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BackgroundTo meet the growing health needs of older people, the Chinese government has introduced internet-based home care services. However, most rural older people have not yet benefited from such services, and the willingness to use these services and the factors influencing them remain unclear.ObjectiveWe aim to investigate the current willingness of rural older people to use internet-based home care services and analyze the factors.MethodsWe conducted a cross-sectional study across multiple centers using general information and self-developed questionnaires. Qualitative interviews, a literature review and the Delphi method were employed to develop the questionnaire. A total score of the questionnaire above 78 or higher indicates a high willingness to use internet-based home care services. Descriptive statistics, t-tests, one-way ANOVA, and multiple linear regression were used to explore the factors that influence the willingness of rural older people to use internet-based home care services.ResultsWe surveyed 349 rural older people. The total score of rural older people’s willingness to use internet-based home care services was 84.49 ± 10.88, indicating high willingness, with the highest score for the dimension of perceived usefulness and lower scores for the dimension of perceived ease of use. Multiple linear regression analysis revealed that gender, education level, residence status, number of chronic diseases, and knowledge of internet-based home care services were the most important factors for rural older people (all p

BackgroundThe purpose of this study was to understand the current status of traditional Chinese medicine (TCM) health literacy among rural older adults people and its influencing factors.MethodsThis study used a random number table method to select one prefecture from Henan Province, China and used a convenience sampling method to select 200 rural older adults who met the inclusion criteria in a township in northern Henan from March to April 2023. A cross-sectional survey was conducted using a general information questionnaire and a traditional Chinese medicine health literacy questionnaire, and the influencing factors of rural older adults were analyzed using univariate analysis of variance (ANOVA) and multiple linear regression.ResultsThe total TCM health literacy score of 200 rural older adults people was 84.14 ± 6.709. One-way ANOVA revealed that six factors, including education level, marital status, type of occupation, presence of family members engaged in medical-related work, main economic sources, and monthly income, influenced the TCM health literacy score of rural older adults people (p

Abstract The continuous increase of saline-alkali areas worldwide has led to the emergence of saline-alkali conditions, which are the primary abiotic stress or hindering the growth of plants. Beet is among the main sources of sugar, and its yield and sugar content are notably affected by saline-alkali stress. Despite sugar beet being known as a salt-tolerant crop, there are few studies on the mechanisms underlying its salt tolerance, and previous studies have mainly delineated the crop’s response to stress induced by NaCl. Recently, advancements in miRNA-mRNA network analysis have led to an increased understanding of how plants, including sugar beet, respond to stress. In this study, seedlings of beet variety "N98122" were grown in the laboratory using hydroponics culture and were exposed to salt stress at 40 days of growth. According to the phenotypic adaptation of the seedlings' leaves from a state of turgidity to wilting and then back to turgidity before and after exposure, 18 different time points were selected to collect samples for analysis. Subsequently, based on the data of real-time quantitative PCR (qRT-PCR) of salt-responsive genes, the samples collected at the 0, 2.5, 7.5, and 16 h time points were subjected to further analysis with experimental materials. Next, mRNA-seq data led to the identification of 8455 differentially expressed mRNAs (DEMs) under exposure to salt stress. In addition, miRNA-seq based investigation retrieved 3558 miRNAs under exposure to salt stress, encompassing 887 known miRNAs belonging to 783 families and 2,671 novel miRNAs. With the integrated analysis of miRNA-mRNA network, 57 miRNA-target gene pairs were obtained, consisting of 55 DEMIs and 57 DEMs. Afterwards, we determined the pivotal involvement of aldh2b7, thic, and δ-oat genes in the response of sugar beet to the effect of salt stress. Subsequently, we identified the miRNAs novel-m035-5p and novel-m0365-5p regulating the aldh gene and miRNA novel-m0979-3p regulating the thic gene. The findings of miRNA and mRNA expression were validated by qRT-PCR.

Abstract Due to the relatively brief domestication history of sugar beet (Beta vulgaris ssp. vulgaris), our understanding of the genomic diversity and functional genes in its cultivars is limited, resulting in slow breeding progress. To address this issue, a total of 306 germplasm materials of major cultivars and breeding lines from China, the USA, and Europe were selected for genome resequencing. We investigated population structure and genetic diversity and performed selective scanning of genomic regions, identifying six novel genes associated with important agronomic traits: the candidate genes DFAX2 and P5CS for skin roughness; the candidate genes FRO5, GL24, and PPR91 for root yield and sugar yield, and the pleiotropic candidate gene POLX for flourishing growth vigour, plant height, crown size, flesh coarseness, and sugar yield. In addition, we constructed a protein–protein interaction network map and a phenotype-gene network map, which provide valuable information for identifying and characterizing functional genes affecting agronomic traits in sugar beet. Overall, our study sheds light on the future improvement of sugar beet agronomic traits at the molecular level.

Abstract Mutation-induced malfunction of ten-eleven translocation methylcytosine dioxygenase 2 (TET2) is widely reported in haematological malignancies. However, the role of TET2 in solid cancers, including colorectal cancer (CRC), is unclear. Here, we found that TET2 malfunction in CRC is mostly due to decreased nuclear localization and that nuclear localization of TET2 is correlated with better survival of patients. To explore the underlying mechanisms, 14 immortalized solid tumour cell lines and 12 primary CRC cell lines were used. TET2 was mostly detected in the nucleus, and it induced significant DNA demethylation and suppressed cell growth by demethylating RORA and SPARC in cell lines like SW480. While in cell lines like SW620, TET2 was observed in the cytosol and did not affect DNA methylation or cell growth. Further examination with immunoprecipitation–mass spectrometry illustrated that β-catenin activation was indispensable for the nuclear localization and tumour suppression effects of TET2. In addition, the β-catenin pathway activator IM12 and the TET2 activator vitamin C were used simultaneously to enhance the effects of TET2 under low-expression conditions, and synergistic inhibitory effects on the growth of cancer were observed both in vitro and in vivo. Collectively, these data suggest that β-catenin-mediated nuclear localization of TET2 is an important therapeutic target for solid tumours.

Abstract Objective To investigate the status quo of nursing information ability of nurses in county-level hospitals and analyze its influencing factors. Methods In June 2022, a total of 303 on-the-job clinical nurses from 3 county-level hospitals in Hebi City, Henan Province were selected as subjects by convenience sampling method. General data questionnaire and self-rating nursing information ability scale were used to investigate them. Results The total score of nursing information ability of 303 nurses in county hospitals of Hebi City, Henan Province was (77.72 ± 18.76). There were statistically significant differences in the scores of nursing information ability among different ages, working years, positions, education, marriage, monthly income, whether they had learned computer-related knowledge and skills, and whether they had participated in the learning or training of nursing information system (all p

Personalized recommender systems play a crucial role in assisting users in discovering items of interest from vast amounts of information across various domains. However, developing accurate personalized recommender systems remains challenging due to the need to balance model architectures, input feature combinations, and fusion of heterogeneous data sources. This study investigates the impacts of these factors on recommendation performance using the MovieLens and Book Recommendation datasets. Six models, including single-task neural networks, multi-task learning, and baselines, were evaluated with various input feature combinations using Root Mean Squared Error (RMSE) and Mean Absolute Error (MAE). The multi-task learning approach achieved significantly lower RMSE and MAE by effectively leveraging heterogeneous data sources for personalized recommendations through a shared neural network architecture. Furthermore, incorporating user data and content data progressively enhanced performance compared to using only item identifiers. The findings highlight the importance of advanced model architectures and fusing heterogeneous data sources for high-quality recommendations, providing valuable insights for designing effective recommender systems across diverse domains.

Abstract Background Microvascular invasion (MVI) is an independent detrimental risk factor for tumor recurrence and poor survival in hepatocellular carcinoma (HCC). Competitive endogenous RNA (ceRNA) networks play a pivotal role in the modulation of carcinogenesis and progression among diverse tumor types. However, whether the ceRNA mechanisms are engaged in promoting the MVI process in patients with HCC remains unknown. Methods A ceRNA regulatory network was constructed based on RNA‐seq data of patients with HCC from The Cancer Genome Atlas (TCGA) database. In total, 10 hub genes of the ceRNA network were identified using four algorithms: “MCC,” “Degree,” “Betweenness,” and “Stress.” Transcriptional expressions were verified by in situ hybridization using clinical samples. Interactions between ceRNA modules were validated by luciferase reporting assay. Logistic regression analysis, correlation analysis, enrichment analysis, promoter region analysis, methylation analysis, and immune infiltration analysis were performed to further investigate the molecular mechanisms and clinical transformation value. Results The ceRNA regulatory network featuring a tumor invasion phenotype consisting of 3 long noncoding RNAs, 3 microRNAs, and 93 mRNAs was constructed using transcriptional data from the TCGA database. Systemic analysis and experimentally validation identified a ceRNA network (PVT1/miR‐1258/DUSP13 axis) characterized by lipid regulatory potential, immune properties, and abnormal methylation states in patients with HCC and MVI. Meanwhile, 28 transcriptional factors were identified as potential promotors of PVT1 with 3 transcriptional factors MXD3, ZNF580, and KDM1A promising as therapeutic targets in patients with HCC and MVI. Furthermore, miR‐1258 was an independent predictor for MVI in patients with HCC. Conclusion The PVT1/DUSP13 axis is significantly associated with MVI progression in HCC patients. This study provides new insight into mechanisms related to lipids, immune phenotypes, and abnormal epigenetics in oncology research.

Prefabricated installation, a pivotal study in the realm of contemporary construction practices, delves into the utilization of prefabrication within mechanical, electrical, and plumbing (MEP) systems. Despite its ascending prominence, the domain grapples with ambiguities in application pathways, uncertain developmental trajectories, and the absence of a holistic technical paradigm. This research endeavors to bridge these gaps by conducting a thorough and multidimensional investigation into the current landscape of prefabricated MEP installation initiatives. This study meticulously dissects the paradigm from five critical vantage points: historical evolution, standards and regulations, life cycle analysis, technological applications, and corporate implementation strategies. At present, there is still a lack of standards and specifications specifically for the field of assembled MEP installation. The analysis reveals a trend towards intelligent and sustainable installation practices in prefabricated MEP projects. The research predominantly focuses on the design, production, and installation stages. Notably, building information modeling (BIM) emerges as the most prominent technology, followed by the Internet of Things (IoT) and 3D laser scanning, with extended reality (XR) technologies gaining traction. Large, state-owned construction firms are spearheading innovative applications in this realm. In summary, this paper provides an overview and outlook for the development direction and the application of cutting-edge technologies in prefabricated MEP installation projects, with the aim of supporting the industry’s advancement.

BackgroundActive aging has been listed as an important indicator to measure the quality of life of the older adults and the construction of the senior care system. There is an imbalance between the supply and demand of senior care services for the disabled older adults in rural areas, and the quality of life needs to be improved.ObjectivesWe aimed to analyze the current situation of active aging and the influencing factors of the rural disabled older adults, in order to provide a reference basis for improving the quality of life of the rural disabled older adults.MethodsWe conducted a multicenter and cross-sectional study, using the Barthel Index Scale and Chinese version of the Active Aging Scale, to facilitate the selection of 304 rural older adults with disability in 26 villages under Henan Province for a questionnaire survey.ResultsThe mean score for the level of active aging of rural older adults with disability was 1.87 (SD 0.36), with the highest score for the dimension of being self-reliant (Mean2.29, SD 0.61) and lower scores for the dimension of active contribution to society (Mean 1.37, SD 0.55) and building up financial security (Mean 1.37, SD 0.57). The results of the multiple regression analysis showed higher levels of active aging among the disabled older adults with retirement pay, mild disability, and longer time per activity/rehabilitation exercise (p

Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect multiple systems. Sjögren's syndrome (SS) is an autoimmune disease that may be primary SS (pSS) or occur together with other autoimmune diseases, including SLE. This study aimed to explore the shared gene signatures in SLE and pSS. Methods Gene expression data sets of SLE (GSE50772 and GSE81622) and pSS (GSE84844 and GSE48378) were obtained and analyzed for differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs). A protein–protein interaction (PPI) network was constructed. Gene ontology (GO) and KEGG pathway enrichment analysis were carried out for the DEGs. Results We screened 232 and 110 DEGs from the SLE and pSS data sets, respectively. We found 32 shared DEGs, which were all upregulated in patients compared with controls. Among these 32 DEGs, 11 genes showed a more than twofold change in all data sets (IFI27, IFI44L, RSAD2, IFIT1, IFI44, USP18, IFI6, HERC5, EPSTI1, OAS1, and OAS3). PPI analysis showed that 29 genes interacted with each other. GO analysis showed that these 32 shared DEGs were mainly enriched in biological processes associated with the type I interferon signaling pathway, defense response to viruses, response to viruses, negative regulation of viral genome replication, and the immune response. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that these 32 DEGs were related to virus infection. Conclusion This study showed that alterations to biological processes associated with the response to virus infection play critical roles in both SLE and pSS.

IDO1-mediated tryptophan metabolism plays an important role in creating an immunosuppressive tumour microenvironment. Here, the authors show that deubiquitinase USP14 regulates immune suppression by inducing IDO1 stabilization and suggest USP14 as a potential therapeutic target to improve immunotherapy in colorectal cancer.

Abstract Background Distant metastasis is the prominent factor for cancer-induced death of gastric cancer in which peritoneum is one of the dominating targets of gastric cancer metastasis. However, there is still a lack of effective predictive indicators and treatment methods for gastric cancer patients with peritoneal metastasis. Methods A clustering assay was used to investigate the cell aggregates formation ability. While the soft agar assay and anoikis assay were performed to detect the anchorage-independent growth and anoikis-resistant ability respectively. Luciferase activity assay, western blotting and immunofluorescence were used to explore the effect of HMMR on AKT signaling activity. The peritoneal implantation model was examined to explore the role of HMMR in vivo. Results Silencing of HMMR expression markedly reduced the peritoneal metastasis of gastric cancer cells through reducing cell–cell interactions. Mechanistically, HA-HMMR could activate Akt signaling, thus succeeding in distant colonization and metastatic outgrowth. Importantly, inducible depletion of HMMR significantly abrogates peritoneal implantation of gastric cancer in vitro and in vivo. Conclusion Our study highlights that HMMR promotes peritoneal implantation of gastric cancer. A better understanding of HMMR’s functions and mechanism might provide a novel therapeutic target and prognostic marker for metastatic gastric cancer.

BackgroundDifferent intratumoral microbiotaexist in different tumors and play a crucial function in carcinogenesis. However, whether they impact clinical outcomes in esophageal squamous cell carcinoma (ESCC) and their mechanism remain unclear.Methods16S rDNA amplicon sequencing was performed on surgically resected samples from 98 ESCC patients to analyze intratumoral microbiome abundance and composition. Multiplex fluorescent immunohistochemistry staining was used to profile the phenotypes of immune infiltrates in the tumor microenvironment (TME).ResultsPatients with higher intratumoral Shannon index had significantly worse surgical outcomes. When patients were divided into short-term survivors and long-term survivors based on the median survival time, both intratumoral alpha-diversity and beta-diversity were found to be significantly inconsistent, and the relative abundance of Lactobacillus and Leptotrichia emerged as the two microorganisms that probably influenced the survival of ESCC patients. Only Lactobacillus in ESCC was validated to significantly worsen patients’ prognoses and to be positively correlated with the Shannon index. Multivariate analysis revealed that the intratumoral Shannon index, the relative abundance of Lactobacillus, and the pathologic tumor–node–metastasis (pTNM) stage were independently associated with patients’ overall survival. Furthermore, the relative abundance of both Lactobacillus and Shannon index was positively correlated with the proportions of PD-L1+ epithelial cells (ECs) and tumor-associated macrophages (TAMs). The Shannon index was negatively correlated with the proportions of natural killer (NK) cells in the TME.ConclusionsA high abundance of intratumoral Lactobacillus and bacterial alpha-diversity was associated with the formation of the immunosuppressive TME and predicted poor long-term survival in ESCC patients.

Abstract Background Tertiary lymphoid structures (TLSs) play key roles in tumour adaptive immunity. However, the prognostic value and molecular properties of TLSs in oesophageal squamous cell carcinoma (ESCC) patients have not been studied. Methods The prognostic values of the presence and maturation status of tumour‐associated TLSs were determined in 394 and 256 ESCC patients from Sun Yat‐sen University Cancer Center (Centre A) and the Cancer Hospital of Shantou University Medical College (Centre B), respectively. A deep‐learning (DL) TLS classifier was established with haematoxylin and eosin (H&E)‐stained slides using an inception‐resnet‐v2 neural network. Digital spatial profiling was performed to determine the cellular and molecular properties of TLSs in ESCC tissues. Results TLSs were observed in 73.1% of ESCCs from Centre A via pathological examination of H&E‐stained primary tumour slides, among which 42.9% were TLS‐mature and 30.2% were TLS‐immature tumours. The established DL TLS classifier yielded favourable sensitivities and specificities for patient TLS identification and maturation evaluation, with which 55.1%, 39.5% and 5.5% of ESCCs from Centre B were identified as TLS‐mature, TLS‐immature and TLS‐negative tumours. Multivariate analyses proved that the presence of mature TLSs was an independent prognostic factor in both the Centre A and Centre B cohorts (p < .05). Increased proportions of proliferative B, plasma and CD4+ T helper (Th) cells and increased B memory and Th17 signatures were observed in mature TLSs compared to immature ones. Intratumoural CD8+ T infiltration was increased in TLS‐mature ESCC tissues compared to mature TLS‐absent tissues. The combination of mature TLS presence and high CD8+ T infiltration was associated with the best survival in ESCC patients. Conclusions Mature TLSs improve the prognosis of ESCC patients who underwent complete resection. The use of the DL TLS classifier would facilitate precise and efficient evaluation of TLS maturation status and offer a novel probability of ESCC treatment individualization.

Sugar beet (Beta vulgaris L.) is an important sugar-producing and energy crop worldwide. The sugar beet pure line IMA1 independently bred by Chinese scientists is a standard diploid parent material that is widely used in hybrid-breeding programs. In this study, a high-quality, chromosome-level genome assembly for IMA1was conducted, and 99.1% of genome sequences were assigned to nine chromosomes. A total of 35,003 protein-coding genes were annotated, with 91.56% functionally annotated by public databases. Compared with previously released sugar beet assemblies, the new genome was larger with at least 1.6 times larger N50 size, thereby substantially improving the completeness and continuity of the sugar beet genome. A Genome-Wide Association Studies analysis identified 10 disease-resistance genes associated with three important beet diseases and five genes associated with sugar yield per hectare, which could be key targets to improve sugar productivity. Nine highly expressed genes associated with pollen fertility of sugar beet were also identified. The results of this study provide valuable information to identify and dissect functional genes affecting sugar beet agronomic traits, which can increase sugar beet production and help screen for excellent sugar beet breeding materials. In addition, information is provided that can precisely incorporate biotechnology tools into breeding efforts.

With global urbanization and industrialization, environmental pollution and food safety problems caused by soil heavy metal pollution occur frequently. To realize the safe utilization of cultivated land resources in high-risk areas of heavy metal pollution, we present an approach to safe utilization classification and management in this study. A typical agricultural area around industrial and mining enterprises located in the economic belt of the Yangtze River Delta was chosen as the research area with cultivated soil as the research object. A total of 1,139 geochemical survey sampling sites and soil survey data were used for this research. Initially, the potential ecological risk index was used to assess the potential ecological risk of heavy metals in cultivated soil, and key soil physical and chemical indicators were chosen to assess soil resilience. Next, the safe utilization classification of cultivated land was carried out by combining the potential ecological risk of soil heavy metals with soil resilience. Then, the specific classification management strategy was developed according to ecological risk factor types and crop types. The results showed that the production and operation activities of industrial and mining enterprises in the study area contributed significantly to soil Cd and Hg pollution, and the potential ecological risk of heavy metals in the surrounding soil was high. The soil resilience of cultivated land in the study area was generally not high. The clay content and cation exchange capacity (CEC) were the main strong restrictive indicators, while CaO, soil organic carbon (SOC), and pH were the main medium restrictive indicators. Natural conditions such as topography, hydrogeology, and soil-forming parent material differed by region, resulting in different restrictive factors. There were 16 safe utilization types in the study area. Different management strategies were proposed based on various soil potential ecological risks, soil resilience, ecological risk factor types, and crop types. This study can offer fresh perspectives on the safe utilization classification and management of land resources in high-risk areas of soil pollution and serve as a reference for sustainable intensification.

Capacitive deionization (CDI) has been investigated for brackish water desalination, selective removal of ions, and water softening. We used humic acid (HA) and alginate sodium (SA) to simulate different kinds of natural organic matter to investigate the fouling phenomena during CDI operation. Adsorption amount and energy efficiency were studied. Results showed that both SA and HA could decrease the removal of NaCl during CDI operation. There existed a slight decrease of energy consumption in SA solutions which was opposite to that in HA solutions. HA can compete with ions adsorbed by electrodes and attach to electrodes adhesively, resulting in co-ion repulsion. SA is not sensitive to electrical field and its fouling is not obvious. The amount of adsorbed Mg2+ would increase from 0.927 mg/g to 1.508 mg/g in ten cycles' operation and the increment of Ca2+ was from 1.885 mg/g to 2.878 mg/g in SA solutions. This increase of adsorption was due to the complexation between SA and cations. Simultaneously, energy consumption was decreased. In HA solutions, energy consumption of Mg2+ and Ca2+ adsorption increased. In ten cycles' operations, both HA and SA could reduce the efficiency of CDI operation. The types of organic substances are important factors in fouling of CDI electrodes. HIGHLIGHTS The mechanisms of humic acid and sodium alginate fouling were investigated in CDI operation.; Humic acid was able to make fouling of electrodes worse during CDI operation.; Alginate sodium acted as a medium in increasing the amount of adsorption and energy efficiency.;

Historically, the cognition and management of cultivated land quality (CLQ) have been fragmented, leading to an inability to meet contemporary scenarios and requirements of China’s agricultural development and cultivated land protection. This study aimed to systematically recognize the concepts, elements, connotations, and dimensions of CLQ and build a new cultivated land quality evaluation (CQE) system. Initially, we deduced the concept of CLQ through the clear concept of “quality” in line with international standards. Next, we connected CLQ with the framework of farmland ecosystem service cascades and clarified the element structure of CLQ based on the structure of farmland ecosystems. Then, based on the multi-level human well-being that farmland ecosystems can provide, the connotations and dimensions of CLQ was determined. Using Wen County within Henan Province as a case study site, we constructed a CQE system for empirical analysis and comparative verification, showing that the new system was better than the existing one. This study helped to clarify the CLQ and provided a theoretical basis and technical reference for sustainable intensification (SI) and multi-directional protection and supervision of cultivated land.

Abstract Background Large numbers of adipose-derived stem cells (ADSCs) are easily obtained and have been demonstrated to protect against ultraviolet B (UVB)-induced skin photoaging. Extracellular vesicles (EVs) exhibit some of the same effects as the cells from which they originate and have many advantages over stem cells. In particular, their application circumvents many safety concerns associated with cell therapy. Thus, as a cell-free agent, adipose-derived stem cell extracellular vesicles (ADSC-EVs) have anti-photoaging potential. However, the protective effects of ADSC-EVs in skin photoaging remain uncertain. Methods To investigate the effect of ADSC-EVs on mice with UVB-induced photoaging, 150 μg and 300 μg ADSC-EVs were subcutaneously injected weekly into photoaging mice for 8 weeks. The protective effect was evaluated by gross assessment and hematoxylin and eosin, Masson’s trichrome, and β-galactosidase staining. Proliferating cell nuclear antigen, CD68, and dihydroethidium staining were performed to evaluate cell proliferation, inflammation infiltration, and reactive oxygen species (ROS) production, respectively. In vitro, 100 μg/mL and 200 μg/mL ADSC-EVs were used to treat photoaging fibroblasts (FBs). β-galactosidase staining and collagen 1 and matrix metalloproteinase 3 (MMP-3) expression were analyzed to evaluate FB senescence. To explain the protective mechanism of ADSC-EVs, their role in regulating ROS production, antioxidant enzyme expression, cell cycle arrest, and inflammation was evaluated. Results In vivo, we showed that ADSC-EVs decreased skin wrinkles in mice with UVB-induced photoaging, while promoting epidermal cell proliferation and attenuating macrophage infiltration and ROS production. In vitro, we showed that ADSC-EVs increased FB activity and protected FBs from UVB-induced senescence, attenuated raw 264.7 cell differentiation from M0 to M1 macrophages, reduced intracellular ROS production, promoted antioxidant enzyme expression, and rescued FBs from cell cycle arrest. Conclusion The anti-photoaging effect of ADSC-EVs was attributed to their ability to attenuate ROS production and the inflammatory response, which are key factors in MMP activation and collagen degradation. Graphical abstract

Abstract Background Although ongoing development of therapeutic strategies contributes to the improvements in clinical management, clear cell renal cell carcinoma (ccRCC) deaths originate mainly from radiochemoresistant and metastatic disease. Transcription factor SALL4 has been implicated in tumorigenesis and metastasis of multiple cancers. However, it is not known whether SALL4 is involved in the pathogenesis of ccRCC. Methods Analyses of clinical specimen and publicly available datasets were performed to determine the expression level and clinical significance of SALL4 in ccRCC. The influence of SALL4 expression on ccRCC tumor growth, metastasis and vascularity was evaluated through a series of in vitro and in vivo experiments. Western blotting, immunofluorescence staining and integrative database analysis were carried out to investigate the underlying mechanism for SALL4-mediated oncogenic activities in ccRCC. Results SALL4 expression was increased in ccRCC and positively correlated with tumor progression and poor prognosis. SALL4 could promote ccRCC cell proliferation, colony formation, cell cycle progression, migration, invasion and tumorigenicity and inhibit cell senescence. Further investigation revealed a widespread association of SALL4 with individual gene transcription and the involvement of SALL4 in endothelium development and vasculogenesis. In the context of ccRCC, SALL4 promoted tumor vascularization by recruiting endothelial cells. In addition, we found that SALL4 could exert its tumor-promoting effect via modulating Akt/GSK-3β axis and VEGFA expression. VHL mutation and DNA hypomethylation may be involved in the upregulation of SALL4 in ccRCC. Conclusions Overall, our results provide evidence that upregulated SALL4 can function as a crucial regulator of tumor pathogenesis and progression in ccRCC, thus offering potential therapeutic strategies for future treatment.

Abstract Background Chondromesenchymal hamartoma of the chest wall is a rare, benign disease that usually presents at birth or in early infancy. It typically involves one or more ribs, forming a unilateral or bilateral extrapleural mass. Patients may be asymptomatic or complain of mild respiratory distress depending on tumor size and location. To the best of our knowledge, only two of the approximately 100 cases reported so far are adults. Case presentation We present two cases of chondromesenchymal hamartoma. The first case involved the left fifth rib in a 24-year-old male, in close proximity to the fifth vertebral body in the left posterior mediastinum, mimicking a posterior mediastinal tumor on imaging. The tumor was excised via thoracoscopy and the patient had an uneventful postoperative course. The second case was that of a 5-month-old boy, who had a tumor involving the left fifth and sixth ribs which caused thoracic cage collapse. Following en bloc resection of the tumor and the involved rib segments, the patient was transferred to the intensive care unit for treatment of pulmonary infection and disseminated intravascular coagulation (DIC). He was discharged from the hospital in stable condition 11 days later. On histopathology, the tumor was found to be a chondromesenchymal hamartoma with immature spindle-shaped mesenchymal cells, plate-like hyaline cartilage, areas of woven bone formation, endochondral ossification and calcification, osteoclastic giant cells, and secondary aneurysmal bone cysts. Conclusions Although the presently reported cases have morphological characteristics similar to previously reported ones, they had distinct radiological and clinical characteristics. Patient 1 is only the third report of an adult with chondromesenchymal hamartoma. His case was characterized by its radiological appearance mimicking a posterior mediastinal tumor. Patient 2 represents the first documentation of DIC as a postoperative complication following excision of a chondromesenchymal hamartoma. We present these two cases to provide clinicopathological insights regarding this extremely rare tumor that are relevant to both pathologists and clinicians.

Abstract Background Astrocyte-elevated gene-1 (AEG-1) is over-expressed in many cancer cells and has multiple key functions in tumor initiation and progression. Currently, targeted-AEG-1 siRNA is one of the most common techniques to down-regulate AEG-1 expression, but the lack of tumor specificity and available delivery system make it difficult to enter clinical trials. Methods In this study, we creatively developed an adenovirus-mediated anti-AEG-1 single-chain antibody fragment (ScFv) expression system driven by a tumor specific promoter, and experimented with it in human cervical carcinoma cells to investigate the effect on tumor’s proliferation and apoptosis. Results The results showed that of HeLa and SiHa cells treated with this recombinant anti-AEG-1 ScFv adenovirus not only inhibited cell growth, but induced apoptosis both in vitro and in vivo. Furthermore, we also observed that the expressions of several apoptosis-related genes like Akt 1 and c-Myc decreased, while NF-κB (p65) and cleaved caspase 3 increased on protein levels in vivo. Conclusion We concluded that stathmin promoter-driving anti-AEG-1 ScFv adenoviral system may be a breakthrough for its dual-specificity, and serve as an adjuvant tumor specific therapy method in the treatment for human cervical cancers.

Abstract Background It was reported that tumor-expressed dickkopf-related (DKK) proteins affect micro-environment. However, the influence of DKK1 on colorectal cancer (CRC) liver oligometastases (CRCLOM) remains unclear. Methods CRC cases after resection of liver oligometastases were enrolled in Sun Yat-Sen University Cancer Center with intact clinical data. Serum DKK1 was detected by ELISA assay. Immunofluorescent staining examination for CD3 and CD8 in slices were also conducted. Results Among 65 patients included, the recurrence-free survival (RFS) and overall survival (OS) were significantly better in the low serum DKK1 group (RFS: P = 0.021; OS: P = 0.043). DKK1 was overexpressed in stage IV CRC patients in TCGA data. The number of CD8+ tumor-infiltrating lymphocytes (TILs) in invasive margin of CRC liver oligometastases was significantly higher in low serum DKK1 group (P = 0.042). Conclusion Elevated serum DKK1 level was associated with poorer RFS and OS, and less CD8+ TILs in invasive margin in CRC liver oligometastases. DKK1 might serve as a supplementalprognostic factor for clinical risk score and a potential target for immunotherapy.

Background and objective The detection of driver oncogenes of lung cancer is of great importance. There are various gene detection techniques nowadays which are different from each other. We carried out this study to investigate the specificity and sensitivity of assay panels based on an Amplification Refractory Mutation System-polymerase chain reaction (ARMS-PCR) technique of Amplification Mutation Specific System (AMSS) in detection of lung cancer gene mutation. To estimate the applicable value of assay panels in clinical settings. Methods We collected cancer tissue specimens or fluid specimens from 309 patients. Mutation results were presented for those samples previously detected by ARMS-PCR. In comparison, we carried out AMSS-PCR using (epidermal growth factor receptor, EGFR) assay panel and Six-Alliance assay panel as well as Sanger sequencing. Software SPSS 22.0 (SPSS IBM) was used for statistical analysis. Results The rates of consistency between the results by assay panels and Sanger sequencing or ARMS-PCR were 97.41% and 97.73%, respectively. Besides, EGFR assay panel had higher consistency rates with other detection methods than Six-Alliance assay panel. As for consistency test, the Kappa values of assay panels with Sanger sequencing, assay panels with ARMS-PCR, and ARMS-PCR with Sanger sequencing were 0.946, 0.953, and 0.913, respectively. The receiver operating characteristic curve (ROC) area under curve (AUC) of assay panels was 0.976 referring to Sanger sequencing, and 0.975 as ARMS-PCR was referred to. Conclusion AMSS-PCR can make an optimal cancer gene mutation detection method for clinical settings.

We propose a novel and simple scheme for photonic frequency eightfold millimeter wave (mm-wave) generation with optical carrier suppression based on only one single-drive Mach–Zehnder modulator (MZM). According to our theoretical analysis and experimental demonstration, by adopting designed direct current bias voltage of MZM and the amplitude voltage of the radio frequency (RF) drive signal, two fourth-order optical subcarriers are generated via a single-drive MZM. Furthermore, the corresponding optical central carrier and undesired sidebands are suppressed simultaneously. Based on our proposed scheme, the generation of 72-GHz optical mm-wave by an RF signal of 9 GHz without any optical filtering is experimentally demonstrated. The radio-over-fiber system with 3.5-Gb/s OOK downstream link based on this generated 72-GHz mm-wave is also experimentally demonstrated. As we know, it is the first time to realize frequency eightfold mm-wave signal generation with simultaneous carrier suppression by using only one single-drive MZM in experiment.

Tumor response to preoperative chemoradiotherapy and postoperative survival differs among patients with locally advanced rectal cancer. The objective was to find correlations of mutated oncogenes and clinical outcomes in locally advanced rectal cancer. A total of 70 patients with preoperative preoperative chemoradiotherapy followed by radical surgery at a single cancer center between 2006 and 2012 were enrolled. Pretreatment tumor biopsy samples were assayed for 238 mutation hotspots harboring 19 oncogenes by time-of-flight mass spectrometry and OncoCarta Array. Oncogene mutations were found in 48.6% of patients (34/70). KRAS was the most frequent driver mutation, found in 35.7% of patients (25/70), followed by PIK3CA (14.3%), NRAS (5.7%), FLT3 (2.9%), and BRAF (1.4%). Multiple gene mutations were observed in eight patients (11.4%). Tumors with KRAS mutations responded poorly to preoperative chemoradiotherapy (p = 0.044). Patients with oncogene mutations had worse 3-year disease-free survival than those without mutations (67.2% vs 94.2%, p = 0.010). Patients with KRAS or RAS mutations had lower 3-year disease-free survival (68% vs 88.3%, p = 0.016; 65.5% vs 92.3%, p = 0.004, respectively) and 3-year overall survival (88% vs 95.4%, p = 0.020; 89.7% vs 94.9%, p = 0.036, respectively) than those without KRAS or RAS mutations. Oncogene mutation status affected tumor response to treatment and long-term survival in locally advanced rectal cancer.

The mechanical properties of parallel bamboo strand lumber beams could be improved by aramid fiber reinforced polymer (AFRP). So far, no investigation has been conducted on the strengthening of engineering bamboo beams using AFRP. In order to study the efficiency of AFRP reinforcement on parallel bamboo strand lumber beams, 13 beams had been tested and analyzed. Strain gauges and Laser Displacement Sensors were used for the tests. By sensing the strain and deformation data for the specimens under the applied loads, the results showed that AFRP can effectively improve the flexural mechanical properties of parallel bamboo strand lumber beams. However, this reinforcement cannot increase the deflection of bamboo beams indefinitely. When the cloth ratio was 0.48, the deflection of the specimens reached its maximum. With the increase of cloth ratio, the stiffness of parallel bamboo strand lumber beams was increasing. When the cloth ratio reached 0.72%, compared with the un-reinforced specimen, the stiffness increased by 15%. Therefore, it can be inferred that bonding AFRP on the considered specimens can increase the stiffness of parallel bamboo strand lumber beams. The ductility of the specimen can be effectively enhanced by adopting the AFRP provision.

Trastuzumab has been approved for human epidermal growth factor receptor 2 (HER2)-positive advanced gastric and gastroesophageal junction cancers (GC and GJC) in combination with chemotherapy. The aim of this HER2 early/advanced gastric epidemiology (HER-EAGLE) study was to evaluate the frequency of HER2 over-expression and to evaluate agreement on HER2 status assessment in GC and GJC patients in local laboratories versus a central laboratory in China. Tumor samples from 734 GC or GJC patients who were enrolled at 11 different hospitals in China were examined. HER2 status was assessed by immunohistochemistry (IHC), and followed by dual-color silver-enhanced in Situ hybridization (DSISH) in IHC 2+ cases. Clinicopathologic characteristics were collected from all of the patients. HER2-positive tumors were identified in 12.0% (88/734) of the GC and GJC cases. There were significantly higher rates of HER2 positivity in patients with GJC (GJC: 18.1%, GC: 9.7%, P=0.002), and intestinal-type cancers using the Lauren classification (intestinal: 23.6%, diffuse/mixed: 4.3%, P

Several conserved neutralizing epitopes have been identified in the HIV Env protein and among these, the MPER of gp41 has received great attention and is widely recognized as a promising target. However, little success has been achieved in eliciting MPER-specific HIV neutralizing antibodies by a number of different vaccine strategies. We investigated the ability of HA/gp41 chimeric protein-based vaccines, which were designed to enhance the exposure of the MPER in its native conformation, to induce MPER-specific HIV neutralizing antibodies. In characterization of the HA/gp41 chimeric protein, we found that by mutating an unpaired Cys residue (Cys-14) in its HA1 subunit to a Ser residue, the modified chimeric protein HA-C14S/gp41 showed increased reactivity to a conformation-sensitive monoclonal antibody against HA and formed more stable trimers in VLPs. On the other hand, HA-C14S/gp41 and HA/gp41 chimeric proteins expressed on the cell surfaces exhibited similar reactivity to monoclonal antibodies 2F5 and 4E10. Immunization of guinea pigs using the HA-C14S/gp41 DNA or VLP vaccines induced antibodies against the HIV gp41 as well as to a peptide corresponding to a segment of MPER at higher levels than immunization by standard HIV VLPs. Further, sera from vaccinated guinea pigs were found to exhibit HIV neutralizing activities. Moreover, sera from guinea pigs vaccinated by HA-C14S/gp41 DNA and VLP vaccines but not the standard HIV VLPs, were found to neutralize HIV pseudovirions containing a SIV-4E10 chimeric Env protein. The virus neutralization could be blocked by a MPER-specific peptide, thus demonstrating induction of MPER-specific HIV neutralizing antibodies by this novel vaccine strategy. These results show that induction of MPER-specific HIV neutralizing antibodies can be achieved through a rationally designed vaccine strategy.

OBJECTIVES: Pathological complete response has shown a better prognosis for patients with locally advanced rectal cancer after preoperative chemoradiotherapy. However, correlations between post-chemoradiotherapy clinical factors and pathologic complete response are not well confirmed. The aim of the current study was to identify post-chemoradiotherapy clinical factors that could serve as indicators of pathologic complete response in locally advanced rectal cancer. METHODS: This study retrospectively analyzed 544 consecutive patients with locally advanced rectal cancer treated at Sun Yat-sen University Cancer Center from December 2003 to June 2014. All patients received preoperative chemoradiotherapy followed by surgery. Univariate and multivariate regression analyses were performed to identify post-chemoradiotherapy clinical factors that are significant indicators of pathologic complete response. RESULTS: In this study, 126 of 544 patients (23.2%) achieved pathological complete response. In multivariate analyses, increased pathological complete response rate was significantly associated with the following factors: post-chemoradiotherapy clinical T stage 0-2 (odds ratio=2.098, 95% confidence interval=1.023-4.304, p=0.043), post-chemoradiotherapy clinical N stage 0 (odds ratio=2.011, 95% confidence interval=1.264-3.201, p=0.003), interval from completion of preoperative chemoradiotherapy to surgery of >7 weeks (odds ratio=1.795, 95% confidence interval=1.151-2.801, p=0.010) and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml (odds ratio=1.579, 95% confidence interval=1.026-2.432, p=0.038). CONCLUSIONS: Post-chemoradiotherapy clinical T stage 0-2, post-chemoradiotherapy clinical N stage 0, interval from completion of chemoradiotherapy to surgery of >7 weeks and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml were independent clinical indicators for pathological complete response. These findings demonstrate that post-chemoradiotherapy clinical factors could be valuable for post-operative assessment of pathological complete response.