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1.
Adv Mater ; : e2206855, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36082538

RESUMO

Compared with raw rectorite microplatelets (RMs), rectorite nanosheets (RNs) have considerably greater application prospect in the preparation of advanced composite materials because of their larger aspect ratio, higher surface reactivity, and intrinsically superior mechanical and physical properties. However, the difficulty in efficient preparation of RNs significantly limits their large-scale applications. Here, a scalable polyvinylpyrrolidone-assisted stirring approach was developed to prepare ultrathin RNs from the abundant natural RMs. A higher production rate (∼0.675 g h-1 ) was achieved compared with that of most other nanosheets. Additionally, instead of using conventional time- and energy-consuming high-speed centrifugation, an efficient poly (dienedimethylammonium chloride)-assisted sedimentation strategy was proposed here to rapidly separate the exfoliated RNs from the RN dispersion. Then, the RNs were co-assembled with aramid nanofibres (ANFs) into large-scale nacre-mimetic ANF-RN nanopapers with considerably enhanced mechanical, electrical insulating, and high-temperature resistant properties compared with pure ANF nanopapers and ANF-RM micropapers. Moreover, these properties were superior to those of previously reported ANF-based nanopapers and commercial insulating micropapers. This article is protected by copyright. All rights reserved.

2.
Front Pharmacol ; 13: 953004, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36052141

RESUMO

Background: Low grade of sterile inflammation plays detrimental roles in the progression of diabetic kidney disease (DKD). Sappanone A (SA), a kind of homoisoflavanone isolated from the heartwood of Caesalpinia sappan, exerts anti-inflammatory effects in acute kidney injury. However, whether SA has beneficial effects on diabetic kidney disease remains further exploration. Methods and Results: In the present study, uninephrectomized male mice were treated with Streptozotocin (STZ, 50 mg/kg) for five consecutive days to induce diabetes. Next, the diabetic mice were administered orally with SA (10, 20, or 30 mg/kg) or vehicle once per day. Our results showed that STZ treatment significantly enhanced damage in the kidney, as indicated by an increased ratio of kidney weight/body weight, elevated serum creatinine and blood urea nitrogen (BUN), as well as increased 24-h urinary protein excretion, whereas SA-treated mice exhibited a markedly amelioration in these kidney damages. Furthermore, SA attenuated the pathological changes, alleviated fibrotic molecules transforming growth factor-ß1 (TGF-ß1) and Collagen-IV (Col-IV) production, decreased inflammatory cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) expression in STZ-treated mice. Similarly, in glomerular mesangial cells, SA pretreatment decreased high glucose (HG)-induced proliferation, inflammatory cytokines excretion, and fibrotic molecules expression. Mechanistically, SA decreased the expression of nuclear factor kappa B (NF-κB) and restored the expression of total NF-κB inhibitor alpha (IκBα) both in vivo and in vitro. Conclusion: Our data suggest that SA may prevent diabetes-induced kidney inflammation and fibrosis by inhibiting the NF-κB pathway. Hence, SA can be potential and specific therapeutic value in DKD.

3.
Eur J Pharm Biopharm ; 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36087879

RESUMO

Co-amorphous technology is an emerging approach for pharmaceutical engineering of drugs and drug leads with improved physicochemical properties and bioavailability. Platensimycin (PTM) is a promising natural antibiotic lead that acts on bacterial fatty acid synthase and exhibits excellent antibacterial activity. Despite great strides to improve its poor pharmacokinetics by medicinal chemistry and nanotechnology, there are no convenient oral delivery systems developed. Here, a co-amorphous system of PTM and berberine chloride (BCL) was developed for oral delivery of PTM. Co-amorphous PTM-BCL was prepared by rotary vacuum evaporation method, and systematically characterized by powder X-ray diffraction, temperature modulated differential scanning calorimetry, Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). Compared with PTM or BCL alone, the equilibrium solubility and dissolution rate of both of them in the co-amorphous systems decreased significantly, showing the characteristics of sustained release. The molecular interactions between PTM and BCL were mediated by strong charged-mediated hydrogen bonds, based on FTIR, XPS, and NMR-based techniques. The co-amorphous PTM-BCL system showed excellent physiochemical stability at room and elevated (40 °C) temperature under dry conditions. The combination of PTM and BCL showed increased killing of a clinical isolated methicillin-resistant Staphylococcus aureus strain in killing checkerboard assays. Finally, co-amorphous PTM-BCL exhibited 2- or 3-fold longer half-life in rats than that of crystalline and amorphous PTM upon oral administration, respectively. Our study suggests a rational approach to realize the full potential of potent antibiotic PTM, which may be conveniently adapted for engineering of other important pharmaceutics.

4.
Mod Pathol ; 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36088477

RESUMO

We aimed to detect the clinicopathological features and immune microenvironment of double-hit/triple-hit lymphoma in the gastrointestinal tract (GI-DHL/THL) and identify the best diagnostic strategies. A total of 114 cases, including 15 GI-DHL/THL, 42 non-GI-DHL/THL and 57 control diffuse large B-cell lymphoma (DLBCL) cases, were comparatively analyzed for their clinicopathological characteristics, the expression of the immune-regulatory checkpoint PD-L1 and immune microenvironment. We applied univariate and multivariate analyses to determine predictors of DHL/THL. GI-DHL/THL patients showed a higher prevalence of previous infection with hepatitis B virus (HBV) than those with GI-DLBCL. Morphologically, 87% of cases exhibited features of DLBCL. Regarding immunohistochemistry results, the MYC protein expression and the Ki-67 proliferation index were significantly higher in the GI-DHL/THL group than in the GI-DLBCL group. The main source of PD-L1 expression in DHL was tumor-associated macrophages, whereas some tumor cells were positive for PD-L1 in GI-DLBCL cases, as determined through multiplex immunofluorescence staining. The multivariable logistic analysis suggested that 5 variables, namely, age, Mum1, CD10, MYC, and HBV infection status, reflect the risk of DHL/THL. The GI-DHL/THL group show different clinicopathological features and immune microenvironments from DLBCL, which might suggest that different signaling pathways are involved. More work is needed to elucidate the pathogenic mechanism of GI-DHL/THL.

5.
J Card Surg ; 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36047383

RESUMO

OBJECTIVE: This study aimed to detect the predictors of vein graft disease (VGD) progression between 1 week and 1 year after surgery and to evaluate the impact of secondary prevention medications. METHODS: A total of 218 consecutive patients underwent surgical coronary revascularization were evaluated by coronary computed tomography angiography both at 1-week and 1-year follow-up. Logistic regression analyses were performed to investigate the predictors of VGD progression. A risk score (0-4) was set up to evaluate implementation result of secondary prevention measures according to 1-year follow-up result. Association between VGD progression and the risk score was assessed. RESULTS: VGD progression occurred in 11.3% of saphenous vein grafts (SVG) and 22.1% of patients. At the patient level, poor vein graft (odds ratio [OR] = 4.25), noncontrolled hyperlipidemia (OR = 3.01), and diabetes mellitus (DM) (OR = 2.96) were predictors, while diameter of SVG (mm, OR = 0.35) was protective factor. At the graft level, DM (OR = 3.52), noncontrolled hyperlipidemia (OR = 2.33), and peripheral artery disease (PAD) (OR = 2.20) were predictors, while number of SVGs (OR = 0.63), diameter of SVG (mm, OR = 0.39), and mean graft flow >25 ml/min (OR = 0.35) were protective factors. VGD progression was significantly associated with the risk score at both the patient (OR = 1.52) and the graft level (OR = 1.38). CONCLUSIONS: Poor vein graft, noncontrolled hyperlipidemia and DM were predictors of VGD progression between 1 week and 1 year after surgery at the patient level, while larger SVG diameter was a protective factor. DM, PAD and noncontrolled hyperlipidemia were predictors at the graft level, while a number of SVGs, larger SVG diameter, and mean graft flow >25 ml/min were protective factors. Implementation failure of secondary prevention medications was associated with VGD progression from as early as 1 year after surgery.

6.
Foods ; 11(17)2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-36076735

RESUMO

Cardiovascular disease (CVD) has become the leading cause of death worldwide. Many recent studies have pointed out that Lactiplantibacillus plantarum (Lb. plantarum) has great potential in reducing the risk of CVD. Lb. plantarum is a kind of lactic acid bacteria (LAB) widely distributed in fermented food and the human intestinal tract, some strains of which have important effects on human health and the potential to be developed into probiotics. In this review, we summarize the mechanism of potential probiotic strains of Lb. plantarum against CVD. It could regulate the body's metabolism at the molecular, cellular, and population levels, thereby lowering blood glucose and blood lipids, regulating blood pressure, and ultimately reducing the incidence of CVD. Furthermore, since Lb. plantarum is widely utilized in food industry, we highlight some of the most important new developments in fermented food for combating CVD; providing an insight into these fermented foods can assist scientists in improving the quality of these foods as well as alleviating patients' CVD symptoms. We hope that in the future functional foods fermented by Lb. plantarum can be developed and incorporated into the daily diet to assist medication in alleviating CVD to some extent, and maintaining good health.

8.
Quant Imaging Med Surg ; 12(9): 4474-4487, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36060584

RESUMO

Background: Noninvasive assessment of programmed death-ligand 1 (PD-L1) expression status in non-small cell lung cancer (NSCLC) is necessary. This study arm to investigate the value of 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET), diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), and amide proton transfer-weighted imaging (APTWI) in the assessment of PD-L1 status in NSCLC. Methods: This is a prospective diagnostic study. A total of 76 patients with NSCLC underwent chest 18F-FDG PET/magnetic resonance imaging (MRI). Parameters maximum standardized uptake value (SUVmax), quantitate the metabolic tumor volume (MTV), total lesion glycolysis (TLG), apparent diffusion coefficient (ADC), diffusion coefficient (D), pseudo diffusion coefficient (D*), and perfusion fraction (f), and magnetization transfer ratio asymmetry at 3.5 ppm [MTRasym (3.5 ppm)] from 18F-FDG PET, DWI, IVIM, and APTWI, respectively, were compared. The optimal combination of parameters was investigated using logistic regression models and evaluated by area under the receiver operating characteristic (ROC) curve (AUC). The bootstrap with 1,000 samples was used for model validation. Results: SUVmax, MTV, TLG, and MTRasym (3.5 ppm) were higher and D and f were lower in PD-L1 positive NSCLC than in PD-L1 negative NSCLC (all P<0.05). Logistic analysis showed that the combination of MTRasym (3.5 ppm), D, and SUVmax had the strongest predictive value for the differentiation of PD-L1 positive and PD-L1 negative NSCLC [AUC, 0.946; 95% confidence interval (CI): 0.869-0.985; sensitivity, 85.29%; specificity, 91.67%; P all <0.001]. The verification model showed the combination of MTRasym (3.5 ppm), D, and SUVmax had the strongest predictive value, and its ROC curve and calibration curve showed good accuracy (AUC, 0.919, 95% CI: 0.891-0.937) and consistency. Conclusions: Multi-parametric 18F-FDG PET/MRI is beneficial for the non-invasive assessment of PD-L1 status in NSCLC patients, and the combination of SUVmax, D, and MTRasym (3.5 ppm) may serve as a prognostic biomarker to guide immunotherapy.

9.
J Med Chem ; 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36069713

RESUMO

Activation of the stimulator of interferon genes (STING) pathway to achieve antitumor response is an attractive approach for cancer immunotherapy. In this study, we report the identification of BSP16 (LF250) as a potent, orally available STING agonist. BSP16 strongly activates STING signaling in human and mouse cells and binds STING as a homodimer. A 2.4 Å cocrystal structure revealed that BSP16 could induce the "closed" conformation of STING. In vivo studies revealed that BSP16 is well tolerated, has an excellent pharmacokinetic profile as an oral drug, and induces tumor regression and durable antitumor immunity. The promising bioactivities of BSP16 make it valuable for further development as an antitumor agent.

10.
Nat Genet ; 54(9): 1332-1344, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36071172

RESUMO

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.


Assuntos
Estudo de Associação Genômica Ampla , Comportamento Sedentário , Actinina/genética , Estudos Transversais , Exercício Físico/fisiologia , Humanos , Atividades de Lazer
11.
BMC Med Genomics ; 15(1): 192, 2022 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-36088317

RESUMO

BACKGROUND: Concurrent variation in adiposity and inflammation suggests potential shared functional pathways and pleiotropic disease underpinning. Yet, exploration of pleiotropy in the context of adiposity-inflammation has been scarce, and none has included self-identified Hispanic/Latino populations. Given the high level of ancestral diversity in Hispanic American population, genetic studies may reveal variants that are infrequent/monomorphic in more homogeneous populations. METHODS: Using multi-trait Adaptive Sum of Powered Score (aSPU) method, we examined individual and shared genetic effects underlying inflammatory (CRP) and adiposity-related traits (Body Mass Index [BMI]), and central adiposity (Waist to Hip Ratio [WHR]) in HLA participating in the Population Architecture Using Genomics and Epidemiology (PAGE) cohort (N = 35,871) with replication of effects in the Cameron County Hispanic Cohort (CCHC) which consists of Mexican American individuals. RESULTS: Of the > 16 million SNPs tested, variants representing 7 independent loci were found to illustrate significant association with multiple traits. Two out of 7 variants were replicated at statistically significant level in multi-trait analyses in CCHC. The lead variant on APOE (rs439401) and rs11208712 were found to harbor multi-trait associations with adiposity and inflammation. CONCLUSIONS: Results from this study demonstrate the importance of considering pleiotropy for improving our understanding of the etiology of the various metabolic pathways that regulate cardiovascular disease development.


Assuntos
Adiposidade , Pleiotropia Genética , Adiposidade/genética , Hispânico ou Latino/genética , Humanos , Inflamação/genética , Obesidade/genética
12.
J Gastrointest Oncol ; 13(4): 1516-1524, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36092314

RESUMO

Background: Advances in surgical, anesthesia, and nursing techniques have allowed the development of laparo-gastroscopic esophagectomy (LGE) as a minimally invasive treatment of esophageal cancer. This study summarizes the experience of patient whole-process nursing management for patients who received LGE. Methods: The implementation of LGE at Zhongshan Hospital, Fudan University, was initiated in June 2020. The procedure is indicated for patients with thoracic conditions that can compromise the outcomes of traditional surgical procedures, and is performed coordinately by thoracic surgeons and endoscopists. A whole-process nursing protocol covering peri-operative patient management was proposed based on the LGE procedure. The operative outcomes were analyzed in this study. Results: The data of 10 consecutive patients who received LGE and the whole-process nursing protocol were analyzed, and all patients were compliant with the nursing protocol. Intra-operatively, there were no complications or conversions to other surgical methods. Post-operatively, pulmonary complications occurred in 2 cases [1 patient experienced aspiration, underwent preventive tracheotomy, and was discharged on postoperative day (POD) 10; 1 patient developed a left pleural effusion requiring puncture and drainage, and was discharged on POD 7]. The 30-day mortality was not recorded from the primary LGE cohort. Conclusions: The whole-process nursing protocol showed safety and feasibility for patients who underwent LGE. In the future, more specialized and whole-process nursing management will be carried out for patients undergoing such operations.

13.
J Tissue Eng ; 13: 20417314221122123, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36093432

RESUMO

To study the biological functions and applications of human amniotic epithelial cell-derived extracellular vesicles (hAEC-EVs), the cargos of hAEC-EVs were analyzed using miRNA sequencing and proteomics analysis. The hAECs and hAEC-EVs in this study had specific characteristics. Multi-omics analyses showed that extracellular matrix (ECM) reorganization, inhibition of excessive myofibroblasts, and promotion of target cell adhesion to the ECM were their primary functions. We evaluated the application of hAEC-EVs for corneal alkali burn healing in rabbits and elucidated the fundamental mechanisms. Slit-lamp images revealed that corneal alkali burns induced central epithelial loss, stromal haze, iris, and pupil obscurity in rabbits. Slit-lamp examination and histological findings indicated that hAEC-EVs facilitated re-epithelialization of the cornea after alkali burns, reduced scar formation and promoted the restoration of corneal tissue transparency. Significantly fewer α-SMA-positive myofibroblasts were observed in the hAEC-EV-treated group than the PBS group. HAEC-EVs effectively promoted the proliferation and migration of hCECs and hCSCs in vitro and activated the focal adhesion signaling pathway. We demonstrated that hAEC-EVs were excellent cell-free candidates for the treatment of ECM lesion-based diseases, including corneal alkali burns. HAEC-EVs promoted ECM reorganization and cell adhesion of target tissues or cells via orderly activation of the focal adhesion signaling pathway.

14.
Eur J Protistol ; 86: 125921, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36126378

RESUMO

Two colonial sessilid peritrichs, Epistylis qingdaoensis n. sp. and Carchesium cyclopidarum Nenninger, 1948, were isolated from a marine crustacean and a freshwater mayfly, respectively. Morphological characters for each species were revealed by in vivo observations and silver staining methods. Epistylis qingdaoensis n. sp. is characterized by the apperance of the colony which is up to 250 µm high and usually contains fewer than eight zooids, the single-layered peristomial lip, the conspicuously conical peristomial disc, and the structure of infundibular polykinety 3 which comprises three isometric ciliary rows. Carchesium cyclopidarum is recognized by the colony height of about 600 µm, the small zooid size of 35-50 × 20-30 µm, and the low number of silverlines. Phylogenetic analyses based on small subunit ribosomal DNA sequences were performed to reveal their evolutionary relationships. Surprisingly, neither species clustered with its congeners. Epistylis qingdaoensis n. sp. nested within a clade of Zoothamnium species that was sister to a clade comprising core Epistylis species and several Zoothamnium species. Carchesium cyclopidarum nested within a clade comprising solitary peritrichs and was distantly related to the type species of Carchesium, C. polypinum. These findings imply for the first time that Carchesium is non-monophyletic.

15.
Cell Discov ; 8(1): 94, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36127333

RESUMO

Skull base chordoma (SBC) is a bone cancer with a high recurrence rate, high radioresistance rate, and poorly understood mechanism. Here, we profiled the transcriptomes of 90,691 single cells, revealed the SBC cellular hierarchies, and explored novel treatment targets. We identified a cluster of stem-like SBC cells that tended to be distributed in the inferior part of the tumor. Combining radiated UM-Chor1 RNA-seq data and in vitro validation, we further found that this stem-like cell cluster is marked by cathepsin L (CTSL), a gene involved in the packaging of telomere ends, and may be responsible for radioresistance. Moreover, signatures related to partial epithelial-mesenchymal transition (p-EMT) were found to be significant in malignant cells and were related to the invasion and poor prognosis of SBC. Furthermore, YL-13027, a p-EMT inhibitor that acts through the TGF-ß signaling pathway, demonstrated remarkable potency in inhibiting the invasiveness of SBC in preclinical models and was subsequently applied in a phase I clinical trial that enrolled three SBC patients. Encouragingly, YL-13027 attenuated the growth of SBC and achieved stable disease with no serious adverse events, underscoring the clinical potential for the precision treatment of SBC with this therapy. In summary, we conducted the first single-cell RNA sequencing of SBC and identified several targets that could be translated to the treatment of SBC.

17.
Acta Biomater ; 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36087867

RESUMO

Mineralized collagen fibrils (MCFs) are the fundamental building blocks of bone tissue and contribute significantly to the mechanical behavior of bone. However, it is still largely unknown how the collagen network in bone responds to aging and the disuse normally accompanying it. Utilizing atomic force microscopy, nanoindentation and Raman spectroscopy, age-related alterations in the microstructure and mechanical properties of murine cortical tibia at multiple scales were investigated in this study. The potential difference in the responses of bone to disuse at different ages was studied. The results indicated that the age- and disuse-related alterations in bone initiate from MCFs in the bone matrix. The D-periodic spacing, radial elastic modulus of a single MCF and the mineral-to-matrix ratio on the cortical bone surface were larger in aged mice than in adult mice. Disuse, on the other hand, mainly has a major influence on aged mice, particularly on the morphology and mechanical properties of MCFs, but it only has modest effects on adult bone. These findings revealed insights into the morphological and mechanical adaptation of mineralized collagen fibrils in murine cortical bone to aging and disuse. STATEMENT OF SIGNIFICANCE: Bone is a complex structured composite material consisting of an interwoven framework of collagen fibrils reinforced by mineral particles and embedded in an extrafibrillar mineralized matrix. Utilizing atomic force microscopy, nanoindentation and Raman spectroscopy, this study suggests that the effects of aging, as well as the accompanying disuse, on the morphology and mechanical properties of bone initiate from the mineralized collagen fibril level. More interestingly, the MCF in the bone of aged mice seems to be more sensitive to disuse than that in adult mice. These findings significantly further the current understanding of the adaptation process of bone to aging at the mineralized collagen fibril level and provide direct insights into the physiological response of bone to aging and the abnormal mechanical environment.

19.
Chem Commun (Camb) ; 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36106578

RESUMO

Electrostatically assembled ultrathin rhodium nanosheet-gold nanowire nanocomposites (Rh-Au CNSs) were used as an advanced electrocatalyst for the methanol oxidation reaction, which revealed a mass activity of 355 mA mgRh-1 at 0.607 V potential, much higher than single metal Rh nanosheets (273 mA mgRh-1) and commercial Rh nanoparticles (165 mA mgRh-1).

20.
Sleep Med Rev ; 65: 101691, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36099873

RESUMO

Sleep is a complex physiological process and is a critical determinant of physical and mental health. In the past decades, significant progress has been made in understanding the neural mechanisms of sleep and awakening. However, the initiation and maintenance of the sleep-wake cycle is regulated not only by the central system but is also affected by signals from peripheral tissues. Growing evidence shows that the microbiota-gut-brain axis contributes to the regulation of sleep behavior both directly and indirectly and may play a critical role in the etiology and pathogenesis of sleep disorders. Sleep deprivation leads to dysfunction of gut microbiota and sleep disorders are accompanied by altered gut microbiota composition. In this review, we describe the bidirectional relationships between sleep and gut microbiota and summarize the abnormal characteristics of gut bacteria in distinct conditions including sleep disturbances, sleep disorders and sleep disorders comorbid with neuropsychiatric disorders. We also examine the potential routes of microbiota-gut-brain axis in sleep and gut microbiome interactions, including metabolic, immune, and neural pathways, and propose microbiota-targeted interventions for improving sleep. Manipulating gut microbiota may be a promising avenue for the development of novel interventions for sleep disorders.

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