[Effect of Hei Xiaoyaosan regulating p38MAPK/Beclin-1/Bcl-2 pathway on autophagy level in Alzheimer's disease model rats].

To explore the effect of Hei Xiaoyaosan on autophagy levels in Alzheimer's disease(AD). A total of 100 4-month-old Wistar male rats were randomly selected as a blank group, and 10 rats were taken as a sham operation group and injected with 1 µL of normal saline on both sides of the hippocampus. The other rats were injected with Aß_(1-42) solution in the hippocampus to replicate the AD model. Fifty successfully modeled rats were selected and randomly divided into the model group, Aricatio group(0.5 mg·kg~(-1)), and high, medium, and low dose groups of Hei Xiaoyaosan(15.30, 7.65, and 3.82 g·kg~(-1)), with 10 rats in each group. The rats were administered by continuous gavage for 42 days. Morris water maze was used to detect the learning and memory ability of rats, and Hoechst staining was used to observe the pathological changes of nerve cells in the hippocampal CA1 region. The mRNA expression of p38MAPK, Beclin-1, and Bcl-2 was detected by RT-qPCR.Western blot was used to detect the expressions of p38MAPK, Beclin-1, Bcl-2, APP, and related proteins. The level of Aß_(1-42) in the hippocampus was detected by ELISA, and the expression level of LC3Ⅱ in the hippocampus was detected by immunohistochemistry. The experimental results showed that compared with the blank group, the learning and memory ability of rats in the model group decreased(P<0.01). The nuclei in the CA1 region of the hippocampus showed blue bright spots and were closely arranged. The mRNA expression of p38MAPK was up-regulated, and the mRNA expressions of Beclin-1 and Bcl-2 were down-regulated(P<0.01). The expressions of p38MAPK, p-p38MAPK, and APP were increased, while those of Beclin-1, Bcl-2, and p-Bcl-2 were decreased(P<0.01). The expression of Aß_(1-42) was increased(P<0.01). The relative expression of LC3Ⅱ decreased(P<0.01). Compared with the model group, the learning and memory ability of rats in each administration group was improved(P<0.05 or P<0.01). The nuclei in the CA1 region of the hippocampus gradually became clear, showing light blue. The mRNA expression of p38MAPK was down-regulated(P<0.01), and that of Beclin-1 and Bcl-2 was increased(P<0.05 or P<0.01). The expressions of p38MAPK, p-p38MAPK, and APP were down-regulated, while those of Beclin-1, Bcl-2, and p-Bcl-2 were up-regulated(P<0.05 or P<0.01). The expression of Aß_(1-42) was decreased(P<0.01). The relative expression of LC3Ⅱ was increased(P<0.01). It can be concluded that Hei Xiaoyaosan can improve the cognitive ability of AD model rats, and its potential mechanism may be related to regulating the p38MAPK/Beclin-1/Bcl-2 signaling pathway, increasing the level of autophagy, and reducing the accumulation of Aß_(1-42).

L-Citrulline Ameliorates Iron Metabolism and Mitochondrial Quality Control via Activating AMPK Pathway in Intestine and Improves Microbiota in Mice with Iron Overload.

SCOPE: Oxidative stress caused by iron overload tends to result in intestinal mucosal barrier dysfunction and intestinal microbiota imbalance. As a neutral and nonprotein amino acid, L-Citrulline (L-cit) has been implicated in antioxidant and mitochondrial amelioration properties. This study investigates whether L-cit can alleviate iron overload-induced intestinal injury and explores the underlying mechanisms. METHODS AND RESULTS: C57BL/6J mice are intraperitoneally injected with iron dextran, then gavaged with different dose of L-cit for 2 weeks. L-cit treatment significantly alleviates intestine pathological injury, oxidative stress, ATP level, and mitochondrial respiratory chain complex activities, accompanied by ameliorating mitochondrial quality control. L-cit-mediated protection is associated with the upregulation of Glutathione Peroxidase 4 (GPX4) expression, inhibition Nuclear Receptor Coactivator 4 (NCOA4)-mediated ferritinophagy and ferroptosis, and improvement of gut microbiota. To investigate the underlying molecular mechanisms, Intestinal Porcine Epithelial Cell line-J2 (IPEC-J2) cells are treated with L-cit or AMP-activated Protein Kinase (AMPK) inhibitor. AMPK signaling has been activated by L-cit. Notably, Compound C abolishes L-cit's protection on intestinal barrier, mitochondrial function, and antioxidative capacity in IPEC-J2 cells. CONCLUSION: L-cit may restrain ferritinophagy and ferroptosis to regulate iron metabolism, and induce AMPK pathway activation, which contributes to exert antioxidation, ameliorate iron metabolism and mitochondrial quality control, and improve intestinal microbiota. L-cit is a promising therapeutic strategy for iron overload-induced intestinal injury.

Submerged plant-biochar composite system exhibits effective control over residual organic pollutants in the benthic organisms of aquaculture ponds.

As of now, submerged plants and biochar have demonstrated significant benefits in aquaculture pond sediment remediation. However, there is limited research on the synergistic effects of biochar and submerged plants in mitigating hydrophobic organic contaminant (HOC) accumulation in aquaculture benthic organisms and in controlling the nutrient (nitrogen and phosphorus) levels in aquaculture water. This study assesses a submerged plant-biochar system's efficacy in removing HOCs from simulated freshwater aquaculture ponds. Vallisneria natans was planted in sediment with varying levels of wheat straw biochar, while Corbicula fluminea served as the targeted benthic organism. The bioaccumulation experiment identified the optimal biochar ratio for the Vallisneria natans-biochar system in controlling HOCs in aquaculture products. Analyses included final accumulation concentrations in benthic organisms, changes in freely-dissolved concentrations in aquaculture sediment, and a mass balance calculation to explore key factors in their removal from the system. Results indicated that the Vallisneria natans-1.5% biochar composite system achieved optimal control of HOCs in sediment and aquaculture products. Biochar addition to the sediment in the composite system demonstrated a "promotion with low addition, inhibition with high addition" effect on Vallisneria natans growth. Notably, the addition of 1.5% biochar (VN1.5 group) significantly promoted the growth of Vallisneria natans leaves and roots. Comparing the final pollutant proportions in different environmental media, concentrations in water (0.20%-1.8%), clam accumulation (0.032%-0.11%), and plant absorption (0.10%-0.44%) constituted a minimal portion of the overall pollutant load in the system. The majority of pollutants (24%-65%) were degraded in the aquaculture environment, with microbial degradation likely playing a predominant role. Bacterial phyla, particularly Proteobacteria and Firmicutes, were identified as potential direct contributors to pollutant degradation in the Vallisneria natans-biochar system.

Pushing the thinness limit of silver films for flexible optoelectronic devices via ion-beam thinning-back process.

Reducing the silver film to 10 nm theoretically allows higher transparency but in practice leads to degraded transparency and electrical conductivity because the ultrathin film tends to be discontinuous. Herein, we developed a thinning-back process to address this dilemma, in which silver film is first deposited to a larger thickness with high continuity and then thinned back to a reduced thickness with an ultrasmooth surface, both implemented by a flood ion beam. Contributed by the shallow implantation of silver atoms into the substrate during deposition, the thinness of silver films down to 4.5 nm can be obtained, thinner than ever before. The atomic-level surface smooth permits excellent visible transparency, electrical conductivity, and the lowest haze among all existing transparent conductors. Moreover, the ultrathin silver film exhibits the unique robustness of mechanical flexibility. Therefore, the ion-beam thinning-back process presents a promising solution towards the excellent transparent conductor for flexible optoelectronic devices.

A national study exploring the association between triglyceride-glucose index and risk of hyperuricemia events in adults with hypertension.

Background: The triglyceride-glucose (TyG) index has been recommended as a practical surrogate of insulin resistance (IR). However, the association between the TyG index and hyperuricemia among adults with hypertension remains to be elucidated. Methods: We included and analyzed 3134 HTN patients and 4233 non-HTN participants from the cross-sectional 2013-2018 U.S. National Health and Nutrition Examination Surveys (NHANES). Multivariable logistic regression and restricted cubic splines (RCS) were used to explore the association between the TyG index and hyperuricemia. Stratifed analyses were performed to assess the association in populations with different subgroups of hypertension. Results: The prevalence of hyperuricemia was higher in HTN patients (28.00 %) than in non-HTN participants (12.47 %). The multivariable logistic regression showed that the TyG index was significantly associated with hyperuricemia. After multivariable adjustment, higher TyG index levels were found to be associated with a higher prevalence of hyperuricemia in HTN patients (OR: 2.39, 95 % CI: 1.37-4.17, Ptrend < 0.001) and non-HTN participants (OR: 2.61, 95 % CI: 1.45-4.69, Ptrend < 0.001). Restricted cubic spline regression showed linearity of the associations between the TyG index and hyperuricemia (p-nonlinear > 0.05). In the subgroup analysis suggested that the positive association seemed to be strong among male, alcohol use, and diabetes group (P for interaction < 0.05). Conclusions: TyG index, a practical surrogate of IR, was linearly and positively associated with hyperuricemia in HTN and non-HTN participants. Proactive measures are needed to prevent the comorbidity of IR-driven hyperuricemia in the future.

Mechanisms of mitophagy and oxidative stress in cerebral ischemia-reperfusion, vascular dementia, and Alzheimer's disease.

Neurological diseases have consistently represented a significant challenge in both clinical treatment and scientific research. As research has progressed, the significance of mitochondria in the pathogenesis and progression of neurological diseases has become increasingly prominent. Mitochondria serve not only as a source of energy, but also as regulators of cellular growth and death. Both oxidative stress and mitophagy are intimately associated with mitochondria, and there is mounting evidence that mitophagy and oxidative stress exert a pivotal regulatory influence on the pathogenesis of neurological diseases. In recent years, there has been a notable rise in the prevalence of cerebral ischemia/reperfusion injury (CI/RI), vascular dementia (VaD), and Alzheimer's disease (AD), which collectively represent a significant public health concern. Reduced levels of mitophagy have been observed in CI/RI, VaD and AD. The improvement of associated pathology has been demonstrated through the increase of mitophagy levels. CI/RI results in cerebral tissue ischemia and hypoxia, which causes oxidative stress, disruption of the blood-brain barrier (BBB) and damage to the cerebral vasculature. The BBB disruption and cerebral vascular injury may induce or exacerbate VaD to some extent. In addition, inadequate cerebral perfusion due to vascular injury or altered function may exacerbate the accumulation of amyloid ß (Aß) thereby contributing to or exacerbating AD pathology. Intravenous tissue plasminogen activator (tPA; alteplase) and endovascular thrombectomy are effective treatments for stroke. However, there is a narrow window of opportunity for the administration of tPA and thrombectomy, which results in a markedly elevated incidence of disability among patients with CI/RI. It is regrettable that there are currently no there are still no specific drugs for VaD and AD. Despite the availability of the U.S. Food and Drug Administration (FDA)-approved clinical first-line drugs for AD, including memantine, donepezil hydrochloride, and galantamine, these agents do not fundamentally block the pathological process of AD. In this paper, we undertake a review of the mechanisms of mitophagy and oxidative stress in neurological disorders, a summary of the clinical trials conducted in recent years, and a proposal for a new strategy for targeted treatment of neurological disorders based on both mitophagy and oxidative stress.

Status and developmental trends in recombinant collagen preparation technology.

Recombinant collagen is a pivotal topic in foundational biological research and epitomizes the application of critical bioengineering technologies. These technological advancements have profound implications across diverse areas such as regenerative medicine, organ replacement, tissue engineering, cosmetics and more. Thus, recombinant collagen and its preparation methodologies rooted in genetically engineered cells mark pivotal milestones in medical product research. This article provides a comprehensive overview of the current genetic engineering technologies and methods used in the production of recombinant collagen, as well as the conventional production process and quality control detection methods for this material. Furthermore, the discussion extends to foresee the strides in physical transfection and magnetic control sorting studies, envisioning an enhanced preparation of recombinant collagen-seeded cells to further fuel recombinant collagen production.

Transmission dynamics of SARS-COV-2 in China: impact of public health interventions

COVID-19 has become a global pandemic. However, the impact of the public health interventions in China needs to be evaluated. We established a SEIRD model to simulate the transmission trend of China. In addition, the reduction of the reproductive number was estimated under the current forty public health interventions policies. Furthermore, the infection curve, daily transmission replication curve, and the trend of cumulative confirmed cases were used to evaluate the effects of the public health interventions. Our results showed that the SEIRD curve model we established had a good fit and the basic reproductive number is 3.38 (95% CI, 3.25-3.48). The SEIRD curve show a small difference between the simulated number of cases and the actual number; the correlation index (H2) is 0.934, and the reproductive number (R) has been reduced from 3.38 to 0.5 under the current forty public health interventions policies of China. The actual growth curve of new cases, the virus infection curve, and the daily transmission replication curve were significantly going down under the current public health interventions. Our results suggest that the current public health interventions of China are effective and should be maintained until COVID-19 is no longer considered a global threat.