Network analysis of histopathological image features and genomics data improving prognosis performance in clear cell renal cell carcinoma.

INTRODUCTION: Clear cell renal cell carcinoma is the most common type of kidney cancer, but the prediction of prognosis remains a challenge. METHODS: We collected whole-slide histopathological images, corresponding clinical and genetic information from the The Cancer Imaging Archive and The Cancer Genome Atlas databases and randomly divided patients into training (n = 197) and validation (n = 84) cohorts. After feature extraction by CellProfiler, we used 2 different machine learning techniques (Least Absolute Shrinkage and Selector Operation-regularized Cox and Support Vector Machine-Recursive Feature Elimination) and weighted gene co-expression network analysis to select prognosis-related image features and genes, respectively. These features and genes were integrated into a joint model using random forest and used to create a nomogram that combines other predictive indicators. RESULTS: A total of 4 overlapped features were identified, represented by the computed histopathological risk score in the random forest model, and showed predictive value for overall survival (test set: 1-year area under the curves (AUC) = 0.726, 3-year AUC = 0.727, and 5-year AUC = 0.764). The histopathological-genetic risk score (HGRS) integrating the genetic information computed performed better than the model that used image features only (test set: 1-year AUC = 0.682, 3-year AUC = 0.734, and 5-year AUC = 0.78). The nomogram (gender, stage, and HGRS) achieved the highest net benefit according to decision curve analysis compared to HGRS or clinical model. CONCLUSION: This study developed a histopathological-genetic-related nomogram by combining histopathological features and clinical predictors, providing a more comprehensive prognostic assessment for clear cell renal cell carcinoma patients.

Dissecting the dynamic cellular transcriptional atlas of adult teleost testis development throughout the annual reproductive cycle.

Teleost testis development during the annual cycle involves dramatic changes in cellular compositions and molecular events. In this study, the testicular cells derived from adult black rockfish at distinct stages - regressed, regenerating and differentiating - were meticulously dissected via single-cell transcriptome sequencing. A continuous developmental trajectory of spermatogenic cells, from spermatogonia to spermatids, was delineated, elucidating the molecular events involved in spermatogenesis. Subsequently, the dynamic regulation of gene expression associated with spermatogonia proliferation and differentiation was observed across spermatogonia subgroups and developmental stages. A bioenergetic transition from glycolysis to mitochondrial respiration of spermatogonia during the annual developmental cycle was demonstrated, and a deeper level of heterogeneity and molecular characteristics was revealed by re-clustering analysis. Additionally, the developmental trajectory of Sertoli cells was delineated, alongside the divergence of Leydig cells and macrophages. Moreover, the interaction network between testicular micro-environment somatic cells and spermatogenic cells was established. Overall, our study provides detailed information on both germ and somatic cells within teleost testes during the annual reproductive cycle, which lays the foundation for spermatogenesis regulation and germplasm preservation of endangered species.

MR radiomics predicts pathological complete response of esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy: a multicenter study.

BACKGROUND: More than 40% of patients with resectable esophageal squamous cell cancer (ESCC) achieve pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT), who have favorable prognosis and may benefit from an organ-preservation strategy. Our study aims to develop and validate a machine learning model based on MR radiomics to accurately predict the pCR of ESCC patients after nCRT. METHODS: In this retrospective multicenter study, eligible patients with ESCC who underwent baseline MR (T2-weighted imaging) and nCRT plus surgery were enrolled between September 2014 and September 2022 at institution 1 (training set) and between December 2017 and August 2021 at institution 2 (testing set). Models were constructed using machine learning algorithms based on clinical factors and MR radiomics to predict pCR after nCRT. The area under the curve (AUC) and cutoff analysis were used to evaluate model performance. RESULTS: A total of 155 patients were enrolled in this study, 82 in the training set and 73 in the testing set. The radiomics model was constructed based on two radiomics features, achieving AUCs of 0.968 (95%CI 0.933-0.992) in the training set and 0.885 (95%CI 0.800-0.958) in the testing set. The cutoff analysis resulted in an accuracy of 82.2% (95%CI 72.6-90.4%), a sensitivity of 75.0% (95%CI 58.3-91.7%), and a specificity of 85.7% (95%CI 75.5-96.0%) in the testing set. CONCLUSION: A machine learning model based on MR radiomics was developed and validated to accurately predict pCR after nCRT in patients with ESCC.

Different roles of host and habitat in determining the microbial communities of plant-feeding true bugs.

BACKGROUND: The true bugs (Heteroptera) occupy nearly all of the known ecological niches of insects. Among them, as a group containing more than 30,000 species, the phytophagous true bugs are making increasing impacts on agricultural and forestry ecosystems. Previous studies proved that symbiotic bacteria play important roles in these insects in fitting various habitats. However, it is still obscure about the evolutionary and ecological patterns of the microorganisms of phytophagous true bugs as a whole with comprehensive taxon sampling. RESULTS: Here, in order to explore the symbiotic patterns between plant-feeding true bugs and their symbiotic microorganisms, 209 species belonging to 32 families of 9 superfamilies had been sampled, which covered all the major phytophagous families of true bugs. The symbiotic microbial communities were surveyed by full-length 16S rRNA gene and ITS amplicons respectively for bacteria and fungi using the PacBio platform. We revealed that hosts mainly affect the dominant bacteria of symbiotic microbial communities, while habitats generally influence the subordinate ones. Thereafter, we carried out the ancestral state reconstruction of the dominant bacteria and found that dramatic replacements of dominant bacteria occurred in the early Cretaceous and formed newly stable symbiotic relationships accompanying the radiation of insect families. In contrast, the symbiotic fungi were revealed to be horizontally transmitted, which makes fungal communities distinctive in different habitats but not significantly related to hosts. CONCLUSIONS: Host and habitat determine microbial communities of plant-feeding true bugs in different roles. The symbiotic bacterial communities are both shaped by host and habitat but in different ways. Nevertheless, the symbiotic fungal communities are mainly influenced by habitat but not host. These findings shed light on a general framework for future microbiome research of phytophagous insects. Video Abstract.

Enhanced prediction of postoperative radiotherapy-induced esophagitis in non-small cell lung cancer: Dosiomic model development in a real-world cohort and validation in the PORT-C randomized controlled trial.

BACKGROUND: Radiotherapy-induced esophagitis (RE) diminishes the quality of life and interrupts treatment in patients with non-small cell lung cancer (NSCLC) undergoing postoperative radiotherapy. Dosimetric models showed limited capability in predicting RE. We aimed to develop dosiomic models to predict RE. METHODS: Models were trained with a real-world cohort and validated with PORT-C randomized controlled trial cohort. Patients with NSCLC undergoing resection followed by postoperative radiotherapy between 2004 and 2015 were enrolled. The endpoint was grade ≥2 RE. Esophageal three-dimensional dose distribution features were extracted using handcrafted and convolutional neural network (CNN) methods, screened using an entropy-based method, and selected using minimum redundancy and maximum relevance. Prediction models were built using logistic regression. The areas under the receiver operating characteristic curve (AUC) and precision-recall curve were used to evaluate prediction model performance. A dosimetric model was built for comparison. RESULTS: A total of 190 and 103 patients were enrolled in the training and validation sets, respectively. Using handcrafted and CNN methods, 107 and 4096 features were derived, respectively. Three handcrafted, four CNN-extracted and three dosimetric features were selected. AUCs of training and validation sets were 0.737 and 0.655 for the dosimetric features, 0.730 and 0.724 for handcrafted features, and 0.812 and 0.785 for CNN-extracted features, respectively. Precision-recall curves revealed that CNN-extracted features outperformed dosimetric and handcrafted features. CONCLUSIONS: Prediction models may identify patients at high risk of developing RE. Dosiomic models outperformed the dosimetric-feature model in predicting RE. CNN-extracted features were more predictive but less interpretable than handcrafted features.

Electronic Interactions on Platinum/(Metal-Oxide)-Based Photocatalysts Boost Selective Photoreduction of CO2 to CH4.

By supporting platinum (Pt) and cadmium sulfide (CdS) nanoparticles on indium oxide (In2 O3 ), we fabricated a CdS/Pt/In2 O3 photocatalyst. Selective photoreduction of carbon dioxide (CO2 ) to methane (CH4 ) was achieved on CdS/Pt/In2 O3 with electronic Pt-In2 O3 interactions, with CH4 selectivity reaching to 100 %, which is higher than that on CdS/Pt/In2 O3 without electronic Pt-In2 O3 interactions (71.7 %). Moreover, the enhancement effect of electronic Pt-(metal-oxide) interactions on selective photoreduction of CO2 to CH4 also occurs by using other common metal oxides, such as photocatalyst supports, including titanium oxide, gallium oxide, zinc oxide, and tungsten oxide. The electronic Pt-(metal-oxide) interactions separate photogenerated electron-hole pairs and convert CO2 into CO2 δ- , which can be easily hydrogenated into CH4 via a CO2 δ- →HCOO*→HCO*→CH*→CH4 path, thus boosting selective photoreduction of CO2 to CH4 . This offers a new way to achieve selective photoreduction of CO2 .

300 Million years of coral treaders (Insecta: Heteroptera: Hermatobatidae) back to the ocean in the phylogenetic context of Arthropoda.

Among hundreds of insect families, Hermatobatidae (commonly known as coral treaders) is one of the most unique. They are small, wingless predaceous bugs in the suborder Heteroptera. Adults are almost black in colour, measuring about 5 mm in body length and 3 mm in width. Thirteen species are known from tropical coral reefs or rocky shores, but their origin and evolutionary adaptation to their unusual marine habitat were unexplored. We report here the genome and metagenome of Hermatobates lingyangjiaoensis, hitherto known only from its type locality in the South China Sea. We further reconstructed the evolutionary history and origin of these marine bugs in the broader context of Arthropoda. The dated phylogeny indicates that Hexapoda diverged from their marine sister groups approximately 498 Ma and that Hermatobatidae originated 192 Ma, indicating that they returned to an oceanic life some 300 Myr after their ancestors became terrestrial. Their origin is consistent with the recovery of tropical reef ecosystems after the end-Triassic mass extinction, which might have provided new and open niches for them to occupy and thrive. Our analyses also revealed that both the genome changes and the symbiotic bacteria might have contributed to adaptations necessary for life in the sea.

Higher Lung and Heart Doses Decrease Early and Long-Term Survival, Respectively, in Patients With Non-Small Cell Lung Cancer Undergoing Postoperative Radiation.

Purpose: Cardiopulmonary toxic effects may reduce the efficacy of postoperative radiation therapy (PORT) in patients with non-small cell lung cancer (NSCLC). However, few studies have examined whether the heart and lung doses affect overall survival (OS). We investigated the correlation of heart and lung doses with OS in patients with NSCLC undergoing PORT. Methods and Materials: This retrospective analysis included 307 patients with NSCLC undergoing PORT. The total dose was 50 Gy. Landmark analyses were performed at 36 months, with hazard ratios (HRs) calculated separately for events occurring up to 36 months (early survival) and after 36 months (long-term survival). Stabilized inverse probability of treatment weighting (sIPTW) was performed to balance the characteristics of the high- and low-dose groups. We performed sensitivity analyses at 24 and 48 months. Results: The median follow-up period was 67.42 months. Heart doses were significantly correlated with long-term survival (HR, 1.14; P = .015) but not with early survival (HR, 0.97; P = .41) or whole survival (HR, 1.02; P = .58). Lung doses were marginally significantly correlated with early survival (HR, 1.03; P = .07) but not with long-term survival (HR, 1.00; P = .85) or whole survival (HR, 1.02; P = .12). Higher heart and lung doses were associated with decreased long-term and early survival, respectively, before and after sIPTW. Landmark analyses at 24 and 48 months showed consistent results. Conclusions: For patients with NSCLC undergoing PORT, a higher heart dose was associated with decreased long-term survival, whereas a higher lung dose was associated with decreased early survival.

Radiotherapy Improves Survival of Patients With Lymphovascular Invasion in pT1b Esophageal Squamous Cell Cancer After Endoscopic Submucosal Dissection.

INTRODUCTION: Adjuvant radiotherapy is recommended for pT1b esophageal squamous cell cancer (ESCC) after endoscopic submucosal dissection (ESD). However, it is unclear whether additional radiotherapy can improve patient survival. This study aimed to evaluate the efficacy of adjuvant radiotherapy after ESD for pT1b ESCC. METHODS: This was a multicenter, cross-sectional study involving 11 hospitals in China. Between January 2010 and December 2019, patients with T1bN0M0 ESCC treated with or without adjuvant radiotherapy after ESD were included. Survival between groups was compared. RESULTS: Overall, 774 patients were screened, and 161 patients were included. Forty-seven patients (29.2%) received adjuvant radiotherapy after ESD (RT group) and 114 (70.8%) underwent ESD alone (non-RT group). There were no significant differences in overall survival (OS) and disease-free survival (DFS) between the RT and non-RT groups. Lymphovascular invasion (LVI) was the only prognostic factor. In the LVI+ group, adjuvant radiotherapy significantly improved survival (5-year OS: 91.7% vs 59.5%, P = 0.050; 5-year DFS: 92.9% vs 42.6%, P = 0.010). In the LVI- group, adjuvant radiotherapy did not improve survival (5-year OS: 83.5% vs 93.9%, P = 0.148; 5-year DFS: 84.2% vs 84.7%, P = 0.907). The standardized mortality ratios were 1.52 (95% confidence interval 0.04-8.45) in the LVI+ group with radiotherapy and 0.55 (95% confidence interval 0.15-1.42) in the LVI- group without radiotherapy. DISCUSSION: Adjuvant radiotherapy could improve survival in pT1b ESCC with LVI+ other than LVI- after ESD. Selective adjuvant radiotherapy based on LVI status achieved survival rates similar to those of the general population.

Efficacy and safety of neoadjuvant immunotherapy combined with chemoradiotherapy or chemotherapy in esophageal cancer: A systematic review and meta-analysis.

Background: Significant progress has been made in the investigation of neoadjuvant immune-chemoradiotherapy (NICRT) and neoadjuvant immune-chemotherapy (NICT) on the outcomes of esophageal cancer patients. To summarize the current developments, a systematic review and meta-analysis were conducted to evaluate the efficacy and safety of neoadjuvant immunotherapy combined with chemoradiotherapy or chemotherapy. Methods: A search strategy of prospective studies on esophageal cancer receiving neoadjuvant immunotherapy was predefined to scan PubMed, Embase, Cochrane, and additional major conferences for prospective studies. Efficacy was assessed by pathological complete response (pCR), major pathological response (MPR), and R0 resection rates. Safety was evaluated based on the incidence of grade ≥ 3 treatment-related adverse events (TRAEs), neoadjuvant therapy completion rate, surgical resection rate, and surgical delay rate. Differences between the NICRT and NICT groups were also analyzed. Results: A total of 38 studies qualified for the analysis. The pooled pCR, MPR, and R0 resection rates were 30, 58, and 99%, respectively. The pCR and MPR in the NICRT vs. NICT group were 38% vs. 28% (p=0.078) and 67% vs. 57% (p=0.181), respectively. The pooled incidence of grade ≥ 3 TRAEs was 24% (NICRT,58%, I2 = 61% vs. NICT,18%, I2 = 79%; p<0.001). In addition, the pooled neoadjuvant therapy completion and surgical resection rates were 92% and 85%, respectively; the difference was not statistically significant between the NICRT and NICT groups. Conclusions: Neoadjuvant immunotherapy combined with chemoradiotherapy or chemotherapy is effective and safe in the short term for locally advanced esophageal cancer. However, further randomized trials are needed to confirm which combined model is more favorable. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021284266, identifier CRD42021284266.

Real world practice of postoperative radiotherapy for patients with completely resected pIIIA-N2 non-small cell lung cancer: a national survey of radiation oncologists in China.

BACKGROUND: Results from Lung ART and PORT-C trials suggest that postoperative radiotherapy (PORT) cannot routinely be recommended as standard treatment in completely resected pIIIA-N2 NSCLC patients, but their effects on the real-world practice of PORT in China remain unclear. METHODS: A national cross-section survey was conducted by using an online survey service. Participants were voluntarily recruited using a river sampling strategy. A link to the survey was posted on websites of radiation oncologist associations and tweets from public WeChat accounts. The survey collected the real names of participants to ensure that they were board-certified radiation oncologists. RESULTS: A total of 484 radiation oncologists were included with a median age of 40 years (IQR, 35-47). A total of 377 (77.9%) participants were male, and 282 (58.1%) had more than 10 years of clinical experience practicing thoracic radiotherapy. Before Lung ART and PORT-C trials were published, 313 (64.7%) respondents recommended PORT, 11 (2.3%) did not recommend it, and 160 (33.1%) reported that they made decisions based on risk factors. After the presentation of two trials, only 42 (8.7%) did not recommend PORT, while 108 (22.3%) recommended it, and 334 (69.0%) made decisions based on risk factors. The five most commonly considered risk factors among these 334 respondents were as follows: nodal extracapsular extension, the highest lymph node (LN) station involved, the number of dissected mediastinal LN stations, the number of positive mediastinal LN stations, and surgical approaches. In addition, the majority of all 484 respondents recommended a total dose of 50 Gy, lung stump + ipsilateral hilus + regions containing positive LNs as the targeted region, lung V20 < 25%, and heart V30 < 40% as dose constraints for PORT. CONCLUSION: Most Chinese radiation oncologists recommended PORT for completely resected IIIA-N2 NSCLC patients based on risk factors, especially status of LN station.

New insights into membrane fouling during direct membrane filtration of municipal wastewater and fouling control with mechanical strategies.

Direct membrane filtration (DMF) technology achieves energy self-sufficiency through carbon recovery and utilization from municipal wastewater. To control its severe membrane fouling and improve DMF technology, targeted research on fouling behaviour and mechanisms is essential. In this study, a DMF reactor equipped with a flat-sheet ceramic membrane was conducted under three scenarios: without control, with intermittent aeration, and with periodic backwash. This system achieved efficient carbon concentration with chemical oxygen demand below 50 mg/L in permeate. Membrane fouling was dominated by intermediate blocking and cake filtration. And reversible external resistance accounted for over 85 % of total resistance. Predominant membrane foulants were free proteins, whose deposition underlies the attachment of cells and biopolymers. Backwash decreased the fouling rate and increased fouling layer porosity by indiscriminately detaching foulants from the membrane surface. While aeration enhanced the back transport of large particles and microbial activity, causing a relatively thin and dense fouling layer containing more microorganisms and ß-d-glucopyranose polysaccharides, which implies a higher biofouling potential during long-term operation. In addition, aeration combined with backwash enhanced fouling control fivefold over either one alone. Therefore, simultaneous operation of backwash and other mechanical methods that can provide shear without stimulating aerobic microbial activity is a preferred strategy for minimizing membrane fouling during DMF of municipal wastewater.

Research on Robot Screwing Skill Method Based on Demonstration Learning.

A robot screwing skill learning framework based on teaching-learning is proposed to improve the generalization ability of robots for different scenarios and objects, combined with the experience of a human operation. This framework includes task-based teaching, learning, and summarization. We teach a robot to twist and gather the operation's trajectories, define the obstacles with potential functions, and counter the twisting of the robot using a skill-learning-based dynamic movement primitive (DMP) and Gaussian mixture model-Gaussian mixture regression (GMM-GMR). The hole-finding and screwing stages of the process are modeled. In order to verify the effectiveness of the robot tightening skill learning model and its adaptability to different tightening scenarios, obstacle avoidance trends and tightening experiments were conducted. Obstacle avoidance and tightening experiments were conducted on the robot tightening platform for bolts, plastic bottle caps, and faucets. The robot successfully avoided obstacles and completed the twisting task, verifying the effectiveness of the robot tightening skill learning model and its adaptability to different tightening scenarios.

The differential impacts of social deprivation and social fragmentation on suicides: A lesson from Hong Kong.

INTRODUCTION: Little research has conducted to examine the association between social deprivation and social fragmentation, overall and method-specific suicide risk, and how these associations may change over time. This study investigated the association between social deprivation and social fragmentation with overall and method-specific suicide in Hong Kong from 1999 to 2018. METHODS: Suicide death data of each small tertiary planning unit (STPU) was obtained from the Census and Statistics Department of Hong Kong. Socio-economic characteristics in STPU level were obtained from Census and Bi-census. Exploratory principal component analysis was used to construct the social deprivation (SDI) and social fragmentation indices (SFI) based on the socio-economic characteristics. Bayesian hierarchical modelling was conducted to explore the association between SDI and SFI with overall and method-specific suicide over time, controlling for population density and male-to-female ratio. RESULTS: Higher risk of suicide was generally observed around Kowloon Peninsula and some parts in the Northern, Northwestern and Southwestern areas depending on methods. The effect of SDI and SFI on suicide risk varied by years and methods. In 2014-2018, for every 10% increase in SDI, the suicide risk for overall, jumping, hanging, and charcoal burning elevated by 22% (95%Crl = 10%-37%), 26% (95%Crl = 12%-41%), 31% (95%Crl = 14%-51%), and 21% (95%Crl = 4%-42%) respectively. CONCLUSION: Spatial variations and effects of SDI and SFI on overall and method-specific suicide risks varied by different periods. SDI was observed to be a stronger factor in the recent years. Situations should be monitored, and interventions should be implemented and adjusted accordingly to the changes.

Symbiotic Microorganisms and Their Different Association Types in Aquatic and Semiaquatic Bugs.

True bugs (Hemiptera, suborder Heteroptera) constitute the largest suborder of nonholometabolous insects and occupy a wide range of habitats various from terrestrial to semiaquatic to aquatic niches. The transition and occupation of these diverse habitats impose various challenges to true bugs, including access to oxygen for the aquatic species and plant defense for the terrestrial phytophagans. Although numerous studies have demonstrated that microorganisms can provide multiple benefits to terrestrial host insects, a systematic study with comprehensive higher taxa sampling that represents aquatic and semiaquatic habitats is still lacking. To explore the role of symbiotic microorganisms in true bug adaptations, 204 samples belonging to all seven infraorders of Heteroptera were investigated, representing approximately 85% of its superfamilies and almost all known habitats. The symbiotic microbial communities of these insects were analyzed based on the full-length amplicons of the bacterial 16S rRNA gene and fungal ITS region. Bacterial communities varied among hosts inhabiting terrestrial, semiaquatic, and aquatic habitats, while fungal communities were more related to the geographical distribution of the hosts. Interestingly, co-occurrence networks showed that species inhabiting similar habitats shared symbiotic microorganism association types. Moreover, functional prediction analyses showed that the symbiotic bacterial community of aquatic species displayed richer amino acid and lipid metabolism pathways, while plant-feeding true bugs benefited more from the symbiont-provided xenobiotics biodegradation pathway. These results deepened the recognition that symbiotic microorganisms were likely to help heteropterans occupy diverse ecological habitats and provided a reference framework for further studies on how microorganisms affect host insects living in various habitats. IMPORTANCE Symbiotic bacteria and fungi generally colonize insects and provide various benefits for hosts. Although numerous studies have investigated symbionts in terrestrial plant-feeding insects, explorations of symbiotic bacterial and fungal communities in aquatic and semiaquatic insects are rare. In this study, the symbiotic microorganisms of 204 aquatic, semiaquatic, and terrestrial true bugs were explored. This comprehensive taxon sampling covers ~85% of the superfamilies of true bugs and most insect habitats. Analyses of the diversity of symbionts demonstrated that the symbiotic microbial diversities of true bugs were mainly affected by host habitats. Co-occurrence networks showed that true bugs inhabiting similar habitats shared symbiotic microbial association types. These correlations between symbionts and hosts together with the functions of bacterial communities indicated that symbiotic microbial communities may help true bugs adapt to (semi)aquatic habitats.

Famitinib enhances the antitumor effect of radioimmunotherapy in murine lung cancer.

BACKGROUND: Combining antiangiogenic therapy with radioimmunotherapy is believed to further improve antitumor efficacy, but there is still a lack of evidence to support this. This study aimed to investigate the role of the tumor vascular-targeted agent famitinib with a combination of radiotherapy and an immune checkpoint inhibitor in murine lung cancer. METHODS: The effect of VEGFA and HIF1A on clinical prognosis and the tumor immune microenvironment was analyzed using public databases. Enrichment analyses of post-irradiation gene expression and mRNAs related to immunotherapy efficacy were carried out based on GEO datasets. A C57BL/6 mouse subcutaneous tumor model was used to evaluate the antitumor effects of different treatment schemes. The tumor immunophenotyping was identified by flow cytometry. RESULTS: We demonstrated that high level of VEGFA and HIF1A expression in lung cancer was related to poor prognosis and immunosuppressive tumor microenvironment. In a mouse model, the triple therapy of famitinib, radiotherapy and immunotherapy had the most dramatic antitumor activity. It significantly increased tumor infiltrating lymphocytes and reversed the immunosuppressive state of the tumor microenvironment in mice. Compared with radioimmunotherapy, the addition of famitinib further promoted the infiltration of CD8+ T cells and M1 type tumor associated macrophages, and reduced the number of myeloid suppressor cells. Therefore, triple therapy converted the immunosuppressive tumor microenvironment into an immunostimulatory one. CONCLUSION: Famitinib can synergize with radioimmunotherapy by regulating the tumor immune microenvironment in murine lung cancer.

Identification and functional analysis of dual-specificity phosphatases (DUSP) genes in Japanese flounder (Paralichthys olivaceus) against temperature and Edwardsiella tarda stress.

Dual-specificity Phosphatases (DUSPs) are not only the key regulators of dephosphorylating and inactivating mitogen-activated protein kinases (MAPKs), but play a crucial role in the immune response. However, the role of DUSP genes in Japanese flounder (PoDUSPs) is still unclear. In this study, 28 DUSP genes in Japanese flounder were identified and classified based on the whole genome database. Phylogenetic analysis and protein structure analysis revealed that DUSPs had highly conserved domains in teleosts. Molecular evolution analysis indicated that the PoDUSP genes were conservative during evolution and were functional-constrained. Meanwhile, PoDUSP genes were found to express in different embryonic and larval stages which might play the role of sentinel in healthy organisms. Furthermore, PoDUSP genes' expression profiles after temperature stress and Edwardsiella tarda (E. tarda) infection were determined in Japanese flounder without precedent, and the results demonstrated that Podusp1, Podusp2 and Podusp16 were more respective to temperature variation whereas Podusp1 and Podusp6 were more respective to E. tarda infection. In summary, our results provide useful resources for understanding the immune responsibilities of DUSP genes in flatfish.

Fast and efficient electrocatalytic oxidation of glucose triggered by Cu2O-CuO nanoparticles supported on carbon nanotubes.

Electrocatalytic glucose oxidation reaction (GOR) is the key to construct sophisticated devices for fast and accurately detecting trace glucose in blood and food. Herein, a noble-metal-free Cu/C-60 catalyst is fabricated by supporting Cu2O-CuO nanoparticles on carbon nanotubes through a novel discharge process. For GOR, Cu/C-60 shows a sensitivity as high as 532 µA mM-1 cm-2, a detection limit as low as 1 µM and a steady-state response time of only 5.5 s. Moreover, Cu/C-60 has outstanding stability and anti-interference ability to impurities. The synergistic effect of Cu2O-CuO could improve the adsorption and conversion of glucose, thus enhancing GOR performance. By using Cu/C-60, we fabricate a three-electrode chip. A portable and compact electrochemical system is constructed by connecting the three-electrode chip with Cu/C-60 to an integrated circuit board and a mobile phone for recording and displaying data. The portable and compact electrochemical system results in a GOR sensitivity of 501 µA mM-1 cm-2, which is close to the data measured on the bloated electrochemical workstation. The detection limit of the portable and compact electrochemical system in GOR is 50 µM. This is higher than those obtained on the bloated electrochemical workstation, but is much lower than the common blood glucose concentration of human body (>3 mM). This demonstrates the accuracy, reasonability and applicability of the portable and compact electrochemical system. The results of the present work are helpful for fabricating fast, efficient and portable devices for detecting trace amount of glucose in blood and food.

Comparison of different neoadjuvant treatments for resectable locoregional esophageal cancer: A systematic review and network meta-analysis.

PURPOSE: The best pattern of neoadjuvant therapy for resectable locoregional esophageal cancer has not been determined. Our study evaluated the efficacy and postoperative events of different treatments using the Bayesian network meta-analysis. METHODS: We systematically tracked randomized clinical trials from the Medline, EMBASE, and Cochrane Library databases. The following treatments were included: neoadjuvant chemoradiation followed by surgery (NCRT + S), neoadjuvant chemotherapy followed by surgery (NCT + S), neoadjuvant radiotherapy followed by surgery (NRT + S), and surgery alone (S). The Revised Cochrane risk-of-bias tools were used to assess the quality of included trials. Overall survival (OS) and progression-free survival or disease-free survival (PFS/DFS) were assessed through hazard ratios (HR). Locoregional recurrence, distant metastasis, postoperative mortality, and postoperative morbidity were assessed through odds ratios (OR). These outcomes were compared between different treatments through Bayesian network meta-analysis. RESULTS: Twenty trials with 4384 patients were included. Compared with S, only NCRT + S could significantly improve OS for patients with esophageal cancer (HR = 0.78, 95% confidence interval [CI] 0.68-0.88). NCRT + S and NCT + S significantly improved PFS/DFS compared with S (NCRT + S vs. S, HR = 0.72, 95% CI 0.63-0.81; NCT + S vs. S, HR = 0.81, 95% CI 0.69-0.97). NCRT + S significantly reduced both locoregional recurrence (OR = 0.67, 95% CI 0.51-0.88) and distant metastasis (OR = 0.63, 95% CI 0.45-0.90) compared with S. There were no differences in postoperative morbidity between the four treatments. However, NCRT + S also increased postoperative mortality compared with S (OR = 1.77, 95% CI 1.09-2.82) and NCT + S (OR = 1.96, 95% CI 1.11-3.51). CONCLUSION: NCRT + S is the most efficient neoadjuvant treatment for resectable locoregional esophageal cancer. However, NCRT + S increases the risk of postoperative mortality but not morbidity.