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Microplastic pollution poses a significant threat to the ecosystem, encompassing not only aquatic organisms but also plants and human health due to their capacity for bioaccumulation, driven by their minute size and persistence. Although previous research predominantly centered on the effects of microplastics in ocean environments, it is vital to recognize that their ultimate destination is often rivers and estuaries, serving as more precise point sources for analysis. This research focuses on a comprehensive investigation involving the monitoring and modeling of microplastic distribution and concentration within the Delaware estuary. Grab and net sampling methods were employed across Philadelphia, Camden, and Wilmington, Delaware, to examine the distribution, concentration, and characteristics of these pollutants. The findings indicate that microplastic's diameters varied from 90 µm to 1000 µm along the Delaware River, with 71% of particles in grab samples under 500 µm. In contrast, 66% of particles in net samples exceeded 500 µm. Moreover, concentrations in grab samples ranged from 0.24072 to 7.08 particles/m3, whereas net samples showed significantly lower concentrations, ranging from 0.000059 to 0.00268 particles/m3. The investigation discovered a range of plastic compounds, most notably polyester, polypropylene, and polyethylene, with fibers being the most common shape. Furthermore, the concentration and composition of microplastics were closely linked to urbanization, population density, and industrial activities. Analysis using the Delaware River Basin Commission's 3D hydrodynamics model revealed that microplastics predominantly stayed in upper water layers for up to 20 days and moved toward the opposite bank from their release point, influenced by current dynamics. These findings not only enhance our comprehension of microplastic pollution in freshwater ecosystems but also establish a foundational framework for future research aimed at developing effective management and remediation strategies, particularly for ecosystems near to the Delaware estuary. This study provides essential data that can inform policy decisions and conservation initiatives designed to reduce the environmental impact of microplastics. [ABSTRACT FROM AUTHOR]

Antimetabolite antitumor drugs interfere with nucleic acid and DNA synthesis, causing cancer cell death. However, they also affect rapidly dividing normal cells and cause serious side effects. Doxifluridine (5′-deoxy-5-fluorouridine [5′-DFUR]), a 5-fluorouracil (5-FU) prodrug converted to 5-FU by thymidine phosphorylase (TP), exerts antitumor effects. Since TP is distributed in tumor and normal tissues, 5′-DFUR features side effects. Here we designed a series of novel 5′-DFUR derivatives based on high nitroreductase (NTR) levels in the hypoxic microenvironment of tumor tissues by introducing nitro-containing moieties into the 5′-DFUR structure. These derivatives exert their antitumor effects by producing 5-FU under the dual action of TP and NTR in the tumor microenvironment. The derivatives were synthesized and their stability, release, and cytotoxicity evaluated in vitro and antitumor activity evaluated in vivo. Compound 2c, featuring nitrofuran fragments, was stable in phosphate-buffered saline and plasma at different pH values and reduced rapidly in the presence of NTR. The in vitro cytotoxicity evaluation indicated that compound 2c showed excellent selectivity in the MCF-7 and HT29 cell lines. Moreover, it exhibited antitumor effects comparable to those of 5′-DFUR in vivo without significant toxic side effects. These results suggest that compound 2c is a promising antitumor prodrug. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a common metabolic disease that poses a severe threat to human health. Despite a range of therapeutic approaches, there remains a lack of effective and safe therapies with the existing drugs. Therefore, there is an urgent need to develop novel, effective, and safe therapeutic strategies for DM. Free fatty acid receptor 4 (FFAR4), also known as GPR120, is a member of the G protein-coupled receptor family, which has received considerable attention as an attractive new therapeutic target for treating DM. In the present study, based on the structure of TUG-891, which has excellent activity and selectivity, a series of novel FFAR4 agonists was designed by replacing the phenylpropanoic acid β position carbon atom with an oxygen atom, while replacing the linking oxymethylene with an amide-linking group. The target compounds were evaluated for FFAR4 agonistic activity, and the preferred compounds were evaluated for selectivity, oral glucose tolerance in normal ICR mice, antidiabetic activity in diet-induced obese (DIO) mice, pharmacokinetic properties in ICR mice and molecular modeling studies. The results showed that compound 10f possessed excellent FFAR4 agonistic activity and selectivity, significantly improved glucose tolerance in normal ICR mice, lowered blood glucose and promoted insulin secretion in a dose-dependent manner in DIO mice, and showed favorable pharmacokinetic properties. These results indicate that compound 10f may be a promising compound that deserves further structure–activity relationship and pharmacological studies for the development of antidiabetic drugs. [ABSTRACT FROM AUTHOR]

Forest fires pose a catastrophic threat to Earth's ecology as well as threaten human beings. Timely and accurate monitoring of forest fires can significantly reduce potential casualties and property damage. Thus, to address the aforementioned problems, this paper proposed an unmanned aerial vehicle (UAV) based on a lightweight forest fire recognition model, Fire-Net, which has a multi-stage structure and incorporates cross-channel attention following the fifth stage. This is to enable the model's ability to perceive features at various scales, particularly small-scale fire sources in wild forest scenes. Through training and testing on a real-world dataset, various lightweight convolutional neural networks were evaluated on embedded devices. The experimental outcomes indicate that Fire-Net attained an accuracy of 98.18%, a precision of 99.14%, and a recall of 98.01%, surpassing the current leading methods. Furthermore, the model showcases an average inference time of 10 milliseconds per image and operates at 86 frames per second (FPS) on embedded devices. [ABSTRACT FROM AUTHOR]

As genotypic and phenotypic mutations that enhance survivability are preserved during tumor evolution, some cancer cells tend to develop resistance to a particular programmed death, leading to the failure of cancer monotherapy. Fortunately, the combinational therapy of apoptosis and ferroptosis holds potential for addressing this tumor heterogeneity. Herein, a multifunctional free radical initiator was prepared by coating DHA-loaded mesoporous polydopamine (MPDA) nanospheres with Fe3+-tannic acid (TA) complexes and hyaluronic acid (HA) to achieve oxidative stress amplification and apoptosis/ferroptosis sensitization. This nanoplatform MPDA/DHA@Fe–TA@HA, denoted as MDTFH, was equipped with active targeting and tumor microenvironment (TME) activation, facilitating precise delivery and tumor-specific toxicity of chemotherapeutic agents, DHA. Upon exposure to the HAase-rich and acidic TME, the HA coating and Fe–TA networks would dissociate gradually, triggering the controlled release of Fe3+ and internal DHA. Subsequently, the Fe3+/Fe2+ conversion driven by glutathione (GSH) depletion would catalyze the Fenton reaction and DHA toxification to produce ˙OH and ˙C, that is, chemodynamic therapy (CDT) and chemotherapy (CT) were activated, respectively. Moreover, the superior photothermal therapy (PTT) effect stimulated by NIR irradiation could improve the efficacy of CDT and CT, which together with hyperthermia-induced tumor sensitivity intensify oxidative stress and lipid peroxidation, thus leading to apoptosis and ferroptosis. It was demonstrated in a 4T1 tumor-bearing mice model that MDTFH can significantly inhibit tumor growth through synergistic PTT/CT/CDT effects. Overall, this work provides a feasible paradigm to design multimodal therapeutic strategies inducing ferroptosis and apoptosis for cancer precision therapy. [ABSTRACT FROM AUTHOR]

PIO, a synthetic ligand for PPAR[gamma], is used clinically to treat T2DM. However, little is known about its protective effects on endothelium and the underlying mechanisms. In this study, we sought to investigate the protective effects of PIO on endothelium and its probable mechanisms: 95% confluent wild type (WT) HUVECs and [PPAR[gamma].sup.Low]-HUVECs that we first injured with HG (33 mmol x [L.sup.- 1]) were first pretreated with 10 [micro]mol x [L.sup.-1] of GW9662 for 30 min, and then treated the cells with different concentrations of PIO (5,10, or 20 [micro]mol x [L.sup.-1]) for 24 h. Finally, we measured the levels of NO, ET1, TNF[alpha], and IL6 in the cell culture supernatant. These cells were then used to determine cell viability, caspase3 activity, the levels of IKK[alpha]/[beta] mRNA, IKK[alpha]/[beta], and NF[kappa]B-p65. Severe dysfunction and activation of IKK[alpha]/[beta]-NF[kappa]B signaling occurred after we exposed HUVECs to HG. Conversely, treatment with PIO significantly attenuated the dysfunction and the activation of IKK[alpha]/[beta]-NF[kappa]B signaling induced by HG in a dose-dependent manner. Moreover, the protective effects of PIO were completely abrogated by GW9662 or down-regulation of PPAR[gamma]. Taken together, the results indicate that PIO protects HUVECs against the HG-induced dysfunction through the inhibition of IKK[alpha]/[beta]-NF[kappa]B signaling mediated by PPAR[gamma]. Key words: pioglitazone, high glucose, nitric oxide, endothelial cell, PPAR[gamma]. La pioglitazone (PIO), un ligand synthetique du recepteur y active par les proliferateurs de peroxysomes (ou PPAR[gamma] pour peroxisome proliferator activated receptor [gamma]), est utilisee en clinique pour traiter le diabete sucre de type 2 (T2DM). Cependant, on sait peu de choses de ses effets protecteurs sur l'endothelium et des modes d'action sous-jacents. Dans ces travaux, nous avons cherche a etudier les effets protecteurs du PIO sur l'endothelium et ses modes d'action probables. Nous avons expose au prealable des cellules HUVEC PPAR[gamma]Bas et de type sauvage confluentes a 95 % et lesees par du glucose a haute concentration (GHC, 33 mmol x [L.sup.-1]) a du GW9662 a 10 [micro]mol x [L.sup.- 1] pendant 30 min, puis a diverses concentrations de PIO (5,10, ou 20 [micro]mol x [L.sup.-1]) pendant 24 h. Enfin, nous avons dose les taux de NO, d'endotheline 1 (ET1), de facteur de necrose tumorale alpha (TNF[alpha]) et d'interleukine 6 (IL6). Nous avons utilise les cellules afin d'etablir la viabilite cellulaire et l'activite de la caspase 3, ainsi que les taux d'ARNm de la kinase IKK[alfa]/[beta] (inhibitory [kappa]B kinase [alfa]/[beta]), de kinase IKK[alfa]/[beta] et de proteine p65 du facteur nucleaire [kappa]B (NF[kappa]B).Undysfonctionnementetune activation serieux de lavoie de signalisation IKK[alfa]/[beta]-NF[kappa]B sont survenus apres l'exposition des cellules HUVEC au GHC. Inversement, l'exposition a la PIO a permis d'attenuer nettement, et de maniere proportionnelle a la dose, le dysfonctionnement et l'activation de la voie de signalisation IKK[alfa]/[beta]-NF[kappa]B provoques par le GHC. En outre, les effets protecteurs de la PIO etaient reduits a neant par le GW9662 ou la regulation a la baisse du PPAR[gamma]. Dans l'ensemble, la PIO permet de proteger les cellules HUVEC contre le dysfonctionnement provoque par le GHC par l'intermediaire de l'inhibition de la voie de signalisation IKK[alfa]/[beta]-NF[kappa]B dont la mediation est assuree par le PPAR[gamma]. [Traduit par la Redaction] Mots-cles: pioglitazone, glucose a haute concentration, oxyde nitrique, cellule endotheliale, PPAR[gamma]., Introduction Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia. Chronic hyperglycemia results in target organ impairment through oxidative stress, etc., resulting in angiopathy, retinopathy, renopathy, and neuropathy, [...]

Background: NADPH oxidase 2 (NOX2) is highly expressed in injured brain tissues. We determined serum NOX2 levels of aneurysmal subarachnoid hemorrhage (aSAH) patients and further investigated correlation of serum NOX2 levels with disease severity, delayed cerebral ischemia (DCI) plus prognosis after aSAH. Methods: Serum NOX2 levels were measured in 123 aSAH patients and 123 healthy controls. World Federation of Neurological Surgeons scale (WFNS) score and modified Fisher (mFisher) score were utilized to assess disease severity. Modified Rankin scale (mRS) score was used to evaluate the clinical prognosis at 90 days after aSAH. Relations of serum NOX2 levels to DCI and 90-day poor prognosis (mRS score of 3– 6) were analyzed using multivariate analysis. Receiver operating characteristic curve (ROC) was built to evaluate the prognostic predictive capability. Results: Serum NOX2 levels in aSAH patients, compared with healthy controls, were significantly increased, and were independently correlated with WFNS score, mFisher score and post-stroke 90-day mRS score. Patients with poor prognosis or DCI had significantly higher serum NOX2 levels than other remainders, and serum NOX2 levels independently predicted 90-day poor prognosis and DCI. Serum NOX2 had high prognosis and DCI predictive abilities, and their areas under ROC curve were similar to those of WFNS score and mFisher score. Conclusion: Serum NOX2 levels are significantly associated with hemorrhage severity, poor 90-day prognosis and DCI in aSAH patients. Hence, complement NOX2 may serve as a potential prognostic biomarker after aSAH. [ABSTRACT FROM AUTHOR]