RESUMO
Water ice and other volatiles that accumulated in the Moon's polar regions are among the top priority targets for lunar exploration, due to their significances in both lunar geology and extraterrestrial resource utilization. Locating suitable landing sites and determining the provenance of sampled/measured surface materials are critical for future landed missions. Here, we map over 800 sites of plains terrains in the Moon's south polar region, with a total surface area of ~46,000 km2. Orbital measurements and analog studies show that most of these plains have apparently higher albedo and lower iron content than volcanic mare plains, suggesting an origin of ejecta-induced debris flows from distant impact craters, especially from the Schrödinger basin. Our findings suggest that the entire lunar south polar region probably have experienced contributions from distant basin materials. We recommend these plains as priority landing sites for future exploration of lunar polar volatiles and early bombardment history.
RESUMO
Introduction: Migrant workers in China are migrants from the rural to the urban areas who usually work in the cities and return to the countryside after a certain period. Due to China's strict household registration system, they differ significantly from urban residents' access to public services. However, at the same time, China's workers are facing a severe phenomenon of overwork, and the group of migrant workers is even more hard-hit by overwork, which will cause various adverse effects on workers and society and should attract the attention of all sectors of society. Methods: This paper focuses on the impact of digital financial inclusion on the overwork of migrant workers. This study considered cross-sectional data containing 98,047 samples based on the 2017 China Migrants Dynamic Survey 2017 (CMDS) and China Municipal Statistical Yearbook after robustness tests and heterogeneity analysis using probit models. Results: (1) digital financial inclusion can effectively alleviate overwork among migrant workers; (2) the impact of digital finance on overwork is more significant for the new generation, digitized industries, and self-employed migrant workers; it is also more significant for the South, East, and small and medium-sized cities than for the North, the Midwest, and large cities; (3) job quality and income are crucial factors in how digital financial inclusion affects overwork among migrant workers. Digital financial inclusion can improve the quality of employment for migrant workers and alleviate overwork. However, the income substitution effect partially reduces the inhibitory impact of digital financial inclusion on overwork. Conclusion: Continuously promote the development of digital inclusive finance, improve laws and regulations, and protect the labor rights and interests of migrant workers. At the same time, vocational training and skills upgrading for rural migrant workers should be strengthened to improve the quality of their employment so that they can leave the secondary labor market and enter the primary labor market.
Assuntos
Migrantes , Humanos , China , Migrantes/estatística & dados numéricos , Estudos Transversais , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Inquéritos e Questionários , Emprego/estatística & dados numéricos , População Rural/estatística & dados numéricosRESUMO
BACKGROUND: 5-Hydroxymethylcytosine-enriched gene profiles and regions show tissue-specific and tumor specific. There is a potential value to explore cell-free DNA 5-hydroxymethylcytosine feature biomarkers for early gastric cancer detection. METHODS: A matched caseâcontrol study design with 50 gastric cancer patients and 50 controls was performed to sequence the different 5-hydroxymethylcytosine modification features of cell free DNA. Significantly differential 5-hydroxymethylcytosine modification genes were identified to construct a gastric cancer diagnostic model. Data set from GEO was used as an external testing set to test the robustness of the diagnostic model. RESULTS: Accounting for more than 90% of 5-hydroxymethylcytosine peaks were distributed in the gene body in both the gastric cancer and control groups. The diagnostic model was developed based on five different 5-hydroxymethylcytosine modification genes, FBXL7, PDE3A, TPO, SNTG2 and STXBP5. The model could effectively distinguish gastric cancer patients from controls in the training (AUC = 0.95, sensitivity = 88.6%, specificity = 94.3%), validation (AUC = 0.87, sensitivity = 73.3%, specificity = 93.3%) and testing (AUC = 0.90, sensitivity = 81.9%, specificity = 90.2%) sets. The risk scores of the controls from the model were significantly lower than those of gastric cancer patients in both our own data (P < 0.001) and GEO external testing data (P < 0.001), and no significant difference between different TNM stage patients (P = 0.09 and 0.66). Furthermore, there was no significant difference between the healthy control and benign gastric disease patients in the testing set from GEO (P = 0.10). CONCLUSIONS: The characteristics of 5-hydroxymethylcytosine in cell free DNA are specific to gastric cancer patients, and the diagnostic model constructed by five genes' 5-hydroxymethylcytosine features could effectively identify gastric cancer patients.
Assuntos
5-Metilcitosina , Biomarcadores Tumorais , Ácidos Nucleicos Livres , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , 5-Metilcitosina/análogos & derivados , Biomarcadores Tumorais/genética , Masculino , Estudos de Casos e Controles , Feminino , Pessoa de Meia-Idade , Ácidos Nucleicos Livres/genética , Idoso , Detecção Precoce de Câncer/métodos , Metilação de DNARESUMO
The occurrence and progression of tumors are inseparable from glucose metabolism. With the development of tumors, the volume increases gradually and the nutritional supply of tumors cannot be fully guaranteed. The tumor microenvironment changes and glucose deficiency becomes the common stress environment of tumors. Here, we discuss the mutual influences between glucose deprivation and other features of the tumor microenvironment, such as hypoxia, immune escape, low pH, and oxidative stress. In the face of a series of stress responses brought by glucose deficiency, different types of tumors have different coping mechanisms. We summarize the tumor studies on glucose deficiency in the last decade and review the genes and pathways that determine the fate of tumors under harsh conditions. It turns out that most of these genes help tumor cells survive in glucose-deprivation conditions. The development of related inhibitors may bring new opportunities for the treatment of tumors.
RESUMO
Background: Little is known about the microbiology and outcomes of chemotherapy-associated febrile illness among patients in sub-Saharan Africa. Understanding the microbiology of febrile illness could improve antibiotic selection and infection-related outcomes. Methods: From September 2019 through June 2022, we prospectively enrolled adult inpatients at the Uganda Cancer Institute who had solid tumors and developed fever within 30 days of receiving chemotherapy. Evaluation included blood cultures, malaria rapid diagnostic tests, and urinary lipoarabinomannan testing for tuberculosis. Serum cryptococcal antigen was evaluated in participants with human immunodeficiency virus (HIV). The primary outcome was the mortality rate 40 days after fever onset, which we estimated using Cox proportional hazards models. Results: A total of 104 febrile episodes occurred among 99 participants. Thirty febrile episodes (29%) had ≥1 positive microbiologic result. The most frequently identified causes of infection were tuberculosis (19%) and bacteremia (12%). The prevalence of tuberculosis did not differ by HIV status. The 40-day case fatality ratio was 25%. There was no difference in all-cause mortality based on HIV serostatus, presence of neutropenia, or positive microbiologic results. A universal vital assessment score of >4 was associated with all-cause mortality (hazard ratio, 14.5 [95% confidence interval, 5-42.7]). Conclusions: The 40-day mortality rate among Ugandan patients with solid tumors who developed chemotherapy-associated febrile illness was high, and few had an identified source of infection. Tuberculosis and bacterial bloodstream infections were the leading diagnoses associated with fever. Tuberculosis should be included in the differential diagnosis for patients who develop fever after receiving chemotherapy in tuberculosis-endemic settings, regardless of HIV serostatus.
RESUMO
Traumatic brain injury (TBI) is a major cause of death and disability that involves brain dysfunction due to external forces. Here, we found lower levels of Ubiquinol-cytochrome c reductase, complex III subunit XI (Uqcr11) expression in the cerebral cortex of TBI mice. A neuronal damage model was constructed using H2O2 or hypoxia reoxygenation (H/R) in vitro. We found that Uqcr11 overexpression attenuated the H2O2-or H/R-induced damage by preventing oxidative stress and neuronal apoptosis in HT22 cells. Moreover, up-regulated Uqcr11 contributed to the restoration of motor, learning, and memory in C57BL/6 mice after TBI, and its underlying mechanism may be associated with promoting neuron survival and inhibited oxidative stress. Collectively, our findings demonstrated that oxidative stress as well as neuronal apoptosis can be ameliorated post-TBI by Uqcr11 overexpression, which provides a potential therapeutic target for TBI.
Assuntos
Lesões Encefálicas Traumáticas , Peróxido de Hidrogênio , Camundongos , Animais , Camundongos Endogâmicos C57BL , Lesões Encefálicas Traumáticas/metabolismo , Apoptose , Estresse OxidativoRESUMO
The clinical management of patients with indeterminate pulmonary nodules is associated with unintended harm to patients and better methods are required to more precisely quantify lung cancer risk in this group. Here, we combine multiple noninvasive approaches to more accurately identify lung cancer in indeterminate pulmonary nodules. We analyzed 94 quantitative radiomic imaging features and 41 qualitative semantic imaging variables with molecular biomarkers from blood derived from an antibody-based microarray platform that determines protein, cancer-specific glycan, and autoantibody-antigen complex content with high sensitivity. From these datasets, we created a PSR (plasma, semantic, radiomic) risk prediction model comprising nine blood-based and imaging biomarkers with an area under the receiver operating curve (AUROC) of 0.964 that when tested in a second, independent cohort yielded an AUROC of 0.846. Incorporating known clinical risk factors (age, gender, and smoking pack years) for lung cancer into the PSR model improved the AUROC to 0.897 in the second cohort and was more accurate than a well-characterized clinical risk prediction model (AUROC = 0.802). Our findings support the use of a multi-omics approach to guide the clinical management of indeterminate pulmonary nodules.
RESUMO
Multispectral stealth technology including terahertz (THz) band will play an increasingly important role in modern military and civil applications. Here, based on the concept of modularization design, two kinds of flexible and transparent metadevices were fabricated for multispectral stealth, covering the visible, infrared (IR), THz, and microwave bands. First, three basic functional blocks for IR, THz, and microwave stealth are designed and fabricated by using flexible and transparent films. And then, via modular assembling, that is, by adding or removing some stealth functional blocks or constituent layers, two multispectral stealth metadevices are readily achieved. Metadevice 1 exhibits THz-microwave dual-band broadband absorption, with average measured absorptivity of 85% in 0.3-1.2 THz and higher than 90% in 9.1-25.1â GHz, suitable for THz-microwave bi-stealth. Metadevice 2 is for IR and microwave bi-stealth, with measured absorptivity higher than 90% in 9.7-27.3â GHz and low emissivity around 0.31 in 8-14 µm. Both metadevices are optically transparent and able to maintain good stealth ability under curved and conformal conditions. Our work offers an alternative approach for designing and fabricating flexible transparent metadevices for multispectral stealth, especially for applications in nonplanar surfaces.
RESUMO
Small cell lung cancer (SCLC) elicits the generation of autoantibodies that result in unique paraneoplastic neurological syndromes. The mechanistic basis for the formation of such autoantibodies is largely unknown but is key to understanding their etiology. We developed a high-dimensional technique that enables detection of autoantibodies in complex with native antigens directly from patient plasma. Here, we used our platform to screen 1009 human plasma samples for 3600 autoantibody-antigen complexes, finding that plasma from patients with SCLC harbors, on average, fourfold higher disease-specific autoantibody signals compared with plasma from patients with other cancers. Across three independent SCLC cohorts, we identified a set of common but previously unknown autoantibodies that are produced in response to both intracellular and extracellular tumor antigens. We further characterized several disease-specific posttranslational modifications within extracellular proteins targeted by these autoantibodies, including citrullination, isoaspartylation, and cancer-specific glycosylation. Because most patients with SCLC have metastatic disease at diagnosis, we queried whether these autoantibodies could be used for SCLC early detection. We created a risk prediction model using five autoantibodies with an average area under the curve of 0.84 for the three cohorts that improved to 0.96 by incorporating cigarette smoke consumption in pack years. Together, our findings provide an innovative approach to identify circulating autoantibodies in SCLC with mechanistic insight into disease-specific immunogenicity and clinical utility.
Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Pulmonares/patologia , Autoanticorpos , Processamento de Proteína Pós-TraducionalRESUMO
Intravenous busulfan doses are often personalized to a target plasma exposure (targeted busulfan) using an individual's busulfan clearance (BuCL). We evaluated whether BuCL could be predicted by a predose plasma panel of 841 endogenous metabolomic compounds (EMCs). In this prospective cohort of 132 hematopoietic cell transplantation (HCT) patients, all had samples collected immediately before busulfan administration (preBU) and 96 had samples collected 2 weeks before busulfan (2-week-preBU). BuCL was significantly associated with 37 EMCs after univariate linear regression analysis and controlling for false discovery (< 0.05) in the 132 preBU samples. In parallel, with preBU samples, we included all 841 EMCs in a least absolute shrinkage and selection operator-penalized regression which selected 13 EMCs as predominantly associated with BuCL. Then, we constructed a prediction model by estimating coefficients for these 13 EMCs, along with sex, using ordinary least-squares. When the resulting linear prediction model was applied to the 2-week-preBU samples, it explained 40% of the variation in BuCL (adjusted R2 = 0.40). Pathway enrichment analysis revealed 18 pathways associated with BuCL. Lysine degradation followed by steroid biosynthesis, which aligned with the univariate analysis, were the top two pathways. BuCL can be predicted before busulfan administration with a linear regression model of 13 EMCs. This pharmacometabolomics method should be prioritized over use of a busulfan test dose or pharmacogenomics to guide busulfan dosing. These results highlight the potential of pharmacometabolomics as a precision medicine tool to improve or replace pharmacokinetics to personalize busulfan doses.
Assuntos
Bussulfano , Transplante de Células-Tronco Hematopoéticas , Humanos , Estudos Prospectivos , Medicina de Precisão , Farmacogenética , Metabolômica , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodosRESUMO
This study was aimed to investigate the accuracy of anteroposterior chest radiography for tip position verification for the umbilical venous catheters in neonates compared to ultrasound. A search in the PubMed, Embase, the Cochrane Library, and EBSCO was conducted to evaluate all the related articles on umbilical venous catheter (UVC), ultrasound AND neonates updated to August, 2020. Study selection, data extraction, and quality assessment were performed independently by two investigators. Random effects model was used to estimate the pooled sensitivity, specificity, and diagnostic odds ratio (DOR). The summary receiver operator characteristic (SROC) curve was constructed, and the area under the SROC curve (AUC) was calculated. Fourteen related studies were finally included for meta-analysis. The overall diagnostic sensitivity and speciï¬city of X-ray on tip verification of UVC were 0.90 (95% CI 0.71-0.97) and 0.82 (95% CI 0.53-0.95), respectively. The pooled DOR was 3.69 (95% CI 1.64-5.71). The AUC was 0.93 (95% CI 0.90-0.95). The meta-regression analysis suggested that study sample size, study design, different US confirming method, and different gold standard in original design might be potential sources of heterogeneity. Our conclusion is that the commonly used anteroposterior X-ray is not reliable in identifying the exact anatomical location of UVC tip in neonates. Studies suggested ultrasound or echocardiography with saline contrast injection could be the gold standard for verification of catheter location and should be considered whenever possible, especially in premature patients. More studies are needed to expand the use of ultrasound or echocardiography in tip position confirming of UVCs.
Assuntos
Ecocardiografia , Dispositivos de Acesso Vascular , Recém-Nascido , Humanos , Ultrassonografia , Radiografia , CatéteresRESUMO
China's health system is facing severe challenges from social transition and the double burden of population aging and non-communicable diseases. Addressing the tension between the public's increasing demand for health services and the limited availability of medical resources has become a critical issue for health care policymakers and medical insurance fund administrators. In promoting its medical insurance system reform, China is actively developing health technology assessment (HTA) with principles and applications adapted to the Chinese context. This study aims to analyze the evolution of HTA in China with a focus on context, actors, process, content, and challenges encountered through applying a modified verson of Walt and Gilson's policy triangle framework. Currently, HTA plays an indispensable part in the reform of China's health care and medical insurance system, especially in the formulation and adjustment of the National Reimbursement Drug List (NRDL). While HTA is increasingly used in China, there remain challenges, such as the slow development of HTA related disciplines, lack of an independent national HTA authority, and limited scope in the use of HTA. Despite the identified challenges, HTA has the potential to support a wide range of applications in China's health care sector, building on the progress achieved over the last three decades.
Assuntos
Reforma dos Serviços de Saúde , Avaliação da Tecnologia Biomédica , China , Avaliação da Tecnologia Biomédica/métodos , Humanos , Reforma dos Serviços de Saúde/métodos , Reforma dos Serviços de Saúde/tendências , Setor de Assistência à Saúde/tendências , Política de Saúde , Seguro Saúde/tendências , Seguro Saúde/estatística & dados numéricosRESUMO
Food consumption induces oxidative stress in humans, but the changes in oxidative stress levels after a regular meal are still unclear. We conducted an experimental study on 20 healthy volunteers (10 males, 10 females), who matched in age (±2 years). They were given a regular diet (total energy of 704 kcal, which contains 75 g of carbohydrates, 35 g of protein, and 29 g of lipids) at 11:30 a.m. after a fast of over 12 h. We collected 6-repeated measures of venous blood samples at 2-h intervals via heparin anticoagulant tubes immediately after the meal (indicated as "0" h) and up to 10 h post-consumption. Biomarkers included plasma fluorescent products, plasma malondialdehyde, plasma total antioxidant capacity, and plasma superoxide dismutase. FlOPs were measured at three excitation/emission wavelengths (FlOP_320, FlOP_360, and FlOP_400). The average age and BMI for the twenty participants were 22.70 ± 1.98 years and 20.67 ± 2.34 kg/m2, respectively. Within 10 h after the meal, the overall trend of FlOPs were generally similar. There was no evidence of dose response for any of the three FlOPs (all P > 0.05). However, levels of MDA decreased with the time of fasting (P linear and P quadratic < 0.05), with the biggest decrease occurring between 0 and 2 h post-meal. The overall trend of T-AOC and SOD levels also decreased with fasting time (P linear and P quadratic < 0.05), though an increase was observed between 0 and 2 h following consumption. Levels of MDA, T-AOC, and SOD but not FlOPs, decreased with fasting time.
RESUMO
Purpose: Gastric cancer (GC) remains a prevalent aggressive tumor with high morbidity and mortality globally. The identification of GC subtypes based on molecular features improved the prediction of prognosis and the selection of targeted therapies. PTEN is a characteristic tumor suppressor, while its association with different GC subtypes was unknown. Patients and Methods: The cohort consisted of 248 patients diagnosed with gastric cancer who were hospitalized and received radical gastrectomy. In addition, PTEN gene expression matrix of STAD was retrieved from TCGA. The mRNA and protein levels of PTEN and PD-L1 were detected using qRT-PCR and IHC staining. Multivariate logistic regression and Kaplan-Meier analysis were used to examine the relationship between PTEN expression and clinical characteristics. Results: In our study, PTEN was downregulated in gastric tumors both in mRNA and protein levels. Its inactivation was closely linked to higher histological grade (P = 0.005), neural invasion (P = 0.012), depth of invasion (P = 0.021), lymph metastasis (P = 0.026), and TNM stage (P = 0.001) of GC in the present study. Moreover, according to the molecular subtypes, high PTEN expression was related to high TPS score of PD-L1 positively (P = 0.010) but was not associated with MSI and EBV infection. Further, TCGA data validated that PTEN was indeed correlated with histological grade and invasion depth and positively related to PD-L1 expression (R = 0.29, adjusted P < 0.001). Conclusion: The above results suggested that PTEN expression was a useful marker in gastric carcinogenesis and progression and in the selection of immunotherapy-based treatments for GC patients.
RESUMO
Bud dormancy, which enables damage from cold temperatures to be avoided during winter and early spring, is an important adaptive mechanism of deciduous fruit trees to cope with seasonal environmental changes and temperate climates. Understanding the regulatory mechanism of bud break in fruit trees is highly important for the artificial control of bud break and the prevention of spring frost damage. However, the molecular mechanism underlying the involvement of MYB TFs during the bud break of peach is still unclear. In this study, we isolated and identified the PpMYB52 (Prupe.5G240000.1) gene from peach; this gene is downregulated in the process of bud break, upregulated in response to ABA and downregulated in response to GA. Overexpression of PpMYB52 suppresses the germination of transgenic tomato seeds. In addition, Y2H, Bimolecular fluorescence complementation (BiFC) assays verified that PpMYB52 interacts with a RING-type E3 ubiquitin ligase, PpMIEL1, which is upregulated during bud break may positively regulate peach bud break by ubiquitination-mediated degradation of PpMYB52. Our findings are the first to characterize the molecular mechanisms underlying the involvement of MYB TFs in peach bud break, increasing awareness of dormancy-related molecules to avoid bud damage in perennial deciduous fruit trees.
RESUMO
Ferredoxin is involved in many biological processes, such as carbon fixation, nitrogen assimilation, chlorophyll metabolism, and fatty acid synthesis, and it plays a role in plant resistance to stress. However, the functions of Fds in peach during stress are unclear. In this study, 11 members of the peach Fd gene family were identified and divided into six groups (I- VI). We carried out bioinformatics analysis on these sequences, analyzed the physical and chemical properties of PpFd protein and the cis-elements in its promoter region, and predicted and compared the differences in gene structure and conserved protein motifs among groups. The results showed that the PpFd protein was highly conserved in plant species. In addition, overexpression of PpFd08 significantly increased the tolerance of transgenic tomato to high-temperature stress. The transcriptome analysis and qRT-PCR results of PpFd08 transgenic apple calli showed that PpFd08 might enhance heat resistance by modulating the expression of heat tolerance related genes. The results of this study provide a new understanding for the further study of the function of PpFd protein in peach and a candidate gene for improving the heat resistance of peach.
Assuntos
Prunus persica , Termotolerância , Ferredoxinas/metabolismo , Genoma de Planta/genética , Família Multigênica , Prunus persica/genética , Prunus persica/metabolismo , Termotolerância/genéticaRESUMO
PURPOSE: Leiomyosarcoma and liposarcoma frequently express PD-L1 but are generally resistant to PD-1/PD-L1 inhibition (immune checkpoint inhibitor). Trabectedin is FDA approved for leiomyosarcoma and liposarcoma. This study aimed to evaluate the safety and efficacy of trabectedin with anti-PD-L1 antibody avelumab in patients with advanced leiomyosarcoma and liposarcoma. PATIENTS AND METHODS: A single-arm, open-label, Phase 1/2 study tested avelumab with trabectedin for advanced leiomyosarcoma and liposarcoma. The phase I portion evaluated safety and feasibility of trabectedin (1, 1.2, and 1.5 mg/m2) with avelumab at standard dosing. Primary endpoint of the phase II portion was objective response rate (ORR) by RECIST 1.1. Correlative studies included T-cell receptor sequencing (TCRseq), multiplex IHC, and tumor gene expression. RESULTS: 33 patients were evaluable: 24 with leiomyosarcoma (6 uterine and 18 non-uterine) and 11 with liposarcoma. In Phase 1, dose-limiting toxicities (DLT) were observed in 2 of 6 patients at both trabectedin 1.2 and 1.5 mg/m2. The recommended Phase 2 dose (RP2D) was 1.0 mg/m2 trabectedin and 800-mg avelumab. Of 23 patients evaluable at RP2D, 3 (13%) had partial response (PR) and 10 (43%) had stable disease (SD) as best response. Six-month PFS was 52%; median PFS was 8.3 months. Patients with PR had higher Simpson Clonality score on TCRseq from peripheral blood mononuclear cells versus those with SD (0.182 vs. 0.067, P = 0.02) or progressive disease (0.182 vs. 0.064, P = 0.01). CONCLUSIONS: Although the trial did not meet the primary objective response rate endpoint, PFS compared favorably with prior studies of trabectedin warranting further investigation.
Assuntos
Leiomiossarcoma , Lipossarcoma , Anticorpos Monoclonais Humanizados , Antineoplásicos Alquilantes/uso terapêutico , Antígeno B7-H1/genética , Humanos , Leiomiossarcoma/tratamento farmacológico , Leiomiossarcoma/genética , Leiomiossarcoma/patologia , Leucócitos Mononucleares/patologia , Lipossarcoma/tratamento farmacológico , Lipossarcoma/genética , Lipossarcoma/patologia , TrabectedinaRESUMO
Patients with metastatic soft tissue sarcoma (STS) have a poor prognosis and few available systemic treatment options. Trabectedin is currently being investigated as a potential adjunct to immunotherapy as it has been previously shown to kill tumor-associated macrophages. In this retrospective study, we sought to identify biomarkers that would be relevant to trials combining trabectedin with immunotherapy. We performed a single-center retrospective study of sarcoma patients treated with trabectedin with long-term follow-up. Multiplex gene expression analysis using the NanoString platform was assessed, and an exploratory analysis using the lasso-penalized Cox regression and kernel association test for survival (MiRKAT-S) methods investigated tumor-associated immune cells and correlated their gene signatures to patient survival. In total, 147 sarcoma patients treated with trabectedin were analyzed, with a mean follow-up time of 5 years. Patients with fewer prior chemotherapy regimens were more likely to stay on trabectedin longer (pairwise correlation = -0.17, p = 0.04). At 5 years, increased PD-L1 expression corresponded to worse outcomes (HR = 1.87, p = 0.04, q = 0.199). Additionally, six immunologic gene signatures were associated with up to 7-year survival by MiRKAT-S, notably myeloid-derived suppressor cells (p = 0.023, q = 0.058) and M2 macrophages (p = 0.03, q = 0.058). We found that the number of chemotherapy regimens prior to trabectedin negatively correlated with the number of trabectedin cycles received, suggesting that patients may benefit from receiving trabectedin earlier in their therapy course. The correlation of trabectedin outcomes with immune cell infiltrates supports the hypothesis that trabectedin may function as an immune modulator and supports ongoing efforts to study trabectedin in combination with immunotherapy. Furthermore, tumors with an immunosuppressive microenvironment characterized by macrophage infiltration and high PD-L1 expression were less likely to benefit from trabectedin, which could guide clinicians in future treatment decisions.
RESUMO
Terpene synthase (TPS) is related to the production of aromatic substances, but there are few studies on the impact of abiotic stress on TPS and its molecular mechanism, especially in peaches. This study found that salt resistance and abscisic acid (ABA) sensitivity of transgenic tomatoes were enhanced by overexpression of PpTPS1. Moreover, it was found that PpTPS1 interacted with and antagonized the expression of the bZIP transcription factor ABA INSENSITIVE 5 (PpABI5), which is thought to play an important role in salt suitability. In addition, PpTCP1, PpTCP13, and PpTCP15 were found to activate the expression of PpTPS1 by yeast one-hybrid (Y1H) and dual-luciferase assays, and they could also be induced by ABA. In summary, PpTPS1 may be involved in the ABA signaling regulatory pathway and play an important role in salt acclimation, providing a new reference gene for the improvement of salt resistance in peaches.
RESUMO
BACKGROUND: Previous researches have associated Helicobacter pylori (H. pylori) with a prognosis of gastric cancer (GC), however, without a concert conclusion. This study aimed to study this issue further by a prospective cohort study and a meta-analysis. METHODS: Histologically diagnosed gastric cancer (GC) patients were recruited into the primary prospective cohort study between January 2009 to December 2013. All the patients were followed-up periodically to record information on post-surgery therapy and overall survival status. The pre-surgery status of H. pylori was measured by enzyme-linked immunosorbent assay. A meta-analysis was conducted after retrieving related researches in the databases of PubMed and Embase up to April 2020. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were summarized to validate the relationship between H. pylori infection and the survival time of GC patients. I2 statistics and Q test were used to assess the heterogeneity. Sensitivity analyses were performed using Galbraith's plot, leave-one-out analysis, subgroup analyses and meta-regression to explore the sources of heterogeneity and the stability of the summary results. RESULTS: A total of 743 GC patients with radical tumorectomy were included prospectively and 516 (69.4%) were positive on H. pylori. H. pylori-positive patients tended to survive longer than -negative ones (HR 0.92, 95%CI: 0.74-1.15), though the tendency was not statistically significant. Cohort studies on the prognosis of GC were retrieved comprehensively by assessing the full-text and 59 published studies, together with the result of our study, were included in the further meta-analysis. The summarized results related the positive status of H. pylori to better overall survival (HR 0.81, 95%CI: 0.72-0.90) and disease-free survival (HR 0.83, 95%CI: 0.67-0.99). Results from subgroup analyses indicated that the pooled magnitude of this association was relatively lower in studies not referring to H. pylori in title and abstract. CONCLUSIONS: In conclusion, gastric cancer patients with H. pylori have a better prognosis than patients of H. pylori negative. More stringent surveillance strategies may be necessary for patients with H. pylori negative at cancer diagnosis.