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1.
Adv Sci (Weinh) ; : e2400185, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38896792

RESUMEN

In vitro models coupled with multimodal approaches are needed to dissect the dynamic response of local tumor immune microenvironment (TIME) to immunotherapy. Here the patient-derived primary lung cancer organoids (pLCOs) are generated by isolating tumor cell clusters, including the infiltrated immune cells. A function-associated single-cell RNA sequencing (FascRNA-seq) platform allowing both phenotypic evaluation and scRNA-seq at single-organoid level is developed to dissect the TIME of individual pLCOs. The analysis of 171 individual pLCOs derived from seven patients reveals that pLCOs retain the TIME heterogeneity in the parenchyma of parental tumor tissues, providing models with identical genetic background but various TIME. Linking the scRNA-seq data of individual pLCOs with their responses to anti-PD-1 (αPD-1) immune checkpoint blockade (ICB) allows to confirm the central role of CD8+ T cells in anti-tumor immunity, to identify potential tumor-reactive T cells with a set of 10 genes, and to unravel the factors regulating T cell activity, including CD99 gene. In summary, the study constructs a joint phenotypic and transcriptomic FascRNA-seq platform to dissect the dynamic response of local TIME under ICB treatment, providing a promising approach to evaluate novel immunotherapies and to understand the underlying molecular mechanisms.

2.
3.
Sci Total Environ ; 938: 173353, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38795999

RESUMEN

Inevitably, aerobic biological treatment processes generate emissions of ammonia (NH3) and greenhouse gas (GHGs) emissions, especially nitrous oxide (N2O). The rapid bio-drying process (RBD) for food waste (FW) alleviates issues arising from its substantial growth. However, its emissions of NH3 and N2O remain unknown, and the correlation with nitrogen components in the substrate remains unclear, significantly impeding its widespread adoption. Here, the nitrogen loss and its mechanisms in RBD were investigated, and the results are as follows: The total emission of NH3 and N2O were1.42 and 1.16 mg/kg FW (fresh weight), respectively, achieving a 98 % reduction compared to prior studies. Structural equation modeling demonstrates that acid ammonium nitrogen (AN) decomposition chiefly generates NH3 in compost (p < 0.001). Strong correlation (p < 0.001) exists between amino acid nitrogen (AAN) and AN. In-depth analysis of microbial succession during the process reveals that the enrichment of Brevibacterium, Corynebacterium, Dietzia, Fastidiosipila, Lactobacillus, Mycobacterium, Peptoniphilus, and Truepera, are conducive to reducing the accumulation of AN and AAN in the substrate, minimizing NH3 emissions (p < 0.05). While Pseudomonas, Denitrobacterium, Nitrospira, and Bacillus are identified as key species contributing to N2O emissions during the process. Correlation analysis between physicochemical conditions and microbial succession in the system indicates that the moisture content and NO3- levels during the composting process provide suitable conditions for the growth of bacteria that contribute to NH3 and N2O emissions reduction, these enrichment in RBD process minimizing NH3 and N2O emissions. This study can offer crucial theoretical and data support for the resource utilization process of perishable organic solid waste, mitigating NH3 and GHGs emissions.


Asunto(s)
Amoníaco , Nitrógeno , Óxido Nitroso , Óxido Nitroso/análisis , Amoníaco/análisis , Nitrógeno/análisis , Eliminación de Residuos/métodos , Contaminantes Atmosféricos/análisis , Residuos de Alimentos , Gases de Efecto Invernadero/análisis , Alimento Perdido y Desperdiciado
4.
Odontology ; 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38565694

RESUMEN

As a safe, effective, economical, and convenient technique, tooth whitening is one of the most popular treatments for improving tooth discoloration. This review summarizes the theoretical and recent research developments in the classification and mechanisms of tooth discoloration, as well as the principles, agents, effects, and side effects of tooth whitening techniques. The aim is to provide a basis for the clinical treatment of tooth whitening techniques and to suggest possible new ideas for further research. The accepted mechanism of whitening is the redox reaction of oxides in the whitening reagent, and the whitening effect is remarkable. However, side effects such as tooth sensitivity and irritation of gum and other oral soft tissues can still occur. It is recommended that more monitoring be carried out in the clinic to monitor these side effects, and care should be taken to protect the soft tissues in the mouth during office whitening procedures. Furthermore, there is a need to develop new additives or natural whitening products to reduce the occurrence of side effects.

5.
Oral Dis ; 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38439057

RESUMEN

OBJECTIVE: This study aimed to investigate the expression of tight junction, its distribution pattern in oral lichen planus samples and its potential association with the severity of oral lichen planus. MATERIALS AND METHODS: Cross-sectional study designs were conducted. Transcriptome sequencing was conducted using oral mucosal tissues from 22 patients with oral lichen planus and 11 healthy controls. Immunohistochemistry and quantitative reverse transcription PCR were performed to verify the expression of claudin-1, claudin-4, occludin and zonula occludens-1 in oral mucosal tissues from another 30 patients with oral lichen planus and 26 healthy controls. The relationship between tight junction protein expression and oral lichen planus severity was explored using correlation analysis. RESULTS: 5603 and 2475 differentially expressed genes were upregulated and downregulated respectively, in oral lichen planus tissues. KEGG analysis showed that tight junctions including CLDN1, CLDN4, OCLN and TJP1 were downregulated in oral lichen planus. Claudin-1, claudin-4, occludin and zonula occludens-1 expression was verified to be significantly lower in oral lichen planus. Furthermore, correlation analyses showed that decreased occludin expression was positively related to oral lichen planus severity. CONCLUSION: Decreased expression of TJ barrier proteins may be associated with the development of oral lichen planus.

6.
J Med Virol ; 96(3): e29544, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38511577

RESUMEN

The impact of SARS-CoV-2 infection shortly after vaccination on vaccine-induced immunity is unknown, which is also one of the concerns for some vaccinees during the pandemic. Here, based on a cohort of individuals who encountered BA.5 infection within 8 days after receiving the fourth dose of a bivalent mRNA vaccine, preceded by three doses of inactivated vaccines, we show that booster mRNA vaccination provided 48% protection efficacy against symptomatic infections. At Day 7 postvaccination, the level of neutralizing antibodies (Nabs) against WT and BA.5 strains in the uninfected group trended higher than those in the symptomatic infection group. Moreover, there were greater variations in Nabs levels and a significant decrease in virus-specific CD4+ T cell response observed in the symptomatic infection group. However, symptomatic BA.5 infection significantly increased Nab levels against XBB.1.9.1 and BA.5 (symptomatic > asymptomatic > uninfected group) at Day 10 and resulted in a more gradual decrease in Nabs against BA.5 compared to the uninfected group at Day 90. Our data suggest that BA.5 infection might hinder the early generation of Nabs and the recall of the CD4+ T cell response but strengthens the Nab and virus-specific T cell response in the later phase. Our data confirmed that infection can enhance host immunity regardless of the short interval between vaccination and infection and alleviate concerns about infections shortly after vaccination, which provides valuable guidance for developing future vaccine administration strategies.


Asunto(s)
Anticuerpos Neutralizantes , Vacunación , Humanos , Inmunización Secundaria , ARN Mensajero/genética , Vacunas Combinadas , Anticuerpos Antivirales
7.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(1): 32-38, 2024 Feb 18.
Artículo en Chino | MEDLINE | ID: mdl-38318893

RESUMEN

OBJECTIVE: To detect key genes of local glucocorticoid therapy in oral lichen planus (OLP) through transcriptome sequencing. METHODS: The study prospectively enrolled 28 symptomatic patients who visitied Department of Oral Mucosa, Peking University Hospital of Stomatology from November 2019 to March 2023. Topical inunction of 0.1 g/L of dexamethasone was applied for 1 min, 3 times daily for 4 weeks. The patients' signs and pain symptoms were recorded and they were classified as effective group and ineffective group according to the treatment outcome. Their mucosa samples were collected before treatment. After isolating total RNA, transcriptome sequencing was performed. The gene expression data obtained by sequencing were analyzed differently using the DESeq2 package in R software, and the Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis was performed on the basis of the hypergeometric distribution algorithm to describe the biological function of differentially expressed genes (DEGs), accordingly detecting sensitivity related molecular affecting therapeutic effect of dexamethasone. RESULTS: After 4 weeks treatment by topical dexamethasone, 13 cases of the 28 OLP patients responding well with the sign score reducing from 7.0 (4.5, 9.0) to 5.0 (3.0, 6.3), pain score decreasing from 5.0 (2.0, 5.5) to 2.0 (0.0, 3.5), oral health impact profile lessening from 5.0 (3.5, 9.0) to 1.0 (0.0, 5.0) significantly (P<0.01) were classified as effective group and 15 cases with poor response to the drug were sorted as ineffective group. There were no significant differences of demographic and baseline levels of clinical features, especially disease severity between these two groups. A total of 499 DEGs including 274 upregulated and 225 downregulated genes were identified between effective group and ineffective group. KEGG enrichment analysis showed that upregulated genes in effective group compared with ineffective group including CLDN8, CTNNA3, MYL2 and MYLPF were associated with leukocyte transendothelial migration, while downregulated genes were significantly enriched in tumor necrosis factor (TNF), interleukin-17 (IL-17), nuclear factor kappa B (NF-κB) signaling pathways, and cortisol synthesis and secretory. CONCLUSION: High expressions of CLDN8, CTNNA3, MYL2 and MYLPF genes in patients with oral lichen planus have a good clinical response to topical dexamethasone, while patients with high expression genes of inflammation pathway such as TNF, IL-17, NF-κB and cortisol synthesis and secretion received poor effect.


Asunto(s)
Glucocorticoides , Liquen Plano Oral , Humanos , Glucocorticoides/uso terapéutico , FN-kappa B , Interleucina-17/genética , Interleucina-17/uso terapéutico , Transcriptoma , Liquen Plano Oral/tratamiento farmacológico , Liquen Plano Oral/genética , Liquen Plano Oral/metabolismo , Hidrocortisona/uso terapéutico , Dexametasona/uso terapéutico , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Dolor/tratamiento farmacológico
8.
Anal Chem ; 95(48): 17679-17690, 2023 12 05.
Artículo en Inglés | MEDLINE | ID: mdl-37971891

RESUMEN

Somatic mutation is a valuable biomarker for tracking tumor progression and migration due to its distinctive feature in various tumors and its wide distribution throughout body fluids. However, accurately detecting somatic mutations from the abundant DNA of noncancerous origins remains a practical challenge in the clinic. Herein, we developed an ultraspecific method, called tweezer PCR, for detecting low-abundance mutations inspired by the design of DNA origami. The high specificity of tweezer PCR relies on a tweezer-shaped primer containing six basic functional units: a primer, a hairpin, a linker, a blocker, a spacer, and a toehold. After optimizing the structure of the tweezer-shaped primer and enhancing its specificity by adding additional Mg2+ and Na+, tweezer PCR distinguished as low as 20 copies of mutations from 2 million copies of wild-type templates per test. By testing synthesized plasmids and plasma samples gathered from nonsmall-cell lung cancer patients, tweezer PCR showed higher specificity and robustness for detecting low-copy-number mutations in contrast with digital droplet PCR. Additionally, the need for conventional instruments makes tweezer PCR a practically accessible method for testing low-abundance mutations. Because of its numerous advantages, we believe that tweezer PCR offers a precise, robust, and pragmatic tool for cancer screening, prognosis, and genotyping in the clinic.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Mutación , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Reacción en Cadena de la Polimerasa/métodos , ADN , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología
9.
Environ Sci Technol ; 57(48): 19965-19978, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-37972223

RESUMEN

Bioaerosol pollution poses a substantial threat to human health during municipal food waste (FW) recycling. However, bioaerosol-borne antibiotic-resistant genes (ARGs) have received little attention. Herein, 48 metagenomic data were applied to study the prevalence of PM2.5-borne ARGs in and around full-scale food waste treatment plants (FWTPs). Overall, FWTP PM2.5 (2.82 ± 1.47 copies/16S rRNA gene) harbored comparable total abundance of ARGs to that of municipal wastewater treatment plant PM2.5 (WWTP), but was significantly enriched with the multidrug type (e.g., AdeC/I/J; p < 0.05), especially the abundant multidrug ARGs could serve as effective indicators to define resistome profiles of FWTPs (Random Forest accuracy >92%). FWTP PM2.5 exhibited a decreasing enrichment of total ARGs along the FWTP-downwind-boundary gradient, eventually reaching levels comparable to urban PM2.5 (1.46 ± 0.21 copies/16S rRNA gene, N = 12). The combined analysis of source-tracking, metagenome-assembled genomes (MAGs), and culture-based testing provides strong evidence that Acinetobacter johnsonii-dominated pathogens contributed significantly to shaping and disseminating multidrug ARGs, while abiotic factors (i.e., SO42-) indirectly participated in these processes, which deserves more attention in developing strategies to mitigate airborne ARGs. In addition, the exposure level of FWTP PM2.5-borne resistant pathogens was about 5-11 times higher than those in urban PM2.5, and could be more severe than hospital PM2.5 in certain scenarios (<41.53%). This work highlights the importance of FWTP in disseminating airborne multidrug ARGs and the need for re-evaluating the air pollution induced by municipal FWTP in public health terms.


Asunto(s)
Genes Bacterianos , Eliminación de Residuos , Humanos , Alimentos , ARN Ribosómico 16S , Bacterias/genética , Antibacterianos/farmacología , Material Particulado
10.
J Dent Sci ; 18(4): 1638-1644, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37799923

RESUMEN

Background/purpose: Dyslipidemia and a high fat diet may increase the predisposition for accumulating body fat in patients with oral lichen planus (OLP). This study aimed to investigate the risk factors obesity, dietary patterns, and lipid metabolism. Materials and methods: A population-based case-control study was conducted between September 2020 and October 2021, recruiting 275 pairs of OLP cases and controls. Information on lipid profiles, diet frequency and waist circumference were gathered. Principal component and factor analysis were used to analyze the semi-quantitative dietary frequency survey data of patients to extract specific dietary patterns. Results: Univariate analysis showed that total cholesterol, triglycerides, and low-density lipoprotein were significantly higher in the OLP group than the control and other oral mucosal disease groups (P < 0.05, P < 0.001, and P < 0.001, respectively). Compared with the baseline group, obese and overweight patients were more common in the OLP group. Dyslipidemia was more common in the OLP group (68%) compared to the healthy mucosa group (32%; P < 0.001, OR = 4.52, 95% CI = 2.49-8.18). Four dietary patterns were described among the subjects. The traditional prone animal food pattern (OR: 24.81, 95% CI: 6.05-101.71, P < 0.001) and animal food pattern (OR: 28.77, 95% CI: 8.10-102.15, P = 0.001) were associated with an increased risk of OLP. Conclusion: The results indicated that a high-fat diet, dyslipidemia and obesity were strongly linked to disease progression in OLP. A diet high in processed food and fat could increase the risk of OLP.

12.
Arch Oral Biol ; 153: 105751, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37379635

RESUMEN

OBJECTIVE: This study was presented to reveal the most distinct microbial prevalence in recurrent aphthous stomatitis (RAS) lesions compared to healthy controls. DESIGN: The case-control studies were selected in electronic databases until Nov 2022 with key search terms, and the eligible publications were screened and analyzed by independent authors. RESULTS: A total of 14 studies were identified, which included 531 cases of active states of RAS (AS-RAS), 92 cases of passive states of RAS (PS-RAS) and 372 healthy controls. The most sample pattern was the mucosa swab performed in 8 of 14 studies, biopsies in 3 studies, followed by micro-brush, and saliva. A variety of bacteria in higher or lower abundance were observed in RAS lesions. CONCLUSIONS: The etiopathogenesis of RAS may not be ascribed to a single pathogen. A possible explanation is that microbial interactions modify immune response or destroy the epithelial integrity, thus contributing to the development of the condition.


Asunto(s)
Microbiota , Estomatitis Aftosa , Humanos , Recurrencia , Estudios de Casos y Controles
13.
Environ Sci Pollut Res Int ; 30(30): 74742-74753, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37249772

RESUMEN

Mature landfill leachate is known for nitrogen-removal challenging and meantime was considered as an important sink of antibiotic resistance genes (ARGs). The added external carbon sources, enabling the short-cut nitrification and denitrification, may facilitate the proliferation of bacteria that possibly carry ARGs. However, this speculation has yet to be studied. Here, we explored the effects of glucose, sodium acetate, and methanol supplements on ARGs during whole-run and short-cut treatment processes. The results showed that sodium acetate supplement during short-cut process efficiently reduced the abundances of total ARGs (0.84-1.99 copies/16S rRNA) and integrons (0.59-1.20 copies/16S rRNA), which were highly enhanced by methanol addition during whole-run treatment process (total ARGs: 3.60-11.01 copies/16S rRNA, integrons: 1.20-4.69 copies/16S rRNA). Indirect gradient analysis showed that the variation of ARGs was not correlated with the supplement of different external carbon source. Correlation analysis indicated that dominant intl1 (55.99 ± 17.61% of integrons) showed positively significant correlations with all detected ARGs expect for sul2 and ermB (p < 0.05), suggesting the significant role on ARGs dissemination. Redundancy analysis illustrated that the potential hosts of intl1, intl2, sul1, tetQ, tetM, mefA, and mexF were dominant Bacteroidetes and Actinobacteria. Interestingly, the numbers and significant extent of correlations under the supplement of sodium acetate during short-cut denitrification process were obviously declined, and it was in accordance with ARGs reduced by sodium acetate supplement, suggesting sodium acetate displayed the efficient ARGs reduction during short-cut process. In summary, this study provides a comparative understanding of the effects on ARGs by different carbon source supplements during nitrification-denitrification processes of leachate; sodium acetate is the optimal carbon source.


Asunto(s)
Antibacterianos , Desnitrificación , Antibacterianos/farmacología , ARN Ribosómico 16S/genética , Metanol , Nitrificación , Acetato de Sodio/farmacología , Bacterias/genética , Genes Bacterianos , Farmacorresistencia Microbiana/genética
14.
Clin Cancer Res ; 29(16): 3162-3171, 2023 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-37256648

RESUMEN

PURPOSE: Adenoid cystic carcinoma (ACC) is a heterogeneous malignancy, and no effective systemic therapy exists for metastatic disease. We previously described two prognostic ACC molecular subtypes with distinct therapeutic vulnerabilities, ACC-I and ACC-II. In this study, we explored the ACC tumor microenvironment (TME) using RNA-sequencing and spatial biology to identify potential therapeutic targets. EXPERIMENTAL DESIGN: Tumor samples from 62 ACC patients with available RNA-sequencing data that had been collected as part of previous studies were stained with a panel of 28 validated metal-tagged antibodies. Imaging mass cytometry (IMC) was performed using the Fluidigm Helios CyTOF instrument and analyzed with Visiopharm software. The B7-H4 antibody-drug conjugate AZD8205 was tested in ACC patient-derived xenografts (PDX). RESULTS: RNA deconvolution revealed that most ACCs are immunologically "cold," with approximately 30% being "hot." ACC-I tumors with a poor prognosis harbored a higher density of immune cells; however, spatial analysis by IMC revealed that ACC-I immune cells were significantly restricted to the stroma, characterizing an immune-excluded TME. ACC-I tumors overexpressed the immune checkpoint B7-H4, and the degree of immune exclusion was directly correlated with B7-H4 expression levels, an independent predictor of poor survival. Two ACC-I/B7-H4-high PDXs obtained 90% complete responses to a single dose of AZD8205, but none were observed with isotype-conjugated payload or in an ACC-II/B7-H4 low PDX. CONCLUSIONS: Spatial analysis revealed that ACC subtypes have distinct TMEs, with enrichment of ACC-I immune cells that are restricted to the stroma. B7-H4 is highly expressed in poor-prognosis ACC-I subtype and is a potential therapeutic target.


Asunto(s)
Carcinoma Adenoide Quístico , Humanos , Carcinoma Adenoide Quístico/tratamiento farmacológico , Carcinoma Adenoide Quístico/genética , Inhibidor 1 de la Activación de Células T con Dominio V-Set , Pronóstico , Biomarcadores de Tumor , Microambiente Tumoral
15.
Environ Pollut ; 325: 121448, 2023 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-36931489

RESUMEN

Aldehydes and ketones in urban air continue to receive regulatory and scientific attention for their environmental prevalence and potential health hazard. However, current knowledge of the health risks and losses caused by these pollutants in food waste (FW) treatment processes is still limited, especially under long-term exposure. Here, we presented the first comprehensive assessment of chronic exposure to 21 aldehydes and ketones in urban FW-air environments (e.g., storage site, mechanical dewatering, and composting) by coupling substantial measured data (383 samples) with Monte Carlo-based probabilistic health risk and impact assessment models. The results showed that acetaldehyde, acetone, 2-butanone and cyclohexanone were consistently the predominant pollutants, although the significant differences in pollution profiles across treatment sites and seasons (Adonis test, P < 0.001). According to the risk assessment results, the estimated cancer risk (CR; mean range: 1.6 × 10-5-1.12 × 10-4) and non-cancer risk (NCR; mean range: 2.98-22.7) triggered by aldehydes and ketones were both unacceptable in most cases (CR: 37.8%-99.3%; NCR: 54.2%-99.8%), and even reached the limit of concern to CR (1 × 10-4) in some exposure scenarios (6.18%-16.9%). Application of DALYs (disability adjusted life years) as a metric for predicting the damage suggested that exposure of workers to aldehydes and ketones over 20 years of working in FW-air environments could result in 0.02-0.14 DALYs per person. Acetaldehyde was the most harmful constituent of all targeted pollutants, which contributed to the vast majority of health risks (>88%) and losses (>90%). This study highlights aldehydes and ketones in FW treatments may be the critical pollutants to pose inhalation risks.


Asunto(s)
Contaminantes Atmosféricos , Contaminantes Ambientales , Eliminación de Residuos , Humanos , Aldehídos/análisis , Exposición por Inhalación/análisis , Contaminantes Atmosféricos/análisis , Cetonas/análisis , Monitoreo del Ambiente , Alimentos , China/epidemiología , Acetaldehído
16.
J Clin Oncol ; 41(15): 2843-2851, 2023 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-36898078

RESUMEN

PURPOSE: We conducted a phase II trial evaluating the efficacy of VEGFR inhibitor axitinib and PD-L1 inhibitor avelumab in patients with recurrent/metastatic adenoid cystic carcinoma (R/M ACC). PATIENTS AND METHODS: Eligible patients had R/M ACC with progression within 6 months before enrollment. Treatment consisted of axitinib and avelumab. The primary end point was objective response rate (ORR) per RECIST 1.1; secondary end points included progression-free survival (PFS), overall survival (OS), and toxicity. Simon's optimal two-stage design tested the null hypothesis of ORR ≤5% versus ORR ≥20% at 6 months; ≥4 responses in 29 patients would reject the null hypothesis. RESULTS: Forty patients enrolled from July 2019 to June 2021; 28 were evaluable for efficacy (six screen failures; six evaluable for safety only). The confirmed ORR was 18% (95% CI, 6.1 to 36.9); there was one unconfirmed partial response (PR). Two patients achieved PR after 6 months; thus, the ORR at 6 months was 14%. The median follow-up time for surviving patients was 22 months (95% CI, 16.6 to 39.1 months). The median PFS was 7.3 months (95% CI, 3.7 to 11.2 months), 6-month PFS rate was 57% (95% CI, 41 to 78), and median OS was 16.6 months (95% CI, 12.4 to not reached months). Most common treatment-related adverse events (TRAEs) included fatigue (62%), hypertension (32%), and diarrhea (32%). Ten (29%) patients had serious TRAEs, all grade 3; four patients (12%) discontinued avelumab, and nine patients (26%) underwent axitinib dose reduction. CONCLUSION: The study reached its primary end point with ≥4 PRs in 28 evaluable patients (confirmed ORR of 18%). The potential added benefit of avelumab to axitinib in ACC requires further investigation.


Asunto(s)
Carcinoma Adenoide Quístico , Humanos , Axitinib/efectos adversos , Carcinoma Adenoide Quístico/tratamiento farmacológico , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos
17.
J Am Dent Assoc ; 154(4): 350-354, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-35339262
18.
Cell Discov ; 8(1): 136, 2022 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-36543767

RESUMEN

The effects of different SARS-CoV-2 vaccinations and variant infection histories on imprinting population immunity and their influence on emerging escape mutants remain unclear. We found that Omicron (BA.1) breakthrough infection, regardless of vaccination with two-dose mRNA vaccines (M-M-o) or two-dose inactivated vaccines (I-I-o), led to higher neutralizing antibody levels against different variants and stronger T-cell responses than Delta breakthrough infection after two-dose inactivated vaccine vaccination (I-I-δ). Furthermore, different vaccination-infection patterns imprinted virus-specific T-cell differentiation; M-M-ο showed higher S/M/N/E-specific CD4+ T cells and less portion of virus-specific CD45RA+CD27-CD8+ T cells by ex vivo assay. Breakthrough infection groups showed higher proliferation and multi-function capacity by in vitro assay than three-dose inactivated vaccine inoculated group (I-I-I). Thus, under wide vaccination coverage, the higher immunogenicity with the Omicron variant may have helped to eliminate the population of Delta variant. Overall, our data contribute to our understanding of immune imprinting in different sub-populations and may guide future vaccination programs.

19.
Artículo en Inglés | MEDLINE | ID: mdl-35886358

RESUMEN

Great efforts have been exerted in reducing carbon emissions in design, construction and operation stages. However, little attention is paid to the quantification of carbon emissions in construction waste recycling at the end-of-life stage. This study aims to quantitatively analyze the carbon emission of construction waste in Shanghai City, PR China. A grey model is used to forecast the generation amount of construction waste, and a life cycle assessment is performed to estimate the carbon emission of construction waste. In this study, both the carbon emission of recycling activities (environmental costs), and the equivalent amount of carbon generated from alternative materials (environmental benefit) are considered. Here, recycling 1 ton (t) of construction waste in Shanghai can save 100.4 kg CO2-e. The total carbon-emission-saving potential can be increased from 0.31 million t CO2-e (2022) to 0.35 million t CO2-e (2031). The carbon emission of recycling concrete, brick, steel, wood and mortar, identified as the key components of construction waste, is investigated. This research can help to reduce carbon emissions and further achieve carbon neutrality for Shanghai City. The proposed methods can also be applied to other regions, especially when the data for construction waste are insufficient.


Asunto(s)
Industria de la Construcción , Administración de Residuos , Animales , Carbono , Dióxido de Carbono , China , Industria de la Construcción/métodos , Materiales de Construcción , Estadios del Ciclo de Vida , Reciclaje/métodos , Administración de Residuos/métodos
20.
J Hazard Mater ; 437: 129423, 2022 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-35752052

RESUMEN

Odor pollution is one of the most critical issues in food waste (FW) recycling and has significant implications for human health. However, knowledge of their occurrence and spatiotemporally dynamic in urban FW streams is limited, making it not conducive to implement targeted odor management. This work followed the occurrence of 81 odor compounds (OCs) in nine FW-air environments along the Shanghai's FW streams for one year. Results showed that NH3, acetic acid, acetaldehyde, acetone, 2-butanone, and methylene chloride were consistently the predominant OCs, despite the distinct differences in OCs profiles across seasons and treatment sites. Ridge regression and principal coordinate analysis demonstrated that seasons might play a non-negligible role in shaping odor profiles, and ambient temperature and humidity could account for the seasonal variation in OCs levels. Based on the modified fuzzy synthetic evaluation system, the screened priority pollutants in different FW-air environments were found broadly similar and the regulated air pollutants released via FW should be expanded to aldehyde and ketone compounds, especially for acetaldehyde. To our knowledge, this study is the first to track the spatiotemporal footprints of OCs within urban FW streams, and provides new insights into the control policy on FW-derived odor issues for megacities.


Asunto(s)
Odorantes , Eliminación de Residuos , Acetaldehído , China , Alimentos , Humanos , Odorantes/análisis , Políticas
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