Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 56
Filtrar
1.
Nature ; 629(8010): 98-104, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38693411

RESUMO

Photobiocatalysis-where light is used to expand the reactivity of an enzyme-has recently emerged as a powerful strategy to develop chemistries that are new to nature. These systems have shown potential in asymmetric radical reactions that have long eluded small-molecule catalysts1. So far, unnatural photobiocatalytic reactions are limited to overall reductive and redox-neutral processes2-9. Here we report photobiocatalytic asymmetric sp3-sp3 oxidative cross-coupling between organoboron reagents and amino acids. This reaction requires the cooperative use of engineered pyridoxal biocatalysts, photoredox catalysts and an oxidizing agent. We repurpose a family of pyridoxal-5'-phosphate-dependent enzymes, threonine aldolases10-12, for the α-C-H functionalization of glycine and α-branched amino acid substrates by a radical mechanism, giving rise to a range of α-tri- and tetrasubstituted non-canonical amino acids 13-15 possessing up to two contiguous stereocentres. Directed evolution of pyridoxal radical enzymes allowed primary and secondary radical precursors, including benzyl, allyl and alkylboron reagents, to be coupled in an enantio- and diastereocontrolled fashion. Cooperative photoredox-pyridoxal biocatalysis provides a platform for sp3-sp3 oxidative coupling16, permitting the stereoselective, intermolecular free-radical transformations that are unknown to chemistry or biology.


Assuntos
Aminoácidos , Biocatálise , Acoplamento Oxidativo , Processos Fotoquímicos , Aminoácidos/biossíntese , Aminoácidos/química , Aminoácidos/metabolismo , Biocatálise/efeitos da radiação , Evolução Molecular Direcionada , Radicais Livres/química , Radicais Livres/metabolismo , Glicina/química , Glicina/metabolismo , Glicina Hidroximetiltransferase/metabolismo , Glicina Hidroximetiltransferase/química , Indicadores e Reagentes , Luz , Acoplamento Oxidativo/efeitos da radiação , Fosfato de Piridoxal/metabolismo , Estereoisomerismo , Aminoácidos de Cadeia Ramificada/química , Aminoácidos de Cadeia Ramificada/metabolismo
2.
J Biol Chem ; 300(5): 107233, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38552738

RESUMO

The NACHT, leucine-rich repeat, and pyrin domains-containing protein 3 (collectively known as NLRP3) inflammasome activation plays a critical role in innate immune and pathogenic microorganism infections. However, excessive activation of NLRP3 inflammasome will lead to cellular inflammation and tissue damage, and naturally it must be precisely controlled in the host. Here, we discovered that solute carrier family 25 member 3 (SLC25A3), a mitochondrial phosphate carrier protein, plays an important role in negatively regulating NLRP3 inflammasome activation. We found that SLC25A3 could interact with NLRP3, overexpression of SLC25A3 and knockdown of SLC25A3 could regulate NLRP3 inflammasome activation, and the interaction of NLRP3 and SLC25A3 is significantly boosted in the mitochondria when the NLRP3 inflammasome is activated. Our detailed investigation demonstrated that the interaction between NLRP3 and SLC25A3 disrupted the interaction of NLRP3-NEK7, promoted ubiquitination of NLRP3, and negatively regulated NLRP3 inflammasome activation. Thus, these findings uncovered a new regulatory mechanism of NLRP3 inflammasome activation, which provides a new perspective for the therapy of NLRP3 inflammasome-associated inflammatory diseases.

3.
PLoS One ; 19(3): e0301066, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38547302

RESUMO

BACKGROUND: Subacromial spurs are considered the one of the pathology underlying shoulder impingement syndrome. Furthermore, few studies have focused on the morphology of the subacromial spurs in normal Chinese people. This study aimed to study the spur distribution and to illustrate the morphology of spurs, which may help guide the extent of acromioplasty. METHODS: A total of 93 normal individuals were enrolled, and both shoulders of all enrolled individuals were analyzed. The subjects were divided and classified into three different groups by ages: group I = 18-40 years, group II = 41-60 years, and group III ≥ 61 years. The osteophyte distribution, osteophyte area, subacromial surface area and osteophyte area/subacromial surface area ratio were measured and illustrated using Mimics and 3-matic software. The shape of the acromion was classified according to the Bigliani and Morrison classification system. The acromial angle was also classified. Then, the relationship between osteophytes, acromial classification and acromial angle was analyzed. RESULTS: Type II (curved shape) was the most common type of acromion, and the hooked shape was a rare form. A significant increase in the left subacromial surface area in males was observed in group III compared with group I (P < 0.001) and group II (P = 0.004). The total spur/subacromial area ratio was significantly higher in group II than I. An obvious increase in the right subacromial area was observed in group III compared with group I (P = 0.004). Furthermore, there was a significant increase in the right spur area (P = 0.021) and total spur/subacromial area ratio (P = 0.006) in females in group II compared with group I. Fewer spurs were observed on the left than on the right side (p = 0.0482). One spur was most common among type II acromions (29/36) (80.56%) on the left side and the right side (34/52, 65.38%). CONCLUSIONS: Spurs osteophytes are mainly distributed with an irregular shape and mostly run through the medial and lateral sides of the subacromial surface in normal subjects. The characteristics of subacromial spurs are so diverse that a surgeon must conduct subacromial decompression completely based on the morphology of individual spurs.


Assuntos
Acrômio , População do Leste Asiático , Osteófito , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Acrômio/diagnóstico por imagem , Acrômio/anatomia & histologia , Artroplastia , Osteófito/diagnóstico por imagem , Osteófito/patologia , Síndrome de Colisão do Ombro/diagnóstico por imagem , Pessoa de Meia-Idade
4.
Biomed Pharmacother ; 173: 116366, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38458013

RESUMO

Hepatocellular carcinoma (HCC) has a poor prognosis, and the efficacy of current therapeutic strategies is extremely limited in advanced diseases. Our previous study reported that protein tyrosine phosphatase receptor epsilon (PTPRE) is a promoting factor in HCC progression. In this study, our objective was to evaluate the treatment effect of PTPRE inhibitors in different HCC preclinical models. Our results indicated that the PTPRE inhibitory compound 63 (Cpd-63) inhibited tumor cell proliferation, migration, and HCC organoid growth. Mechanism research revealed that Cpd-63 could inhibit the expression of MYC and MYC targets by inhibiting the activation of SRC. Additionally, we found that Cpd-63 could improve the response of sorafenib in HCC cells. In conclusion, we demonstrated that the PTPRE inhibitors represented a potential therapeutic agent for HCC management.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Carcinoma Hepatocelular/patologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias Hepáticas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos
5.
Cancer Biol Med ; 21(4)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38425216

RESUMO

OBJECTIVE: The human cluster of differentiation (CD)300A, a type-I transmembrane protein with immunoreceptor tyrosine-based inhibitory motifs, was investigated as a potential immune checkpoint for human natural killer (NK) cells targeting hematologic malignancies (HMs). METHODS: We implemented a stimulation system involving the CD300A ligand, phosphatidylserine (PS), exposed to the outer surface of malignant cells. Additionally, we utilized CD300A overexpression, a CD300A blocking system, and a xenotransplantation model to evaluate the impact of CD300A on NK cell efficacy against HMs in in vitro and in vivo settings. Furthermore, we explored the association between CD300A and HM progression in patients. RESULTS: Our findings indicated that PS hampers the function of NK cells. Increased CD300A expression inhibited HM lysis by NK cells. CD300A overexpression shortened the survival of HM-xenografted mice by impairing transplanted NK cells. Blocking PS-CD300A signals with antibodies significantly amplified the expression of lysis function-related proteins and effector cytokines in NK cells, thereby augmenting the ability to lyse HMs. Clinically, heightened CD300A expression correlated with shorter survival and an "exhausted" phenotype of intratumoral NK cells in patients with HMs or solid tumors. CONCLUSIONS: These results propose CD300A as a potential target for invigorating NK cell-based treatments against HMs.


Assuntos
Neoplasias Hematológicas , Células Matadoras Naturais , Receptores Imunológicos , Humanos , Células Matadoras Naturais/imunologia , Animais , Camundongos , Receptores Imunológicos/metabolismo , Receptores Imunológicos/genética , Receptores Imunológicos/imunologia , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/terapia , Ensaios Antitumorais Modelo de Xenoenxerto , Feminino , Antígenos CD/metabolismo , Antígenos CD/imunologia , Masculino , Linhagem Celular Tumoral , Citotoxicidade Imunológica , Fosfatidilserinas/metabolismo
6.
Int J Biol Macromol ; 260(Pt 2): 129599, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38246455

RESUMO

Addressing highly flammable and easily breeding bacteria property via environmentally friendly approach was critical for the large-scale application of lyocell fibers. Herein, a bio-based coating constructed by layer-by-layer deposition of adenosine triphosphate (ATP), chitosan (CS), and polyethyleneimine (PEI) was successfully fabricated to obtain excellent fire-resistant and antimicrobial lyocell fabrics (LBL/Lyocell). The resulted fabrics with add-on of 11.5 wt% achieved the limiting oxygen index (LOI) of 32.0 %. Meanwhile, compared with the pure lyocell fabrics, the peak of heat release rate (PHRR), total heat release (THR), and fire growth rate (FIGRA) of LBL/Lyocell fabrics decreased by 75.2 %, 61.0 % and 69.8 % in cone calorimetric test (CCT), respectively. By characterizing the gaseous products and solid residues, the presence of the ATP/CS/PEI coating could not only quickly form the dense expanded carbon layer by itself, but also promote the conversion of cellulose into thermal-stability residues, thus reducing the release of combustible substances during combustion and protecting the lyocell fabrics. In addition, LBL/Lyocell showed excellent antimicrobial properties with 99.99 % antibacterial rates against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). This bio-based coating was a promising candidate for efficiently flame-retardant cellulose fibers with excellent antibacteria.


Assuntos
Quitosana , Retardadores de Chama , Escherichia coli , Polietilenoimina , Staphylococcus aureus , Trifosfato de Adenosina , Antibacterianos/farmacologia , Celulose
7.
Molecules ; 28(24)2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38138493

RESUMO

This study's objective was to examine the protective effect and mechanism of a novel polysaccharide (AYP) from Auricularia cornea var. Li. on alcoholic liver disease in mice. AYP was extracted from the fruiting bodies of Auricularia cornea var. Li. by enzymatic extraction and purified by DEAE-52 and Sephacryl S-400. Structural features were determined using high-performance liquid chromatography, ion exchange chromatography and Fourier-transform infrared analysis. Additionally, alcoholic liver disease (ALD) mice were established to explore the hepatoprotective activity of AYP (50, 100 and 200 mg/kg/d). Here, our results showed that AYP presented high purity with a molecular weight of 4.64 × 105 Da. AYP was composed of galacturonic acid, galactose, glucose, arabinose, mannose, xylose, rhamnose, ribos, glucuronic acid and fucose (molar ratio: 39.5:32.9:23.6:18.3:6.5:5.8:5.8:3.3:2:1.1). Notably, AYP remarkably reduced liver function impairment (alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC)), nitric oxide (NO) and malondialdehyde (MDA) of the liver and enhanced the activity of antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione (gGSH)) in mice with ALD. Meanwhile, the serum level of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) were reduced in ALD mice treated by AYP. Furthermore, the AYPH group was the most effective and was therefore chosen to further investigate its effect on the intestinal microbiota (bacteria and fungi) of ALD mice. Based on 16s rRNA and ITS-1 sequencing data, AYP influenced the homeostasis of intestinal microbiota to mitigate the damage of ALD mice, possibly by raising the abundance of favorable microbiota (Muribaculaceae, Lachnospiraceae and Kazachstania) and diminishing the abundance of detrimental microbiota (Lactobacillus, Mortierella and Candida). This discovery opens new possibilities for investigating physiological activity in A. cornea var. Li. and provides theoretical references for natural liver-protecting medication research.


Assuntos
Microbioma Gastrointestinal , Hepatopatias Alcoólicas , Camundongos , Animais , RNA Ribossômico 16S , Hepatopatias Alcoólicas/tratamento farmacológico , Hepatopatias Alcoólicas/prevenção & controle , Hepatopatias Alcoólicas/patologia , Fígado , Polissacarídeos/química
8.
Radiology ; 309(1): e230806, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37787671

RESUMO

Background Clinicians consider both imaging and nonimaging data when diagnosing diseases; however, current machine learning approaches primarily consider data from a single modality. Purpose To develop a neural network architecture capable of integrating multimodal patient data and compare its performance to models incorporating a single modality for diagnosing up to 25 pathologic conditions. Materials and Methods In this retrospective study, imaging and nonimaging patient data were extracted from the Medical Information Mart for Intensive Care (MIMIC) database and an internal database comprised of chest radiographs and clinical parameters inpatients in the intensive care unit (ICU) (January 2008 to December 2020). The MIMIC and internal data sets were each split into training (n = 33 893, n = 28 809), validation (n = 740, n = 7203), and test (n = 1909, n = 9004) sets. A novel transformer-based neural network architecture was trained to diagnose up to 25 conditions using nonimaging data alone, imaging data alone, or multimodal data. Diagnostic performance was assessed using area under the receiver operating characteristic curve (AUC) analysis. Results The MIMIC and internal data sets included 36 542 patients (mean age, 63 years ± 17 [SD]; 20 567 male patients) and 45 016 patients (mean age, 66 years ± 16; 27 577 male patients), respectively. The multimodal model showed improved diagnostic performance for all pathologic conditions. For the MIMIC data set, the mean AUC was 0.77 (95% CI: 0.77, 0.78) when both chest radiographs and clinical parameters were used, compared with 0.70 (95% CI: 0.69, 0.71; P < .001) for only chest radiographs and 0.72 (95% CI: 0.72, 0.73; P < .001) for only clinical parameters. These findings were confirmed on the internal data set. Conclusion A model trained on imaging and nonimaging data outperformed models trained on only one type of data for diagnosing multiple diseases in patients in an ICU setting. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Kitamura and Topol in this issue.


Assuntos
Aprendizado Profundo , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Radiografia , Bases de Dados Factuais , Pacientes Internados
9.
Int J Biol Macromol ; 253(Pt 7): 127349, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37838134

RESUMO

The design of flame-retardant cellulose fabrics suffered from deterioration on wearing performance and environmental issue. Here, we developed facile construction of bio-based high fire-safety cellulose fabrics (lyocell) that exploited the bio-based flame-retardant coating (APD) by adenosine triphosphate (ATP) and dicyandiamide (DCD) via ionic reaction. The rich phosphorus/nitrogen elements of APD enabled the excellent fire safety of APD/Lyocell. Specifically, the APD/Lyocell2 had a higher limiting oxygen index (LOI) value of 29.3 %, a lower peak of heat release rate (PHRR, decreasing by 66.6 %), and a reduced total heat rate (THR, lowered by 56.5 %) with respect to pure lyocell fabrics. Interestingly, the APD/Lyocell2 exhibited well flame-retardant durability via passing the vertical burning test after 100 rubs. The satisfactory flame-retardant behaviors of APD/Lyocell derived from the excellent synergistic effect on the gaseous-solid phases, where APD could release more non-flammable gasses and generate phosphoric acid, polyphosphoric acid, etc. to accelerate itself and cellulose dehydration into char residues during combustion. More importantly, the wearing performance of APD/Lyocell fabrics, such as handle, air permeability and tensile strength, etc. almost remained after treatment. The ease of operation and use of bio-based coating made it a promising option to obtain the practical lyocell fabrics with flame-retardancy.


Assuntos
Celulose , Retardadores de Chama , Trifosfato de Adenosina , Gases , Temperatura Alta
10.
J Mater Chem B ; 11(44): 10613-10624, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37877316

RESUMO

Immune checkpoint (ICP) blockade (ICB) is one of the most promising immunotherapies for acute myeloid leukemia (AML). However, owing to their heterogeneity, AML cells may cause uncoordinated metabolic fluxes and heterogeneous immune responses, inducing the release of a spatiotemporally sensitive immune response marker. Timely and in situ detection of immune responses in ICB therapy is important for therapeutic strategy adjustment. Herein, we constructed an all-in-one nanoprobe for self-driving ICB and simultaneously detecting an immune response in the same AML cell in vivo, thus enabling accurate evaluation of heterogenetic immune responses in living AML mice without additional drug treatment or probe processes. The nature-inspire polydopamine (PDA) nanoparticles loaded with an ICP blocker were targeted to the leukocyte immunoglobulin like receptor B4 (a new ICP) of AML cells to induce the release of immune response marker granzyme B (GrB). The PDA nanoparticles were additionally paired with carbon-derived graphene quantum dots (GQDs) to construct a full-organic 'turn-on' bionanoprobe that can transfer fluorescence resonance energy for GrB detection. This multifunctional nanoprobe was validated for triggering ICB therapy and monitoring the changes of GrB levels in real-time both in vitro and in vivo. The organic nanoprobe showed excellent permeability and retention in tumor cells and high biocompatibility in vivo. This bionanoprobe orderly interacted with the upstream ICP molecules and downstream signal molecule GrB, thereby achieving in situ immune response signals within the therapeutic efficacy evaluation window.


Assuntos
Leucemia Mieloide Aguda , Nanopartículas , Pontos Quânticos , Camundongos , Animais , Inibidores de Checkpoint Imunológico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Imunidade
11.
Metabolism ; 148: 155690, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37717724

RESUMO

BACKGROUND: The liver regulates metabolic balance during fasting-feeding cycle. Hepatic adaptation to fasting is precisely modulated on multiple levels. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) is a negative regulator of immunity that reduces several liver pathologies, but its physiological roles in hepatic metabolism are largely unknown. METHODS: TIPE2 expression was examined in mouse liver during fasting-feeding cycle. TIPE2-knockout mice, liver-specific TIPE2-knockout mice, liver-specific TIPE2-overexpressed mice were examined for fasting blood glucose and pyruvate tolerance test. Primary hepatocytes or liver tissues from these mice were evaluated for glucose production, lipid accumulation, gene expression and regulatory pathways. TIPE2 interaction with Raf-1 and TIPE2 transcription regulated by PPAR-α were examined using gene overexpression or knockdown, co-immunoprecipitation, western blot, luciferase reporter assay and DNA-protein binding assay. RESULTS: TIPE2 expression was upregulated in fasted mouse liver and starved hepatocytes, which was positively correlated with gluconeogenic genes. Liver-specific TIPE2 deficiency impaired blood glucose homeostasis and gluconeogenic capacity in mice upon fasting, while liver-specific TIPE2 overexpression elevated fasting blood glucose and hepatic gluconeogenesis in mice. In primary hepatocytes upon starvation, TIPE2 interacted with Raf-1 to accelerate its ubiquitination and degradation, resulting in ERK deactivation and FOXO1 maintenance to sustain gluconeogenesis. During prolonged fasting, hepatic TIPE2 deficiency caused aberrant activation of ERK-mTORC1 axis that increased hepatic lipid accumulation via lipogenesis. In hepatocytes upon starvation, PPAR-α bound with TIPE2 promoter and triggered its transcriptional expression. CONCLUSIONS: Hepatocyte TIPE2 is a PPAR-α-induced Raf-1 inactivator that sustains hepatic gluconeogenesis and prevents excessive hepatic lipid accumulation, playing beneficial roles in hepatocyte adaptation to fasting.

12.
Redox Biol ; 67: 102877, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37690164

RESUMO

The senescence of adipose stem cells (ASCs) impairs healthy adipose tissue remodeling, causing metabolic maladaptation to energy surplus. The intrinsic molecular pathways and potential therapy targets for ASC senescence are largely unclear. Here, we showed that visceral ASCs were prone to senescence that was caused by reactive oxygen species (ROS) overload, especially mitochondrial ROS. These senescent ASCs failed to sustain efficient glucose influx, pentose phosphate pathway (PPP) and redox homeostasis. We showed that CD90 silence restricted the glucose uptake by ASCs and thus disrupted their PPP and anti-oxidant system, resulting in ASC senescence. Notably, fibroblast growth factor 21 (FGF21) treatment significantly reduced the senescent phenotypes of ASCs by augmenting CD90 protein via glycosylation, which promoted glucose influx via the AKT-GLUT4 axis and therefore mitigated ROS overload. For diet-induced obese mice, chronic administration of low-dose FGF21 relieved their visceral white adipose tissue (VAT) dysfunction and systemic metabolic disorders. In particular, VAT homeostasis was restored in FGF21-treated obese mice, where ASC repertoire was markedly recovered, accompanied by CD90 elevation and anti-senescent phenotypes in these ASCs. Collectively, we reveal a molecular mechanism of ASC senescence by which CD90 downregulation interferes glucose influx into PPP and redox homeostasis. And we propose a FGF21-based strategy for healthy VAT remodeling, which targets CD90 glycosylation to correct ASC senescence and therefore combat obesity-related metabolic dysfunction.


Assuntos
Tecido Adiposo Branco , Glucose , Animais , Camundongos , Tecido Adiposo/metabolismo , Tecido Adiposo Branco/metabolismo , Senescência Celular , Glucose/metabolismo , Glicosilação , Camundongos Obesos , Obesidade/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Antígenos Thy-1/metabolismo
13.
Sci Rep ; 13(1): 10666, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37393383

RESUMO

When clinicians assess the prognosis of patients in intensive care, they take imaging and non-imaging data into account. In contrast, many traditional machine learning models rely on only one of these modalities, limiting their potential in medical applications. This work proposes and evaluates a transformer-based neural network as a novel AI architecture that integrates multimodal patient data, i.e., imaging data (chest radiographs) and non-imaging data (clinical data). We evaluate the performance of our model in a retrospective study with 6,125 patients in intensive care. We show that the combined model (area under the receiver operating characteristic curve [AUROC] of 0.863) is superior to the radiographs-only model (AUROC = 0.811, p < 0.001) and the clinical data-only model (AUROC = 0.785, p < 0.001) when tasked with predicting in-hospital survival per patient. Furthermore, we demonstrate that our proposed model is robust in cases where not all (clinical) data points are available.


Assuntos
Cuidados Críticos , Diagnóstico por Imagem , Humanos , Estudos Retrospectivos , Área Sob a Curva , Fontes de Energia Elétrica
14.
Sci Rep ; 13(1): 12098, 2023 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-37495660

RESUMO

Although generative adversarial networks (GANs) can produce large datasets, their limited diversity and fidelity have been recently addressed by denoising diffusion probabilistic models, which have demonstrated superiority in natural image synthesis. In this study, we introduce Medfusion, a conditional latent DDPM designed for medical image generation, and evaluate its performance against GANs, which currently represent the state-of-the-art. Medfusion was trained and compared with StyleGAN-3 using fundoscopy images from the AIROGS dataset, radiographs from the CheXpert dataset, and histopathology images from the CRCDX dataset. Based on previous studies, Progressively Growing GAN (ProGAN) and Conditional GAN (cGAN) were used as additional baselines on the CheXpert and CRCDX datasets, respectively. Medfusion exceeded GANs in terms of diversity (recall), achieving better scores of 0.40 compared to 0.19 in the AIROGS dataset, 0.41 compared to 0.02 (cGAN) and 0.24 (StyleGAN-3) in the CRMDX dataset, and 0.32 compared to 0.17 (ProGAN) and 0.08 (StyleGAN-3) in the CheXpert dataset. Furthermore, Medfusion exhibited equal or higher fidelity (precision) across all three datasets. Our study shows that Medfusion constitutes a promising alternative to GAN-based models for generating high-quality medical images, leading to improved diversity and less artifacts in the generated images.


Assuntos
Artefatos , Rememoração Mental , Difusão , Modelos Estatísticos , Oftalmoscopia , Processamento de Imagem Assistida por Computador
15.
J Orthop Sci ; 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37330353

RESUMO

BACKGROUND: For patients with rotator cuff tear (RCT), the contra-lateral shoulders have higher risk of RCT than general population. It has been proved by several previous studies. The focus of this study is to obtain the data of contra-lateral rotator cuff tear in Chinese population, and to find the rules of contra-lateral rotator cuff tear through statistical analysis. METHODS: From March 2016 to January 2020, patients who underwent shoulder arthroscopic surgery were included in the study, we conduct bilateral shoulder ultrasound before surgery, patients information collection include gender, age, occupation and whether received contra-lateral rotator cuff surgery within 1-3 years. The above information was statistically analyzed. RESULTS: According to the inclusion and exclusion criteria, 401 patients were included. The incidence of contra-lateral rotator cuff tear was 24.3%, 5.58% of them underwent contra-lateral rotator cuff repair surgery within 3 years. The degree of contra-lateral rotator cuff tear was positively correlated with the degree of the primary side; Patients with full-thickness rotator cuff tear were more likely to have contra-lateral rotator cuff tear than patients with partial rotator cuff tear. For patients with supraspinatus tendon tear, the contra-lateral rotator cuff tear risk increases, For patients with subscapularis muscle tear, the contra-lateral rotator cuff tear risk doesn't increases. Contra-lateral rotator cuff tear is related to age, the risk of contra-lateral rotator cuff tear is higher in elderly patients. CONCLUSIONS: The contra-lateral RCT data obtained in our study was 24.3%, significantly lower than that of previous studies. The reasons may include ethnic variation, lifestyle, and proportion of heavy physical labor. The condition of contra-lateral rotator cuff is closely related to affected side rotator cuff tear.

16.
Cell Rep ; 42(5): 112424, 2023 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-37086405

RESUMO

Adipose-derived stem cells (ASCs) drive healthy visceral adipose tissue (VAT) expansion via adipocyte hyperplasia. Obesity induces ASC senescence that causes VAT dysfunction and metabolic disorders. It is challenging to restrain this process by biological intervention, as mechanisms of controlling VAT ASC senescence remain unclear. We demonstrate that a population of CX3CR1hi macrophages is maintained in mouse VAT during short-term energy surplus, which sustains ASCs by restraining their senescence, driving adaptive VAT expansion and metabolic health. Long-term overnutrition induces diminishment of CX3CR1hi macrophages in mouse VAT accompanied by ASC senescence and exhaustion, while transferring CX3CR1hi macrophages restores ASC reservoir and triggers VAT beiging to alleviate the metabolic maladaptation. Mechanistically, visceral ASCs attract macrophages via MCP-1 and shape their CX3CR1hi phenotype via exosomes; these macrophages relieve ASC senescence by promoting the arginase1-eIF5A hypusination axis. These findings identify VAT CX3CR1hi macrophages as ASC supporters and unravel their therapeutic potential for metabolic maladaptation to obesity.


Assuntos
Adipócitos , Gordura Intra-Abdominal , Animais , Camundongos , Gordura Intra-Abdominal/metabolismo , Adipócitos/metabolismo , Macrófagos/metabolismo , Obesidade/metabolismo , Senescência Celular , Tecido Adiposo/metabolismo , Receptor 1 de Quimiocina CX3C/metabolismo
17.
BMC Pregnancy Childbirth ; 23(1): 262, 2023 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-37072728

RESUMO

BACKGROUND: Appropriate breastfeeding training for midwives is necessary to enhance their knowledge, attitude, and practice (KAP). However, evidence surrounding the effects of midwife breastfeeding training programmes is insufficient to draw a conclusion of its effectiveness on breastfeeding initiation, duration, and rates. OBJECTIVE: The aim of this systematic review was to identify, summarise, and critically analyse the available literature to evaluate the effects of midwife breastfeeding training programmes on the midwives' KAP towards breastfeeding and breastfeeding initiation, duration and rates among postnatal mothers. METHODS: Nine English and six Chinese databases were searched with relevant key words. The methodological quality of the included studies were assessed by two reviewers independently using the Joanna Briggs Institute critical appraisal checklists. RESULTS: Nine English and one Chinese articles were included in this review. Five articles investigating midwives' KAP towards breastfeeding reported positive results (p < 0.05). The meta-analysis revealed that breastfeeding training programmes significantly improved midwives' breastfeeding-related knowledge and skills (standardised mean difference = 1.33; 95% confidence interval, 0.98 to 1.68; p < 0.01; I2 = 36%), as well as their attitude towards breastfeeding (p < 0.05). An additional five articles measured the effects of breastfeeding training programmes on the initiation, duration, and rates of breastfeeding among postnatal mothers. Following the implementation of a breastfeeding training programme for midwives, mothers had significantly longer durations of exclusive breastfeeding (p < 0.05), fewer breastfeeding challenges (p < 0.05) (e.g. breast milk insufficiency), and higher satisfaction with breastfeeding counselling (p < 0.01), and fewer infants received breast milk substitutes in their first week of life without medical reasons (p < 0.05) in the intervention group compared with the control group. However, no significant effects were seen on the initiation and rates of breastfeeding after implementation of the programmes. CONCLUSIONS: This systematic review has demonstrated that midwife breastfeeding training programmes could improve midwives' KAP towards breastfeeding. However, the breastfeeding training programmes had limited effects on breastfeeding initiation and rates. We suggest that future breastfeeding training programme should incorporate counselling skills alongside breastfeeding knowledge and skills training. REVIEW REGISTRATION: This systematic review has been registered in the International prospective register of systematic reviews (PROSPERO) (ID: CRD42022260216).


Assuntos
Aleitamento Materno , Tocologia , Lactente , Feminino , Gravidez , Humanos , Tocologia/educação , Mães , Aconselhamento , Leite Humano
18.
Toxics ; 11(3)2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36977039

RESUMO

[Background] Metal exposure is suspected to be correlated to kidney function. However, the combined effects of co-exposing to multiple metals, especially both toxic and protective metals, have not been completely evaluated. [Method] A prospective cohort study was conducted with the "135" cohort for the evaluation of how plasma metal levels are correlated to kidney function in a midlife and elderly community in southern China. An amount of 1368 subjects without kidney disease at baseline were enrolled in the final analysis. By using linear regression and logistic regression models, the correlation of individual metal values with renal function parameters was assessed. Measuring of the multiple metal exposure level was performed by principal component analysis (PCA). [Results] Diminished renal function, as evaluated based on fast kidney function decline, or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, was positively associated with the plasma concentrations of chromium and potassium, but it was negatively associated with selenium and iron (p < 0.05). In multiple-metal analyses, linear and logistic regression models showed that the iron and chromium exposure pattern had a protective effect on renal function, whereas the sodium and potassium exposure pattern and the cadmium and lead exposure pattern increased the risk for fast kidney function decline, and eGFR < 60 mL/min/1.73 m2. [Conclusions] Certain metals, including chromium, potassium, selenium, and iron, were correlated with kidney function in a midlife and elderly community in China. In addition, the potential combined influences of co-exposing to multiple metals were observed.

19.
Environ Sci Pollut Res Int ; 30(4): 9820-9840, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36059015

RESUMO

In this paper, we study the existence form and development pattern of leachate level in the pile through a case of high water level landfill. The innovation of this paper is to consider not only the infiltration of rainfall, but also the internal source water of waste as the source of leachate. There is one main water level and multiple layers of stagnant water levels in this study area. The main water level of the pile first appears along the base slope of the landfill, and the trend of development is to connect from the bottom pile upwards layer by layer. The connection point of each layer gradually moves from the upstream side to the downstream side with time, and the main water level is formed by the gradual connection of the stagnant water level in each layer of the pile. Piles filled with slope as the base surface, and the stagnant water level in the pile first develops on the slope. And piles that are filled with a gentle base surface, and stagnant water level in the pile is uniformly developed on the base surface. At least one layer of stagnant water level exists in each layer of the pile, and multiple saturated zones occur in landfills with gentle base surfaces, and the saturation zone of the upper and lower waste pile will be penetrated. Depending on the form of leachate water level present in the pile, the location can be reasonably chosen for engineered precipitation of the landfill, and based on the development trend of each water level in the pile, it can provide a reference for the site selection and design of the landfill.


Assuntos
Eliminação de Resíduos , Poluentes Químicos da Água , Poluentes Químicos da Água/análise , Água , Instalações de Eliminação de Resíduos
20.
Chin Med Sci J ; 38(4): 273-278, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38163740

RESUMO

Objective To explore the optimal administration route of tranexamic acid (TXA) in shoulder arthroscopic surgery. Methods Patients undergoing arthroscopic rotator cuff repair were randomly divided into four groups: control group (without TXA treatment), intravenous group (TXA was intravenously administered 10 minutes before surgery), irrigation group (TXA was added to the irrigation fluid during subacromial decompression and acromioplasty), and intravenous plus irrigation group (TXA was applied both intravenously and via intra-articular irrigation). The primary outcome was visual clarity assessed with visual analog scale (VAS) score, and the secondary outcomes included irrigation fluid consumption and time to subacromial decompression and acromioplasty procedure. Results There were 134 patients enrolled in the study, including 33 in the control group, 35 in the intravenous group, 32 in the irrigation group, and 34 in the intravenous plus irrigation group. The median and interquartile range of VAS scores for the intravenous, irrigation, and intravenous plus irrigation groups were 2.70 (2.50, 2.86) (Z = -3.677, P = 0.002), 2.67 (2.50, 2.77) (Z = -3.058, P < 0.001), and 2.91 (2.75, 3.00) (Z = -6.634, P < 0.001), respectively, significantly higher than that of the control group [2.44 (2.37, 2.53)]. Moreover, the control group consumed more irrigation fluid than the intravenous group, irrigation group, and intravenous plus irrigation group (all P < 0.05). The intravenous plus irrigation group consumed less irrigation fluid than either the intravenous group or the irrigation group (both P < 0.001). There was no difference in subacromial decompression and acromioplasty operative time among the four groups. Conclusion TXA applied both topically and systematically can improve intraoperative visual clarity, and the combined application is more effective.


Assuntos
Ácido Tranexâmico , Humanos , Ácido Tranexâmico/uso terapêutico , Ombro , Artroscopia/métodos , Descompressão Cirúrgica/métodos , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA