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Abstract Purpose To explore the value of tissue quantitative diffusion analysis of ultrasound elastography in the diagnosis of early-stage chronic kidney disease (CKD). Methods The observation group comprised 54 patients with early-stage CKD treated at Fuzhou No 7 Hospital, and the control group consisted of 40 healthy individuals who underwent physical examinations at the same hospital. The renal parenchyma of the participants were examined using ultrasonography, color Doppler ultrasonography, and tissue quantitative diffusion analysis of ultrasound elastography. Renal dimensions (diameter, thickness, and renal parenchyma thickness), interlobar artery blood flow parameters, and 11 elastic characteristic values were analyzed and compared between the two groups. The area under the receiver-operating characteristic (ROC) curve, cut-off values, sensitivity, and specificity were calculated using the ROC curve analysis. Results There were no significant differences in the blood flow parameters of the interlobar artery and the dimensions of renal meridians between the two groups. In the observation group, the mean (MEAN) decreased, while the blue area ratio and skewness, increased, compared to the control group (p 0.7). Notably, the best cut-off value of the MEAN was found to be 106, indicating that a MEAN value less than 106 represented early-stage CKD. Also, this cutoff value had a sensitivity of 80% and a specificity of 81%. Conclusion Tissue quantitative diffusion analysis of ultrasound elastography can quantitatively evaluate renal parenchymal damage in early-stage CKD using quantitative diffusion parameters, with the MEAN parameter, having a cutoff of 106, being particularly effective. This parameter and cutoff value offer a valuable tool for the early detection and diagnosis of CKD, potentially improving patient outcomes through earlier intervention. Clinical trial number Not applicable.

ABSTRACT This study aimed to explore the effect of cyclosporine (CsA) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in systemic lupus erythematosus (SLE) patients to provide a valuable reference for clinical treatment strategies in the context of the long-term risk of SARS-CoV-2 infection. SLE patients who visited the Rheumatology Outpatient Department of Fujian Medical University Union Hospital between 1 May and 31 October 2022 were included. Data on SARS-CoV-2 infection in patients between 1 November 2022 and 31 July 2023 were obtained by telephone follow-up. Patients were divided into two groups according to whether CsA was used during the observation period: the glucocorticoid or hydroxychloroquine group and the CsA group. To assess the robustness of the results, Data sets 1 and 2 were established to be analyzed independently. Multivariate logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for symptomatic coronavirus disease (COVID-19). A total of 184 patients were included, among whom 129 were definite symptomatic COVID-19 patients; 29 were presumptive symptomatic COVID-19 patients; and 4 had signs and symptoms of COVID-19, but tested negative for SARS-CoV-2 in a virological test. According to the multivariable-adjusted models, CsA was associated with lower odds of symptomatic COVID-19 (P = 0.042, OR = 0.316, 95% CI: 0.104–0.959 in Data set 1 and P = 0.021, OR = 0.257, 95% CI: 0.081–0.812 in Data set 2). CsA is associated with lower odds of contracting symptomatic COVID-19. The use of CsA may be considered an appropriate therapeutic option for disease management in patients with rheumatic diseases who have severe disease activity and persistent SARS-CoV-2 infection.IMPORTANCEOur study indicated that cyclosporine may reduce the risk of symptomatic COVID-19 in systemic lupus erythematosus patients in spite of its immunosuppressive effects. This study provides a reference for clinical treatment strategies for AIIRD patients in the context of the long-term risk of SARS-CoV-2 infection.

AIM: To investigate the underlying mechanism of dry environment (autumn dryness) affecting the lacrimal glands in rats. METHODS: Twenty Sprague-Dawley rats were randomly divided into two groups. The rats were fed in specific pathogen free environment as the control group (n=10), and the rats fed in dry environment as the dryness group (n=10). After 24d, lacrimal glands were collected from the rats. The tissues morphology was observed by hematoxylin-eosin (HE) staining. Tandem mass tags (TMT) quantitative proteomics analysis technology was used to screen the differential expressed proteins of lacrimal glands between the two groups, then bioinformatics analysis was performed. Further, the immunohistochemical (IHC) method was used to verify the target proteins. RESULTS: In dryness group, the lacrimal glands lobule atrophied, the glandular cavities enlarged, the sparse nuclear distribution and scattered inflammatory infiltration between the acinus were observed. The proteomics exhibited that a total of 195 up-regulated and 236 down-regulated differential expressed proteins screened from the lacrimal glands of rats. It was indicated that the biological processes (BP) of differential expressed proteins mainly included cell processes and single BP. The cellular compositions of differential expressed proteins mainly located in cells, organelles. The molecular functions of differential expressed proteins mainly included binding, catalytic activity. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the differential expressed proteins mainly involved lysosome, complement and coagulation cascade, and ribosome pathway. The IHC result verified that the up-regulated expression proteins of Protein S100A9 (S100A9), Annexin A1 (Anxa1), and Clusterin (Clu) in lacrimal glands of rats in dryness group were higher than control group. CONCLUSION: The up-regulated expression proteins of S100A9, Anxa1, and Clu may be the potential mechanisms of dry eye symptoms caused by dry environment. This study provides clues of dry environments causing eye-related diseases for further studies.

Background Lung metastasis is the primary cause of breast cancer-related mortality. Neutrophil extracellular traps (NETs) are involved in the progression of breast cancer. However, the mechanism of NET formation is not fully understood. This study posits that tumor cell-released autophagosomes (TRAPs) play a crucial role in this process.Methods TRAPs were isolated from breast cancer cell lines to analyze their impact on NET formation in both human and mouse neutrophils. The study used both in vitro and in vivo models, including Toll-like receptor 4 (TLR4−/−) mice and engineered breast cancer cell lines. Immunofluorescence, ELISA, Western blotting, RNA sequencing, and flow cytometry were employed to dissect the signaling pathways leading to NET production and to explore their immunosuppressive effects, particularly focusing on the impact of NETs on T-cell function. The therapeutic potential of targeting TRAP-induced NETs and their immunosuppressive functions was evaluated using DNase I and αPD-L1 antibodies. Clinical relevance was assessed by correlating circulating levels of TRAPs and NETs with lung metastasis in patients with breast cancer.Results This study showed that TRAPs induced the formation of NETs in both human and mouse neutrophils by using the high mobility group box 1 and activating the TLR4-Myd88-ERK/p38 signaling axis. More importantly, PD-L1 carried by TRAP-induced NETs inhibited T-cell function in vitro and in vivo, thereby contributing to the formation of lung premetastatic niche (PMN) immunosuppression. In contrast, Becn1 KD-4T1 breast tumors with decreased circulating TRAPs in vivo reduced the formation of NETs, which in turn attenuated the immunosuppressive effects in PMN and resulted in a reduction of breast cancer pulmonary metastasis in murine models. Moreover, treatment with αPD-L1 in combination with DNase I that degraded NETs restored T-cell function and significantly reduced tumor metastasis. TRAP levels in the peripheral blood positively correlated with NET levels and lung metastasis in patients with breast cancer.Conclusions Our results demonstrate a novel role of TRAPs in the formation of PD-L1-decorated NETs, which may provide a new strategy for early detection and treatment of pulmonary metastasis in patients with breast cancer.

ObjectiveThis study aimed to quantify the severity of metabolic syndrome(MetS) and investigate its association with cardiovascular disease(CVD) risk on Chinese adults.Methods13,500 participants from the Zhejiang Adult Chronic Disease Study were followed up between 2010 and 2021. A continuous MetS severity score derived from the five components of MetS was used to quantify MetS severity, and the association between MetS severity and the risk of incident CVD was assessed using Cox proportional hazard and restricted cubic spline regression.ResultsBoth the presence and severity of MetS were strongly associated with CVD risk. MetS was related to an increased risk of CVD (hazard ratio(HR):1.700, 95% confidence interval(CI): 1.380–2.094). Compared with the hazard ratio for CVD in the lowest quartile of the MetS severity score, that in the second, third, and highest quartiles were 1.812 (1.329–2.470), 1.746 (1.265–2.410), and 2.817 (2.015–3.938), respectively. A linear and positive dose-response relationship was observed between the MetS severity and CVD risk (P for non-linearity = 0.437). Similar results were found in various sensitivity analyses.ConclusionThe MetS severity score was significantly associated with CVD risk. Assessing MetS severity and further ensuring intervention measures according to the different severities of MetS may be more useful in preventing CVD.

Abstract Tumor cell-released LC3+ extracellular vesicles (LC3+ EVs) participate in immunosuppression during autophagy and contribute to the occurrence and development of breast cancer. In view of the strong association between the LC3+ EVs and breast cancer, developing an effective strategy for the quantitative detection of LC3+ EVs levels with high sensitivity to identify LC3+ EVs as new biomarkers for accurate diagnosis of breast cancer is crucial, but yet not been reported. Herein, an ultrasensitive electrochemical immunosensor is presented for the quantitative determination of LC3+ EVs using a three-dimensional graphene oxide hydrogel-methylene blue composite as a redox probe, showing a low detection limit and a wide linear range. With this immunosensor, the expression levels of LC3+ EVs in various practical sample groups including different cancer cell lines, the peripheral blood of tumor-bearing mice before and after immunotherapy, and the peripheral blood from breast cancer patients with different subtypes and stages were clearly distinguished. This study demonstrated that LC3+ EVs were superior as biomarkers for the accurate diagnosis of breast cancer compared to traditional biomarkers, particularly for cancer subtype discrimination. This work would provide a new noninvasive detection tool for the early diagnosis and prognosis assessment of breast cancer in clinics.

The carbonate rock of the Qiulitage Formation is a significant stratum for oil and gas exploration in the Tarim Basin. To elucidate its environmental characteristics, we conducted tests and analyses of trace elements, carbon, and oxygen isotopes of the carbonate rocks of the Qiulitage Formation in the Kekeqigankake section of the Keping area. The results reveal that δ13C values range between −1.7‰ and 4.3‰, with an average value of 1.645‰. δ18O values fluctuate from −11.4‰ to −6‰, with an average value of −8.2475‰. Z values (paleosalinity) vary from 120.33 to 131.67, significantly exceeding 120 with an average value of 126.52, indicating a marine sedimentary environment. Paleotemperature values (T) range from 12.75 to 29.09 °C, with an average value of 21.36 °C, suggesting warm climate conditions. The Sr/Ba (3.42~24.39) and Sr/Cu (57.5~560) ratios are elevated, while Th/U (

3′,5′-Cyclic adenosine monophosphate (cAMP) is an important metabolite that is specifically enriched in jujube. However, the effect of cAMP on jujube cellular responses has not been comprehensively studied. Here, we established jujube cell suspension cultures and investigated the calcium influx in response to cAMP treatment through protoplast isolation and fluorescence intensity. Firstly, cAMP treatment could promote jujube growth and increase the content of endogenous cAMP. Using transcriptome analysis with transgenic Arabidopsis plants overexpressing adenylate cyclase (ZjAC) as a positive control, we identified 60 calcium-related differential expressed genes (DEGs) that contributed to the calcium signaling and inter- or intra-cellular responses. Pharmacological treatments such as cAMP and the calcium ionophore A23187 could induce ZjAC expression, the accumulation of cAMP and calcium influx in jujube cells, while ethylene glycol tetraacetic acid (EGTA) or bithionol treatment inhibited these changes. Moreover, the calcium channels and transporters in calcium influx, such as the ZjCNGC2 channel and the mitogen activated protein (MAP) kinase pathway, could be activated by cAMP treatment. In summary, our findings demonstrated that cAMP biosynthesis is dependent on calcium influx and the amplifying effect between calcium and cAMP may be involved in intracellular signal induction, which might contribute to the growth and development of jujube.

Abstract Background Currently, there is no consensus on the most appropriate technique for obtaining lateral hip radiographs after cephalomedullary nail (CMN) surgery. The aim of this study was to investigate the distribution of two commonly used postoperative lateral hip radiographic methods (classic lateral view and modified lateral view) and try to find out which one is better suited for this situation. Methods A retrospective analysis was conducted on 146 patients who underwent surgical fixation for extracapsular hip fractures between January 2018 and June 2022. The main outcome measured was the angle between the straight part of the CMN and the lag screw/blade on hip lateral X-rays (CMNA). The lateral hip radiographs were categorized into two groups based on different lateral hip radiographic methods. CMNA, patient age, gender, fracture classification based on the 2018 AO classification, nail length (short/long), surgical side (left/right), height, weight, BMI, preoperative waiting time, postoperative imaging interval were collected and compared between the two groups. Results The distribution trend of CMNA significantly differs between two types of hip joint lateral radiographic methods. Specifically, the classic lateral method exhibits a significantly bimodal and skewed distribution with a median (p25, p75) of -21.6° (-31.2°, -8°), whereas the modified lateral method presents a normal distribution with a mean ± SD of +7.57° ± 14.4°. The difference in the Mean Rank between the classic (47.10) and the modified (102.96) lateral methods is statistically significant (P

Quantification of measurable residual disease (MRD) correlates with the risk of leukemia recurrence in adults with B-cell acute lymphoblastic leukemia (ALL). However, it remains unknown whether collecting data on cysteine and glycine-rich protein 2 (CSRP2) transcript levels, after completing the second course of consolidation, improves prognosis prediction accuracy. A total of 204 subjects with B-cell ALL were tested for CSPR2 transcripts after completing the second course of consolidation using quantitative real-time polymerase chain reaction (qRT-PCR) and divided into high (N = 32) and low (N = 172) CSRP2 expression cohorts. In multivariable analyses, subjects with high expression of CSRP2 had a higher 5-year cumulative incidence of relapse (CIR) (hazard ratio [HR] = 2.57, 95% confidence interval [CI] 1.38-4.76; P = 0.003), lower 5-year relapse-free survival (RFS) (HR = 3.22, 95% CI 1.75-5.93; P < 0.001), and overall survival (OS) (HR = 4.59, 95% CI 2.64-7.99; P < 0.001) in the whole cohort, as well as in the multi-parameter flow cytometry (MPFC) MRD-negative cohort (for CIR, HR = 2.70, 95% CI 1.19-6.12; for RFS, HR = 4.37, 95% CI 1.94-9.85; for OS, HR = 4.90, 95% CI 2.43-9.90; all P < 0.05). Prognostic analysis showed that allogeneic hematopoietic stem cell transplantation (allo-HSCT) could significantly improve the prognosis of patients with high CSRP2 expression (allo-HSCT vs chemotherapy: 5-year CIR, 52% vs 91%; RFS, 41% vs 9%; OS, 38% vs 20%; all P < 0.05). Our data indicate that incorporating data from CSPR2 transcript levels to the MRD-testing at the end of the second course of consolidation therapy enhances prognosis prediction accuracy in adults with B-cell ALL.

Abstract Background & Aims Capsaicin, a functional component of chili pepper, possesses anti‐inflammatory, analgesic, and anti‐cancer properties. This study aimed to determine the property of capsaicin against hepatocarcinogenesis in vivo and investigate the role of the SIRT1/SOX2 pathway in the mode of action of capsaicin in hepatic progenitor cells (HPCs), which is related to hepatocarcinogenesis. Materials & Methods We prepared a diethylnitrosamine‐induced liver cancer model in rats to examine hepatocarcinogenesis, and delivered liposomal capsaicin through the subcutaneous transposition of the spleen to the liver. Liver sections from rats and hepatocarcinoma patients were stained for the markers of HPCs or SIRT1/SOX2 signaling. SIRT1/SOX2 signalling expression was measured using immunoprecipitation and western blot. Results We found that capsaicin significantly inhibited hepatocarcinogenesis. Notably, capsaicin inhibited HPCs activation in vivo but did not induce apoptosis in the normal hepatic progenitor cell line in rats in vitro. This suggests that capsaicin suppresses hepatocarcinogenesis by inhibiting the stemness of HPCs. Moreover, capsaicin can induce this inhibition by reducing the stability of SOX2. SIRT1 is overexpressed in liver cancer and acts as a tumor promoter via SOX2 deacetylation. Using immunoprecipitation, we identified direct binding between SIRT1 and SOX2. The capsaicin treatment resulted in SIRT1 downregulation which reduced deacetylation, and increased nuclear export as well as subsequent ubiquitous degradation of SOX2. Conclusions Altogether, we report that capsaicin suppresses hepatocarcinogenesis by inhibiting the stemness of HPCs via SIRT1/SOX2 signaling. It may serve as a promising therapeutic candidate for liver cancer.

IntroductionIt was first reported that germ cell tumor patients suffer from hematologic malignancies 37 years ago. Since then, the number of relevant reports has increased each year, with most cases being mediastinal germ cell tumor. Theories have been proposed to explain this phenomenon, including a shared origin of progenitor cells, the effects of treatment, and independent development. However, up to now, no widely accepted explanation exists. The case with acute megakaryoblastic leukemia and intracranial germ cell tumor has never been reported before and the association is far less known.MethodsWe used whole exome sequencing and gene mutation analysis to study the relationship between intracranial germ cell tumor and acute megakaryoblastic leukemia of our patient.ResultsWe report a patient who developed acute megakaryoblastic leukemia after treatment for an intracranial germ cell tumor. Through whole exome sequencing and gene mutation analysis, we identified that both tumors shared the same mutation genes and mutation sites, suggesting they originated from the same progenitor cells and differentiated in the later stage.DiscussionOur findings provide the first evidence supporting the theory that acute megakaryoblastic leukemia and intracranial germ cell tumor has the same progenitor cells.

BackgroundBabao Dan (BBD) is a traditional Chinese medicine that has been widely used as a complementary and alternative medicine to treat chronic liver diseases. In this study, we aimed to observe the effect of BBD on the incidence of diethylnitrosamine (DEN)-initiated hepatocellular carcinoma formation in rats and explored its possible mechanism.MethodsTo verify this hypothesis, BBD was administrated to rats at a dose of 0.5g/kg body weight per two days from the 9th to 12th week in HCC-induced by DEN. Liver injury biomarkers and hepatic inflammatory parameters were evaluated by histopathology as well as serum and hepatic content analysis. We applied immunohistochemical analysis to investigate the expression of CK-19 and SOX-9 in liver tissues. The expression of TLR4 was determined by immunohistochemical, RT-PCR, and western blot analysis. Furthermore, we also detected the efficacy of BBD against primary HPCs neoplastic transformation induced by LPS.ResultsWe observed that DEN could induce hepatocarcinogenesis, and BBD could obviously decrease the incidence. The biochemical and histopathological examination results confirmed that BBD could protect against liver injury and decrease inflammatory infiltration. Immunohistochemistry staining results showed that BBD could effectively inhibit the ductal reaction and the expression of TLR4. The results showed that BBD-serumcould obviously inhibit primary HPCs neoplastic transformation induced by regulating the TLR4/Ras/ERK signaling pathway.ConclusionIn summary, our results indicate that BBD has potential applications in the prevention and treatment of HCC, which may be related to its effect on hepatic progenitor cells malignant transformation via inhibiting the TLR4/Ras/ERK signaling pathway.

Abstract Background For better understanding the mechanism of Reaumuria soongarica community formation in a salt stressed grassland ecosystem, we designed a field experiment to test how leaves salt secretion changes the competitive relationship between species in this plant communities. Results Among the three species (R. soongarica, Stipa glareosa and Allium polyrhizum) of the salt stressed grassland ecosystem, the conductivity of R. soongarica rhizosphere soil was the highest in five soil layers (0–55 cm depth). The high soil conductivity can increase the daily salt secretion rate of plant leaves of R. soongarica. In addition, we found the canopy size of R. soongarica was positively related to the distance from S. glareosa or A. polyrhizum. The salt-tolerance of R. soongarica was significantly higher than the other two herbs (S. glareosa and A. polyrhizum). Moreover, there was a threshold (600 µS/cm) for interspecific competition of plants mediated by soil conductivity. When the soil conductivity was lower than 600 µS/cm, the relative biomass of R. soongarica increased with the soil conductivity increase. Conclusions The efficient salt secretion ability of leaves increases soil conductivity under the canopy. This leads the formation of a “saline island” of R. soongarica. Meanwhile R. soongarica have stronger salt tolerance than S. glareosa and A. polyrhizum. These promote the competitiveness of R. soongarica and inhibit interspecies competition advantage of the other two herbs (S. glareosa and A. polyrhizum) in the plant community. It is beneficial for R. soongarica to establish dominant communities in saline regions of desert grassland.

Phospholipase A and acyltransferase (PLAAT) 4 is a class II tumor suppressor with phospholipid metabolizing abilities. It was characterized in late 2000s, and has since been referred to as ‘tazarotene-induced gene 3’ (TIG3) or ‘retinoic acid receptor responder 3’ (RARRES3) as a key downstream effector of retinoic acid signaling. Two decades of research have revealed the complexity of its function and regulatory roles in suppressing tumorigenesis. However, more recent findings have also identified PLAAT4 as a key anti-microbial effector enzyme acting downstream of interferon regulatory factor 1 (IRF1) and interferons (IFNs), favoring protection from virus and parasite infections. Unveiling the molecular mechanisms underlying its action may thus open new therapeutic avenues for the treatment of both cancer and infectious diseases. Herein, we aim to summarize a brief history of PLAAT4 discovery, its transcriptional regulation, and the potential mechanisms in tumor prevention and anti-pathogen defense, and discuss potential future directions of PLAAT4 research toward the development of therapeutic approaches targeting this enzyme with pleiotropic functions.

BackgroundInflammatory mechanisms play important roles in intracerebral hemorrhage (ICH) and have been linked to the development of stroke-associated pneumonia (SAP). The neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR) and systemic inflammation response index (SIRI) are inflammatory indexes that influence systemic inflammatory responses after stroke. In this study, we aimed to compare the predictive value of the NLR, SII, SIRI and PLR for SAP in patients with ICH to determine their application potential in the early identification of the severity of pneumonia.MethodsPatients with ICH in four hospitals were prospectively enrolled. SAP was defined according to the modified Centers for Disease Control and Prevention criteria. Data on the NLR, SII, SIRI and PLR were collected at admission, and the correlation between these factors and the clinical pulmonary infection score (CPIS) was assessed through Spearman’s analysis.ResultsA total of 320 patients were enrolled in this study, among whom 126 (39.4%) developed SAP. The results of the receiver operating characteristic (ROC) analysis revealed that the NLR had the best predictive value for SAP (AUC: 0.748, 95% CI: 0.695-0.801), and this outcome remained significant after adjusting for other confounders in multivariable analysis (RR=1.090, 95% CI: 1.029-1.155). Among the four indexes, Spearman’s analysis showed that the NLR was the most highly correlated with the CPIS (r=0.537, 95% CI: 0.395-0.654). The NLR could effectively predict ICU admission (AUC: 0.732, 95% CI: 0.671-0.786), and this finding remained significant in the multivariable analysis (RR=1.049, 95% CI: 1.009-1.089, P=0.036). Nomograms were created to predict the probability of SAP occurrence and ICU admission. Furthermore, the NLR could predict a good outcome at discharge (AUC: 0.761, 95% CI: 0.707-0.8147).ConclusionsAmong the four indexes, the NLR was the best predictor for SAP occurrence and a poor outcome at discharge in ICH patients. It can therefore be used for the early identification of severe SAP and to predict ICU admission.

Abstract Hainan Island had experienced several cold–warm and dry–humid fluctuations since the Late Pleistocene period, resulting in separating and connecting from the mainland several times with the cyclic rise and fall of sea level. The fluctuations can change the biota and ecological environment in the island. Cycas taiwaniana Carruthers is endemic to Hainan Island and is classified as endangered by the International Union for Conservation of Nature (IUCN). To comprehensively understand the genetic dynamics of C. taiwaniana, we sampled 12 wild populations in Hainan Island and one cultivated population in Fujian province, and analyzed the genetic diversity, genetic structure, and demographic history based on the molecular data. Results revealed that C. taiwaniana had relatively low genetic diversity and high genetic differentiation. Haplotypes of C. taiwaniana diversified during the Pleistocene based on the chloroplast DNA (cpDNA) and the concatenated nuclear DNA (nDNA) data. Genetic cluster analyses based on the microsatellite (SSR) data showed that the 12 wild populations were separated into three clusters which could be three evolutionary significant units (ESUs), indicating three basic units of protection were identified. Moreover, we also confirmed the cultivated population FJ derived from the DLS1‐GSL clade. Demographic inference from different data was discordant, but overall, it uncovered that C. taiwaniana had experienced population contraction events twice during the Pleistocene and Holocene, and then expanded recently. Our study elucidated the population genetic characteristics of C. taiwaniana, and guided us to develop targeted conservation and management strategies for this endangered species.

The G-protein-coupled receptor GPR84, activated by medium-chain fatty acids, primarily expressed in macrophages and microglia, is involved in inflammatory responses and retinal development in mammals and amphibians. However, our understanding of its structure, function, tissue expression, and signaling pathways in fish is limited. In this study, we cloned and characterized the coding sequence of GPR84 (ciGPR84) in grass carp. A phylogenetic analysis revealed its close relationship with bony fishes. High expression levels of GPR84 were observed in the liver and spleen. The transfection of HEK293T cells with ciGPR84 demonstrated its responsiveness to medium-chain fatty acids and diindolylmethane (DIM). Capric acid, undecanoic acid, and lauric acid activated ERK and inhibited cAMP signaling. Lauric acid showed the highest efficiency in activating the ERK pathway, while capric acid was the most effective in inhibiting cAMP signaling. Notably, DIM did not activate GPR84 in grass carp, unlike in mammals. These findings provide valuable insights for mitigating chronic inflammation in grass carp farming and warrant further exploration of the role of medium-chain fatty acids in inflammation regulation in this species.

The TanDEM-X DEM is a valuable data source for estimating glacier mass balance. However, the accuracy of TanDEM-X elevation over glaciers can be affected by microwave penetration and phase decorrelation. To investigate the bias of TanDEM-X DEMs of glaciers on the Tibetan Plateau, these DEMs were subtracted from SPOT-6 DEMs obtained around the same time at two study sites. The average bias over the studied glacier areas in West Kunlun (175.0 km2) was 2.106 ± 0.012 m in April 2014, and it was 1.523 ± 0.011 m in Geladandong (228.8 km2) in October 2013. By combining backscatter coefficients and interferometric coherence maps, we found surface decorrelation and baseline decorrelation can cause obvious bias in addition to microwave penetration. If the optical/laser data and winter TanDEM-X data were used as new and historic elevation sources for mass-balance measurements over an arbitrary observation period of 10 years, the glacier mass loss rates in West Kunlun and Geladandong would be potentially underestimated by 0.218 ± 0.016 and 0.158 ± 0.011 m w.e. a−1, respectively. The impact is therefore significant, and users should carefully treat the bias of TanDEM-X DEMs when retrieving a geodetic glacier mass balance.

We observed the surge velocity, terminus advance, lake formation and outburst, as well as its downstream impacts at Shisper Glacier in the Karakoram, Pakistan and suggest potential nature-based risk-reduction solutions. A recent surge started in late 2017 with increased velocity since April 2018 and a resulting terminus advance from June 2018. Bi-modal peak velocity of 19.2 ± 0.16 m/day was observed in April-May 2018 and May-June 2019. Also, the terminus advance blocked the river from the adjacent Muchuhar Glacier repeatedly since November 2018. Lake outbursts were observed in June 2019 and April 2020. Relying on observations of the lake area and peak discharge of 142 m3 s−1 in 2019 and 85 m3 s−1 April 2020, outburst were simulated using the BASEMENT software. Simulations and field observations show that even at high discharge, damages were mainly observed along the main river channel, causing strong bank erosion rather than widespread inundation of land. The ice-dammed lake is potentially hazardous until the blocked stream completely disappears in future. Our results suggest that the biggest lake outburst hazard lies in its erosion potential with damages to infrastructure closest to the river and large sediments transport to the downstream Hunza River.

Abstract Background Wild Amur tigers are a sparsely populated species, and the conservation of this species is of great concern worldwide, but as an important health risk factor, parasite infection in them is not fully understanding. Results In this study, sixty-two faecal samples were collected to investigate the frequency and infection intensity of Toxocara cati and Toxascaris leonina in wild Amur tigers. The T. cati and T. leonina eggs were preliminary identified by microscopy, and confirmed by molecular techniques. Infection intensity was determined by the modified McMaster technique. Phylogenetic trees demonstrated that T. cati of wild Amur tiger had a closer relationship with which of other wild felines than that of domestic cats. T. leonina of Amur tiger and other felines clustered into one clade, showing a closer relationship than canines. The average frequency of T. cati was 77.42% (48/62), and the frequency in 2016 (100%) were higher than those in 2013 (P = 0.051,

BackgroundApproximately 30% of Chinese individuals with cytogenetically normal acute myeloid leukemia (CN-AML) have biallelic CEBPA (biCEBPA) mutations. The prognosis and optimal therapy for these patients are controversial in clinical practice.MethodsIn this study, we performed targeted region sequencing of 236 genes in 158 individuals with this genotype and constructed a nomogram model based on leukemia-free survival (LFS). Patients were randomly assigned to a training cohort (N =111) and a validation cohort (N =47) at a ratio of 7:3. Risk stratification was performed by the prognostic factors to investigate the risk-adapted post-remission therapy by Kaplan–Meier method.ResultsAt least 1 mutated gene other than CEBPA was identified in patients and mutation number was associated with LFS (61.6% vs. 39.0%, P =0.033), survival (85.6% vs. 62.9%, P =0.030) and cumulative incidence of relapse (CIR) (38.4% vs. 59.5%, P =0.0496). White blood cell count, mutations in CFS3R, KMT2A and DNA methylation related genes were weighted to construct a nomogram model and differentiate two risk subgroups. Regarding LFS, low-risk patients were superior to the high-risk (89.3% vs. 33.8%, P

Abstract Background Babao Dan (BBD), a traditional Chinese medicine, has been used as a complementary and alternative medicine to treat multifarious liver diseases. In this study, we aimed to observe its protective effect on ethanol-induced liver injury and explore potential mechanisms. Methods Mice pretreated with BBD (0.125, 0.25 and 0.5 g/kg BW) were administrated by ethanol gavage (5 g/kg BW). Liver injury biomarkers and hepatic redox parameters were evaluated by histopathology as well as serum and hepatic content analysis. AML-12 cell was also utilized to determine the efficacy of BBD against ethanol-induced hepatotoxicity. Results Drunkenness experiment showed that the latency was significantly increased and the drunken sleep time was decreased in mice pretreated with BBD. We then found that BBD could reduce hepatic lipid peroxidation and steatosis induced by ethanol exposure. BBD could also suppress ethanol-induced depletion of hepatic antioxidant enzyme. Besides that, BBD treatment lessened the induction of hepatic cytochrome P450 2E1, a major contributor to ethanol-mediated oxidative stress, and up-regulated the expression of nuclear factor erythroid 2-related factor 2 and its two transcriptional targets hemeoxygenase-1 and glutamate-cysteine ligase catalytic subunit. Furthermore, autophagy induced by BBD contributed to hepatoprotection activity. Conclusions Our results suggest that BBD can markedly dispel acute ethanol-induced hepatotoxicity through multiple pathways including attenuation of ethanol-mediated oxidative stress, enhancement of the oxidative defense systems and activation of autophagy.

Abstract Background CD4+ T cells are critical effectors of anti-tumor immunity, but how tumor cells influence CD4+ T cell effector function is not fully understood. Tumor cell-released autophagosomes (TRAPs) are being recognized as critical modulators of host anti-tumor immunity during tumor progression. Here, we explored the mechanistic aspects of TRAPs in the modulation of CD4+ T cells in the tumor microenvironment. Methods TRAPs isolated from tumor cell lines and pleural effusions or ascites of cancer patients were incubated with CD4+ T cells to examine the function and mechanism of TRAPs in CD4+ T cell differentiation and function. TRAPs-elicited CD4+ T cells were tested for their suppression of effector T cell function, induction of regulatory B cells, and promotion of tumorigenesis and metastasis in a mouse model. Results Heat shock protein 90α (HSP90α) on the surface of TRAPs from malignant effusions of cancer patients and tumor cell lines stimulated CD4+ T cell production of IL-6 via a TLR2–MyD88–NF-κB signal cascade. TRAPs-induced autocrine IL-6 further promoted CD4+ T cells secretion of IL-10 and IL-21 via STAT3. Notably, TRAPs-elicited CD4+ T cells inhibited CD4+ and CD8+ effector T cell function in an IL-6- and IL-10-dependent manner and induced IL-10-producing regulatory B cells (Bregs) via IL-6, IL-10 and IL-21, thereby promoting tumor growth and metastasis. Consistently, inhibition of tumor autophagosome formation or IL-6 secretion by CD4+ T cells markedly retarded tumor growth. Furthermore, B cell or CD4+ T cell depletion impeded tumor growth by increasing effector T cell function. Conclusions HSP90α on the surface of TRAPs programs the immunosuppressive functions of CD4+ T cells to promote tumor growth and metastasis. TRAPs or their membrane-bound HSP90α represent important therapeutic targets to reverse cancer-associated immunosuppression and improve immunotherapy.

Background: Zuotai (mainly β-HgS)-containing 70 Wei-Zhen-Zhu-Wan (70W, Rannasangpei) is a famous Tibetan medicine for treating cardiovascular and gastrointestinal diseases. We have shown that 70W protected against CCl4 hepatotoxicity. CCl4 is metabolized via cytochrome P450 (CYP) to produce reactive metabolites. Whether 70W has any effect on CYPs is unknown and such effects should be compared with mercury compounds for safety evaluation. Methods: Mice were given clinical doses of 70W (0.15-1.5 g/kg, po), Zuotai (30 mg/kg, po), and compared to HgCl2 (33.6 mg/kg, po) and MeHg (3.1 mg/kg, po) for seven days. Liver RNA and protein were isolated for qPCR and Western-blot analysis. Results: 70W and Zuotai had no effects on hepatic mRNA expression of Cyp1a2, Cyp2b10, Cyp3a11, Cyp4a10 and Cyp7a1, and corresponding nuclear receptors [aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor-α (PPARα); farnesoid X receptor (FXR)]. In comparison, HgCl2 and MeHg increased mRNA expression of Cyp1a2, Cyp2b10, Cyp4a10 and Cyp7a1 except for Cyp3a11, and corresponding nuclear receptors except for PXR. Western-blot confirmed mRNA results, showing increases in CYP1A2, CYP2B1, CYP2E1, CYP4A and CYP7A1 by HgCl2 and MeHg only, and all treatments had no effects on CYP3A. Conclusions: Zuotai and Zuotai-containing 70W at clinical doses had minimal influence on hepatic CYPs and corresponding nuclear receptors, while HgCl2 and MeHg produced significant effects. Thus, the use of total Hg content to evaluate the safety of HgS-containing 70W is inappropriate.

Luminescent Pb2+-based metal–organic frameworks (MOFs) belong to a new class of multifunctional molecular materials with interesting luminescence properties and potential applications within a single crystalline phase. In this mini review, we present the recent advances that have been achieved in their applications as single-phase white-light emitting materials and chemosensors in the last decade. We focus on the trends in the modification of their structures and luminescence by various bridging ligands, and subsequently their multifunctional applications, which may affect the future development of the field.

In this study, we determined the complete chloroplast genome of Cycas hongheensis (Cycadaceae), one of the first-class protected plants in China. The chloroplast genome is 162,048 bp in length with 133 genes, including 87 protein-coding genes, eight ribosomal RNA genes, and 37 transfer RNA genes. The overall GC content is 39.4%. Phylogenomic analysis showed that C. hongheensis as sister to all other Cycas species that with reported chloroplast genomes. The chloroplast genome of C. hongheensis reported here will contribute to further comparative chloroplast genome of Cycads and helpful to study the phylogeography of Cycadaceae.

ObjectivePolycystin-1 (PC-1) is a protein encoded by the gene of polycystic kidney disease-1 (PKD-1). This study was designed to investigate the regulatory mechanisms of PC-1 on phenotypes of aortic vascular smooth muscle cells (VSMCs) and functions of extracellular matrix (ECM) in thoracic aortic dissection (TAD).MethodsAortic tissues from patients with TAD and healthy controls were collected, primary aortic VSMCs were also isolated. Immunohistochemistry, immunofluorescence, and immunocytochemistry was used to visualize the target proteins. Western blot and RT-qPCR were used to examine the expression of mRNA and proteins. Lentivirus infection was used to downregulate or overexpress PC-1.ResultsCompared with the control group, expression of PC-1 and the contractile phenotypic markers of VSMCs were decreased in TAD group, whereas expression of the synthetic markers of VSMCs, matrix metalloproteinase (MMP)-2, collagen I and collagen III were increased. The phosphorylation of mTOR, S6K and S6 were also elevated in TAD group. PC-1 downregulation of aortic VSMCs inhibited the expression of the contractile markers, but elevated the expression of the synthetic markers, MMP-2, collagen I and collagen III compared with the control group. The phosphorylation of mTOR, S6K and S6 were also increased in PKD-1-knockdown VSMCs. PC-1 upregulation reversed all these expression characteristics in aortic VSMCs. Furthermore, rapamycin treatment to PKD-1-knockdown VSMCs inhibited the effects caused by PC-1 downregulation.ConclusionOur study revealed PC-1 downregulation induces aortic VSMCs phenotypic alteration and ECM remodeling via activation of mTOR/S6K/S6 signaling pathway. Downregulation of PC-1 might be a potential mechanism for the development and progression of TAD. Rapamycin might be a potential inhibitor to attenuate the development and progression of TAD.

Abstract Background Tumor-associated macrophages (TAMs) facilitate tumor progression via establishment of an immunosuppressive tumor microenvironment (TME). However, it is poorly understood how tumor cells could functionally modulate TAMs. Our previous work indicated that tumor cell-released autophagosomes (TRAPs), a type of LC3-II+ double-membrane extracellular vesicles (EVs) was sufficient to suppress anti-tumor immune responses by inducing IL-10-producing B cells and immune suppressive neutrophils. Here, we hypothesized that TRAPs may participate in regulating macrophage polarization. Methods TRAPs isolated from multiple murine tumor cell lines and pleural effusions or ascites of cancer patients were incubated with bone marrow-derived macrophages (BMDMs) and monocytes, respectively. Cellular phenotypes were examined by flow cytometry, ELISA and quantitative PCR. TRAPs treated BMDMs were tested for the ability to suppress T-cell proliferation in vitro, and for promotion of tumor growth in vivo. Transwell chamber and neutralization antibodies were added to ascertain the inhibitory molecules expressed on BMDMs exposed to TRAPs. Knockout mice were used to identify the receptors responsible for TRAPs-induced BMDMs polarization and the signaling mechanism was examined by western blot. Autophagy-deficient tumors were profiled for phenotypic changes of TAMs and IFN-γ secretion of T cells by flow cytometry. The phenotype of monocytes from pleural effusions or ascites of cancer patients was assessed by flow cytometry. Results TRAPs converted macrophages into an immunosuppressive M2-like phenotype characterized by the expression of PD-L1 and IL-10. These macrophages inhibited the proliferation of both CD4+ and CD8+ T cells in vitro, and promoted tumor growth mainly through PD-L1 in vivo. TRAPs-induced macrophage polarization was dependent on TLR4-mediated MyD88-p38-STAT3 signaling. In vivo studies indicated that disruption of autophagosome formation in B16F10 cells by silencing the autophagy gene Beclin1 resulted in a remarkable delay in tumor growth, which was associated with reduced autophagosome secretion, TAMs reprogramming and enhanced T cell activation. Moreover, the levels of LC3B+ EVs appeared to correlate significantly with up-regulation of PD-L1 and IL-10 in matched monocytes from effusions or ascites of cancer patients, and TRAPs isolated from these samples could also polarize monocytes to an M2-like phenotype with increased expression of PD-L1, CD163 and IL-10, decreased expression of HLA-DR, and T cell-suppressive function. Conclusions These findings suggest the TRAPs-PD-L1 axis as a major driver of immunosuppression in the TME by eliciting macrophage polarization towards an M2-like phenotype, and highlight the potential novel therapeutic approach of simultaneously targeting autophagy and PD-L1.

Based on the coal demand under the 1.5 °C scenario, the amount of coal production in China was estimated in this study. According to the mutual relationship between the factors influencing coal production, an econometric model was constructed based on simultaneous equations, and the synergistic effect of each factor on the coal industry was estimated under the 1.5 °C scenario. Then, predictions were respectively made in the five aspects: coal production, coal science and technology progress, employment number, safe production level, and occupational health level, in different scenarios from 2016 to 2050. The results showed that before 2040, the comprehensive negative effect of the 1.5 °C situation is more than or equals to the positive effect. The 1.5 °C scenario has the biggest negative impact on employment, whose solution should be the focus. By 2050, the positive effects of the 1.5 °C scenario exceed the negative effect because of the enhancement in technical level and in the attention given to the whole production. Safety is improved, and health defects decline and the most obvious positive effect is on the ecological environment. The decrease of coal production will reduce the ecological environmental damage and significantly improve the ecological environment. In general, the prediction of 1.5 °C scenario promotes the increase of scientific production capacity and promotes the orderly development of coal. It has strengthened the safety and health protection degree, made the coal industry more efficient and competitive, and avoided or reduced the impact of coal development on the ecological environment and achieved environmental friendliness. However, the 1.5 °C situation also increases the employment pressure of the society, which affects the economic development of the major coal producing areas, but the situation can be overcome through the transformation and upgrading of the region. Finally, the impacts of various factors under the 1.5 °C scenario were evaluated through a unified comparison of the synergistic effect monetization using the cost and payment willingness methods. Based on the research results, suggestions on the regulation of coal production were proposed relating to resettlement of workers, protection of the ecological environment, and improvement of workers' health. Keywords: 1.5 °C scenario, Synergistic effect, Effect monetization

Background/Aims: The objective of this study was to investigate the potential role of IL-17 in the development of nasopharyngeal carcinoma (NPC) and to screen microRNAs (miRNAs) that potentially target IL-17 in NPC cells. Methods: Blood was collected from NPC patients and normal subjects, and plasma IL-17 concentration was quantified by enzyme-linked immunosorbent assay. An immortalized normal human nasopharyngeal epithelial cell line, NP69, was treated with or without human IL-17 (15 ng/mL) for various times, and expression of IL-1ß, IL-6, IL-12, and TNF-α mRNA was assessed by real-time reverse transcription PCR. The candidate miRNAs that potentially target IL-17 were predicted by a bioinformatics strategy. The selected miR-135a mimic was transfected into primary NPC cells, and cell proliferation was assessed by MTT assay. Results: The concentration of plasma IL-17 was significantly higher in the NPC patients (92.5 ± 7.3 pg/mL) than in the control subjects (56.8 ± 2.9 pg/mL). In response to IL-17 treatment, the mRNA expression of IL-1ß and IL-6 was significantly upregulated and reached a peak at 12 h, followed by a slight decrease at 24 h, while the mRNA expression of IL-12 and TNF-α was significantly upregulated at 12 h and remained high even at 48 h after exposure to IL-17. Moreover, miR-135a specifically targets IL-17 and was dramatically downregulated in NPC cells compared with NP69 cells. Transfection of exogenous miR-135a mimic resulted in significant suppression of IL-17 secretion and subsequent inhibition of NPC cell proliferation. Conclusions: Blood IL-17 was significantly higher in NPC patients compared with normal subjects. Expression of miR-135a in the cancer cells isolated from nasopharyngeal tumors was significantly lower than that in NP69 cells, and suppression of IL-17 by miR-135a mimic resulted in significant inhibition of NPC cell proliferation. These findings suggested that downregulation of miR-135a may contribute to the development of NPC via the mechanism of IL-17 stimulation of proinflammatory cytokine expression.

When dealing with complex multiobjective problems, particle swarm optimization algorithm is easy to fall into local optimum and lead to uneven distribution. Therefore, this paper presents a hybrid multiobjective particle swarm optimization algorithm based on R2 indicator (R2HMOPSO) for solving multiobjective optimization problem. The proposed algorithm uses the sigmoid function mapping method to adjust the inertia weight and learning factors in order to tradeoffs the exploration and exploitation process effectively. In addition, simulation binary crossover operator is designed to reinitialize the particles to improve the search capability of the algorithm and to prevent particles from falling into local optimum and premature convergence. R2 indicator is incorporated into the R2HMOPSO algorithm so as to deal with the solutions of uneven distribution on the true Pareto front. Besides, polynomial mutation is used to maintain diversity in the external archive. The improved algorithm is evaluated on standard benchmarks. By comparing it with four state-of-the-art multiobjective optimization algorithms, the simulation results show that R2HMOPSO algorithm is competitive and effective in terms of convergence and distribution.

Scutellarin, a bioactive flavone isolated from Scutellaria baicalensis, has anti-inflammatory, anti-neurotoxic, anti-apoptotic and anti-oxidative effects and has been used to treat cardiovascular and cerebrovascular diseases in China. However, the mechanisms by which scutellarin mediates neuroprotection in cerebral ischemia remain unclear. The interaction between scutellarin and nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) was assessed by molecular docking study, which showed that scutellarin selectively binds to NOX2 with high affinity. Cultures of primary astrocytes isolated from the cerebral cortex of neonatal Sprague-Dawley rats were pretreated with 2, 10 or 50 μM scutellarin for 30 minutes. The astrocytes were then subjected to oxygen/glucose deprivation by incubation for 2 hours in glucose-free Dulbecco's modified Eagle's medium in a 95% N2/5% CO2 incubator, followed by simulated reperfusion for 22 hours. Cell viability was assessed by cell counting kit-8 assay. Expression levels of NOX2, connexin 43 and caspase-3 were assessed by western blot assay. Reactive oxygen species were measured spectrophotometrically. Pretreatment with 10 or 50 μM scutellarin substantially increased viability, reduced the expression of NOX2 and caspase-3, increased the expression of connexin 43, and diminished the levels of reactive oxygen species in astrocytes subjected to ischemia-reperfusion. We also assessed the effects of scutellarin in vivo in the rat transient middle cerebral artery occlusion model of cerebral ischemia-reperfusion injury. Rats were given intraperitoneal injection of 100 mg/kg scutellarin 2 hours before surgery. The Bederson scale was used to assess neurological deficit, and 2,3,5-triphenyltetrazolium chloride staining was used to measure infarct size. Western blot assay was used to assess expression of NOX2 and connexin 43 in brain tissue. Enzyme-linked immunosorbent assay was used to detect 8-hydroxydeoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (4-HNE) and 3-nitrotyrosin (3-NT) in brain tissue. Immunofluorescence double staining was used to determine the co-expression of caspase-3 and NeuN. Pretreatment with scutellarin improved the neurological function of rats with focal cerebral ischemia, reduced infarct size, diminished the expression of NOX2, reduced levels of 8-OHdG, 4-HNE and 3-NT, and reduced the number of cells co-expressing caspase-3 and NeuN in the injured brain tissue. Furthermore, we examined the effect of the NOX2 inhibitor apocynin. Apocynin substantially increased connexin 43 expression in vivo and in vitro. Collectively, our findings suggest that scutellarin protects against ischemic injury in vitro and in vivo by downregulating NOX2, upregulating connexin 43, decreasing oxidative damage, and reducing apoptotic cell death.

Suffering from structural deterioration and natural disasters, the resilience of civil structures in the face of extreme loadings inevitably drops, which may lead to catastrophic structural failure and presents great threats to public safety. Earthquake-induced extreme loading is one of the major reasons behind the structural failure of buildings. However, many buildings in earthquake-prone areas of China lack safety monitoring, and prevalent structural health monitoring systems are generally very expensive and complicated for extensive applications. To facilitate cost-effective building-safety monitoring, this study investigates a method using cost-effective MEMS accelerometers for buildings’ rapid after-earthquake assessment. First, a parameter analysis of a cost-effective MEMS sensor is conducted to confirm its suitability for building-safety monitoring. Second, different from the existing investigations that tend to use a simplified building model or small-scaled frame structure excited by strong motions in laboratories, this study selects an in-service public building located in a typical earthquake-prone area after an analysis of earthquake risk in China. The building is instrumented with the selected cost-effective MEMS accelerometers, characterized by a low noise level and the capability to capture low-frequency small-amplitude dynamic responses. Furthermore, a rapid after-earthquake assessment scheme is proposed, which systematically includes fast missing data reconstruction, displacement response estimation based on an acceleration response integral, and safety assessment based on the maximum displacement and maximum inter-story drift ratio. Finally, the proposed method is successfully applied to a building-safety assessment by using earthquake-induced building responses suffering from missing data. This study is conducive to the extensive engineering application of MEMS-based cost-effective building monitoring and rapid after-earthquake assessment.

Abstract Background Defects of the growth arrest DNA damage-inducible gene 45β (Gadd45β) play an important role in the progression of tumor and confer resistance to chemotherapy. However, the role of Gadd45β in the apoptosis of hepatocellular carcinoma is still not clear. Purpose of this study was to explore the effect of Gadd45β on the apoptosis of liver cancer cells, and the possible mechanism was examined. Result In this study, we first confirmed the decreased expression of Gadd45β in human liver cancer tissues and human liver cancer cell lines, when compared to the peri-tumor liver tissue and normal liver cells. And, it was found that Gadd45β could inhibit the stemness of liver cancer cells, enhancing the apoptosis of cancer cells induced by chemotherapy. Furthermore, the results showed that HCC tissues and cell lines showed a higher methylation status in Gadd45β promoter than that in peri-tumor tissues and normal liver cells. Methylation was then reversed by pretreatment of SMMC-7721 and Hep-3B with 5-azacytidine which is the DNA methyltransferase inhibitor. And the 5-azacytidine decreased the stemness of SMMC-7721 and Hep-3B, enhanced the sensitivity of SMMC-7721 and Hep-3B to cisplatin. Conclusions Methylation mediated Gadd45β expression inhibited the stemness of liver cancer cells, promoting the chemotherapy-induced apoptosis. Thus Gadd45β may be the potential target for enhancing the chemosensitivity of human hepatocellular carcinoma.

Abstract Hepatocyte nuclear factor-1beta plays an important role in the development and progression of liver cancer. In recent years, the expression of HNF-1β has been reported to be associated with risk for a variety of cancers. The purpose of this study is to investigate whether the expression of HNF-1β promotes the malignancy of HCC and its mechanism. We retrospectively investigated the expression of HNF-1β in 90 patients with hepatocellular carcinoma and found that the high expression of HNF-1β indicated poor prognosis. We overexpressed HNF-1β in liver cancer cell lines and found the expression of liver progenitor cell markers and stemness were upregulated. The invasion ability and epithelial-mesenchymal transition (EMT)-associated genes were also significantly higher in liver cancer cells overexpressing HNF-1β than in the control group. A mechanistic study suggested the activation of the Notch signalling pathway probably plays a key role downstream of HNF-1β. More importantly, HNF-1β promoted tumourigenesis of HCC cells in vivo. In conclusion, high expression of HNF-1β not only promoted the de-differentiation of HCC cells into liver cancer stem cells through activating the Notch pathway but also enhanced the invasive potential of HCC cells and EMT occurrence, which would contribute to the enhancement of cell migration and invasion.

Our previous studies have confirmed that tumor cell-released autophagosomes (TRAP) could induce the differentiation of B cells into IL-10+ regulatory B cells (Bregs) with suppressive activities on T lymphocytes. However, the mechanism of TRAP-mediated immune suppression is still largely unclear. Herein, we sought to assess the immunomodulatory effect of TRAPs on human neutrophils, a major immune cell type that infiltrates human tumor tissues. We found that TRAPs enriched from malignant effusions or ascites of cancer patients and tumor cell lines were rapidly and effectively phagocytized by neutrophils through macropinocytosis and promoted neutrophil apoptosis via reactive oxygen species (ROS) generation and caspase-3 activation. Moreover, the apoptotic neutrophils that have phagocytized TRAPs inhibited the proliferation and activation of CD4+ T and CD8+ T cells in a cell contact- and ROS-dependent manner. These findings define a novel TRAP-mediated mechanism in neutrophils that potentially suppresses the anti-tumor T cell immunity and highlight TRAPs as an important target for future tumor immunotherapy.

Metastatic melanoma is an aggressive skin cancer and is one of the global malignancies with high mortality and morbidity. It is essential to identify and verify diagnostic biomarkers of early metastatic melanoma. Previous studies have systematically assessed protein biomarkers and mRNA-based expression characteristics. However, molecular markers for the early diagnosis of metastatic melanoma have not been identified. To explore potential regulatory targets, we have analyzed the gene microarray expression profiles of malignant melanoma samples by co-expression analysis based on the network approach. The differentially expressed genes (DEGs) were screened by the EdgeR package of R software. A weighted gene co-expression network analysis (WGCNA) was used for the identification of DEGs in the special gene modules and hub genes. Subsequently, a protein-protein interaction network was constructed to extract hub genes associated with gene modules. Finally, twenty-four important hub genes (RASGRP2, IKZF1, CXCR5, LTB, BLK, LINGO3, CCR6, P2RY10, RHOH, JUP, KRT14, PLA2G3, SPRR1A, KRT78, SFN, CLDN4, IL1RN, PKP3, CBLC, KRT16, TMEM79, KLK8, LYPD3 and LYPD5) were treated as valuable factors involved in the immune response and tumor cell development in tumorigenesis. In addition, a transcriptional regulatory network was constructed for these specific modules or hub genes, and a few core transcriptional regulators were found to be mostly associated with our hub genes, including GATA1, STAT1, SP1, and PSG1. In summary, our findings enhance our understanding of the biological process of malignant melanoma metastasis, enabling us to identify specific genes to use for diagnostic and prognostic markers and possibly for targeted therapy.

Assessment of variety distinctness is important for both the registration and the protection of particular variety. However, the current testing system, which assesses a range of morphological characters of each pair of varieties grown side-by-side, is time-consuming and is not suitable for the assessment of hundreds of samples. The objective of this study was to develop a procedure for the assessment of wheat variety distinctness using simple sequence repeat (SSR) markers. A comparison between the molecular and morphological profile of 797 varieties was made. On the basis of the comparison, pairs of varieties with a genetic similarity value (GSV) ≤90% were deemed to be distinct, accounting for ∼85% of varieties assessed in wheat regional trials. For the remaining ∼15% of varieties, GSVs between different varieties were >90%, among which ∼35% were not distinct and the other ∼65% were distinct. Therefore, if given a GSV>90%, the pairs of varieties should be morphologically assessed in the field. To avoid any errors in the assessments, we proposed the elimination of contaminant plants from the sample before comparing the varietal genotypes, scoring of the genotype at each locus with a pair of allele numbers when constructing a molecular profile, and faithfully recording two alleles at a non-homozygous locus. To reduce the workload and cost, a three-grade markers comparison among varieties is suggested. In addition, 80 SSR markers and a technical procedure for assessment of wheat variety distinctness have been proposed. Based on the procedure, the distinctness assessment of ∼85% of all wheat varieties is completed in our laboratory annually. Consequently, total field assessment has been reduced considerably.

Background:. Intravascular ultrasound (IVUS) examination can provide useful information during endovascular stent graft repair. However, its actual clinical utility in thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (type B-AD) remains unclear, especially in complicated aortic dissection. We evaluated the effect of IVUS as a complementary tool during TEVAR. Methods:. From September 2011 to April 2012, we conducted a prospective cohort study of 47 consecutive patients with “complicated” type B-AD diagnosed. We divided the patients into two groups: IVUS-assisted TEVAR group and TEVAR using angiography alone group. The general procedure of TEVAR was performed. We evaluated the perioperative and follow-up events. Patient demographics, comorbidities, preoperative images, dissection morphology, details of operative strategy, intraoperative events, and postoperative course were recorded. Results:. A total of 47 patients receiving TEVAR were enrolled. Among them (females, 8.51%; mean age, 57.38 ± 13.02 years), 13 cases (27.66%) were selected in the IVUS-assisted TEVAR group, and 34 were selected in the TEVAR group. All patients were symptomatic. The average diameter values of IVUS measurements in the landing zone were greater than those estimated by computed tomography angiography (31.82 ± 4.21 mm vs. 30.64 ± 4.13 mm, P < 0.001). The technique success rate was 100%. Among the postoperative outcomes, statistical differences were only observed between the IVUS-assisted TEVAR group and TEVAR group for total operative time and the amount of contrast used (P = 0.013 and P < 0.001, respectively). The follow-up ranged from 15 to 36 months for the IVUS-assisted TEVAR group and from 10 to 35 months for the TEVAR group (P = 0.646). The primary endpoints were no statistical difference in the two groups. Conclusions:. Intraoperative IVUS-assisted TEVAR is clinically feasible and safe. For the endovascular repair of “complicated” type B-AD, IVUS may be helpful for understanding dissection morphology and decrease the operative time and the amount of contrast used.

As a critical variable to characterize the biophysical processes in ecological environment, and as a key indicator in the surface energy balance, evapotranspiration and urban heat islands, Land Surface Temperature (LST) retrieved from Thermal Infra-Red (TIR) images at both high temporal and spatial resolution is in urgent need. However, due to the limitations of the existing satellite sensors, there is no earth observation which can obtain TIR at detailed spatial- and temporal-resolution simultaneously. Thus, several attempts of image fusion by blending the TIR data from high temporal resolution sensor with data from high spatial resolution sensor have been studied. This paper presents a novel data fusion method by integrating image fusion and spatio-temporal fusion techniques, for deriving LST datasets at 30 m spatial resolution from daily MODIS image and Landsat ETM+ images. The Landsat ETM+ TIR data were firstly enhanced based on extreme learning machine (ELM) algorithm using neural network regression model, from 60 m to 30 m resolution. Then, the MODIS LST and enhanced Landsat ETM+ TIR data were fused by Spatio-temporal Adaptive Data Fusion Algorithm for Temperature mapping (SADFAT) in order to derive high resolution synthetic data. The synthetic images were evaluated for both testing and simulated satellite images. The average difference (AD) and absolute average difference (AAD) are smaller than 1.7 K, where the correlation coefficient (CC) and root-mean-square error (RMSE) are 0.755 and 1.824, respectively, showing that the proposed method enhances the spatial resolution of the predicted LST images and preserves the spectral information at the same time.

Large-scale longwall mining of shallow coal seams may cause mining-induced fractures that can project completely through to the surface. This could lead to a series of mine safety and environmental issues, further deteriorating the already fragile ecological environment in the Western mining areas in China. Therefore, an accurate and effective understanding of the spatiotemporal evolution law of mining-induced fractures in overlying strata and its relationship to upper aquifers is critical. In this paper, the application of the geophysical-chemical properties of radon in mining engineering is explored as a potential solution to the shortcomings of existing surveying methods. A radioactive measurement method is proposed for the detection of the development of mining-induced fractures from overlying strata to the surface in the Baoshan Coal Mine (BCM). The on-site test indicated that the first weighting step is approximately 60 m, the average periodic weighting step is approximately 20 m, and the influence coverage of the advanced abutment pressure is approximately 30 m. The presented method could be used as an indirect technical support to increase the safety of coal mining by acting as a simple, fast, and reliable method of detecting mining-induced fractures in overlying strata.