lncRNA PAARH impacts liver cancer cell proliferation by engaging miR­6512­3p to target LASP1.

Long non-coding (lnc)RNAs serve a pivotal role as regulatory factors in carcinogenesis. The present study aimed to assess the involvement of the lncRNA progression and angiogenesis-associated RNA in hepatocellular carcinoma (PAARH) in liver cancer, along with the associated underlying mechanism. Through the use of reverse transcription-quantitative (RT-q)PCR, differences in the expression levels of PAARH in HepG2, HEP3B2.1.7, HCCLM3, Huh-7 and MHCC97-H liver cancer cell lines and THLE-2 epithelial cell lines were evaluated. The liver cancer cell line with the greatest, significantly different, level of expression relative to the normal liver cell line was selected for subsequent experiments. Using ENCORI database, the putative target genes of the microRNA (miR) miR-6512-3p were predicted. Cells were then transfected with lentiviruses carrying short-hairpin-PAARH to interfere with PAARH expression. Subsequently, HepG2 liver cancer cells were transfected with a miR-6512-3p mimic and an inhibitor, and the expression levels of miR-6512-3p and the LIM and SH3 domain protein 1 (LASP1) in cells were assessed using RT-qPCR analysis. Cell proliferation was subsequently evaluated using colony formation assays, and immunofluorescence and western blotting were used to assess the expression level of LASP1 in transfected cells. The binding interaction between miR-6512-3p and LASP1 was further evaluated using a dual-luciferase reporter gene assay. Liver cancer cells were found to exhibit higher expression levels of PAARH compared with normal liver cells. Following PAARH interference, the expression level of miR-6512-3p was significantly increased, whereas that of LASP1 was significantly decreased, resulting in a reduction in cell proliferation. In liver cancer cells, miR-6512-3p overexpression led to a significant reduction in the LASP1 level and reduced proliferation, whereas suppressing miR-6512-3p led to a significant increase in LASP1 levels and increased proliferation. Additionally, the inhibition of miR-6512-3p caused the states of low LASP1 expression and reduced cell proliferation to be reversed. LASP1, a recently identified target gene of miR-6512-3p, was demonstrated to be suppressed by miR-6512-3p overexpression, thereby inhibiting liver cancer cell proliferation. Taken together, the findings of the present study demonstrate that the lncRNA PAARH may enhance liver cancer cell proliferation by engaging miR-6512-3p to target LASP1.

OsMAPK6 phosphorylation and CLG1 ubiquitylation of GW6a non-additively enhance rice grain size through stabilization of the substrate.

The chromatin modifier GRAIN WEIGHT 6a (GW6a) enhances rice grain size and yield. However, little is known about its gene network determining grain size. Here, we report that MITOGEN-ACTIVED PROTEIN KINASE 6 (OsMAPK6) and E3 ligase CHANG LI GENG 1 (CLG1) interact with and target GW6a for phosphorylation and ubiquitylation, respectively. Unexpectedly, however, in vitro and in vivo assays reveal that both of the two post-translational modifications stabilize GW6a. Furthermore, we uncover two major GW6a phosphorylation sites (serine142 and threonine186) targeted by OsMAPK6 serving an important role in modulating grain size. In addition, our genetic and molecular results suggest that the OsMAPK6-GW6a and CLG1-GW6a axes are crucial and operate in a non-additive manner to control grain size. Overall, our findings identify a previously unknown mechanism by which phosphorylation and ubiquitylation non-additively stabilize GW6a to enhance grain size, and reveal correlations and interactions of these posttranslational modifications during rice grain development.

Predicting tall-cell subtype of papillary thyroid carcinomas independently with preoperative multimodal ultrasound.

OBJECTIVES: This study aimed to explore the differences between tall-cell subtype of papillary thyroid carcinoma (TCPTC) and classical papillary thyroid carcinoma (cPTC) using multimodal ultrasound, and identify independent risk factors for TCPTC to compensate the deficiency of preoperative cytological and molecular diagnosis on PTC subtypes. METHODS: 46 TCPTC patients and 92 cPTC patients were included. Each patient received grey-scale ultrasound, color Dopplor flow imaging (CDFI) and shear-wave elastography (SWE) preoperatively. Clinicopathologic information, grey-scale ultrasound features, CDFI features and SWE features of 98 lesion were compared using univariate analysis to find out predictors of TCPTC, based on which, a predictive model was built to differentiate TCPTC from cPTC and validated with 40 patients. RESULTS: Univariate and multivariate analysis identified that extrathyroidal extension (OR, 15.12; 95% CI, 2.26-115.44), aspect ratio (≥0.91) (OR, 29.34; 95% CI, 1.29-26.23), and maximum diameter ≥ 14.6 mm (OR, 20.79; 95% CI, 3.87-111.47) were the independent risk factors for TCPTC. Logistic regression equation: p = 1/1+ExpΣ[-5.099 + 3.004 × (if size ≥14.6 mm)+2.957 × (if aspect ratio≥0.91)+2.819 × (if extra-thyroidal extension)]. The prediction model had a good discrimination performance for TCPTC: the AUC, sensitivity and specificity were 0.928, 0.848 and 0.954 in cohort 1, and the corresponding values in cohort 2 were 0.943, 0.923 and 0.926. CONCLUSION: Ultrasound has potential for differential diagnosis of TCPTC from cPTC. A prediction model based on ultrasound characteristics (extrathyroidal extension, aspect ratio ≥0.91, and maximum diameter ≥14.6 mm) was useful to predict TCPTC. ADVANCES IN KNOWLEDGE: Multimodal ultrasound prediction of TCPTC were supplements to preoperative cytological diagnosis and molecular diagnosis on PTC subtypes.

Chemical characterisation of essential oil from Sambucus williamsii Hance leaves and its hepatoprotective effects.

This study is the first to examine the effect of leaves of Sambucus williamsii Hance essential oil on acute liver injury. According to gas chromatography-mass spectrometry analysis, the major constituents of S. williamsii essential oil (SEO)were (S)-falcarinol (62.66%), 17-pentatriacontene (7.78%) and tetrapentacontane (8.64%). Mice were pre-treated with SEO for 6 days followed by inducing liver injury with CCl4. The results indicated that SEO protected the liver against CCl4-induced injuries. Elevated levels of alanine-aminotransferase (ALT), aspartate amino-transferase (AST), alkaline phosphatase (ALP) in serum were significantly reduced on SEO pre-treatment. SEO pre-treatment significantly inhibited the oxidative stress and inflammation. Furthermore, toll-like receptor-4 (TLR4)/nuclear factor kappa-B (NF-κB) signalling pathways were significantly modulated by SEO in the liver tissue. The findings demonstrate that the essential oil of S. williamsii has enhancing the resistance to CCl4-induced liver injury.

[Effects of Pesticides Use on Pesticides Residues and Its Environmental Risk Assessment in Xingkai Lake（China）].

Xingkai Lake, located in Heilongjiang Province, is an important fishery and agricultural base and is seriously polluted by agricultural non-point sources. To clarify the residual status of many pesticides in the surface water of Xingkai Lake, 27 types of pesticides, herbicides, and their degradation products were analyzed in rice paddy, drainage, and surface water around Xingkai Lake (China) during the rice heading and maturity periods. The results showed that all 27 types of pesticides, herbicides, and their degradation products were detected during the rice heading period, and the total concentration ranged from 247.97 to 6 094.49 ng·L-1. Additionally, 25 species were detected during the rice maturity period, and the total concentration ranged from 485.36 to 796.23 ng·L-1. In comparison, more pesticides, herbicides, and derived degradation products were detected during the heading period, and their total concentration was higher as well. During the rice heading period, atrazine, simetryn, and paclobutrazol were the main detected pesticides, atrazine and isoprothiolane were the main pesticides detected during the maturity period. The distribution characteristics of pesticides and herbicides in the surface water around Xingkai Lake (China) was similar to that in drainage, so they were probably imported from the drainage and rice paddy. The average risk quotient (RQ) values of atrazine, simetryn, prometryn, butachlor, isoprothiolane, and oxadiazon were higher than 0.1 in drainage and Xingkai Lake (China), which showed a potential risk to aquatic organisms.

The ARPKD Protein DZIP1L Regulates Ciliary Protein Entry by Modulating the Architecture and Function of Ciliary Transition Fibers.

Serving as the cell's sensory antennae, primary cilia are linked to numerous human genetic diseases when they malfunction. DZIP1L, identified as one of the genetic causes of human autosomal recessive polycystic kidney disease (ARPKD), is an evolutionarily conserved ciliary basal body protein. Although it has been reported that DZIP1L is involved in the ciliary entry of PKD proteins, the underlying mechanism remains elusive. Here, an uncharacterized role of DZIP1L is reported in modulating the architecture and function of transition fibers (TFs), striking ciliary base structures essential for selective cilia gating. Using C. elegans as a model, C01G5.7 (hereafter termed DZIP-1) is identified as the sole homolog of DZIP1L, which specifically localizes to TFs. While DZIP-1 or ANKR-26 (the ortholog of ANKRD26) deficiency shows subtle impact on TFs, co-depletion of DZIP-1 and ANKR-26 disrupts TF assembly and cilia gating for soluble and membrane proteins, including the ortholog of ADPKD protein polycystin-2. Notably, the synergistic role for DZIP1L and ANKRD26 in the formation and function of TFs is highly conserved in mammalian cilia. Hence, the findings illuminate an evolutionarily conserved role of DZIP1L in TFs architecture and function, highlighting TFs as a vital part of the ciliary gate implicated in ciliopathies ARPKD.

Diagnostic utility of immunohistochemistry in detection of NPM1 mutations in acute myeloid leukemia with a patchy distribution.

Nucleophosmin 1 (NPM1) mutations occur in approximately one-third cases of adult de novo acute myeloid leukemia (AML). Identification of NPM1 mutations is important for classification, risk stratification, tailored therapy, and monitoring minimal residual disease. Mutational analysis is widely used for detecting NPM1 mutations. Immunochemistry assessing abnormal cytoplasmic localization of NPM1 protein has been used as a surrogate marker for NPM1 mutations. We present a case of AML with mutated NPM1 that was missed by sequencing analysis but detected by immunohistochemistry. This case highlights the value of immunohistochemistry in identifying NPM1 mutations in a subset of AML cases.

Neural substrates of the interaction between effort-expenditure reward decision-making and outcome anticipation.

OBJECTIVE: Reward anticipation is important for future decision-making, possibly due to re-evaluation of prior decisions. However, the exact relationship between reward anticipation and prior effort-expenditure decision-making, and its neural substrates are unknown. METHOD: Thirty-three healthy participants underwent fMRI scanning while performing the Effort-based Pleasure Experience Task (E-pet). Participants were required to make effort-expenditure decisions and anticipate the reward. RESULTS: We found that stronger anticipatory activation at the posterior cingulate cortex was correlated with slower reaction time while making decisions with a high-probability of reward. Moreover, the substantia nigra was significantly activated in the prior decision-making phase, and involved in reward-anticipation in view of its strengthened functional connectivity with the mammillary body and the putamen in trial conditions with a high probability of reward. CONCLUSIONS: These findings support the role of reward anticipation in re-evaluating decisions based on the brain-behaviour correlation. Moreover, the study revealed the neural interaction between reward anticipation and decision-making.

Epigenetic regulation of H3K27me3 in laying hens with fatty liver hemorrhagic syndrome induced by high-energy and low-protein diets.

BACKGROUND: Fatty liver hemorrhagic syndrome (FLHS) in the modern poultry industry is primarily caused by nutrition. Despite encouraging progress on FLHS, the mechanism through which nutrition influences susceptibility to FLHS is still lacking in terms of epigenetics. RESULTS: In this study, we analyzed the genome-wide patterns of trimethylated lysine residue 27 of histone H3 (H3K27me3) enrichment by chromatin immunoprecipitation-sequencing (ChIP-seq), and examined its association with transcriptomes in healthy and FLHS hens. The study results indicated that H3K27me3 levels were increased in the FLHS hens on a genome-wide scale. Additionally, H3K27me3 was found to occupy the entire gene and the distant intergenic region, which may function as silencer-like regulatory elements. The analysis of transcription factor (TF) motifs in hypermethylated peaks has demonstrated that 23 TFs are involved in the regulation of liver metabolism and development. Transcriptomic analysis indicated that differentially expressed genes (DEGs) were enriched in fatty acid metabolism, amino acid, and carbohydrate metabolism. The hub gene identified from PPI network is fatty acid synthase (FASN). Combined ChIP-seq and transcriptome analysis revealed that the increased H3K27me3 and down-regulated genes have significant enrichment in the ECM-receptor interaction, tight junction, cell adhesion molecules, adherens junction, and TGF-beta signaling pathways. CONCLUSIONS: Overall, the trimethylation modification of H3K27 has been shown to have significant regulatory function in FLHS, mediating the expression of crucial genes associated with the ECM-receptor interaction pathway. This highlights the epigenetic mechanisms of H3K27me3 and provides insights into exploring core regulatory targets and nutritional regulation strategies in FLHS.

Regioselective super-assembly of Prussian blue analogue.

The construction of high-asymmetrical structures demonstrates significant potential in improving the functionality and distinctness of nanomaterials, but remains a considerable challenge. Herein, we develop a one-pot method to fabricate regioselective super-assembly of Prussian blue analogue (PBA) -- a PBA anisotropic structure (PBA-AS) decorated with epitaxial modules--using a step-by-step epitaxial growth on a rapidly self-assembled cubic substrate guided by thiocyanuric acid (TCA) molecules. The epitaxial growth units manifest as diverse geometric shapes, which are predominantly concentrated on the {100}, {111}, or {100}+{111} crystal plane of the cubic substrate. The crystal plane and morphology of epitaxial module can be regulated by changing the TCA concentration and reaction temperature, enabling a high level of controllability over specific assembly sites and structures. To illustrate the advantage of the asymmetrical structure, phosphated PBA-AS demonstrates improved performance in the oxygen evolution reaction compared to simple phosphated PBA nanocube. This method offers valuable insights for designing asymmetrical nanomaterials with intricate architectures and versatile functionalities.

[Differences in the Elderly Care Service Demand,Preference,and Tendency Between Urban and Rural Areas in the Pearl River Delta].

Objective To understand the differences in the demand,preference,and tendency for elderly care services between urban and rural areas in the Pearl River Delta (PRD),and to provide reference for the planning and balanced allocation of elderly care resources in urban and rural areas. Methods Using the multi-stage stratified random sampling method,we selected 7 community health service centers in 2 prefecture-level cities in the PRD and conducted a questionnaire survey on the elderly care service demand,preference,and tendency among 1919 regular residents aged 60 years and above who attended the centers. Results A total of 641 urban elderly residents (33.4%) and 1278 rural elderly residents (66.6%) were surveyed in the PRD.The urban and rural elderly residents showed differences in the child number (χ2=43.379,P<0.001),willingness to purchase socialized elderly care services (χ2=104.141,P<0.001),and attitudes to the concept of raising child to avoid elderly hardship (χ2=65.632,P<0.001).The proportion (71.8%) of rural elderly residents who prefer family-based elderly care was higher than that (57.1%) of urban elderly residents (χ2=41.373,P<0.001).The proportion (62.2%) of urban elderly residents clearly expressing their willingness to choose institutions for elderly care was higher than that (44.0%) of rural elderly residents (χ2=57.007,P<0.001).Compared with family-based elderly care,the willingness to choose institutional or community-based in-house elderly care was low among the urban elderly residents with surplus monthly household income or balanced income and expenditure;urban males,those with college education background or above,and those who purchased socialized elderly care services tended to prefer community-based in-house elderly care.In rural areas,the elderly residents who had local household registry were prone to choose institutional or community-based in-house elderly care,while those who had more than one child and those who were satisfied with the current living conditions were less willing to choose community-based in-house elderly care. Conclusions It is suggested that the urban-rural differences in the elderly care service demand,preference and tendency should be fully considered in the planning and allocation of urban and rural elderly care resources.Efforts remain to be made to develop diversified social elderly care services tailored to the characteristics of urban and rural areas.

Evaluation of monolithic crystal detector with dual-ended readout utilizing multiplexing method.

Objective.Monolithic crystal detectors are increasingly being applied in positron emission tomography (PET) devices owing to their excellent depth-of-interaction (DOI) resolution capabilities and high detection efficiency. In this study, we constructed and evaluated a dual-ended readout monolithic crystal detector based on a multiplexing method.Approach.We employed two 12 × 12 silicon photomultiplier (SiPM) arrays for readout, and the signals from the 12 × 12 array were merged into 12 X and 12 Y channels using channel multiplexing. In 2D reconstruction, three methods based on the centre of gravity (COG) were compared, and the concept of thresholds was introduced. Furthermore, a light convolutional neural network (CNN) was employed for testing. To enhance depth localization resolution, we proposed a method by utilizing the mutual information from both ends of the SiPMs. The source width and collimation effect were simulated using GEANT4, and the intrinsic spatial resolution was separated from the measured values.Main results.At an operational voltage of 29 V for the SiPM, an energy resolution of approximately 12.5 % was achieved. By subtracting a 0.8 % threshold from the total energy in every channel, a 2D spatial resolution of approximately 0.90 mm full width at half maximum (FWHM) can be obtained. Furthermore, a higher level of resolution, approximately 0.80 mm FWHM, was achieved using a CNN, with some alleviation of edge effects. With the proposed DOI method, a significant 1.36 mm FWHM average DOI resolution can be achieved. Additionally, it was found that polishing and black coating on the crystal surface yielded smaller edge effects compared to a rough surface with a black coating.Significance.The introduction of a threshold in COG method and a dual-ended readout scheme can lead to excellent spatial resolution for monolithic crystal detectors, which can help to develop PET systems with both high sensitivity and high spatial resolution.

Cep131-Cep162 and Cby-Fam92 complexes cooperatively maintain Cep290 at the basal body and contribute to ciliogenesis initiation.

Cilia play critical roles in cell signal transduction and organ development. Defects in cilia function result in a variety of genetic disorders. Cep290 is an evolutionarily conserved ciliopathy protein that bridges the ciliary membrane and axoneme at the basal body (BB) and plays critical roles in the initiation of ciliogenesis and TZ assembly. How Cep290 is maintained at BB and whether axonemal and ciliary membrane localized cues converge to determine the localization of Cep290 remain unknown. Here, we report that the Cep131-Cep162 module near the axoneme and the Cby-Fam92 module close to the membrane synergistically control the BB localization of Cep290 and the subsequent initiation of ciliogenesis in Drosophila. Concurrent deletion of any protein of the Cep131-Cep162 module and of the Cby-Fam92 module leads to a complete loss of Cep290 from BB and blocks ciliogenesis at its initiation stage. Our results reveal that the first step of ciliogenesis strictly depends on cooperative and retroactive interactions between Cep131-Cep162, Cby-Fam92 and Cep290, which may contribute to the complex pathogenesis of Cep290-related ciliopathies.

Clonal integration of stress signal induces morphological and physiological response of root within clonal network.

Clonal integration of defense or stress signal induced systemic resistance in leaf of interconnected ramets. However, similar effects of stress signal in root are poorly understood within clonal network. Clonal fragments of Centella asiaticas with first-young, second-mature, third-old and fourth-oldest ramets were used to investigate transportation or sharing of stress signal among interconnected ramets suffering from low water availability. Compared with control, oxidative stress in root of the first-young, second-mature and third-old ramets was significantly alleviated by exogenous ABA application to the fourth-oldest ramets as well as enhancement of antioxidant enzyme (SOD, POD, CAT and APX) activities and osmoregulation ability. Surface area and volume in root of the first-young ramets were significantly increased and total length in root of the third-old ramets was significantly decreased. POD activity in root of the fourth-oldest and third-old ramets was significantly enhanced by exogenous ABA application to the first-young ramets. Meanwhile, total length and surface area in root of the fourth-oldest and third-old ramets were significantly decreased. Ratio of belowground to aboveground biomass in the whole clonal fragments was significantly increased by exogenous ABA application to the fourth-oldest or first-young ramets. It is suggested that transportation or sharing of stress signal may induce systemic resistance in root of interconnected ramets. Specially, transportation or sharing of stress signal against phloem flow was observed in the experiment. Possible explanation is that rapid recovery of foliar photosynthesis in first-young ramets subjected to exogenous ABA application can partially reverse phloem flow within clonal network. Thus, our experiment provides insight into ecological implication on clonal integration of stress signal.

From the archives of MD Anderson Cancer Center: Monomorphic epitheliotropic intestinal T-cell lymphoma: A case with an unusual immunophenotype and discussion of differential diagnosis.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare and aggressive T-cell neoplasm associated with poor survival. We report a case of MEITL that presented as an ulcerated mass in the jejunum with perforation. Microscopic examination showed that the neoplasm involved the full thickness of the intestinal wall, extended into the mesentery, and was composed of monomorphic, small to medium-size cells. Immunohistochemical analysis showed that the neoplastic cells were positive for T-cell receptor (TCR) delta, CD3, CD7, CD8 (small subset), BCL-2 and TIA-1, and negative for TCR beta, CD4, CD5, CD10, CD20, CD30, CD34, CD56, CD57, CD99, ALK, cyclin D1, granzyme B, MUM1/IRF4, and TdT. The Ki-67 proliferation index was approximately 50 %. In situ hybridization for Epstein-Barr virus-encoded RNA (EBER ISH) was negative. Next-generation sequencing (NGS) analysis showed mutations involving SETD2 and STAT5B. The patient was treated with aggressive chemotherapy and consolidative autologous stem cell transplant and had clinical remission, but relapsed after about one year. Retreatment led to another one-year interval of clinical remission, but at last follow up the patient has relapsed disease involving the ileum and colon. We also discuss the differential diagnosis of MEITL.

Integrated photocatalysis adsorption processes for oxytetracycline removal: using volborthite and its composite with g-C3N4.

The photocatalytic-adsorption performance of the composites of volborthite (CuVA) and graphitic carbon nitride (g-C3N4) was studied in this work using oxytetracycline (OTC) as model pollutant under LED light irradiation. CuVA at different weight percentages (10, 30, 50), namely, C10, C30, and C50, were loaded onto graphitic carbon nitride using wet chemical method. The physical, chemical, and optical properties were evaluated via various analytical techniques. Through integrated adsorption-photocatalytic process, no significant photocatalytic reaction occurred in g-C3N4 and the composite even after 4 h of irradiation. The setup was modified such that each run was conducted in the presence and absence of light. Aside from photolysis and g-C3N4, all composites performed better under the presence of light in which CuVA improved the most from ~ 50% down to ~ 20% of initial concentration. CuVA performed almost identically (80% removal of OTC) under the presence of light irradiation at ambient temperature (22 °C) and in the dark at 32 °C, confirming that temperature was the contributing factor to the improvement instead of light. CuVA exhibited excellent adsorption capacity of 171 mg/g and adsorption rate of 90% towards the removal of highly concentrated OTC (100 mg/L) under optimized parameters of pH 5.0 and at 42 °C after 3 h of adsorption process. Life cycle assessment revealed that close to 50% of fresh 100 ppm OTC could be removed after five cycles without any desorption process.

Lactobacillus rhamnosus GG ameliorates hyperuricemia in a novel model.

Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA.