Enhanced IFN Sensing by Aggressive Chronic Lymphocytic Leukemia Cells.

Type I IFN is made by cells in response to stress. Cancer cells exist in a state of stress, but their IFN response is complex and not completely understood. This study investigated the role of autocrine IFN in human chronic lymphocytic leukemia (CLL) cells. CLL cells were found to make low amounts of IFN via TANK-binding kinase 1 pathways, but p-STAT1 and -STAT2 proteins along with IFN-stimulated genes that reflect IFN activation were variably downregulated in cultured CLL cells by the neutralizing IFNAR1 Ab anifrolumab. Patients with CLL were segregated into two groups based on the response of their leukemia cells to anifrolumab. Samples associated with more aggressive clinical behavior indicated by unmutated IGHV genes along with high CD38 and p-Bruton's tyrosine kinase expression exhibited responses to low amounts of IFN that were blocked by anifrolumab. Samples with more indolent behavior were unaffected by anifrolumab. Hypersensitivity to IFN was associated with higher expression of IFNAR1, MX1, STAT1, and STAT2 proteins and lower activity of negative regulatory tyrosine phosphatases. Autocrine IFN protected responsive CLL cells from stressful tissue culture environments and therapeutic drugs such as ibrutinib and venetoclax in vitro, in part by upregulating Mcl-1 expression. These findings suggest hypersensitivity to IFN may promote aggressive clinical behavior. Specific blockade of IFN signaling may improve outcomes for patients with CLL with higher-risk disease.

Effect of Ibrutinib on the IFN Response of Chronic Lymphocytic Leukemia Cells.

The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has profound activity in chronic lymphocytic leukemia (CLL) but limited curative potential by itself. Residual signaling pathways that maintain survival of CLL cells might be targeted to improve ibrutinib's therapeutic activity, but the nature of these pathways is unclear. Ongoing activation of IFN receptors in patients on ibrutinib was suggested by the presence of type I and II IFN in blood together with the cycling behavior of IFN-stimulated gene (ISG) products when IFN signaling was blocked intermittently with the JAK inhibitor ruxolitinib. IFN signaling in CLL cells from human patients was not prevented by ibrutinib in vitro or in vivo, but ISG expression was significantly attenuated in vitro. ISGs such as CXCL10 that require concomitant activation of NF-κB were decreased when this pathway was inhibited by ibrutinib. Other ISGs, exemplified by LAG3, were decreased as a result of inhibited protein translation. Effects of IFN on survival remained intact as type I and II IFN-protected CLL cells from ibrutinib in vitro, which could be prevented by ruxolitinib and IFNR blocking Abs. These observations suggest that IFNs may help CLL cells persist and specific targeting of IFN signaling might deepen clinical responses of patients on ibrutinib.

Opioid-reduced anesthesia based on esketamine in gynecological day surgery: a randomized double-blind controlled study.

BACKGROUND: Opioid-reduced anesthesia may accelerate postoperative rehabilitation by reducing opioid-related side effects. The objective was to investigate the feasibility of opioid-reduced general anesthesia based on esketamine and to observe postoperative nausea and vomiting (PONV), postoperative pain, hemodynamics and other adverse reactions in gynecological day surgery compared with the traditional opioid-based anesthesia program. METHOD: This study was conducted as a prospective parallel-group randomized controlled trial. A total of 141 adult women undergoing gynecological day surgery were included. Patients were randomly assigned to receive traditional opioid-based anesthesia (Group C) with alfentanil, or opioid-reduced anesthesia (a moderate-opioid group (Group MO) and low-opioid group (Group LO) with esketamine and alfentanil). For anesthesia induction, the three groups received 20, 20, 10 µg/kg alfentanil respectively and Group LO received an additional 0.2 mg/kg esketamine. For maintenance of anesthesia, the patients in Group C received 40 µg/kg/h alfentanil, and those in Group MO and Group LO received 0.5 mg/kg/h esketamine. RESULTS: Patients in the three groups had comparable clinical and surgical data. A total of 33.3% of patients in Group C, 18.4% of patients in Group MO and 43.2% of patients in Group LO met the primary endpoint (p = 0.033), and the incidence of nausea within 24 hours after surgery in Group MO was lower than in Group LO (p < 0.05). The extubation time, median length of stay in the hospital after surgery and visual analog scale (VAS) of postoperative pain were equivalent in the three groups. The frequencies of adverse hemodynamic events in the MO 1(0, 2) and LO 0(0, 1) groups were significantly decreased (p < 0.05). Compared with Group C, the median length of stay in the postanesthesia care unit (PACU) in Group LO was increased, 60.0 (36.25, 88.75) vs. 42.5 (25, 73.75) minutes (p < 0.05). CONCLUSIONS: Opioid-reduced anesthesia based on esketamine is feasible and provides effective analgesia for patients. Esketamine provided a positive analgesic effect and the opioid-reduced groups showed more stable hemodynamics. However, less or no use of opioids did not result in a more comfortable prognosis. TRIAL REGISTRATION: This study was registered at Chictr.org.cn (NO. ChiCTR2100053153 ); November 13, 2021.

Capacitive Removal of Fluoride Ions via Creating Multiple Capture Sites in a Modulatory Heterostructure.

Fluoride pollution has become a major concern because of its adverse effects on human health. However, the removal capacity of defluorination agents in traditional methods is far from satisfactory. Herein, capacitive removal of F- ions via creating multiple capture sites in a modulatory heterostructure has been originally demonstrated. The heterostructure of uniformly dispersed Al2O3 coating on hollow porous nitrogen-doped carbon frameworks was precisely synthesized by atomic layer deposition. An exceptional F- ion removal efficiency at 1.2 V (95.8 and 92.9% in 5 and 10 mg/L F- solutions, respectively) could be finally achieved, with a good regeneration ability after 20 consecutive defluorination cycles. Furthermore, we investigated the removal mechanisms of F- ions by in situ Raman, in situ X-ray diffraction, and ex situ X-ray photoelectron spectroscopy measurements. The promotional removal capacity was realized by the multiple capture sites of the reversible conversion of Al-F species and the insertion of F- ions into the carbon skeleton. This work offers an important new pathway and deep understanding for efficient removal of F- ions from wastewater.

Genome­wide integrated analysis demonstrates widespread functions of lncRNAs in mammary gland development and lactation in dairy goats.

BACKGROUND: The mammary gland is a unique organ for milk synthesis, secretion and storage, and it undergoes cyclical processes of development, differentiation, lactation and degeneration. At different developmental periods, the biological processes governing mammary gland physiology and internal environmental homeostasis depend on a complex network of genes and regulatory factors. Emerging evidence indicates that lncRNAs have arbitrarily critical functions in regulating gene expression in many organisms; however, the systematic characteristics, expression, and regulatory roles of lncRNAs in the mammary gland tissues of dairy goats have not been determined. RESULT: In the present study, we profiled long noncoding RNA (lncRNA) expression in the mammary gland tissues of Laoshan dairy goats (Capra hircus) from different lactation periods at the whole-genome level, to identify, characterize and explore the regulatory functions of lncRNAs. A total of 37,249 transcripts were obtained, of which 2381 lncRNAs and 37,249 mRNAs were identified, 22,488 transcripts, including 800 noncoding transcripts and 21,688 coding transcripts, differed significantly (p ≤ 0.01) among the different lactation stages. The results of lncRNA-RNA interaction analysis showed that six known lncRNAs belonging to four families were identified as the precursors of 67 known microRNAs; 1478 and 573 mRNAs were predicted as hypothetical cis-regulation elements and antisense mRNAs, respectively. GO annotation and KEGG analysis indicated that the coexpressed mRNAs were largely enriched in biological processes related to such activities as metabolism, immune activation, and stress,., and most genes were involved in pathways related to such phenomena as inflammation, cancer, signal transduction, and metabolism. CONCLUSIONS: Our results clearly indicated that lncRNAs involved in responses to stimuli, multiorganism processes, development, reproductive processes and growth, are closely related to mammary gland development and lactation.

Trace-Fe-Enhanced Capacitive Deionization of Saline Water by Boosting Electron Transfer of Electro-Adsorption Sites.

Capacitive deionization (CDI) is a promising water purification technology. However, the current ion adsorption capacity of CDI electrode materials is still an issue, which cannot meet the rapid demand of clean water from saline water. Herein, trace-Fe-enhanced removal of ions from saline water via CDI is presented. The ion adsorption capacity of CDI electrodes is up to 36.25 mg g-1 in a 500 mg L-1 NaCl media at 1.2 V together with stable regeneration property. In situ Raman and ex situ XPS measurements unravel the removal mechanism of ions from saline water, and the reinforced adsorption of ions is due to the introduction of trace Fe boosting electron transfer of electro-adsorption sites during the CDI process. This work presents a promising solution to highly efficient capacitive deionization for saline water.

Perturbation of gut bacteria induces a coordinated cellular immune response in the purple sea urchin larva.

This corrects the article DOI: 10.1038/icb.2016.51.

Genome-wide analysis reveals signatures of selection for important traits in domestic sheep from different ecoregions.

BACKGROUND: Throughout a long period of adaptation and selection, sheep have thrived in a diverse range of ecological environments. Mongolian sheep is the common ancestor of the Chinese short fat-tailed sheep. Migration to different ecoregions leads to changes in selection pressures and results in microevolution. Mongolian sheep and its subspecies differ in a number of important traits, especially reproductive traits. Genome-wide intraspecific variation is required to dissect the genetic basis of these traits. RESULTS: This research resequenced 3 short fat-tailed sheep breeds with a 43.2-fold coverage of the sheep genome. We report more than 17 million single nucleotide polymorphisms and 2.9 million indels and identify 143 genomic regions with reduced pooled heterozygosity or increased genetic distance to each other breed that represent likely targets for selection during the migration. These regions harbor genes related to developmental processes, cellular processes, multicellular organismal processes, biological regulation, metabolic processes, reproduction, localization, growth and various components of the stress responses. Furthermore, we examined the haplotype diversity of 3 genomic regions involved in reproduction and found significant differences in TSHR and PRL gene regions among 8 sheep breeds. CONCLUSIONS: Our results provide useful genomic information for identifying genes or causal mutations associated with important economic traits in sheep and for understanding the genetic basis of adaptation to different ecological environments.

Perturbation of gut bacteria induces a coordinated cellular immune response in the purple sea urchin larva.

The purple sea urchin (Strongylocentrotus purpuratus) genome sequence contains a complex repertoire of genes encoding innate immune recognition proteins and homologs of important vertebrate immune regulatory factors. To characterize how this immune system is deployed within an experimentally tractable, intact animal, we investigate the immune capability of the larval stage. Sea urchin embryos and larvae are morphologically simple and transparent, providing an organism-wide model to view immune response at cellular resolution. Here we present evidence for immune function in five mesenchymal cell types based on morphology, behavior and gene expression. Two cell types are phagocytic; the others interact at sites of microbial detection or injury. We characterize immune-associated gene markers for three cell types, including a perforin-like molecule, a scavenger receptor, a complement-like thioester-containing protein and the echinoderm-specific immune response factor 185/333. We elicit larval immune responses by (1) bacterial injection into the blastocoel and (2) seawater exposure to the marine bacterium Vibrio diazotrophicus to perturb immune state in the gut. Exposure at the epithelium induces a strong response in which pigment cells (one type of immune cell) migrate from the ectoderm to interact with the gut epithelium. Bacteria that accumulate in the gut later invade the blastocoel, where they are cleared by phagocytic and granular immune cells. The complexity of this coordinated, dynamic inflammatory program within the simple larval morphology provides a system in which to characterize processes that direct both aspects of the echinoderm-specific immune response as well as those that are shared with other deuterostomes, including vertebrates.

Eutrophication-Driven Hypoxia in the East China Sea off the Changjiang Estuary.

Coastal hypoxia is an increasingly recognized environmental issue of global concern to both the scientific community and the general public. We assessed the relative contributions from marine and terrestrially sourced organic matter that were responsible for oxygen consumption in a well-studied seasonal coastal hypoxic zone, the East China Sea off the Changjiang Estuary. Our fieldwork was conducted in August 2011 during reinstatement of a subsurface hypoxia, when we observed a continuous decline of dissolved oxygen along with production of dissolved inorganic carbon resulting from organic carbon remineralization. On the basis of a three end-member mixing model and determinations of the stable isotopic compositions of dissolved inorganic carbon (δ(13)CDIC), the end product of particulate organic carbon (POC) degradation, we quantified the δ(13)C value of the remineralized organic carbon (δ(13)COCx), which was -18.5 ± 1.0‰. This isotopic composition was very similar to the δ(13)C of marine sourced POC produced in situ (-18.5 ± 0.3‰) rather than that of the terrestrially sourced POC (-24.4 ± 0.2‰). We concluded that marine-sourced organic matter, formed by eutrophication-induced marine primary production, was the dominant oxygen consumer in the subsurface hypoxic zone in the East China Sea off the Changjiang Estuary.

Three slow skeletal muscle troponin genes in small-tailed Han sheep (Ovis aries): molecular cloning, characterization and expression analysis.

To explore the basic characteristics and expressing profile of the three slow skeletal muscle troponin genes TNNC1 (Troponin C type 1), TNNI1 (troponin I type 1) and TNNT1 (troponin T type 1). Three purebred Dorper sheep and another three purebred small-tailed Han sheep were selected. The sequence of the genes from the small-tailed Han sheep was cloned using rapid amplification of cDNA ends and reverse transcription-polymerase chain reaction; The characteristics of the predicted amino acids sequences were analyzed using bioinformatics analysis software; Gene expression analyses were performed using quantitative reverse transcription PCR. The full-length cDNA sequences of the genes were 707, 898, and 1001 bp, respectively, and were submitted to GenBank under accession numbers KR153938, KT218688 and KT218690. The three predicted proteins were predicted to be hydrophilic, non-secretory proteins and contain several phosphorylation sites. Multiple alignments and phylogenetic tree analyses showed that the predicted proteins were relatively conserved in mammals. The expression results of the three genes in eight tissues of Dorper and small-tailed Han sheep revealed that the three genes had a similar mRNA expression pattern, whereas distinct differences were observed among the eight tissues of the two sheep species. We cloned the full-length cDNA of the three genes, analyzed the amino acid sequences, and determined the expression levels of the genes. These results might play important roles in facilitating the future research of the three genes.

De novo assembly and characterization of the skeletal muscle transcriptome of sheep using Illumina paired-end sequencing.

OBJECTIVE: In order to enrich the ovine genome and provide a basis for future molecular genetics and functional genomics analyses in sheep, we used de novo assembly to establish transcriptomes of skeletal muscle tissues of Dorper and Small-tailed Han sheep. RESULTS: A total of 103,058,824 clean Illumina paired-end sequencing reads from the two libraries were assembled into 145,524 unigenes in a de novo project. There were 5718 unigenes showing differential expression between the two transcriptomes, and 7437 coding SSRs were exploited. After further assembly, we identified a total of 70,348 all-unigenes with an average length of 863 bp; 35,201 of these all-unigenes could be annotated in the Nr database, and 12,219 were found in the clusters of orthologous groups database. Gene ontology searches indicated cell and binding as the main terms. Among 258 Kyoto Encyclopedia of Genes and Genomes database pathways, protein and amino acid metabolism pathways were the most commonly identified. CONCLUSION: We analyzed the ovine muscle transcriptome using high-throughput sequencing technology. Many unigenes were assembled and numerous molecular markers and differential expressed unigenes were identified.

An ancient role for Gata-1/2/3 and Scl transcription factor homologs in the development of immunocytes.

Although vertebrate hematopoiesis is the focus of intense study, immunocyte development is well-characterized in only a few invertebrate groups. The sea urchin embryo provides a morphologically simple model for immune cell development in an organism that is phylogenetically allied to vertebrates. Larval immunocytes, including pigment cells and several blastocoelar cell subtypes, emerge from a population of non-skeletal mesodermal (NSM) precursors that is specified at the blastula stage. This ring of cells is first partitioned into oral and aboral fields with distinct blastocoelar and pigment cell gene regulatory programs. The oral field is subsequently specified into several distinct immune and non-immune cell types during gastrulation. Here we characterize the oral NSM expression and downstream function of two homologs of key vertebrate hematopoietic transcription factors: SpGatac, an ortholog of vertebrate Gata-1/2/3 and SpScl, an ortholog of Scl/Tal-2/Lyl-1. Perturbation of SpGatac affects blastocoelar cell migration at gastrulation and later expression of immune effector genes, whereas interference with SpScl function disrupts segregation of pigment and blastocoelar cell precursors. Homologs of several transcription regulators that interact with Gata-1/2/3 and Scl factors in vertebrate hematopoiesis are also co-expressed in the oral NSM, including SpE-protein, the sea urchin homolog of vertebrate E2A/HEB/E2-2 and SpLmo2, an ortholog of a dedicated cofactor of the Scl-GATA transcription complex. Regulatory analysis of SpGatac indicates that oral NSM identity is directly suppressed in presumptive pigment cells by the transcription factor SpGcm. These findings provide part of a comparative basis to understand the evolutionary origins and regulatory biology of deuterostome immune cell differentiation in the context of a tractable gene regulatory network model.

Coastal acidification induced by tidal-driven submarine groundwater discharge in a coastal coral reef system.

We identified a barely noticed contributor, submarine groundwater discharge (SGD), to acidification of a coastal fringing reef system in Sanya Bay in the South China Sea based on time-series observations of Ra isotopes and carbonate system parameters. This coastal system was characterized by strong diel changes throughout the spring to neap tidal cycle of dissolved inorganic carbon (DIC), total alkalinity, partial pressure of CO2 (pCO2) and pH, in the ranges of 1851-2131 µmol kg(-1), 2182-2271 µmol kg(-1), 290-888 µatm and 7.72-8.15, respectively. Interestingly, the diurnal amplitudes of these parameters decreased from spring to neap tides, governed by both tidal pumping and biological activities. In ebb stages during the spring tide, we observed the lowest salinities along with the highest DIC, pCO2 and Ra isotopes, and the lowest pH and aragonite saturation state. These observations were consistent with a concurrent SGD rate up to 25 and 44 cm d(-1), quantified using Darcy's law and (226)Ra, during the spring tide ebb, but negligible at flood tides. Such tidal-driven SGD of low pH waters is another significant contributor to coastal acidification, posing additional stress on coastal coral systems, which would be even more susceptible in future scenarios under higher atmospheric CO2.

Inhibition of acid-sensing ion channel currents by propofol in rat dorsal root ganglion neurons.

Acid-sensing ion channels (ASICs), part of the epithelial sodium channel/degenerin family, are activated by extracellular protons. The ASICs play a significant role in the acidosis-mediated perception of pain. The anaesthetic agent propofol also exerts antinociceptive effects, but the underlying mechanisms for this effect are not clear. We used whole-cell patch clamping to investigate the effect of propofol on proton-gated currents in: (i) rat dorsal root ganglion (DRG) neurons; and (ii) HEK293 cells transfected with either ASIC1a or ASIC3. Propofol inhibited the amplitude of proton-gated currents in DRG neurons, but did not change the sensitivity of ASICs to H(+). Notably, propofol altered acid-evoked excitability of rat DRG neurons and decreased the number of action potentials induced by acid stimuli. In addition, we demonstrated that propofol inhibited ASICs by directly binding with these channels in HEK293 cells. These results suggest that propofol inhibits proton-gated currents in DRG neurons and that inhibition of proton-gated currents explains, in part, the antinociceptive effects of propofol in primary afferent neurons.

[Parameters of oxygen uptake and carbon dioxide output ventilatory efficiency during exercise are index of circulatory function in normal subjects].

OBJECTIVE: To observe oxygen uptake efficiency plateau (OUEP, i.e.highest V˙O2/V˙E) and carbon dioxide output efficiency (lowest V˙E/V˙CO2) parameter changes during exercise in normal subjects. METHODS: Five healthy volunteers performed the symptom limited maximal cardiopulmonary exercise test (CPET) at Harbor-UCLA Medical Center. V˙O2/V˙E and V˙E/V˙CO2 were determined by both arterial and central venous catheters. After blood gas analysis of arterial and venous sampling at the last 30 seconds of every exercise stage and every minute of incremental loading, the continuous parameter changes of hemodynamics, pulmonary ventilation were monitored and oxygen uptake ventilatory efficiency (V˙O2/V˙E and V˙E/V˙CO2) was calculated. RESULTS: During CPET, as the loading gradually increased, cardiac output, heart rate, mixed venous oxygen saturation, arteriovenous oxygen difference, minute ventilation, minute alveolar ventilation, tidal volume, alveolar ventilation and pulmonary ventilation perfusion ratio increased near-linearly (P < 0.05-0.01, vs.resting); arterial oxygen concentration maintained at a high level without significant change (P > 0.05); stroke volume, respiratory rate, arterial partial pressure of carbon dioxide, arterial blood hydrogen ion concentration and dead space ventilation ratio significantly changed none-linearly (compare resting state P < 0.05-0.01).OUE during exercise increased from 30.9 ± 3.3 at resting state to the highest plateau 46.0 ± 4.7 (P < 0.05 vs.resting state), then, declined gradually after anaerobic threshold (P < 0.05-0.01, vs.OUEP) and reached 36.6 ± 4.4 at peak exercise. The V˙E/V˙CO2 during exercise decreased from the resting state (39.2 ± 6.5) to the minimum value (24.2 ± 2.4) after AT for a few minutes (P > 0.05 vs.earlier stage), then gradually increased after the ventilatory compensation point (P < 0.05 vs.earlier stage) and reached to 25.9 ± 2.7 at peak exercise. CONCLUSIONS: Cardiac and lung function as well as metabolism change during CPET is synchronous.In the absence of pulmonary limit, appearing before and after anaerobic threshold, OUEP and lowest V˙E/V˙CO2 could be used as reliable parameters representing the circulatory function.

[Imaging analysis of burst injury of the lungs in coal miners workers].

OBJECTIVE: To investigate the imaging features of burst injury of the lung in coal miners and to provide reference for clinical diagnosis and treatment. METHODS: A retrospective analysis was performed on the clinical data and imaging findings of 78 patients with burst injury of the lung. RESULTS: The imaging findings of burst injury of the lung were variable and complex, and they varied over time. Eleven cases showed no abnormalities on X-ray and CT within 24 h, but abnormalities appeared within 3 d; 53 cases showed abnormalities on X-ray and CT and had an exacerbation within 3 d; 8 cases showed improvements when reexamined. Among the 78 patients examined by X-ray and (or) CT, ground glass-like shadows were noted in 15 cases, interstitial changes in 13 cases, segmental consolidation in 24 cases, and diffuse consolidation in 26 cases. The complications included pneumothorax (n = 35), hemothorax (n = 28), costal fracture (n = 24), and pulmonary infection (n = 27). CONCLUSION: X-ray plain film and CT offer a reliable basis for early diagnosis of burst injury of the lung. CT is superior to X-ray plain film in detecting lesions, so chest CT should be performed as early as possible to remedy burst injury of the lung.

An Autoregressive-Based Kalman Filter Approach for Daily PM2.5 Concentration Forecasting in Beijing, China.

With the acceleration of urbanization, air pollution, especially PM2.5, has seriously affected human health and reduced people's life quality. Accurate PM2.5 prediction is significant for environmental protection authorities to take actions and develop prevention countermeasures. In this article, an adapted Kalman filter (KF) approach is presented to remove the nonlinearity and stochastic uncertainty of time series, suffered by the autoregressive integrated moving average (ARIMA) model. To further improve the accuracy of PM2.5 forecasting, a hybrid model is proposed by introducing an autoregressive (AR) model, where the AR part is used to determine the state-space equation, whereas the KF part is used for state estimation on PM2.5 concentration series. A modified artificial neural network (ANN), called AR-ANN is introduced to compare with the AR-KF model. According to the results, the AR-KF model outperforms the AR-ANN model and the original ARIMA model on the predication accuracy; that is, the AR-ANN obtains 10.85 and 15.45 of mean absolute error and root mean square error, respectively, whereas the ARIMA gains 30.58 and 29.39 on the corresponding metrics. It, therefore, proves that the presented AR-KF model can be adopted for air pollutant concentration prediction.

Hydrographic proxies for submarine groundwater discharge in the Jiulong River estuary and global perspectives.

Submarine groundwater discharge (SGD) significantly impacts most coastal waters. However, its quantification, depending on chemical tracers/proxies, limits its parameterization in numerical models. This study explored the hydrographic proxies of SGD in the Jiulong River estuary (JRE) using 226Ra and 228Ra as SGD tracers. Our results showed significant monthly fluctuations in the flux of SGD, with a peak in June and a minimum in April. On average, the flux of SGD was equivalent to 10 ± 1.67 % of the concurrent river discharge, with the area-normalized rate of 0.007 ± 0.017 to 0.13 ± 0.04 m/day. Positive SGD response to river discharge implies a connection with the surface runoff of the shallow aquifers. Furthermore, the flux of SGD presented a significant negative correlation with the return flow factor and flushing time of the estuary. The radium activities in the estuary were positively correlated with water depth, indicating that SGD was not driven by tidal pumping. Instead, physical mixing in low to middle salinity regions predominated such behavior of radium. Our results indicate that river discharge, flushing time and return flow factor may serve as hydrographic proxies of SGD in the JRE and potentially be applicable in parameterization of SGD in numerical models in similar coastal ecosystems. Globally, a positive correlation between SGD flux and river discharge emphasizes the latter as a general proxy in estuaries.

Identification of VRK1 as a Novel Potential Biomarker for Prognosis and Immunotherapy in Hepatocellular Carcinoma.

Background: Research has indicated that VRK1 is essential for the tumor cell cycle. However, its prognostic and immunotherapeutic predictive significance has not been documented in hepatocellular carcinoma (HCC). Methods: The TCGA, ICGC, and GSE14520 datasets were used to investigate VRK1 expression and its predictive significance of survival outcomes. The qRT-PCR and immunohistochemistry (IHC) were used to confirm the findings. The immunotherapeutic response of VRK1 was anticipated by the IMvigor210 cohort. Lastly, the association between immune infiltration, m6A modification, and functional enrichment of differentially expressed genes (DEGs) was investigated in connection to VRK1 expression. Results: VRK1 expression was markedly elevated on both the mRNA and protein levels in HCC. In HCC patients, a high expression of VRK1 was linked to a poor prognosis. Furthermore, there was a substantial positive correlation seen between increased VRK1 expression and the response rate to anti-PD-L1 immunotherapy. Relationships between VRK1 and m6A-related genes as well as different immune cells were shown by correlation studies. Lastly, enrichment analysis revealed a tight relationship between VRK1 and important biological functions, including DNA replication, cell cycle control, and fatty acid metabolism. Conclusion: Our research reveals the potential of VRK1 as a novel biomarker for prognosis and immunotherapy response in HCC patients.