possible mechanisms of action. The administration of GLOs was able to reduce the severity of dextran sulphate sodium-induced colitis by protecting mice from weight loss, reductions in colon length, inflammatory infiltration, and colon damage. Gut microbiota composition analysis showed that at the phylum level, GLOs could restore the composition of Bacteroidetes and decrease the level of Firmicutes. Consistently, it increased the contents of beneficial microbial metabolites and short-chain fatty acids in the mouse colitis model. In conclusion, GLOs could comprise a promising functional food strategy to alleviate UC symptoms.

13.
Biomed Res Int ; 2021: 3490881, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395612

RESUMO

Objective: To evaluate the stress status of fracture site caused by femoral neck shortening and to analyze the stress of fracture site and the implants from the finite element point of view. Methods: CT scan data of hip of a normal adult female were collected. Three-dimensional reconstruction MICs and related module function simulation was used to establish the postoperative shortening model of femoral neck fracture with Pauwels angle > 50°, which was treated with cannulated screws. The models were divided into four groups: normal femoral neck, shortening in 2.5 mm, shortening in 7.5 mm, and shortening in 12.5 mm. The finite element analysis software msc.nastran2012 was used, and the data of maximum stress and stress nephogram of fracture site and implants were carried out. Results: From normal femoral neck to shortening in 12.5 mm of the femoral neck, the maximum tensile stress increased gradually in the fracture site above the cannulated screws while compressive stress decreased gradually in the fracture site below the cannulated screws, and the maximum stress of the cannulated screws increased gradually with obvious stress concentration at the screw holes in the fracture site, and the peak value of stress concentration was about 179 MPa. Conclusion: The biomechanical environment of the fracture site changed by femoral neck shortening. With the increasing of femoral neck shortening, the stress of the fracture site and implants would be uneven; then, the stability of fracture site would become worse, and the possibility of implant sliding or even breakage would be increased.


Assuntos
Fraturas do Colo Femoral/cirurgia , Fixação Interna de Fraturas/instrumentação , Consolidação da Fratura , Osteoporose Pós-Menopausa/complicações , Fenômenos Biomecânicos , Parafusos Ósseos , Feminino , Fraturas do Colo Femoral/etiologia , Análise de Elementos Finitos , Humanos , Pessoa de Meia-Idade , Modelos Anatômicos , Osteoporose Pós-Menopausa/cirurgia , Pressão
15.
Prostate ; 81(15): 1179-1190, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34418127

RESUMO

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common male genitourinary system disease. As a neuroendocrine hormone, melatonin possesses a variety of biological functions, among which its anti-inflammatory effects have recently drawn substantial attention. The purpose of the current research was to study the effect of melatonin on CP/CPPS and the underlying mechanisms using a mouse model of experimental autoimmune prostatitis (EAP). METHODS: The EAP mouse model was successfully established by subcutaneously injecting a mixture of prostate antigen and complete Freund's adjuvant. On Day 42, hematoxylin-eosin staining was used to evaluate the histological appearance of prostate tissues. Chronic pelvic pain development was assessed by suprapubic allodynia. The levels of inflammation-related cytokines, such as interferon-γ, interleukin (IL)-17, and IL-1ß, were detected by enzyme-linked immunosorbent assay. Then, we explored the anti-inflammatory effects of melatonin on CP/CPPS by Western blotting and immunohistochemical staining, by measuring the expression of silent information regulator 1 (Sirt1) and NLRP3 inflammasome-related proteins in EAP mice. RESULTS: The EAP model mice exhibited severe diffuse leukocyte infiltration and significantly increased pelvic pain compared to the control mice. In the melatonin treatment group, the histological appearance of the prostate tissues, pelvic pain development, and the levels of proinflammatory cytokines were significantly alleviated compared to the EAP + dimethyl sulfoxide group. Furthermore, we found that the protective effects of melatonin were achieved through activation of the Sirt1 pathway and downregulation of the NLRP3 inflammasome. CONCLUSIONS: The results indicated that melatonin could attenuate prostate inflammation and pelvic pain by inhibiting the NLRP3 inflammasomes signaling pathway through the activation of Sirt1 in mice with EAP, and these efforts should provide a promising therapeutic strategy for CP/CPPS.

16.
Phys Rev Lett ; 127(4): 041102, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34355954

RESUMO

Gravitational waves from a source moving relative to us can suffer from special-relativistic effects such as aberration. The required velocities for these to be significant are on the order of 1000 km s^{-1}. This value corresponds to the velocity dispersion that one finds in clusters of galaxies. Hence, we expect a large number of gravitational-wave sources to have such effects imprinted in their signals. In particular, the signal from a moving source will have its higher modes excited, i.e., (3,3) and beyond. We derive expressions describing this effect and study its measurability for the specific case of a circular, nonspinning extreme-mass-ratio inspiral. We find that the excitation of higher modes by a peculiar velocity of 1000 km s^{-1} is detectable for such inspirals with signal-to-noise ratios of ≳20. Using a Fisher matrix analysis, we show that the velocity of the source can be measured to a precision of just a few percent for a signal-to-noise ratio of 100. If the motion of the source is ignored, parameter estimates could be biased, e.g., the estimated masses of the components through a Doppler shift. Conversely, by including this effect in waveform models, we could measure the velocity dispersion of clusters of galaxies at distances inaccessible to light.

17.
Acta Pharmacol Sin ; 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34349235

RESUMO

ß-Adrenergic receptor (ß-AR) overactivation is a major pathological factor associated with cardiac diseases and mediates cardiac inflammatory injury. Glibenclamide has shown anti-inflammatory effects in previous research. However, it is unclear whether and how glibenclamide can alleviate cardiac inflammatory injury induced by ß-AR overactivation. In the present study, male C57BL/6J mice were treated with or without the ß-AR agonist isoprenaline (ISO) with or without glibenclamide pretreatment. The results indicated that glibenclamide alleviated ISO-induced macrophage infiltration in the heart, as determined by Mac-3 staining. Consistent with this finding, glibenclamide also inhibited ISO-induced chemokines and proinflammatory cytokines expression in the heart. Moreover, glibenclamide inhibited ISO-induced cardiac fibrosis and dysfunction in mice. To reveal the protective mechanism of glibenclamide, the NLRP3 inflammasome was further analysed. ISO activated the NLRP3 inflammasome in both cardiomyocytes and mouse hearts, but this effect was alleviated by glibenclamide pretreatment. Furthermore, in cardiomyocytes, ISO increased the efflux of potassium and the generation of ROS, which are recognized as activators of the NLRP3 inflammasome. The ISO-induced increases in these processes were inhibited by glibenclamide pretreatment. Moreover, glibenclamide inhibited the cAMP/PKA signalling pathway, which is downstream of ß-AR, by increasing phosphodiesterase activity in mouse hearts and cardiomyocytes. In conclusion, glibenclamide alleviates ß-AR overactivation-induced cardiac inflammation by inhibiting the NLRP3 inflammasome. The underlying mechanism involves glibenclamide-mediated suppression of potassium efflux and ROS generation by inhibiting the cAMP/PKA pathway.

18.
Mol Neurodegener ; 16(1): 48, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-34281568

RESUMO

BACKGROUND: Understanding the long-term effects of coronavirus disease 2019 (COVID-19) on cognitive function is essential for monitoring the cognitive decline in the elderly population. This study aims to assess the current cognitive status and the longitudinal cognitive decline in elderly patients recovered from COVID-19. METHODS: This cross-sectional study recruited 1539 COVID-19 inpatients aged over 60 years who were discharged from three COVID-19-designated hospitals in Wuhan, China, from February 10 to April 10, 2020. In total, 466 uninfected spouses of COVID-19 patients were selected as controls. The current cognitive status was assessed using a Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40) and the longitudinal cognitive decline was assessed using an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Cognitive assessments were performed 6 months after patient discharge. RESULTS: Compared with controls, COVID-19 patients had lower TICS-40 scores and higher IQCODE scores [TICS-40 median (IQR): 29 (25 to 32) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR): 3.19 (3.00 to 3.63) vs. 3.06 (3.00 to 3.38), p < 0.001]. Severe COVID-19 patients had lower TICS-40 scores and higher IQCODE scores than non-severe COVID-19 patients [TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR): 3.63 (3.13 to 4.31) vs. 3.13 (3.00 to 3.56), p < 0.001] and controls [TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR) 3.63 (3.13 to 4.31) vs. 3.06 (3.00 to 3.38), p < 0.001]. Severe COVID-19 patients had a higher proportion of cases with current cognitive impairment and longitudinal cognitive decline than non-severe COVID-19 patients [dementia: 25 (10.50 %) vs. 9 (0.69 %), p < 0.001; Mild cognitive impairment (MCI): 60 (25.21 %) vs. 63 (4.84 %), p < 0.001] and controls [dementia: 25 (10.50 %) vs. 0 (0 %), p < 0.001; MCI: 60 (25.21 %) vs. 20 (4.29 %), p < 0.001)]. COVID-19 severity, delirium and COPD were risk factors of current cognitive impairment. Low education level, severe COVID-19, delirium, hypertension and COPD were risk factors of longitudinal cognitive decline. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with an increased risk of long-term cognitive decline in elderly population. COVID-19 patients, especially severe patients, should be intensively monitored for post-infection cognitive decline.


Assuntos
COVID-19/complicações , Disfunção Cognitiva/virologia , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , China , Disfunção Cognitiva/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2
19.
Cancer Discov ; 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34301793

RESUMO

Using a panel of cancer cell lines, we characterized a novel degrader of AKT, MS21. In mutant PI3K/PTEN pathway lines, AKT degradation was superior to AKT kinase inhibition for reducing cell growth and sustaining lower signaling over many days. AKT degradation but not kinase inhibition profoundly lowered Aurora kinase B (AURKB) protein, which is known to be essential for cell division, and induced G2/M arrest and hyperploidy. PI3K activated AKT phosphorylation of AURKB on threonine 73, which protected it from proteasome degradation. A mutant of AURKB (T73E) that mimics phosphorylation and blocks degradation rescued cells from growth inhibition. Degrader resistant lines were associated with low AKT phosphorylation, wild type PI3K/PTEN status, and mutation of KRAS/BRAF. Pan-cancer analysis identified that 19% of cases have PI3K/PTEN pathway mutation without RAS pathway mutation, suggesting that these cancer patients could benefit from AKT degrader therapy that leads to loss of AURKB.

20.
Front Immunol ; 12: 705232, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34295340

RESUMO

Increasing evidence supports that N6-methyladenosine (m6A) mRNA modification may play an important role in regulating immune responses. Intestinal epithelial cells orchestrate gastrointestinal mucosal innate defense to microbial infection, but underlying mechanisms are still not fully understood. In this study, we present data demonstrating significant alterations in the topology of host m6A mRNA methylome in intestinal epithelial cells following infection by Cryptosporidium parvum, a coccidian parasite that infects the gastrointestinal epithelium and causes a self-limited disease in immunocompetent individuals but a life-threatening diarrheal disease in AIDS patients. Altered m6A methylation in mRNAs in intestinal epithelial cells following C. parvum infection is associated with downregulation of alpha-ketoglutarate-dependent dioxygenase alkB homolog 5 and the fat mass and obesity-associated protein with the involvement of NF-кB signaling. Functionally, m6A methylation statuses influence intestinal epithelial innate defense against C. parvum infection. Specifically, expression levels of immune-related genes, such as the immunity-related GTPase family M member 2 and interferon gamma induced GTPase, are increased in infected cells with a decreased m6A mRNA methylation. Our data support that intestinal epithelial cells display significant alterations in the topology of their m6A mRNA methylome in response to C. parvum infection with the involvement of activation of the NF-кB signaling pathway, a process that modulates expression of specific immune-related genes and contributes to fine regulation of epithelial antimicrobial defense.

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