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1.
Artigo em Inglês | MEDLINE | ID: mdl-34982184

RESUMO

Although therapeutic cancer vaccines have been gaining substantial ground, the development of cancer vaccines is impeded because of the undegradability of delivery systems, ineffective delivery of tumor antigens and weak immunogenicity of adjuvants. Here, we made use of a whole glucan particle (WGP) to encapsulate ovalbumin (OVA), thereby formulating a novel cancer vaccine. Results from in vitro experiments showed that WGP-OVA not only induced the activation of bone marrow-derived macrophages (BMDMs) including driving M0 BMDM polarization to the M1 phenotype, upregulating the costimulatory molecules and inducing the generation of cytokines, but also facilitated antigen presentation. After oral administration of the WGP-OVA formulation to mice with OVA-expressing tumors, these particles can increase tumor-infiltrating OVA-specific CD8+ CTLs and repolarize tumor-associated macrophages (TAMs) toward M1-like phenotype, which led to delayed tumor progression. These findings revealed that WGP could serve as both an antigen delivery system and an adjuvant system for promising cancer vaccines.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34990549

RESUMO

Two-dimensional (2D) hybrid perovskites have been extensively studied as the promising light-sensitive materials in the photodetectors owing to their improved structural stability over that of their three-dimensional counterparts. However, the application of the 2D perovskite-based photodetector in the near-infrared (NIR) region is obstructed by the large intrinsic optical band gap. Herein, we develop a novel van der Waals heterostructure composed of few-layer 2D perovskite/MoS2 nanoflakes, which exhibits high-sensitivity detection performance over a broad spectral region, from the visible region to the telecommunication wavelength (i.e., 1550 nm). In particular, the photoresponsivity and specific detectivity under an 860 nm laser reach 121 A W-1 and 4.3 × 1014 Jones, respectively, whereas the individual nanoflakes show no response under the same wavelength. Meanwhile, the response time at the microsecond (µs) level is obtained, shortened by around 3 orders of magnitude compared to that of the constituting layers. The sensitive and ultrafast photoresponse at the NIR wavelength stems from the strong interlayer transition of sub-band-gap photons and the rapid separation of the photogenerated carriers by the built-in field within the heterojunction area. Our results not only provide an effective approach to achieve sub-band-gap photodetection in 2D perovskite-based structures but also suggest a universal strategy to fabricate high-performance optoelectronic devices.

3.
Drug Deliv ; 29(1): 203-213, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34985396

RESUMO

The construction of multifunctional oncotherapy nanoplatforms that combine diagnosis and treatment remains challenging. Nanodroplets (NDs), which simultaneously enhance ultrasound imaging and therapeutic effects, are a potential strategy for non-invasive drug delivery. To achieve the goals of precise medicine, novel SP94 peptide-modified and doxorubicin-loaded ultrasonic NDs (SP94-DOX-NDs) for castration-resistant prostate cancer (CRPC) targeting and treatment were constructed in this study. The characteristics, contrast-enhanced ultrasound imaging (CEUI), targeting ability to glucose-regulated protein 78 (GRP78)-overexpressing CRPC and anticancer effect of the SP94-DOX-NDs were assessed. The desired SP94-NDs were successfully prepared using the nanoemulsification method using a certain proportion of SP94-PEG-chitosan, perfluoropentane (PFP), Tween 20, and lecithin. SP94-NDs with a size of ∼300 nm showed great biocompatibility and CEUI ability. Compared with blank NDs, SP94-NDs exhibited higher tumor-specific targeting ability due to conjugation between the SP94 peptide and GRP78-overexpressing 22RV1 cells. Most importantly, in vitro and in vivo investigations showed that SP94-DOX-NDs combined with ultrasound could specifically deliver DOX into 22RV1 cells and thereby demonstrated a stronger anticancer effect than DOX-NDs and DOX. Thus, SP94-DOX-NDs may provide an efficient approach for the real-time imaging of tumors and triggered, accurate drug delivery to tumors.

4.
Molecules ; 27(1)2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-35011557

RESUMO

Pyrene molecules containing NBN-doped polycyclic aromatic hydrocarbons (PAHs) have been synthesized by a simple and efficient intermolecular dehydration reaction between 1-pyrenylboronic acid and aromatic diamine. Pyrene-B (o-phenylenediamine) with a five-membered NBN ring and pyrene-B (1,8-diaminonaphthalene) with a six-membered NBN ring show differing luminescence. Pyrene-B (o-phenylenediamine) shows concentration-dependent luminescence and enhanced emission after grinding at solid state. Pyrene-B (1,8-diaminonaphthalene) exhibits a turn-on type luminescence upon fluoride ion addition at lower concentration, as well as concentration-dependent stability. Further potential applications of Pyrene-B (o-phenylenediamine) on artificial light-harvesting film were demonstrated by using commercial NiR dye as acceptor.

5.
J Cell Physiol ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35023144

RESUMO

The sterile inflammation (SI) of the urinary tract is a common problem requiring serious consideration after prostatectomy. This study mainly focuses on the role of the reactive oxygen species-NLR family, pyrin domain-containing 3 (ROS-NLRP3) signaling pathway in SI after thulium laser resection of the prostate (TmLRP). Urinary cytokines were determined in patients who received TmLRP, and heat shock protein 70 (HSP70) was detected in the resected tissues. The involvement of ROS signaling in HSP70-induced inflammation was explored in THP-1 cells with or without N-acetyl- l-cysteine (NAC) pretreatment. The function of NLRP3 and Caspase-1 was determined by Western blot analysis, enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction. These phenomena and mechanisms were verified by the beagle models that received TmLRP. Clinical urine samples after TmLRP showed high expression of inflammatory factors and peaked 3-5 days after surgery. The high expression of HSP70 in the resected tissues was observed. After HSP70 stimulation, the expression of ROS, NLRP3, Caspase-1, and interleukin-18 (IL-18) increased significantly and could be reduced by ROS inhibitor NAC. The expression of IL-1ß and IL-18 could be inhibited by NLRP3 or Caspase-1 inhibitors. In beagle models that received TmLRP, HSP70, NLRP3, Caspase-1, IL-1ß, and IL-18 were highly expressed in the wound tissue or urine, and could also be reduced by NAC pretreatment. Activation of the ROS-NLRP3 signaling pathway induces SI in the wound after prostatectomy. Inhibition of this pathway may be effective for clinical prevention and treatment of SI and related complications after prostatectomy.

6.
Neural Regen Res ; 17(8): 1776-1784, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35017438

RESUMO

As a highly evolutionary conserved long non-coding RNA, metastasis associated lung adenocarcinoma transcript 1 (MALAT1) was first demonstrated to be related to lung tumor metastasis by promoting angiogenesis. To investigate the role of MALAT1 in traumatic brain injury, we established mouse models of controlled cortical impact and cell models of oxygen-glucose deprivation to mimic traumatic brain injury in vitro and in vivo. The results revealed that MALAT1 silencing in vitro inhibited endothelial cell viability and tube formation but increased migration. In MALAT1-deficient mice, endothelial cell proliferation in the injured cortex, functional vessel density and cerebral blood flow were reduced. Bioinformatic analyses and RNA pull-down assays validated enhancer of zeste homolog 2 (EZH2) as a downstream factor of MALAT1 in endothelial cells. Jagged-1, the Notch homolog 1 (NOTCH1) agonist, reversed the MALAT1 deficiency-mediated impairment of angiogenesis. Taken together, our results suggest that MALAT1 controls the key processes of angiogenesis following traumatic brain injury in an EZH2/NOTCH1-dependent manner.

7.
J Neurosurg Spine ; : 1-9, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996038

RESUMO

OBJECTIVE: The traditional anterior approach for multilevel severe cervical ossification of the posterior longitudinal ligament (OPLL) is demanding and risky. Recently, a novel surgical procedure-anterior controllable antedisplacement and fusion (ACAF)-was introduced by the authors to deal with these problems and achieve better clinical outcomes. However, to the authors' knowledge, the immediate and long-term biomechanical stability obtained after this procedure has never been evaluated. Therefore, the authors compared the postoperative biomechanical stability of ACAF with those of more traditional approaches: anterior cervical discectomy and fusion (ACDF) and anterior cervical corpectomy and fusion (ACCF). METHODS: To determine and assess pre- and postsurgical range of motion (ROM) (2 Nm torque) in flexion-extension, lateral bending, and axial rotation in the cervical spine, the authors collected cervical areas (C1-T1) from 18 cadaveric spines. The cyclic fatigue loading test was set up with a 3-Nm cycled load (2 Hz, 3000 cycles). All samples used in this study were randomly divided into three groups according to surgical procedures: ACDF, ACAF, and ACCF. The spines were tested under the following conditions: 1) intact state flexibility test; 2) postoperative model (ACDF, ACAF, ACCF) flexibility test; 3) cyclic loading (n = 3000); and 4) fatigue model flexibility test. RESULTS: After operations were performed on the cadaveric spines, the segmental and total postoperative ROM values in all directions showed significant reductions for all groups. Then, the ROMs tended to increase during the fatigue test. No significant crossover effect was detected between evaluation time and operation method. Therefore, segmental and total ROM change trends were parallel among the three groups. However, the postoperative and fatigue ROMs in the ACCF group tended to be larger in all directions. No significant differences between these ROMs were detected in the ACDF and ACAF groups. CONCLUSIONS: This in vitro biomechanical study demonstrated that the biomechanical stability levels for ACAF and ACDF were similar and were both significantly greater than that of ACCF. The clinical superiority of ACAF combined with our current results showed that this procedure is likely to be an acceptable alternative method for multilevel cervical OPLL treatment.

8.
Cell Death Differ ; 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-34997207

RESUMO

A recent mutation analysis suggested that Non-Structural Protein 6 (NSP6) of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a key determinant of the viral pathogenicity. Here, by transcriptome analysis, we demonstrated that the inflammasome-related NOD-like receptor signaling was activated in SARS-CoV-2-infected lung epithelial cells and Coronavirus Disease 2019 (COVID-19) patients' lung tissues. The induction of inflammasomes/pyroptosis in patients with severe COVID-19 was confirmed by serological markers. Overexpression of NSP6 triggered NLRP3/ASC-dependent caspase-1 activation, interleukin-1ß/18 maturation, and pyroptosis of lung epithelial cells. Upstream, NSP6 impaired lysosome acidification to inhibit autophagic flux, whose restoration by 1α,25-dihydroxyvitamin D3, metformin or polydatin abrogated NSP6-induced pyroptosis. NSP6 directly interacted with ATP6AP1, a vacuolar ATPase proton pump component, and inhibited its cleavage-mediated activation. L37F NSP6 variant, which was associated with asymptomatic COVID-19, exhibited reduced binding to ATP6AP1 and weakened ability to impair lysosome acidification to induce pyroptosis. Consistently, infection of cultured lung epithelial cells with live SARS-CoV-2 resulted in autophagic flux stagnation, inflammasome activation, and pyroptosis. Overall, this work supports that NSP6 of SARS-CoV-2 could induce inflammatory cell death in lung epithelial cells, through which pharmacological rectification of autophagic flux might be therapeutically exploited.

9.
BMC Pulm Med ; 22(1): 2, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34980056

RESUMO

BACKGROUND: Serum lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA) and CYFRA21-1 are the commonly used biomarkers to identify patients with autoimmune pulmonary alveolar proteinosis (APAP). However, it is not clear which of the biomarkers is more sensitive to the severity of the patient's condition. METHODS: APAP patients numbering 151 were enrolled in this study. All patients' severity was assessed through the severity and prognosis score of PAP (SPSP). According to the respective laboratory upper limits of serum levels of LDH, CEA and CYFRA21-1, APAP patients were divided into higher and lower-level groups. Patients were divided into five groups based on SPSP. 88 patients had completed six months of follow-up. We calculated sensitivity, specificity, and critical point of LDH, CEA and CYFRA21-1 between APAP patients and normal control group, and between grade 1-2 and 3-5 through receiving operating characteristics (ROC) curve. RESULTS: Serum LDH, CEA and CYFRA21-1 levels of patients with PAP were higher and distinctly related to PaO2, FVC, FEV1, DLCO, HRCT scores and SPSP. The SPSP of patients in higher-level LDH, CEA and CYFRA21-1 groups were higher than those of corresponding lower-level groups. Based on SPSP results, the patients were divided into five groups (grade I, 20; grade II, 37; grade III, 40; grade IV, 38; grade V, 16). The serum level of CYFRA21-1 of patients with APAP in grade II was higher than that of patients in grade I and lower than that of patients in grade III. Serum CYFRA21-1 of patients with APAP after six months were higher than the baseline among the aggravated group. Serum LDH, CEA and CYFRA21-1 levels after six months among patients in the relieved group of patients with APAP were lower than the baseline. ROC correlating LDH, CEA and CYFRA21-1 values with APAP severity (between grade 1-2 and 3-5) showed an optimal cutoff of LDH of over 203 U/L (< 246 U/L), CEA of over 2.56 ug/L (< 10 ug/L), and CYFRA21-1 of over 5.57 ng/ml (> 3.3 ng/ml) (AUC: 0.815, 95% CI [0.748-0.882], sensitivity: 0.606, specificity: 0.877). CONCLUSION: Serum CYFRA21-1 level was more sensitive in revealing the severity of APAP than LDH and CEA levels among mild to moderate forms of disease.

10.
Theranostics ; 12(2): 639-656, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34976205

RESUMO

Rationale: B cells have emerged as key regulators in protective cancer immunity. However, the activation pathways induced in B cells during effective immunotherapy are not well understood. Methods: We used a novel localized ablative immunotherapy (LAIT), combining photothermal therapy (PTT) with intra-tumor delivery of the immunostimulant N-dihydrogalactochitosan (GC), to treat mice bearing mouse mammary tumor virus-polyoma middle tumor-antigen (MMTV-PyMT). We used single-cell RNA sequencing to compare the transcriptional changes induced by PTT, GC and PTT+GC in B cells within the tumor microenvironment (TME). Results: LAIT significantly increased survival in the tumor-bearing mice, compared to the treatment by PTT and GC alone. We found that PTT, GC and PTT+GC increased the proportion of tumor-infiltrating B cells and induced gene expression signatures associated with B cell activation. Both GC and PTT+GC elevated gene expression associated with antigen presentation, whereas GC elevated transcripts that regulate B cell activation and GTPase function and PTT+GC induced interferon response genes. Trajectory analysis, where B cells were organized according to pseudotime progression, revealed that both GC and PTT+GC induced the differentiation of B cells from a resting state towards an effector phenotype. The analyses confirmed upregulated interferon signatures in the differentiated tumor-infiltrating B cells following treatment by PTT+GC but not by GC. We also observed that breast cancer patients had significantly longer survival time if they had elevated expression of genes in B cells that were induced by PTT+GC therapy in the mouse tumors. Conclusion: Our findings show that the combination of local ablation and local application of immunostimulant initiates the activation of interferon signatures and antigen-presentation in B cells which is associated with positive clinical outcomes for breast cancer. These findings broaden our understanding of LAIT's regulatory roles in remodeling TME and shed light on the potentials of B cell activation in clinical applications.

11.
J Ethnopharmacol ; 283: 114716, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34626781

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Tribuli (FT) has been commonly used as a traditional medicine for thousands of years. With the diverse uses of FT, more attention has been paid to its hepatorenal toxicity. However, the compounds causing the hepatorenal toxicity of FT remain undetermined. Terrestrosin D (TED), a major spirostanol saponin isolated from FT, may exert hepatorenal toxicity. AIM OF THE STUDY: This study aimed to evaluate the potential hepatorenal toxicity of TED, and preliminarily explore the possible mechanism of TED-induced hepatorenal toxicity. MATERIALS AND METHODS: Cytotoxicity assays, a repeated-dose 28-day in-vivo study, a toxicokinetic study, and a tissue distribution study were used to evaluate the potential hepatorenal toxicity of TED. Furthermore, network pharmacology was applied to preliminarily explore the possible mechanism of TED-induced hepatorenal toxicity. RESULTS: Both the in vitro and in vivo studies showed that the spirostanol saponin TED had potential hepatorenal toxicity. Nonetheless, hepatorenal toxicity induced by oral treatment with TED at a dosage range of 5 - 15 mg/kg daily for 28 consecutive days to Sprague-Dawley (SD) rats was reversible after 14 days of TED withdrawal. The toxicokinetic study demonstrated that the systematic exposure of SD rats to TED had an accumulation phenomenon and a dose-dependent trend after a 28-day repeated-dose oral administration. The tissue distribution study revealed that TED had a targeted distribution in the liver and kidneys accompanied by a phenomenon of accumulation in SD rats. Network pharmacology combined with molecular docking methods was used to screen for the key targets (HSP90AA1, CNR1, and DRD2) and the key pathways of TED-induced hepatorenal toxicity. CONCLUSIONS: The spirostanol saponin TED, a major spirostanol saponin isolated from FT, had potential hepatorenal toxicity.

12.
Eur J Med Chem ; 227: 113898, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34656898

RESUMO

The poly (ADP-ribose) polymerase (PARP) inhibitors play a crucial role in cancer therapy. However, most approved PARP inhibitors have lower selectivity to PARP-1 than to PARP-2, so they will inevitably have side effects. Based on the different catalytic domains of PARP-1 and PARP-2, we developed a strategy to design and synthesize highly selective PARP-1 inhibitors. Compounds Y17, Y29, Y31 and Y49 showed excellent PARP-1 inhibition, and their IC50 values were 0.61, 0.66, 0.41 and 0.96 nM, respectively. Then, Y49 (PARP-1 IC50 = 0.96 nM, PARP-2 IC50 = 61.90 nM, selectivity PARP-2/PARP-1 = 64.5) was proved to be the most selective inhibitor of PARP-1. Compounds Y29 and Y49 showed stronger inhibitory effect on proliferation in BRCA1 mutant MX-1 cells than in other cancer cells. In the MDA-MB-436 xenotransplantation model, Y49 was well tolerated and showed remarkable single dose activity. The design strategy proposed in this paper is of far-reaching significance for the further construction of the next generation of selective PARP-1 inhibitors.

13.
Eur J Med Chem ; 227: 113918, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34688014

RESUMO

SUMOylation and deSUMOylation plays an important role in DNA damage response and the formation of radiotherapy resistance. SENP1 is the main specific isopeptidase to catalyze deSUMOylation modification. Inhibiting SENP1 upregulates cancer cell radiosensitivity and it becomes a promising target for radiosensitization. Herein, based on the structure of ursolic acid (UA), a total of 53 pentacyclic triterpene derivatives were designed and synthesized as SENP1 inhibitors. Ten derivatives exhibited better SENP1 inhibitory activities than UA and the preliminary structure-activity relationship was discussed. Most of the UA derivatives were low-cytotoxic, among which compound 36 showed the best radiosensitizing activity with the SER value of 1.45. It was the first study to develop small molecular SENP1 inhibitors as radiosensitizers.

15.
Neural Regen Res ; 17(3): 577-586, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34380897

RESUMO

MicroRNA-491-5p (miR-491-5p) plays an important role in regulating cell proliferation and migration; however, the effect of miR-491-5p on neovascularization after traumatic brain injury remains poorly understood. In this study, a controlled cortical injury model in C57BL/6 mice and an oxygen-glucose deprivation model in microvascular endothelial cells derived from mouse brain were established to simulate traumatic brain injury in vivo and in vitro, respectively. In the in vivo model, quantitative real-time-polymerase chain reaction results showed that the expression of miR-491-5p increased or decreased following the intracerebroventricular injection of an miR-491-5p agomir or antagomir, respectively, and the expression of miR-491-5p decreased slightly after traumatic brain injury. To detect the neuroprotective effects of miR-491-p, neurological severity scores, Morris water maze test, laser speckle techniques, and immunofluorescence staining were assessed, and the results revealed that miR-491-5p downregulation alleviated neurological dysfunction, promoted the recovery of regional cerebral blood flow, increased the number of lectin-stained microvessels, and increased the survival of neurons after traumatic brain injury. During the in vitro experiments, the potential mechanism of miR-491-5p on neovascularization was explored through quantitative real-time-polymerase chain reaction, which showed that miR-491-5p expression increased or decreased in brain microvascular endothelial cells after transfection with an miR-491-5p mimic or inhibitor, respectively. Dual-luciferase reporter and western blot assays verified that metallothionein-2 was a target gene for miR-491-5p. Cell counting kit 8 (CCK-8) assay, flow cytometry, and 2?,7?-dichlorofluorescein diacetate (DCFH-DA) assay results confirmed that the downregulation of miR-491-5p increased brain microvascular endothelial cell viability, reduced cell apoptosis, and alleviated oxidative stress under oxygen-glucose deprivation conditions. Cell scratch assay, Transwell assay, tube formation assay, and western blot assay results demonstrated that miR-491-5p downregulation promoted the migration, proliferation, and tube formation of brain microvascular endothelial cells through a metallothionein-2-dependent hypoxia-inducible factor-1α/vascular endothelial growth factor pathway. These findings confirmed that miR-491-5p downregulation promotes neovascularization, restores cerebral blood flow, and improves the recovery of neurological function after traumatic brain injury. The mechanism may be mediated through a metallothionein-2-dependent hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway and the alleviation of oxidative stress. All procedures were approved by Ethics Committee of the First Affiliated Hospital of Chongqing Medical University, China (approval No. 2020-304) on June 22, 2020.

16.
Spectrochim Acta A Mol Biomol Spectrosc ; 264: 120267, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34419828

RESUMO

In this paper, a fast and efficient analytical strategy was proposed that chemometrics assisted with excitation-emission fluorescence matrices was used to quantify carbaryl (CAR) and thiabendazole (TBZ) in peach, soil and sewage. Even if there are serious overlapped peaks and unknown interferences in fluorescence analysis, the second-order calibration method based on alternating trilinear decomposition (ATLD) algorithm can be used to analyze CAR and TBZ in peach, soil and sewage. The recoveries of CAR and TBZ in peach are 110.4% and 99.7% and their standard deviations are lower than 2.1% and 0.3%, respectively. In addition, the accuracy of the method was assessed with figures of merit as well as intra-day and inter-day precision. The limit of detection, the limit of quantitation of CAR and TBZ in peach are 1.2 ng mL-1 and 0.3 ng mL-1, 3.5 ng mL-1 and 0.8 ng mL-1, respectively. And their root-mean-square error of prediction are 17.0 ng mL-1 and 5.0 ng mL-1 and there are high sensitivity and selectivity in this method. Meanwhile, the results obtained by ATLD algorithm were compared with those obtained by the self-weighted alternate trilinear decomposition algorithm (SWATLD) and the parallel factor analysis (PARAFAC) algorithm, and statistical methods such as the t-test, F-test and the elliptic joint confidence region were used to evaluate for analysis. There were no significant differences among these methods. At last, high performance liquid chromatography-fluorescence detector (HPLC-FLD) was used to evaluate the accuracy and reliability of the proposed method. These results are satisfactory and indicate that the proposed method can be used for accurate and rapid determination of pesticides in complex systems.


Assuntos
Carbaril , Tiabendazol , Algoritmos , Calibragem , Cromatografia Líquida de Alta Pressão , Reprodutibilidade dos Testes , Espectrometria de Fluorescência
17.
Sci Total Environ ; 802: 149849, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34455273

RESUMO

Promoting land use planning through ecosystem service (ES) protection is a crucial approach for maintaining landscape sustainability. Identifying ES bundles to serve landscape functional zoning can provide a new perspective for sustainable land use planning. Taking the Beijing metropolitan region as a study area, we quantitatively assessed the spatiotemporal distributions of multiple ESs, from 1980 to 2017, based on land use changes. By combining ES patterns and comprehensive ecosystem service (CES), distinct ES bundles were identified through the clustering method. Based on the ES bundles, landscape functional zones were then established. We further developed improved land use scenarios to conserve ESs in selected towns of different functional zones by exploring dominant factors influencing ESs. Results showed that most of ESs decreased due to the expansion of developed lands. According to the classification of ES bundles, Beijing can be classified into three landscape functional zones at town level: the ecological conservation region (ECR), food production region (FPR), and urban development region (UDR). For each landscape functional zone, the town with the greatest decline in CES value was selected. Associated with the influencing factors of ESs, local land use patterns, and ecological protection policies, corresponding multi-step improved land use scenarios were designed. These scenarios were demonstrated to be effective in conserving ESs in the selected towns: (1) the agricultural expansion scenario, which enhanced food provision services in the ECR; (2) the forest conservation scenario, which enhanced habitat and recreational services in the FPR; and (3) the developed land optimization scenario, which enhanced a range of regulating services in the UDR. Overall, this study used landscape functional zoning as a nexus to connect ES patterns and land use management. The optimized land use strategies can provide references for conserving ESs and enhancing landscape sustainability in Beijing and other similar metropolitan areas worldwide.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Pequim , China , Florestas
18.
Sci Total Environ ; 803: 149805, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34492494

RESUMO

Accurate, high spatial and temporal resolution water quality monitoring in inland waters is vital for environmental management. However, water quality monitoring in inland waters by satellite remote sensing remains challenging due to low signal-to-noise ratios (SNRs) and instrumental resolution limitations. We propose the concept of proximal remote sensing for monitoring water quality. The proximal hyperspectral imager, developed by Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences (CAS) and Hikvision Digital Technology, Ltd., is a high spatial, temporal and spectral resolution (1 nm) sensor for continuous observation, allowing for effective and practical long-term monitoring of inland water quality. In this study, machine learning and empirical algorithms were developed and validated using in situ total nitrogen (TN), total phosphorus (TP), chemical oxygen demand (COD) concentrations and spectral reflectance from Lake Taihu (N = 171), the Liangxi River (N = 94) and the Fuchunjiang Reservoir (N = 109) covering different water quality. Our dataset includes a large range for three key water quality parameters of TN from 0.93 to 6.46 mg/L, TP from 0.04 to 0.62 mg/L, and COD from 1.32 to 15.41 mg/L. Overall, the back-propagation (BP) neural network model had an accuracy of over 80% for TN (R2 = 0.84, RMSE = 0.33 mg/L, and MRE = 11.4%) and over 90% for TP (R2 = 0.93, RMSE = 0.02 mg/L, and MRE = 12.4%) and COD (R2 = 0.91, RMSE = 0.66 mg/L, and MRE = 9.3%). Our results show that proximal remote sensing combined with machine learning algorithms has great potential for monitoring water quality in inland waters.


Assuntos
Tecnologia de Sensoriamento Remoto , Qualidade da Água , Monitoramento Ambiental , Lagos , Rios
19.
Neural Regen Res ; 17(1): 163-169, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34100452

RESUMO

Studies have shown that downregulation of nuclear-enriched autosomal transcript 1 (Neat1) may adversely affect the recovery of nerve function and the increased loss of hippocampal neurons in mice. Whether Neat1 has protective or inhibitory effects on neuronal cell apoptosis after secondary brain injury remains unclear. Therefore, the effects of Neat1 on neuronal apoptosis were observed. C57BL/6 primary neurons were obtained from the cortices of newborn mice and cultured in vitro, and an oxygen and glucose deprivation cell model was established to simulate the secondary brain injury that occurs after traumatic brain injury in vitro. The level of Neat1 expression in neuronal cells was regulated by constructing a recombinant adenovirus to infect neurons, and the effects of Neat1 expression on neuronal apoptosis after oxygen and glucose deprivation were observed. The experiment was divided into four groups: the control group, without any treatment, received normal culture; the oxygen and glucose deprivation group were subjected to the oxygen and glucose deprivation model protocol; the Neat1 overexpression and Neat1 downregulation groups were treated with Neat1 expression intervention techniques and were subjected to the in oxygen and glucose deprivation protocol. The protein expression levels of neurons p53-induced death domain protein 1 (PIDD1, a pro-apoptotic protein), caspase-2 (an apoptotic priming protein), cytochrome C (a pro-apoptotic protein), and cleaved caspase-3 (an apoptotic executive protein) were measured in each group using the western blot assay. To observe changes in the intracellular distribution of cytochrome C, the expression levels of cytochrome C in the cytoplasm and mitochondria of neurons from each group were detected by western blot assay. Differences in the cell viability and apoptosis rate between groups were detected by cell-counting kit 8 assay and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, respectively. The results showed that the apoptosis rate, PIDD1, caspase-2, and cleaved caspase-3 expression levels significantly decreased, and cell viability significantly improved in the Neat1 overexpression group compared with the oxygen and glucose deprivation group; however, Neat1 downregulation reversed these changes. Compared with the Neat1 downregulation group, the cytosolic cytochrome C level in the Neat1 overexpression group significantly decreased, and the mitochondrial cytochrome C level significantly increased. These data indicate that Neat1 upregulation can reduce the release of cytochrome C from the mitochondria to the cytoplasm by inhibiting the PIDD1-caspase-2 pathway, reducing the activation of caspase-3, and preventing neuronal apoptosis after oxygen and glucose deprivation, which might reduce secondary brain injury after traumatic brain injury. All experiments were approved by the Animal Ethics Committee of the First Affiliated Hospital of Chongqing Medical University, China, on December 19, 2020 (approval No. 2020-895).

20.
Food Chem ; 375: 131722, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34922275

RESUMO

The non-enzymatic degradation of ready-to-eat sea cucumber (RSC) was closely related to the quality of sea cucumber products. When stored at 37 °C for 0-30 d, the hardness of RSC decreased by 86.7% and the proportion of free water increased by 12.71%. The content of free hydroxyproline increased from 8.33 µg/g to 24.12 µg/g. Label-free quantitative proteomics analysis showed that protein was prone to break at the sites of G, Q, N, D, and L, and the peptide bonds in QI, DL, NL, RI, EF and SY were much more liable to break. Edman degradation method showed that the breakage sites of RSC were at S, D, H, E, and V. NL, NA and NG calculated by B3LYP/6-31G(d) showed that the relative free energies in the initial cyclization step were 53.20, 143.53 and 78.10 kcal/mol, respectively, which may be the rate-determining step for peptide bond cleavage.


Assuntos
Pepinos-do-Mar , Animais , Ciclização , Hidroxiprolina , Proteínas , Água
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