Abstract Background Sensorineural hearing loss (SNHL) poses a major threat to both physical and mental health; however, there is still a lack of effective drugs to treat the disease. Recently, novel biological therapies, such as mesenchymal stem cells (MSCs) and their products, namely, exosomes, are showing promising therapeutic potential due to their low immunogenicity, few ethical concerns, and easy accessibility. Nevertheless, the precise mechanisms underlying the therapeutic effects of MSC-derived exosomes remain unclear. Results Exosomes derived from MSCs reduced hearing and hair cell loss caused by neomycin-induced damage in models in vivo and in vitro. In addition, MSC-derived exosomes modulated autophagy in hair cells to exert a protective effect. Mechanistically, exogenously administered exosomes were internalized by hair cells and subsequently upregulated endocytic gene expression and endosome formation, ultimately leading to autophagy activation. This increased autophagic activity promoted cell survival, decreased the mitochondrial oxidative stress level and the apoptosis rate in hair cells, and ameliorated neomycin-induced ototoxicity. Conclusions In summary, our findings reveal the otoprotective capacity of exogenous exosome-mediated autophagy activation in hair cells in an endocytosis-dependent manner, suggesting possibilities for deafness treatment. SNHL (SNHL health however disease Recently therapies (MSCs products namely immunogenicity concerns accessibility Nevertheless MSCderived MSC unclear neomycininduced neomycin induced vitro addition effect Mechanistically formation survival ototoxicity summary exosomemediated exosome mediated endocytosisdependent endocytosis dependent manner treatment

Abstract Pulsed Electric field (PEF) cell lysis technology, as a new technology, has been widely used in the fields of food sterilization. Nowadays, there are still several problems in PEF cell lysis: low cell lysis rate, high temperature rise, the presence of low velocity regions, etc. In this study, COMSOL Multiphysics was used to conduct simulation research, and the electric field, flow field and temperature field of plate treatment chamber, coaxial treatment chamber and co-field treatment chamber were coupled to simulate, and the advantages and disadvantages of the three classical treatment chamber structures were analyzed. In addition, this paper proposes a new structure of the co-field treatment chamber. Through the comparison and simulation of the coupling between our design and other four structures, the electric field intensity of our design treatment area is 20.03 kV/m, which is 46.2% higher than the highest of others. The temperature rise within 1s is 0.93 K, which is 2/3 lower than others. Our design almost eliminates the peak electric field area at the junction between the inside of the electrode and the insulator, and the maximum electric field intensity in this area is reduced by 24.4% compared with others.

Abstract Objective: This study aimed to perform a meta-analysis to investigate the diagnostic safety and accuracy of Ultrasound-Guided Core Needle Biopsy (US-CNB) Axillary Lymph Nodes (ALNs) region in patients with Breast Cancer (BC). Methods: The authors searched the electronic databases PubMed, Scopus, Embase, and Web of Science for clinical trials about US-CNB for the detection of ALNs in breast cancer patients. The authors extracted and pooled raw data from the included studies and performed statistical analyses using Meta-DiSc 1.4 and Review Manager 5.3 software. A random effects model was used to calculate the data. At the same time, data from the Ultrasound-guided Fine-Needle Aspiration (US-FNA) were introduced for comparison with the US-CNB. In addition, the subgroup was performed to explore the causes of heterogeneity. (PROSPERO ID: CRD42022369491). Results: In total, 18 articles with 2521 patients were assessed as meeting the study criteria. The overall sensitivity was 0.90 (95% CI [Confidence Interval], 0.87‒0.91; p = 0.00), the overall specificity was 0.99 (95% CI 0.98‒ 1.00; p = 0.62), the overall area under the curve (AUC) was 0.98. Next, in the comparison of US-CNB and US-FNA, US-CNB is better than US-FNA in the diagnosis of ALNs metastases. The sensitivity was 0.88 (95% CI 0.84‒ 0.91; p = 0.12) vs. 0.73 (95% CI 0.69‒0.76; p = 0.91), the specificity was 1.00 (95% CI 0.99‒1.00; p = 1.00) vs. 0.99 (95% CI 0.67‒0.74; p = 0.92), and the AUC was 0.99 vs. 0.98. Subgroup analysis showed that heterogeneity may be related to preoperative Neoadjuvant Chemotherapy (NAC) treatment, region, size of tumor diameter, and the number of punctures. Conclusion: US-CNB has a satisfactory diagnostic performance with good specificity and sensitivity in the preoperative diagnosis of ALNs in BC patients.

Abstract This study aimed to investigate the molecular mechanism of Picrasma quassioides Benn against inflammation by means of network pharmacology. The paper will provide a reference for multi-target and multi-channel treatment of inflammation with traditional Chinese medicine. Through screening and analysis, 11 active ingredients and 109 anti-inflammation prediction targets were obtained and constructed a compound-target network. The targets such as VEGFA, TLR4 and STAT3 may play a crucial role. Network enrichment analysis showed that the 109 potential targets constitute a number of pathways or inflammatory reactions closely related to inflammation, including NF-κB signaling pathway and MAPK signaling pathway. The docking results indicated that the binding energy of Picrasidine Y and the inflammatory factors VEGFA is the highest. This study predicted the role of multiple active compounds in the alkaloids of Picrasma in the inflammatory response, and provided a theoretical basis for the anti-inflammatory mechanism of Picrasma.

Abstract The increase of the obesity pandemic worldwide over the last several decades has generated a constant need for the scientific world to develop new possibilities to combat obesity. Since the discovery that brown adipose tissue (BAT) exists in adult humans, and BAT activation contributes to a negative energy balance, much more attention has been focused on the understanding of the molecular switches and their different regulatory mechanisms turning on energy expenditure. Recent insights have revealed that a range of stimuli including cold exposure, physical activity and diet, and critical transcription molecules such as PPARγ, PRDM16, PGC-1α and UCP1, aiming at the induction of BAT activation, could cause the browning of white adipose tissue, thereby dissipating energy and increasing heat production. An increasing number of studies that point to the white adipose tissue (WAT) browning strategies aiming at diet-induced and/or genetically determined obesity have been tested in mouse models as well as in human studies. Findings suggested that browning stimulating drugs have been currently or previously assayed as a therapy against obesity. As PPARα agonists, fibrate drugs effectively reduced plasma triglyceride, increased high-density lipoproteins, and improved glycemic control and heat production in brown adipose tissue, which has been used in the treatment of metabolic disorders. Many kinds of natural products promote white adipose tissue browning, such as alkaloids, flavonoids, terpenoids, and long-chain fatty acids, which can also ameliorate metabolic disorders including obesity, insulin resistance and diabetes. The aim of this review is to summarize the transcriptional regulators as well as the various mediators that have been regarded as potential therapeutic targets in the process of WAT browning.

Resumen La creciente prevalencia mundial de la obesidad en las últimas décadas ha hecho que la comunidad científica siga necesitando desarrollar nuevas posibilidades para luchar contra la obesidad. Desde que se descubrió que el tejido adiposo pardo (TAP) existe en los adultos y que la activación del TAP contribuye al equilibrio energético negativo, se ha prestado más atención a la comprensión de los interruptores moleculares y sus diferentes mecanismos de regulación del consumo de energía. Estudios recientes han demostrado que una serie de estímulos, incluyendo la exposición al frío, la actividad física y la dieta, y moléculas clave de transcripción como PPARγ, PRDM16, PGC-1α y UCP1, dirigidos a inducir la activación del TAP, podrían causar un pardeamiento del tejido adiposo blanco (TAB), disipando energía y aumentando la producción de calor. Se han realizado un número cada vez mayor de estudios sobre estrategias de pardeamiento del TAB para la obesidad inducida por la dieta y/o genéticamente determinada, tanto en modelos de ratón como en modelos de líneas celulares humanas in vitro. Desafortunadamente, el potencial terapéutico de estas estrategias de pérdida de peso mediante la inducción de la activación del TAP y el pardeamiento del TAB no se ha confirmado en seres humanos. El objetivo de esta revisión es resumir los reguladores de la transcripción y los mediadores que se consideran objetivos terapéuticos potenciales en el proceso de pardeamiento del TAB.

RESUMO: O Cazaquistão está localizado no interior da Ásia Central. Suas virtuosas vantagens geográficas e grande potencial de produção de grãos a tornam um dos exportadores de grãos mais importantes do mundo. A pesquisa sobre o problema do comércio de grãos no Cazaquistão é de grande importância para a segurança alimentar. Este estudo mede sua competitividade internacional por meio do índice IMS, índice RCA, índice TC e calcula a competitividade internacional e analisa os fatores influenciadores da exportação de grãos por meio da construção de um modelo gravimétrico estendido e mede seu potencial exportador. Os resultados mostram que o Cazaquistão tem uma baixa participação no mercado internacional de grãos; no entanto, trigo, cevada e trigo sarraceno têm fortes vantagens de exportação; o nível de desenvolvimento econômico e a distância econômica têm promovido significativamente a escala das exportações de grãos. Embora a distância geográfica, a diferença no PIB per capita e o fato de os países parceiros comerciais terem aderido à União Econômica da Eurásia têm causado obstáculos às exportações de grãos. O potencial de exportação do Cazaquistão para seis países, incluindo Rússia, Quirguistão e China mostra uma tendência de “alta”, seu potencial de exportação para seis países, incluindo Tajiquistão e Ucrânia, mostra uma tendência“ estável ”e sua exportação para nove países, incluindo Polônia e Alemanha. O potencial mostra uma tendência de “declínio”.

ABSTRACT: Kazakhstan is located in the hinterland of Central Asia. Its virtuous geographical advantages and huge grain production potential make it one of the most important grain exporters in the world. The research on the problem of the grain trade in Kazakhstan is of great significance for food security. This study measured its international competitiveness using the International Market Share Index, the Revealed Comparative Advantage Index, Trade competitiveness index and calculated the international competitiveness and analyzed the influencing factors of grain export by constructing an extended gravity model and measured its export potential. Results showed that Kazakhstan has a low share of the international grain market; however, wheat, barley, and buckwheat have strong export advantages; the level of economic development and economic distance has significantly promoted the scale of grain exports. While geographical distance, the difference in GDP per capita, and the fact whether trading partner countries have joined the Eurasian Economic Union have caused obstacles to grain exports. Kazakhstan’s export potential to 6 countries including Russia, Kyrgyzstan and China shows an upward” trend, its export potential to 6 countries including Tajikistan and Ukraine showing a “stable” trend, and its export to 9 countries included Poland and Germany. The potential showed a “declining” trend.

Abstract To study the exact effect of purple wheat (PW) on dyslipidaemia in rats so as to lay the foundation of a dietary therapy for hyperlipidaemia. A total of 42 rats were randomly divided into two groups: normal control group (NC) consisting of 12 rats were fed with standard diet in the whole testing process, the other group rats were fed with high-fat diet to induce dyslipidaemia. The dyslipidaemic rats were averagely divided into three groups: dyslipidaemia control group (DC) with 60% common wheat flour, PW1 group with diet containing 60% purple wheat Jizimai1 flour, PW3 group with 60% purple wheat Jizimai3 flour. Six weeks later, the weight-gain-ratio of the rats in PW1 and PW3 groups were lower as compared to the rats in DC and NC groups. Further, we found that the levels of triglyceride, total cholesterol and low-density lipoprotein in the PW1 and PW3 groups were significantly reduced to almost that of normal levels. Finally, the results of hematoxylin and eosin staining showed that intaking of Jizimai1 and Jizimai3 could repair hepatocyte steatosis and kidney injury due to dyslipidaemia. Purple wheat diet therapy reduced lipid metabolism disorders and the liver tissue and renal injury in hyperlipidaemic rats.

Abstract To explore the critical care treatment and clinical outcome of patients with severe aneurysmal subarachnoid hemorrhage (SaSAH), and to provide clinical evidence for the treatment of patients with SaSAH. 160 patients with SaSAH of Hunt and Hess (H&H) grade III or above in the neurosurgical critical care unit at ourospital between June 2016 and June 2018 were enrolled in this study. Patients were treated with brain protective bundle based on step-wised protocol under multimodal monitoring and followed up for 3 months. The incidence of various clinical complications and the clinical prognosis after discharge were statistically analyzed. Furthermore, it carried on the correlation analysis to the risk factors and the prognosis. In 160 patients with SaSAH, 127 patients had responsible aneurysms located in the anterior circulation, and the other 33 patients were located in the posterior circulation. 70 patients (43.8%) underwent transcranial clipping, 81 patients (50.6%) underwent endovascular embolization and 9 patients (5.6%) did not intervene. Patients with IV and V grades of Glasgow Outcome Scale (GOS) were considered good recovery, and those with grade I, II and III were poor prognosis. The 30-day good prognosis rate was 41.3% (66/160) and the poor prognosis rate was 58.7% (94/160). Multivariate logistic regression analysis showed that the Hunt & Hess classification correlated well with prognosis (OR: 4.367,95% CI, 2.254-8.460, P < 0.001). The clinical prognosis of patients with SaSAH is still poor. In particular, under the critical care of neurosurgery, the application of brain protective bundle based on step-wised protocol under multimodal monitoring might improve the clinical prognosis of patients with SaSAH.

Abstract To explore the protective activity of ginger (Zingiber officinale) root ethanol extract (GRE) on the neuroinflammation induced by lipopolysaccharide in microglial cells. Ginger has been investigated as a neuroprotective and anti-aging agent. Nevertheless, ginger extract attenuates neuroinflammation in microglia have not been discovered in depth. The results showed that GRE had high total phenolic and (55.63 ± 0.16 mg GAE/g) and total flavonoid content (4.33 ± 0.17 mg QUE/g), and antioxidant activity. GRE inhibited the release of cytokines and inflammatory mediators including COX-2, PGE2, Nitric oxide, interleukin-6, TNF-α, and iNOS. GRE ameliorated microglia-mediated neuronal insults via upregulating the expression of Bax and reducing the expression of Bcl-2. GRE suppressed NF-κB and AKT/STAT3, and the MAPK pathway in the neuroinflammatory response. In conclusions, GRE positively affected anti-neuroinflammatory and neuroprotective activity without serious side effects, which might be used as a functional food additive and/or therapeutic material for the management and prevention of neurodegenerative diseases.

Abstract The objective of the current study was to assess the antioxidant activity of different solvents containing Humulus japonicus extract (HJE) and their antioxidant effects on neurons. H. japonicus ethanol extracts (HEEs) together with H. japonicus water extracts (HWEs) were generated via extraction of H. japonicus leaves with 30%, 50%, and 80% ethanol solutions under a hot water temperature of 121 °C. HEEs showed higher levels of bioactive compounds, such as total flavonoids and polyphenols, with stronger antioxidant activities in contrast to HWEs. HEE (80%) showed the highest content of bioactive compounds and antioxidant activity. Next, we used a H2O2-induced rat model of pheochromocytoma PC12 cells to investigate the antioxidant activity and cellular signal regulation of 80% HEEs. The results showed that HJEs resisted oxidative stress via MAPK and/or AKT-NRF2 and NF-kappa B signaling pathways and upregulated antioxidant enzymes such as SOD, catalase, HO-1, and OGG1, thereby reducing intracellular ROS levels. Further, HJE promoted neuronal survival by upregulating sirtuin 1 expression. This study provides evidence supporting the potential benefits of HJE in preventing oxidative stress in PC12 cells, suggesting its application as a promising functional food additive or therapeutic agent for the prevention and the treatment of oxidative stress-related neurodegenerative diseases.

Abstract To investigate the effect of licorice on anti-liver fibrosis actions, we present systematic review and meta-analysis via systematic literature between 2010 and 2020 from the electronic databases, PubMed, Cochrane Library, Embase, ISI. A software program (Endnote X8) has been utilized for managing the electronic titles. Searches were performed with mesh terms. Mean differences between two groups (Glycyrrhizic acid and control group) with 95% confidence interval (CI), fixed effect model and Inverse-variance method were calculated. Random effects were used to deal with potential heterogeneity and I2 showed heterogeneity. The Meta analysis and forest plots have been evaluated with the Stata V16. A total of 184 potentially relevant titles and abstracts were found during the electronic and manual search. Finally, a total of four publications fulfilled the inclusion criteria required for this systematic review. TGF-β1 mRNA expression significantly decreased following Glycyrrhizic acid relative to the control group and Glycyrrhizic acid significantly decreased expression of TGF-β1 mRNA, which was about 2.90 times that in the control group. Mean difference between Glycyrrhizic acid and control group was -18.12 U/L (MD, -18.12 U/L 95% CI 30.02 U/L, -6.22 U/L. P = 0.00). Glycyrrhizic acid reduced TGF-β1, Smads mRNAs, hypdroxyproline, alanine aminotransferase.

Abstract The aim of this study was to evaluate the inhibitory effect and mechanism of collagen degradation by Pectinase-assisted Halophyte Complex Extract (PHCE) in hairless mice. Collagen expression in vitro was measured using Enzyme-linked Immunosorbent Assay (ELISA) and Western blotting. After collecting mice skin in vivo, histological analysis was performed with Hematoxylin & Eosin (H & E) and trichrome stain. Molecular expression was measured by western blot analysis. In HaCaT cells, the collagen expression level was increased compared to the positive control group. Epidermal thickness inhibition and collagen expression levels were also increased in the skin of a hairless mouse model. Western blot analysis confirmed the increase in collagen and elastin by inhibiting phosphorylation of NF-κB and decreasing the expression of matrix metalloproteinases-1 (MMP-1) and matrix metalloproteinases-9 (MMP-9). The skin protective effect of PHCE is considered to be due to inhibition of MMPs expression through inhibition of NF-κB activation. Therefore, PHCE can be considered as a candidate material as a food material that can improve skin damage caused by UV rays.

Abstract Humulus japonicus (HJ) is administered to patients with pulmonary disease and skin disease owing to its anti-inflammatory and antioxidant effects. Lately, HJ has been shown to exert impacts on protection against neurodegenerative sickness. Nevertheless, its impacts on microglia have not been discovered in depth. As a result, anti-inflammatory impacts of HJ ethanol extract (HJE) and its active compound luteolin on lipopolysaccharide-stimulated SIM-A9 cells were investigated. The results showed that HJE luteolin inhibited generation of interleukin-1β, tumor necrosis factor-α, nitric oxide, interleukin-6, together with prostaglandin E2, iNOS, COX-2 along with HO-1 induction. Furthermore, HJE and luteolin reduced degrees of NF-κB pathway components within cytoplasm and nucleus, while reducing cytoplasmic MAPK levels and increasing Nrf2 levels in the cytoplasm and nucleus. In conclusion, our results demonstrate that HJE might exhibit neuroprotective effects and could be used as a novel drug for various neurological diseases.

Abstract Selenium (Se) is a nutritionally important micronutrient for humans. The use of Se fertilizers is often the most feasible approach to precisely increase Se contents in rice grains, but the effects of common commercial Se fertilizers on producing Se-rich rice remain to be investigated. In this study, we compared the effects of liquid and granular Se fertilizers on the accumulation of Se and heavy metals in rice grains of four different varieties in field. Results showed that Se accumulation in rice grains was affected by the form of fertilizers, applied concentrations of Se fertilizers, and rice varieties. Liquid fertilizer displayed significantly higher Se transfer efficiency than granular fertilizer, whereas the granular fertilizer had a slightly higher effect on organic Se accumulation. More than 95.5% Se in grains were organic Se, with selenomethionine (SeMet) being the dominant one. The proportion of organic selenocysteine (SeCys2) in grains was significantly higher in treatments with liquid fertilizer. Both forms of fertilizers significantly reduced the accumulation of cadmium, lead, and arsenic. Collectively, our study provides a reference for producing Se-rich rice in a more competitive manner in practice.

Abstract To explore the protective impact of the ginger root ethanol extract (GRE) against the oxidative stress induced by 6-hydroxydopamine (6-OHDA) and apoptotic and its mechanism. Parkinson's disease (PD) model was established using 6-OHDA in the cells of rat adrenal pheochromocytoma (PC12). The GRE pretreatment increased PC12 cell viability of injury induced by 6-OHDA. The GRE effectively suppressed 6-OHDA-induced death, apoptosis through decreased Bax and cleaved-caspase 3 expression, and up-regulated expression of B-cell lymphoma 2 (Bcl-2). GRE also inhibited 6-OHDA-inducel oxidative stress, decreased reactive oxygen species (ROS) and up-regulates the heme oxygenase (HO-1), antioxidant enzymes, catalase and, glutathione (GSH), superoxide dismutase (SOD), 8-oxoguanine glycosylase1 (OGG1) and NAD(P)H quinone oxidoreductase1 (NQO1). Besides, GRE up-regulating Protein kinase B (Akt), nuclear erythroid 2-related factor 2 (Nrf2), down-regulating nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) translocation, together with the mitogen-activated protein kinase (MAPK) phosphorylation. In conclusions, the GRE prevented apoptosis and oxidative stress in 6-OHDA-induced PC12 cells. The ginger ethanol extract could be treatment and prevention of PD.