The Biogeochemical Cycling of Dissolved Organic Nitrogen in Estuarine Sediments

Benthic fluxes and pore-water profiles of dissolved organic nitrogen and carbon (DON and DOC, respectively) were determined in seasonal studies at contrasting sites in Chesapeake Bay. Pore-water dissolved organic matter (DOM) concentrations were elevated over bottom-water values, generally increased with depth, and ranged from 15 to similar to 160 μM for DON and ~200-2000 μM for DOC. Pore-water DOM concentrations and the C:N ratio of this material showed spatial (depth) and temporal changes that varied among the sites studied. These trends appeared to be related to differences in the types of sediment organic matter (SOM) undergoing remineralization, as well as differences in the biogeochemical processes occurring in the sediments (e.g., the presence or absence of bioturbation and bioirrigation). Measured DON fluxes ranged from essentially zero to similar to 0.4 mmol m-2 d-1, and together with benthic DOC fluxes were coupled to seasonal trends in temperature and SOM remineralization rates. On an annual basis, benthic DON fluxes were a small fraction (similar to 3%) of benthic inorganic nitrogen fluxes. At an anoxic nonbioturbated site measured DON fluxes were essentially identical to calculated diffusive DON fluxes, whereas at a bioturbated and bioirrigated site, measured DON fluxes were much greater than calculated fluxes. The molar ratios of DOC to DON benthic fluxes ranged from ~2 to 6 and were lower than those of pore-water DOM, which were \u3e similar to 10. This implies that DOM accumulating in these sediment pore waters was carbon-rich compared with the DOM that was either remineralized or escaped the sediment as a benthic flux. These measured benthic DON fluxes and estimated DON fluxes from continental margin sediments combine to yield a lower limit for the integrated sediment DON flux to the oceans that is similar to a value estimated previously. These net DON inputs to the oceans are small compared with internal oceanic DON cycling rates, although sediment DON fluxes and riverine DON inputs are roughly of the same order. At the same time, our results also suggest that the DON escaping from these sediments may not be inherently refractory because of its observed low C:N ratio. This implies that estuarine sediments land perhaps marine sediment in general) may not be a major source of refractory DON to the oceans

Molecular basis for heat desensitization of TRPV1 ion channels.

The transient receptor potential vanilloid 1 (TRPV1) ion channel is a prototypical molecular sensor for noxious heat in mammals. Its role in sustained heat response remains poorly understood, because rapid heat-induced desensitization (Dh) follows tightly heat-induced activation (Ah). To understand the physiological role and structural basis of Dh, we carried out a comparative study of TRPV1 channels in mouse (mV1) and those in platypus (pV1), which naturally lacks Dh. Here we show that a temperature-sensitive interaction between the N- and C-terminal domains of mV1 but not pV1 drives a conformational rearrangement in the pore leading to Dh. We further show that knock-in mice expressing pV1 sensed heat normally but suffered scald damages in a hot environment. Our findings suggest that Dh evolved late during evolution as a protective mechanism and a delicate balance between Ah and Dh is crucial for mammals to sense and respond to noxious heat

Synthesis and Antitumor Activity of N-Triazol-5-yl-oxazolidin-4-one Derivatives.

Fifteen novel N-triazol-5-yl-oxazolidin-4-ones were synthesized through a few of steps from the benzaldehydes. It was found that N-iodosuccinimide (NIS) can promote intramolecular amination reaction which is the key step of the syntheses, which will be used as new method for the intramolecular formation of nitrogen-containing heterocycles. Part of the compounds were evaluated for their anticancer activity. Among them, compounds 6a, 6b and 6c showed moderate antiprolifiration activity toward human breast cancer cells MDA-MB-231 cell lines, while the mild activity of 6a, 6b and 6d against human cervical cancer HeLa cell lines was confirmed in vitro assay

Ligands of Therapeutic Utility for the Liver X Receptors.

Liver X receptors (LXRs) have been increasingly recognized as a potential therapeutic target to treat pathological conditions ranging from vascular and metabolic diseases, neurological degeneration, to cancers that are driven by lipid metabolism. Amidst intensifying efforts to discover ligands that act through LXRs to achieve the sought-after pharmacological outcomes, several lead compounds are already being tested in clinical trials for a variety of disease interventions. While more potent and selective LXR ligands continue to emerge from screening of small molecule libraries, rational design, and empirical medicinal chemistry approaches, challenges remain in minimizing undesirable effects of LXR activation on lipid metabolism. This review provides a summary of known endogenous, naturally occurring, and synthetic ligands. The review also offers considerations from a molecular modeling perspective with which to design more specific LXRβ ligands based on the interaction energies of ligands and the important amino acid residues in the LXRβ ligand binding domain

Quantity and clinical relevance of circulating endothelial progenitor cells in human ovarian cancer

<p>Abstract</p> <p>Background</p> <p>Circulating bone marrow-derived endothelial progenitor cells (EPCs) have been reported to participate in tumor angiogenesis and growth; however, the role of circulating EPCs in tumor progression is controversial. The role of circulating EPCs in ovarian cancer progression and angiogenesis has not yet been investigated.</p> <p>Methods</p> <p>The number of circulating EPCs in the peripheral blood in 25 healthy volunteers and 42 patients with ovarian cancer was determined by flow cytometry. EPCs were defined by co-expression of CD34 and vascular endothelial growth factor receptor 2 (VEGFR2). In addition, we determined CD34 and VEGFR2 mRNA levels by real-time reverse transcription-polymerase chain reaction. Plasma levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were determined by enzyme-linked immunosorbent assay.</p> <p>Results</p> <p>Circulating levels of EPCs were significantly increased in ovarian cancer patients, correlating with tumor stage and residual tumor size. Higher levels of EPCs were detected in patients with stage III and IV ovarian cancer than in patients with stage I and II disease. After excision of the tumor, EPCs levels rapidly declined. Residual tumor size greater than 2 cm was associated with significantly higher levels of EPCs. In addition, high circulating EPCs correlated with poor overall survival. Pretreatment CD34 mRNA levels were not significantly increased in ovarian cancer patients compared with healthy controls; however, VEGFR2 expression was increased, and plasma levels of VEGF and MMP-9 were also elevated.</p> <p>Conclusions</p> <p>Our results demonstrate the clinical relevance of circulating EPCs in ovarian cancer. EPCs may be a potential biomarker to monitor ovarian cancer progression and angiogenesis and treatment response.</p

An Early Evaluation of GPT-4V(ision)

In this paper, we evaluate different abilities of GPT-4V including visual understanding, language understanding, visual puzzle solving, and understanding of other modalities such as depth, thermal, video, and audio. To estimate GPT-4V's performance, we manually construct 656 test instances and carefully evaluate the results of GPT-4V. The highlights of our findings are as follows: (1) GPT-4V exhibits impressive performance on English visual-centric benchmarks but fails to recognize simple Chinese texts in the images; (2) GPT-4V shows inconsistent refusal behavior when answering questions related to sensitive traits such as gender, race, and age; (3) GPT-4V obtains worse results than GPT-4 (API) on language understanding tasks including general language understanding benchmarks and visual commonsense knowledge evaluation benchmarks; (4) Few-shot prompting can improve GPT-4V's performance on both visual understanding and language understanding; (5) GPT-4V struggles to find the nuances between two similar images and solve the easy math picture puzzles; (6) GPT-4V shows non-trivial performance on the tasks of similar modalities to image, such as video and thermal. Our experimental results reveal the ability and limitations of GPT-4V and we hope our paper can provide some insights into the application and research of GPT-4V.Comment: Technical Report. Data are available at https://github.com/albertwy/GPT-4V-Evaluatio

Causal analysis of the gut microbiota in differentiated thyroid carcinoma: a two-sample Mendelian randomization study

Objective: Numerous studies have highlighted an association between the gut microbiota (GM) and thyroid tumors. Employing Mendelian randomization methodology, we seek to elucidate the causal link between the gut microbiota and thyroid neoplasms.Methods: We procured data from the Mibiogen database encompassing 211 distinct gut microbiota taxa, alongside extensive genome-wide association studies (GWAS) summary data for differentiated thyroid carcinoma (DTC). Our principal analytical approach involved the application of the Inverse-Variance Weighted method (IVW) within the framework of Mendelian randomization. Simultaneously, we conducted sensitivity analyses to assess result heterogeneity, horizontal pleiotropy, and outcome stability.Results: IVW analysis revealed a dual role of the GM in thyroid carcinoma. The phylum Actinobacteria (OR, 0.249 [95% CI, 0.121–0.515]; p &lt; 0.001) was associated with a decreased risk of DTC. Conversely, the genus Ruminiclostridium9 (OR, 11.276 [95% CI, 4.406–28.860]; p &lt; 0.001), class Mollicutes (OR, 5.902 [95% CI, 1.768–19.699]; p = 0.004), genus RuminococcaceaeUCG004 (OR, 3.831 [95% CI, 1.516–9.683]; p = 0.005), genus Paraprevotella (OR, 3.536 [95% CI, 1.330–9.401]; p = 0.011), and phylum Tenericutes (OR, 5.902 [95% CI, 1.768–19.699]; p = 0.004) were associated with an increased risk of DTC.Conclusion: Our findings underscore that the presence of genus Ruminiclostridium9, class Mollicutes, genus RuminococcaceaeUCG004, genus Paraprevotella, and phylum Tenericutes is associated with an elevated risk of DTC, whereas the presence of the phylum Actinobacteria is linked to a decreased risk. These discoveries enhance our comprehension of the relationship between the GM and DTC