Intestinal nanoparticle delivery and cellular response: a review of the bidirectional nanoparticle-cell interplay in mucosa based on physiochemical properties.

Orally administered nanocarriers play an important role in improving druggability, promoting intestinal absorption, and enhancing therapeutic applications for the treatment of local and systemic diseases. However, the delivering efficiency and cell response in mucosa to orally administered nanocarriers is affected by the physiological environment and barriers in the gastrointestinal tract, the physicochemical properties of the nanocarriers, and their bidirectional interactions. Goblet cells secrete and form extracellular mucus, which hinders the movement of nanoparticles. Meanwhile, intestinal epithelial cells may absorb the NPs, allowing for their transcytosis or degradation. Conversely, nanoparticle-induced toxicity may occur as a biological response to the nanoparticle exposure. Additionally, immune response and cell functions in secretions such as mucin, peptide, and cytokines may also be altered. In this review, we discuss the bidirectional interactions between nanoparticles and cells focusing on enterocytes and goblet cells, M cells, and immune cells in the mucosa according to the essential role of intestinal epithelial cells and their crosstalk with immune cells. Furthermore, we discuss the recent advances of how the physiochemical properties of nanoparticles influence their interplay, delivery, and fate in intestinal mucosa. Understanding the fate of nanoparticles with different physiochemical properties from the perspective of their interaction with cells in mucosa provides essential support for the development, rational design, potency maximation, and application of advanced oral nanocarrier delivery systems.

Herb-Nanoparticle Hybrid System for Improved Oral Delivery Efficiency to Alleviate Breast Cancer Lung Metastasis.

Background: Metastasis is a complex process involving multiple factors and stages, in which tumor cells and the tumor microenvironment (TME) play significant roles. A combination of orally bioavailable therapeutic agents that target both tumor cells and TME is conducive to prevent or impede the progression of metastasis, especially when undetectable. However, sequentially overcoming intestinal barriers, ensuring biodistribution in tumors and metastatic tissues, and enhancing therapeutic effects required for efficient therapy remain challenging. Methods: Inspired by the unique chemical features of natural herbs, we propose an oral herb-nanoparticle hybrid system (HNS) formed through the self-binding of Platycodon grandiflorum-Curcuma zedoaria (HG), a herb pair/group used in clinical practice to treat breast cancer metastasis, to lipid-polymer nanoparticles (LPNs) loaded with silibinin. The molecular structure responsible for HG association with LPNs was assessed using surface-enhanced Raman spectroscopy for HNS surface chemistry characterization. Moreover, the molecular class of HG was identified using UPLC-Orbitrap-MS/MS to further confirm the surface binding. Mucus diffusion and in vivo biodistribution were evaluated using in vitro multiple-particle tracking and environment-responsive fluorescence probe in 4T1 tumor-bearing mice, respectively. The alleviation of breast cancer metastasis was assessed in 4T1 tumor-bearing mice, and the underlying mechanism was investigated. Results: The HNS reduced particle-mucus interactions by altering hydrophilicity and surface characteristics compared to LPNs. The epithelium transportation of HNS and absorption through Peyer's patch in mice were improved, promoting their biodistribution in the lung and tumor tissues. Furthermore, the HNS alleviated lung metastasis by inducing cell apoptosis and regulating the expression of MMP-9 and TGF-ß1, which altered the TME in 4T1 tumor-bearing mice. Conclusion: HNS provides an appealing system with multi-component binding of herbal medicine to facilitate both oral nanoparticle delivery efficiency and the alleviation of lung metastasis. This strategy may potentially help improve treatment for patients with breast cancer.

LRPPRC regulates malignant behaviors, protects mitochondrial homeostasis, mitochondrial function in osteosarcoma and derived cancer stem-like cells.

BACKGROUND: Leucine-rich pentatricopeptide repeat containing (LRPPRC) is a potential oncogene in multiple tumor types, including lung adenocarcinoma, esophageal squamous cell carcinoma and gastric cancer. LRPPRC exerts its tumor-promoting effects mainly by regulating mitochondrial homeostasis and inducing oxidative stress. However, the exact role and mechanisms by which LRPPRC acts in osteosarcoma and osteosarcoma-derived cancer stem-like cells (CSCs), which potentially critically contribute to recurrence, metastasis and chemoresistance, are still largely unclear. METHODS: LRPPRC level in osteosarcoma cells and CSCs were detected by western blot. Effects of LRPPRC on CSCs were accessed after LRPPRC knockdown by introducing lentivirus containing shRNA targeting to LRPPRC mRNA. RESULTS: we found that LRPPRC was highly expressed in several osteosarcoma cell lines and that LRPPRC knockdown inhibited malignant behaviors, including proliferation, invasion, colony formation and tumor formation, in MG63 and U2OS cells. Enriched CSCs derived from MG63 and U2OS cells presented upregulated LRPPRC levels compared to parental cells (PCs), and LRPPRC knockdown markedly decreased the sphere-forming capacity. These findings demonstrate that LRPPRC knockdown decreased stemness in CSCs. Consistent with a previous report, LRPPRC knockdown decreased the expression levels of FOXM1 and its downstream target genes, including PRDX3, MnSOD and catalase, which are responsible for scavenging reactive oxygen species (ROS). Expectedly, LRPPRC knockdown increased the accumulation of ROS in osteosarcoma and osteosarcoma-derived CSCs under hypoxic conditions due to the decrease in ROS scavenging proteins. Moreover, LRPPRC knockdown sensitized osteosarcomas and CSCs against carboplatin, a ROS-inducing chemoagent, and promoted apoptosis. Furthermore, LRPPRC knockdown significantly decreased the mitochondrial membrane potential, disturbed mitochondrial homeostasis and led to mitochondrial dysfunction. CONCLUSION: Taken together, these findings indicated that LRPPRC exerts critical roles in regulating mitochondrial homeostasis, mitochondrial function and tumorigenesis in osteosarcomas and osteosarcoma-derived CSCs. This suggests that LRPPRC might be a promising therapeutic target for osteosarcomas.

Oral membrane-biomimetic nanoparticles for enhanced endocytosis and regulation of tumor-associated macrophage.

Enterocyte uptake with high binding efficiency and minor endogenous interference remains a challenge in oral nanocarrier delivery. Enterocyte membrane-biomimetic lipids may universally cooperate with endogenous phosphatidyl choline via a biorthogonal group. In this study, we developed a sophorolipid-associated membrane-biomimetic choline phosphate-poly(lactic-co-glycolic) acid hybrid nanoparticle (SDPN). Aided by physical stability in the gastrointestinal tract and rapid mucus diffusion provided by association with sophorolipid, these nanoparticles show improved endocytosis, driven by dipalmitoyl choline phosphate-phosphatidyl choline interaction as well as its optimized membrane fluidity and rigidity. Luteolin- and silibinin-co-loaded with SDPN alleviated breast cancer metastasis in 4T1 tumor-bearing mice by regulating the conversion of tumor-associated M2 macrophages into the M1 phenotype and reducing the proportion of the M2-phenotype through co-action on STAT3 and HIF-1α. In addition, SDPN reduces angiogenesis and regulates the matrix barrier in the tumor microenvironment. In conclusion, this membrane-biomimetic strategy is promising for improving the enterocyte uptake of oral SDPN and shows potential to alleviate breast cancer metastasis.

[Effects of Platycodonis Radix-Curcumae Rhizoma on oral nanoparticle uptake and in vitro inhibition against breast cancer metastasis].

This study combined the herbal pair Platycodonis Radix-Curcumae Rhizoma(PR-CR) possessing an inhibitory effect on tumor cell proliferation and metastasis with the active component of traditional Chinese medicine(TCM) silibinin-loaded nanoparticles(NPs) with a regulatory effect on tumor microenvironment based on the joint effect on tumor cells and tumor microenvironment to inhi-bit cell metastasis. The effects of PR-CR on the cellular uptake of NPs and in vitro inhibition against breast cancer proliferation and metastasis were investigated to provide an experimental basis for improving nanoparticle absorption and enhancing therapeutic effects. Silibinin-loaded lipid-polymer nanoparticles(LPNs) were prepared by the nanoprecipitation method and characterized by transmission electron microscopy. The NPs were spherical or quasi-spherical in shape with obvious core-shell structure. The mean particle size was 107.4 nm, Zeta potential was-27.53 mV. The cellular uptake assay was performed by in vitro Caco-2/E12 coculture cell model and confocal laser scanning microscopy(CLSM), and the results indicated that PR-CR could promote the uptake of NPs. Further, in situ intestinal absorption assay by the CLSM vertical scanning approach showed that PR-CR could promote the absorption of NPs in the enterocytes of mice. The inhibitory effect of NPs on the proliferation and migration of 4T1 cells was analyzed using 4T1 breast cancer cells and co-cultured 4T1/WML2 cells, respectively. The results of the CCK8 assay showed that PR-CR-containing NPs could enhance the inhibition against the proliferation of 4T1 breast cancer cells. The wound healing assay indicated that PR-CR-containing NPs enhanced the inhibition against the migration of 4T1 breast cancer cells. This study enriches the research on oral absorption of TCM NPs and also provides a new idea for utilizing the advantages of TCM to inhibit breast cancer metastasis.

Epidemiological characteristics and spatiotemporal clustering of scarlet fever in Liaoning Province, China, 2010-2019.

BACKGROUND: To explore the epidemiological characteristics and spatiotemporal distribution of scarlet fever in Liaoning Province, which could provide scientific evidence for the formulation and improvement of prevention and control strategies and measures. METHODS: Data on scarlet fever cases and population were obtained from the China Information System for Disease Control and Prevention in Liaoning Province between 2010 and 2019. We examined the spatial and spatiotemporal clusters of scarlet fever across Liaoning Province using the Moran's I, local indicators of spatial association, local Gi* hotspot statistics, and Kulldorff's retrospective space-time scan statistical analysis. RESULTS: Between 1st January 2010 and 31st December 2019, 46,652 cases of scarlet fever were reported in Liaoning Province, with an annual average incidence of 10.67 per 100,000. The incidence of scarlet fever had obvious seasonality with high incidence in early summer June and early winter December. The male-to-female ratio was 1.53:1. The highest incidence of cases occurred in 3-9 year old children. The most likely spatiotemporal cluster and the secondary clusters were detected in urban regions of Shenyang and Dalian, Liaoning Province. CONCLUSIONS: The incidence of scarlet fever has obvious spatiotemporal clustering, with the high-risk areas mainly concentrated in urban area of Shenyang and Dalian, Liaoning Province. Control strategies need to focus on high-risk season, high-risk areas and high-risk populations in order to reduce the incidence of scarlet fever.

Development and evaluation of nomograms for predicting osteoarthritis progression based on MRI cartilage parameters: data from the FNIH OA biomarkers Consortium.

BACKGROUND: Osteoarthritis (OA) is a leading cause of disability worldwide. However, the existing methods for evaluating OA patients do not provide enough comprehensive information to make reliable predictions of OA progression. This retrospective study aimed to develop prediction nomograms based on MRI cartilage that can predict disease progression of OA. METHODS: A total of 600 subjects with mild-to-moderate osteoarthritis from the Foundation for National Institute of Health (FNIH) project of osteoarthritis initiative (OAI). The MRI cartilage parameters of the knee at baseline were measured, and the changes in cartilage parameters at 12- and 24-month follow-up were calculated. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to extract the valuable characteristic parameters at different time points including cartilage thickness, cartilage volume, subchondral bone exposure area and uniform cartilage thickness in different sub regions of the knee, and the MRI cartilage parameters score0, scoreΔ12, and scoreΔ24 at baseline, 12 months, and 24 months were constructed. ScoreΔ12, and scoreΔ24 represent changes between 12 M vs. baseline, and 24 M vs. baseline, respectively. Logistic regression analysis was used to construct the nomogram0, nomogramΔ12, and nomogramΔ24, including MRI-based score and risk factors. The area under curve (AUC) was used to evaluate the differentiation of nomograms in disease progression and subgroup analysis. The calibration curve and Hosmer-Lemeshow (H-L) test were used to verify the calibration of the nomograms. Clinical usefulness of each prediction nomogram was verified by decision curve analysis (DCA). The nomograms with predictive efficacy were analyzed by secondary analysis. Internal verification was assessed using bootstrapping validation. RESULTS: Each nomogram included cartilage score, KL grade, WOMAC pain score, WOMAC disability score, and minimum joint space width. The AUC of nomogram0, nomogramΔ12, and nomogramΔ24 in predicing the progression of radiology and pain were 0.69, 0.64, and 0.71, respectively. All three nomograms had good calibration. Analysis by DCA showed that the clinical effectiveness of nomogramΔ24 was higher than others. Secondary analysis showed that nomogram0 and nomogramΔ24 were more capable of predicting OA radiologic progression than pain progression. CONCLUSION: Nomograms based on MRI cartilage change were useful for predicting the progression of mild to moderate OA.

Epidemiological characteristics of severe fever with thrombocytopenia syndrome and its relationship with meteorological factors in Liaoning Province, China.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS), one kind of tick-borne acute infectious disease, is caused by a novel bunyavirus. The relationship between meteorological factors and infectious diseases is a hot topic of current research. Liaoning Province has reported a high incidence of SFTS in recent years. However, the epidemiological characteristics of SFTS and its relationship with meteorological factors in the province remain largely unexplored. METHODS: Data on reported SFTS cases were collected from 2011 to 2019. Epidemiological characteristics of SFTS were analyzed. Spearman's correlation test and generalized linear models (GLM) were used to identify the relationship between meteorological factors and the number of SFTS cases. RESULTS: From 2011 to 2019, the incidence showed an overall upward trend in Liaoning Province, with the highest incidence in 2019 (0.35/100,000). The incidence was slightly higher in males (55.9%, 438/783), and there were more SFTS patients in the 60-69 age group (31.29%, 245/783). Dalian City and Dandong City had the largest number of cases of SFTS (87.99%, 689/783). The median duration from the date of illness onset to the date of diagnosis was 8 days [interquartile range (IQR): 4-13 days]. Spearman correlation analysis and GLM showed that the number of SFTS cases was positively correlated with monthly average rainfall (rs = 0.750, P < 0.001; ß = 0.285, P < 0.001), monthly average relative humidity (rs = 0.683, P < 0.001; ß = 0.096, P < 0.001), monthly average temperature (rs = 0.822, P < 0.001; ß = 0.154, P < 0.001), and monthly average ground temperature (rs = 0.810, P < 0.001; ß = 0.134, P < 0.001), while negatively correlated with monthly average air pressure (rs = -0.728, P < 0.001; ß = -0.145, P < 0.001), and monthly average wind speed (rs = -0.272, P < 0.05; ß = -1.048, P < 0.001). By comparing both correlation coefficients and regression coefficients between the number of SFTS cases (dependent variable) and meteorological factors (independent variables), no significant differences were observed when considering immediate cases and cases with lags of 1 to 5 weeks for dependent variables. Based on the forward and backward stepwise GLM regression, the monthly average air pressure, monthly average temperature, monthly average wind speed, and time sequence were selected as relevant influences on the number of SFTS cases. CONCLUSION: The annual incidence of SFTS increased year on year in Liaoning Province. Incidence of SFTS was affected by several meteorological factors, including monthly average air pressure, monthly average temperature, and monthly average wind speed.

Evaluation of carbon sink in the Taklimakan Desert based on correction of abnormal negative CO2 flux of IRGASON.

Studies showing that deserts can sequester CO2 through non-photosynthetic processes have contributed to locating missing carbon sinks. However, the contradiction between the desert CO2 flux obtained by different observation methods leads to uncertainty in evaluating desert carbon sequestration. This has caused scepticism regarding desert carbon sequestration after years of research. Through a comparative experiment in the non-vegetated shifting sand of the Taklimakan Desert (TD), it was found that if the abnormal negative CO2 flux observed by IRGASON during the day was not corrected, the carbon sequestration of the TD would be overestimated. The CO2 flux observed by EC155 is highly consistent with that of LI-COR8100A and can reflect the real CO2 exchange in the desert. The CO2 flux observed by EC155 was used to correct the results of IRGASON. Results show that the expansion/contraction of soil air containing CO2 caused by the change in the daily average soil temperature difference (T0-10cm) drives CO2 exchange in shifting sand. This results in diurnal variation of CO2 release caused by shifting sand during the day and CO2 absorption at night, and a unimodal distribution of CO2 exchange caused by shifting sand throughout the year. From April to September (T0-10cm > 2 °C), the shifting sand releases CO2 as a carbon source. In the other months (T0-10cm < 2 °C), the shifting sand absorbs CO2 as a carbon sink. The stronger absorption shows that the shifting sand in the TD provides carbon sequestration, with a CO2 uptake rate of ~148.85 × 104 tons a-1. This suggests that deserts play an active role in locating the missing carbon sinks and mitigating climate change, and that the status of deserts in the global carbon cycle cannot be ignored.

COVID-19 Outbreak Caused by Contaminated Packaging of Imported Cold-Chain Products - Liaoning Province, China, July 2020.

What is known about this topic? Few major outbreaks of coronavirus disease 2019 (COVID-19) have occurred in China after major non-pharmaceutical interventions and vaccines have been deployed and implemented. However, sporadic outbreaks that had high possibility to be linked to cold chain products were reported in several cities of China.. What is added by this report? In July 2020, a COVID-19 outbreak occurred in Dalian, China. The investigations of this outbreak strongly suggested that the infection source was from COVID-19 virus-contaminated packaging of frozen seafood during inbound unloading personnel contact. What are the implications for public health practice? Virus contaminated paper surfaces could maintain infectivity for at least 17-24 days at -25 ℃. Exposure to COVID-19 virus-contaminated surfaces is a potential route for introducing the virus to a susceptible population. Countries with no domestic transmission of COVID-19 should consider introducing prevention strategies for both inbound travellers and imported goods. Several measures to prevent the introduction of the virus via cold-chain goods can be implemented.

Defining matrix Gla protein expression in the Dunkin-Hartley guinea pig model of spontaneous osteoarthritis.

BACKGROUND: Matrix Gla (γ-carboxyglutamate) protein (MGP) is considered a strong inhibitor of ectopic calcification, and it has been associated with OA severity, although not conclusively. We utilized male Dunkin-Hartley (DH) guinea pigs to investigate the expression of MGP throughout aging and disease pathogenesis in a spontaneous model. METHOD: Twenty-five male DH guinea pigs were obtained and nurtured to several timepoints, and then randomly and equally divided by age into five subgroups (1-, 3-, 6-, 9-, and 12-months, with the 1-month group as the reference group). DH guinea pigs in each group were euthanized at the designated month-age and the left or right medial tibial plateaus cartilages were randomly excised. OA severity was described by modified Mankin Score (MMS) at microscopy (Safranin O/Fast Green stain). Proteomic evaluation using isobaric tags for relative and absolute quantification (iTRAQ) was performed to validate the age-related changes in the MGP profiles, and immunohistochemistry (IHC) methods were applied for semi-quantitative determination of MGP expression in articular cartilage. RESULTS: The histopathologic findings validated the increasing severity of cartilage degeneration with age in the DH guinea pigs. The MMS showed significant, stepwise (every adjacent comparison P < 0.05) disease progression with month-age. The iTRAQ indicated that MGP levels increased significantly with advancing age (P < 0.05), as supported by the IHC result (P < 0.05). CONCLUSION: Increased expression of MGP in male DH guinea pigs was present throughout aging and disease progression and may be link to increased OA severity. Further studies are needed to investigate and confirm the association between MGP levels and OA severity.

Novel nomogram for predicting the progression of osteoarthritis based on 3D-MRI bone shape: data from the FNIH OA biomarkers consortium.

BACKGROUND: Osteoarthritis(OA) is a major source of pain, disability, and socioeconomic cost in worldwide. However, there is no effective means for the early diagnosis of OA, nor can it accurately predict the progress of OA. To develop and validate a novel nomogram to predict the radiographic progression of mild to moderate OA based on three-dimensional(3D)-MRI bone shape and bone shape change during 24 months. METHOD: Analysis of publicly available data from the Foundation for the National Institutes of Health (FNIH) OA Biomarkers Consortium. Radiographic progression was defined as minimum radiographic narrowing of the medial tibiofemoral joint space of ≥ 0.7 mm from baseline at 24, 36, or 48 months. There were 297 knees with radiographic progression and 303 without. The bone shapes of the tibia, femur, and patella were evaluated by 3D-MRI at the baseline and at 24 months. Two nomograms were separately established by multivariate logistic regression analysis using clinical risk factors, bone shape at baseline (nomogram 0), or bone shape change at 24 months (nomogram Δ24). The discrimination, calibration, and usefulness were selected to evaluate the nomograms. RESULTS: There were significant differences between groups in baseline Kellgren-Lawrence (KL) grade, gender, age, and tibia, femur, and patella shape. The areas under the curve (AUC) of nomogram 0 and nomogram Δ24 were 0.66 and 0.75 (p < 0.05), with accuracy of 0.62 and 0.69, respectively. Both nomograms had good calibration. The decision curve analysis ( DCA) showed that nomogram Δ24 had greater clinical usefulness than nomogram 0 when the risk threshold ranged from 0.04 to 0.86. CONCLUSIONS: Nomograms based on 3D-MRI bone shape change were useful for predicting the radiographic progression of mild to moderate OA.

Erastin induces apoptotic and ferroptotic cell death by inducing ROS accumulation by causing mitochondrial dysfunction in gastric cancer cell HGC­27.

Erastin, a classical inducer of non­apoptotic cell death, exerts cytotoxicity in several types of cancer cells, including gastric cancer cells, by depleting glutathione, which is a primary cellular antioxidant, thus causing reactive oxygen species (ROS) accumulation. Although numerous studies have focused on the non­apoptotic cell death induced by erastin, whether erastin induces apoptosis remains unknown. The present study confirmed the cytotoxicity of erastin in HGC­27 cells and used a 30% inhibitory concentration (IC30, approximately 6.23 µM) for further analysis. The cell cycle analysis revealed that 6.23 µM of erastin inhibited proliferation by blocking the cell cycle at the G1/G0 phase. Further analysis also showed that 6.23 µM of erastin clearly inhibited HGC­27 malignant behaviors, including migration, invasion, colony formation and tumor formation in soft agar. The observation of ROS accumulation due to erastin treatment led to determination of the effects of erastin on mitochondrial function and, as expected, erastin treatment decreased transcriptional activity and ATP production in mitochondria and disrupted the mitochondrial potential; these effects were reversed by the addition of the ROS scavenger NAC. To evaluate the effect of erastin in inducing apoptosis, HGC­27 cells were treated with 6.23 µM of erastin for 7 days and then analyzed. Evident apoptotic cell death was induced by erastin and this apoptosis was reversed by the addition of an apoptosis inhibitor (zVAD) or NAC but not by the addition of a ferroptosis inhibitor (ferrostatin­1). Furthermore, the detection of caspase­3 and poly (adenosine diphosphate­ribose) polymerase (PARP) also confirmed that treatment with erastin promoted the cleavage of caspase­3 and PARP, which are hallmarks of apoptosis. Taken together, the present study revealed that a low dose of erastin inhibited malignant behavior and induced apoptosis by causing mitochondrial dysfunction.

Hemorrhagic Fever with Renal Syndrome - Liaoning Province, China, 1999-2018.

What is already known on this topic? Hemorrhagic fever with renal syndrome (HFRS) is endemic in Liaoning Province. Both Seoul and Hantaan virus are circulating in rodents, and epidemic outbreaks and sporadic cases have been recorded every year since the disease was recognized. What is added by this report? The epidemic trend of HFRS over the past 20 years (1999-2018) in Liaoning was analyzed, which showed both regional complexity and consistence with the epidemic in China. Genetic and antigenic stability of the circulating hantavirus were demonstrated, which suggested the effectiveness of the approved inactivated vaccine currently used in China. What are the implications for public health practice? Precise risk-based strategic practices that are integrated and regional are required for further improvement of the prevention and control of HFRS.

Synchronous Response Analysis of Features for Remote Sensing Crop Classification Based on Optical and SAR Time-Series Data.

Accurate crop classification is the basis of agricultural research, and remote sensing is the only effective measuring technique to classify crops over large areas. Optical remote sensing is effective in regions with good illumination; however, it usually fails to meet requirements for highly accurate crop classification in cloud-covered areas and rainy regions. Synthetic aperture radar (SAR) can achieve active data acquisition by transmitting signals; thus, it has strong resistance to cloud and rain interference. In this study, we designed an improved crop planting structure mapping framework for cloudy and rainy regions by combining optical data and SAR data, and we revealed the synchronous-response relationship of these two data types. First, we extracted geo-parcels from optical images with high spatial resolution. Second, we built a recurrent neural network (RNN)-based classifier suitable for remote sensing images on the geo-parcel scale. Third, we classified crops based on the two datasets and established the network. Fourth, we analyzed the synchronous response relationships of crops based on the results of the two classification schemes. This work is the basis for the application of remote sensing data for the fine mapping and growth monitoring of crop planting structures in cloudy and rainy areas in the future.

Long non­coding RNA linc00239 promotes malignant behaviors and chemoresistance against doxorubicin partially via activation of the PI3K/Akt/mTOR pathway in acute myeloid leukaemia cells.

Long non­coding RNAs (lncRNAs) are known to be involved in the processes of tumourigenesis and malignant behaviours in many types of cancer, including acute myeloid leukaemia (AML). Accumulating evidence has revealed that novel lncRNAs exerted critical roles in these processes. In the present study, we investigated the effects of lncRNA linc00239 (NR_026774.1), which is 662 φnucleotides (nt) in length and was found to be upregulated in AML patients, on malignant behaviours and chemosensitivity in AML cells, including KG­1 and HL­60. linc00239 expression was detected in KG­1 and HL­60 cells by quantitative PCR and northern blotting, and it was found that linc00239 is detectable by both of these assays. After knockdown or overexpression of linc00239 in AML cells, the results revealed that the presence of linc00239 promoted proliferation, colony formation and migration ability. Furthermore, the presence of linc00239 increased chemoresistance to doxorubicin in AML cells partially by preventing doxorubicin­induced apoptotic cell death. It was also determined that the presence of linc00239 was related to activation of the phosphatidylinositol 3­kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. Inhibition of PI3K/Akt/mTOR using 1 µM NVP­BEZ235 (BEZ) abolished the inhibitory effect of linc00239 on chemosensitivity and the preventative effect on doxorubicin­induced cell death. Collectively, our data revealed that linc00239 is a novel tumour promoter in AML cells and indicated that it is a potential therapeutic target.

A Novel Francisella-Like Endosymbiont in Haemaphysalis longicornis and Hyalomma asiaticum, China.

Francisella tularensis causes a highly infectious zoonotic disease tularemia. Both Haemaphysalis longicornis and Hyalomma asiaticum are widely distributed in China, but the presence of Francisella and Francisella-like endosymbionts (FLEs) in the two tick species is poorly understood. Therefore, a total of 627 H. longicornis (471 adults and 156 nymphs) and 88 Hy. asiaticum ticks (adults) were collected, of which 88 were from Bole of Xinjiang, 236 from Liaoyang, and 176 from Shenyang of Liaoning, and 215 from Wuhan of Hubei. Notably, five H. longicornis pools from Liaoyang of Liaoning province might have harbored F. tularensis, showing a minimum prevalence of 2.12% (5/236). This study should alert the health department and veterinarians working within the region to prevent and control the emergence of tularemia. After the screening of 16S rRNA and tul4 genes, the results revealed that FLEs were detected in Hy. asiaticum ticks in Bole and in H. longicornis ticks in Liaoyang and Shenyang. Their infection rate was 100% (88/88), 3.39% (8/236 is a minimum), and 8.52% (15/176), respectively. Phylogenetic analyses indicated that the sequence named bole in Hy. Asiaticum from Bole, the sequence named liaoyang1 in H. longicornis from Liaoyang, and the sequence named shanyang1 in H. longicornis from Shenyang shared consistent 16S rRNA sequence, and the difference between Chinese FLEs and the known FLEs was obvious. These findings suggest that this FLE species might be a potentially novel FLE circulating in H. longicornis and Hy. asiaticum from China.

Analysis of imaging characteristics of primary malignant bone tumors in children.

The present study aimed to investigate the imaging characteristics of primary malignant bone tumors in children. The imaging results of 34 children with primary malignant bone tumors confirmed by histopathological diagnosis between March 2008 and January 2014 were retrospectively analyzed. In total, 25 patients had osteosarcoma, with radiography and computed tomography (CT) showing osteolytic bone destruction or/and osteoblastic bone sclerosis, an aggressive periosteal reaction, a soft-tissue mass and cancerous bone. The tumors appeared as mixed magnetic resonance imaging (MRI) signals that were inhomogeneously enhanced. A total of 5 patients presented with Ewing sarcoma, with radiography and CT showing invasive bone destruction and a soft-tissue mass. Of the 5 cases, 2 showed a laminar periosteal reaction. The tumors were shown to have mixed low signal on T1-weighted images (T1WI) and high signal on T2-weighted images (T2WI); 1 case showed marked inhomogeneous enhancement. Another 3 patients exhibited chondrosarcoma. Of these cases, 1 was adjacent to the cortex of the proximal tibia, and presented with local cortical bone destruction and a soft-tissue mass containing scattered punctate and amorphous calcifications. MRI revealed mixed low T1 signal and high T2 signals. Another case was located in the medullary cavity of the distal femur, with radiography revealing a localized periosteal reaction. The tumor appeared with mixed MRI signals, and with involvement of the epiphysis and epiphyseal plates. Radiography and CT of the third case showed bone destruction in the right pubic ramus, with patchy punctate, cambered calcifications in the soft-tissue mass. MRI of the soft-tissue mass revealed isointensity on T1WI and heterogeneous hyperintensity on T2WI. Ossifications and the septum appeared as low T1WI and T2WI. Of the 34 patients, 1 patient presented with lymphoma involving the T12, L1 and L2 vertebrae. CT showed vertebral bone destruction, a soft-tissue mass and a compression fracture of L1. MRI showed a soft-tissue mass with low T1 signal and high T2 signal and marked inhomogeneous enhancement. Overall, osteosarcoma was the most common primary malignant bone tumor, followed by Ewing sarcoma, chondrosarcoma and lymphoma. Osteoblastic or osteolytic bone destruction, an invasive periosteal reaction, soft-tissue masses, a tumor matrix and inhomogeneous enhancement were important imaging features of malignant bone tumors.

Phylogenetic Characteristics of Anthrax Outbreaks in Liaoning Province, China, 2001-2015.

Anthrax is a continuous threat in China, especially in rural regions. In July 2015, an anthrax outbreak occurred in Xifeng County, Liaoning Province. A total of 10 cutaneous anthrax cases were reported, with 210 people under medical observation. In this study, the general characteristics of human anthrax outbreak occurred in Liaoning Province were described, and all cases were caused by butchering and contacting sick animal. Meanwhile, the phylogenetic relationship between outbreak-related isolates/samples of the year 2015 and previous Bacillus anthracis strains was analyzed by means of canonical single nucleotide polymorphisms (canSNP), multiple-locus variable-number tandem repeat analysis (MLVA) with 15 markers and single-nucleotide repeats (SNR) analysis. There are two canSNP subgroups found in Liaoning, A.Br.001/002 and A.Br.Ames, and a total of six MLVA 15 genotypes and five SNR genotypes were observed. The strain collected from anthrax outbreak in Xifeng County in 2015 was classified as A.Br.001/002 subgroup and identified as MLVA15-29 genotype, with same SNR profile (CL10: 17, CL12: 15, CL33: 29, and CL35: 13). So we conclude that the same clone of B.anthracis caused the anthrax outbreak in Xifeng County in 2015, and this clone is different to previous isolates. Strengthening public health education in China is one of the most important measures to prevent and control anthrax.

Efficacy and Safety of Vasopressin Receptor Antagonists for Euvolemic or Hypervolemic Hyponatremia: A Meta-Analysis.

Hyponatremia, defined as a nonartifactual serum sodium level <135 mmol/L, is the most common fluid and electrolyte abnormality in clinical practice. Traditional managements (fluid restriction, hypertonic saline and loop diuretics, etc.) are difficult to maintain or ineffective. Recently, vasopressin receptor antagonists (VRAs) have shown promise for the treatment of hyponatremia. We aimed to conduct a meta-analysis to evaluate the efficacy and safety of VRAs in patients with euvolemic or hypervolemic hyponatremia. We searched Pubmed, Cochrane Library, Web of Science and Springer, etc. (latest search on June 4, 2015) for English publications with randomized controlled trials. Two authors independently screened the citations and extracted data. We calculated pooled relative risk (RR), risk difference (RD), weighted mean difference (WMD) or standard mean difference (SMD), and 95% confidence intervals (CIs) by using random and fixed effect models. We collected data from 18 trials involving 1806 patients. Both random and fixed effect meta-analyses showed that VRAs significantly increased the net change of serum sodium concentration (WMD(random) = 4.89 mEq/L, 95%CIs = 4.35-5.43 and WMD(fixed) = 4.70 mEq/L, 95%CIs = 4.45-4.95), response rate (RR(random )= 2.77, 95%CIs = 2.29-3.36 and RR(fixed) = 2.95, 95%CIs = 2.56-3.41), and 24-hour urine output (SMD(random) = 0.82, 95%CIs = 0.65-1.00 and SMD(fixed) = 0.79, 95%CIs = 0.66-0.93) compared to placebo. Furthermore, VRAs significantly decreased body weight (WMD(random) = -0.87 kg, 95%CIs = -1.24 to -0.49 and WMD(fixed) = -0.91 kg, 95%CIs = -1.22 to -0.59). In terms of safety, rates of drug-related adverse events (AEs), rapid sodium level correction, constipation, dry mouth, thirst, and phlebitis in the VRA-treated group were greater than those in control group. However, there was no difference in the total number of AEs, discontinuations due to AEs, serious AEs, death, headache, hypotension, nausea, anemia, hypernatremia, urinary tract infection, renal failure, pyrexia, upper gastrointestinal bleeding, diarrhea, vomiting, peripheral edema, and dizziness between the 2 groups. Random effect meta-analyses showed that post treatment urine osmolality, supine systolic blood pressure, and diastolic blood pressure were lowered (WMD(random) = -233.07 mOsmol/kg, 95%CIs = -298.20-147.94; WMD(random) = -6.11 mmHg, 95%CIs = -9.810 to -2.41; WMD(random )= -2.59 mmHg, 95%CIs = -4.06 to -1.11, respectively), but serum osmolality was increased (WMD(random) = 9.29 mOsmol/kg, 95%CIs = 5.56-13.03). There was no significant change from baseline in serum potassium concentration between the 2 groups (WMD(fixed) = 0.00 mmHg, 95%CIs = -0.07-0.06). VRAs are relatively effective and safe for the treatment of hypervolemic and euvolemic hyponatremia.