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TDR measures the rate of vibration decay along rail in dB/m. Higher TDR leads to lower noise radiation. However, new railways are often having low TDR due to the use of resilient fasteners (to provide vibration isolation between rail and supporting structure for ground borne noise concerns), which leads to high noise radiation. Rail damper is used to increase TDR (thus reduces railway noise), where TMD is an efficient damping mechanism dissipating the vibration energy of the rail. TMD provides reactive damping force, maximised after a few cycles of oscillations. TMD force is stronger with continuous excitation than impulse excitation. For convenient purposes in the industry, TDR measurements are primarily conducted by impulse method, which do not allow sufficient time to include reactive TMD force. Therefore, impulse excitation TDR is smaller than continuous excitation TDR. Continuous excitation TDR is considered to reflect more of the real case of wheel/rail interaction excitation during train running. Besides, TDR in terms of time decay in dB/s is an alternative approach for evaluating noise performance of the rail. This paper presents TDR measurement results under different conditions, e.g., impulse excitation against continuous excitation; freely supported short rail (~6m), short rail (~6m) with resilient fastener support as well as site measurements in continuous welded rails.

Increasing evidences showed that ovulatory dysfunction, possibly caused by luteinized unruptured follicular follicle syndrome (LUFS), is one of the reasons for endometriosis-related infertility. The present study was conducted to explore the potential effect of elevated progesterone in follicular fluid (FF) on ovulation in endometriosis. A prospective study including 50 ovarian endometriosis patients and 50 control patients with matched pairs design was conducted with alterations in FF and peritoneal fluid (PF) components identified by metabolomics analyses and differentially expressed genes in granulosa cells (GCs) identified by transcriptome analysis. Patients with endometriosis exhibited a significantly higher progesterone level in serum, FF, and PF. Granulosa cells from endometriosis patients revealed decreased expression of HPGD, COX-2, and suppressed NF-ĸB signaling. Similarly, progesterone treatment in vitro downregulated HPGD and COX2 expression and suppressed NF-ĸB signaling in granulosa tumor-like cell line KGN (Bena Culture Collection, China) and primarily cultured GCs, as manifested by decreased expressions of IL1R1, IRAK3, reduced pIĸBα/IĸBα ratio, and nucleus translocation of p65. On the contrary, TNF-α treatment increased expression of IL1R1, IRAK3, pIĸBα, p65, and HPGD in GCs. One potential p65 binding site was identified in the promoter region of HPGD by chromatin immunoprecipitation. In conclusion, we found that intrafollicular progesterone might downregulate HPGD and COX-2 in GCs via suppressing the NF-ĸB signaling pathway, shedding light on the mechanism underlying the endometriosis-related ovulatory dysfunction.

Central post-stroke pain (CPSP) is a highly refractory form of central neuropathic pain that has been poorly studied mechanistically. Recent observations have emphasized the critical role of the spinal dorsal horn in CPSP. However, the underlying mechanisms remain unclear. In this study, rats were subjected to thalamic hemorrhage to investigate the role of spinal monocyte chemoattractant protein-1 (MCP-1) and C-C motif chemokine receptor 2 (CCR2) in the development of CPSP. Immunohistochemical staining and ELISA were used to assess the expression changes of c-Fos, Iba-1, GFAP, MCP-1, and CCR2 in the dorsal horn of the lumbar spinal cord following thalamic hemorrhage, and the involvement of spinal MCP-1 in CPSP was examined by performing intrathecal anti-MCP-1 mAb injection to neutralize the spinal extracellular MCP-1. We demonstrated that intra-thalamic collagenase microinjection induced persistent bilateral mechanical pain hypersensitivity and facilitated the spontaneous pain behaviors evoked by intraplantar bee venom injection. Accompanying CPSP, the expression of c-Fos, Iba-1, and GFAP in the lumbar spinal dorsal horn was significantly increased up to 28 days post-intra-thalamic collagenase microinjection. Intrathecal injection of minocycline and fluorocitrate dramatically reverses the bilateral mechanical pain hypersensitivity. Moreover, intra-thalamic collagenase microinjection dramatically induced the up-regulation of MCP-1 but had no effect on the expression of CCR2 in the bilateral lumbar spinal dorsal horn, and MCP-1 was primarily localized in the neuron. Intrathecal injection of anti-MCP-1 mAb was also able to reverse CPSP and reduce the expression of c-Fos, Iba-1, and GFAP in the lumbar spinal dorsal horn. These findings indicated that spinal MCP-1 contributes to CPSP by mediating the activation of spinal neurons and glial cells following thalamic hemorrhage stroke, which may provide insights into pharmacologic treatment for CPSP.

This study analyzed the role of G1 to S phase transition 1 protein (GSPT1) in promoting progression of liver cancer cells.A bioinformatics database was used to analyze the expression levels of GSPT1 in liver cancer tissues and the prognosis of patients. Subsequently, Western blotting and quantitative PCR were used to verify the expression levels of GSPT1 between normal hepatocytes and hepatoma cells. We used a CRISPR/Cas9 system to construct knockouts of GSPT1 in HepG2 and HCCLM9 liver cancer cells. The effect of GSPT1 on liver cancer cell migration and invasion was analyzed using flow cytometry, migration, and tumor formation assays.The Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset indicated that GSPT1 expression was upregulated in liver cancer cell lines, and patients with liver cancer had poor prognosis. Knockout of GSPT1 in cells significantly inhibited tumor proliferation, cell migration, and growth in vivo.In this study, we found that GSPT1 promotes the migration and invasion of liver cancer cells.

Tripartite motif (TRIM) proteins comprise a large family of RING-type ubiquitin E3 ligases that regulate important biological processes. In this study, full-length MnTRIM32 cDNA was obtained from oriental river prawn Macrobrachium nipponense, and eight MnTRIM32 isoforms generated by alternative splicing were identified. The open reading frames of the eight MnTRIM32 isoforms were predicted to be separately composed of 402, 346, 347, 346, 414, 358, 359, and 358 amino acid residues. Protein structural analysis revealed that all MnTRIM32 isoforms contained a RING domain and a coiled coil region. MnTRIM32 was ubiquitously expressed in all tissues tested, with the highest expression in the hepatopancreas. The mRNA levels of MnTRIM32 in the gills, stomach, and intestine of prawns were found to undergo time-dependent enhancement following white spot syndrome virus (WSSV) stimulation. Double-stranded RNA interference studies revealed that MnTRIM32 silencing significantly downregulated the expression levels of interferon (IFN) regulatory factor MnIRF, IFN-like factor MnVago4, and tumor necrosis factor MnTNF. Furthermore, knockdown of MnTRIM32 in WSSV-challenged prawns increased the expression of VP28 and the number of WSSV copies, suggesting that MnTRIM32 plays a positive role in limiting WSSV infection. These findings provided strong evidence for the important role of MnTRIM32 in the antiviral innate immunity of M. nipponense.

To investigate the instability behaviours of municipal solid waste under the reduction of effective means stress, consolidated undrained (CU), constant shear drained (CSD) and constant shear undrained (CSU) tests were conducted on artificial waste specimens. In CU tests, the effective stress paths were modified by considering the particle compressibility, and the waste specimens did not exhibit pre-failure softening behaviours. Instability of the waste was observed in CSD tests, but was not observed in CSU tests. When the waste specimens became unstable, the axial strains increased rapidly and the volume was severely dilated. Softening of the waste specimens, manifested in the inability to maintain constant deviatoric stresses, was also observed. For waste specimens with similar void ratios, the instability points were located around an instability line (IL), and the slope of the IL decreased with an increase in the void ratio. Some factors, including the stress path and deformation characteristic of waste, may lead to the instability of waste specimens in CSD tests by influencing the effects of reinforcements. In engineered landfills, high pore pressure is often generated in waste mass and then leads to the obvious reduction of the effective stress of waste; thus, waste instability needs to be considered in the safety evaluation of waste slopes.

The assumption that the gas is a connected phase leads to underestimation of the gas pressure in municipal solid waste (MSW) landfills. In this study, the high gas pressure is shown, by way of field investigations and laboratory experiments, to be caused by foam in the landfills. The field investigations indicated that environmental disasters that have occurred at several landfills in China were caused by high gas or pore pressures. During drilling in these landfills, it was found that a mixture of foam and leachate was ejected from the borehole. The laboratory experiments indicated that foam generation in the landfills was attributable to the two-stage anaerobic biodegradation behaviours of MSWs. Volatile fatty acids (VFAs) decreased the surface tension of the leachate, enabling it to generate foam. The foam's composite index was adopted to evaluate foaming ability and foam stability of the leachate. Meanwhile, the liquid film in the foam divided the gas into a disconnected phase and remarkably increased its flow resistance. An experimental apparatus was designed to compare quantitatively the flow resistances of foam and gas in MSWs. When the foam and gas were injected into a saturated waste column at the same rate, the pressure drop of the foam (412 kPa) was 2·54 times that of the connected-phase gas (162 kPa), thereby resulting in lower residual liquid saturation for foam displacement. The unsaturated permeability coefficient of the foam was about an order of magnitude lower than that of the gas. Owing to the low permeability of waste to foam and continuous gas generation, high gas pressures are easily developed in wet landfills.

Niacin is indispensable for the growth and development of aquatic animals. However, the correlations between dietary niacin supplementations and the intermediary metabolism of crustaceans are still poorly elucidated. This study explored the effects of different dietary niacin levels on the growth, feed utilization, energy sensing, and glycolipid metabolism of oriental river prawn Macrobrachium nipponense. Prawns were fed with different experimental diets containing graded niacin levels (15.75, 37.62, 56.62, 97.78, 176.32, and 339.28 mg/kg, respectively) for 8 weeks. Weight gain, protein efficiency, feed intake, and hepatopancreas niacin contents all maximized in the 176.32 mg/kg group with significance noted with the control group ( P < 0.05 ), whereas the opposite was true for feed conversion ratio. Hepatopancreas niacin concentrations increased significantly ( P < 0.05 ) as dietary niacin levels increased, and peaked at the 339.28 mg/kg group. Hemolymph glucose, total cholesterol, and triglyceride concentrations all maximized in the 37.62 mg/kg group, while total protein concentration reached the highest value in the 176.32 mg/kg group. The hepatopancreas mRNA expression of AMP-activated protein kinase α and sirtuin 1 peaked at the 97.78 and 56.62 mg/kg group, respectively, and then both decreased as dietary niacin levels increased furtherly ( P < 0.05 ). Hepatopancreas transcriptions of the genes related to glucose transportation, glycolysis, glycogenesis, and lipogenesis all increased with increasing niacin levels up to 176.32 mg/kg, but decreased significantly ( P < 0.05 ) as dietary niacin levels increased furtherly. However, the transcriptions of the genes related to gluconeogenesis and fatty acid β-oxidation all decreased significantly ( P < 0.05 ) as dietary niacin levels increased. Collectively, the optimum dietary niacin demand of oriental river prawn is 168.01-169.08 mg/kg. In addition, appropriate doses of niacin promoted the energy-sensing capability and glycolipid metabolism of this species.

Vibration control of composite structures with distributed masses under random loadings is a significant issue. Adjustability of dynamic characteristics including response spectrum peaks and valleys is important for structural vibration control. The vibration control design in space contains structure and conformation designs which combination results in periodic composite structures. In the present paper, spatial periodicity control design is proposed. Stochastic response adjustable performance of a visco-elastomer sandwich plate with harmonic distribution of geometrical and physical parameters and distributed supported masses under random base motion loading is studied. Both facial layer thickness and core layer modulus of the sandwich plate are considered as harmonic distribution in length and width directions as well as periodically distributed masses. Partial differential equations of coupling motions of the sandwich plate system are derived and converted into ordinary differential equations for multi-mode coupling vibration. Generalized stiffness, damping, and mass coefficients are functions of the harmonic distribution parameters. An analysis solution with frequency response function and response spectral density expressions of the sandwich plate system is obtained. Numerical results are given to show the response adjustable performance through the harmonic geometrical and physical parameters and distributed masses. The results have a potential application to stochastic vibration control or dynamic optimization design of smart composite structure systems.

Bulbus eleutherinis is a classical traditional Dai medicine, and has been widely used in clinical treatment of coronary heart disease (CHD) in Yunnan, China. Naphthoquinone, as the main active compound in Bulbus eleutherinis in treating CHD, mainly contain isoeleutherin, eleutherin, and eleutherol. This study aimed to investigate the in vivo parameters of isoeleutherin, eleutherin, and eleutherol. In this work, male Sprague Dawley (SD) rats were treated with the three compounds by oral administration, and then blood and tissue samples were collected. A novel UPLC-MS/MS (ultra-performance liquid chromatography-tandem mass spectrometry) method has been developed to determine the absolute oral bioavailability, and the tissue distribution profile of the compounds. Acetonitrile and 0.1% (v/v) solution of formic acid were selected as the mobile phase of the chromatogram. C18 column was employed. Betamethasone was used as an internal standard in the method. The detection was performed with a multireaction monitor of scan type in positive ion mode by MS/MS. Our data showed linearity of the method with r over 0.9983. Lower limits of quantification of isoeleutherin, eleutherin, and eleutherol were 1.00, 3.84, and 0.498 ng/mL, respectively. The overall precision of the compounds was less than 12.68%, recoveries ranged from 85.44 to 103.83%, and the accuracy of the compounds in plasma was between 91.56 and 110.75%. The stability assay showed that they were stable (87.83–114.62%) under different conditions in plasma. For oral administration, the half-lives of isoeleutherin, eleutherin, and eleutherol was 6.11, 7.30, and 3.07 hours, respectively. The absolute oral bioavailabilities were 5.38, 4.64, and 2.47%, respectively. Moreover, the three components had the highest distribution in small intestine. In conclusion, the established method was successfully applied to the determination of the in vivo parameters of the three components in SD rats. This work provides a reference for the development of new drugs of Bulbus eleutherinis in the future.

Zhuang-E Shi,1 Meng-Yu Zhang,1 Jian-Yu Liu,1 Wen-Di Zhang,1 Dong-Mei Hu,1 Qing-Xiang Wang,1 Xiu-Li Ji,2 Yuan-Yuan Jiang,3 Yi-Qing Qu3 1Department of Pulmonary and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Shandong Key Laboratory of Infectious Respiratory Diseases, Jinan, People’s Republic of China; 2Department of Pulmonary Disease, Jinan Traditional Chinese Medicine Hospital, Jinan, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, Qilu Hospital of Shandong University, Shandong Key Laboratory of Infectious Respiratory Diseases, Jinan, People’s Republic of ChinaCorrespondence: Yi-Qing Qu, Department of pulmonary and Critical Care Medicine, Qilu Hospital of Shandong University, Shandong Key Laboratory of Infectious Respiratory Diseases, Jinan, People’s Republic of China, Tel +86 531 8216 9335, Fax +86 531 8296 7544, Email quyiqing@sdu.edu.cnPurpose: Chronic obstructive pulmonary disease (COPD) is a predominant cause of mortality worldwide. Autophagy, which depends on a lysosomal degradation pathway, plays an essential role in the occurrence of COPD. The aim of our study was to identify the potential function of autophagy and construct a BCL2-related competing endogenous RNA (ceRNA) network that induces autophagy in COPD.Methods: Blood sample data from GSE31568, GSE24709, and GSE61741 were collected from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs in COPD and controls were identified via GEO2R. Transcription factors were obtained from FunRich. DIANA, miRDB, miRTarBase, and TargetScan were used to predict target genes of miRNAs. Autophagy genes were collected from the Human Autophagy Database (HADb). The GSE151052 dataset was used to identify autophagy-related differentially expressed genes in tissues. Functional enrichment and protein–protein interaction (PPI) network analyses were conducted via Metascape and the STRING network. Spearman correlation analysis was used to analyze the relationship between autophagy-related differentially expressed genes and lung function. The BCL2-related ceRNA network was modeled by Cytoscape.Results: We obtained 41 differentially expressed miRNAs and 10 significantly different transcription factors. We identified 19 autophagy-related differentially expressed genes that were significantly different (P< 0.05) in tissue samples. The most significant enrichment in Metascape was an autophagy item, which further confirmed autophagy participation in the occurrence of COPD. PPI network analysis found four genes (BCL2, BECN1, MAPK8, and ITPR1), among which BCL2 was correlated with both FEV1/FVC and FEV1 prediction. Finally, the BCL2-related ceRNA network was constructed to clarify the interaction of RNAs and occurrence of autophagy, including 18 miRNAs and 65 lncRNAs.Conclusion: We identified 19 autophagy-related differentially expressed genes that participated in COPD; among them, BCL2 was correlated with lung function, and a BCL2-related ceRNA network was constructed, which further revealed the potential mechanism of autophagy involvement in COPD.Keywords: COPD, autophagy, bioinformatics, lung function, BCL2, ceRNA

A Bayesian dynamic linear model (BDLM) framework for data modeling and forecasting is proposed to evaluate the performance of an operational cable-stayed bridge, that is, Ting Kau Bridge in Hong Kong, by using SHM strain field data acquired. One of the major challenges in dealing with the existing in-service bridge under extreme typhoon loads is to forecast structural behavior using the typhoon response exhibiting non-stationarity, large data fluctuations and strong randomness. The first attempt for SHM data modeling during extreme events, that is, typhoons, using BDLM framework, was conducted in this study. The data from multiple sensors are analyzed for one-step, multi-step ahead forecasting and missing data imputation. The overall bridge behavior is incorporated into a forecasting model by superposition of forecasting results of trend (representing the structural baseline response), periodic component (response component evolving regularly over time), and autoregressive component (time-dependent error) through BDLM algorithm. The results demonstrate that the BDLM framework yielded more accurate calculations compared with Gaussian process and Variational Heteroscedasticity Gaussian Process methods with respect to one-step ahead forecasting for strain data under typhoons. Multi-step ahead forecasting was successfully carried out both for non-typhoon and typhoon responses within an acceptable precision range. The correlation between periodic component and temperature was also investigated. Regarding missing data imputation, BLDM algorithm can generate robust results due to making full use of the monitoring data both before and after the missing segments.

Herein, we revealed the factors that affect the emission in mixed-ligand metal-organic frameworks (MOFs) with the combination of terephthalic acid (BDC), 2-aminoterephthalic acid (BDC-NH

Background Aberrant post transcriptional modifications of RNA, such as 5-methylcytosine modifications, have been frequently observed in breast cancer (BC). The M5C core catalytic enzyme NSUN2 gene was found to be co-amplified with the oncogenic transcription factor MYC in BC. However, the function of m5C modification in the immune response and metabolism to BC remains unknown. Therefore, we aimed to investigate the crosstalk between NSUN2 and MYC in BC microenvironment. Methods We investigated the function of NSUN2 in breast cancer using vivo and vitro assays. Next, the co-occurrence of NSUN2 and MYC in BC were tested by cBioPortal analysis. Co-immunoprecipitation and mass spectrometry were performed to determine the interact between NSUN2 and MYC. Then, correlation between the expression of NSUN2 and BC microenvironment were explored by CAMOIP, PCR and western-blotting. Additionally, RNA sequencing (RNA-Seq), Gene Set Enrichment Analysis (GSEA) were used to investigate the underlying mechanism of NSUN2 in BC. Results In the current study, increased expression of NSUN2 was observed in BC tissue compared to that in the adjacent normal tissue. Elevated NSUN2 levels were associated with poor prognosis in patients with BC. NSUN2 knockout (KO) suppressed cell proliferation, migration, and invasion; induced apoptosis in vitro; and repressed tumor growth in vivo. Subsequently, we determined NSUN2 can interact with MYC protein, and found that immune infiltration and glycolysis were increased in the NSUN2 KO BC cell line. In addition, RNA sequencing demonstrated that the differentially expressed genes in BC cells after NSUN2 KO were significantly enriched in the negative regulation of immune processes and metabolic processes. Conclusions Overall, NSUN2 overexpression drove immunosuppression and promoted BC progression. NSUN2 can interact with MYC protein, thereby being involved in the functional regulation of MYC target genes. Our findings suggest that NSUN2 may act as a potential therapeutic target for BC in the context of MYC amplification.

The brown planthopper (BPH), Nilaparvata lugens, is one of the most destructive pests of rice. Given the threats posed by insecticide resistance to its control, eco-friendly strategies based on microbial pathogens emerged as a promising biocontrol alternative. In the present study, we isolated a native fungal pathogen against BPH from infected BPH cadavers and preliminarily identified as a strain of Aspergillus fumigatus based on morphological and molecular methods. Laboratory bioassay revealed that this fungal strain was highly virulent to BPH both at nymphal and adult stages, with the median lethal times (LT50) of 7.5 and 5.8 days under high conidial concentration of 1 × 109 conidia mL–1. A genome-wide view of gene expressions in BPH against fungal attack was analyzed by transcriptomic sequencing and consequently a large number of differentially expressed genes that mainly involved in host immune defense and cell detoxification were found. RNAi-mediated knockdown of an upregulated gene encoding a serine protease (NlSPN) could cause a significant decrease in BPH survival. Combination of dsRNA injection and fungal infection showed an additive effect on BPH mortality, which provided clues to develop new pest management strategies against BPH.

Spatial cognition enables animals to navigate the environment. Impairments in spatial navigation are often preclinical signs of Alzheimer’s disease (AD) in human. Therefore, evaluating spatial memory deficits is valuable when assessing incipient AD in animal models. The Chinese tree shrew, a close relative of primates, possesses many features that make it suitable for AD research. However, there is a scarcity of reliable behavior paradigms to monitor changes in spatial cognition in this species. To address this, we established reward-based paradigms in the radial-arm maze and the cheeseboard maze for tree shrew, and tested spatial memory of a group of twelve male animals in both tasks, along with a control water maze test, before and after bilateral lesions to the hippocampus, the brain region essential for spatial navigation. Tree shrews memorized target positions during training, and their task performance improved gradually until reaching a plateau in all three mazes. After the lesion, spatial learning was compromised in both newly-developed tasks, whereas memory retrieval was impaired in the water maze. Furthermore, individual task performance in both dry-land paradigms depended heavily on the size of remaining hippocampal tissue. Notably, all lesioned animals displayed spatial memory deficits in the cheeseboard task, but not in the other two paradigms. Our results suggest that the cheeseboard task currently represents the most sensitive paradigm for assessing spatial memory in tree shrew, with the potential to monitor progressive cognitive declines in aged or genetically modified animals developing AD-like symptoms.Significance StatementCognitive tests that monitor impairments in spatial memory play a crucial role in evaluating animal models with early-stage Alzheimer’s disease (AD). The Chinese tree shrew possesses many features suitable for an AD model, yet behavior tests assessing spatial cognition in this species are lacking. Here we developed novel behavior paradigms tailored to measure spatial memory in tree shrews and evaluated their sensitivity to changes in spatial learning by examining a group of hippocampus-lesioned animals. Our results indicate that the cheeseboard task effectively detects impairments in spatial memory and holds potential for monitoring the progressive cognitive decline in aged or genetically modified tree shrews that develop AD-like symptoms. This research may facilitate the use of tree shrew model in AD research.

Background Melatonin is considered to be a polyfunctional master regulator in animals and higher plants. Exogenous melatonin inhibits plant infection by multiple diseases; however, the role of melatonin in Cucumber green mottle mosaic virus (CGMMV) infection remains unknown. Results In this study, we demonstrated that exogenous melatonin treatment can effectively control CGMMV infection. The greatest control effect was achieved by 3 days of root irrigation at a melatonin concentration of 50 μM. Exogenous melatonin showed preventive and therapeutic effects against CGMMV infection at early stage in tobacco and cucumber. We utilized RNA sequencing technology to compare the expression profiles of mock-inoculated, CGMMV-infected, and melatonin+CGMMV-infected tobacco leaves. Defense-related gene CRISP1 was specifically upregulated in response to melatonin, but not to salicylic acid (SA). Silencing CRISP1 enhanced the preventive effects of melatonin on CGMMV infection, but had no effect on CGMMV infection. We also found exogenous melatonin has preventive effects against another Tobamovirus, Pepper mild mottle virus (PMMoV) infection. Conclusions Together, these results indicate that exogenous melatonin controls two Tobamovirus infections and inhibition of CRISP1 enhanced melatonin control effects against CGMMV infection, which may lead to the development of a novel melatonin treatment for Tobamovirus control.

Aim To evaluate association between pretreatment serum metrics and best corrected visual acuity ( BCVA) of patients with macular edema secondary to retinal vein occlusion and its subtypes after intravitreal ranibizumab or conbercept implant. Methods This prospective research included 201 patients(201 eyes) who were diagnosed with macular edema secondary to retinal vein occlusion at Heibei Eye Hospital between January 2020 and January 2021, who all received intravitreal anti- vascular endothelial growth factor treatment. Serum metrics were measured before the first treatment, and correlations between BCVA and each of four parameters— platelets, neutrophil- to- lymphocyte ratio(NLR), platelet- to- lymphocyte ratio(PLR) and monocyte- to- lymphocyte ratio(MLR)— were analyzed to identify predictors of effective intravitreal injection treatment outcomes. Results The mean platelets was significantly different in the effective and ineffective group for RVO-ME (273.02 ± 41.49 × 109/L,214.54 ± 44.08 × 109/L P Conclusion Higher pretreatment platelets and PLR were associated with BCVA in patients with RVO- ME and its subtypes who were treated with anti- VEGF drugs. The platelets and PLR may be used as predictive and prognostic tools for effective intravitreal injection treatment outcomes.

The ER-tropic viruses hijack the host cellular ER as the replication platform of the life cycle, which can lead to strong ER stress. The UPR and related transcriptional cascades triggered by ER stress play a crucial role in viral replication and pathogenesis, but little is known about these underlying mechanisms.

Supplementary Table S2 lists the target sequences for siRNAs.

Supplementary material and methods described the details, including cell culture, in situ hybridization, cell proliferation and colony formation assay, wound healing assay, cell invasion assays, western blot, RIP and ChIP assays, co-immunoprecipitation, and luciferase reporter assay.

Accumulating evidence suggests that long noncoding RNA (lncRNA) plays important regulatory roles in cancer biology. However, the involvement of lncRNA in colorectal carcinoma progression remains largely unknown, especially in colorectal carcinoma metastasis. In this study, we investigated the changes in lncRNA expression in colorectal carcinoma and identified a new lncRNA, the antisense transcript of SATB2 (SATB2-AS1), as a key regulator of colorectal carcinoma progression. SATB2-AS1 was frequently downregulated in colorectal carcinoma cells and tissues, and patients whose tumors expressed SATB2-AS1 at low levels had a shorter overall survival and poorer prognosis. Downregulation of SATB2-AS1 significantly promoted cell proliferation, migration, and invasion in vitro and in vivo, demonstrating that it acts as a tumor suppressor in colorectal carcinoma. SATB2-AS1 suppressed colorectal carcinoma progression by serving as a scaffold to recruit p300, whose acetylation of H3K27 and H3K9 at the SATB2 promoter upregulated expression of SATB2, a suppressor of colorectal carcinoma growth and metastasis. SATB2 subsequently recruited HDAC1 to the Snail promoter, repressing Snail transcription and inhibiting epithelial-to-mesenchymal transition. Taken together, these data reveal SATB2-AS1 as a novel regulator of the SATB2-Snail axis whose loss facilitates progression of colorectal carcinoma.Significance:These data show that the lncRNA SATB2-AS1 mediates epigenetic regulation of SATB2 and Snail expression to suppress colorectal cancer progression.See related commentary by Li, p. 3536

Supplementary Table S1 lists the primer sequences used for PCR.

Supplementary Figures S1 through S11. (1) Supplementary Figure S1 shows the ectopical overexpressing of SATB2-AS1 in two CRC cell lines by lentivirus delivery. (2) Supplementary Figure S2 shows the effect of SATB2-AS1 on apoptosis in CRC cells. (3) Supplementary Figure S3 shows the effect of SATB2-AS1 knockdown mediated by siRNA on CRC cell proliferation, invasion and migration in vitro. (4) Supplementary Figure S4 shows the expression levels of SATB2 mRNA in CRC and adjacent non-cancerous tissues. (5) Supplementary Figure S5 shows the regulatory effect of SATB2-AS1 expression by SATB2. (6) Supplementary Figure S6 shows the effect of SATB2-AS1 on SATB2 mRNA stability. (7) Supplementary Figure S7 shows the enrichment amount of ZEB1-AS1 and PACER RNA with the p300 antibody by RIP assay. (8) Supplementary Figure S8 shows the regulatory effect of SATB2-AS1 on p300 mRNA. (9) Supplementary Figure S9 shows the inhibitory effects of SATB2-AS1 on M5 cells requiring p300 and SATB2. (10) Supplement Figure S10 shows the occupancy ability of p300 on Snail promoter by ChIP assay. (11) Supplementary Figure S11 shows the regulatory effect of Snail on SATB2-AS1 expression.

Supplementary Table S3 shows the correlation between the clinicopathological features and SATB2-AS1 expression.

Background Central post-stroke pain (CPSP) is an intractable and disabling central neuropathic pain that severely affects patients’ lives, well-being, and socialization abilities. However, CPSP has been poorly studied mechanistically and its treatment remains challenging. Here, we used a rat model of CPSP induced by thalamic hemorrhage to investigate its underlying mechanisms and the effect of stellate ganglion block (SGB) on CPSP and emotional comorbidities. Methods Thalamic hemorrhage was produced by injecting collagenase IV into the ventral-posterolateral nucleus (VPL) of the right thalamus. The up-and-down method with von Frey hairs was used to measure the mechanical allodynia. Behavioral tests were carried out to examine depressive and anxiety-like behaviors including the open field test (OFT), elevated plus maze test (EPMT), novelty-suppressed feeding test (NSFT), and forced swim test (FST). The peri-thalamic lesion tissues were collected for immunofluorescence, western blotting, and enzyme-linked immunosorbent assay (ELISA). Genetic knockdown of thalamic hypoxia-inducible factor-1α (HIF-1α) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) with microinjection of HIF-1α siRNA and NLRP3 siRNA into the VPL of thalamus were performed 3 days before collagenase injection into the same regions. Microinjection of lificiguat (YC-1) and MCC950 into the VPL of thalamus were administrated 30 min before the collagenase injection in order to inhibited HIF-1α and NLRP3 pharmacologically. Repetitive right SGB was performed daily for 5 days and laser speckle contrast imaging (LSCI) was conducted to examine cerebral blood flow. Results Thalamic hemorrhage caused persistent mechanical allodynia and anxiety- and depression-like behaviors. Accompanying the persistent mechanical allodynia, the expression of HIF-1α and NLRP3, as well as the activities of microglia and astrocytes in the peri-thalamic lesion sites, were significantly increased. Genetic knockdown of thalamic HIF-1α and NLRP3 significantly attenuated mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. Further studies revealed that intra-thalamic injection of YC-1, or MCC950 significantly suppressed the activation of microglia and astrocytes, the release of pro-inflammatory cytokines, the upregulation of malondialdehyde (MDA), and the downregulation of superoxide dismutase (SOD), as well as mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. In addition, repetitive ipsilateral SGB significantly restored the upregulated HIF-1α/NLRP3 signaling and the hyperactivated microglia and astrocytes following thalamic hemorrhage. The enhanced expression of pro-inflammatory cytokines and the oxidative stress in the peri-thalamic lesion sites were also reversed by SGB. Moreover, LSCI showed that repetitive SGB significantly increased cerebral blood flow following thalamic hemorrhage. Most strikingly, SGB not only prevented, but also reversed the development of mechanical allodynia and anxiety- and depression-like behaviors induced by thalamic hemorrhage. However, pharmacological activation of thalamic HIF-1α and NLRP3 with specific agonists significantly eliminated the therapeutic effects of SGB on mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. Conclusion This study demonstrated for the first time that SGB could improve CPSP with comorbid anxiety and depression by increasing cerebral blood flow and inhibiting HIF-1α/NLRP3 inflammatory signaling.

Background: Endothelial cells in the tumor microenvironment play an important role in the development of kidney renal clear cell carcinoma (KIRC). We wanted to further identify the function of endothelial cells in KIRC patients by integrating single-cell and bulk RNA sequencing data.Methods: Online databases provide the original data of this study. An endothelial-related prognostic index (ERPI) was constructed and validated by R version 3.6.3 and relative packages.Results: The ERPI consisted of three genes (CCND1, MALL, and VWF). Patients with high ERPI scores were significantly correlated with worse prognosis than those with low ERPI scores in the TCGA training group, TCGA test group, and GSE29609 group. A positive correlation was identified between the ERPI score and poor clinical features. The results of functional analysis indicated that ERPI was significantly associated with immune-related activities. We suggested that patients with high ERPI scores were more likely to benefit from immunotherapy based on the results of immune checkpoints, tumor microenvironment, stemness index, and TCIA, while patients with low ERPI scores were sensitive to gemcitabine, docetaxel, paclitaxel, axitinib, pazopanib, sorafenib, and temsirolimus according to the results of the “pRRophetic” algorithm. Therefore, this ERPI may help doctors choose the optimal treatment for patients with KIRC.Conclusion: By integrating single-cell and bulk RNA sequencing data from KIRC patients, we successfully identified the key genes from the perspective of endothelial cells in the tumor microenvironment and constructed ERPIs that had positive implications in precision medicine.

Liver fibrosis is the common consequence of almost all liver diseases and has become an urgent clinical problem without efficient therapies. Recent evidence has shown that hepatocytes-derived extracellular vesicles (EVs) play important roles in liver pathophysiology, but little is known about the role of damaged hepatocytes-derived EVs in hepatic stellate cell (HSC) activation and following fibrosis. Tetramethylpyrazine (TMP) from Ligusticum wallichii Franchat exhibits a broad spectrum of biological activities including liver protection. In this study, we investigated whether TMP exerted liver-protective action through regulating EV-dependent intercellular communication between hepatocytes and HSCs. Chronic liver injury was induced in mice by CCl

The proton conductivity of a single crystal of Co–Co phosphonate along the c axis is 1.5 times higher than that of isostructural Ni–Co phosphonate, originating from the slight pKa difference of water molecules coordinated to Co2+ or Ni2+ centers.

Objective To develop and validate a nomogram model for predicting chronic ocular graft-versus-host disease (coGVHD) in patients after allogenic haematopoietic stem cell transplantation (allo-HSCT). Methods This study included 61 patients who survived at least 100 days after allo-HSCT. Risk factors for coGVHD were screened using LASSO regression, then the variables selected were subjected to logistic regression. Nomogram was established to further confirm the risk factors for coGVHD. Receiver operating characteristic (ROC) curves were constructed to assess the performance of the predictive model with the training and test sets. Odds ratios and 95% confidence intervals (95% CIs) were calculated by using logistic regression analysis. Results Among the 61 patients, 38 were diagnosed with coGVHD. We selected five texture features: lymphocytes (LYM) (OR = 2.26), plasma thromboplastin antecedent (PTA) (OR = 1.19), CD3 + CD25 + cells (OR = 1.38), CD3 + HLA-DR + cells (OR = 0.95), and the ocular surface disease index (OSDI) (OR = 1.44). The areas under the ROC curve (AUCs) of the nomogram with the training and test sets were 0.979 (95% CI, 0.895–1.000) and 0.969 (95% CI, 0.846–1.000), respectively.And the Hosmer–Lemeshow test was nonsignificant with the training (p = 0.9949) and test sets (p = 0.9691). Conclusion We constructed a nomogram that can assess the risk of coGVHD in patients after allo-HSCT and help minimize the irreversible loss of vision caused by the disease in high-risk populations.

Additional file 1: Figure S1. Transcriptome sequencing quality. Figure S2. Silence efficiency of CRISP1 at VIGS 10 dpi. Figure S3. Expression level of PR1a in response to CGMMV and melatonin treatment. Figure S4. Original picture for Fig.1. Figure S5. Original picture for Fig.2. Figure S6. Original picture for Fig.5. Figure S7. Original picture for Fig.7C. Figure S8. Original picture for Fig.7F.