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1.
J Environ Manage ; 366: 121694, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38971066

RESUMO

The total organic carbon (OC) from plant litter in riparian zones is an important nutrient source for aquatic organisms and plays a crucial role in the nutrient cycling of river ecosystems. Nevertheless, the total amount of OC in dammed rivers gradually decreases, and the restoration methods are rarely researched. A hypothesis was proposed that the periodic inundation altered the process of OC release from plant litter. To explore the impact of periodic inundation on OC release from litter in the riparian zone, litter bags in situ tests were conducted in the Yalong River. Three inundation treatments were conducted for the test samples, which were NS (never submerged by water), PIS (periodic submerged), and PMS (permanent submerged). Results indicated that the amount of OC released from litters in PIS treatment was about 1.1 times that in PMS treatment, and about 2.1 times that in NS treatment. The average release rate coefficient k of PIS treatment (at mean water level) was the highest (12.8 × 10-4 d-1), followed by PMS treatment (11.0 × 10-4 d-1), and NS treatment (5.6 × 10-4 d-1), which demonstrated that the periodic inundation was critical for OC release. The mean water level was a demarcation line where there was a significant difference in the release of OC in the riparian zone (p < 0.05). Flow velocity alone could account for 84% of the variation in OC release rate, while the flow velocity and inundation duration together could achieve an explanatory degree of 86%. This research can provide a valuable scientific basis for the protection and restoration of river ecosystems, especially for the recovery of OC concentration in dammed rivers.

2.
JHEP Rep ; 6(7): 101099, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38974366

RESUMO

Background & Aims: Combined 18F-fluorodeoxyglucose (FDG) and 11C-acetate (dual-tracer) positron-emission tomography/computed tomography (PET/CT) is being increasingly performed for the management of hepatocellular carcinoma (HCC), although its role is not well defined. Therefore, we evaluated its effectiveness in (i) staging, (ii) characterization of indeterminate lesions on conventional imaging, and (iii) detection of HCC in patients with unexplained elevations in serum alpha-fetoprotein (AFP) levels. Methods: We retrospectively assessed 525 consecutive patients from three tertiary centers between 2014 and 2020. For staging, we recorded new lesion detection rates, changes in the Barcelona Clinic Liver Cancer (BCLC) classification, and treatment allocation due to dual-tracer PET/CT. To characterize indeterminate lesions and unexplained elevation of serum AFP levels, the sensitivity and specificity of dual-tracer PET/CT in diagnosing HCC were evaluated. A multidisciplinary external review and a cost-benefit analysis of patients for metastatic screening were also performed. Results: Dual-tracer PET/CT identified new lesions in 14.3% of 273 staging patients, resulting in BCLC upstaging in 11.7% and treatment modifications in 7.7%. It upstaged 8.1% of 260 patients undergoing metastatic screening, with estimated savings of US$495 per patient. It had a sensitivity and specificity of 80.7% (95% CI 71.2-88.6%) and 94.8% (95% CI 90.4-98.6%), respectively, for diagnosing HCC in 201 indeterminate lesions. It detected HCC in 45.1% of 51 patients with unexplained elevations in serum AFP concentrations. External review revealed substantial agreement between local and external image interpretation and patient assessment (n = 273, κ = 0.822; 95% CI 0.803-0.864). Conclusions: Dual-tracer PET/CT provides added value beyond conventional imaging in patients with HCC by improving staging, confirming HCC diagnosis with high accuracy in patients with indeterminate lesions, and detecting HCC in patients with unexplained elevation of serum AFP. Impact and implications: Compared to CT or MRI, dual-tracer positron-emission tomography/computed tomography (PET/CT) led to upstaging in 12% of patients with hepatocellular carcinoma (HCC) undergoing staging, resulting in treatment modification in 8% of cases and a cost saving of US$495 per patient. It also accurately detected HCC in high-risk cases where CT or MRI were equivocal or normal. Dual-tracer PET/CT provides added value beyond conventional imaging in patients with HCC by improving staging, confirming HCC diagnosis with high accuracy in patients with indeterminate lesions, and detecting HCC in patients with unexplained elevation of serum AFP.

3.
JAMA Netw Open ; 7(6): e2415998, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38857045

RESUMO

Importance: Whether stereotactic body radiotherapy (SBRT) as a bridge to liver transplant for hepatocellular carcinoma (HCC) is effective and safe is still unknown. Objective: To investigate the feasibility of SBRT before deceased donor liver transplant (DDLT) for previously untreated unresectable HCC. Design, Setting, and Participants: In this phase 2 nonrandomized controlled trial conducted between June 1, 2015, and October 18, 2019, 32 eligible patients within UCSF (University of California, San Francisco) criteria underwent dual-tracer (18F-fluorodeoxyglucose and 11C-acetate [ACC]) positron emission tomography with computed tomography (PET-CT) and magnetic resonance imaging (MRI) with gadoxetate followed by SBRT of 35 to 50 Gy in 5 fractions, and the same imaging afterward while awaiting DDLT. Statistical analysis was performed on an intention-to-treat basis between October 1 and 31, 2023. Intervention: Patients received SBRT followed by DDLT when matched deceased donor grafts were available. Main Outcomes and Measures: Coprimary end points were progression-free survival (PFS) and objective response rates (ORRs) by the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), modified RECIST (mRECIST), and PET Response Criteria in Solid Tumors (PERCIST). Secondary end points were local control rate, overall survival (OS), and safety. Results: A total of 32 patients (median age, 59 years [IQR, 54-63 years]; 22 men [68.8%]) with 56 lesions received SBRT. After a median follow-up of 74.6 months (IQR, 40.1-102.9 months), the median PFS was 17.6 months (95% CI, 6.6-28.6 months), and the median OS was 60.5 months (95% CI, 29.7-91.2 months). The 5-year PFS was 39.9% (95% CI, 19.9%-59.9%), and the 5-year OS was 51.3% (95% CI, 31.7%-70.9%). In terms of number of patients, ORRs were 62.5% ([n = 20] 95% CI, 54.2%-68.7%) by RECIST 1.1, 71.9% ([n = 23] 95% CI, 63.7%-79.0%) by mRECIST, and 78.1% ([n = 25] 95% CI, 73.2%-86.7%) by PERCIST. In terms of number of lesions, ORRs were 75.0% ([n = 42] 95% CI, 61.6%-80.8%) by RECIST 1.1, 83.9% ([n = 47] 95% CI, 74.7%-90.6%) by mRECIST, and 87.5% ([n = 49] 95% CI, 81.3%-98.6%) by PERCIST. Twenty patients with 36 lesions received DDLT, of whom 15 patients (75.0%) with 21 lesions (58.3%) exhibited pathologic complete response. Multivariable analyses revealed that pretreatment metabolic tumor volume (MTV) based on ACC (hazard ratio [HR], 1.06 [95% CI, 1.01-1.10]; P = .01) and complete metabolic response (CMR) by PERCIST (HR, 0.31 [95% CI, 0.10-0.96]; P = .04) were associated with PFS, while pretreatment MTV based on ACC (HR, 1.07 [95% CI, 1.03-1.16]; P = .01), total lesion activity based on ACC (HR, 1.01 [95% CI, 1.00-1.02]; P = .02), and CMR by PERCIST (HR, 0.21 [95% CI, 0.07-0.73]; P = .01) were associated with OS. Toxic effects associated with SBRT were reported for 9 patients (28.1%), with 1 grade 3 event. Conclusions and Relevance: This phase 2 nonrandomized controlled trial demonstrated promising survival and safety outcomes of SBRT before DDLT for unresectable HCC. Future randomized clinical trials are warranted.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Radiocirurgia , Humanos , Radiocirurgia/métodos , Masculino , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/cirurgia , Feminino , Pessoa de Meia-Idade , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/mortalidade , Idoso , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Intervalo Livre de Progressão
4.
J Environ Manage ; 363: 121309, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38848638

RESUMO

Multiple uncertainties such as water quality processes, streamflow randomness affected by climate change, indicators' interrelation, and socio-economic development have brought significant risks in managing water quantity and quality (WQQ) for river basins. This research developed an integrated simulation-optimization modeling approach (ISMA) to tackle multiple uncertainties simultaneously. This approach combined water quality analysis simulation programming, Markov-Chain, generalized likelihood uncertainty estimation, and interval two-stage left-hand-side chance-constrained joint-probabilistic programming into an integration nonlinear modeling framework. A case study of multiple water intake projects in the Downstream and Delta of Dongjiang River Basin was used to demonstrate the proposed model. Results reveal that ISMA helps predict the trend of water quality changes and quantitatively analyze the interaction between WQQ. As the joint probability level increases, under strict water quality scenario system benefits would increase [3.23, 5.90] × 109 Yuan, comprehensive water scarcity based on quantity and quality would decrease [782.24, 945.82] × 106 m3, with an increase in water allocation and a decrease in pollutant generation. Compared to the deterministic and water quantity model, it allocates water efficiently and quantifies more economic losses and water scarcity. Therefore, this research has significant implications for improving water quality in basins, balancing the benefits and risks of water quality violations, and stabilizing socio-economic development.


Assuntos
Rios , Qualidade da Água , Incerteza , Abastecimento de Água , Modelos Teóricos , Mudança Climática
5.
Oncologist ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38885304

RESUMO

BACKGROUND: Sarcopenia or skeletal muscle depletion is a poor prognostic factor for gastric cancer (GC). However, existing cutoff values of skeletal muscle index (SMI) for defining sarcopenia have been found to have limitations when clinically applied. This study aimed to determine the optimal cutoff for SMI to predict severe toxicities of chemotherapy and overall survival (OS) in patients with advanced GC. METHODS: Patients with metastatic gastric adenocarcinoma who received first-line palliative chemotherapy between January 2014 and December 2021 at Queen Mary Hospital, Hong Kong, were included in this study. The SMI was determined via a pre-chemotherapy computed tomography scan. Optimal cutoff points of SMI were identified by recursive partitioning analysis. Univariate and multivariate analyses evaluating risk factors of severe chemotherapy toxicities and OS were also performed. RESULTS: A total of 158 patients (male: 108 (68.4%), median age: 65.3) were included. The SMI cutoff to define low SMI was ≤33 cm2/m2 for males and ≤28 cm2/m2 for females; 30 patients (19.0%) had low SMI. Patients with low SMI had a higher incidence of hematological toxicities (63.3% vs 32.0%, P = .001) and non-hematological toxicities (66.7% vs 36.7%, P = .003). Multivariable analysis indicated that low SMI and low serum albumin (≤28 g/L) were independent predictive factors of hematological toxicity, while low SMI and neutrophil-lymphocyte ratio ≥5 were predictive factors of non-hematological toxicity. Moreover, patients with low SMI had a significantly shorter OS (P = .011), lower response rate to chemotherapy (P = .045), and lower utilization of subsequent lines of treatment (P < .001). CONCLUSIONS: Using pre-chemotherapy SMI cutoff (≤33 cm2/m2 for males and 28 cm2/m2 for females) one can identify individuals with a higher risk of severe chemotherapy toxicities and worse prognosis.

6.
Nat Commun ; 15(1): 4894, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38849338

RESUMO

Synthetic biology applications require finely tuned gene expression, often mediated by synthetic transcription factors (sTFs) compatible with the human genome and transcriptional regulation mechanisms. While various DNA-binding and activation domains have been developed for different applications, advanced artificially controllable sTFs with improved regulatory capabilities are required for increasingly sophisticated applications. Here, in mammalian cells and mice, we validate the transactivator function and homo-/heterodimerization activity of the plant-derived phytochrome chaperone proteins, FHY1 and FHL. Our results demonstrate that FHY1/FHL form a photosensing transcriptional regulation complex (PTRC) through interaction with the phytochrome, ΔPhyA, that can toggle between active and inactive states through exposure to red or far-red light, respectively. Exploiting this capability, we develop a light-switchable platform that allows for orthogonal, modular, and tunable control of gene transcription, and incorporate it into a PTRC-controlled CRISPRa system (PTRCdcas) to modulate endogenous gene expression. We then integrate the PTRC with small molecule- or blue light-inducible regulatory modules to construct a variety of highly tunable systems that allow rapid and reversible control of transcriptional regulation in vitro and in vivo. Validation and deployment of these plant-derived phytochrome chaperone proteins in a PTRC platform have produced a versatile, powerful tool for advanced research and biomedical engineering applications.


Assuntos
Luz , Chaperonas Moleculares , Fitocromo , Animais , Humanos , Camundongos , Fitocromo/metabolismo , Fitocromo/genética , Chaperonas Moleculares/metabolismo , Chaperonas Moleculares/genética , Regulação da Expressão Gênica/efeitos da radiação , Transcrição Gênica/efeitos da radiação , Células HEK293 , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética
7.
Liver Cancer ; 13(3): 265-276, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38756147

RESUMO

Introduction: While combination of stereotactic body radiotherapy (SBRT) and immunotherapy are promising, their efficacy and safety have not been compared with SBRT-alone in patients with unresectable hepatocellular carcinoma (HCC). Methods: This retrospective study included 100 patients with nonmetastatic, unresectable HCC in two hospitals. Eligible patients had tumor nodules ≤3 and Child-Pugh liver function score of A5 to B7. Seventy patients received SBRT-alone, and 30 patients underwent combined SBRT and immunotherapy (SBRT-IO). Overall survival (OS), time to progression (TTP), overall response rate (ORR), and toxicity were analyzed. We adjusted for the potential confounding factors using propensity score matching. Results: The median tumor size was 7.3 cm (range, 2.6-18 cm). Twenty-five (25%) of patients had vascular invasion. Before propensity score matching, the 1-year and 3-year OS rate was 89.9% and 59.8% in the SBRT-IO group and 75.7% and 42.3% in SBRT-alone group (p = 0.039). After propensity score matching (1:2), 25 and 50 patients were selected from the SBRT-IO and SBRT-alone group. The 1-year and 3-year OS was 92.0% and 63.9% in the SBRT-IO group versus 74.0% and 43.3% in the SBRT-alone group (p = 0.034). The 1-year and 3-year TTP was better in SBRT-IO group (1-year: 68.9% vs. 58.9% and 3-year: 61.3% vs. 32.5%, p = 0.057). The ORR of 88% (complete response [CR]: 56%, partial response [PR]: 22%) in SBRT-IO arm was significantly better than 50% (CR: 20%, PR: 30%) in the SBRT-alone arm (p = 0.006). Three patients (12%) developed ≥grade 3 immune-related treatment adverse events (n = 2 hepatitis, n = 1 dermatitis) leading to permanent treatment discontinuation. Conclusion: Adding immunotherapy to SBRT resulted in better survival with manageable toxicities. Prospective randomized trial is warranted.

8.
J Environ Manage ; 360: 121155, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38761624

RESUMO

The establishment of large hydropower stations in the main stream poses a threat to fish habitats. Selecting suitable tributaries as alternative habitats is a practical measure for ecological environment protection during large hydropower station's construction. The small dams constructed on certain tributaries need to be removed in order to restore river connectivity. The removal of dams will activate hydro-sedimentary dynamics and change the original habitat in terms of topography and hydrodynamics. To explore the evolution of fish habitats following the removal of small dams, a dam-removed reach of a habitat-alternative tributary was selected as the research object, and the model of water-sediment transport and riverbed evolution in strongly disturbed dam-removed reaches and the model of fish habitat suitability evaluation were established. The key parameters calibration and model verification were completed by field monitoring results. The simulation results showed dramatic evolution in the reservoir riverbed in the initial stage after dam removal and during the high discharge period. One year after dam removal, there was a noticeable 4.0 m incision in front of the dam, along with a decrease in channel slope at the dam site from about 4.8% to approximately 1.5%. Downstream of the dam, alterations to the riverbed were mainly concentrated near the dam, and sedimentary bodies with a height of around 2.0 m have formed on the left bank following the high discharge period. The fish habitat in most areas of the dam-removed reach was suitable, except for the downstream high-velocity area. To compare the evolution process of fish habitat under two dam removal periods in wet and dry seasons, two dam removal schemes were implemented in March and June. The results showed that the riverbed evolved more gradually in the March scheme, creating a larger and continuous suitable habitat for fish. Therefore, the March scheme was recommended. By revealing the evolutionary pattern of fish habitat after dam removal, this research provides a reliable model for assessing and restoring habitats in dam-removed reaches, and enjoys significant implications for protecting river ecology in hydropower development reaches.


Assuntos
Ecossistema , Rios , Animais , Peixes , Centrais Elétricas , Conservação dos Recursos Naturais
9.
J Med Internet Res ; 26: e53724, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38739441

RESUMO

Large language models showed interpretative reasoning in solving diagnostically challenging medical cases.


Assuntos
Simulação por Computador , Diagnóstico por Computador
10.
Sci Total Environ ; 926: 171940, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38527539

RESUMO

Saltmarsh, a prominent buffer ecosystem, has been identified as an important sink for nitrogen (N) pollutants from marine- and land-based anthropogenic activities. However, how the enriched anthropogenic N impacts saltmarsh sustainability has been neglected due to limited understanding of marsh resilience based on seedling establishment and population dispersal under anthropogenic N inputs. This study combined mesocosm experiments and model simulations to quantify the effects of increased anthropogenic N on the seedling-based vegetation expansion of Spartina alterniflora. The results indicated that seedling survivals, growth rates, and morphological indicators were inhibited by 20.08 %, 37.14 %, and > 35.56 %, respectively, under 1.5 gN/kg anthropogenic N. The sensitivity rate of vegetation expansion was increased by 70 % with 1 gN/kg increased N concentration under the scenario of low seedling density (< 15 m/yr). These findings revealed an important unidentified weakness of the marsh development process to anthropogenic N inputs. Finally, we highlighted the importance of appropriate protection measures to control nutrient pollution in salt marshes. Our study provides new insights for enhancing the resilience and sustainability of saltmarsh ecosystems.


Assuntos
Ecossistema , Resiliência Psicológica , Plântula , Nitrogênio , Áreas Alagadas , Poaceae/fisiologia
11.
Cancer Imaging ; 24(1): 42, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38520026

RESUMO

BACKGROUND: Positron Emission Tomography (PET) with combined [18F]-FDG and [11C]-acetate (dual-tracer) is used for the management of hepatocellular carcinoma (HCC) patients, although its prognostic value and underlying molecular mechanism remain poorly understood. We hypothesized that radiotracer uptake might be associated with tumor hypoxia and validated our findings in public and local human HCC cohorts. METHODS: Twelve orthotopic HCC xenografts were established using MHCC97L cells in female nude mice, with 5 having undergone hepatic artery ligation (HAL) to create tumor hypoxia in vivo. Tumors in both Control and HAL-treated xenografts were imaged with [11C]-acetate and [18F]-FDG PET-MR and RNA sequencing was performed on the resected tumors. Semiquantitative analysis of PET findings was then performed, and the findings were then validated on the Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort and patients from our institution. RESULTS: HAL-treated mice showed lower [11C]-acetate (HAL-treated vs. Control, tumor-to-liver SUV ratio (SUVTLR): 2.14[2.05-2.21] vs 3.11[2.75-5.43], p = 0.02) but not [18F]-FDG (HAL-treated vs. Control, SUVTLR: 3.73[3.12-4.35] vs 3.86[3.7-5.29], p = 0.83) tumor uptakes. Gene expression analysis showed the PET phenotype is associated with upregulation of hallmark hypoxia signature. The prognostic value of the hypoxia gene signature was tested on the TCGA-LIHC cohort with upregulation of hypoxia gene signature associated with poorer overall survival (OS) in late-stage (stage III and IV) HCC patients (n = 66, OS 2.05 vs 1.67 years, p = 0.046). Using a local cohort of late-stage HCC patients who underwent dual-tracer PET-CT, tumors without [11C]-acetate uptake are associated with poorer prognosis (n = 51, OS 0.25 versus 1.21 years, p < 0.0001) and multivariable analyses showed [11C]-acetate tumor uptake as an independent predictor of OS (HR 0.17 95%C 0.06-0.42, p < 0.0001). CONCLUSIONS: [11C]-acetate uptake is associated with alteration of tumor hypoxia gene expression and poorer prognosis in patients with advanced HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Feminino , Animais , Camundongos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/genética , Prognóstico , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Camundongos Nus , Compostos Radiofarmacêuticos , Tomografia por Emissão de Pósitrons , Acetatos , Expressão Gênica
12.
Eur Radiol ; 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38460014

RESUMO

OBJECTIVES: The study aimed to compare the diagnostic accuracies of 2-[18F]FDG PET/CT and contrast-enhanced CT (ceCT) after neoadjuvant chemotherapy (NACT) in advanced ovarian cancer (OC). MATERIALS AND METHODS: This study consisted historical observational cohort and prospective validation cohort. Patients with newly diagnosed stage III-IV OC scheduled for NACT were recruited, with imaging performed after three to six cycles of NACT before interval debulking surgery. Nineteen regions in the abdominopelvic cavity were scored for the presence and absence of disease, referenced to the intra-operative findings or histological specimens. Diagnostic metrics were compared using McNemar's test. RESULTS: In the historical cohort (23 patients, age 58 ± 13), 2-[18F]FDG PET had an overall accuracy (Acc) 82%, sensitivity (Sen) 38%, specificity (Spe) 97%, positive predictive value (PPV) 79% and negative predictive value (NPV) 82%; ceCT had an overall Acc 86%, Sen 64%, Spe 93%, PPV 75% and NPV 89%. In the prospective cohort (46 patients, age 59 ± 9), 2-[18F] FDG PET had an overall Acc 87%, Sen 48%, Spe 98%, PPV 84% and NPV 88%; ceCT had an overall Acc 89%, Sen 66%, Spe 95%, PPV 77% and NPV 91%. No significant difference was demonstrated between the two imaging modalities (p > 0.05). High false-negative rates were observed in the right subdiaphragmatic space, omentum, bowel mesentery and serosa. High omental metabolic uptake after NACT was associated with histological non-responders (p < 0.05). CONCLUSION: 2-[18F]FDG PET/CT had no additional value over ceCT with comparable diagnostic accuracy in detecting disease after NACT in advanced OC. CLINICAL RELEVANCE STATEMENT: 2-[18F]FDG PET/CT is not superior to contrast-enhanced CT in determining disease after neoadjuvant chemotherapy in advanced ovarian cancer; contrast-enhanced CT should be suffice for surgical planning before interval debulking surgery. KEY POINTS: • Additional value of 2-[18F]FDG PET/CT over contrast-enhanced CT is undefined in detecting disease after neoadjuvant chemotherapy. • 2-[18F]FDG PET/CT has comparable diagnostic accuracy compared to contrast-enhanced CT. • Contrast-enhanced CT will be suffice for surgical planning after neoadjuvant chemotherapy.

13.
Mol Cell ; 84(8): 1585-1600.e7, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38479385

RESUMO

Myriad physiological and pathogenic processes are governed by protein levels and modifications. Controlled protein activity perturbation is essential to studying protein function in cells and animals. Based on Trim-Away technology, we screened for truncation variants of E3 ubiquitinase Trim21 with elevated efficiency (ΔTrim21) and developed multiple ΔTrim21-based targeted protein-degradation systems (ΔTrim-TPD) that can be transfected into host cells. Three ΔTrim-TPD variants are developed to enable chemical and light-triggered programmable activation of TPD in cells and animals. Specifically, we used ΔTrim-TPD for (1) red-light-triggered inhibition of HSV-1 virus proliferation by degrading the packaging protein gD, (2) for chemical-triggered control of the activity of Cas9/dCas9 protein for gene editing, and (3) for blue-light-triggered degradation of two tumor-associated proteins for spatiotemporal inhibition of melanoma tumor growth in mice. Our study demonstrates that multiple ΔTrim21-based controllable TPD systems provide powerful tools for basic biology research and highlight their potential biomedical applications.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Camundongos , Animais , Proteína 9 Associada à CRISPR/genética , Proteína 9 Associada à CRISPR/metabolismo , Proteínas/metabolismo , Proteólise , Mamíferos/metabolismo
14.
J Environ Manage ; 351: 119894, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38154219

RESUMO

Deep learning methods exhibited significant advantages in mapping highly nonlinear relationships with acceptable computational speed, and have been widely used to predict water quality. However, various model selection and construction methods resulted in differences in prediction accuracy and performance. Hence, a unified deep learning framework for water quality prediction was established in the paper, including data processing module, feature enhancement module, and data prediction module. In the established model, the data processing module based on wavelet transform method was applied to decomposing complex nonlinear meteorology, hydrology, and water quality data into multiple frequency domain signals for extracting self characteristics of data cyclic and fluctuations. The feature enhancement module based on Informer Encoder was used to enhance feature encoding of time series data in different frequency domains to discover global time dependent features of variables. Finally, the data prediction module based on the stacked bidirectional long and short term memory network (SBiLSTM) method was employed to strengthen the local correlation of feature sequences and predict the water quality. The established model framework was applied in Lijiang River in Guilin, China. The maximum relative errors between the predicted and observed values for dissolved oxygen (DO), chemical oxygen demand (CODMn) were 12.4% and 20.7%, suggesting a satisfactory prediction performance of the established model. The validation results showed that the established model was superior to all other models in terms of prediction accuracy with RMSE values 0.329, 0.121, MAE values 0.217, 0.057, SMAPE values 0.022, 0.063 for DO and CODMn, respectively. Ablation tests confirmed the necessity and rationality of each module for the established model framework. The established method provided a unified deep learning framework for water quality prediction.


Assuntos
Aprendizado Profundo , Qualidade da Água , China , Hidrologia , Meteorologia , Oxigênio
15.
J Contam Hydrol ; 261: 104285, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38154436

RESUMO

The release of phosphorus from sediment is an important source of endogenous phosphorus in water bodies and is an important factor affecting the total phosphorus content in river system. Water velocity is key factor affecting the rate of phosphorus release from sediments. In this paper, the effects of water velocity on the release of phosphorus from sediments in a plateau cold water type river were investigated. The ecological environment of plateau cold water rivers is sensitive and fragile. The changes in environmental conditions can easily lead to changes in the overall water quality of rivers. Therefore, exploring the release process of phosphorus in plateau cold water rivers under changes in hydrodynamic conditions is important for protecting the ecological environment of plateau rivers. The results showed that the release of total phosphorus from sediments followed a first-order kinetic process, when the flow velocity was lower than the threshold velocity of sediments. The total phosphorus release coefficient of sediment linearly increased with increases in water flow velocity. The total phosphorus release coefficient of sediment was related to the flow velocity by kTP20=3.03v/vc+0.08v

Assuntos
Rios , Poluentes Químicos da Água , Fósforo , Poluentes Químicos da Água/análise , Sedimentos Geológicos , Qualidade da Água , China , Monitoramento Ambiental/métodos
16.
J Mech Behav Biomed Mater ; 149: 106230, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37976993

RESUMO

OBJECTIVES: Guided bone regeneration (GBR) is a well-established method for repairing hard tissue deficiency in reconstructive dentistry. The aim of this study was to investigate the barrier function, osteogenic activity and immunomodulatory ability of a novel bi-layered asymmetric membrane loaded with demineralized dentin matrix (DDM). METHODS: DDM particles were harvested from healthy, caries-free permanent teeth. Electrospinning technique was utilized to prepare bi-layered DDM-loaded poly(lactic-co-glycolic acid) (PLGA)/poly(lactic acid) (PLA) membranes (abbreviated as DPP bilayer membranes). We analyzed the membranes' surface properties, cytocompatibility and barrier function, and evaluated their osteogenic activity in vitro. In addition, its effects on the osteogenic immune microenvironment were also investigated. RESULTS: Synthetic DPP bilayer membranes presented suitable surface characteristics and satisfactory cytocompatibility. Transwell assays showed significant fewer migrated cells by the DPP bilayer membranes compared with blank control, with or without in vitro degradation (all P < 0.001). In vitro experiments indicated that our product elevated messenger ribonucleic acid (mRNA) expression levels of osteogenic genes alkaline phosphatase (ALP), osteopontin (OPN), osteocalcin (OCN) and runt-related transcription factor 2 (Runx2). Among all groups, 20% DPP bilayer membrane displayed highest ALP activity (P < 0.001). Furthermore, DPP bilayer membranes enhanced the mRNA expression of M2 macrophage markers and increased the proportion of CD206+ M2 macrophages by 100% (20% DPP: P < 0.001; 30% DPP: P < 0.001; 40% DPP: P < 0.05), thus exerting an inflammation suppressive effect. CONCLUSIONS: DPP bilayer membranes exhibited notable biological safety and osteogenic activity in vitro, and have potential as a prospective candidate for GBR approach in the future.


Assuntos
Regeneração Óssea , Regeneração Tecidual Guiada , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Osteogênese , RNA Mensageiro
17.
J Contam Hydrol ; 259: 104255, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37852028

RESUMO

Co-existence of microplastics, nanomaterials, and antibiotics may lead to intensified multifaceted pollution, which may influence their fate in soils. This study investigated the co-transport behavior of polystyrene microplastics (PS) and compound pollutants of graphene oxide (GO) and tetracycline (TC). Packed column experiments for microplastic with or without combined pollutants were performed in KCl (10 and 30 mM) and CaCl2 solutions (0.3 and 1 mM). The results showed transport of PS was facilitated at low ionic strengths and inhibited at high ionic strengths by GO with or without TC under examined conditions. Carrier effect of GO as well as the aggregation of PS in the presence of co-exiting GO or GO-TC could be the contributor. Although the existence of TC relieved the ripening phenomenon of PS and GO deposition due to enhanced electronegativity of sand media, the effect of GO on the PS transport has not been significantly impacted, indicating the dominant role of GO during cotransport process. Furthermore, the transport of PS was increased by TC owing to competition for deposition sites on sand surfaces. In turn, the transport of TC was mainly affected by PS whether graphene was present or not. The increase in electrostatic repulsive force (transport-promoting) and addition adsorption sites (transport-inhibiting) may be responsible for the observations. Our findings could improve understandings of complex environmental behaviors of microplastics and provide insight into investigation on cotransport of emerging contaminants under various conditions relevant to the subsurface environment.


Assuntos
Poluentes Ambientais , Grafite , Microplásticos , Plásticos , Porosidade , Areia , Tetraciclina , Antibacterianos
18.
J Environ Manage ; 348: 119277, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37839199

RESUMO

The rapid urbanization has accelerated the destruction of regional ecosystems, triggering ecological risks and threatening sustainable development. Landscape ecological risk (LER) evaluation is an effective tool to mitigate such negative impacts. However, the existing evaluation systems exhibit certain subjectivity. Therefore, an improved LER evaluation method was proposed, which incorporates ecosystem services (ESs) to characterize landscape vulnerability. The method was validated using the Pearl River Delta urban agglomeration (PRDUA) as the study area. The results showed that the optimal grain size and extent for landscape pattern analysis in the PRDUA were determined to be 150 m and 6km × 6 km, respectively. The comparison results with the traditional LER evaluation method demonstrated the improved method's superior rationality and reliability. The hotspot analysis based on the Getis-Ord Gi* method revealed that the hotspots of LER were mainly concentrated in the densely populated areas of the south-central region of the PRDUA. The coupling coordination degree (CCD) between LERs and ESs showed four different levels of development in both temporal and spatial dimensions, generally dominated by moderately balanced development and lagging ESs, reflecting the unbalanced ecological environment and socio-economic development of the PRDUA. It is recommended that the ecosystems in the PRDUA be managed and protected separately according to the delineated Ecological Protection Area (EPA), Urban Built-up Area (UBA), and Urban Ecological Boundary Area (UEBA). This study can provide an important reference for regional ecosystem conservation and management.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Reprodutibilidade dos Testes , Urbanização , Rios , China , Cidades
19.
Hepatobiliary Surg Nutr ; 12(5): 715-735, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37886207

RESUMO

Background: The finding of pancreatic cystic lesions (PCL) on incidental imaging is becoming increasingly common. International studies report a prevalence of 2.2-44.7% depending on the population, imaging modality and indication for imaging, and the prevalence increases with age. Patients with PCL are at risk of developing pancreatic cancer, a disease with a poor prognosis. This publication summarizes recommendations for the diagnosis and management of PCL and post-operative pancreatic exocrine insufficiency (PEI) from a group of local specialists. Methods: Clinical evidence was consolidated from narrative reviews and consensus statements formulated during two online meetings in March 2022. The expert panel included gastroenterologists, hepatobiliary surgeons, oncologists, radiologists, and endocrinologists. Results: Patients with PCL require careful investigation and follow-up due to the risk of malignant transformation of these lesions. They should undergo clinical investigation and pancreas-specific imaging to classify lesions and understand the risk profile of the patient. Where indicated, patients should undergo pancreatectomy to excise PCL. Following pancreatectomy, patients are at risk of PEI, leading to gastrointestinal dysfunction and malnutrition. Therefore, such patients should be monitored for symptoms of PEI, and promptly treated with pancreatic enzyme replacement therapy (PERT). Patients with poor response to PERT may require increases in dose, addition of a proton pump inhibitor, and/or further investigation, including tests for pancreatic function. Patients are also at risk of new-onset diabetes mellitus after pancreatectomy; they should be screened and treated with insulin if indicated. Conclusions: These statements are an accurate summary of our approach to the diagnosis and management of patients with PCL and will be of assistance to clinicians treating these patients in a similar clinical landscape.

20.
PeerJ ; 11: e15034, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36949763

RESUMO

Background: We previously showed that higher SARS-CoV-2 viral load correlated with smaller thyroid volumes among COVID-19 survivors at 2 months after acute COVID-19. Our current follow-up study evaluated the evolution of thyroid volumes and thyroiditis features within the same group of patients 6 months later. Methods: Adult COVID-19 survivors who underwent thyroid ultrasonography 2 months after infection (USG1) were recruited for follow-up USG 6 months later (USG2). The primary outcome was the change in thyroid volume. We also reassessed thyroiditis features on USG, thyroid function and anti-thyroid antibodies. Results: Fifty-four patients were recruited (mean age 48.1 years; 63% men). The mean thyroid volume increased from USG1 to USG2 (11.9 ± 4.8 to 14.5 ± 6.2 mL, p < 0.001). Thirty-two patients (59.3%) had significant increase in thyroid volume by ≥15%, and they had a median increase of +33.3% (IQR: +20.0% to +45.0%). Multivariable logistic regression analysis showed that only higher baseline SARS-CoV-2 viral load independently correlated with significant thyroid volume increase on USG2 (p = 0.022). Among the seven patients with thyroiditis features on USG1, six (85.7%) had the features resolved on USG2. None had new thyroiditis features on USG2. All abnormal thyroid function during acute COVID-19 resolved upon USG1 and USG2. Conclusion: Most COVID-19 survivors had an increase in thyroid volume from early convalescent phase to later convalescent phase. This increase correlated with high initial SARS-CoV-2 viral load. Together with the resolution of thyroiditis features, these may suggest a transient direct atrophic effect of SARS-CoV-2 on the thyroid gland with subsequent recovery of thyroid volume and thyroiditis features.


Assuntos
COVID-19 , Tireoidite , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , COVID-19/diagnóstico por imagem , Seguimentos , SARS-CoV-2 , Estudos Prospectivos , Ultrassonografia , Sobreviventes
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