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1.
Bioact Mater ; 19: 115-126, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35475030

RESUMO

Nanoparticle-based therapeutics represent potential strategies for treating atherosclerosis; however, the complex plaque microenvironment poses a barrier for nanoparticles to target the dysfunctional cells. Here, we report reactive oxygen species (ROS)-responsive and size-reducible nanoassemblies, formed by multivalent host-guest interactions between ß-cyclodextrins (ß-CD)-anchored discoidal recombinant high-density lipoprotein (NP3 ST) and hyaluronic acid-ferrocene (HA-Fc) conjugates. The HA-Fc/NP3 ST nanoassemblies have extended blood circulation time, specifically accumulate in atherosclerotic plaque mediated by the HA receptors CD44 highly expressed in injured endothelium, rapidly disassemble in response to excess ROS in the intimal and release smaller NP3 ST, allowing for further plaque penetration, macrophage-targeted cholesterol efflux and drug delivery. In vivo pharmacodynamicses in atherosclerotic mice shows that HA-Fc/NP3 ST reduces plaque size by 53%, plaque lipid deposition by 63%, plaque macrophage content by 62% and local inflammatory factor level by 64% compared to the saline group. Meanwhile, HA-Fc/NP3 ST alleviates systemic inflammation characterized by reduced serum inflammatory factor levels. Collectively, HA-Fc/NP3 ST nanoassemblies with ROS-responsive and size-reducible properties exhibit a deeper penetration in atherosclerotic plaque and enhanced macrophage targeting ability, thus exerting effective cholesterol efflux and drug delivery for atherosclerosis therapy.

2.
J Environ Sci (China) ; 125: 712-722, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36375952

RESUMO

The sulfur-containing odor emitted from sludge composting could be controlled by sulfide oxidizing bacteria, yet mesophilic strains show inactivation during the thermophilic stage of composting. Aimed to investigate and characterize the thermotolerant bacterium that could oxidize sulfide into sulfate, a heterotrophic strain was isolated from sewage sludge composting and identified as Paenibacillus naphthalenovorans LYH-3. The effects of various environmental factors on sulfide oxidation capacities were studied to optimize the sulfate production, and the highest production rate (27.35% ± 0.86%) was obtained at pH 7.34, the rotation speed of 161.14 r/min, and the inoculation amount of 5.83% by employing Box-Behnken design. The results of serial sulfide substrates experiments indicated that strain LYH-3 could survive up to 400 mg/L of sulfide with the highest sulfide removal rate (88.79% ± 0.35%) obtained at 50 mg/L of sulfide. Growth kinetic analysis presented the maximum specific growth rate µm (0.5274 hr-1) after 22 hr cultivation at 50°C. The highest enzyme activities of sulfide quinone oxidoreductase (0.369 ± 0.052 U/mg) and sulfur dioxygenase (0.255 ± 0.014 U/mg) were both obtained at 40°C, and the highest enzyme activity of sulfite acceptor oxidoreductase (1.302 ± 0.035 U/mg) was assessed at 50°C. The results indicated that P. naphthalenovorans possessed a rapid growth rate and efficient sulfide oxidation capacities under thermophilic conditions, promising a potential application in controlling sulfur-containing odors during the thermophilic stage of sludge composting.


Assuntos
Compostagem , Paenibacillus , Esgotos/química , Sulfatos , Cinética , Sulfetos , Óxidos de Enxofre , Oxirredutases , Enxofre
3.
Bioact Mater ; 21: 1-19, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36017071

RESUMO

Although nano-immunotherapy has advanced dramatically in recent times, there remain two significant hurdles related to immune systems in cancer treatment, such as (namely) inevitable immune elimination of nanoplatforms and severely immunosuppressive microenvironment with low immunogenicity, hampering the performance of nanomedicines. To address these issues, several immune-regulating camouflaged nanocomposites have emerged as prevailing strategies due to their unique characteristics and specific functionalities. In this review, we emphasize the composition, performances, and mechanisms of various immune-regulating camouflaged nanoplatforms, including polymer-coated, cell membrane-camouflaged, and exosome-based nanoplatforms to evade the immune clearance of nanoplatforms or upregulate the immune function against the tumor. Further, we discuss the applications of these immune-regulating camouflaged nanoplatforms in directly boosting cancer immunotherapy and some immunogenic cell death-inducing immunotherapeutic modalities, such as chemotherapy, photothermal therapy, and reactive oxygen species-mediated immunotherapies, highlighting the current progress and recent advancements. Finally, we conclude the article with interesting perspectives, suggesting future tendencies of these innovative camouflaged constructs towards their translation pipeline.

4.
Platelets ; 34(1): 2131752, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36210791

RESUMO

This study investigated the effect of L-PRF on promoting full-thickness skin grafting for the treatment of diabetic foot ulcer wounds and attempted to characterize the mechanism. In a retrospective study, we centrifugated 10-20 ml of venous blood at 1006.2 g for 20 min. The fibrin clot between the top oligocellular plasma layer and the bottom erythrocyte layer was extracted and directly used, without compression, to cover the wound after debridement. Patients who received L-PRF before skin grafting underwent surgery earlier than patients in the control group. Skin necrosis occurred in 7 patients (28%) in the L-PRF group and 16 (64%) in the control group. The difference was statistically significant, P < .05. The postoperative infection rate in the control group (56%) was significantly higher than that in the L-PRF group (24%), P < .05. During a mean follow-up of 1 year, ulcer recurrence occurred in 9 patients (36%) in the control group compared with 4 patients (16%) in the L-PRF group, P < .05. The final amputation rate was also higher in the control group (48%) than in the L-PRF group (20%). The difference is statistically significant, P < .05. The Maryland scale score and SF-36 score of the two groups of patients after treatment were significantly better than those before treatment, and the difference was statistically significant (P < .05). The L-PRF group (94.80 ± 4.14) had better foot scores at the last follow-up after treatment than the control group (88.84 ± 5.22) (P < .05). The results showed that L-PRF played a positive role in the treatment of Wagner grade 4 ulcer gangrene with free full-thickness skin grafts.


What is the context?● Diabetic foot is a serious complication in the later stage of the disease course of diabetic patients. The incidence rate is increasing year by year. In severe cases, it can lead to amputation or even death.● For diabetic ulcer wounds, dressings such as L-PRF or autologous fat are often used in the initial stage to speed up wound healing. For advanced wounds, especially patients with local tissue gangrene, simple wound dressings cannot meet the needs of wounds. People often use skin flaps or different types of skin grafts to treat advanced wounds.● Flap or skin grafting has been shown to be effective, but because of the patient's own neurovascular injury and infection, the rate of graft necrosis and ulcer recurrence is extremely high. What is new?● This study discusses the treatment of advanced wounds in diabetes. After thorough debridement and before skin grafting, we first covered the wound with L-PRF and observed the wound condition. Studies have shown that the use of L-PRF can allow the original poor wound to be reconstructed: the content of growth factors and growth-related cells is increased, blood circulation is improved and granulation tissue growth, bone and tendon exposure is improved, and infection is controlled. What is the impact?● This study provides evidence that using L-PRF to reconstruct wounds can greatly shorten the preparation time for elective surgery. Reconstructed wounds can better accept free skin grafts, and the incidence of postoperative complications and amputation (particularly, toe amputation) is also lower.


Assuntos
Diabetes Mellitus , Pé Diabético , Humanos , Pé Diabético/cirurgia , Transplante de Pele , Fibrina/uso terapêutico , Gangrena/cirurgia , Estudos Retrospectivos , Cicatrização , Leucócitos , Dedos do Pé/cirurgia
5.
J Zhejiang Univ Sci B ; 23(11): 968-974, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36379615

RESUMO

Multiple myeloma (MM) is a common malignant hematological tumor in adults, which is characterized by clonal malignant proliferation of plasma cells in the bone marrow and secretion of a large number of abnormal monoclonal immunoglobulins (M protein), leading to bone destruction, hypercalcemia, anemia, and renal insufficiency (Alexandrakis et al., 2015; Yang et al., 2018). Since a large number of new drugs, represented by proteasome inhibitors and immunomodulators, have been successfully used to treat MM, treatment efficacy and survival of patients have been significantly improved. However, due to the high heterogeneity of this disease, patients have responded differently to treatments with these new drugs (Palumbo and Anderson, 2011; Wang et al., 2016; Huang et al., 2020). Growth and survival of MM cells depend on the bone marrow microenvironment, especially numerous inflammatory cytokines secreted by myeloma cells and bone marrow stromal cells, such as vascular endothelial growth factor (VEGF), interleukin (IL)|-6, transforming growth factor-|ß (TGF||-||ß), and IL-10. These cytokines can promote the growth of myeloma cells, induce angiogenesis, and inhibit antitumor immunity, and are often linked to patient prognosis (Kumar et al., 2017). In this era of new drugs, the prognostic values of the serum levels of these cytokines in MM need further evaluation.


Assuntos
Mieloma Múltiplo , Adulto , Humanos , Mieloma Múltiplo/tratamento farmacológico , Interleucina-10 , Fator A de Crescimento do Endotélio Vascular , Citocinas , Interleucina-6/metabolismo , Progressão da Doença , Microambiente Tumoral
6.
Int J Ophthalmol ; 15(11): 1845-1851, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36404961

RESUMO

AIM: To investigate the effects of micro-injection of botulinum toxin A (BTXA) on acute acquired comitant esotropia (AACE). METHODS: A total of 33 AACE patients who underwent BTXA micro-injection at Renmin Hospital of Wuhan University from September 1st, 2019 to July 1st, 2021 were retrospective analyzed. Esotropia, eye alignment, stereopsis, and complications were examined at baseline (except complications), 1wk, 1, 3, and 6mo after injection. RESULTS: The average angle of deviation before injection was (+20.24±6.80)Δ at near and (+24.76±6.43)Δ at distance, while (+5.15±5.85)Δ at near and (+7.30±6.17)Δ at distance 6mo after treatment (P<0.05). Six months after injection, the stereopsis of patients had improved. The number of patients having no stereopsis (>800 seconds of arc) decreased from 11 to 3. The number of patients having peripheral stereopsis (300-800 seconds of arc), macular stereopsis (70-200 seconds of arc) and central concave stereopsis (≤60 seconds of arc) increased from 10 to 11, 10 to 12, and 2 to 7, respectively. At the follow-ups at 1wk, 1, 3, and 6mo after injection, success rates were 96.97%, 96.97%, 93.94% and 87.88%, respectively. One week after injection, two patients (6.07%) showed subconjunctival hemorrhage; three patients (9.09%) showed limited eye movement and one patient (3.03%) showed mild vertical strabismus. All the symptoms disappeared by the final follow-up. CONCLUSION: Micro-injection of BTXA can reduce diplopia and improve binocular vision function of AACE patients. Furthermore, the operation is relatively safe with few complications, making it an ideal treatment modality for AACE.

7.
World J Oncol ; 13(5): 289-298, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36406192

RESUMO

Background: As one of the most widely used anti-diabetic drugs for type II diabetes, metformin has been shown to exhibit anti-cancer activity in recent years. Epidermal growth factor (EGF) and its receptor, EGFR, play important roles in cancer metastasis in various tumors, including breast cancer. Epithelial-mesenchymal transition (EMT) is a critical process for cancer invasion and metastasis. In this study, we use EGF as a metastatic inducer to investigate the effect of metformin on cancer cell migration, invasion and EMT. Methods: Human breast cancer MCF-7 cells were exposed to EGF with or without metformin or N-acetyl cysteine (NAC). The effects of metformin on breast cancer cell proliferation were analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The production of reactive oxygen species (ROS) was tested using 2,7-dichlorodihydrofluorecein diacetate (DCFH-DA). The migratory and invasive abilities of tumor cells were analyzed using wound healing assay and transwell invasion assay, respectively. The expressions of E-cadherin, N-cadherin and Snail were tested using real-time quantitative polymerase chain reaction (qRT-PCR) and western blotting at mRNA and protein levels. The activation of protein kinase B (Akt) and nuclear factor kappa B (NF-κB) were measured by western blotting. Results: Our results showed that metformin inhibited breast cancer cell proliferation in a dose-dependent manner with or without EGF. EGF-induced alterations in cell morphology that are characteristic of EMT were reversed by metformin. Metformin also inhibited the EGF-modulated expression of E-cadherin, N-cadherin and Snail and further suppressed cell invasion and migration. In addition, metformin suppressed EGF-induced phosphorylation of Akt and NF-κB. ROS is involved in EGF-induced cancer invasion and activation of phosphatidylinositol 3-kinase (PI3K)/Akt/NF-κB pathway. Conclusion: Taken together, these data indicate that metformin suppresses EGF-induced breast cancer cell migration, invasion and EMT through the inhibition of the PI3K/Akt/NF-κB pathway. These results provide a novel mechanism to explain the role of metformin as a potent anti-metastatic agent in breast cancer cells.

8.
Front Nutr ; 9: 1006440, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36407509

RESUMO

Ultrasonic washing has been proved to be an abiotic elicitor to induce the accumulation of phenolics in some fruit and vegetables. However, the feasibility of ultrasonic washing on the accumulation of phenolics in fresh-cut red cabbages has not yet been reported. Therefore, the effects of ultrasonic washing on the phenolics and related phenolic metabolism enzymes of fresh-cut red cabbages, as well as quality and microbial safety during cold storage, were investigated. Firstly, the single-factor tests were used to optimize the ultrasonic processing parameters, including frequency mode, frequency amplitude, power density, frequency cycle time, and ultrasonic washing. Then the activities of the enzymes related to phenolic metabolisms after optimal ultrasound treatment were investigated, including phenylalanine ammonia-lyase (PAL), polyphenol oxidase (PPO), and peroxidase (POD). Additionally, the quality and microbial safety of fresh-cut red cabbages stored at 4°C under the optimal ultrasound treatment were evaluated. The results showed that the content of soluble phenolics (SPs) in fresh-cut red cabbages increased significantly during storage under the optimal conditions (28 ± 2 kHz, 60 W/L, 400 ms, and 20 min) compared with the control (P < 0.05). The PAL activity was activated and the PPO and POD activities were inhibited after ultrasonic washing, which contributed to the increase in the content of SPs. Meanwhile, the storage quality and microbial safety of fresh-cut red cabbages were improved. Ultrasonic washing reduced the weight loss and respiration rate and improved the color and texture characteristics. Additionally, the fresh-cut red cabbages after ultrasonic washing showed more retention of ascorbic acid (AA), total soluble proteins (TSPs), total soluble sugars (TSSs), and total soluble solids (SSs) compared with the control. Finally, ultrasonic washing effectively inhibited the growth of bacteria, molds and yeasts, which is beneficial to the extension of the shelf-life of fresh-cut red cabbages. Therefore, ultrasonic washing can be used as a tool to increase the content of SPs in fresh-cut red cabbages while retaining quality attributes and microbial safety.

9.
Nat Commun ; 13(1): 7043, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36396665

RESUMO

Current therapies for HER2-positive breast cancer have limited efficacy in patients with triple-positive breast cancer (TPBC). We conduct a multi-center single-arm phase 2 trial to test the efficacy and safety of an oral neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib (a CDK4/6 inhibitor) in patients with treatment-naïve, stage II-III TPBC with a Karnofsky score of ≥70 (NCT04486911). The primary endpoint is the proportion of patients with pathological complete response (pCR) in the breast and axilla. The secondary endpoints include residual cancer burden (RCB)-0 or RCB-I, objective response rate (ORR), breast pCR (bpCR), safety and changes in molecular targets (Ki67) from baseline to surgery. Following 5 cycles of 4-week treatment, the results meet the primary endpoint with a pCR rate of 30.4% (24 of 79; 95% confidence interval (CI), 21.3-41.3). RCB-0/I is 55.7% (95% CI, 44.7-66.1). ORR is 87.4%, (95% CI, 78.1-93.2) and bpCR is 35.4% (95% CI, 25.8-46.5). The mean Ki67 expression reduces from 40.4% at baseline to 17.9% (P < 0.001) at time of surgery. The most frequent grade 3 or 4 adverse events are neutropenia, leukopenia, and diarrhoea. There is no serious adverse event- or treatment-related death. This fully oral, chemotherapy-free, triplet combined therapy has the potential to be an alternative neoadjuvant regimen for patients with TPBC.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Humanos , Feminino , Terapia Neoadjuvante/métodos , Letrozol/uso terapêutico , Neoplasias da Mama/patologia , Antígeno Ki-67 , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico
11.
Glob Chang Biol ; 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36408718

RESUMO

Atmospheric nitrogen (N) deposition is composed of both inorganic N (IN) and organic N (ON), and these sources of N may exhibit different impacts on ecosystems. However, our understanding of the impacts of N deposition is largely based on experimental gradients of INs or more rarely ONs. Thus, the effects of N deposition on ecosystem productivity and biodiversity may be biased. We explored the differential impacts of N addition with different IN:ON ratios (0:10, 3:7, 5:5, 7:3, and 10:0) on aboveground net primary productivity (ANPP) of plant community and plant diversity in a typical temperate grassland with a long-term N addition experiment. Soil pH, litter biomass, soil IN concentration, and light penetration were measured to examine the potential mechanisms underlying species loss with N addition. Our results showed that N addition significantly increased plant community ANPP by 68.33-105.50% and reduced species richness by 16.20-37.99%. The IN:ON ratios showed no significant effects on plant community ANPP. However, IN-induced species richness loss was about 2.34 times of ON-induced richness loss. Soil pH was positively related to species richness, and they exhibited very similar response patterns to IN:ON ratios. It implies that soil acidification accounts for the different magnitudes of species loss with IN and ON additions. Overall, our study suggests that it might be reasonable to evaluate the effects of N deposition on plant community ANPP with either IN or ON addition. However, the evaluation of N deposition on biodiversity might be overestimated if only IN is added or underestimated if only ON is added.

12.
Biomed Pharmacother ; 156: 113954, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36411638

RESUMO

Vascular aging, a major risk factor for cardiovascular disease, contributes to morbidity and mortality in older people. Mitochondria play an important role in vascular aging. In endothelial and smooth muscle cells, multiple changes in the mitochondrial structure and function contribute to aging, including the effects of mitochondrial oxidative stress, mitochondrial DNA mutations, mitochondrial dynamics, and mitophagy. Mitochondrial dysfunction also contributes to other age-related molecular and cellular mechanisms, such as crosstalk with telomeres, senescence-associated secretory phenotypes, and low-grade inflammation. Thus, enhancing mitochondrial biogenesis, reducing oxidative stress, recovering dynamics, and mitophagy have been suggested as effective interventions to delay vascular aging and age-related cardiovascular diseases. Furthermore, accumulating evidence has shown that commonly used herbs and their natural compounds have great potential to improve mitochondrial function during vascular aging. Herein, we review the cellular and molecular mechanisms of mitochondrial effects on vascular aging, emphasizing the efficacy of natural compounds in the treatment of vascular aging by improving mitochondrial structure and function. We aim to provide new insights into delaying vascular aging and preventing cardiovascular diseases.


Assuntos
Doenças Cardiovasculares , Humanos , Mitocôndrias/genética , Mitofagia , Dinâmica Mitocondrial
13.
Chem Biodivers ; 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36382445

RESUMO

Eleven polyphenols, classified as flavonoid glycosides, flavonoid aglycones, and phenolic acids, are important bioactive components in the capitula of Coreopsis tinctoria (CCT). Nevertheless, their full pharmacokinetic profiles have not been demonstrated simultaneously. Therefore, a liquid chromatography - tandem mass spectrometry (LC-MS/MS) method was developed in the present work and used it to study the pharmacokinetics of these 11 compounds. We performed LC-MS/MS with a gradient mobile phase composed of water containing 0.1% formic acid and acetonitrile containing 0.1% formic acid on a Proshell 120 SB C18 column (2.1 mm × 100 mm, 2.7 µm). We achieved a good chromatographic peak shape, resolution, and mass signal response, and multiple reaction monitoring facilitated the simultaneous detection of 11 analytes. In addition, we validated the selectivity, correlation coefficient, precision, extraction recovery, matrix effects, and stability of the LC-MS/MS method to be acceptable for 11 analytes in rat plasma. Subsequently, rats were orally administered with 50% ethanol eluent of CCT (ECCT). Nine of 11 polyphenols were absorbed quickly (except for QCD and TCA), and their plasma levels peaked within 40 min. The exposure and Cmax values of flavonoid glycosides and phenolic acids were lower than those of flavonoid aglycones. This is the first report to demonstrate the pharmacokinetics of 11 polyphenols in ECCT, which may play an important role in future studies of the bioactive components of ECCT and their bioactive mechanisms.

14.
Int J Mol Sci ; 23(21)2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36361585

RESUMO

The metalloprotease ADAM17 is a key regulator of the TNFα, IL-6R and EGFR signaling pathways. The maturation and function of ADAM17 is controlled by the seven-membrane-spanning proteins iRhoms1 and 2. The functional properties of the ADAM17/iRhom1 and ADAM17/iRhom2 complexes differ, in that stimulated shedding of most ADAM17 substrates tested to date can be supported by iRhom2, whereas iRhom1 can only support stimulated shedding of very few ADAM17 substrates, such as TGFα. The first transmembrane domain (TMD1) of iRhom2 and the sole TMD of ADAM17 are important for the stimulated shedding of ADAM17 substrates by iRhom2. However, little is currently known about how the iRhoms interact with different substrates to control their stimulated shedding by ADAM17. To provide new insights into this topic, we tested how various chimeras between iRhom1 and iRhom2 affect the stimulated processing of the EGFR-ligands TGFα (iRhom1- or 2-dependent) and EREG (iRhom2-selective) by ADAM17. This uncovered an important role for the TMD7 of the iRhoms in determining their substrate selectivity. Computational methods utilized to characterize the iRhom1/2/substrate interactions suggest that the substrate selectivity is determined, at least in part, by a distinct accessibility of the substrate cleavage site to stimulated ADAM17. These studies not only provide new insights into why the substrate selectivity of stimulated iRhom2/ADAM17 differs from that of iRhom1/ADAM17, but also suggest new approaches for targeting the release of specific ADAM17 substrates.


Assuntos
Proteínas de Transporte , Fator de Crescimento Transformador alfa , Fator de Crescimento Transformador alfa/metabolismo , Proteínas de Transporte/metabolismo , Proteína ADAM17/metabolismo , Proteínas de Membrana/metabolismo , Transdução de Sinais , Receptores ErbB/metabolismo
15.
Comput Intell Neurosci ; 2022: 9917691, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36387767

RESUMO

Accurate retinal blood vessels segmentation is an important step in the clinical diagnosis of ophthalmic diseases. Many deep learning frameworks have come up for retinal blood vessels segmentation tasks. However, the complex vascular structure and uncertain pathological features make blood vessel segmentation still very challenging. This paper proposes a novel multimodule concatenation via a U-shaped network for retinal vessels segmentation, which is based on atrous convolution and multikernel pooling. The proposed network structure retains three layers of the essential structure of U-Net, in which the atrous convolution combining the multikernel pooling blocks are designed to obtain more contextual information. The spatial attention module is concatenated with the dense atrous convolution module and the multikernel pooling module to form a multimodule concatenation. And different dilation rates are selected by cascading to acquire a larger receptive field in atrous convolution. Adequate comparative experiments are conducted on these public retinal datasets: DRIVE, STARE, and CHASE_DB1. The results show that the proposed method is effective, especially for microvessels. The code will be released at https://github.com/rocklijun/MC-UNet.


Assuntos
Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , Processamento de Imagem Assistida por Computador/métodos , Algoritmos , Vasos Retinianos/diagnóstico por imagem , Retina
16.
Sci Total Environ ; 858(Pt 2): 159954, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36347297

RESUMO

The purpose of this study was to access the effects of thermotolerant nitrifying microorganisms and sulfur-oxidizing bacteria on microbial community and enzyme activity involved in nitrogen­sulfur metabolism during laboratory-scale sewage sludge (SS) composting,and to do a microbial-environmental factor association analysis to promote composting key species for nitrogen­sulfur transformation in the body. The microbial community structure and the activities variation of six key enzyme involved were detected. The microbial inocula added had little impact on the diversity of the microbial community but changed its succession direction, and the abundance of Actinobacteria was decreased obviously of inoculation treatment (TR). The three dominant genera and indicator species in TR were significantly correlated with the conversion of nitrogen and sulfur. The addition of microbial inocula promoted the conversion of nitrogen and sulfur in SS compost, and increased the activities of the key enzymes and the microbial genera involved in nitrogen­sulfur conversion. In other words, the nitrification and sulfur oxidation were enhanced simultaneously in the later stage of composting in TR.

17.
Fitoterapia ; 163: 105343, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36328169

RESUMO

In this study, it was confirmed at first time that the crude extracts of Psoralea corylifolia seeds (PCE34) can reduce serum lipids (AST, ALT, TG, TC, LDL, ALP, ACP and LDH), body weight and serum sugar, increase HDL and serum insulin in hyperlipidemic wistar rat induced by high-fat diet in vivo. Furthermore, eight new chalcones 1-8, one new flavanone 12, one new coumarin 14, three new meroterpenes 15-17 and one new bakuchiol 20 together with seven known compounds (9-11, 13, 18-19 and 21) were isolated from the PCE34. Their structures were elucidated based on analyses of their spectroscopic (UV, CD, NMR and HREIMS) data. All the isolates were evaluated for in vitro inhibitory activity against DGAT1/2, PTP1B and α-Glucosidase. Among them, compounds 1-3, 8-11, 14-17, 19 and 20 were found to exhibit selective inhibitory activity on DGAT1 with IC50 values ranging from 66.7 ± 1.2 to 87.2 ± 1.3 µM; 1, 8-12, 14 and 20 has the best inhibit active on PTP1B with IC50 values ranging from 13.8 ± 1.1 to 19.1 ± 1.6 µM; 1-12 and 14 displayed the significant inhibitory activities on α-Glucosidase with IC50 values ranging from 29.1 ± 1.2 to 79.4 ± 1.2 µM.

18.
J Environ Manage ; 326(Pt A): 116733, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36372033

RESUMO

The emission of H2S odors predominantly occurred at the thermophilic phase of composting, which could cause odorous gas pollution and reduce the fertilizer value of composting products. And sulfur-oxidizing bacteria (SOB) possess oxidative capacities for inorganic sulfur compounds with nitrate applied as electron acceptors. Therefore, this study aimed to assess the effectiveness of combined additives (SOB inoculants and nitrate) on the bacterial community diversity, sulfur-oxidizing gene abundances, and metabolic function prediction at the thermophilic stage of sewage sludge composting. The highest sulfate contents were increased by 1.02-1.34 folds, and the abundances of the sulfur-oxidizing genes (sqr, pdo, sox, and sor) were also enhanced by adding the combined additives. Network patterns revealed a strengthened interaction of inoculants and sulfur functional genes. Microbial functional pathways predicted higher metabolic levels of carbohydrate and amino acid metabolisms with the addition of combined additives, and the predicted relative abundances of sulfur metabolism and nitrogen metabolism were increased by 19.3 ± 2.5% and 24.7 ± 4.1%, respectively. Heatmap analysis showed that the SOB might have a competitive advantage over the indigenous denitrifying bacteria in using nitrate for biochemical reactions. Correlation analyses suggested that sulfur-oxidizing efficacy could be indirectly affected by the environmental parameters through changing the structure of bacterial community. These findings provide new insights toward an optimized inoculation strategy of using SOB and nitrate to enhance sulfur preservation and modulate the bacterial communities at the thermophilic phase of sewage sludge composting.

19.
Front Oncol ; 12: 1037831, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36419880

RESUMO

Breast cancer has a high mortality rate among malignant tumors, with metastases identified as the main cause of the high mortality. Dysbiosis of the gut microbiota has become a key factor in the development, treatment, and prognosis of breast cancer. The many microorganisms that make up the gut flora have a symbiotic relationship with their host and, through the regulation of host immune responses and metabolic pathways, are involved in important physiologic activities in the human body, posing a significant risk to health. In this review, we build on the interactions between breast tissue (including tumor tissue, tissue adjacent to the tumor, and samples from healthy women) and the microbiota, then explore factors associated with metastatic breast cancer and dysbiosis of the gut flora from multiple perspectives, including enterotoxigenic Bacteroides fragilis, antibiotic use, changes in gut microbial metabolites, changes in the balance of the probiotic environment and diet. These factors highlight the existence of a complex relationship between host-breast cancer progression-gut flora. Suggesting that gut flora dysbiosis may be a host-intrinsic factor affecting breast cancer metastasis and progression not only informs our understanding of the role of microbiota dysbiosis in breast cancer development and metastasis, but also the importance of balancing gut flora dysbiosis and clinical practice.

20.
Clin Exp Med ; 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36422737

RESUMO

Although platinum-based chemotherapy can improve pathologic complete response (pCR) in patients with triple-negative breast cancer (TNBC), the impact on survival of platinum-based neoadjuvant and adjuvant chemotherapy is still controversial. Our meta-analysis aimed at analyzing survival with platinum-based neoadjuvant and adjuvant chemotherapy in patients with TNBC. We searched PubMed, EMBASE, MEDLINE, Cochrane databases, and several major conferences up to January 2021. Fixed and random models were used for our meta-analysis. Disease-free survival (DFS), overall survival (OS), and side effects data were extracted from the included literature in addition to the corresponding pooled hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CIs). A total of nine studies involving 3247 patients were included. The pooled analysis suggested that compared with anthracycline- and/or paclitaxel-based chemotherapy, platinum-based chemotherapy could further improve DFS (HR = 0.56, 95% CI 0.45-0.67, p < 0.01) and OS (HR = 0.54, 95% CI 0.38-0.70, p < 0.01) in patients with TNBC. The subgroup analysis showed that platinum-based chemotherapy could further improve DFS (HR = 0.59, 95% CI 0.43-0.74, p < 0.01) and OS (HR = 0.61, 95% CI 0.40-0.83, p < 0.01) in neoadjuvant chemotherapy and DFS (HR = 0.53, 95% CI 0.37-0.69, p < 0.01) and OS (HR = 0.46, 95% CI 0.23-0.69, p < 0.01) in adjuvant chemotherapy compared with anthracycline- and/or paclitaxel-based chemotherapy in patients with TNBC. In addition, compared with anthracycline-based chemotherapy, platinum-based chemotherapy without anthracycline chemotherapy could further improve DFS (HR = 0.53, 95% CI 0.37-0.70, p < 0.01) and OS (HR = 0.46, 95%CI 0.19-0.72, p < 0.01) in patients with TNBC. Compared with anthracycline- and/or paclitaxel-based chemotherapy, all-grade diarrhea, fatigue, and grade ≥ 3 anemia were higher in platinum-based chemotherapy. In contrast, all-grade anemia, leukopenia, neutropenia, peripheral neuropathy, myalgia/arthralgia, cardiac toxicity were lower in platinum-based chemotherapy; grade ≥ 3 leukopenia, neutropenia and myalgia/arthralgia were also lower. Compared with anthracycline- and/or paclitaxel-based chemotherapy, platinum-based chemotherapy was more associated with improved DFS and OS in TNBC patients. The benefit of survival is consistent with platinum-based neoadjuvant and adjuvant chemotherapy. The side effects of platinum-based chemotherapy are tolerable.

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