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Background: Fructus cannabis (Hemp seed), the dried and mature fruit of Cannabis sativa L., was reported to have effects against Alzheimer's disease (AD) in different experimental models. However, either chemical composition or mechanisms of action was not clear. Our previous work isolated and identified diverse phenylpropionamides such as cannabisin A-F, caffeoyltyramine and feryroyltyramine from hemp seed, which showed antioxidant and anti-neuroinflammatory activity in cell models. Purpose: To study the anti-AD effect and mechanism of the total phenylpropionamides (TPA) extract from hemp seed using APPswe/PS1dE9 mice model. Methods: TPA extract was prepared via extraction and column chromatography techniques, then analyzed and measured using HPLC, HPLC-MS and Folin-Ciocalteu method. The extract was administered by gavage to APPswe/PS1dE9 mice. The learning memory ability of mice were examined using new object recognition test and Morris water maze. Hematoxylin and Eosin staining was used to observe the morphology of neuronal cells in the hippocampal region of brain tissue; ELISA was used to measure the content of IL-1β, TNF-α, IL-6, superoxide dismutase (SOD), malondialdehyde (MDA) in the brain tissue; the deposition of Aβ protein was measured by immunohistochemistry and Western blotting; the activation of microglia was measured by immunofluorescence. The expression of APP, PS1, SIRT1, and ADAM10 proteins was measured by Western blotting. Results: Folin-Ciocalteu method showed the total phenylpropionamides content was 238.03 μg caffeic acid equivalent /mg TPA. HPLC and HPLC-MS analysis showed the contents of N-trans-caffeoyltyramine, cannabisin A and B were 20.16 μg/mg, 32.16 μg/mg and 214.35 μg/mg, respectively, in TPA extract. TPA treatment significantly increased the survival rate of APP/PS1 mice, improved the learning and memory ability, reversed the neural cell damage in the hippocampal region, and reduced Aβ deposition and activated microglia in brain tissue. Meanwhile, the administration decreased the neuroinflammatory factors TNF-α, IL-6, IL-1β expression, increased antioxidant enzyme SOD activity, and attenuated MDA expression. Western blotting showed that TPA administration increased SIRT1 and ADAM10 protein expression and decreased APP and PS1 protein expression. Conclusion: TPA improved learning memory capacity, increased survival rate, attenuated neuroinflammation, oxidative stress, microglia activation and hippocampal apoptosis, and reduced amyloid deposition via the SIRT1-ADAM10 pathway in APP/PS1 mice.

Objectives: To describe a bladder cuff excision method modified with ureteral catheterization to better visualize the ureteral orifice during robot-assisted nephroureterectomy (RANU). Methods: We retrospectively analyzed 66 patients with upper urinary tract urothelial carcinoma of the renal pelvis and/or upper-mid ureter treated between January 2020 and January 2023. Among them, 32 patients (group A) underwent RANU supported by ureteral catheterization, and the remaining patients (group B) received routine transperitoneal RANU. Postoperative cystoscopy was performed routinely to compare the rates of residual ureteral orifice between the two groups. Results: Surgeries were completed uneventfully in all 66 patients, without blood transfusion or conversion to open procedures. The operative time, estimated blood loss, and postoperative length of hospital stay were similar between both groups. However, the mean time required for BCE in group A was shorter than that in group B (9.5 min vs. 16.0 min, p = 0.006). Cystoscopy at postoperative three months showed no ipsilateral ureteral orifice in group A, but residual ureteral orifice was found in 23.5% of patients in group B. During a short follow-up period of 16 months, no patients in group A experienced bladder tumor recurrence. However, two patients (5.9%) in group B developed bladder tumor recurrence, with one experiencing local tumor recurrence at the level of the ureteral stump. Conclusions: Our novel technique enables complete ureteral retrieval, accurate and rapid bladder cuff excision, which makes the procedure less invasive and safely reproducible during robot-assisted nephroureterectomy.

Growing evidence suggests that the presence of cancer stem cells (CSCs) is a major challenge in current tumor treatments, especially the transition from non-CSCs to differentiation of CSCs for evading conventional therapies and driving metastasis. Here we propose a therapeutic strategy of synergistic differentiation therapy and phototherapy to induce differentiation of CSCs into mature tumor cells by differentiation inducers and synergistic elimination of them and normal cancer cells through phototherapy. In this work, we synthesized a biomimetic nanoplatform loaded with IR-780 and all-trans retinoic acid (ATRA) via biomineralization. This method can integrate aluminum ions into small-sized protein carriers to form nanoclusters, which undergo responsive degradation under acidic conditions and facilitate deep tumor penetration. With the help of CSC differentiation induced by ATRA, IR-780 inhibited the self-renewal of CSCs and cancer progression by generating hyperthermia and reactive oxygen species in a synergistic manner. Furthermore, ATRA can boost immunogenic cell death induced by phototherapy, thereby strongly causing a systemic anti-tumor immune response and efficiently eliminating CSCs and tumor cells. Taken together, this dual strategy represents a new paradigm of targeted eradication of CSCs and tumors by inducing CSC differentiation, improving photothermal therapy/photodynamic therapy and enhancing antitumor immunity.

Resistance to breast cancer (BCa) chemotherapy severely hampers the patient's prognosis. MicroRNAs provide a potential therapeutic prospect for BCa. In this study, the reversal function of microRNA34a (miR34a) on doxorubicin (Dox) resistance of BCa and the possible mechanism was investigated. We found that the relative level of miR34a was significantly decreased in Dox-resistant breast cancer cell MCF-7 (MCF-7/A) compared with Dox-sensitive MCF-7 cells. Transfection with miR34a significantly suppressed the invasion, migration, adhesion of MCF-7/A cells without inhibiting their growth obviously. The combination of miR34a and Dox could significantly inhibit the proliferation, migration, invasion and induce the apoptosis of MCF-7/A cells. The synergistic effect of this combination on resistant MCF-7/A cells has no obvious relation with the expressions of classical drug-resistant proteins P-GP, MRP and GST-π, while closely related with the down-regulation on TOP2A and BCRP. Moreover, we found both protein and mRNA expression of Snail were significantly up-regulated in MCF-7/A cells in comparison with MCF-7 cells. Transfection with small interfering RNA (siRNA) of Snail could inhibit the invasion, migration and adhesion of drug-resistant MCF-7/A cells, while high-expression of Snail could remarkably promote the invasion, migration and adhesion of MCF-7 cells, which might be related with regulation of N-cadherin and E-cadherin. Transfection with miR34a in MCF-7/A cells induced a decrease of Snail expression. The potential binding sites of miR34a with 3′ UTR of Snail were predicted by miRDB target prediction software, which was confirmed by luciferase reporter gene method. Results showed that the relative activity of luciferase was reduced in MCF-7/A cells after co-transfection of miR34a and wild type (wt)-Snail, while did not change by co-transfection with miR34a and 3′ UTR mutant type (mut) Snail. Combination of miR34a and Dox induced a stronger decrease of Snail in MCF-7/A cells in comparison to miR34a or Dox treatment alone. What’ more, for the first time, we also found miR34a combined with Dox could obviously inhibit the expression of Snail through suppressing Notch/NF-κB and RAS/RAF/MEK/ERK pathway in MCF-7/A cells. In vivo study indicated that combination of miR34a and Dox significantly slowed down tumor growth in MCF-7/A nude mouse xenograft model compared with Dox alone, which was manifested by the down-regulation of Snail and pro-apoptosis effect in tumor xenografts. These results together underline the relevance of miR34a-driven regulation of Snail in drug resistance and co-administration of miR34a and Dox may produce an effective therapy outcome in the future in clinic.

Summary: Background: Stroke and dementia are the leading causes of neurological disease burden. Detrimental effects of air pollution on both conditions are increasingly recognised, while the impacts on the dynamic transitions have not yet been explored, and whether critical time intervals exist is unknown. Methods: This prospective study was conducted based on the UK Biobank. Annual average air pollution concentrations at baseline year 2010 estimated by land-use regression models were used as a proxy for long-term air pollution exposure. Associations between multiple air pollutants (PM2.5, PM2.5-10, and NO2) indicated by air pollution score and the dynamic transitions of stroke and dementia were estimated, and the impacts during critical time intervals were explored. The date cutoff of this study was February 29, 2020. Findings: During a median follow-up of 10.9 years in 413,372 participants, 6484, 3813, and 376 participants developed incident stroke, dementia, and comorbidity of stroke and dementia. For the overall transition from stroke to comorbid dementia, the hazard ratio (HR) for each interquartile range (IQR) increase in air pollution score was 1.38 (95% CI, 1.15, 1.65), and the risks were limited to two time intervals (within 1 year and over 5 years after stroke). As for the transition from dementia to comorbid stroke, increased risk was only observed during 2–3 years after dementia. Interpretation: Our findings suggested that air pollution played an important role in the dynamic transition of stroke and dementia even at concentrations below the current criteria. The findings provided new evidence for alleviating the disease burden of neurological disorders related to air pollution during critical time intervals. Funding: The State Scholarship Fund of China Scholarship Council.

In this paper, the microstructure evolution and thermal stability of nanocrystalline (NC) AZ31-2.5 wt%VP magnesium matrix composites were studied, while the hardness was analyzed. The results showed that the NC AZ31-2.5 wt%VP still kept NC scale after annealing at 300 °C and 350 °C. Even at 400 °C and 450 °C, the grain size of the annealed composite only grew to 113 nm and 132 nm, which was still in ultrafine grain scale, illustrating excellent thermal stability of NC AZ31-2.5 wt%VP. Furthermore, the V particles, which was uniformly distributed in the Mg matrix, had no obvious change in dimension after annealing, while it also had no new phase formed. The stabilization mechanism was expounded and found that the pinning effect of V particles effectively inhibited the grain growth of Mg matrix at high temperature. In addition, the grain growth kinetics equation (D6−D06=kt) was utilized to explain the grain growth behavior of NC AZ31-2.5 wt%VP, and the activation energy (Ea) of grain growth was calculated to be 130.9 kJ/mol, which was much higher than that of pure Mg (92 kJ/mol). Eventually, the hardness of NC AZ31-2.5 wt%VP was contrastive studied and the hardness evolution curves at different temperatures were obtained. After annealing treatment was performed at 450 °C for 180min, the hardness remained at 80 HV, which was higher than that of as-cast AZ31 (53 HV).

Objectives: Recent studies have linked exposure to road traffic noise or air pollution with incident type 2 diabetes (T2D), but investigation on their co-exposure was limited and underlying mechanisms remain unclear. We hypothesized that long-term co-exposure to road traffic noise and air pollution increases the risk of incident T2D via the development of metabolic syndrome (MetS). Methods: This prospective study included 390,834 participants in UK Biobank. Cumulative risk index (CRI), the health-based weighted levels of multiple exposures, was applied to characterize the co-exposure to 24-hour road traffic noise (Lden), particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5), and nitrogen dioxide (NO2). Lden was modeled by the Common Noise Assessment Methods in Europe and air pollutant levels were measured by the Land Use Regression model at participants’ residential addresses. Incident T2D was ascertained through linkages to inpatient hospital records. MetS was defined by five (central obesity, triglycerides, HDL cholesterol, glucose, and blood pressure) or six factors (C-reactive protein additionally). Cox proportional hazard models were used to assess the association between environmental exposures and incident T2D, and mediation analyses were applied to investigate the role of MetS. Results: After a median of 10.9 years of follow-up, 13,214 (3.4%) incident T2D cases were ascertained. The exposure to Lden, PM2.5, and NO2, as well as their co-exposure, were significantly associated with an elevated risk of incident T2D, with HRs of 1.03 (95%CI: 1.00, 1.05) per 3.5 dB(A) increase in Lden, 1.05 (95%CI: 1.01, 1.10) per 1.3 μg/m3 increase in PM2.5, 1.07 (95%CI: 1.02, 1.11) per 9.8 μg/m3 increase in NO2, and 1.06 (95%CI: 1.02, 1.09) per interquartile range increase in CRI. MetS significantly mediated 43.5%− 54.7% of the CRI-T2D relationship. Conclusions: Long-term co-exposure to road traffic noise and air pollution is associated with an elevated risk of incident T2D, which may partly be mediated by MetS.

In order to clarify the effect of Fe-based amorphous alloy on the separation mechanism and corrosion behavior of Cu-based immiscible coatings, 10 wt% Fe-based amorphous powder was designed into 90 wt% pure Cu powder to produce the amorphous alloy reinforced Cu-based immiscible coatings by laser melting deposition. The self-organized microstructure and corrosion behavior of immiscible coatings with different laser energy densities were investigated. When the different laser energy densities are adopted, many carbides (M23C6 and M12C) are dispersed in the lower α-Fe layer and large amounts of α-Fe particles containing carbides are embedded in the upper ε-Cu layer due to liquid phase separation. With increasing laser energy density (LED), the α-Fe dendrites are coarser and the area of carbides decrease. The interface of coating and substrate experiences a transition from “poor bonding (gaps) to “good bonding” and “crack debonding”. Moreover, the corrosion characteristics of immiscible coatings also experience a transformation from “crevice corrosion” to “enhanced protection of passive films” and “reduced protection of passive films”. As a result, the corrosion resistance increases first then decreases and the immiscible coating deposited by the LED of 31.25 J/mm2 exhibits the highest corrosion resistance.

A comprehensive understanding of the changing patterns and the contribution of each component of the forest ecosystem to evapotranspiration is necessary for an accurate assessment of biological quality, terrestrial ecosystem production, energy exchange, and water use efficiency. In this study, two methods (i.e., the sap-flow and lysimeter methods) were used to partition evapotranspiration (ET) into evaporation(E) and transpiration(T) components using stable isotope techniques. The factors affecting the contribution of T to ET (FT) were evaluated. The results showed that FT presents seasonal variation patterns throughout the year. Both methods accurately simulated the ET partitioning and its seasonal variation. The ET value estimated by the sap-flow method was less than that estimated by the lysimeter method. In contrast, the simulated value of T calculated using the lysimeter method was higher than that calculated by the sap-flow method. However, this was within allowable limits. The lysimeter method is more accurate and suitable for monitoring forest ecosystem evapotranspiration in practical experiments. This study provides a technical reference for the optimal calculation method of ET partitioning using a stable isotope-based technique. It provides baseline information to better understand water vapour exchange in forest ecosystems in China.

Arsenic exists universally in freshwater and marine environments, threatening the survival of aquatic organisms and human health. To elucidate arsenic bioaccumulation and biotransformation processes in aquatic organisms, this review evaluates the dissolved uptake, dietary assimilation, biotransformation, and elimination of arsenic in aquatic organisms and discusses the major factors influencing these processes. Environmental factors such as phosphorus concentration, pH, salinity, and dissolved organic matter influence arsenic absorption from aquatic systems, whereas ingestion rate, gut passage time, and gut environment affect the assimilation of arsenic from foodstuffs. Arsenic bioaccumulation and biotransformation mechanisms differ depending on specific arsenic species and the involved aquatic organism. Although some enzymes engaged in arsenic biotransformation are known, deciphering the complicated synthesis and degradation pathway of arsenobetaine remains a challenge. The elimination of arsenic involves many processes, such as fecal excretion, renal elimination, molting, and reproductive processes. This review facilitates our understanding of the environmental behavior and biological fate of arsenic and contributes to regulation of the environmental risk posed by arsenic pollution.

Application investigations of rapid biochemical oxygen demand (BOD) online analyzer for surface water in Wuxi, China were carried out since 2013. The analyzer adopted a novel working principle, that is, the oxygen concentration of the sample to be tested was regarded as a reference, and the oxygen consumption by the biofilm reactor (BFR) was calculated according to the difference between the reference and sample effluent from BFR. The BFR was fabricated via a cultivation process using naturally occurring microbial seeds from in site surface water. This analytical principle was first presented and clearly clarified, and the impact of microbial endogenous respiration to the measured values was also proposed and analyzed. The improved analyzers were equipped in three application sites with significant differences in BOD concentration, for the purpose of evaluating the feasibility and applicability of the proposed method. This study revealed that the online analyzer could continually operate over 30 days without human intervention and additional chemical reagent consumption. The obtained rapid BOD trend line showed that this analyzer could track the fluctuation of the biodegradable organic compound level timely and accurately. The innovative analytical method, as well as the outstanding adaptation and well accuracy rating, provided the highlights for wide applications in the future. Keywords: Biofilm reactor, Biochemical oxygen demand (BOD), Application demonstration, Online analysis