Riverine fluxes of different species of phosphorus in the Pearl River estuary.

Phosphorus is the most limiting nutrient in coastal waters of China, particularly in the Pearl River (PR) estuary. Rivers have different P forms including dissolved inorganic phosphorus (DIP), dissolved organic phosphorus (DOP), particulate inorganic phosphorus (PIP), and particulate organic phosphorus (POP). Their input to coastal seas has been overlooked. We hypothesize that DIP is a small fraction of total phosphorus (TP). We investigated these P forms and estimated their fluxes in PR eight outlets during 2015-2019. DIP on average is only a 30.90 % fraction of TP with PIP, POP and DOP accounting for 22.43, 31.56 and 15.37 %, respectively. The average annual fluxes of TP, DIP, DOP, PIP and POP were 12.58×, 3.34×, 1.68×, 3.19× and 4.26 × 106 mol/month, respectively, which are regulated by runoff and suspended particulate matter (SPM). The finding reveals the importance of other P forms for phytoplankton in the Pearl River estuary and their bio-availability deserves further study.

A novel hydrogen sulfide donor reduces neuroinflammation and seizures by activating ATP-sensitive potassium channels.

Epilepsy is a common neurological disorder worldwide. Hydrogen sulfide (H2S) has been found to have anti-seizure effects. However, its mechanism remains to be explored. In the present study, we showed that a novel H2S donor attenuated neuroinflammation by up-regulating ATP-sensitive potassium channel (KATP) expression to reduce seizures. The novel H2S donor significantly reduced the expression of TNF-α and increased the expression of IL-10 in LPS-treated BV2 cells and the hippocampus of pilocarpine-induced epileptic mice. The modulatory effects of the H2S donor on inflammatory cytokines were prevented by glibenclamide, a common KATP channels blocker. The H2S donor promoted the expression of KATP channel subunits SUR2 and Kir6.1 in LPS-treated BV2 cells and the hippocampus of pilocarpine-induced epileptic mice. In addition, the H2S donor reduced the electroencephalography amplitude of hippocampal epileptic waves and reduced seizures in pilocarpine-induced epileptic mice, which were also attenuated by glibenclamide. These results indicated that the novel H2S donor reduced seizures and regulated microglial inflammatory cytokines by activating KATP channels, which may provide a prospective therapeutic strategy for the anti-seizure effects of H2S donor.

Psychosocial stressors and breast cancer gene expression in the Black Women's Health Study.

PURPOSE: Prior studies indicate that the physiologic response to stress can affect gene expression. We evaluated differential gene expression in breast cancers collected from Black women with high versus low exposure to psychosocial stressors. METHODS: We analyzed tumor RNA sequencing data from 417 Black Women's Health Study breast cancer cases with data on early life trauma and neighborhood disadvantage. We conducted age-adjusted differential gene expression analyses and pathway analyses. We also evaluated Conserved Transcriptional Response to Adversity (CTRA) contrast scores, relative fractions of immune cell types, T cell exhaustion, and adrenergic signaling. Analyses were run separately for estrogen receptor positive (ER+; n = 299) and ER- (n = 118) cases. RESULTS: Among ER+ cases, the top differentially expressed pathways by stress exposure were related to RNA and protein metabolism. Among ER- cases, they were related to developmental biology, signal transduction, metabolism, and the immune system. Targeted analyses indicated greater immune pathway enrichment with stress exposure for ER- cases, and possible relevance of adrenergic signaling for ER+ cases. CTRA contrast scores did not differ by stress exposure, but in analyses of the CTRA components, ER- breast cancer cases with high neighborhood disadvantage had higher pro-inflammatory gene expression (p = 0.039) and higher antibody gene expression (p = 0.006) compared to those with low neighborhood disadvantage. CONCLUSION: There are multiple pathways through which psychosocial stress exposure may influence breast tumor biology. Given the present findings on inflammation and immune response in ER- tumors, further research to identify stress-induced changes in the etiology and progression of ER- breast cancer is warranted.

Fan-in/fan-out for heterogeneous 19-core fibers based on metasurfaces with nonuniform phase plates.

In space-division-multiplexed transmission systems, it is essential to realize fan-in/fan-out devices that connect the cores between multicore fibers and single-mode fibers. In this Letter, we propose a metasurface-based fan-in/fan-out device with nonuniform phase plates for heterogeneous 19-core fibers across the full C band. Our results show that an average insertion loss of 0.85 dB and a maximum crosstalk of -25.5 dB can be achieved at 1550 nm. Across the C band, the insertion loss and crosstalk are better than 2.78 dB and -19.96 dB, respectively. The proposed concept can flexibly handle various fiber configurations without additional complexity.

Creation and preservation of superoscillation in a dielectric optical waveguide.

Superoscillation refers to a phenomenon where a band-limited wave locally oscillates faster than its highest Fourier component. Current research on optical superoscillations predominantly lies on the basis of free-space waves. As the optical waveguides play a key role in energy and information transportation, guided waves with precisely controlled deep-subwavelength features offers unprecedented flexibility for applications. In this Letter, we numerically show that, by superimposing eigenmodes of a multimode SiO2 waveguide and forcing the resultant field to pass through a set of predetermined points, superoscillatory fields in various shapes can be formed in preset cross-sectional planes. Furthermore, by padding prescribed intensities in multiple cross sections, we successfully create a persistent superoscillatory saddle.

Co-Gasification Synergistic Characteristics of Sewage Sludge and High-Sodium Coal.

A comprehensive study was conducted to assess the co-gasification characteristics of sewage sludge and high-sodium coal. As the gasification temperature increased, the CO2 concentration was decreased, and the concentrations of CO and H2 were increased, while the change of CH4 concentration was not obvious. As the coal blending ratio increased, the H2 and CO concentrations initially increased and then decreased, while the CO2 concentration initially decreased and then increased. The mixture of sewage sludge and high-sodium coal shows the synergistic effect of co-gasification, and the synergistic effect was to promote the gasification reaction positively. The average activation energies of co-gasification reactions were calculated by the OFW method, and the average activation energy initially decreases and then increases as the coal blending ratio increases. Both fluidized-bed gasification and thermogravimetric analyzer gasification show that the optimum coal blending ratio is 0.6. Overall, these results provide a theoretical basis for the industrial application of sewage sludge and high-sodium coal co-gasification.

Comparison of gene set scoring methods for reproducible evaluation of multiple tuberculosis gene signatures.

Rationale: Many blood-based transcriptional gene signatures for tuberculosis (TB) have been developed with potential use to diagnose disease, predict risk of progression from infection to disease, and monitor TB treatment outcomes. However, an unresolved issue is whether gene set enrichment analysis (GSEA) of the signature transcripts alone is sufficient for prediction and differentiation, or whether it is necessary to use the original statistical model created when the signature was derived. Intra-method comparison is complicated by the unavailability of original training data, missing details about the original trained model, and inadequate publicly-available software tools or source code implementing models. To facilitate these signatures' replicability and appropriate utilization in TB research, comprehensive comparisons between gene set scoring methods with cross-data validation of original model implementations are needed. Objectives: We compared the performance of 19 TB gene signatures across 24 transcriptomic datasets using both re-rebuilt original models and gene set scoring methods to evaluate whether gene set scoring is a reasonable proxy to the performance of the original trained model. We have provided an open-access software implementation of the original models for all 19 signatures for future use. Methods: We considered existing gene set scoring and machine learning methods, including ssGSEA, GSVA, PLAGE, Singscore, and Zscore, as alternative approaches to profile gene signature performance. The sample-size-weighted mean area under the curve (AUC) value was computed to measure each signature's performance across datasets. Correlation analysis and Wilcoxon paired tests were used to analyze the performance of enrichment methods with the original models. Measurement and Main Results: For many signatures, the predictions from gene set scoring methods were highly correlated and statistically equivalent to the results given by the original diagnostic models. PLAGE outperformed all other gene scoring methods. In some cases, PLAGE outperformed the original models when considering signatures' weighted mean AUC values and the AUC results within individual studies. Conclusion: Gene set enrichment scoring of existing blood-based biomarker gene sets can distinguish patients with active TB disease from latent TB infection and other clinical conditions with equivalent or improved accuracy compared to the original methods and models. These data justify using gene set scoring methods of published TB gene signatures for predicting TB risk and treatment outcomes, especially when original models are difficult to apply or implement.

A Review of Hydroxylated and Methoxylated Brominated Diphenyl Ethers in Marine Environments.

Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) and methoxylated polybrominated diphenyl ethers (MeO-PBDEs) are present in the marine environment worldwide. Both OH-PBDEs and MeO-PBDEs are known natural products, whereas OH-PBDEs may also be metabolites of PBDEs. There is growing concern regarding OH-PBDEs as these compounds seem to be biological active than PBDEs. In the present study, we reviewed the available data on the contamination of OH/MeO-PBDEs in the marine environment worldwide, including seawater, marine sediment, marine plants, invertebrates, fish, seabirds and mammals. Bioaccumulation and biomagnification of OH/MeO-PBDEs in the marine food web were summarized as well. This study also proposes the future research of OH/MeO-PBDEs, including the production and the synthesis pathway of OH/MeO-PBDEs, the toxicokinetics of OH/MeO-PBDEs and the toxicology and human exposure risk assessment.

Bioaccumulation and Biomagnification of Hexabromocyclododecane in Marine Biota from China: A Review.

Hexabromocyclododecane (HBCD) was listed in Annex A of the Stockholm Convention on Persistent Organic Pollutants for its persistence, bioaccumulation and toxicity, and pose significant adverse effects on natural environments and human health. HBCDs are ubiquitously found in marine environments worldwide and can be biomagnified in marine organisms with a high trophic level. In the present study, we reviewed the available data on contamination of HBCDs in the marine biota from China, including mollusks, crustaceans, fish and mammals. Bioaccumulation and biomagnification of HBCDs in the marine food web were summarized as well. This study also prospected the future research of HBCDs, including the transport and fluxes of HBCDs to and within the marine environment, the biomagnification of HBCDs in different ecosystems, and the metabolism of HBCDs in different marine species.

Strong Coupling Superconductivity in Ca-Intercalated Bilayer Graphene on SiC.

The metal-intercalated bilayer graphene has a flat band with a high density of states near the Fermi energy and thus is anticipated to exhibit an enhanced strong correlation effect and associated fascinating phenomena, including superconductivity. By using a self-developed multifunctional scanning tunneling microscope, we succeeded in observing the superconducting energy gap and diamagnetic response of a Ca-intercalated bilayer graphene below a critical temperature of 8.83 K. The revealed high value of gap ratio, 2Δ/kBTc ≈ 5.0, indicates a strong coupling superconductivity, while the variation of penetration depth with temperature and magnetic field indicates an isotropic s-wave superconductor. These results provide crucial experimental clues for understanding the origin and mechanism of superconductivity in carrier-doped graphene.

Immunopathogenic overlap between COVID-19 and tuberculosis identified from transcriptomic meta-analysis and human macrophage infection.

Current and previous tuberculosis (TB) increase the risk of COVID-19 mortality and severe disease. To identify mechanisms of immunopathogenic interaction between COVID-19 and TB, we performed a systematic review and patient-level meta-analysis of COVID-19 transcriptomic signatures, spanning disease severity, from whole blood, PBMCs, and BALF. 35 eligible signatures were profiled on 1181 RNA-seq samples from 853 individuals across the spectrum of TB infection. Thirteen COVID-19 gene-signatures had significantly higher "COVID-19 risk scores" in active TB and latent TB progressors compared with non-progressors and uninfected controls (p<0·005), in three independent cohorts. Integrative single-cell-RNAseq analysis identified FCN1- and SPP1-expressing macrophages enriched in severe COVID-19 BALF and active TB blood. Gene ontology and protein-protein interaction networks identified 12-gene disease-exacerbation hot spots between COVID-19 and TB. Finally, we in vitro validated that SARS-CoV-2 infection is increased in human macrophages cultured in the inflammatory milieu of Mtb-infected macrophages, correlating with TMPRSS2, IFNA1, IFNB1, IFNG, TNF, and IL1B induction.

Influence Mechanism of Water-Soluble Sodium on Zhundong Coal Pyrolysis.

An inherent water-soluble sodium-loaded coal sample was prepared using crown ether for this study. The pyrolysis process of an inherent water-soluble sodium-loaded coal sample and a water-soluble sodium compound-loaded coal sample was researched by thermogravimetric analysis (TGA). Also, the pyrolysis kinetics of the coal samples were analyzed and researched by the distributed activation energy model (DAEM). The results show that the inherent water-soluble sodium is mainly concentrated on coal particles, which further aggravates the degree of the pyrolysis reaction. The presence of sodium can promote the weight loss of coal samples in the preliminary stage of pyrolysis and the thermal condensation stage, block the escape of volatile matter during the main pyrolysis period, and inhibit the process of graphitization of char. The activation energy of pyrolysis increases with the carbon conversion rate, and the presence of sodium can reduce the activation energy under the same carbon conversion rate.

Development and Validation of a Parsimonious Tuberculosis Gene Signature Using the digital NanoString nCounter Platform.

BACKGROUND: Blood-based biomarkers for diagnosing active tuberculosis (TB), monitoring treatment response, and predicting risk of progression to TB disease have been reported. However, validation of the biomarkers across multiple independent cohorts is scarce. A robust platform to validate TB biomarkers in different populations with clinical end points is essential to the development of a point-of-care clinical test. NanoString nCounter technology is an amplification-free digital detection platform that directly measures mRNA transcripts with high specificity. Here, we determined whether NanoString could serve as a platform for extensive validation of candidate TB biomarkers. METHODS: The NanoString platform was used for performance evaluation of existing TB gene signatures in a cohort in which signatures were previously evaluated on an RNA-seq dataset. A NanoString codeset that probes 107 genes comprising 12 TB signatures and 6 housekeeping genes (NS-TB107) was developed and applied to total RNA derived from whole blood samples of TB patients and individuals with latent TB infection (LTBI) from South India. The TBSignatureProfiler tool was used to score samples for each signature. An ensemble of machine learning algorithms was used to derive a parsimonious biomarker. RESULTS: Gene signatures present in NS-TB107 had statistically significant discriminative power for segregating TB from LTBI. Further analysis of the data yielded a NanoString 6-gene set (NANO6) that when tested on 10 published datasets was highly diagnostic for active TB. CONCLUSIONS: The NanoString nCounter system provides a robust platform for validating existing TB biomarkers and deriving a parsimonious gene signature with enhanced diagnostic performance.

Microplastic-induced apoptosis and metabolism responses in marine Dinoflagellate, Karenia mikimotoi.

Microplastics (MPs) occur widely in marine environments, and disturb the balance of aquatic ecosystems. In this study, programmed cell apoptosis in marine dinoflagellate, Karenia mikimotoi exposed to 10 mg L-1 micro/nanoplastics (MPs/NPs; polystyrene and polymethyl methacrylate) for 72 h was assessed. Prior to the toxicity assay, MPs/NPs were dialyzed to remove possible additives. Cell viability, membrane integrity, cell apoptosis, and total DNA concentration were measured to assess programmed cell apoptosis in K. mikimotoi following exposure to MPs/NPs. A transcriptome analysis was used to explore the potential toxic mechanism of MPs to K. mikimotoi. Programmed cell apoptosis was related to the size of MPs/NPs, and NPs could more easily impair cell viability, and reduced cell membrane integrity and DNA concentration. NP particles caused continuous apoptosis of K. mikimotoi compared to MP particles. Size had the greatest effect on toxicity in K. mikimotoi. In conclusion, the results evidenced that both MPs and NPs have a negative impact on the marine dinoflagellate, K. mikimotoi. However, NPs were more harmful to K mikimotoi than MPs, highlighting the potential ecological problems associated with exposure to NPs.

Hydroxychloroquine/chloroquine in patients with COVID-19 in Wuhan, China: a retrospective cohort study.

BACKGROUND: Since the COVID-19 pandemic, several therapeutic agents have been used in COVID-19 management. However, the results were controversial. Here, we aimed to evaluate the efficacy and safety of hydroxychloroquine (HCQ)/chloroquine (CQ) in COVID-19. METHODS: We retrospectively reviewed the medical charts of patients with COVID-19 admitted to an inpatient ward in Wuhan from 2020/Feb/08 to 2020/Mar/05. Patients with HCQ/CQ and age, gender, disease severity matched ones without HCQ/CQ were selected at a 1:2 ratio. The clinical, laboratory and imaging findings were compared between these two groups. The multivariate linear regression analysis was performed to identify the factors that might influence patients' virus shedding periods (VSPs). RESULTS: A total of 14 patients with HCQ/CQ and 21 matched ones were analyzed. The HCQ/CQ treatment lasted for an average of 10.36 ± 3.12 days. The mean VSPs were longer in the HCQ/CQ treatment group (26.57 ± 10.35 days vs. 19.10 ± 7.80 days, P = 0.020). There were 3 patients deceased during inpatient period, two patients were with HCQ/CQ treatment (P = 0.551). In the multivariate linear regression analysis, disease durations at admission (t = 3.643, P = 0.001) and HCQ/CQ treatment (t = 2.637, P = 0.013) were independent parameters for patients' VSPs. One patient with CQ had recurrent first-degree atrioventricular block (AVB) and obvious QTc elongation, another one complained about dizziness and blurred vision which disappeared after CQ discontinuation. One patient with HCQ had transient AVB. CONCLUSIONS: In summary, we identify that the HCQ/CQ administration is not related to less mortality cases at later phase of COVID-19. More studies are needed to explore whether HCQ/CQ treatment would lead to SARS-Cov-2 RNA clearance delay or not.

Tocilizumab for Severe COVID-19 Pneumonia: Experience from 5 Geriatric Chinese Patients with 6 Months Follow-up.

Objective: To enable physicians to understand the efficacy and safety of Tocilizumab (TCZ) in patients with severe coronavirus disease-2019 (COVID-19). Methods: We respectively reviewed the clinical records, laboratory results, and chest computed tomography (CT) scans of 5 geriatric patients with severe COVID-19 treated with TCZ during their inpatient hospitalization period in Wuhan from February 08, 2020 to April 04, 2020. The survival status of the patients in the third and the sixth month after being discharged was followed up and recorded. Results: On the fourteenth day after TCZ administration, periphery oxygen saturation rate (SpO2) returned to normal in 4 patients. The serum Interleukin-6 (IL-6) levels altered in five patients after TCZ infusion. One patient rapidly progressed to acute respiratory distress syndrome (ARDS) and died of multiple organ failures eventually. The other 4 patients were cured and discharged from the hospital. During the inpatient hospitalization period, two patients suffered from virus shedding periods (VSPs) delay, and one patient had mild upper respiratory tract infection. One patient died of esophageal carcinoma one month after being discharged. The other 3 patients survived despite mild cough and insomnia. Serum-specific IgG type antibody titer was decreased in one patient. Six months after being discharged, the other three patients were in good condition. Conclusion: TCZ may be an efficient therapeutic option for patients with COVID-19. However, the possibility of VSPs delay, secondary infection, serum protective antibody tilter attenuation, and long-term survival status should be addressed before TCZ therapy initiation.

Systematic evaluation of transcriptomic disease risk and diagnostic biomarker overlap between COVID-19 and tuberculosis: a patient-level meta-analysis.

BACKGROUND: The novel coronavirus, SARS-CoV-2, has increased the burden on healthcare systems already strained by a high incidence of tuberculosis (TB) as co-infection and dual presentation are occurring in syndemic settings. We aimed to understand the interaction between these diseases by profiling COVID-19 gene expression signatures on RNA-sequencing data from TB-infected individuals. METHODS: We performed a systematic review and patient-level meta-analysis by querying PubMed and pre-print servers to derive eligible COVID-19 gene expression signatures from human whole blood (WB), PBMCs or BALF studies. A WB influenza dataset served as a control respiratory disease signature. Three large TB RNA-seq datasets, comprising multiple cohorts from the UK and Africa and consisting of TB patients across the disease spectrum, were chosen to profile these signatures. Putative "COVID-19 risk scores" were generated for each sample in the TB datasets using the TBSignatureProfiler package. Risk was stratified by time to TB diagnosis in progressors and contacts of pulmonary and extra-pulmonary TB. An integrative analysis between TB and COVID-19 single-cell RNA-seq data was performed and a population-level meta-analysis was conducted to identify shared gene ontologies between the diseases and their relative enrichment in COVID-19 disease severity states. RESULTS: 35 COVID-19 gene signatures from nine eligible studies comprising 98 samples were profiled on TB RNA-seq data from 1181 samples from 853 individuals. 25 signatures had significantly higher COVID-19 risk in active TB (ATB) compared with latent TB infection (p <0·005), 13 of which were validated in two independent datasets. FCN1 - and SPP1 -expressing macrophages enriched in BALF during severe COVID-19 were identified in circulation during ATB. Shared perturbed ontologies included antigen presentation, epigenetic regulation, platelet activation, and ROS/RNS production were enriched with increasing COVID-19 severity. Finally, we demonstrate that the overlapping transcriptional responses may complicate development of blood-based diagnostic signatures of co-infection. INTERPRETATION: Our results identify shared dysregulation of immune responses in COVID-19 and TB as a dual risk posed by co-infection to COVID-19 severity and TB disease progression. These individuals should be followed up for TB in the months subsequent to SARS-CoV-2 diagnosis.

Protective effect of ferulic acid on STZ-induced diabetic nephropathy in rats.

Diabetic nephropathy (DN) is a major and severe complication of diabetes mellitus. Ferulic acid (FA), a phenolic compound widespread in fruits and plants, displays a variety of pharmacological activities including regulating blood glucose and lipids, anti-oxidation, anti-inflammation and anti-fibrosis. The study was aimed to investigate the renal protective effects of FA on diabetic rats and elucidate the underlying mechanisms. FA (100 mg kg-1, i.g., once a day) was administered to DN rats for 8 weeks. The organ coefficient of kidneys was calculated. Levels of UP, BUN, Cr, FBG, TC and TG in serum were measured. Activities of SOD, CAT and GPx and the content of MDA in renal tissues were assayed. Pathological changes in renal tissues were observed by HE staining, PAS staining, PASM staining, Masson staining and transmission electron microscopy. p-NF-κB p65, TNF-α, TGF-ß1, collagen IV, nephrin and podocin protein expressed in renal tissues were determined by immunohistochemistry and western blotting. Results showed that FA significantly improved the kidney organ coefficient, decreased the UP, BUN, Cr, FBG, TC and TG levels in serum, increased SOD, CAT and GPx activities, reduced MDA content in renal tissues and alleviated pathological injury of the renal tissues. What's more, long-term treatment with FA considerably down-regulated the expressions of p-NF-κB p65, TNF-α, TGF-ß1 and collagen IV proteins, and up-regulated the expressions of nephrin and podocin proteins in renal tissues. FA could be a renoprotective agent by attenuating oxidative stress, inflammation, and fibrosis, as well as improving podocyte injury in STZ-induced DN rats.

Secreted TGF-beta-induced protein promotes aggressive progression in bladder cancer cells.

Background: Transforming growth factor-beta-induced (TGFBI) is an exocrine protein, which has been found to be able to promote the development of nasopharyngeal carcinoma, glioma, pancreatic cancer, and other tumors. However, there is currently no report concerning the relationship between TGFBI and invasive progression of bladder cancer (BCa). Methods: IHC staining, qRT-PCR and Western blot were used to analyze TGFBI and EMT markers levels. In vivo tumorigenesis was performed by xenograft tumor model. Results: In this study, we found that both mRNA and protein levels of TGFBI were significantly up-regulated in muscle invasive bladder cancer (MIBC) tissues compared with non-muscle-invasive bladder cancer (NMIBC) tissues. The high expression level of TGFBI was positively correlated with high histological grade and advanced clinical stage, and BCa patients with high TGFBI levels exhibited poor prognoses. We further confirmed that high expression level of TGFBI can promote proliferation, invasive progression, and epithelial-to-mesenchymal transition (EMT) of BCa cells in vitro, as well as promote tumor growth and EMT in vivo, while silencing of TGFBI inhibited these malignant phenotypes. TGFBI was involved in the up-regulation of EMT by inducing the expression level of Slug, Vimentin, Snail, MMP2, and MMP9 genes, while it down-regulated the expression level of E-cadherin. Moreover, Western blot analysis was carried out to demonstrate that BCa cell lines stably transfected with expression of TGFBI, a secreted protein. Furthermore, conditional medium containing TGFBI protein also resulted in enhanced EMT and malignant phenotype of BCa cells. Conclusion: Our results indicate that high expression level of TGFBI promotes EMT, proliferation, and invasive progression of BCa cells, and TGFBI is a potential therapeutic target and prognostic marker for BCa.