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Salvinorin A (SA) exerts neuroprotection and improves neurological outcomes in ischemic stroke models in rodents. In this study, we investigated whether intranasal SA administration could improve neurological outcomes in a monkey ischemic stroke model. The stroke model was induced in adult male rhesus monkeys by occluding the middle cerebral artery M2 segment with an autologous blood clot. Eight adult rhesus monkeys were randomly administered SA or 10% dimethyl sulfoxide as control 20 min after ischemia. Magnetic resonance imaging was used to confirm the ischemia and extent of injury. Neurological function was evaluated using the Non-Human Primate Stroke Scale (NHPSS) over a 28-day observation period. SA significantly reduced infarct volume (3.9 ± 0.7 cm 3 vs. 7.2 ± 1.0 cm 3 ; P  =   0.002), occupying effect (0.3 ± 0.2% vs. 1.4 ± 0.3%; P  =   0.002), and diffusion limitation in the lesion (-28.2 ± 11.0% vs. -51.5 ± 7.1%; P  =   0.012) when compared to the control group. SA significantly reduced the NHPSS scores to almost normal in a 28-day observation period as compared to the control group ( P  =   0.005). Intranasal SA reduces infarct volume and improves neurological outcomes in a rhesus monkey ischemic stroke model using autologous blood clot.

Early reperfusion is increasingly prioritized in ischemic stroke care, but outcomes remain suboptimal. Therefore, there is an urgent need to find neuroprotective approaches that can be combined with reperfusion to maximize efficacy. Here, the neuroprotective mechanisms behind therapeutic hypothermia were evaluated in a monkey model of ischemic stroke. Focal ischemia was induced in adult rhesus monkeys by placing autologous clots in the middle cerebral artery. Monkeys were treated with tissue plasminogen activator (t-PA) alone or t-PA plus selective intra-arterial cooling (SI-AC). Serial MRI scans and functional deficit were evaluated after ischemia. Histopathology and immunohistochemistry analysis were performed after the final MRI scan. t-PA plus SI-AC treatment led to a higher rate of MRI tissue rescue, and significantly improved neurologic deficits and daily activity scores compared with t-PA alone. In peri-infarct areas, higher fractional anisotropy values and greater fiber numbers were observed in models receiving t-PA plus SI-AC. Histological findings indicated that myelin damage, spheroids, and spongiosis were significantly ameliorated in models receiving SI-AC treatment. White matter integrity was also improved by SI-AC based on immunochemical staining. Our study demonstrates that SI-AC can be effectively combined with t-PA to improve both structural and functional recovery in a monkey model of focal ischemia. These findings provide proof-of-concept that it may be feasible to add neuroprotective agents as adjunctive treatments to reperfusion therapy for stroke.

Nearly all stroke neuroprotection modalities, including selective intra-arterial cooling (SI-AC), have failed to be translated from bench to bed side. Potentially overlooked reasons may be biological gaps, inadequate attention to reperfusion states and mismatched attention to neurological benefits. To advance stroke translation, we describe a novel thrombus-based stroke model in adult rhesus macaques. Intra-arterial thrombolysis with tissue plasminogen activator leads to three clinically relevant outcomes - complete, partial, and no recanalization based on digital subtraction angiography. We also find reperfusion as a prerequisite for SI-AC-induced benefits, in which models with complete or partial reperfusion exhibit significantly reduced infarct volumes, mitigated neurological deficits, improved upper limb motor dysfunction in both acute and chronic stages; however, no further neuroprotection is observed in those without reperfusion. In summary, we discover reperfusion as a crucial regulator of SI-AC-induced neuroprotection and provide insights of long-term functional benefits in behavior and imaging levels. Our findings could be important not only for the translational prerequisite and potential molecular targets, but also for this thrombus-thrombolysis model in monkeys as a powerful tool for further translational stroke studies.

Triamcinolone acetonide (TCA) abuse in cosmetics is a common phenomenon. A rapid lateral flow immunochromatographic assay (ICA) was developed for the quantitative detection of TCA using a probe based on upconversion luminescence nanoparticles. Lanthanide-doped upconversion nanoparticles (UCNPs) were synthesized in a system comprising water and ethylene glycol, and a silicon dioxide layer was covered at the carboxyl site. A binding site protection strategy was used to decrease the background signal of UCNPs-ICA. Using dexamethasone derivative as a coating antigen, the optimal UCNPs-ICA exhibits good dynamic linear detection for TCA in the range 1.0-100 ng mL -1 with a median inhibitory concentration of 9.8 ng mL -1 . The detection limits for TCA in a cosmetic sample are 20 μg kg -1 . The pretreatment of samples only needs dilution with water, suggesting the assay can quantitate TCA on-site using a portable upconversion luminescence reader with a cumulative analysis time of only 10 min., (Copyright © 2019. Published by Elsevier B.V.)

The present study reports a mechanochemical (MC) process for effective recovery of copper (Cu) and precious metals (i.e. Pd and Ag) from e-waste scraps. Results indicated that the mixture of K 2 S 2 O 8 and NaCl (abbreviated as K 2 S 2 O 8 /NaCl hereafter) was the most effective co-milling reagents in terms of high recovery rate. After co-milling with K 2 S 2 O 8 /NaCl, soluble metallic compounds were produced and consequently benefit the subsequent leaching process. 99.9% of Cu and 95.5% of Pd in the e-waste particles could be recovered in 0.5mol/L diluted HCl in 15min. Ag was concentrated in the leaching residue as AgCl and then recovered in 1mol/L NH 3 solution. XRD and XPS analysis indicated that elemental metals in the raw materials were transformed into their corresponding oxidation state during ball milling process at low temperature, implying that solid-solid phase reactions is the reaction mechanism. Based on the results and thermodynamic parameters of the probable reactions, possible reaction pathways during ball milling were proposed. Suggestion on category of e-waste for ball milling process was put forward according to the experiment results. The designed metal recovery process of this study has the advantages of highly recovery rate and quick leaching speed. Thus, this study offers a promising and environmentally friendly method for recovering valuable metals from e-waste., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

To assess the impacts of bioturbation at the water-sediment interface on the bioaccumulation of hexabromocyclododecane diastereoisomers (HBCDDs) by pelagic organisms and the bioisomerization and enantioselectivity therein, we built microcosms containing water, mirror carp (Cyprinus carpio), and sediment. The microcosms were sorted into two groups, with or without loach (Misgurnus anguillicaudatus) living at the water-sediment interface. A 50-d accumulation test was conducted by spiking the microcosms with the three main HBCDD diastereoisomers (α-, β-, and γ-HBCDDs) separately. The HBCDDs were mainly associated with the sediment. The dissolved organic matter and suspended particulate matter content increased due to loach bioturbation, which promoted the release of sediment-associated HBCDDs and led to enhanced HBCDD bioaccumulation in the carp. Isomerization from β- and γ-HBCDD to α-HBCDD occurred in the carp, and the amounts of isomerization did not increase proportionally with increasing bioaccumulation. Moreover, the enantioselectivity of the HBCDD diastereoisomers showed species-specific differences between mirror carp and loach, and no significant change in the enantioselectivity in the carp was observed in the presence of loach., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: To comprehensively investigate the predictive value of thyroid hormone sensitivity parameters for cervical lymph node metastasis in patients diagnosed with differentiated thyroid cancer (DTC) undergoing total thyroidectomy and neck lymph node dissection., Methods: A retrospective cohort study was conducted involving patients diagnosed with DTC and evaluated for cervical lymph node metastasis. Relevant demographic, tumour, lymph node and thyroid hormone sensitivity parameter data were extracted from medical records and laboratory reports. Thyroid hormone sensitivity parameters including thyroxine (T4), triiodothyronine (T3), thyroid-stimulating hormone (TSH), thyroglobulin (Tg), thyroglobulin antibodies (TgAbs), thyroid peroxidase antibody, thyroid hormone receptor α and TSH receptor antibody were assessed. Statistical analyses including descriptive statistics, comparative analysis, Pearson's correlation analysis, logistic regression analysis, receiver operating characteristic (ROC) analysis and construction of a multivariable prediction model based on machine learning using the xgbTree method were employed to evaluate the associations and predictive value of thyroid hormone sensitivity parameters for cervical lymph node metastasis., Results: The study revealed significant associations between several thyroid hormone sensitivity parameters and cervical lymph node metastasis in patients with DTC. Specifically, higher levels of T4, T3, Tg, TgAbs and TSH receptor antibody were associated with lymph node metastasis. Pearson's correlation analysis, logistic regression analysis and ROC analysis further underscored the predictive performance of these parameters, with strong overall discriminative abilities. The machine learning-based prediction model demonstrated promising performance with a high area under the curve (AUC) of 0.979., Conclusions: The findings provide compelling evidence for the predictive value of thyroid hormone sensitivity parameters, particularly T3, T4, Tg, TgAbs and TSH receptor antibody, in identifying and evaluating the likelihood of cervical lymph node metastasis in patients with DTC. These parameters hold potential implications for risk stratification, clinical decision-making and personalized management strategies, contributing to improved outcomes for patients at risk of lymph node metastasis.

In this study, two ecological types of earthworms were exposed to soil samples that were artificially contaminated with individual hexabromocyclododecane (HBCD) diastereomers (α-, β-, and γ-HBCDs) to investigate the bioaccumulation, depuration, enantiomer selectivity and isomerization of HBCDs in earthworms. The uptake rate constant (ku), bioaccumulation factor (BAF), biota soil accumulation factor (BSAF), and half-life (t1/2) for the α-HBCD were the highest among the three diastereomers. The bioaccumulation parameters of the three diastereoisomers differed between the two ecologically different species of earthworms. The BSAF values of α- and γ-HBCDs were substantially higher in Eisenia fetida than those in Metaphire guillelmi, with the higher lipid and protein contents in E. fetida as the primary reason for this difference. The other processes, such as uptake, depuration, metabolism and isomerization, also differed between the two species and led to a difference in the bioaccumulation of β-HBCD. The β- and γ-HBCDs were bioisomerized to α-HBCD in the earthworms, but to a greater extent in E. fetida. The highest BSAF, t1/2 of α-HBCD and the bioisomerization of β- and γ-HBCDs to α-HBCD might explain in part why α-HBCD was the dominant isomer in biota samples. Most of the enantiomer fractions (EFs) for the three HBCD diastereoisomers in the earthworms were different from those in standard samples (p<0.05), indicating that enantiomer selectivity occurred. Moreover, the trends and extent of the enantioselectivity were different between the two species. Additionally, the EFs of α-HBCD that was bioisomerized from β- or γ-isomers were also different from those in the standards (p<0.05), which likely reflect the integration of several processes, such as enantioselective isomerization and the subsequent selective metabolism of the produced α-HBCD or selective excretion of the enantiomers., (Copyright © 2015 Elsevier B.V. All rights reserved.)